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the present invention provides that the activation of mir - 221 and mir - 222 is regulated , at least in part , by the met oncogene and the c - jun transcription factor , and which , in turn , down - regulates pten and timp3 . activation of met signaling is a frequent genetic event observed in liver and lung cancer development . ap - 1 is a complex of dimeric basic region - leucine zipper proteins that belong to the jun ( c - jun , junb , jund ), fos ( c - fos , fosb , fra - 1 and fra - 2 ), maf and atf subfamilies c - jun is the most potent transcriptional activator in its group , whose transcriptional activity is attenuated and sometimes antagonized by junb . the fos proteins , which cannot homodimerize , form stable heterodimers with jun proteins and thereby enhance their dna binding activity . the present inventors focused on these two ap - 1 subfamilies , and in particular on c - jun and c - fos , although they found by bioinformatics search ( tess database ) that also atf - 1 and jund , could be potential transcription factors involved in mir - 221 and mir - 222 activation . the present invention demonstrates that c - jun and not c - fos is involved in mir - 221 and mir - 222 activation and that c - jun has one binding site in the mir - 221 / mir - 222 promoter region . the induction of ap - 1 is mostly mediated by the jnk cascades . by using anisomycin , an antibiotic which activates the jnk cascade , the inventors found an increase of mir - 221 / mir - 222 expression in huh7 hepatocarcinoma cells , as consequence of c - jun phosphorylation . intriguingly , when the inventors grew huh7 cells in serum free medium , they did not observe any variation in the expression level of mir - 221 and mir - 222 or pten and timp3 , showing that met activation is important for mir - 221 and mir - 222 transcription regulation and subsequent cellular migration . to address this issue the inventors investigated calu - 1 and snu - 387 cell migration and invasion after met silencing . migratory and invasive capabilities of both cell lines were reduced after met oncogene silencing ( fig1 a - 17b ). furthermore , a xenograft model of calu - 1 cells in which c - met was silenced by using an shmet plasmid ( fig1 c ), showed that mice injected with calu - 1 shmet cells are more sensitive to trail inducing apoptosis compared to the mice injected with the sh control ( fig1 d - 17e ). thus met confers not only a tumor growth advantage but also resistance to trail - inducing apoptosis over control tumors in vivo . therefore , met oncogene regulates mir - 221 and mir - 222 levels and , accordingly , cellular invasion and migration through c - jun transcription factor and jnk activation ( fig8 ). taken together , these data highlight a mechanism , involving met , through which mir - 221 and mir - 222 promote tumorigenesis and metastasis . thus approaches targeting met receptor and / or mir - 221 and mir - 222 in order to sensitize nsclc and hcc to trail - inducing apoptosis , but also in the prevention and inhibition of lung cancer and hepatocellular carcinoma , are included in the present invention . in the present invention , there are identified major mrna targets and signaling pathways that mediate mir - 221 and mir - 222 regulation in a wide panel of nsclc and hcc - derived cell lines . in vitro and in vivo experiments reveal that elevated levels of mir - 221 and mir - 222 in nsclcs and hccs correlates with pten and timp3 down - regulation , indicating that these two micrornas are a causal factor in the down - regulation of pten and timp3 in these types of cancers . the inventors examined the effects of mir - 221 and mir - 222 and their targets on cell survival and trail resistance . interestingly , the inventors found that after mir - 221 / mir - 222 enforced expression , or pten and timp3 down regulation , trail - sensitive nsclc and hcc cells became resistant to trail - inducing apoptosis , although pten down regulation was slightly more effective than that of timp3 . the present invention provides methods to affect mir - 221 and mir222 expression , since it is now proved that mir - 221 and mir - 222 expression is a “ prerequisite ” of trail - resistant nsclc and hcc cells . importantly , tumor stratification , on the basis of mir - 221 / mir - 222 expression levels , could be used as prognostic tool to predict trail - sensitivity or trail - resistance in the treatment of nsclcs and hccs . the present invention also discloses that mir - 221 and mir - 222 block pten expression leading to activation of the akt pathway , showing that mir - 221 and mir - 222 plays an important role in cell growth and invasiveness by targeting the pten / akt pathway . in this regard , cell cycle analysis evidenced an increase in cell growth tightly linked to the g1 to s shift , which is in agreement with modulation of pten and also of p27kip1 , a known regulator of the g1 / s cell cycle checkpoint and a downstream effector of pten . nsclc and hcc cells overexpressing mir - 221 and mir - 222 are not only trail - resistant but they also show an increase in migration and invasion capabilities , compared to cells expressing lower levels of mir - 221 and mir - 222 cells . moreover , mir - 221 and mir - 222 are herein shown to promote cell migration , invasion and growth via direct repression of pten and timp3 expression and of downstream pathways involving akt and erks phosphorylation , and the activation of mmp - 3 and mmp - 9 . further , pten and timp3 loss in h460 tumor xenograft conferred not only a significant tumor growth advantage but also a resistance to trail - inducing apoptosis over control tumors also in vivo . interestingly , the timp3 knockdown tumors were more vascularized than the control tumors , highlighting its role in angiogenesis and tumor formation . the identification of mir - 221 and mir - 222 as important regulators of tumor cell proliferation , migration , and invasion of nsclc and hcc , in vitro and in vivo , provides insights into the role of these mirnas in hepatic and lung oncogenesis and tumor behavior . the effects of mir - 221 and mir - 222 and their targets on cell survival and trail resistance were examined . interestingly , after mir - 221 / mir - 222 enforced expression , or pten and timp3 downregulation , trail - sensitive nsclc and hcc cells became resistant to trail - inducing apoptosis , although pten down regulation was slightly more effective than that of timp3 . this indicates that mir - 221 and mir - 222 overexpression is a “ prerequisite ” of trail - resistant nsclc and hcc cells . importantly , tumor stratification , on the basis of mir - 221 / mir - 222 expression levels , could be used as prognostic tool to predict trail - sensitivity or trail - resistance in the treatment of nsclcs and hccs . it is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not intended to limit the scope of the current teachings . in this application , the use of the singular includes the plural unless specifically stated otherwise . the use of the word “ a ” or “ an ” when used in conjunction with the term “ comprising ” in the claims and / or the specification may mean “ one ,” but it is also consistent with the meaning of “ one or more ,” “ at least one ,” and “ one or more than one .” also , the use of “ comprise ”, “ contain ”, and “ include ”, or modifications of those root words , for example but not limited to , “ comprises ”, “ contained ”, and “ including ”, are not intended to be limiting . the term “ and / or ” means that the terms before and after can be taken together or separately . for illustration purposes , but not as a limitation , “ x and / or y ” can mean “ x ” or “ y ” or “ x and y ”. it is understood that an mirna is derived from genomic sequences or a gene . in this respect , the term “ gene ” is used for simplicity to refer to the genomic sequence encoding the precursor mirna for a given mirna . however , embodiments of the invention may involve genomic sequences of a mirna that are involved in its expression , such as a promoter or other regulatory sequences . the term “ mirna ” generally refers to a single - stranded molecule , but in specific embodiments , molecules implemented in the invention will also encompass a region or an additional strand that is partially ( between 10 and 50 % complementary across length of strand ), substantially ( greater than 50 % but less than 100 % complementary across length of strand ) or fully complementary to another region of the same single - stranded molecule or to another nucleic acid . thus , nucleic acids may encompass a molecule that comprises one or more complementary or self - complementary strand ( s ) or “ complement ( s )” of a particular sequence comprising a molecule . for example , precursor mirna may have a self - complementary region , which is up to 100 % complementary mirna probes of the invention can be or be at least 60 , 65 , 70 , 75 , 80 , 85 , 90 , 95 , or 100 % complementary to their target . the term “ combinations thereof ” as used herein refers to all permutations and combinations of the listed items preceding the term . for example , “ a , b , c , or combinations thereof ” is intended to include at least one of : a , b , c , ab , ac , bc , or abc , and if order is important in a particular context , also ba , ca , cb , acb , cba , bca , bac , or cab . unless otherwise noted , technical terms are used according to conventional usage . definitions of common terms in molecular biology may be found in benjamin lewin , genes v , published by oxford university press , 1994 ( isbn 0 - 19 - 854287 - 9 ); kendrew et al . ( eds . ), the encyclopedia of molecular biology , published by blackwell science ltd ., 1994 ( isbn 0 - 632 - 02182 - 9 ); and robert a . meyers ( ed . ), molecular biology and biotechnology : a comprehensive desk reference , published by vch publishers , inc ., 1995 ( isbn 1 - 56081 - 569 - 8 ). in order to facilitate review of the various embodiments of the disclosure , the following explanations of specific terms are provided : adjunctive therapy : a treatment used in combination with a primary treatment to improve the effects of the primary treatment . for example , a patient diagnosed with hcc may undergo liver resection as a primary treatment and antisense mir - 221 and mir - 222 therapy as an adjunctive therapy . candidate : as used herein , a “ candidate ” for therapy is a patient that has trail - resistant trail expression pattern . clinical outcome : refers to the health status of a patient following treatment for a disease or disorder , such as hcc , or in the absence of treatment . clinical outcomes include , but are not limited to , an increase in the length of time until death , a decrease in the length of time until death , an increase in the chance of survival , an increase in the risk of death , survival , disease - free survival , chronic disease , metastasis , advanced or aggressive disease , disease recurrence , death , and favorable or poor response to therapy . control : a “ control ” refers to a sample or standard used for comparison with an experimental sample , such as a tumor sample obtained from a patient having trail - resistant cancer . in some embodiments , the control is a liver sample obtained from a healthy patient or a non - cancerous tissue sample obtained from a patient diagnosed with hcc . in some embodiments , the control is a historical control or standard value ( i . e . a previously tested control sample or group of samples that represent baseline or normal values , such as the level trail expression pattern in non - cancerous tissue ). cytokines : proteins produced by a wide variety of hematopoietic and non - hematopoietic cells that affect the behavior of other cells . cytokines are important for both the innate and adaptive immune responses . decrease in survival : as used herein , “ decrease in survival ” refers to a decrease in the length of time before death of a patient , or an increase in the risk of death for the patient . detecting level of expression : for example , “ detecting the level of mir - 221 and mir - 222 expression ” refers to quantifying the amount of mir - 221 and mir - 222 present in a sample . detecting expression of mir - 221 and mir - 222 , or any microrna , can be achieved using any method known in the art or described herein , such as by qrt - pcr . detecting expression of mir - 221 and mir - 222 includes detecting expression of either a mature form of mir - 221 and mir - 222 or a precursor form that is correlated with mir - 221 and mir - 222 expression . typically , mirna detection methods involve sequence specific detection , such as by rt - pcr . mir - 221 and mir - 222 - specific primers and probes can be designed using the precursor and mature mir - 221 and mir - 222 nucleic acid sequences , which are known in the art and include modifications which do not change the function of the sequences . hepatocellular carcinoma ( hcc ): hcc is a primary malignancy of the liver typically occurring in patients with inflammatory livers resulting from viral hepatitis , liver toxins or hepatic cirrhosis ( often caused by alcoholism ). micrornas are generally 21 - 23 nucleotides in length . micrornas are processed from primary transcripts known as pri - mirna to short stem - loop structures called precursor ( pre )- mirna and finally to functional , mature microrna . mature microrna molecules are partially complementary to one or more messenger rna molecules , and their primary function is to down - regulate gene expression . micrornas regulate gene expression through the rnai pathway . mir - 221 and mir - 222 expression : as used herein , “ low mir - 221 and mir - 222 expression ” and “ high mir - mir - 221 and mir - 222 expression ” are relative terms that refer to the level of mir - 221 and mir - 222 found in a sample , such as a healthy or hcc liver sample . in some embodiments , low and high mir - 221 and mir - 222 expression are determined by comparison of mir - 221 and mir - 222 levels in a group of non - cancerous and hcc liver samples . low and high expression can then be assigned to each sample based on whether the expression of mir - 221 and mir - 222 in a sample is above ( high ) or below ( low ) the average or median mir - 221 and mir - 222 expression level . for individual samples , high or low mir - 221 and mir - 222 expression can be determined by comparison of the sample to a control or reference sample known to have high or low expression , or by comparison to a standard value . low and high mir - 221 and mir - 222 expression can include expression of either the precursor or mature forms or mir - 221 and mir - 222 , or both . patient : as used herein , the term “ patient ” includes human and non - human animals . the preferred patient for treatment is a human . “ patient ” and “ subject ” are used interchangeably herein . pharmaceutically acceptable vehicles : the pharmaceutically acceptable carriers ( vehicles ) useful in this disclosure are conventional . remington &# 39 ; s pharmaceutical sciences , by e . w . martin , mack publishing co ., easton , pa ., 15th edition ( 1975 ), describes compositions and formulations suitable for pharmaceutical delivery of one or more therapeutic compounds , molecules or agents . in general , the nature of the carrier will depend on the particular mode of administration being employed . for instance , parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water , physiological saline , balanced salt solutions , aqueous dextrose , glycerol or the like as a vehicle . for solid compositions ( for example , powder , pill , tablet , or capsule forms ), conventional non - toxic solid carriers can include , for example , pharmaceutical grades of mannitol , lactose , starch , or magnesium stearate . in addition to biologically - neutral carriers , pharmaceutical compositions to be administered can contain minor amounts of non - toxic auxiliary substances , such as wetting or emulsifying agents , preservatives , and ph buffering agents and the like , for example sodium acetate or sorbitan monolaurate . preventing , treating or ameliorating a disease : “ preventing ” a disease ( such as hcc ) refers to inhibiting the full development of a disease . “ treating ” refers to a therapeutic intervention that ameliorates a sign or symptom of a disease or pathological condition after it has begun to develop . “ ameliorating ” refers to the reduction in the number or severity of signs or symptoms of a disease . screening : as used herein , “ screening ” refers to the process used to evaluate and identify candidate agents that affect trail expression patterns . in some cases , screening involves contacting a candidate agent ( such as an antibody , small molecule or cytokine ) with trail - resistant cancer cells and testing the effect of the agent on trail expression patterns . expression of a microrna can be quantified using any one of a number of techniques known in the art and described herein , such as by microarray analysis or by qrt - pcr . small molecule : a molecule , typically with a molecular weight less than about 1000 daltons , or in some embodiments , less than about 500 daltons , wherein the molecule is capable of modulating , to some measurable extent , an activity of a target molecule . therapeutic agent : a chemical compound , small molecule , or other composition , such as an antisense compound , antibody , protease inhibitor , hormone , chemokine or cytokine , capable of inducing a desired therapeutic or prophylactic effect when properly administered to a subject . for example , therapeutic agents for trail - resistant cancer cells include agents that prevent or inhibit development or metastasis of trail - resistant cancer cells . as used herein , a “ candidate agent ” is a compound selected for screening to determine if it can function as a therapeutic agent for trail - resistant cancer cells . in some embodiments , the candidate agent is identified as a therapeutic agent if the agent converts the cell from in trail - resistant cancer cells . “ incubating ” includes a sufficient amount of time for an agent to interact with a cell or tissue . “ contacting ” includes incubating an agent in solid or in liquid form with a cell or tissue . “ treating ” a cell or tissue with an agent includes contacting or incubating the agent with the cell or tissue . therapeutically effective amount : a quantity of a specified pharmaceutical or therapeutic agent sufficient to achieve a desired effect in a subject , or in a cell , being treated with the agent . for example , this can be the amount of a therapeutic agent that decreases expression of mir - 221 and mir - 222 and c - jun or decreases the expression of mir - 221 and mir - 222 in conjunction with increasing pten and / or timp3 thereby prevents , treats or ameliorates trail - resistant cancer cells in a patient . the effective amount of the agent will be dependent on several factors , including , but not limited to the subject or cells being treated , and the manner of administration of the therapeutic composition . trail expression pattern : the comparative expression levels of four genes in a cell , cell culture , or tissue sample , including c - jun , mir - 221 and mir - 222 , pten and timp3 . trail - resistant trail expression pattern : is a trail expression pattern wherein c - jun and mir - 221 and mir - 222 expression is high , and pten and timp3 expression is low compared to control . trail resistant cancer cells , trail resistant cancer , trail resistant tumor cells or tumor , and the like : cells ( in vitro , in situ , in vivo ) which , if challenged with trail , no or little apoptosis in response to trail would be observed compared to control . this definition does not require trail challenge testing of every putative trail resistant cell in order to meet the definition ; rather , sampling , staining , phenotypic or genetic marker identification , known trail status , or any other suggestion of trail resistance , is within the meaning of this definition . trail - sensitive trail expression pattern : is a trail expression pattern wherein c - jun and mir - 221 and mir - 222 expression is low , and pten and timp3 expression is high compared to control . tumor , neoplasia , malignancy or cancer : the result of abnormal and uncontrolled growth of cells . neoplasia , malignancy , cancer and tumor are often used interchangeably and refer to abnormal growth of a tissue or cells that results from excessive cell division . the amount of a tumor in an individual is the “ tumor burden ” which can be measured as the number , volume , or weight of the tumor . a tumor that does not metastasize is referred to as “ benign .” a tumor that invades the surrounding tissue and / or can metastasize is referred to as “ malignant .” tumor - node - metastasis ( tnm ): the tnm classification of malignant tumors is a cancer staging system for describing the extent of cancer in a patient &# 39 ; s body . t describes the size of the primary tumor and whether it has invaded nearby tissue ; n describes any lymph nodes that are involved ; and m describes metastasis . tnm is developed and maintained by the international union against cancer to achieve consensus on one globally recognized standard for classifying the extent of spread of cancer . the tnm classification is also used by the american joint committee on cancer and the international federation of gynecology and obstetrics . in some embodiments , the control is non - cancerous tissue sample obtained from the same patient . in other embodiments , the control is a liver sample obtained from a healthy subject , such as a healthy liver donor . in another example , the control is a standard calculated from historical values . tumor samples and non - cancerous tissue samples can be obtained according to any method known in the art . for example , tumor and non - cancerous samples can be obtained from hcc patients that have undergone liver resection , or they can be obtained by extraction using a hypodermic needle , by microdissection , or by laser capture . control ( non - cancerous ) samples can be obtained , for example , from a cadaveric donor or from a healthy liver donor . in some embodiments , screening comprises contacting the candidate agents with cells . the cells can be primary cells obtained from a patient , or the cells can be immortalized or transformed cells . the candidate agents can be any type of agent , such as a protein , peptide , small molecule , antibody or nucleic acid . in some embodiments , the candidate agent is a cytokine . in some embodiments , the candidate agent is a small molecule . screening includes both high - throughout screening and screening individual or small groups of candidate agents . the sequences of precursor micrornas ( pre - mirnas ) and mature mirnas are publicly available , such as through the mirbase database , available online by the sanger institute ( see griffiths - jones et al ., nucleic acids res . 36 : d154 - d158 , 2008 ; griffiths - jones et al ., nucleic acids res . 34 : d140 - d144 , 2006 ; and griffiths - jones , nucleic acids res . 32 : d109 - d111 , 2004 ). detection and quantification of rna expression can be achieved by any one of a number of methods well known in the art ( see , for example , u . s . patent application publication nos . 2006 / 0211000 and 2007 / 0299030 , herein incorporated by reference ) and described below . using the known sequences for rna family members , specific probes and primers can be designed for use in the detection methods described below as appropriate . in some cases , the rna detection method requires isolation of nucleic acid from a sample , such as a cell or tissue sample . nucleic acids , including rna and specifically mirna , can be isolated using any suitable technique known in the art . for example , phenol - based extraction is a common method for isolation of rna . phenol - based reagents contain a combination of denaturants and rnase inhibitors for cell and tissue disruption and subsequent separation of rna from contaminants . phenol - based isolation procedures can recover rna species in the 10 - 200 - nucleotide range ( e . g ., precursor and mature mirnas , 5s and 5 . 8s ribosomal rna ( rrna ), and ui small nuclear rna ( snrna )). in addition , extraction procedures such as those using trizol ™ or trireagent ™, will purify all rnas , large and small , and are efficient methods for isolating total rna from biological samples that contain mirnas and small interfering rnas ( sirnas ). a microarray is a microscopic , ordered array of nucleic acids , proteins , small molecules , cells or other substances that enables parallel analysis of complex biochemical samples . a dna microarray consists of different nucleic acid probes , known as capture probes that are chemically attached to a solid substrate , which can be a microchip , a glass slide or a microsphere - sized bead . microarrays can be used , for example , to measure the expression levels of large numbers of messenger rnas ( mrnas ) and / or mirnas simultaneously . microarrays can be fabricated using a variety of technologies , including printing with fine - pointed pins onto glass slides , photolithography using pre - made masks , photolithography using dynamic micromirror devices , ink - jet printing , or electrochemistry on microelectrode arrays . microarray analysis of mirnas , for example ( although these procedures can be used in modified form for any rna analysis ) can be accomplished according to any method known in the art ( see , for example , pct publication no . wo 2008 / 054828 ; ye et al ., nat . med . 9 ( 4 ): 416 - 423 , 2003 ; calin et al ., n . engl . j . med . 353 ( 17 ): 1793 - 1801 , 2005 , each of which is herein incorporated by reference ). in one example , rna is extracted from a cell or tissue sample , the small rnas ( 18 - 26 - nucleotide rnas ) are size - selected from total rna using denaturing polyacrylamide gel electrophoresis . oligonucleotide linkers are attached to the 5 ′ and 3 ′ ends of the small rnas and the resulting ligation products are used as templates for an rt - pcr reaction with 10 cycles of amplification . the sense strand pcr primer has a fluorophore attached to its 5 ′ end , thereby fluorescently labeling the sense strand of the pcr product . the pcr product is denatured and then hybridized to the microarray . a pcr product , referred to as the target nucleic acid that is complementary to the corresponding mirna capture probe sequence on the array will hybridize , via base pairing , to the spot at which the capture probes are affixed . the spot will then fluoresce when excited using a microarray laser scanner . the fluorescence intensity of each spot is then evaluated in terms of the number of copies of a particular mirna , using a number of positive and negative controls and array data normalization methods , which will result in assessment of the level of expression of a particular mirna . in an alternative method , total rna containing the small rna fraction ( including the mirna ) extracted from a cell or tissue sample is used directly without size - selection of small rnas , and 3 ′ end labeled using t4 rna ligase and either a fluorescently - labeled short rna linker the rna samples are labeled by incubation at 30 ° c . for 2 hours followed by heat inactivation of the t4 rna ligase at 80 ° c . for 5 minutes . the fluorophore - labeled mirnas complementary to the corresponding mirna capture probe sequences on the array will hybridize , via base pairing , to the spot at which the capture probes are affixed . the microarray scanning and data processing is carried out as described above . there are several types of microarrays than be employed , including spotted oligonucleotide microarrays , pre - fabricated oligonucleotide microarrays and spotted long oligonucleotide arrays . in spotted oligonucleotide microarrays , the capture probes are oligonucleotides complementary to mirna sequences . this type of array is typically hybridized with amplified pcr products of size - selected small rnas from two samples to be compared ( such as non - cancerous tissue and hcc liver tissue ) that are labeled with two different fluorophores . alternatively , total rna containing the small rna fraction ( including the mirnas ) is extracted from the two samples and used directly without size - selection of small rnas , and 3 ′ end labeled using t4 rna ligase and short rna linkers labeled with two different fluorophores . the samples can be mixed and hybridized to one single microarray that is then scanned , allowing the visualization of up - regulated and down - regulated mirna genes in one assay . in pre - fabricated oligonucleotide microarrays or single - channel microarrays , the probes are designed to match the sequences of known or predicted mirnas . there are commercially available designs that cover complete genomes ( for example , from affymetrix or agilent ). these microarrays give estimations of the absolute value of gene expression and therefore the comparison of two conditions requires the use of two separate microarrays . spotted long oligonucleotide arrays are composed of 50 to 70 - mer oligonucleotide capture probes , and are produced by either ink jet or robotic printing . short oligonucleotide arrays are composed of 20 - 25 - mer oligonucleotide probes , and are produced by photolithographic synthesis ( affymetrix ) or by robotic printing . quantitative rt - pcr ( qrt - pcr ) is a modification of polymerase chain reaction used to rapidly measure the quantity of a product of polymerase chain reaction . qrt - pcr is commonly used for the purpose of determining whether a genetic sequence , such as a mir , is present in a sample , and if it is present , the number of copies in the sample . any method of pcr that can determine the expression of a nucleic acid molecule , including a mirna , falls within the scope of the present disclosure . there are several variations of the qrt - pcr method known in the art , three of which are described below . methods for quantitative polymerase chain reaction include , but are not limited to , via agarose gel electrophoresis , the use of sybr green ( a double stranded dna dye ), and the use of a fluorescent reporter probe . the latter two can be analyzed in real - time . with agarose gel electrophoresis , the unknown sample and a known sample are prepared with a known concentration of a similarly sized section of target dna for amplification . both reactions are run for the same length of time in identical conditions ( preferably using the same primers , or at least primers of similar annealing temperatures ). agarose gel electrophoresis is used to separate the products of the reaction from their original dna and spare primers . the relative quantities of the known and unknown samples are measured to determine the quantity of the unknown . the use of sybr green dye is more accurate than the agarose gel method , and can give results in real time . a dna binding dye binds all newly synthesized double stranded dna and an increase in fluorescence intensity is measured , thus allowing initial concentrations to be determined however , sybr green will label all double - stranded dna , including any unexpected pcr products as well as primer dimers , leading to potential complications and artifacts . the reaction is prepared as usual , with the addition of fluorescent double - stranded dna dye . the reaction is run , and the levels of fluorescence are monitored ( the dye only fluoresces when bound to the double - stranded dna ). with reference to a standard sample or a standard curve , the double - stranded dna concentration in the pcr can be determined the fluorescent reporter probe method uses a sequence - specific nucleic acid based probe so as to only quantify the probe sequence and not all double stranded dna . it is commonly carried out with dna based probes with a fluorescent reporter and a quencher held in adjacent positions ( so - called dual - labeled probes ). the close proximity of the reporter to the quencher prevents its fluorescence ; it is only on the breakdown of the probe that the fluorescence is detected . this process depends on the 5 ′ to 3 ′ exonuclease activity of the polymerase involved . the real - time quantitative pcr reaction is prepared with the addition of the dual - labeled probe . on denaturation of the double - stranded dna template , the probe is able to bind to its complementary sequence in the region of interest of the template dna . when the pcr reaction mixture is heated to activate the polymerase , the polymerase starts synthesizing the complementary strand to the primed single stranded template dna . as the polymerization continues , it reaches the probe bound to its complementary sequence , which is then hydrolyzed due to the 5 ′- 3 ′ exonuclease activity of the polymerase , thereby separating the fluorescent reporter and the quencher molecules . this results in an increase in fluorescence , which is detected . during thermal cycling of the real - time pcr reaction , the increase in fluorescence , as released from the hydrolyzed dual - labeled probe in each pcr cycle is monitored , which allows accurate determination of the final , and so initial , quantities of dna . in situ hybridization ( ish ) applies and extrapolates the technology of nucleic acid hybridization to the single cell level , and , in combination with the art of cytochemistry , immunocytochemistry and immunohistochemistry , permits the maintenance of morphology and the identification of cellular markers to be maintained and identified , and allows the localization of sequences to specific cells within populations , such as tissues and blood samples . ish is a type of hybridization that uses a complementary nucleic acid to localize one or more specific nucleic acid sequences in a portion or section of tissue ( in situ ), or , if the tissue is small enough , in the entire tissue ( whole mount ish ). rna ish can be used to assay expression patterns in a tissue , such as the expression of mirnas . sample cells or tissues are treated to increase their permeability to allow a probe , such as a mirna - specific probe , to enter the cells . the probe is added to the treated cells , allowed to hybridize at pertinent temperature , and excess probe is washed away . a complementary probe is labeled with a radioactive , fluorescent or antigenic tag , so that the probe &# 39 ; s location and quantity in the tissue can be determined using autoradiography , fluorescence microscopy or immunoassay . the sample may be any sample as herein described , such as a non - cancerous or hcc liver sample . since the sequences of mir - 26 family members are known , mir - 26 probes can be designed accordingly such that the probes specifically bind mir - 26 . in situ pcr is the pcr based amplification of the target nucleic acid sequences prior to ish . for detection of rna , an intracellular reverse transcription step is introduced to generate complementary dna from rna templates prior to in situ pcr . this enables detection of low copy rna sequences . prior to in situ pcr , cells or tissue samples are fixed and permeabilized to preserve morphology and permit access of the pcr reagents to the intracellular sequences to be amplified . pcr amplification of target sequences is next performed either in intact cells held in suspension or directly in cytocentrifuge preparations or tissue sections on glass slides . in the former approach , fixed cells suspended in the pcr reaction mixture are thermally cycled using conventional thermal cyclers . after pcr , the cells are cytocentrifuged onto glass slides with visualization of intracellular pcr products by ish or immunohistochemistry . in situ pcr on glass slides is performed by overlaying the samples with the pcr mixture under a coverslip which is then sealed to prevent evaporation of the reaction mixture . thermal cycling is achieved by placing the glass slides either directly on top of the heating block of a conventional or specially designed thermal cycler or by using thermal cycling ovens . detection of intracellular pcr products is generally achieved by one of two different techniques , indirect in situ pcr by ish with pcr - product specific probes , or direct in situ pcr without ish through direct detection of labeled nucleotides ( such as digoxigenin - 11 - dutp , fluorescein - dutp , 3h - ctp or biotin - 16 - dutp ), which have been incorporated into the pcr products during thermal cycling . use of mir - 221 and mir - 222 and c - jun , pten and timp3 as predictive markers of prognosis and for identification of therapeutic agents for treatment of trail resistant cancer cells it is disclosed herein that expression patterns of mir - 221 and mir - 222 , c - jun , pten and timp3 are predictors of survival prognosis in trail - resistant patients . trail resistant cancer cells samples ( for example , tissue biopsy samples ) with high mir - 221 and mir - 222 and c - jun expression , along with low pten and timp3 expression compared to non - cancerous tissue from the same subject or from a healthy subject , predicts a decrease in survival . thus , the trail resistant expression pattern status in tumors can be used as a clinical tool in trail - resistant cancer patients &# 39 ; prognosis . in some embodiments , the expression level of the markers herein in a trail - resistant tumor sample is directly compared with the trail resistant expression pattern in surrounding non - cancerous tissue from the same patient . in other embodiments , trail resistant expression pattern in the tumor sample is compared to the trail resistant expression pattern in a liver sample obtained from a healthy subject , such as a liver donor . in some cases , the non - cancerous tissue used as a control sample is obtained from a cadaver . in other embodiments , the trail resistant expression pattern in the tumor sample is compared with a standard level based on historical values . for example , the standard can be set based on average trail resistant expression pattern in non - cancerous liver tissue samples obtained from a cohort of subjects . for instance , the cohort of subjects can be a group of hcc patients enrolled in a clinical trial . the cohort of subject can also be a group of cadaveric donors . finding a trail resistant expression pattern in a hcc tumor sample relative to a control indicates a poor prognosis for the patient and identifies the patient as a good candidate for specialized therapy . as used herein , “ poor prognosis ” generally refers to a decrease in survival , or in other words , an increase in risk of death or a decrease in the time until death . poor prognosis can also refer to an increase in severity of the disease , such as an increase in spread ( metastasis ) of the cancer to other organs . in one embodiment , trail resistant expression pattern is found when the respective markers show at least a 1 . 5 - fold increase or decrease in expression relative to the control . in other embodiments , trail resistant expression pattern is indicated by at least a 2 - fold , at least a 2 . 5 - fold , at least a 3 - fold , at least a 3 . 5 - fold , or at least a 4 - fold increase or decrease in the markers of trail resistant expression pattern relative to the control . the finding that patients with trail resistant tumors having a trail sensitive expression pattern have a better chance of survival indicates that compounds that decrease c - jun , mir - 221 and mir - 222 expression in conjunction with increasing pten and timp3 expression will be useful as therapeutic agents for the treatment of trail resistant tumors . thus , provided herein is a method of identifying therapeutic agents for the treatment of trail resistant cancer cells , comprising screening candidate agents in vitro to select an agent that promote conversion from trail resistant trail expression pattern to trail sensitive trail expression pattern . in some embodiments , screening comprises contacting the candidate agents with trail resistant cancer cells and detecting any change trail expression pattern . the trail resistant cancer cells can be primary cells obtained from a patient , immortalized or transformed cells obtained from a patient , or the cells can be commercially available immortalized cell lines , such as , but not limited to mhcc97 , hepg2 , hep3b or snu - 423 cells . a conversion to trail sensitive expression pattern following treatment with the candidate agent identifies the agent as a therapeutic agent for the treatment of trail resistant cancer . methods of screening candidate agents to identify therapeutic agents for the treatment of disease are well known in the art . methods of detecting expression levels of rna and proteins are known in the art and are described herein , such as , but not limited to , microarray analysis , rt - pcr ( including qrt - pcr ), in situ hybridization , in situ pcr , and northern blot analysis . in one embodiment , screening comprises a high - throughput screen . in another embodiment , candidate agents are screened individually . the candidate agents can be any type of molecule , such as , but not limited to nucleic acid molecules , proteins , peptides , antibodies , lipids , small molecules , chemicals , cytokines , chemokines , hormones , or any other type of molecule that may alter trail expression pattern ( s ) either directly or indirectly . in some embodiments , the candidate agents are molecules that play a role in the nfκb / il - 6 signaling pathway . in other embodiments , the candidate agents are molecules that play a role in the il - 10 , stat3 or interferon - inducible factor signaling networks . in one embodiment , the candidate agents are cytokines . in another embodiment , the candidate agents are small molecules . also described herein is a method for the characterization of trail resistant cancer , wherein at least one feature of trail resistant cancer is selected from one or more of the group consisting of : presence or absence of trail resistant cancer ; diagnosis of trail resistant cancer ; prognosis of trail resistant cancer ; therapy outcome prediction ; therapy outcome monitoring ; suitability of trail resistant cancer to treatment , such as suitability of trail resistant cancer to chemotherapy treatment and / or radiotherapy treatment ; suitability of trail resistant cancer to hormone treatment ; suitability of trail resistant cancer for removal by invasive surgery ; suitability of trail resistant cancer to combined adjuvant therapy . also described herein is a kit for the detection of trail resistant cancer , the kit comprising at least one detection probe comprising c - jun and mir - 221 and mir - 222 or mir - 221 and mir - 222 and pten and / or timp3 . the kit can be in the form or comprises an oligonucleotide array . also described herein is a method for the determination of suitability of a trail resistant cancer patient for treatment comprising : i ) isolating at least one tissue sample from a patient suffering from trail resistant cancer ; ii ) performing the characterization of at least one tissue sample and / or utilizing a detection probe , to identify the trail expression pattern ; iii ) based on the at least one feature identified in step ii ), diagnosing the physiological status of the patient ; iv ) based on the diagnosis obtained in step iii ), determining whether the patient would benefit from treatment of the trail resistant cancer . in certain embodiments , the at least one feature of the cancer is selected from one or more of the group consisting of : presence or absence of the cancer ; type of the cancer ; origin of the cancer ; diagnosis of cancer ; prognosis of the cancer ; therapy outcome prediction ; therapy outcome monitoring ; suitability of the cancer to treatment , such as suitability of the cancer to chemotherapy treatment and / or radiotherapy treatment ; suitability of the cancer to hormone treatment ; suitability of the cancer for removal by invasive surgery ; suitability of the cancer to combined adjuvant therapy . also described herein is a method of for the determination of suitability of a cancer for treatment , wherein the at least one feature of the cancer is suitability of the cancer to treatment , such as suitability of the cancer to chemotherapy treatment and / or radiotherapy treatment ; suitability of the cancer to hormone treatment ; suitability of the cancer for removal by invasive surgery ; suitability of the cancer to combined adjuvant therapy . also described herein is a method for the determination of the likely prognosis of a cancer patient comprising : i ) isolating at least one tissue sample from a patient suffering from cancer ; and , ii ) characterizing at least one tissue sample to identify the trail expression pattern ; wherein the feature allows for the determination of the likely prognosis of the cancer patient . the following examples are provided to illustrate certain particular features and / or embodiments . these examples should not be construed to limit the disclosure to the particular features or embodiments described . to identify putative mir - 221 and mir - 222 targets , a bioinformatics search ( targetscan , pictar , rnhybrid ) was conducted . among the candidate targets , 3 ′- utrs of human pten ( nucleotides 200 - 207 , nm — 000314 ) and human timp3 ( nucleotides 2443 - 2449 , nm — 000362 ) contained regions that matched the seed sequences of hsa - mir - 221 and mir - 222 ( fig1 a ). to ascertain whether pten and timp3 are direct targets of mir - 221 and mir - 222 , pten and timp3 3 ′ utr containing the mir - 221 / mir - 222 binding sites were cloned downstream of the luciferase open reading frame . these reporter constructs were used to transfect meg01 cells , which express very low levels of mir - 221 and mir - 222 ( fig1 b ) and are highly transfectable ( freson et al ., 2005 ). increased expression of these mirs upon transfection , confirmed by qrt - pcr ( fig1 b ), significantly affected luciferase expression , measured as relative luciferase activity ( fig1 c ). conversely , when luciferase assays were performed by using a plasmid harboring the 3 ′ utr of pten and timp3 mrnas , where the binding sites for mir - 221 and mir - 222 were inactivated by site - directed mutagenesis , there was observed a consistent reduction in mir - 221 and mir - 222 inhibitory effect ( fig1 c ). to determine if these micrornas affect pten and timp3 expression in the h460 cellular environment , the consequences of the ectopic expression of mir - 221 and mir - 222 in h460 cells were analyzed . increased expression of these mirs upon transfection was confirmed by qrt - pcr ( fig1 d ) and then the effects on endogenous levels of pten and timp3 were analyzed by western blot ( fig1 e ); mir - 221 and mir - 222 over - expression significantly reduced the endogenous levels of pten and timp3 , compared to h460 cells transfected with scrambled pre - mir . conversely , knockdown of mir - 221 and mir - 222 by 2 ′- o - me - anti - mir - 221 and 2 ′- o - me - anti - mir - 222 , confirmed by qrt - pcr ( fig1 f ) in calu - 1 - lung derived cells with high levels of endogenous mir - 221 and mir - 222 , increased the protein levels of pten and timp3 ( fig1 g ). intriguingly , by quantitative rt - pcr , it was found that pten , but not timp3 mrna levels , were strongly reduced in the mir - 221 and mir - 222 transfected cells ( fig1 h ), indicating that mir - 221 and mir - 222 induce the degradation of pten mrna while timp3 is regulated by these micrornas only at the translational level . pten and timp3 3 ′ utrs are therefore direct targets of mir - 221 and mir - 222 . mir - 221 and mir - 222 are inversely correlated with pten and timp3 expression in nsclc and hcc the endogenous levels of mir - 221 and mir - 222 were evaluated by northern blot in large panels of primary nsclcs and hccs , compared with the normal counterpart . mir - 221 and mir - 222 expression was almost undetectable in normal lung and liver cells but highly expressed in the majority of tumor cell lines . moreover , as assessed by western blot , an inverse correlation between mir - 221 and mir - 222 rna expression and pten and timp3 protein expression was found in most cell lines analyzed ( fig2 a ), confirmed also by qrt - pcr ( fig2 b ). timp3 mrna expression levels was not tested because down - regulation of timp3 mrna after enforced mir - 221 and mir - 222 expression was not observed ( fig1 h ). these results indicate that high expression of mir - 221 and mir - 222 is one of the mechanisms acting to negatively regulate pten and timp3 in nsclc and hcc . to verify whether these micrornas affected pten and timp3 endogenous levels also in hcc , analysis of the effects of the ectopic expression of mir - 221 and mir - 222 in the sk - hep1 cell line , which expresses low levels of mir - 221 and mir - 222 , was performed . as shown in fig3 a , pten and timp3 proteins were reduced in sk - hep1 cells upon mir - 221 and mir - 222 over - expression . conversely , knockdown of mir - 221 and mir - 222 by 2 ′- o - me - anti - mir - 221 and 2 ′- o - me - anti - mir - 222 in snu - 387 cells , which expressed high levels of endogenous mir - 221 and mir - 222 , increased the protein level of pten and timp3 ( fig3 a ). having noted that mir - 221 and mir - 222 down - regulate pten and timp3 expression in both nsclc and hcc - derived cells in culture , regulation in vivo was studied . to answer this question , pten mrna and mir - 221 and mir - 222 expression by qrt - pcr in primary lung tumor specimens was studied , in comparison with normal human lung tissue samples . mir - 221 and mir - 222 were almost undetectable in normal human lung samples and highly expressed in all the tumor samples analyzed . of the 22 primary lung tumors examined , in fact , all exhibited down - regulation of pten and over - expression of mir - 221 and mir - 222 ( fig3 b ). these data further support the finding that pten is a direct target of mir - 221 and mir - 222 also in vivo . to corroborate these findings , in situ hybridization analysis was performed , by using 5 ′- dig - labeled lna probes , on hepatocarcinoma and normal liver tissues , followed by immunohistochemistry for pten and timp3 ( fig3 c ). mir - 221 / mir - 222 and pten / timp3 expressions were inversely related in liver cancers and the adjacent normal / cirrhotic liver tissues . liver cancer cells showed high expression of mir - 221 / mir - 222 and rarely expressed pten or timp3 ( fig3 cg - h - k - l ) whereas the adjacent non - malignant liver expressed pten and timp3 abundantly and rarely showed detectable mir - 221 / mir - 222 signal ( fig3 ca - b - e - f ). mir - 221 / mir - 222 and pten / timp3 expression were also inversely related in lung cancers and the adjacent normal lung tissues ( fig9 ). the majority of cancer cells were positive for mir - 221 and mir - 222 and negative for pten ( fig9 f - 9g ) and timp3 ( fig9 i - 9j ). in fig9 i - 9j mirna expression was evident in the cancer cells and timp3 expression in the surrounding cells . a strong mir - 222 signal ( large arrow ) was found in the nests of tumor cells that are infiltrating the adjacent fibrotic lung tissue ( fig9 k - 9l ). mir - 221 and mir - 222 induce trail resistance in nsclc and hcc by targeting pten and timp3 the effects of mir - 221 and mir - 222 and / or pten - timp3 silencing on cell survival and trail resistance in both nsclc and hcc were studied . first there was performed a proliferation assay on 5 hcc - derived cell lines , three of them ( hepg2 , sk - hep1 and huh 7 ) with low mir - 221 - mir - 222 expression and two ( plc / prf - 5 and snu - 387 ) with high mir - 221 - mir - 222 expression level ( fig4 a ). cells were exposed to trail for 24 hours and subsequently cell proliferation was assessed using an mtt assay . interestingly , cells expressing low levels of mir - 221 and mir - 222 underwent trail - induced cell death , showing a very low proliferation rate , whereas cells over - expressing mir - 221 and mir - 222 did not display sensitivity when exposed to soluble trail ( fig4 a ). moreover , annexin - fitc and caspase 3 / 7 assays on trail - sensitive cell lines sk - hep1 cells , ( fig4 b - 4c ), hepg2 and huh7 ( fig1 a - 10b ), revealed an increase of about 30 - 40 % in trail resistance after mir - 221 and mir - 222 over - expression , as well as after pten and timp3 silencing by pten and timp3 sirnas . trail - sensitive h460 cells also became more resistant to trail inducing - apoptosis after pten and timp3 knockdown , as determined by caspase 3 / 7 activity ( fig4 d ) and annexin - fitc assay ( fig4 e ), although pten silencing was more effective than timp3 . moreover , to further evaluate the contribution of these targets on trail - inducing apoptosis , pten and timp3 sequences were cloned in pcruz - ha plasmid ( santa cruz ) and used to transfect calu - 1 trail - resistant cells . calu - 1 cells became more sensitive to trail inducing - apoptosis after pten and timp3 restoration , alone or in combination , as determined by caspase 3 / 7 activity ( fig4 d ) and annexin - fitc staining ( fig1 a - 11b ). to further investigate the role of timp3 in trail - inducing apoptosis the expression of caspase - 3 ,- 8 - 9 , poly - adp - ribose polymerase ( parp ) and some of the molecule involved in the trail - signaling pathway were tested by western blot after timp3 overexpression in calu - 1 cell line ( fig1 c ). interestingly , the activation of parp and the caspase cascade were observed , as assessed by the appearance of the cleaved fragments . moreover , mc1 - 1 expression was down - regulated while cytochrome c expression increased ( fig1 c ). all together these results suggest an involvement of timp3 in both the extrinsic and intrinsic apoptotic pathways and highlight its role in trail - inducing apoptosis . the same results were obtained after timp3 restoration in snu - 387 cells ( data not shown ). further , the expression and / or the activation of some of the proteins involved in the pi3k / akt pathway after mir - 221 and mir - 222 enforced expression in h460 cells or after mir - 221 / mir - 222 silencing in snu - 387 cells was conducted . as shown in fig5 a , the expression levels of pi3k , akt and its phosphorylated substrate , phospho - glycogen synthase kinase 3 , were elevated by ectopic expression of mir - 221 and mir - 222 , and , in contrast , were decreased by knockdown of mir - 221 and mir - 222 in snu - 387 cells , indicating that mir - 221 and mir - 222 target the pten / akt pathway ( fig5 b ). further investigation of the activation and expression levels of these proteins was conducted . there was found an increase in erks phosphorylation and pak1 expression , as compared with h460 cells transfected with the control mir ( fig5 c ). interestingly , increased expression of metallopeptidase 3 and metallopeptidase 9 was also found , as possible result of timp3 down - regulation ( fig5 a - 5c ). to test if the activation of the previous proteins was pten and / or timp3 - dependent , pten and timp3 were silenced in h460 cells . as shown in fig5 d and e the activation of the erks and pak1 is both pten and timp3 - dependent , while akt phosphorylation is pten - dependent and mmp3 and mmp9 are upregulated after timp3 knockdown . finally , akt inhibition was studied , as it relates to whether it could override mir - 221 and mir - 222 - induced cell survival and trail - resistance . calu - 1 and snu - 387 were transfected with 2 ′- o - methyl ( 2 ′- o - me )- anti - mir - 221 and mir - 222 oligoribonucleotides . cells transfected with 2 ′- o - me - scrambled mir were used as control . blocking mir - 221 and mir - 222 expression considerably sensitized these cells to trail - induced apoptosis , as assessed by caspase 3 / 7 assay ( fig5 f - 5g ). moreover , calu - 1 and snu - 387 cells were treated with the specific akt inhibitor , api - 2 / triciribine , with or without trail . as shown in fig5 f and 5g , api - 2 abrogated mir 221 and mir - 222 - activated akt and significantly inhibited mir - 221 and mir - 222 - induced cell survival and trail resistance . next , to directly compare the growth of tumors with and without pten and timp3 , short hairpin rna ( shrna ) constructs , designed to knockdown gene expression , were used to silence pten and timp3 in h460 cells . an shrna plasmid , encoding a scrambled shrna sequence that does not lead to the specific degradation of any known cellular mrna , was used as control . the consequences of pten and timp3 disruption on tumor growth and trail resistance was assessed in vivo by implanting h460 pten and timp3 knockdown cells into the right dorsal sides of nude mice . trail treatment was initiated 5 days afterwards , when lung carcinoma had been established . pten and timp3 loss ( fig1 a ) conferred not only a significant tumor growth advantage but also resistance to trail - inducing apoptosis over control tumors ( fig1 b - 12 c - 12 d - 2 e - 12 f - 12 g ). in conclusion , pten and timp3 are important targets in trail resistance and play an important role in tumorigenicity of nsclc and hcc cells . pten and timp3 down - regulation by mir - 221 and mir - 222 induces migration and invasiveness in nsclc and hcc cells to directly test the functional role of mir - 221 / mir - 222 in tumorigenesis , these two micrornas were over - expressed , or pten and timp3 were silenced , in h460 and sk - hep1 cells . then , by cell cycle analysis , mir - 221 and mir - 222 and pten sirna h460 transfected cells showed a decrease of g1 and a corresponding increase of the s and g2 - m phases ( fig6 a ). after 72 h of transfection the analysis revealed an earlier onset of dna synthesis induced by mir - 221 and mir - 222 or pten knockdown , paralleled by a faster reduction of g1 cells , contributing to the proliferative advantage ( fig6 a ). the same change was observed in sk - hep1 cells ( fig1 a ). next , the inventors analyzed the effects of mir - 221 and mir - 222 over - expression on cellular migration and invasion of nsclc and hcc cells . interestingly , a significant increase on the migratory ( fig6 b - 6c ) and invasive ( fig6 d ) capabilities of h460 and sk - hep1 ( fig1 b ) cells after mir - 221 and mir - 222 overexpression as well after pten and timp3 downregulation was observed . conversely , when mir - 221 and mir - 222 were down - regulated by transfection with 2 ′- o - me - anti - mir - 221 and mir - 222 , a decrease in cell migration and invasion in both calu - 1 and snu - 387 cells ( fig1 a - 14b ) was observed . met was silenced by using sirna , in calu - 1 and snu - 387 cells and in a gastric cell line ( gtl16 ), previously reported to over - express met oncogene due to dna amplification ( giordano et al ., 1989 ). first , mir - 221 and mir - 222 expression levels were evaluated by qrt - pcr . after met knockdown , mir - 221 and mir - 222 expression was down - regulated in all cell lines analyzed ( fig7 a - 7 b - 7 c ). the same result was obtained by treating gtl16 cells with a met inhibitor , su11274 ( fig1 a ). secondly , by immunostaining , there was observed increased pten and timp3 expression levels after met down - regulation or inhibition , indicating that met is involved in mir - 221 and mir - 222 activation ( fig7 d - 7 e - 7 f ). next , by bioinformatics search ( tess database : http :// www . cbil . upenn . edu / cgi - bin / tess / tess ), it was found that the only transcription factor involved in the met pathway predicted to bind and transcriptionally activate mir - 221 / mir - 222 promoter was ap - 1 . ap - 1 is a dimeric basic region - leucine zipper protein that belongs to the jun and fos subfamilies c - jun is the most potent transcriptional activator in its group . to identify which factor belonging to the ap - 1 family was involved in mir - 221 / mir - 222 transcriptional activation , the correlation between mir - 221 and mir - 222 expression and c - jun and c - fos protein levels in 4 different cell lines ( h460 , calu - 1 , huh7 and snu - 387 ) ( figure s 7 b ) was studied . calu - 1 , highly expressing c - jun and c - fos , were co - transfected with met sirna , c - jun sirna or c - fos sirna . subsequent qrt - pcr amplification showed that met and c - jun down - regulation , but not c - fos knockdown , gave rise to a reduction of ˜ 45 - 50 % in mir - 221 and mir - 222 expression levels , as compared with the negative control ( figure s 7 c ). to further confirm these results luciferase assays were conducted . in previous work , the inventors found that mir - 221 and mir - 222 are transcribed into a single species of 2 . 1 kb rna and the transcription is regulated by the upstream sequence located at − 150 bp / 50 bp from the 5 ′ end of mir - 222 hairpin structure . to determine if the previously identified mir - 221 and mir - 222 promoter region was affected by met / ap1 , the luciferase assay was performed by using the reporter plasmids containing the fragments spanning + 3 ˜− 150 , + 3 ˜− 600 , + 3 ˜− 1000 (+ 1 position corresponds to the 5 ′ terminus of mir - 222 hairpin ) ( fig7 g ) into the pgl3basic vector which harbors the promoter - less luciferase gene ( di leva et al ., unpublished data ). the pgl3b , − 150 , − 600 and − 1000 pgl3b were co - transfected with met sirna , c - jun sirna or c - fos sirna into calu - 1 cells ( fig1 d - 15e ). subsequent luciferase assays showed that met and c - jun down - regulation gave rise to a reduction of ˜ 45 % in luciferase activity , as compared to the basal activity determined by transfection with pgl3b empty vector ; the inventors did not observe a reduction of luciferase activity after c - fos sirna transfection ( fig1 d - 15e ). these data indicate that c - jun and not c - fos is the transcription factor involved in the met pathway , responsible for mir - 221 and mir - 222 activation in nsclc and hcc cells . since the promoter region was responsive to c - jun modulation , to verify a direct binding of c - jun on mir - 221 and mir - 222 promoter , a chromatin immunoprecipitation ( chip ) assays was conducted . first , by bioinformatics analysis , it was found that only one ap - 1 putative binding site is located ˜ 130 bp upstream of the premir - 222 - 5 ′ end . taking into account the predicted ap - 1 binding site , a total of 2 chromatin regions were analyzed ( fig7 g ): one spanning the ap - 1 binding site and the second , as negative control , ˜ 1700 nt upstream of the pre - mir - 222 - 5 ′ end , where the inventors did not find any predicted binding site for ap - 1 . the chip assay of c - jun positive calu - 1 and snu - 387 cells showed remarkable ap - 1 binding at chip analyzed region 2 , proximal to the promoter ( fig7 h - 7i ). no chromatin enrichment by c - jun chip was observed in c - jun negative h460 cells , verifying the specificity of the chip assay . finally , huh7 cells , which show low levels of mir - 221 and mir - 222 , were treated with anisomycin , an antibiotic able to activate jnk kinases , and , thus ap - 1 , mir - 221 and mir - 222 and pten - timp3 expression levels were checked . after c - jun activation ( fig7 m ) by anisomycin , mir - 221 and - 222 expression increased ( mir - 221 = 80 %, mir - 222 = 40 %) as confirmed by qrt - pcr ( fig7 l ), while pten and timp3 expression levels were decreased drastically ( fig7 m ). to further prove that jnk is the intermediate signaling factor between c - met and c - jun and that c - jun knockdown leads to increased pten and timp3 expression , c - met and c - jun in calu - 1 cells were studied and the jnk1 / 2 phosphorylation and pten and timp3 expression were analyzed , respectively . as shown in figure s 7 f , met knockdown reduces jnk1 / 2 phosphorylation while c - jun silencing increases pten / timp3 expression as result of mir - 221 and mir - 222 down modulation . to investigate whether there is a direct relation between met and pten / timp3 in vivo , immunohistochemistry analysis was performed on lung and liver cancer and normal samples . the co - labeling met / pten and met / timp3 showed that pten and timp3 are abundantly expressed only in the normal cells , where met is not present , whereas c - met is expressed exclusively in the cancer cells ( fig1 ). these data confirm that met is implicated in mir - 221 and mir - 222 regulation , at least in part through jnk , ap - 1 and in particular c - jun transcription factor . the 3 ′ utr of the human pten and timp3 genes were pcr amplified using the following primers : pten fw 5 ′- tct aga gac tct gat cca gag aat gaa cc - 3 ′ [ seq id no : 1 ] and pten rw 5 ′- tct aga gtt gcc aca agt gca aag ggg tag gat gtg - 3 ′ [ seq id no : 2 ]; timp3 fw 5 ′- tct aga ctg ggc aaa gaa ggg tct ttc gca aag c - 3 ′ [ seq id no : 3 ] and timp3 rw 5 ′ tct aga ttc caa tag gga gga ggc tgg agg agt ctc - 3 ′ [ seq id no : 4 ] and cloned downstream of the renilla luciferase stop codon in pgl3 control vector ( promega ), giving rise to the p3 ′ utr - pten and p3 ′ utr - timp3 plasmids . these constructs were used to generate , by inverse pcr , the p3 ′- utrmut - pten plasmid - primers : fw : 5 ′- gtt gaa aaa agg ttg ggg gcg ggt gtc atg tat ata c - 3 [ seq id no : 5 ]; rw : 5 ′- gta tat aca tga cac ccg ccc cca acc ttt ttt caa c - 3 ′[ seq id no : 6 ]; p3 ′- utrmut - timp3 plasmid - primers : fw : 5 ′- gta taa ttt aaa atc att ggg cgg cgg gag aca ctt ctg tat ttc - 3 ′ [ seq id no : 7 ]; rw : 5 ′- gaa ata cag aag tgt ctc ccg ccg ccc aat gat ttt aaa tta tac - 3 ′ [ seq id no : 8 ]. meg01 cells were cotransfected with 1 μg of p3 ′ utr - pten or p3 ′ utr - timp3 and with p3 ′ utrmut - pten or p3 ′ utr timp3 plasmids and 1 μg of a renilla luciferase expression construct prl - tk ( promega ) by using lipofectamine 2000 ( invitrogen ). cells were harvested 24 h post - transfection and assayed with dual luciferase assay ( promega ) according to the manufacturer &# 39 ; s instructions . three independent experiments were performed in triplicate . a total of 32 snap - frozen normal and malignant lung tissues ( 19 men and 13 women , median age : 70 . 0 , range : 55 - 82 ) and 60 snap - frozen normal and 60 malignant liver tissues were collected at the ohio state university medical center ( columbus , ohio ). other 72 cancer and normal ( 24 ) lung tissues were purchased from us biomax , inc . all human tissues were obtained according to a protocol approved by the ohio state institutional review board . animal studies were performed according to institutional guidelines . nci - h460 cells were stable transfected by using shpten and timp3 plasmids ( santa cruz ); calu - 1 cells were stable transfected with shmet . after the selection in puromycin for 10 days 5 106 ( h460 ) or 7106 ( calu - 1 ) viable cells were injected s . c . into the right flanks of 6 - wk - old male nude mice ( charles riverbreeding laboratories , wilmington , mass .). treatment started five days ( h460 xenograft ) or ten days ( calu - 1 xenograft ) from tumor cell inoculation by daily ip injections of trail / apo2 ( 10 mg / kg / d ) or vehicle ( pbs ) for two cycles of 5 days . tumor size was assessed every five days by a digital caliper . the tumor volumes were determined by measuring the length ( 1 ) and the width ( w ) and calculating the volume ( v = lw2 / 2 ). 35 days after injection , mice were sacrificed and tumors samples were analyzed by western blot for pten , timp3 and met expression . statistical significance between control and treated animals was evaluated by using student &# 39 ; s t test . animal experiments were conducted after approval of the institutional animal care and use committee , ohio state university . student &# 39 ; s t - test and one - way anova analysis was used to determine significance . all error bars represent the standard error of the mean . pearson correlation coefficient was calculated to test the association between mir - 221 / mir - 222 and pten in the classes normal versus tumor . statistical significance for all the tests , assessed by calculating p - value , was & lt ; 0 . 05 . total proteins from nsclc and hcc cells were extracted with radioimmuno - precipitation assay ( ripa ) buffer ( 0 . 15 mm nacl , 0 . 05 mm tris - hcl , ph 7 . 5 , 1 % triton , 0 . 1 % sds , 0 . 1 % sodium deoxycholate and 1 % nonidet p40 ). sample extract ( 50 μg ) was resolved on 7 . 5 - 12 % sds - polyacrylamide gels ( page ) using a mini - gel apparatus ( bio - rad laboratories ) and transferred to hybond - c extra nitrocellulose . membranes were blocked for 1 h with 5 % nonfat dry milk in tris - buffered saline containing 0 . 05 % tween 20 , incubated overnight with primary antibody , washed and incubated with secondary antibody , and visualized by chemiluminescence . the following primary antibodies were used : anti - pten , anti - c - jun , anti - p - c - jun , anti - fos , anti - p - jnk , anti - mmp3 , anti - mc1 - 1 ( santa cruz ), anti - timp3 ( millipore ) anti - pi3k ( bd biosciences ), anti - erks , anti - phospho erks , anti - akt , anti - p - akt , anti - gsk3b , anti - p - gsk3b ( ser9 ), anti - pak1 anti - caspase - 8 ,- 3 and - 9 , anti - parp , anti - cytochrome c ( cell signaling ) and anti - mmp9 , anti - fadd ( abcam ), anti - 1 - actin antibody ( sigma ). a secondary anti - rabbit or anti - mouse immunoglobulin g ( igg ) antibody peroxidase conjugate ( chemicon ) was used . dna fragments containing the putative regulatory region upstream to mir - 222 / mir - 221 ( from + 1 ˜− 150 nt , + 1 ˜− 600 , + 1 ˜− 1000 (+ 1 position corresponds to the 5 ′ terminus of mir - 222 hairpin ) were amplified and cloned in pgl3basic ( promega ). meg01 cells were transfected with lipofectamine 2000 ( invitrogen ), 1 . 0 g of pgl3basic empty vector or of pgl3 containing the above genomic fragments , 200 ng of renilla luciferase expression construct prl - tk ( promega ) and met , c - jun , c - fos sirnas . after 48 h , 4 cells were lysed and assayed with dual luciferase assay ( promega ) according to the manufacturer &# 39 ; s instructions . three independent experiments were performed in triplicate . the primers utilized for the cloning were the followings : real - time pcr was performed using a standard taqman pcr kit protocol on an applied biosystems 7900ht sequence detection system ( applied biosystems ). the 10 μl pcr reaction included 0 . 67 μl rt product , 1 μl taqman universal pcr master mix ( applied biosystems ), 0 . 2 mm taqman probe , 1 . 5 mm forward primer and 0 . 7 mm reverse primer . the reactions were incubated in a 96 - well plate at 95 ° c . for 10 mm , followed by 40 cycles of 95 ° c . for 15 s and 60 ° c . for 1 min . all reactions were run in triplicate . the threshold cycle ( ct ) is defined as the fractional cycle number at which the fluorescence passes the fixed threshold . the comparative ct method for relative quantization of gene expression ( applied biosystems ) was used to determine mirna expression levels . the y axis represents the 2 (- ct ), or the relative expression of the different mirs . mirs expression was calculated relative to u44 and u48 rrna and multiplied by 104 . experiments were carried out in triplicate for each data point , and data analysis was performed by using software ( bio - rad ). total rna was extracted with trizol solution ( invitrogen according to the manufacturer &# 39 ; s instructions and the integrity of rna was assessed with an agilent bioanalizer 2100 ( agilent , palo alto , calif ., usa ). northern blotting was performed as described by calin et al ., 2002 . the oligonucleotides used as probes were the complementary sequences of the mature mirna ( mirna registry ): 2 ′- o - methyl ( 2 ′- o - me ) oligoribonucleotides were synthesized by fidelity . the sequences of 2 ′- o - me - anti - mir - 221 and 2 ′- o - me - anti - mir - 222 are as follows : 2 ′- o - me - gfp mir ( 5 ′- aaggcaagcugacccugaagu [ seq id no : 17 ]) was used as control . cells were grown in six well plate ( 1 . 7 × 10 6 per well ) for 24 h and transfected 100 nmoli / l / well of 2 ′- o - me - oligoribonucleotides using lipofectamine 2000 . rna and proteins were extracted after 72 h from the transfection . cells were plated in 96 - well plates in triplicate and incubated at 37 ° c . in a 5 % co 2 incubator . super - killer trail ( alexis biochemicals ) was used for 24 - 48 h at 400 ng ml - 1 . cell viability was examined with 3 -( 4 , 5 - dimethylthiazol - 2 - yl )- 2 , 5 - dipheniltetrazolium bromide ( mtt )- cell titer 96 aqueous one solution cell proliferation assay ( promega ), according to the manufacturer &# 39 ; s protocol . metabolically active cells were detected by adding 20 μl of mtt to each well . after 1 h of incubation , the plates were analyzed in a multilabel counter ( bio - rad laboratories ). apoptosis was assessed using annexin v - fitc apoptosis detection kits followed by flowcytometric analysis and caspase 3 / 7 activity . cells were seeded at 1 . 8106 cells per 100 mm dish , grown overnight in 10 % fbs / rpmi , washed with phosphate - buffered saline ( pbs ) and then treated for 24 h with 400 ng / ml trail . following incubation , cells were washed with cold pbs and removed from the plates by trypsinization . the resuspended cells were washed with cold pbs and stained with fitc - conjugated annexin v antibody according to the manufacturer &# 39 ; s instructions ( roche applied science ). cells ( 5 × 10 5 per sample ) were then subjected to flow cytometric analysis . flow cytometry analyses were done as described ( garofalo et al ., 2007 ). the fraction of h460 cells treated with trail was taken as the apoptotic cell population . the percentage of apoptosis indicated was corrected for background levels found in the corresponding untreated controls . statistical analysis was done using two sample t test , assuming equal variance , and p value was calculated based on two - tailed test . for detection of caspase 3 / 7 activity , cells were cultured in 96 - well plates and treated with trail 400 ng / ml and analyzed using caspase - glo 3 / 7 assay kit ( promega ) according to the manufacturer &# 39 ; s instructions . continuous variables are expressed as mean values ± standard deviation ( s . d .). chromatin immunoprecipitation was performed as described by de belle et al ., 2000 with slight modifications . cells ( 5106 ) from h460 , calu - 1 and snu - 387 cell lines were fixed in 1 % formaldehyde for 10 min at 37 ° c . cells were washed with ice - cold 1 pbs , scraped in 1 × pbs plus protease inhibitors , and collected by centrifugation . cell pellets , resuspended in cell lysis buffer [ 50 mmol / l tris - hcl ( ph 8 . 0 ), 10 mmol / l edta , and 1 % sds ] plus protease inhibitors , were then sonicated . dna - protein complexes were immunoprecipitated using 5 g of the anti - c - jun antibody ( santa cruz ) or with rabbit polyclonal igg control ( zymed ). cross - links in the immunoprecipitated chromatin were reversed by heating with proteinase k at 65 ° c . overnight , and dna was purified by the minelute reaction cleanup column ( qiagen ) and resuspended in water . the purified chromatin was subjected to pcr and the products were analyzed by gel electrophoresis using 2 % agarose . the following primers were used : cells were cultured to 80 % confluence and transiently transfected using lipofectamine 2000 with 100 nm anti - pten or with 100 nm anti - timp3 smartpool sirnas or control sirnas ( dharmacon ), a pool of four target specific 20 - 25 nt sirnas designed to knock down gene expression . mirna locked nucleic acid in situ hybridization of formalin fixed , paraffin - embedded tissue section . in situ hybridization ( ish ) was carried out on deparaffinized human lung and liver tissues using previously published protocol ( nuovo et al ., 2009 ), which includes a digestion in pepsin ( 1 . 3 mg / ml ) for 30 minutes . the sequences of the probes containing the six dispersed locked nucleic acid ( lna ) modified bases with digoxigenin conjugated to the 5 ′ end were : the probe cocktail and tissue mirna were co - denatured at 60 ° c . for 5 minutes , followed by hybridization at 37 ° c . overnight and a low stringency wash in 0 . 2 × ssc and 2 % bovine serum albumin at 4 ° c . for 10 minutes . the probe - target complex was seen due to the action of alkaline phosphatase on the chromogen nitroblue tetrazolium and bromochloroindolyl phosphate ( nbt / bcip ). negative controls included the use of a probe which should yield a negative result in such tissues . no counterstain was used , to facilitate co - labeling for pten , timp3 and met proteins . after in situ hybridization for the mirnas , as previously described ( nuovo et al ., 2009 ), the slides were analyzed for immunohistochemistry using the optimal conditions for pten ( 1 : 800 , cell conditioning for 30 minutes ), timp3 ( 1 : 1300 , cell conditioning for 30 minutes ) and met ( 1 : 20 , cell conditioning for 30 minutes ). for the immunohistochemistry , the inventors used the ultrasensitive universal fast red system from ventana medical systems . the inventors used normal liver and lung tissues as controls for these proteins . the percentage of tumor cells expressing pten , timp3 and mir - 221 and mir - 222 was then analyzed with emphasis on co - localization of the respective targets ( mir - 221 or mir - 222 and either pten or timp3 ). media , sera and antibiotics for cell culture were from life technologies , inc . ( grand island , n . y ., usa ). protein electrophoresis reagents were from bio - rad laboratories ( richmond , va ., usa ) and western blotting and ecl reagents from ge healthcare ( piscataway , n . j ., usa ). all other chemicals were from sigma ( st louis , mo ., usa ). human calu - 1 and a549 cell lines were grown in dulbecco &# 39 ; s modified eagle &# 39 ; s medium containing 10 % heat - inactivated fetal bovine serum ( fbs ) and with 2 mm l - glutamine and 100 uml - 1 penicillin - streptomycin . he1299 , h460 , a459 , h1975 , h1299 , h1573 , h23 , plcrf15 , snu - 387 , snu - 423 , snu - 475 cell lines were grown in rpmi containing 10 % heat - inactivated fbs and with 2 mm l - glutamine and 100 uml - 1 penicillin - streptomycin . sk - hepl , hep - g2 , hepg2c3a , hep3b , huh7 were grown in mem supplemented with 10 % fetal bovine serum , 2 mm l - glutamine and 100 uml - 1 penicillin - streptomycin . normal hepatocytes were grown in hepatocytes growth medium ( sciencell ) supplemented with 10 % fetal bovine serum , 2 mm l - glutamine , 1 % of hepatocyte growth supplement ( hgs ) and 100 uml - 1 penicillin - streptomycin . transwell insert chambers with 8 - nm porous membrane ( greiner bio - one ) were used for the assay . cells were washed three times with pbs and added to the top chamber in serum - free media . the bottom chamber was filled with media containing 10 % fbs . cells were incubated for 24 h at 37 ° c . in a 5 % co2 humidified incubator . to quantify migrating cells , cells on the top chamber were removed by using a cotton - tipped swab , and the migrated cells were fixed in pbs , 25 % glutaraldehyde and stained with crystal violet stain , visualized under a phase - contrast microscope , and photographed . cristal violet - stained cells were moreover solubilized in acetic acid and methanol ( 1 : 1 ) and absorbance was measured at 595 nm . the results are means of three independent experiments ± s . d . h460 and sk - hep - 1 cells were placed into the top chamber of a bd falcon hts fluoroblok insert with a membrane containing 8 - nm pores ( bd biosciences ) in 300 l of serum - free dulbecco &# 39 ; s modified eagle medium in triplicate . the inserts were placed into the bottom chamber wells of a 24 - well plate containing dulbecco &# 39 ; s modified eagle medium media and fetal bovine serum ( 10 %) as chemoattractant . cells that migrated through the pores of the membrane to the bottom chamber were labeled with 8 g / ml calcein - am ( molecular probes , eugene , oreg .) in phosphate - buffered saline ( pbs ) for 30 minutes at 37 ° c . the fluorescence of migrated cells was quantified using a fluorometer at excitation wavelengths of 485 nm and emission wavelengths of 530 nm and expressed as arbitrary fluorescence units . data are expressed as mean ± standard error of 4 separate determinations . pten and timp3 cdnas were obtained from h460 cells rna by using the one step rt - pcr kit ( invitrogen ) according to the manufacturer &# 39 ; s instructions . the pcr fragments were amplified by using the following primers : and then cloned in pcruz - ha ( santa cruz ) after digestion with noti - xbai ( pten ) or noti - bglii ( timp3 ). all vectors were controlled by sequencing . bioinformatic analysis was performed by using these specific programs : targetscanl , pictar2 and rnhybrid3 . 1 http :// www . targetscan . org / 2 http :// pictar . bio . nyu . edu / 3 http :// bibiserv . techfak . uni - bielefeld . de / method of treating hcc in patients exhibiting trail sensitive trail expression pattern in hcc tumor samples this example describes a method of selecting and treating hcc patients that are likely to have a favorable response to trail treatment as a therapy . for some hcc patients , trail therapy can prolong survival ( sun et al ., j . cancer res . clin . oncol . 132 ( 7 ): 458 - 465 , 2006 ). however , it would be beneficial to identify patients that are most likely to benefit from trail therapy prior to initiating treatment . it is now disclosed herein that the prognosis of hcc patients expressing trail sensitive trail expression pattern in tumor samples relative to a control ( such as non - cancerous liver tissue obtained from the same patient ) significantly improves after treatment with trail . in contrast , patients expressing trail resistant trail expression pattern in tumor samples do not exhibit a significant increase in survival following trail treatment and thus are not good candidates for such adjunctive treatment . a patient diagnosed with hcc first undergoes liver resection with an intent to cure . hcc tumor and non - cancerous tissue samples are obtained from the portion of the liver tissue removed from the patient . rna is then isolated from the tissue samples using any appropriate method for extraction of small rnas that are well known in the art , such as by using trizol ™. purified rna is then subjected to rt - pcr using primers specific for c - jun and mir - 221 and mir - 222 , optionally in conjunction with pten and / or timp3 . the assay may also be run with mir - 221 and mir - 222 and pten and / or timp3 , without c - jun . these assays are run to determine the expression level of the pertinent rna in the tumor and non - cancerous tissues . if trail sensitive expression pattern is found in the tumor tissue relative to the non - cancerous tissue , the patient is a candidate for trail adjunctive therapy . accordingly , the patient is treated with a therapeutically effective amount of trail a according to methods known in the art . the dose and dosing regimen of trail will vary depending on a variety of factors , such as health status of the patient and the stage of the hcc . typically , trail is administered in many doses over time . alternative treatment method for hcc patients with low expression of mir - 26 this example describes a method of treating a patient diagnosed with hcc in the absence of liver resection . to determine whether a patient diagnosed with hcc is a good candidate for trail therapy , a hcc tumor sample is obtained from the patient that has not undergone liver resection , along with a non - cancerous liver tissue sample . the tissue samples can be obtained according to any method known in the art . for example , the tissue samples can be obtained by performing a biopsy procedure using a hypodermic needle to remove the desired tissues . rna is then isolated from the tissue samples using any appropriate method for extraction of small rnas that are well known in the art , such as by using trizol ™. purified rna is then subjected to rt - pcr using primers specific for mir - 26 to determine the expression level of mir - 26 in the tumor and non - cancerous tissues . if trail sensitive trail expression pattern is found in the tumor tissue relative to the non - cancerous tissue , the patient is a candidate for therapy . accordingly , the patient is treated with a therapeutically effective amount of therapeutic according to methods known in the art . the dose and dosing regimen will vary depending on a variety of factors , such as health status of the patient and the stage of the hcc . typically , treatment is administered in many doses over time . method of treating hcc in patients exhibiting trail resistant trail expression pattern in hcc tumor samples this example describes a method of treating a patient diagnosed with hcc if the patient exhibits a trail resistant trail expression pattern in the hcc tumor . a patient diagnosed with hcc first undergoes liver resection with an intent to cure . hcc tumor and non - cancerous tissue samples are obtained from the portion of the liver tissue removed from the patient . rna is then isolated from the tissue samples using any appropriate method for extraction of small rnas that are well known in the art , such as by using trizol ™. purified rna is then subjected to rt - pcr using primers specific for mir - 26 to determine the expression level of mir - 26 in the tumor and non - cancerous tissues . if trail resistant trail expression pattern is found in the tumor tissue relative to the non - cancerous tissue , the patient is unlikely to respond favorably to trail adjunctive therapy . accordingly , the patient does not receive trail therapy but is considered for other treatment modalities to convert to trail sensitivity . alternatively , the patient is monitored for post - operative signs of disease recurrence . in one particular aspect , there is provided herein a method of diagnosing whether a subject has , or is at risk for developing , hepatocellular carcinoma ( hcc ). the method generally includes measuring the trail expression pattern in a test sample from the subject and determining whether the trail expression pattern in the test sample deviates relative to the level of a trail expression pattern in a control sample , is indicative of the subject either having , or being at risk for developing , hcc . in certain embodiments , the level of the at least one gene product is measured using northern blot analysis . also , in certain embodiments , the level of the at least one gene product in the test sample is less than the level of the corresponding mir gene product in the control sample , and / or the level of the at least one mir gene product in the test sample is greater than the level of the corresponding mir gene product in the control sample . the level of the at least one mir gene product can be measured by reverse transcribing rna from a test sample obtained from the subject to provide a set of target oligodeoxynucleotides ; hybridizing the target oligodeoxynucleotides to a microarray comprising mirna - specific probe oligonucleotides to provide a hybridization profile for the test sample ; and , comparing the test sample hybridization profile to a hybridization profile generated from a control sample . an alteration in the signal of at least one mirna is indicative of the subject either having , or being at risk for developing , hcc . in another aspect , there is provided herein are methods of treating hcc in a subject , where the signal of at least one mirna , relative to the signal generated from the control sample , is de - regulated ( e . g ., down - regulated and / or up - regulated ). also provided herein are methods of diagnosing whether a subject has , or is at risk for developing , a hcc associated with one or more adverse prognostic markers in a subject , by reverse transcribing rna from a test sample obtained from the subject to provide a set of target oligodeoxynucleotides ; hybridizing the target oligodeoxynucleotides to a microarray comprising mirna - specific probe oligonucleotides to provide a hybridization profile for the test sample ; and , comparing the test sample hybridization profile to a hybridization profile generated from a control sample . an alteration in the signal is indicative of the subject either having , or being at risk for developing , the cancer . also provided herein are methods of treating hcc in a subject who has hcc in which at least two gene products of the trail expression pattern genes are down - regulated or up - regulated in the cancer cells of the subject relative to control cells . when the at least two gene products are down - regulated in the cancer cells , the method comprises administering to the subject an effective amount of at least two isolated gene products , such that proliferation of cancer cells in the subject is inhibited . when two or more gene products are up - regulated in the cancer cells , the method comprises administering to the subject an effective amount of at least one compound for inhibiting expression of at least one gene product , such that proliferation of cancer cells in the subject is inhibited . also provided herein are methods of treating hcc in a subject , comprising : determining the amount of at least two trail expression gene products in hcc cells , relative to control cells ; and , altering the amount of the gene products expressed in the hcc cells by : administering to the subject an effective amount of at the at least two gene products , if the amount of the gene products expressed in the cancer cells is less than the amount of the gene products expressed in control cells ; or administering to the subject an effective amount of at least one compound for inhibiting expression of the at least two gene products , if the amount of the gene product expressed in the cancer cells is greater than the amount of the gene product expressed in control cells , such that proliferation of cancer cells in the subject is inhibited . also provided herein are pharmaceutical compositions for treating trail resistant cancer , comprising at least two isolated trail expression pattern gene product and a pharmaceutically - acceptable carrier . in a particular embodiment , the pharmaceutical compositions comprise gene products corresponds to gene products that are down - regulated in hcc cells relative to suitable control cells . in another particular embodiment , the pharmaceutical composition comprises at least one expression regulator ( for example , an inhibitor ) compound and a pharmaceutically - acceptable carrier . also provided herein are pharmaceutical compositions that include at least one expression regulator compound that is specific for a gene product that is up - or down - regulated in hcc cells relative to suitable control cells . any of the compositions described herein may be comprised in a kit . in a non - limiting example , reagents for isolating mirna , labeling mirna , and / or evaluating an mirna population using an array are included in a kit . the kit may further include reagents for creating or synthesizing mirna probes . the kits will thus comprise , in suitable container means , an enzyme for labeling the mirna by incorporating labeled nucleotide or unlabeled nucleotides that are subsequently labeled . it may also include one or more buffers , such as reaction buffer , labeling buffer , washing buffer , or a hybridization buffer , compounds for preparing the mirna probes , and components for isolating mirna . other kits may include components for making a nucleic acid array comprising oligonucleotides complementary to mirnas , and thus , may include , for example , a solid support . for any kit embodiment , including an array , there can be nucleic acid molecules that contain a sequence that is identical or complementary to all or part of any of the sequences herein . the components of the kits may be packaged either in aqueous media or in lyophilized form . the container means of the kits will generally include at least one vial , test tube , flask , bottle , syringe or other container means , into which a component may be placed , and preferably , suitably aliquoted . where there is more than one component in the kit ( labeling reagent and label may be packaged together ), the kit also will generally contain a second , third or other additional container into which the additional components may be separately placed . however , various combinations of components may be comprised in a vial . the kits of the present invention also will typically include a means for containing the nucleic acids , and any other reagent containers in close confinement for commercial sale . such containers may include injection or blow - molded plastic containers into which the desired vials are retained . when the components of the kit are provided in one and / or more liquid solutions , the liquid solution is an aqueous solution , with a sterile aqueous solution being one preferred solution . other solutions that may be included in a kit are those solutions involved in isolating and / or enriching mirna from a mixed sample . however , the components of the kit may be provided as dried powder ( s ). when reagents and / or components are provided as a dry powder , the powder can be reconstituted by the addition of a suitable solvent . it is envisioned that the solvent may also be provided in another container means . the kits may also include components that facilitate isolation of the labeled mirna . it may also include components that preserve or maintain the mirna or that protect against its degradation . the components may be rnase - free or protect against rnases . also , the kits can generally comprise , in suitable means , distinct containers for each individual reagent or solution . the kit can also include instructions for employing the kit components as well the use of any other reagent not included in the kit . instructions may include variations that can be implemented . it is contemplated that such reagents are embodiments of kits of the invention . also , the kits are not limited to the particular items identified above and may include any reagent used for the manipulation or characterization of mirna . it is also contemplated that any embodiment discussed in the context of an mirna array may be employed more generally in screening or profiling methods or kits of the invention . in other words , any embodiments describing what may be included in a particular array can be practiced in the context of mirna profiling more generally and need not involve an array per se . it is also contemplated that any kit , array or other detection technique or tool , or any method can involve profiling for any of these mirnas . also , it is contemplated that any embodiment discussed in the context of an mirna array can be implemented with or without the array format in methods of the invention ; in other words , any mirna in an mirna array may be screened or evaluated in any method of the invention according to any techniques known to those of skill in the art . the array format is not required for the screening and diagnostic methods to be implemented . the kits for using mirna arrays for therapeutic , prognostic , or diagnostic applications and such uses are contemplated by the inventors herein . the kits can include an mirna array , as well as information regarding a standard or normalized mirna profile for the mirnas on the array . also , in certain embodiments , control rna or dna can be included in the kit . the control rna can be mirna that can be used as a positive control for labeling and / or array analysis . the methods and kits of the current teachings have been described broadly and generically herein . each of the narrower species and sub - generic groupings falling within the generic disclosure also form part of the current teachings . this includes the generic description of the current teachings with a proviso or negative limitation removing any subject matter from the genus , regardless of whether or not the excised material is specifically recited herein . also provided herein are the preparation and use of mirna arrays , which are ordered macroarrays or microarrays of nucleic acid molecules ( probes ) that are fully or nearly complementary or identical to a plurality of mirna molecules or precursor mirna molecules and that are positioned on a support material in a spatially separated organization . macroarrays are typically sheets of nitrocellulose or nylon upon which probes have been spotted . microarrays position the nucleic acid probes more densely such that up to 10 , 000 nucleic acid molecules can be fit into a region typically 1 to 4 square centimeters . microarrays can be fabricated by spotting nucleic acid molecules , e . g ., genes , oligonucleotides , etc ., onto substrates or fabricating oligonucleotide sequences in situ on a substrate . spotted or fabricated nucleic acid molecules can be applied in a high density matrix pattern of up to about 30 non - identical nucleic acid molecules per square centimeter or higher , e . g . up to about 100 or even 1000 per square centimeter . microarrays typically use coated glass as the solid support , in contrast to the nitrocellulose - based material of filter arrays . by having an ordered array of mirna - complementing nucleic acid samples , the position of each sample can be tracked and linked to the original sample . a variety of different array devices in which a plurality of distinct nucleic acid probes are stably associated with the surface of a solid support are known to those of skill in the art . useful substrates for arrays include nylon , glass and silicon . the arrays may vary in a number of different ways , including average probe length , sequence or types of probes , nature of bond between the probe and the array surface , e . g . covalent or non - covalent , and the like . the labeling and screening methods described herein and the arrays are not limited in its utility with respect to any parameter except that the probes detect mirna ; consequently , methods and compositions may be used with a variety of different types of mirna arrays . in view of the many possible embodiments to which the principles of our invention may be applied , it should be recognized that the illustrated embodiments are only preferred examples of the invention and should not be taken as a limitation on the scope of the invention . rather , the scope of the invention is defined by the following claims . we therefore claim as our invention all that comes within the scope and spirit of these claims .
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with reference to fig1 and fig2 the schematic drawings show a preferred embodiment of the invention which includes : an elastic filler , such as a sponge ( 3 ), enveloped by the internal lining ( 2 ); an electromagnetic hammering mode massage device ( 4 ) installed centrally within the elastic filler of sponge ( 3 ), including : an electronic circuit box ( 5 ), connected via a conductor ( 6 ) to a control box ( 7 ), installed in a clamping plate frame of the electromagnetic hammering mode massage device , the control box ( 7 ) is fitted with a power supply socket fixed to a side of the cushion by a securing ring ( 10 ) ( see fig2 ). a potentiometer ( 8 ) is provided to perform and adjust the hammering mode massage . as shown in fig3 the electromagnetic hammering mode massage device ( 4 ) comprises an electromagnetic hammering mechanism ( 35 ), a clamping plate frame ( 29 ), and an electric control unit including a circuit box ( 5 ). the electromagnetic hammering mechanism ( 35 ) of the preferred embodiment is situated centrally within the clamping frame ( 29 ). the clamping plate frame ( 29 ) includes a rear plate ( 11 ) and a front plate ( 23 ) with four supporting columns ( 22 ) of equal length are mounted there between so that the front plate ( 23 ) and the rear plate ( 11 ) are spaced parallel to each other . on both the rear plate ( 11 ) and the front plate ( 23 ), holes are provided for mounting the ends of the supporting columns thereto . the four supporting columns ( 22 ) are distributed evenly around a hole ( 30 ) formed in the front plate ( 23 ). a shock - absorbing block ( 21 ) is fixed to a rear surface of the front plate ( 23 ) around the hole ( 30 ) of the front plate ( 23 ). the electromagnetic hammering mechanism ( 35 ) includes a stop block ( 25 ), having a centrally - located through hole formed therein , which is mounted in a through hole formed in the center of a stop plate ( 24 ). a coil frame ( 16 ), wound to form a coil ( 17 ) and mounted in a magnet yoke ( 18 ), has a cylindrical through hole formed in the center of the coil frame ( 16 ). an end of the stop block ( 25 ) which protrudes through the stop plate ( 24 ) is fitted within one end of the coil frame through hole . the magnet yoke ( 18 ) is fastened to the stop plate ( 24 ) so that the coil frame ( 16 ) is also fixed on the stop plate ( 24 ). the magnet yoke ( 18 ) is also provided with a through hole which aligns with the center through hole of the coil frame ( 16 ). a cylindrical armature ( 14 ) is fastened at a lower end to a stop ring ( 12 ). an upper end of the armature ( 14 ) passes through the through hole of the magnet yoke ( 18 ) into the center through hole of the coil frame ( 16 ). the upper end of the armature ( 14 ) is provided with a threaded hole . a shock - absorbing gasket ( 13 ) is installed between the top surface of the stop ring ( 12 ) and the bottom face of the magnet yoke ( 18 ). a sliding rod ( 15 ), which has a threaded lower end , is slideably disposed in the through hole of the stop block ( 25 ). the threaded end of the sliding rod ( 15 ) is engaged with the threaded hole in the upper end of the armature ( 14 ). a hammering head ( 28 ) is attached to the upper end of the sliding rod ( 15 ). a shock absorber structure consisting of a compressible spring ( 26 ) and a shock absorbing ring ( 27 ) is mounted on the sliding rod ( 15 ) between the top face of the stop block ( 25 ) and the bottom face of the hammering head ( 28 ). the stop plate ( 24 ) is provided with guide holes which align with the columns ( 22 ) which allow the stop plate ( 24 ) to slide along the columns ( 22 ). a flange ( 20 ) is disposed in alignment with and immediately under each guide hole of the stop plate ( 24 ). a compressible spring ( 19 ) is fitted around each supporting column ( 22 ) between a lower end face of the flange ( 20 ) and the top surface of the rear plate ( 11 ) so that the whole electromagnetic hammering mechanism ( 35 ) can be elastically installed in the clamping plate frame . after installation of the electromagnetic hammering mechanism in the clamping plate frame , the hammering head ( 28 ) should protrude from the top surface of the front plate ( 23 ) through hole ( 30 ). fig4 shows a block diagram of an electric control unit of the present invention which includes a pulse shaping circuit ( 31 ), a massage status controlling circuit ( 32 ), a pulse - width regulating circuit ( 33 ), and an electronic switch ( 34 ). the beat output of the pulse - shaping circuit ( 31 ) regulates the hammering speed ; the massage status controlling circuit ( 32 ) is brought into operation through the selection switch following the pulse - shaping . hammering intensity is regulated by changing the pulse width with the pulse - width adjustment circuit ( 33 ). the pulse current output from the electronic switch ( 34 ) is transmitted to the magnet coil ( 17 ) of the electromagnetic hammering mechanism ( 35 ) so as to produce an electromagnetic force for driving the hammering head ( 28 ) resulting in the hammering mode massage action . though the preferred embodiment employs only one electromagnetic hammering mechanism , fig4 shows the circuit black diagram for a plurality of electromagnetic hammering mechanisms represented in the block diagram by reference numbers having a subscript 1 - n . the electronic circuit of the present invention is designed to use either alternating or direct current power supply with a voltage of 12v - 220v . it can also incorporate an isolation transformer or a safety device against electric shock . additionally , the device may be provided with a protection function to stop operation upon absence of the person using the device , or an automatic shut - off function activated by temperature control . the device may also be equipped with an audio device for music or a radio set . it is to be understood that the outward appearance of the soft cushion of the present invention , the surface material used for external cover ( 1 ) and the filling material may be selected to meet various requirements . furthermore , changes may be made in details of the other components within the principles of the invention to the full extent indicated by the broad general meaning of the terms in which the appended claims are expressed . for instance , more than one hammering mode massage mechanism may be installed within the soft cushion .
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reference will now be made in detail to the presently preferred embodiments of the invention . each example is provided by way of explanation of the invention , not limitation of the invention . it will be apparent to those skilled in the art that various modifications and variations can be made in the invention without departing from the scope or spirit of the invention . it is intended that the present invention cover such modifications and variations as come within the scope of the claims and their equivalents . in accordance with the objects of the invention , and as illustrated in fig1 an adjustable surface mount adapter 10 is provided . adapter 10 includes an inner wall mount 12 for being disposed on one side of the wall . inner wall mount 12 includes wall contacting surface 14 . the shape and configuration of inner wall mount 12 and wall contacting surface 14 illustrated in fig1 is illustrated as a mere example of an embodiment of the invention . it should be understood that inner wall mount 12 can take on any shape such as hexagonal , square , or the like . in addition , wall contacting surface 14 may take on the form of an annular ring as illustrated in fig1 or , can assume any other suitable configuration such as alternate projections , a flat surface encompassing substantially the entire back surface of wall mount 12 , or the like . in addition , it is within the scope of the claims to include a washer , gasket , or insulation material between inner wall mount 12 and a wall with the washer , gasket , or material thus being the wall contacting surface 14 . inner wall mount 12 also includes a stem portion 16 . stem portion 16 is of a sufficient length to extend through a wall of predetermined thickness , for example for the adapter to be utilized for walls having a thickness of from 1 / 8 inch to 11 / 2 inches , stem portion 16 could be of a length of 21 / 4 inches from the wall contacting surface 14 . it should be understood that stem portion 16 can be of any length depending upon the thickness of the wall adapter 10 is to be utilized with . stem portion 16 also includes a form locking outer diameter surface 18 over at least a portion thereof . in a preferred embodiment as illustrated in the figures , form locking surface 18 comprises a threaded surface 20 . however , it is within the scope of the invention that form locking surface 18 also include a ratcheted surface , a tongue in groove surface , or even a smooth surface to be cemented or glued . for ease of manufacture and assembly of adapter 10 , however , a threaded surface is preferred . inner wall mount 12 further defines an inner diameter 24 sufficient for a pipe of predetermined diameter to be inserted therein . for example , if inner wall mount 12 were to receive a 3 / 4 inch pipe , inner diameter 24 would be approximately 0 . 882 inches . it should be understood that stem portion 16 is essentially hollow and preferably is of the same inner diameter as inner diameter 24 in the mount 12 receiving the pipe . however , such is not a limitation of the invention . for example , in an alternative preferred embodiment , inner wall mount 12 may include a flange or similar structure essentially separating inner diameter portion 24 and stem portion 16 of the mount 12 . in this manner , a pipe inserted into inner diameter 24 would abut against flange 26 and it would not be essential that the inner diameter of stem portion 16 match that of portion 24 . a flange or like structure would also provide for easier alignment and gluing or securing of a pipe within mount 12 . surface mount adapter 10 also includes an outer wall mount 34 as illustrated in the figures . outer wall mount 34 also includes a wall contacting surface 42 and , as discussed above , the shape and configuration of mount 34 and wall contacting surface 42 illustrated in the figures is but a mere example of any suitable configuration . for example , mount 34 may have a hexagonal , circular , or any other profile . outer wall mount 34 includes a receiving portion 37 . receiving portion 37 has a form - locking inner diameter surface 38 for engagement with form - locking surface 18 of stem portion 16 . in the preferred embodiment , form - locking surface 38 is a threaded surface matching the threads on stem portion 16 . in this manner , outer wall mount 34 engages inner wall mount 12 by simply being screwed onto stem portion 16 . in this way , a wall is more or less squeezed between wall contacting surfaces 14 and 42 of mounts 12 and 34 respectively . thus , adapter 10 is non - movably secured directly to the wall and forms a rigid passage therethrough . outer wall mount 34 acts essentially as a nut which is threaded onto stem portion 1b . in this manner , once mount 34 has been secured to inner mount 12 through stem portion 16 , any manner of pipe , fixture , adapter , or the like can be fitted into the open end of stem portion 16 extending through the wall . in a preferred embodiment , as illustrated in fig3 a threaded adapter may be fitted into stem portion 16 for receiving a pipe , fixture , or the like having a diameter different from that of stem portion 16 . also , stem portion 16 may have an inner flange or collar reducing the extreme end diameter thereof . it is preferred that outer wall mount 34 also include a circumferential engagement portion 44 . preferably , portion 44 is formed in the shape of a hexagon or other flat sided configuration for engagement with a wrench so as mount 34 can be easily screwed or tightened onto inner mount 12 . alternatively , outer mount 34 may be simply hand tightened onto inner mount 12 . the components of the present invention preferably are formed of , and compatible with , conventional plastic plumbing materials , such as pvc and cpvc since these materials can be readily glued . other materials require welding or soldering and detract from the invention . fig2 illustrates another embodiment of inner wall mount 12 and stem portion 16 according to the invention . inner wall mount 12 depicted in fig2 would be used for a relatively thick wall and includes a non form - locking or non - engaging portion 22 for extension through the wall . in this embodiment , only form - locking surface 18 would be engaged by outer wall mount 34 . preferably , the stem portion of mount 20 is cut and a pipe of any desired length is inserted between the mount and threaded stem portion . alternatively , the non form - locking portion and threaded portion could comprise a single integral component . thus , it should be understood that the present invention is not limited to any particularly thickness of wall and can be suitably adapted for any type wall . in further accordance with the objects of the present invention , and as depicted in fig3 a plumbing system having a rigid through - wall connection is provided . plumbing system 50 illustrated in fig3 is but a mere example of a system within the scope of the present invention and is illustrated as a supply 30 and faucet or shower head 32 running through wall 28 . it should be understood however that fixture 32 may also be a drain and pipe 30 may also be a drain line instead of a supply header . the present plumbing system is not limited to any particular configuration but is applicable to any through - wall plumbing connection . in the embodiment of fig3 system 50 includes supply pipe 30 disposed on the inner side of wall 28 . inner wall mount 12 is also provided on the inner side of wall 28 and receives pipe 30 therein . inner wall mount 12 is essentially as discussed above and includes stem portion 16 extending through wall 28 having a threaded outer surface . on the outer side of wall 28 , outer wall mount 34 is provided having a threaded receiving portion for engagement with stem portion 16 . mount 34 has a flat sided circumferential portion 44 for allowing mount 34 to be threaded onto stem portion 16 , as discussed above . system 50 further includes plumbing fixture 32 being received in outer wall mount 34 . preferably , an adapter 26 is provided so that fixture 32 is readily removable from outer wall mount 34 . pipe 30 and adapter 26 are easily inserted and glued to mount 12 and stem portion 16 , respectively . also , it is within the scope of the present invention that inner diameter 24 of stem portion 16 be threaded near the end thereof for engagement with a threaded adapter of pipe . however , in the preferred embodiment of the system wherein the components are made of pvc or cpvc material , it is a relatively easy procedure to simply glue fixtures 30 and 32 into the respective mounts 12 and 16 . fixture 32 of the present system 50 can comprise , for example , a shower head , faucet , drain , isolation valve , or any conventional plumbing fixture .
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the present invention is directed to an automatic , self stirring device for stove top and microwave oven cooking , as illustrated in the several figures , where like reference numerals identify like components or features throughout the various views . fig1 illustrates a first embodiment of the stirring device 10 of this invention , where such device is shown removably mounted over a cooking pot . the device comprises a housing 12 , a mounting system 14 to support said housing 12 , a downwardly extending rotating shaft 16 , and a pair of laterally extended , adjustable mixing blades 18 removably attached to the distal end 20 of shaft 16 . the housing 12 , generally rectangular in configuration and fabricated from a high temperature resistant plastic , such as high density polyethylene , comprises four upstanding side walls 22 , a top wall 24 , and a bottom wall 26 , where said bottom wall includes a central opening 28 communicating with the interior thereof . further , the respective side walls 22 include threaded recesses 30 into which components of the mounting system 14 are received . a first embodiment of the mounting system 14 preferably comprises four individually , extendable , telescopic arms 32 . each said arm includes a first arm segment 34 , threaded at one end 35 thereof for engaging a complementary threaded recess 30 in the housing side wall , and a second arm segment 36 slidably received within said first arm segment 34 . the distal end 38 of said second arm segment may include a downwardly projecting stop member 40 , fabricated from rubber , for example , for engaging the periphery of the cooking pot when in the extended position . biasing the second arm segment and stop member 40 against the cooking pot is an internal compression spring 42 . as best seen in fig3 the outer end 43 of the first arm may be provided with an inwardly directed annular flange 45 . cooperating with said flange 45 is an annular rim or stop 47 about the second arm 36 to prevent it from prematurely releasing from the first arm 34 . by this arrangement , the housing 12 may be centrally disposed over a variety of sized circular or rectangular cooking pots . the rotating shaft 16 and adjustable mixing blades 18 are best illustrated in fig1 and 2 . in order to position the blades in close proximity to the bottom of the cooking pot , the rotating shaft 16 preferably comprises a pair telescopically engaged upper and lower shaft segments 44 , 46 , respectively . a first end of upper shaft segment 44 is internally threaded to engage threaded stub 48 , the external rotary member extending from the power source within the housing 12 and extending through opening 28 . the opposite end is provided with an internally positioned , v - shaped plastic latching member 50 , wedged therewithin , where one end thereof includes a nibble 52 communicating exteriorly thereof through an opening 54 . slidably engaging the opposite end is lower shaft segment 46 , where said segment includes a series of openings 56 . these openings 56 cooperate with the latching member 50 to axially position the respective shaft segments to the desired length . the free or distal end of lower shaft segment 46 is provided with a spring biased clip 58 having a blade support 60 extending downwardly through the bite thereof , fig2 . the blade support 60 includes a central wall 62 having a pair of outwardly curved flange members 64 , where the respective flanges along each side at wall 62 define a channel for slidably receiving a mixing blade 18 . by this arrangement , the blades may be positioned to a depth desired , then laterally extended or retracted , as desired , and locked by the clip 58 , to precisely fit the cooking pot . the blades 18 , as best seen in fig1 include a first series of larger holes 66 to facilitate mixing , and a series of smaller holes 68 for selectively engaging the clip 58 . fig3 and 4 are , respectively , side and plan views of the interior of the housing 12 showing primarily the gear mechanism for rotating the main shaft 70 , an extension of threaded stub 48 . the rotating mechanism includes a coiled , torsional spring 72 wound about and connected to said main shaft 70 , and a rubber speed control mechanism 74 to constrain or ensure the torsional spring 72 rotates at a designated rate . otherwise , the spring would unwind immediately . the half spring 76 is an important component of the timer or rotating mechanism . this half spring 76 winds as the pendulum like pallet 78 moves one way and then unwinds forcing the pallet 78 to move the other direction . the balance thereof keeps the oscillary motion initiated by the spring 76 and pallet 78 constant . the pallet 78 , like a pendulum , moves one direction as the escape wheel 80 rotates and then releases the wheel . as this sequence occurs , the other end of the pallet 78 rotates the shaft which loads the half spring 76 . in return , the half spring unwinds causing the pallet 78 to move in the other direction so that it engages the escape wheel again . this sequence of steps causes the escape wheel 80 to revolve once every eight seconds , which is the key to keeping accurate time . the main gear 82 is attached to the spring 72 which turns the gear 82 at a rate of one revolution every four seconds , which in turn is coordinated by the adjacent torque and timing gear trains 84 , 86 , respectively . the center wheel 90 rotates every 20 minutes to give validity to the manual rotary timer dial 92 . by this arrangement , the rotary mechanism provides a 300 : 1 ratio of teeth between the center wheel 90 and the main gear 82 so that the center wheel revolves once per twenty minutes and the main gear 82 revolves once per four seconds . the torsional gear 86 , toward the left of the respective figures , acts as an intermediate between the main gear 82 and the rubber speed control wheel 74 . the satellite wheels 94 , 96 function to transfer a slow angular rotation to the center wheel 90 to a fast revolution of the escape wheel 80 . to assist a non - attendant homemaker in using the stirring device of this invention , an alarm device may be incorporated into the system hereof . for example , when the stirring device runs down , a bell 97 , rung by the mallet 99 , may be provided . the spring 101 ( fig3 ) is loaded when the flexible pivot 103 pulls the mallet 99 back . the spring loads when the time expires forcing the mallet to strike the bell 97 . the flexible pivot 103 ( fig4 ) pulls the mallet back ( to load the spring ) when the main shaft 70 is turned from its initial position via component 105 , which enlarges the radius of the shaft . once the main shaft rotates back to its initial position , i . e ., signifying the expiration of time , the radius decreases by cam washer 107 , releasing the flexible pivot 103 which in turn unleashes the spring and mallet . a second embodiment for the mounting system for positioning the housing 12 of this invention is illustrated by the two views of fig5 and 6 . the modified mounting system comprises a central mounting plate 100 , having a central opening 102 for receiving the threaded stub 48 , as noted above . emanating from the mounting plate 100 is an inner network of connected leg segments 104 having a plurality of free legs 106 radially and angularly extending therefrom . the distal ends 108 of said free legs 106 may include a v - shaped , rubberized foot 109 to secure the network about the rim of the cooking pot . the network , including the free legs 106 , being fabricated from a high temperature resistant plastic , is sufficiently flexible to shift such legs to accommodate different dimensioned cooking vessels . finally , to position and fix the housing 12 the mounting plate 100 , plural apertures 110 may be provided to receive complementary feet 112 extending from the housing base . recognizing that exposed metal parts heated in a microwave oven can cause serious damage , the device hereof uses a heat resistant plastic , up to 500 degrees f ., that protects all metal parts , such as the stainless steel springs . while two embodiments have been described above on the mounting system , it is recognized that variations may be had with respect to the components hereof . therefore , while the invention has been disclosed in preferred forms only , it will be obvious to those skilled in the art that many additions , deletions and modifications can be made therein without departing from the spirit and scope of this invention , and that no undue limits should be imposed thereon except as set forth in the following claims .
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embodiments of the present invention will now be described with reference to the accompanying drawings . fig1 is a diagram schematically illustrating the configuration of an automatic analyzer according to one embodiment of the present invention . the automatic analyzer according to this embodiment includes a sample rack loading unit 1 , an id reading unit 2 , a transfer line 3 , a reexamination transfer line 4 , analysis modules 5 , 6 , 7 , and 8 , a sample rack standby section 9 , a sample rack collecting unit 10 , a second reagent storing unit 100 , and an overall control computer 11 . the analysis modules 5 , 6 , 7 , and 8 and the sample rack loading unit 1 are equipped with control computers 12 , 13 , 14 , 15 , and 16 , respectively . in addition , the overall control computer 11 is equipped with an operation unit 18 and a display unit 19 . the sample rack loading unit 1 is a unit used to load a plurality of sample racks , each of which holds one or more samples ( specimens ). the analysis modules 5 , 6 , 7 , and 8 are units which are capable of separately performing automatic analysis ; they are located along and detachably connected to the transfer line 3 . the transfer line 3 leads to the analysis modules 5 , 6 , 7 , and 8 through lead - in lines 20 , 21 , 22 , and 23 , respectively , so that a sample ( specimen ) can be transferred therebetween . the number of the analysis modules may be arbitrarily determined ; in this embodiment , that number is four . further , in this embodiment , all of the analysis modules are biochemical analysis modules . the analysis modules may also include a combination of a biochemical analysis module and another analysis module ( for example , an electrolyte analysis module ). each of the analysis modules 5 , 6 , 7 , and 8 is provided with a sample dispenser 30 for dispensing a sample ( specimen ) that has been transferred to the analysis module with the sample placed in a sample rack ; and a reaction vessel 31 in which the sample ( specimen ) is made to react . in addition , each of the analysis modules 5 , 6 , 7 , and 8 is further provided with a reagent dispenser 32 for dispensing a reagent into the reaction vessel 31 into which the sample has been dispensed ; and a first reagent storing unit 33 that holds a reagent cassette filled with a reagent to be dispensed into the reaction vessel 31 . in this embodiment , each of the analysis modules 5 and 6 is provided with one first reagent storing unit 33 ; each of the analysis modules 7 and 8 is provided with two first reagent storing units 33 . as above , the analysis modules can each have a single or multiple first reagent storing units 33 . the second reagent storing unit 100 is connected via a reagent transfer line 101 to the first reagent storing units 33 included in the analysis modules 5 , 6 , 7 , and 8 . however , one analysis system need not have only one second reagent storing unit 100 as above ; instead , each analysis module within the analysis system can have one second reagent storing unit 100 . alternatively , one second reagent storing unit 100 can be provided for analysis modules of the same kind such as biochemical analysis modules or electrolyte analysis modules . the second reagent storing unit 100 includes a reagent supply unit 102 to which a user supplies reagents ; and a reagent identification unit 103 for identifying the kinds of the supplied reagents . moreover , the second reagent storing unit 100 may also have the function of refrigerating the reagents so as to store them for a long period of time . when the user operates the automatic analyzer on the basis of , for example , operation set 1 used for periodic medical examinations shown in table 1 , the number of required analysis items is limited , for operation set 1 is used for periodic medical examinations . however , the number of analysis samples registered for each analysis item is large . in contrast , in operation set 2 for nighttime shown in table 1 , many analysis items need to be analyzed due to various night - time analysis requests . however , the number of samples to be analyzed is not larger than those in regular medical examinations , and the number of analysis samples to be registered is thus smaller . when analysis items and the number of analysis samples are registered as an operation set proper for each automatic analyzer operation as above , various operation modes can be supported . a method for changing the operation mode of the automatic analyzer using an operation set will be described in accordance with the process flowchart shown in fig2 . in step 201 shown in fig2 , an operation set is registered for each operation mode . each of the operation sets constitutes a combination of analysis items and analysis sample numbers for the analysis items . in step 202 shown in fig2 , an operation set is selected . reagents required for the selected operation set are then checked to identify analysis items that can be analyzed by all the reagents placed in the first reagent storing unit 33 and in the second reagent storing unit 100 and to calculate the number of tests for each of the identified analysis items . next , in step 207 of fig2 , the operation set is changed . in step 208 of fig2 , reagents are replaced between the first reagent storing unit 33 and the second reagent storing unit 100 . in step 212 of fig2 , relevant reagents are placed in the first reagent storing unit 33 ; the reagents are in agreement with the analysis items and the number of planned analyses for each of the analysis items in the operation set . hereinafter , means for selecting reagents used for the analysis operation based on an operation set is referred to as “ reagent selection means ,” in which operation set analysis items each combined with the scheduled number of analyses are registered . next , steps executed by the reagent selection means will be sequentially described in detail . registration of an operation set , which corresponds to step 201 of fig2 , will be described with reference to fig3 . an operation set name is registered in an operation set list 401 . next , an analysis item is selected from an analysis item list 402 , and the selected analysis item is then added by use of an “ add ” button 403 . unnecessary items can be selected from among analysis items registered in an operation - set item list 404 and deleted by use of a “ delete ” button 405 . radio buttons 406 for selecting a method for setting the number of tests can be used to select the manual setting mode or the automatic setting mode . in the manual setting mode , the user manually sets the number of analyses for each analysis item . after that , the settings which have been set by use of the “ add ” button 403 and the “ delete ” button 405 are fixed by use of an “ update ” button 407 . lastly , the above settings are registered by use of a “ register ” button 408 . the above settings can be cancelled by use of a “ cancel ” button 409 . here , data relating to the operation set includes analysis item names ; the number of tests ; reagent names ; data ( bar code ) used to identify reagent cassettes ; the validity dates of reagents ; and analysis logs . these are written onto recording media built into the overall control computer 11 or the control computers 12 , 13 , 14 , and 15 . this makes it possible to easily set / register an operation set and to easily control transfer of reagents . as step 202 of fig2 , how to select an operation set will be described with reference to fig4 . an operation mode required at a certain point of time is selected from all registered operation sets shown in fig3 ( this embodiment shows a case where “ normal analysis ” is selected by use of an operation - set selection combo box 501 ). a “ check placed reagents ” button 502 is then clicked to identify analysis items that can be analyzed by all reagents placed in the first reagent storing unit 33 and in the second reagent storing unit 100 , and to calculate the number of tests corresponding to each of the analysis items that can be analyzed . in step 203 shown in fig2 , the identified analysis items that can be analyzed by use of all reagents placed in the first reagent storing unit 33 and in the second reagent storing unit 100 , and the calculated number of tests corresponding to each of the analysis items that can be analyzed , both of which have been obtained according to step 202 shown in fig2 , are compared with the analysis items of the operation set selected in fig4 and the scheduled number of analyses corresponding to each of the analysis items respectively . if it is judged that reagents required for the analysis operation based on the operation set are placed , a confirmation screen as shown in fig5 is displayed in step 204 shown in fig2 . clicking a “ close ” button 601 completes the confirmation . however , as a result of the placed reagent check in step 203 shown in fig2 , if it is judged that the reagents required for the analysis operation based on the operation set are not placed , insufficient reagents are displayed as shown in fig6 . this corresponds to step 205 shown in fig2 . in the example shown in fig6 , for the analysis items specified in the selected operation set , and for the scheduled number of analyses corresponding to each of the analysis items , information is displayed in a reagent information list 701 . the displayed information includes : a name of an analysis item for which a reagent is insufficient ; the scheduled number of analyses ( a ) specified in the operation set ; the number of analyses ( b ) that can be made by use of currently placed reagents ; and the insufficient number of tests ( c ). additionally , the number of new reagents ( d ) is displayed . this is the number of additional reagents required to satisfy the scheduled number of analyses specified in the operation set when the user is required to add new reagents . the number of new reagents ( d ) enables the user to know the number of reagents that should be placed . here , as step 206 shown in fig2 , the user places the reagents in the second reagent storing unit 100 . in this case , step 206 shown in fig2 may also be omitted . more specifically , the user is allowed not to place reagents if necessary although the user knows that the reagents are insufficient . in step 207 shown in fig2 , in order to place , in the first reagent storing unit 33 , reagents required for the scheduled number of tests specified in the operation set , a “ change operation set ” button 503 shown in fig4 is clicked . as a result , in step 208 , a reagent is transferred between the first reagent storing unit and the second reagent storing unit . in this case , an insufficient reagent is transferred from the second reagent storing unit 100 to the first reagent storing unit 33 so as to enable analyses , the number of which is equivalent to the scheduled number of analyses corresponding to each analysis item registered in the specified operation set . if the first reagent storing unit 33 does not have empty space for a reagent to be placed therein , with the result that no reagent can be transferred to the first reagent storing unit 33 , a reagent , which is not required for analysis items specified in the operation set , and which is not required for the scheduled number of analyses corresponding to each of the analysis items , is transferred from the first reagent storing unit 33 to the second reagent storing unit 100 . as a result , the first reagent storing unit 33 is provided with empty space for a required reagent to be placed therein . until all reagents , which are required for the analysis items specified in the operation set , and which are required for the scheduled number of analyses corresponding to each of the analysis items , are placed in the first reagent storing unit 33 , reagents are transferred between the first reagent storing unit 33 and the second reagent storing unit 100 . hereinafter , means for , when the first reagent storing unit does not have empty space for a reagent to be placed therein , with the result that all reagents required for analysis operation based on the operation set cannot be completely transferred to the first reagent storing unit , keeping the required reagent waiting in the second reagent storing unit , and for , when the first reagent storing unit is provided with empty space for a reagent to be placed therein , making a judgment as to whether or not to transfer the reagent to the first reagent storing unit , is referred to as “ transferability judgment means ”. incidentally , when a “ cancel ” button 504 shown in fig4 is clicked , the process proceeds to a next step without checking placed reagents , and without changing the operation set . in the case of an operation set in which the scheduled number of analyses corresponding to each analysis item is large , a large number of analysis items may require that a plurality of reagents be placed in the first reagent storing unit 33 on an analysis item basis . in this case , however , in step 209 shown in fig2 , such a situation can also be thought to occur that all reagent , which are required for analysis items specified in the operation set , and which are required for the scheduled number of analyses corresponding to each of the analysis items , cannot be completely transferred to the first reagent storing unit 33 . in such a case , as step 210 shown in fig2 , when reagents which could not be transferred to the first reagent storing unit 33 are kept waiting in the second reagent storing unit 100 ; the reagents are kept waiting in the second reagent storing unit 100 with a higher priority placed on a reagent , the required number of which is two or more for an identical item , and in decreasing order of the scheduled number of analyses specified in the operation set . this enables the first reagent storing unit 33 to always contain at least one reagent required for each of the analysis items specified in the operation set . on the completion of the reagent transfer operation , in step 211 shown in fig2 , a judgment is made again as to whether or not the reagents required for the operation set are placed in the first reagent storing unit 33 and in the second reagent storing unit 100 . the user &# 39 ; s attention is then attracted . here , if it is judged that the reagents required for the operation set are placed , the placement has been completed in step 212 shown in fig2 , and a confirmation screen as shown in fig7 is displayed . clicking a “ close ” button 801 completes the confirmation . however , if it is not judged that the reagents required for the operation set are placed in the first reagent storing unit 33 and in the second reagent storing unit 100 ( for example , there is a case where although insufficient reagents are displayed in step 205 shown in fig2 , the reagents have not yet been placed in step 206 shown in fig2 ; or there is a case where although the reagents have been placed in step 206 shown in fig2 , the reagents are insufficient for the scheduled number of analyses ), then , in step 213 , information is displayed again in the reagent information list 701 as shown in fig6 . the displayed information includes : a name of an analysis item for which a reagent is insufficient ; the scheduled number of analyses ( a ) specified in the operation set ; the number of analyses ( b ) that can be made by currently placed reagents ; the number of insufficient tests ( c ); and the number of new reagents ( d ) required when new reagents are placed . when analysis is started in step 214 shown in fig2 , a reagent which cannot be used for the analysis may occur for some reasons ( for example , the validity time is expired ) in step 215 shown in fig2 , a judgment is made as to whether or not the second reagent storing unit 100 contains a reagent to be transferred to the first reagent storing unit 33 . if it is judged that the second reagent storing unit 100 contains a reagent to be transferred to the first reagent storing unit 33 , a judgment is made in step 216 in fig2 as to whether or not the first reagent storing unit 33 has empty space for a reagent to be placed therein , or whether or not the first reagent storing unit 33 has an area in which a reagent which cannot be used for the analysis is placed . if it is judged to be “ yes ” in step 216 , a reagent kept waiting in the second reagent storing unit 100 is transferred to the empty space or the area in question in step 217 shown in fig2 . in contrast , if it is judged that the first reagent storing unit 33 has empty space for a reagent to be placed therein , or it is judged that the first reagent storing unit 33 has an area in which a reagent which cannot be used for the analysis is placed , then in step 218 , a reagent required for the analysis is transferred to the first reagent storing unit by replacing the reagent which cannot be used for the analysis or a reagent excessively stored in the first reagent storing unit with the reagent kept waiting in the second reagent storing unit 100 . as described above , each reagent kept waiting in the second reagent storing unit 100 is transferred to the first reagent storing unit 33 every time the first reagent storing unit 33 is provided with empty space for a reagent to be placed therein . as a result , even in the case of an operation set in which the scheduled number of analyses corresponding to each analysis item is large ( for example , an operation set used for multi - sample analysis ), analyses can be continued by use of reagents prepared before the start of the analyses . in step 201 shown in fig2 , when the scheduled number of analyses to be specified in the operation set is determined , if “ automatic ” is selected , the user is prompted to specify the day of the week and the time at which analysis will be started , and the day of the week and the time at which the analysis will be ended . accordingly , the scheduled number of analyses corresponding to each analysis item , which are to be made within the specified period of time , is automatically determined on the basis of the number of analyses corresponding to each analysis item recorded as past analysis recording . the number of analyses corresponding to each analysis item within a specified past period of time can be calculated by recording the number of analyses as the analysis recording with the number of analyses linked with information including the measurement date and time of each analysis item , and the kind of examination . hereinafter , the means for automatically determining the scheduled number of analyses corresponding to each analysis item defined in the operation set on the basis of the number of analyses corresponding to each analysis item recorded as the past analysis recording is referred to as “ scheduled - number - of - analyses automatic determination means ”. as an example of a method for automatically determining the scheduled number of analyses , for example , if a period of time is specified at the time of registering an operation set , the average number of analyses corresponding to each analysis item , which have been made within the same time range in the past corresponding to the specified period of time , is automatically determined as the scheduled number of analyses for the specified period of time . the above method will be described with reference to table 2 . when a period of time during which analyses are made , and an analysis item , are specified ( in table 2 , a time range from monday 9 : 00 to monday 17 : 00 is specified as the period of time ; and ast is specified as the analysis item ), analysis recording covering analyses of the specified analysis item made during the specified period of time is extracted from the past analysis recording to calculate the number of analyses for the specified period of time ( table 2 shows the number of analyses measured within the specified period of time on a week basis ). therefore , the average number of analyses measured within the same time range in the past is determined as the scheduled number of analyses for the specified period of time . as another example of the method for automatically determining the scheduled number of analyses , for example , if a period of time is specified at the time of registering an operation set , the maximum number of analyses which have been made within the same time range in the past is automatically determined as the scheduled number of analyses for the specified period of time . in this case , even if requests for analysis accidentally increases , it is possible to minimize the possibility that insufficient reagent will occur . in the above - described embodiments , the above processes can be automatically executed by recording a program for instructing a computer to function as the above means , or a program for instructing the computer to execute the above processes , in a computer - readable storage medium that is built into the overall control computer 11 or the control computers 12 , 13 , 14 , and 15 .
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with reference now to the figures and in particular with reference to fig1 , a pictorial representation of a data processing system in which the present invention may be implemented is depicted in accordance with a preferred embodiment of the present invention . a computer 100 is depicted which includes system unit 102 , video display terminal 104 , keyboard 106 , storage devices 108 such as floppy drives and other types of permanent and removable storage media , and mouse 110 . additional input devices may be included with personal computer 100 , such as , for example , a joystick , touchpad , touch screen , trackball , microphone , and the like . computer 100 can be implemented using any suitable computer , such as an ibm eserver computer or intellistation computer , which are products of international business machines corporation , located in armonk , n . y . although the depicted representation shows a computer , other embodiments of the present invention may be implemented in other types of data processing systems , such as a network computer . computer 100 also preferably includes a graphical user interface ( gui ) that may be implemented by means of systems software residing in computer readable media in operation within computer 100 . fig2 is a block diagram of a data processing system in which the present invention may be implemented . data processing system 200 is an example of a computer , such as computer 100 in fig1 , in which code or instructions implementing the processes of the present invention may be located . data processing system 200 uses a peripheral component interconnect ( pci ) local bus architecture . although the depicted example employs a pci bus , other bus architectures such as accelerated graphics port ( agp ) and industry standard architecture ( isa ) may be used . processor 202 and main memory 204 connect to pci local bus 206 through pci bridge 208 . pci bridge 208 also may include an integrated memory controller and cache memory for processor 202 . additional connections to pci local bus 206 may be made through direct component interconnection or through add - in connectors . in the depicted example , local area network ( lan ) adapter 210 , small computer system interface ( scsi ) host bus adapter 212 , and expansion bus interface 214 connect to pci local bus 206 by direct component connection . in contrast , audio adapter 216 , graphics adapter 218 , and audio / video adapter 219 connect to pci local bus 206 by add - in boards inserted into expansion slots . expansion bus interface 214 provides a connection for a keyboard and mouse adapter 220 , modem 222 , and additional memory 224 . scsi host bus adapter 212 connects to hard disk drive 226 , tape drive 228 , and cd - rom drive 230 . an operating system runs on processor 202 and is used to coordinate and provide control of various components within data processing system 200 in fig2 . the operating system may be a commercially available operating system such as windows xp , which is available from microsoft corporation . an object oriented programming system such as java may run in conjunction with the operating system and provides calls to the operating system from java programs or applications executing on data processing system 200 . “ java ” is a trademark of sun microsystems , inc . instructions for the operating system , the object - oriented programming system , and applications or programs are located on storage devices , such as hard disk drive 226 , and may be loaded into main memory 204 for execution by processor 202 . those of ordinary skill in the art will appreciate that the hardware in fig2 may vary depending on the implementation . other internal hardware or peripheral devices , such as flash read - only memory ( rom ), equivalent nonvolatile memory , or optical disk drives and the like , may be used in addition to or in place of the hardware depicted in fig2 . also , the processes of the present invention may be applied to a multiprocessor data processing system . for example , data processing system 200 , if optionally configured as a network computer , may not include scsi host bus adapter 212 , hard disk drive 226 , tape drive 228 , and cd - rom 230 . in that case , the computer , to be properly called a client computer , includes some type of network communication interface , such as lan adapter 210 , modem 222 , or the like . as another example , data processing system 200 may be a stand - alone system configured to be bootable without relying on some type of network communication interface , whether or not data processing system 200 comprises some type of network communication interface . as a further example , data processing system 200 may be a personal digital assistant ( pda ), which is configured with rom and / or flash rom to provide non - volatile memory for storing operating system files and / or user - generated data . the depicted example in fig2 and above - described examples are not meant to imply architectural limitations . for example , data processing system 200 also may be a notebook computer or hand held computer in addition to taking the form of a pda . data processing system 200 also may be a kiosk or a web appliance . the processes of the present invention are performed by processor 202 using computer implemented instructions , which may be located in a memory such as , for example , main memory 204 , memory 224 , or in one or more peripheral devices 226 - 230 . fig3 is a block diagram illustrating the relationship of software components operating within a computer system that may implement the present invention . java - based system 300 contains platform specific operating system 302 that provides hardware and system support to software executing on a specific hardware platform . jvm 304 is one software application that may execute in conjunction with the operating system . jvm 304 provides a java run - time environment with the ability to execute java application or applet 306 , which is a program , servlet , or software component written in the java programming language . the computer system in which jvm 304 operates may be similar to data processing system 200 or computer 100 described above . however , jvm 304 may be implemented in dedicated hardware on a so - called java chip , java - on - silicon , or java processor with an embedded picojava core . at the center of a java run - time environment is the jvm , which supports all aspects of java &# 39 ; s environment , including its architecture , security features , mobility across networks and platform independence . the jvm is a virtual computer , i . e . a computer that is specified abstractly . certain features are present in every jvm , with some range of design choices that may depend upon the platform on which the jvm is designed to execute . for example , all jvms must execute java bytecodes and may use a range of techniques to execute the instructions represented by the bytecodes . a jvm may be implemented completely in software or somewhat in hardware . this flexibility allows different jvms to be designed for mainframe computers and pdas . the jvm is the name of a virtual computer component that actually executes java programs . java programs are not run directly by the central processor but instead by the jvm , which is itself a piece of software running on the processor . the jvm allows java programs to be executed on a different platform as opposed to only the one platform for which the code was compiled . java programs are compiled for the jvm . in this manner , java is able to support applications for many types of data processing systems , which may contain a variety of central processing units and operating systems architectures . to enable a java application to execute on different types of data processing systems , a compiler typically generates an architecture - neutral file format — the compiled code is executable on many processors , given the presence of the java run - time system . the java compiler generates bytecode instructions that are nonspecific to a particular computer architecture . a bytecode is a machine independent code generated by the java compiler and executed by a java interpreter . a java interpreter is part of the jvm that alternately decodes and interprets a bytecode or bytecodes . these bytecode instructions are designed to be easy to interpret on any computer and easily translated on the fly into native machine code . bytecodes are translated into native code by a just - in - time compiler or jit . a jvm loads class files and executes the bytecodes within them . more specifically , a class loader in the jvm loads these class files . the class loader loads class files from an application and the class files from the java application programming interfaces ( apis ), which are needed by the application . the execution engine that executes the bytecodes may vary across platforms and implementations . one type of software - based execution engine is a just - in - time compiler . with this type of execution , the bytecodes of a method are compiled to native machine code upon successful fulfillment of some type of criteria for jitting a method . the native machine code for the method is then cached and reused upon the next invocation of the method . the execution engine may also be implemented in hardware and embedded on a chip so that the java bytecodes are executed natively . jvms usually interpret bytecodes , but jvms may also use other techniques , such as just - in - time compiling , to execute bytecodes . when an application is executed on a jvm that is implemented in software on a platform - specific operating system , a java application may interact with the host operating system by invoking native methods . a java method is written in the java language , compiled to bytecodes , and stored in class files . a native method is written in some other language and compiled to the native machine code of a particular processor . native methods are stored in a dynamically linked library whose exact form is platform specific . fig4 is a block diagram of a jvm in accordance with a preferred embodiment of the present invention . jvm 400 includes class loader subsystem 402 , which is a mechanism for loading types , such as classes and interfaces , given fully qualified names . jvm 400 also contains runtime data areas 404 , execution engine 406 , native method interface 408 , and memory management 410 . execution engine 406 is a mechanism for executing instructions contained in the methods of classes loaded by class loader subsystem 402 . execution engine 406 may be , for example , java interpreter 412 or just - in - time compiler 414 . native method interface 408 allows access to resources in the underlying operating system . native method interface 408 may be , for example , the java native interface ( jni ). runtime data areas 404 contain native method stacks 416 , java stacks 418 , pc registers 420 , method area 422 , and heap 424 . these different data areas represent the organization of memory needed by jvm 400 to execute a program . java stacks 418 store the state of java method invocations . when a new thread is launched , the jvm creates a new java stack for the thread . the jvm performs only two operations directly on java stacks : it pushes and pops frames . a threads java stack stores the state of java method invocations for the thread . the state of a java method invocation includes its local variables , the parameters with which it was invoked , its return value , if any , and intermediate calculations . java stacks are composed of stack frames . a stack frame contains the state of a single java method invocation . when a thread invokes a method , the jvm pushes a new frame onto the java stack of the thread . when the method completes , the jvm pops the frame for that method and discards it . the jvm does not have any registers for holding intermediate values ; any java instruction that requires or produces an intermediate value uses the stack for holding the intermediate values . in this manner , the java instruction set is well - defined for a variety of platform architectures . program counter ( pc ) registers 420 indicate the next instruction to be executed . each instantiated thread gets its own pc register and java stack . if the thread is executing a jvm method , the value of the pc register indicates the next instruction to execute . if the thread is executing a native method , then the contents of the pc register are undefined . native method stacks 416 stores the state of invocations of native methods . the state of native method invocations is stored in an implementation - dependent way in native method stacks , registers , or other implementation - dependent memory areas . in some jvm implementations , native method stacks 416 and java stacks 418 are combined . method area 422 contains class data , while heap 424 contains all instantiated objects . the constant pool is located in method area 422 in these examples . the jvm specification strictly defines data types and operations . most jvms choose to have one method area and one heap , each of which are shared by all threads running inside the jvm , such as jvm 400 . when jvm 400 loads a class file , it parses information about a type from the binary data contained in the class file . jvm 400 places this type of information into the method area . each time a class instance or array is created , the memory for the new object is allocated from heap 424 . jvm 400 includes an instruction that allocates memory space within the memory for heap 424 , but includes no instruction for freeing that space within the memory . memory management 410 in the depicted example manages memory space within the memory allocated to heap 424 . memory management 410 may include a garbage collector , which automatically reclaims memory used by objects that are no longer referenced . additionally , a garbage collector also may move objects to reduce heap fragmentation . the garbage collector performs operations generally referred to as mark / sweep / compact . these operations are the marking of live objects and coalescing sequences of dead objects and spaces that are not marked as live to thereby free or reclaim memory space . any fragmentation caused by the live objects within the heap is compacted during the compact operation . compaction is a process that moves objects toward one end of the heap with the goal of creating the largest possible contiguous free area or areas . compaction helps to avoid allocating new memory to expand the heap size . objects are marked ( noted as live ) by following chains of references from a set of root objects to all other objects they reach . marks are recorded in an area of memory allocated outside of the heap , referred to as a mark bit array . a single bit in the mark bit array is set as each new live object is discovered . the present invention provides an improved method , apparatus , and computer instructions for determining or identifying memory leaks in a heap , such as java heap . the mechanism of the present invention employs an extra bit in the header of each object in the heap . extra bits may be found in most object implementations . after a normal mark - sweep - compact operation cycle , a user driven mark operation sets a bit in the live objects . this bit is used to identify objects that have not been deallocated at the start of the observation period . the user driven mark operation can also be treated as , for example , a periodic event , such as the passage of some period of time in order to constantly monitor the health of the heap . the period of time may be for example , one hour or several days . next fig5 is a diagram illustrating components used to identify leak in a heap in accordance with a preferred embodiment of the present invention . heap 500 in this example is a java heap and may be implemented as heap 424 in fig4 . memory management 502 manages heap 500 and may be implemented as memory management 410 in fig4 . memory management 502 provides management function , including allocating and deallocating objects in heap 500 . additionally , in these illustrative examples , memory management 502 also includes processes for identifying memory leaks in heap 500 . as illustrated in fig5 , heap 500 contains objects 504 , 506 , 508 , and 510 . additionally , indicators 512 , 514 , 516 , and 518 are present in objects 504 , 506 , 508 , and 510 . these indicators take the form of bits in this illustrative example . of course , the indicators may take other forms , such as a flag or a tag that is associated with the object rather than actually being incorporated within the objects . in one illustrative embodiment , all live objects in heap 500 have their indicators set or marked by memory management 502 . in this illustrative example , indicators 512 , 514 , 516 , and 518 are marked by memory management 502 for objects 504 , 506 , 508 , and 510 . the system is then allowed to run in the production environment over the leakage period . this period of time can last for hours , days , or even weeks . no additional overhead is present while the system leaks . when the observation period ends or when a required event occurs , for example , when the heap gets full or near full , an outofmemory exception , a mark - sweep - compact operation is triggered to get the set of actual live objects . then , memory management 502 performs a query of live objects in heap 500 . memory management 502 marks all objects in heap 500 that do not have their indicator marked and presents these to the user in these illustrative examples . these unmarked objects are new objects and the predominant type that are most likely to be a leaked object . this mechanism is useful for memory leaks , which happen over large periods of time . alternatively , the mechanism of the present invention in memory management 502 clears all indicators on currently live objects and then turns on a jvm - wide marking function . the marking operation is triggered on each allocation operation within the jvm and sets the indicator within the created object . this allocation operation may be initiated by an application needed to create an object . when the transaction is over or the observation period has ended , a mark - sweep - compact is triggered to get a set of actual live objects . the presence of marked objects in heap 500 after this step implies the presence of possible memory leaks . a dump of marked objects in heap 500 provides an indication of the source of the memory leak . by identifying objects involved in a memory leak , the processes creating those objects may be determined . as a result , programmers or other designers may alter these processes analyze these processes as part of a memory leak analysis . fig6 is a flowchart of a process for identifying memory leaks in accordance with a preferred embodiment of the present invention . the process illustrated in fig6 may be implemented in a management process , such as memory management 502 in fig5 . the process begins by identifying live objects in a heap ( step 600 ). the identification process is a mark - sweep - compact operation . most jvms have a method to trigger garbage collection programmatically which can be used for the above purpose . the process marks identified live objects through a user driven mark operation ( step 602 ). in these examples , the process marks the objects by setting an indicator , such as a bit in the header of the objects . the system is exposed to the workload , which seems to cause the memory leak . this workload is also referred to as a target workload . thereafter , process observes the system under a target workload ( step 604 ). next , a determination is made as to whether the observation period threshold has been reached ( step 606 ). this threshold may be set in a number of different ways . for example , the threshold may be reached as to when the heap is full or 90 percent full . another possible example is a user - specified end of observation period . if the observation threshold is reached , the process identifies the unmarked objects ( step 608 ). in this illustrative example , the unmarked objects are objects most likely associated with a memory leak in the heap . the process then presents the identified objects ( step 610 ), with the process terminating thereafter . these objects may be presented in a number of different ways . for example , a listing of objects may be presented or a graphical representation of the objects may be displayed in a graphical user interface ( gui ). with reference again to step 606 , if the number of objects do not reach the observation threshold , the process returns to step 604 . next , fig7 is a flowchart of a process for identifying memory leaks in accordance with a preferred embodiment of the present invention . the process illustrated in fig7 may be implemented in a management process , such as memory management 502 in fig5 . the process begins by cleaning the heap ( mark - sweep - compact ) and clearing all live marked objects in the heap ( step 700 ). the process turns on the marking function ( step 702 ). the marking function in step 702 sets the indicator in each new object being allocated hence . the process then waits for the observation period to complete ( step 704 ). the end of the observation period can be denoted by the end of a transaction or user specified time period or a user input . next , a determination is made as to whether any live marked objects are present ( step 706 ). if live marked objects are present , the process dumps the live marked objects ( step 708 ). these live marked objects are objects most likely causing the memory leak . thereafter , the process presents the results of the dump ( step 710 ), with the process terminating thereafter . the process proceeds to step 710 in step 706 , if live marked objects are not present in the heap . in fig8 is a flowchart of a process for a marking function in accordance with a preferred embodiment of the present invention . the process illustrated in fig8 may be implemented in memory management 502 in fig5 in these illustrative examples . the marking function is called by the jvm memory management after allocation of a new object . the process begins by receiving a request to allocate a new object ( step 800 ). the process allocates the object ( step 802 ), and the process marks the object ( step 804 ), with the process terminating thereafter . the setting and resetting of bits or indictors may be preformed using interfaces supported by the jvm . these interfaces include , for example , ones supported by java virtual machine tools interface ( jvmti ). thus , the present invention provides and improved method , apparatus and computer instructions for identifying memory leaks . the mechanism of the present invention employs indicators associated with objects in a heap . these indicators may be contained within the objects or may reference the objects . live objects are identified and the indicators for these live objects are set or unset in the heap depending on the particular implementation . after an event occurs , the heap is examined and objects likely to be associated with a memory leak may be identified through locating marked or unmarked live objects still present in the heap . it is important to note that while the present invention has been described in the context of a fully functioning data processing system , those of ordinary skill in the art will appreciate that the processes of the present invention are capable of being distributed in the form of a computer readable medium of instructions and a variety of forms and that the present invention applies equally regardless of the particular type of signal bearing media actually used to carry out the distribution . examples of computer readable media include recordable - type media , such as a floppy disk , a hard disk drive , a ram , cd - roms , and dvd - roms . the computer readable media may take the form of coded formats that are decoded for actual use in a particular data processing system . the description of the present invention has been presented for purposes of illustration and description , and is not intended to be exhaustive or limited to the invention in the form disclosed . many modifications and variations will be apparent to those of ordinary skill in the art . the embodiment was chosen and described in order to best explain the principles of the invention , the practical application , and to enable others of ordinary skill in the art to understand the invention for various embodiments with various modifications as are suited to the particular use contemplated .
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in the following detailed description , reference is made to the accompanying drawings , which form a part hereof . in the drawings , similar symbols typically identify similar components , unless context dictates otherwise . the illustrative embodiments described in the detailed description , drawings , and claims are not meant to be limiting . other embodiments may be utilized , and other changes may be made , without departing from the spirit or scope of the subject matter presented herein . the aspects of the present disclosure , as generally described herein , and illustrated in the figures , can be arranged , substituted , combined , separated , and designed in a wide variety of different configurations , all of which are explicitly contemplated herein . some embodiments herein are directed to conveyance assemblies that may include a slide channel and a support channel . each of the slide and support channels may include primary and tertiary support bearings . the primary bearings may be configured to support lateral movement of the slide channel with respect to the support channel . the tertiary support bearings may be configured to provide lateral support between the slide channel and the support channel . sliding or rolling mechanisms in some previous conveyance assemblies did not include lateral support to help to reduce and / or prevent a cargo deck coupled to the rolling mechanism from tilting in a lateral direction relative to the structure that housed the conveyance assemblies . in these and other assemblies , the sliding or rolling mechanisms may be coupled by permanently welding cross - members to secure the desired orientation of the sliding or rolling mechanisms in an installed state . in contrast , in some embodiments of the conveyance assemblies described herein , the tertiary support bearings may provide sufficient lateral support such that cross - members may be eliminated or fixed through a fastener ( e . g ., not welded ) such that a footprint of the conveyance assemblies when disassembled may be smaller than other previous conveyance assemblies . a smaller footprint for a conveyance assembly may reduce storage , shipping , installment , manufacturing , and other costs , along with providing other benefits . fig1 a - 1c illustrate top , side , and cross - sectional views of an example support channel 10 , arranged in accordance with at least one embodiment described herein . the support channel 10 may be defined by first , second , and third sides 11 , 12 , 13 . the second and third sides 12 , 13 may extend orthogonally from the first side 11 , such that the support channel 10 may be substantially rectangular . a first flange 14 a may extend from the second side 12 , away from the third side 13 . a second flange 14 b may extend from the third side 13 , away from the second side 12 . the support channel 10 may include first , second , and third fastener tabs 18 a , 18 b , and 18 c , referred to herein as “ fastener tabs 18 ,” coupled to the first side 11 . the fastener tabs 18 may be configured to receive fasteners to couple the fastener tabs 18 with support cross - members to facilitate the assembly of a support frame , described in further detail below . the support channel 10 may include a primary support bearing 15 operably coupled to the second and third sides 12 , 13 of the support channel 10 . the support channel 10 may include a tertiary support bearing 17 operably coupled to the third fastener tab 18 c . the tertiary support bearing 17 may extend through openings 11 o , 12 o defined , respectively , along the first side 11 and the second side 12 . the primary and tertiary support bearings 15 , 17 may be configured to contact , respectively , a first side 21 and a first flange 24 a of a slide channel 20 ( fig2 a - 2c ), described in further detail below . the support channel 10 may also include a catch member 19 configured to engage with a stop member 29 of the slide channel 20 ( fig2 a - 2c ) to help to reduce and / or prevent overextension of the slide channel 20 with respect to the support channel 10 , described in further detail below . the support channel 10 may be formed from any type or a combination of types of materials . in some embodiments , the support channel 10 may be formed from steel . in particular , the support channel 10 may be formed by roll - forming steel . fig2 a - 2c illustrate bottom , side , and cross - sectional views of the slide channel 20 , arranged in accordance with at least one embodiment described herein . the slide channel 20 may include a first side 21 , a second side 22 , and a third side 23 . the second and third sides 22 , 23 may extend orthogonally from the first side 21 , such that the slide channel 20 may be substantially rectangular . a first flange 24 a may extend from the second side 22 toward the third side 23 . a second flange 24 b may extend from the third side 23 toward the second side 22 . the slide channel 20 may include a primary slide bearing 25 operably coupled to the first side 21 of the slide channel 20 . the slide channel 20 may include first and second secondary slide bearings 26 a , 26 b , referred to herein as “ secondary slide bearings 26 ,” operably coupled to the second and third sides 22 , 23 , respectively , of the slide channel 20 . the slide channel 20 may also include a tertiary slide bearing 27 operably coupled to the third side 23 of the slide channel 20 . the primary slide bearing 25 may be configured to contact the first side 11 of the support channel 10 . the secondary slide bearings 26 may be configured to contact the first and second flanges 14 a , 14 b of the support channel 10 . the tertiary slide bearing 27 may be configured to contact the third side 13 of the support channel 10 . the slide channel 20 may further include a stop member 29 , disposed along the first side 21 . the stop member 29 may be configured to contact the catch member 19 of the support channel 10 to help to reduce and / or prevent overextension of the slide channel 20 with respect to the support channel 10 , described in further detail below . the slide channel 20 may be formed from any type or a combination of types of materials . in some embodiments , the slide channel 20 may be formed from steel . in particular , the slide channel 20 may be formed by roll - forming steel . fig3 a and 3b illustrate cross - sectional views of the support channel 10 of fig1 a - 1c and the slide channel 20 of fig2 a - 2c in an assembled state , arranged in accordance with at least one embodiment described herein . more particularly , fig3 a illustrates the interactions of the primary and tertiary support bearings 15 , 17 with the slide channel 20 . fig3 b illustrates the interactions of the primary , secondary , and tertiary slide bearings 25 , 26 , 27 with the support channel 10 . in the assembled state , the primary and tertiary support bearing 15 , 17 and the primary , secondary , and tertiary slide bearings 25 , 26 , 27 may be located at opposite ends of , respectively , the support and slide channels 10 , 20 . accordingly , the cross - sectional views of fig3 a and 3b may illustrate opposite ends of the support and slide channels 10 , 20 in the assembled state . in the assembled state , the support channel 10 may be at least partially enclosed by the slide channel 20 , the respective second sides 12 , 22 , and the third sides 13 , 23 of the support and slide channels 10 , 20 may be adjacent to one another , and the first and second flanges 24 a , 24 b of the slide channel 20 may overlap with the first and second flanges 14 a , 14 b of the support channel 10 . the first and second flanges 14 a , 14 b of the support channel 10 may extend orthogonally to define a width equal to approximately the length of the first side 21 of the slide channel 20 . the first and second flanges 24 a , 24 b of the slide channel 20 may extend orthogonally to define a space equal to approximately the length of the first side 11 of the support channel 10 . accordingly , longitudinal movement of the slide channel 20 with respect to the support channel 10 may be substantially restricted by the respective flanges 14 a , 14 b , 24 a , 24 b . referencing fig3 a , the primary support bearing 15 may contact the first side 21 of the slide channel 20 to facilitate longitudinal movement of the slide channel 20 with respect to the support channel 10 . the tertiary support bearing 17 may contact the first flange 24 a of the slide channel 20 to help to reduce and / or prevent lateral movement of the slide channel 20 with respect to the support channel 10 . referencing fig3 b , the primary slide bearing 25 may contact the first side 11 of the support channel 10 to facilitate longitudinal movement of the slide channel 20 with respect to the support channel 10 . the secondary slide bearings 26 may contact the first and second flanges 14 a , 14 b of the support channel 10 to further facilitate longitudinal movement of the slide channel 20 with respect to the support channel 10 and to help to reduce and / or prevent accidental or other disassembly of the slide channel 20 from the support channel 10 . the tertiary slide bearing 27 may contact the third side 13 of the support channel 10 to help to reduce and / or prevent lateral movement of the slide channel 20 with respect to the support channel 10 . in the example embodiment , the roll - formed manufacture of the support and slide channels 10 , 20 may allow for smoother longitudinal transition of the slide channel 20 with respect to the support channel 10 . for example , the roll - formed manufacture may reduce or eliminate mil that may form in the slide channel 20 when the slide channel 20 is manufactured using other methods . the substantially rectangular shapes of the support and slide channels 10 , 20 may facilitate smooth contact between the support and slide bearings 15 , 17 , 25 , 26 , 27 and the support and slide channels 10 , 20 , further promoting smooth translation of the slide channel 20 with respect to the support channel 10 and thereby reducing wear on the support or slide bearings 15 , 17 , 25 , 26 , 27 . alternately or additionally , the stop member 29 may contact the catch member 19 as the slide channel 20 slides along the support channel 10 to help to reduce and / or prevent overextension and / or accidental disassembly . modifications , additions , or omissions may be made to the support channel 10 illustrated in fig1 a - 1c and the slide channel 20 illustrated in fig2 a - 2c without departing from the scope of the present disclosure . the proportions and dimensions of the support channel 10 and / or slide channel 20 may vary . accordingly , the dimensions or locations of the support or slide bearings 15 , 17 , 25 , 26 , 27 may vary . furthermore , the number of support or slide bearings 15 , 17 , 25 , 26 , 27 provided on the support and slide channels 10 , 20 may vary . in these and other embodiments , the catch and stop members 19 , 29 may be removable to allow disassembly of the slide channel 20 from the support channel 10 . fig4 illustrates a top view of an example support frame 200 , arranged in accordance with at least one embodiment described herein . the support frame 200 may include first and second support channels 110 a and 110 b , referred to herein as “ support channel ( s ) 110 .” the support channels 110 may substantially embody the support channel 10 described according to fig1 a - 1c . the support frame 200 may further include first , second , and third support cross - members 130 a , 130 b , 130 c , referred to herein as “ support cross - member ( s ) 130 .” the first support cross - member 130 a may be coupled to the first and second support channels 110 a , 110 b at the respective first fastener tabs 18 a . the second support cross - member 130 b may be coupled to the respective second fastener tabs 18 b of the first and second support channels 110 a , 110 b . the third support cross - member 130 c may be coupled to the first and second support channels 110 a , 110 b at the respective third fastener tabs 18 c . the support cross - members 130 may be configured to receive fasteners to facilitate fixation of the support frame 200 to a structure , such as a cargo space inside of a vehicle or other storage space . in other embodiments , the support cross - members 130 may couple to the support channels 110 using other fastener devices . in these and other embodiments , the support cross - members 130 may not be welded to the support channels 110 . fig5 illustrates a bottom view of an example slide frame 300 , arranged in accordance with at least one embodiment described herein . the slide frame 300 may include first and second slide channels 120 a and 120 b , referred to herein as “ slide channel ( s ) 120 .” the slide channels 120 may substantially embody the slide channel 20 described according to fig2 a - 2c . each of the first and second slide channels 120 a , 120 b may include first , second , and third fastener tabs 28 a , 28 b , 28 c , referred to herein as “ fastener tab ( s ) 28 ,” coupled to the second or third side 22 , 23 . the slide frame 300 may further include first , second , third , and fourth slide cross - members 140 a , 140 b , 140 c , 140 d referred to herein as “ slide cross - member ( s ) 140 .” the first slide cross - member 140 a may be coupled to the first and second slide channels 120 a , 120 b at the respective first fastener tabs 28 a . the second slide cross - member 140 b may be coupled to the first and second slide channels 120 a , 120 b at the respective second fastener tabs 28 b . the third slide cross - member 140 c may be coupled to the first and second slide channels 120 a , 120 b at the respective third fastener tabs 28 c . the fourth slide cross - member 140 d may be coupled to the first and second slide channels 120 a , 120 b at the respective proximal ends . the slide cross - members 140 may be configured to receive fasteners to facilitate fixation of an apparatus , such as a container , drawer , or shelf , to the slide frame 300 . in other embodiments , the slide cross - members 140 may couple to the slide channels 120 using other fastener devices . in these and other embodiments , the slide cross - members 140 may not be welded to the slide channels 120 . the slide frame 300 may be configured to support a latch mechanism , described in further detail below . as illustrated in fig6 a - 6d , the slide frame 300 may slidably engage with the support frame 200 to form a slidable conveyance assembly 100 ( referred to herein as the “ assembly 100 ”). the support frame 200 may be configured to be fixed to a structure , such as a cargo space inside of a vehicle or other storage space . the slide frame 300 may be configured to slide with respect to the support frame 200 in a longitudinal direction relative to the cargo space . furthermore , the slide frame 300 may be configured to support any apparatus , such as a container , drawer , and / or a shelf . the apparatus supported thereon may therefore be transitioned in and out of the structure by transitioning the slide frame 300 . the slide channels 120 of the slide frame 300 may be slidably engaged with the support channels 110 of the support frame 200 in an assembled state that substantially embodies the slidable engagement of the assembled state of the slide channel 20 with the support channel 10 described according to fig3 a and 3b . accordingly , the slide channels 120 may slide with respect to the support channels 110 by way of the primary and tertiary support bearings against the slide channels 120 and the primary , secondary , and tertiary slide bearings against the support channels 110 . the first slide channel 120 a may slide with respect to the first support channel 110 a and the second slide channel 120 b may slide with respect to the second support channel 110 b . as a result , the slide frame 300 may slidably transition in a longitudinal direction along the support frame 200 between an unextended state ( fig6 a and 6b ) and an extended state ( fig6 c and 6d ), with little to no lateral movement relative to the support frame 200 . the assembly 100 may further include a latch mechanism 150 . the latch mechanism 150 may include a first latch member 151 having first , second , and third corners 151 a , 151 b , 151 c , a second latch member 152 having first and second ends 152 a , 152 b , a latch rod 153 having first and second ends 153 a , 153 b , and a latch handle 154 at the first end 153 a of the latch rod 153 . the first corner 151 a may be rotatably engaged with a first tab 155 a disposed on the first slide cross - member 140 a . the second corner 151 b may be rotatably engaged with a second tab 155 b disposed on the second end 153 b of the latch rod 153 . the third corner 151 c may be rotatably engaged with the first end 152 a of the second latch member 152 . the latch rod 153 may be manipulated by the latch handle 154 to transition the latch mechanism 150 between an engaged state and an unengaged state . in the engaged state , the second latch member 152 may transition laterally towards the first slide channel 120 a ; in the unengaged state , the second latch member 152 may transition laterally away from the first slide channel 120 a . the latch mechanism 150 may be configured to secure the slide frame 300 with respect to the support frame 200 such that slidable movement of the slide frame 300 with respect to the support frame 200 is restricted at certain points . in some embodiments , the first slide channel 120 a may include a first slot configured to receive the second end 152 b of the second latch member 152 . the first support channel 110 a may include one or more slots configured to align with the first slot of the first slide channel 120 a as the slide frame 300 slides with respect to the support frame 200 . accordingly , at certain points along the slidable transition of the slide frame 300 , the first slot of the first slide channel 120 a may align with one of the one or more slots of the first support channel 110 a , whereupon the latch mechanism 150 may be transitioned into the engaged state , such that the second latch member 152 extends through the slots of both the first support and slide channels 110 a , 120 a , thereby securing the slide frame 300 with respect to the support frame 200 . modifications , additions , or omissions may be made to the assembly 100 illustrated in fig4 - 6d without departing from the scope of the present disclosure . in some embodiments , the support and slide frames 200 , 300 may include fewer or more support and slide cross - members 130 , 140 , respectively , than those illustrated . alternately or additionally , the support and slide cross - members 130 , 140 may be disposed along the support and slide channels 110 , 120 at different locations than those illustrated . in other embodiments , the assembly 100 may not include any support or slide cross - members 130 , 140 . in these and other embodiments , an apparatus supported by the assembly 100 , such as a drawer or shelf , may be coupled to both first and second slide channels 120 a , 120 b of the slide frame 300 such that the first and second slide channels 120 a , 120 b slide along the first and second support channels 110 a , 110 b in unison . alternately or additionally , in some embodiments , the assembly 100 may not include the latch mechanism 150 , or may include more than one latch mechanism 150 , or may include a different type of latch mechanism 150 than that discussed and / or illustrated above . alternately or additionally , the assembly 100 may include fewer or more support and slide channels 110 , 120 . for example , in some embodiments , the assembly 100 may include a single support channel 110 and a single slide channel 120 . alternately or additionally , the assembly 100 may include three or more support channels 110 and a corresponding slide channel 120 for each support channel 110 provided . in these and other embodiments , the number of support and slide channels 110 , 120 provided may vary based on the required width of the assembly 100 , the apparatus supported by the assembly 100 , and / or the weight of the cargo to be supported by the assembly 100 , among other factors . from the foregoing , it will be appreciated that various embodiments of the present disclosure have been described herein for purposes of illustration , and that various modifications may be made without departing from the scope and spirit of the present disclosure . accordingly , the various embodiments disclosed herein are not intended to be limiting , with the true scope and spirit being indicated by the following claims .
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symbols ( reference numerals ) mainly used in the figures indicate the following : 101 denotes signal input ; 102 addition of parity ; 103 addition of subcode ; 104 interleave ; 105 modulation ; 106 a disk ; 107 system control ; 109 a semiconductor circuit for processing recording signals ; 110 output ; 111 a process of putting data together in predetermined units ; 112 error correction ; 113 address detection ; 114 deinterleave ; 115 demodulation ; and 119 a semiconductor circuit for processing reproducing signals . a preferred embodiment of the present invention will be described below with reference to the accompanying drawings . fig2 and 3 show data structures used to record user data according to the present invention . fig1 shows an example in which the size of a record block is changed according to the present invention . fig4 shows a data arrangement obtained as a result of rearranging the data structure shown in fig3 to actually record the data . fig2 shows a data structure of a record unit of data to be recorded on a recording medium according to the present invention . the following description assumes that the recording medium is an optical disk . the record block comprises : in each column , 496 bytes ; and in each row , a sync ( synchronization signal ) of one byte , data of 38 bytes , and 3 sets of a burst error detecting subcode of one byte and data of 38 bytes ; totaling 77 , 736 bytes . the arrow indicates the direction in which data is recorded on a disk . the ldc ( long distance code ) portions constitute user data and are obtained as a result of adding 32 parities to 216 pieces of data , using an rs ( reed solomon ) code . in the figure , the code runs sequentially as a single column indicated by the shaded portion . however , the code may be divided and arranged by means of interleaving . fig3 shows a data arrangement in which each 2k bytes of data is put together into one logical block using the record block shown in fig2 . thus , 32 2k - byte logical blocks can be arranged using the 64k - byte record block . in addition to the above example , the logical blocks may be arranged such that each 2 blocks are aligned in a row . fig4 shows the structure of data obtained as a result of adding error correcting code to the 2k - byte logical blocks 1 to 4 shown in fig3 . as shown in the figure , the error correcting code rs ( 248 , 216 , 31 ) is vertically ( in the column direction ) added to the data . thus , the figure shows a case in which the error correcting code is added to the vertically aligned logical blocks 1 to 4 . however , the error correcting code may be added to the logical blocks 1 , 16 , 2 , and 17 with the same effect . thus , the present invention is not limited to a specific combination of logical blocks ; any combination may be employed by means of regular interleaving . fig1 shows a method for forming and recording a record block smaller than that shown above . as shown in fig2 , the record block a comprises : in each column , 496 bytes ; and in each row , a sync of one byte , data of 38 bytes , and 3 sets of a burst error detecting subcode of one byte and data of 38 bytes ; totaling 77 , 736 bytes . the arrow indicates the direction in which the data is recorded on a disk . the record block b 1 comprises : in each column , 62 bytes ; and in each row , a sync of one byte , data of 38 bytes , and 3 sets of a burst error detecting subcode of one byte and data of 38 bytes , as in the case of the record block a ; totaling 9 , 672 bytes . the direction in which data is recorded on a disk is the same as that for the record block a . data of 2048 bytes and an error check code of 4 bytes collectively form a recorded data unit , and the data of the record block a is made up of 32 recorded data units . as for the record block b 1 , data of 2048 * 4 bytes and an error check code of 4 * 4 bytes collectively form its minimum recorded data unit . the minimum recorded data unit is rearranged , as indicated by the record block b 2 in the figure , to form a structure ( arrangement ) similar to that of the record block a which includes rs code ( error correcting code ), making it possible to use the same method as that employed for the record block a for carrying out ram control to temporarily store data for signal processing or performing error correction processing . that is , error correcting code and then a subcode are added to the structure of the record block b 2 . when recording the data , the data is recorded as the record block b 1 ( using the structure of the record block b 1 ). since the subcode is a code string of 62 bytes , it may be added as a single column or arranged by means of interleaving . incidentally , data of 2048 bytes are roughly 2k bytes . accordingly , the record block b 1 has a data structure for recording 8k bytes of data which includes 62 record block units each arranged in a row . however , the record block b 1 is not limited to this specific data structure , that is , this specific number of bytes , 8k bytes . the record block b 1 ( that is , its data structure ) may be of any size if it can be easily divided and rearranged to form the data structure of the record block a . on the other hand , a data structure made up of small blocks such as those described above may make it impossible to interleave the data , deteriorating the error correction capability . to solve this problem , the same data may be recorded a plurality of times or error correcting parities may be added . fig7 shows a 16k - byte recorded data structure formed from the 8k - byte recorded data structure shown in fig1 . a 32k - byte recorded data structure also can be easily obtained from the 16k - byte recorded data structure using a similar method . fig8 shows an area in the user data area of a dvd in which copy control information is recorded . in the figure , the area cgms ( copy generation management system ) records information on user data , and therefore is not required as management information data . accordingly , management information may be recorded in this area by coding the size of data to be recorded into a few types of code and recording the code . for example , when 2 bits are assigned to the area cgm , the flag “ 00 ” may be used to indicate an 8k byte recorded data . the area for recording such information is not limited to the area cgms . any area can be used to record such information if it is used for user data and not included in the management area . fig8 shows a data structure larger than that shown above . as shown in fig8 , the record block d comprises 32k bytes of data , which is half of the 64k - byte record block a in size . since dvds record data in units of 32k bytes , a record block of this data size can easily be made compatible with a dvd system . with this record block , data to be recorded is added with parities and subcodes and then interleaved such that the data is distributed to enhance the burst error detecting capability . the subcodes may be added after the interleave instead of before the interleave . with the record block a , data is interleaved by adding parities to the data and then , for example , rearranging it . with this arrangement using an interleaving technique , when a burst error has occurred , two apparent burst errors half as long as the actual burst error are detected . therefore , even in the case where data cannot be serially reproduced due to the burst error , the data may be corrected by use of the added parities if the apparent burst errors are within a distance of error correction by use of interleaving . to obtain such effect , the data is interleaved and then the subcodes added to the interleaved data are also interleaved to enhance the error correction capability . since the record block d includes data smaller than that of the record block a , the same interleaving technique as that for the record block a cannot be applied to the record block d . accordingly , the subcodes are interleaved within 248 bytes . by using such a method , it is possible to form and record a record block of 32k bytes . in each of the above descriptions , data is put together in units of a number of bytes close to the nth power of 2 ( n is an integer ). this is not restrictive . to round a fraction , redundant data may be added to produce a number easy to use when combining data . fig9 shows an example of how data to be recorded according to the present invention is actually recorded on a disk . the recording disk has arranged thereon a management information area , a read - in area , a user data area , and a readout area , and data is recorded in a predetermined format in each area . data is recorded in predetermined record blocks having 64k bytes in the user data area . as for the management information area , data is recorded in record blocks having a block size smaller than 64k bytes , namely 4k bytes , 8k bytes , 16k bytes , or 32k bytes . by recording data as described above , it is possible to efficiently record management information in a limited area . it should be noted that even though the management area is provided inside the read - in area in fig9 , this relationship may be reversed . furthermore , if it is known beforehand that there is not enough management area , it may be arranged such that a definition can be established to extend it . for example , the border between the read - in area and the user data area shown in fig5 may not be fixed ( even though it is fixed between 02ffffh and 030000h in terms of ecc block addresses in the figure ), and may be changed . in such a case , the position of the changed border can be recorded in the first portion of a specific area such as the management information area to extend the management area if it is known beforehand that a management area of large size is required . fig1 shows a configuration of a recording apparatus according to the present invention . reference numeral 101 denotes a signal input section for inputting data to be recorded ; 102 an “ addition of parity ” section for adding error correcting code ; 103 an “ addition of subcode ” section for adding information such as addresses in a distributed manner ; 104 an interleave section for rearranging data ; 105 a modulation section for recording data ; and 106 a disk on which the data is recorded . reference numeral 107 denotes a system control circuit for controlling the system , while 109 denotes a semiconductor circuit for processing recording signals . though not shown , a recording means is provided to record data on a recording medium . the term “ a recording means ” here denotes , for example , an optical head . a recording means may further include a recording optical system and a laser for recording . the term “ a combining means ” here indicates a means for putting together data to be recorded on a recording medium in predetermined units so that parities can be added to the data . for example , the process ( section ) 100 for combining data into predetermined units shown in fig1 is a combining means . it should be noted that if there are a plurality of different data units ( that is , each data unit consists of a different number of bytes , etc .) in which data is put together , a different circuit may be used for each data unit , or alternatively a single circuit may be used which is capable of changing the number ( of bytes ) constituting the data unit . further , an error correcting code adding means is a means for adding parities to data to be recorded on a recording medium . for example , the “ addition of parity ” section 102 shown in fig1 is an error correcting code adding means . an error correction code adding means may include a mechanism for storing data in a ram , etc . and writing / reading the data . it should be noted that if there are a plurality of different data units ( that is , each data unit consists of a different number of bytes , etc .) in which data is put together , a different circuit may be used for each data unit as an error correcting code adding means , or alternatively a single circuit may be used for all different data units as an error correcting code adding means by switching among different data units or among different data string units ( each having a different number of bytes , etc .). the system is controlled such that when data to be recorded is management information and small , each piece of data entered from the signal input section is set to be small and is not subjected to ordinary interleave processing but directly subjected to modulation and recorded on a disk by use of changeover switches after it is added with parities and subcodes . in the figure , the addition of subcode 103 is carried out before the interleave . however , it may be carried out after the interleave , depending on the data to be recorded . furthermore , even in the above case in which data is not subjected to the ordinary interleave processing by use of the changeover switches , the data may be subjected to simple interleave processing which is suitable for small data to be recorded . the above processing operations may be switched by a changeover signal from the system control 107 or automatically switched by means of address detection performed inside the semiconductor circuit 109 . fig1 shows a configuration of a reproducing circuit ( apparatus ). a reproduced signal from a disk 106 is demodulated by a demodulation section ( circuit ) 115 and is subjected to address detection by an address detection section 113 . reference numeral 114 denotes a deinterleave section for rearranging data . the data is subjected to error correction by an error correction section 112 , and output from a terminal 111 after the data is put together in predetermined units . reference numeral 119 denotes a semiconductor circuit for processing reproducing signals . the term “ a demodulating means ” here denotes a means for demodulating data in a recording medium . for example , the demodulation circuit 115 in fig1 is a demodulating means . the term “ a reproduction combining means ” here indicates a means for combining data reproduced from a recording medium in predetermined units corresponding to units in which the data was recorded , in order to carry out error correction . this means corresponds to the process ( address detection section ) 113 , shown in fig1 , for detecting the address of data and combining the data in predetermined units . it should be noted that if there are a plurality of different data units ( that is , each data unit consists of a different number of bytes , etc .) in which data is put together , a different circuit may be used for each data unit , or alternatively a single circuit may be used which is capable of changing the number ( of bytes ) constituting the error correction data unit based on the address value . further , an error correcting means is a means for correcting an error in data reproduced from a recording medium . for example , the error correction section 112 shown in fig1 is an error correcting means . an error correcting means may include a mechanism for storing data in a ram , etc . and writing / reading the data . it should be noted that if there are a plurality of different data units ( that is , each data unit consists of a different number of bytes , etc .) in which data is put together , a different circuit may be used for each data unit as an error correcting means , or alternatively a single circuit may be used for all different data units as an error correcting means by switching among different data units or among different data string units ( each having a different number of bytes , etc .). the system is controlled such that when data to be reproduced is management information and small , the unit of data to be reproduced from a recording medium and error - corrected is set to be small and subjected to error correction . when management information data of small size is read out , the location of the data is checked by means of address detection . by controlling changeover switches , the data is not subjected to the ordinary interleave processing before it is stored . then , the data is error - corrected in predetermined record blocks and output . fig1 shows the structure of cpr_mai ( copyright management information ) 403 in the data area in a dvd . of available 48 bits , only 4 bits are currently used . reference numeral b 47 denotes cpm ( copyrighted material ) which indicates whether this sector includes a copyrighted material ; b 46 denotes cp_sec which indicates whether this sector has a specific data structure for a copyright protection system ; and b 45 and b 44 denote cgms ( copy generation management system ) which records copy restriction information . information on control of data copying must be recorded in the data area . however , copy information such as cgms need not be recorded in the management area . accordingly , the following arrangement can be made . the size of a record block in the management area may be coded into a code of 2 bits which is then recorded in the cgms 2 - bit area , making it possible to obtain the size of the record block . fig1 shows a data structure used to record data in units of 4k bytes . in the figure , reference numerals a to h each denote a data unit having 19 bytes in each row and 31 bytes in each column . a record block e 2 comprises : two subcode strings each having 62 bytes including parities ; and 19 code strings each having 248 bytes arranged in a column . these data units ( the record block e 2 ) are rearranged into a record block e 1 having a data structure comprising 31 bytes in each column and 156 bytes in each row . by using such a data structure , it is possible to record data having a size of 4k bytes . incidentally , if the subcode strings s 1 and s 2 in the record block e 2 are divided and rearranged as they are , the positions of the syncs after the rearrangement do not match the arrangement of the user data in the record block e 1 . to solve this problem , as shown in fig1 , the syncs are inserted into specific portions in the structure of the code strings s 1 and s 2 , and data , such as address information , and parities added to the data are put in the other portions . by using such a data structure of the subcodes , it is possible to match the positions of the syncs with the arrangement of the user data . fig1 shows an example in which errors are included in portions of a sync and a subcode when the 4k - byte data structure illustrated in fig1 and 14 is reproduced . in the figure , a sync n . g . and a subcode n . g . are indicated as error examples . specifically , when a sync is not properly detected or erroneous data is included in error correcting code for subcode , the subsequent string must be processed since the string may be erroneous . when a sync detection n . g . or a subcode n . g . occurs , as described above , the error portions included in the data units a to h can be estimated from the position of the sync n . g . or the subcode n . g . as indicated by the shaded portions in the figure . by correcting errors in data based on this information , it is possible to properly decode the data . in such a case , the data may be recorded a plurality of times . fig1 shows another example ( different from the example of fig1 ) in which the case where a sync is not properly detected or erroneous data is included in error correcting code for subcode occurs a plurality of times serially , and the data between the errors is processed since the data may be erroneous . use of such an algorithm increases the reliability of information on the positions of errors in data , making it possible to correct the data by discarding the erroneous portions . fig1 is a flowchart showing a method for processing the data to be recorded described so far , changing the structure of the data . first of all , when data is recorded , it is determined whether the target area is the management area at step 171 , and if it is the user data area , the data is processed in units of 64k bytes . syncs and subcodes are added at step 173 , and the data is interleaved to produce a record data structure at step 174 . if the target area is determined to be the management area at step 171 , on the other hand , the size of the data to be recorded is determined at step 175 . in this case , if the size of the data to be recorded requires that the data be recorded in record units of 64k bytes , a 64k - byte record block is used to record the data as in the case of the user data area . the sizes which require that data be recorded in record units of 64k bytes include sizes a little smaller than 64k bytes ( for example , 60k bytes or so ) and sizes larger than 64k bytes . if the size of the data to be recorded is determined to be small at step 175 , an appropriate record block size is selected based on the size of the data to be recorded at step 179 . as described above , a record block can be configured such that its size is set to be one of various sizes smaller than 64k bytes , such as 32k bytes ( illustrated in fig8 ), 16k bytes ( illustrated in fig7 ), 8k bytes ( illustrated in fig1 ), and 4k bytes ( illustrated in fig1 ). accordingly , by selecting an appropriate record block size based on the size of data to be recorded , it is possible to reduce an amount of data recorded in the management area . then , an identification code is added at step 180 . the identification code indicates the size of a record block . the addition of syncs and subcodes and the conversion of the data arrangement are carried out based on the size of the record block indicated by this identification code . specifically , at step 181 , the data to be recorded and the identification code are added with syncs and subcodes for small sizes . at step 182 , the data is rearranged based on the size to produce data to be recorded . by carrying out such processing , it is possible to record even data of small size in a disk management area . according to the present invention described above , when data is recorded on a recording medium , even data of small size to be recorded can be subjected to recording signal processing in much the same way as ordinary data ( of ordinary size ) to be recorded , making it possible to record data in a management information area in small units . accordingly , it is possible to reduce the time required for recording management information , and efficiently use the management information area .
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the apparatus and methods of the present invention may be employed in particular to improve the detection of an analyte that may be present in a variety of fluids . gases are the preferred fluids according to the practice of the present invention , and therefore the following description of the invention will include a description of the arrangement , construction , and operation of pneumatic devices , and is directed to the control of a plurality of gaseous streams in a detector in a gas chromatographic analytical system ( hereinafter , a chromatograph ). however , for the purposes of the following description , the term &# 34 ; pneumatic &# 34 ; will also be considered to refer to all types of fluids . further examples that are particularly benefited by use of the present invention include supercritical fluid chromatography and high - pressure gas chromatography ( hpgc ). however , it should be understood that the teachings herein are applicable to other analytical instruments , including liquid chromatographs , high - pressure liquid chromatographs ( hplc ), clinical analyzers , flow - injection analyzers , laboratory water purification systems , syringe - type reagent dispensers , manual and automated solid phase extraction ( spe ) instruments , supercritical fluid extraction ( scf ) instruments , stopped - flow spectrophotometers , automated protein or nucleic acid sequencers , and solid phase protein or nucleic acid synthesizers . a new and novel analytical instrument is shown in fig1 and is generally designated chromatograph 10 . in the preferred embodiment , the chromatograph 10 is a hewlett - packard hp6890 gas chromatograph . in order to perform a chromatographic separation of a given sample compound , a sample is injected with a pressurized carrier gas by means of an injector 12 . the carrier gas supplied to injector 12 is provided from a source 12a through one or more pneumatic manifold assemblies 13 , each of which serves in part to control and redirect a plurality of gas flows , including the carrier gas and a plurality of detector gasses of appropriate types , such as air , hydrogen , and make - up gas . the detector gases are provided from respective sources ( one such source 24a is shown ) to the pneumatic manifold assembly 13 . suitable fluid - handling devices such as valves , sensors and the like in the pneumatic manifold assembly 13 are operated under the control of the computer 22 by a way of control signals provided on a data and control lines 28 , 30 . for example , the pneumatic controller 26 effects control of , among other things , fluid flow rate , fluid pressure , fluid flow regulation , and the continuity or discontinuity of flow . as further example , the time during which a particular valve in the pneumatic manifold assembly 13 will remain open and closed in relation to control signals received on the data and control line 28 and in accordance with certain operating conditions of the chromatograph 10 . the control and data line 30 also allows the return of sense information from suitable sensors and signal - interface electronics that are provided in the pneumatic manifold assembly 13 . accordingly , the computer 22 , pneumatic controller 26 , and pneumatic manifold 13 may be operated to effect a modulation of any of the aforementioned gas flows , either individually or in combination . a column 14 is positioned within an oven 16 . the carrier gas / sample combination passing through column 14 is exposed to a temperature profile resulting in part from the operation of a heater 18 within oven 16 . during this profile of changing temperatures , the sample will separate into its components primarily due to differences in the interaction of each component with the column 14 at a given temperature . as the separated components exit the column 14 , they are detected by the detector 24 . as the components exit column 14 they are detected by a flame - based detector ( hereinafter , detector ) 24 . in particular , and in accordance with a feature of the present invention , the pneumatic controller 26 modulates the flow of one or more of the detector gases that are provided to the detector 24 during an ignition sequence , as will be described below . computer 22 maintains overall control of all systems associated with gas chromatograph 10 . it will be recognized that any particular gas chromatograph may include more systems than those described in relation to the present invention . it will also be understood that although computer 22 is shown as a single block , such computer includes a central processing unit and all associated peripheral devices , such as random access memories , read - only memories , input / output isolation devices , clocks and other related electronic components . in the preferred embodiment , the central processor used in computer 22 is a microprocessor . as such , computer 22 includes a memory in which information and programming can be stored and retrieved by known methods . however , it will be appreciated that the programmed control of pneumatic controller 26 can be implemented by other computing means , such as an embedded microprocessor or dedicated controller circuit incorporated in the pneumatic controller 26 . also , the programming associated with computer 22 that is utilized in relation to the present invention will be readily understood from the description herein . an electronic control panel 50 is shown to include at least two main input / output components , namely a keypad 58 , and a display 60 . by monitoring the operation of the chromatograph 10 by signals from certain components , such as the detector 24 , the computer 22 can initiate and maintain certain functions required for an analytical run . consequently , indicating or prompt messages can be generated by computer 22 and displayed on display 60 . operating commands and other information are entered into computer 22 by way of keypad 58 . one particular data type is detector ignition setpoint values and one particular operating command is a detector ignition command , both of which may be prompted by messages displayed on display 60 and the requisite command or data are entered through keypad 58 . another particular type of data is a detector ignition lit offset value , which may be acknowledge by messages displayed on display 60 and modified by commands and data entered through keypad 58 . the ensuing ignition sequence which relates to the present invention is then automatically provided under control of the computer 22 as described below in reference to fig4 and 5 . the control of one or more fluid flow characteristics is provided as shown in fig2 and 3 . in the embodiments illustrated in fig2 and 3 , the computer 22 controls the flow of the make - up fluid , the first fluid , the first detector fluid , and the second detector fluid by transmitting an appropriate signal to the pneumatic controller 26 , which in turn provides respective signals to a respective valve in the pneumatic manifold assembly 13 to increase or decrease the amount of fluid flowing therethrough to the detector 201 . in particular , the fluid flow control in the embodiment illustrated in fig3 is preferably provided via electronic pneumatic control ( epc ). for further details of electronic pneumatic control techniques , one may consult , for example , klein , et al ., u . s . pat . nos . 4 , 994 , 096 and 5 , 108 , 466 , the disclosures of which are incorporated herein by reference . fig2 shows a schematic illustration of a first preferred embodiment of a detector 201 preferably constructed as a fid and a pneumatic control section 202 that is best suited for operation in a non - epc configuration . the detector 201 constructed to include an igniter 211 , an ignition line 212 , and a collector electrode 213 . the igniter 211 and the collector electrode 213 are aligned in the interior of a jet 214 that is mounted in a passageway defined by a fluid - directing structure 210 . an electronic power supply ( not shown ) provides a controlled amount of electrical current or voltage on the ignition line 212 to cause a selectable amount of heat in the igniter 211 . in response , the fluid flow in the proximity of a jet 214 achieves an elevated temperature and is ignited . a vent tube 232 allows the combustion and further passage of the fluid mixture from the detector 201 . the collector electrode 213 is electrically connected to an ion current measurement device ( not shown ) such as an electrometer which is used to measure the magnitude of ionization current that flows from the jet 214 to the collector electrode 213 . the resulting ion current is measured to provide a chromatogram . a fluid mixing structure 222 communicates with the fluid - directing structure 210 for directing the following fluids toward the igniter 211 : a first fluid supplied on a first fluid supply line 224 , a make - up fluid supplied on a make - up fluid line 225 , a first detector fluid supplied on a first detector fluid line 226 , and a second detector fluid supplied on a second detector fluid line 227 . preferably , the first fluid line 224 is integral with the column 14 and hence the first fluid comprises a heated , gaseous combination ( under pressure ) of the sample that is to be analyzed and a carrier gas . the make - up fluid also preferably comprises carrier gas ; the first detector fluid comprises pressurized hydrogen ( h 2 ) gas ; and the second detector fluid comprises air at ambient pressure and temperature . the make - up fluid and the first detector fluid are combined via a conduit 229 connected between the fluid mixing structure 222 , the make - up fluid line 225 , and the first detector fluid line 226 . also included are a make - up fluid pressure regulator 235 , a make - up fluid valve 225v , and a make - up fluid restrictor 225r ; first detector fluid valve 226v and restrictor 226r ; and second detector fluid valve 227v and restrictor 227r . in the instance that the detector 201 is constructed as a fid , it is contemplated that a predetermined pneumatic volume is provided in the second detector fluid line 227 between the valve 227v and the restrictor 227r . ( in the alternative instance that the detector 201 is constructed as a fpd , it is contemplated that a predetermined pneumatic volume would be provided in the first detector fluid line 226 between the valve 226v and the restrictor 226r .) the valves 225v , 226v , and 227v are preferably solenoid valves that are subject to the control of the pneumatic controller 26 as will be described in greater detail below . fig3 illustrates an alternative embodiment 202a of the pneumatic control section 201 of fig2 that is best suited for operation as an epc configuration . that is , in fig3 the valves 225v , 226v , and 227v are preferably provided in the form of proportional valves that are subject to the control of the pneumatic controller 26 according to signals received by the computer 22 from sensors 225s , 226s , and 227s , as will be described in greater detail below . preferably , such sensors are pressure sensors that provide sense signals indicative of the respective pressures in the make - up fluid line 225 , first detector fluid line 226 , and second detector fluid line 227 . in the embodiment illustrated in fig3 sensors 225s , 226s , 227s each sense a particular fluid parameter , such as fluid pressure or fluid flow , and transmits a feedback signal representative of such parameter to the computer 22 . by monitoring the sense signals from sensors 225s , 226s , 227s , the computer 22 can effect near - instantaneous alteration of the flow of each fluid that is provided to the detector 201 at any desired time . in the preferred embodiment of the computer 22 , the procedures necessary to set up or operate chromatograph 10 , so that a particular gas chromatographic separation test or analytical run can be conducted , are automated . the contemplated automation allows the operator to program events using programming via a table of fluid flow setpoints , a run table , and by clock time programming . a plurality of timed events may be programmed in each run table for execution during an analytical run . run time programming allows certain setpoints to change automatically during a run as a function of the chromatographic run time . for example , an event such as detector ignition may be programmed to occur prior to injection . such programming is contemplated as being applicable to the operation of the pneumatic controller , and particularly to the control of at least one of the first detector fluid flow and the second detector fluid flow . certain programmed steps effected by computer 22 in controlling the operation of the pneumatic controller 26 , which relate to and are in accordance with the present invention , are illustrated in fig4 and 5 . in the preferred embodiment , the operator may enter data regarding the operation of the pneumatic controller 26 into the computer 22 by use of the keypad 58 . the computer 22 operates to store the entered information into memory . the data thus entered may include one or more commands that are to be implemented immediately , or if necessary , the entered data may be stored in the form of one or more tables for later access . for example , the programmed events may be arranged in order of execution time in a run table . text denoting the characteristics of each event may be displayed on the display 60 . in the embodiments illustrated in fig2 and 3 , individual fluid streams combine to form a fluid mixture that is restricted to pass the igniter 211 and the collector electrode 213 . the flow characteristics and the composition of the fluid mixture that passes the igniter 211 will determine the success or failure of the ignition mechanism that occurs at the igniter 211 . hence , in a departure from the prior art , the content of the fluid mixture is temporarily altered during certain steps in an ignition sequence , so as to favor the ignition mechanism and thereby facilitate ignition . specifically , the flow of at least one of the fluid streams is modulated to effect either an increase or decrease in the fluid flow . accordingly , and in a particular feature of the present invention , a particular modulation of the flow of the first or second detector fluid during an ignition sequence has been found to facilitate detector ignition . such ignition has been successful in instances that may otherwise be unsuccessful due to the influence of the content and other characteristics of the fluid mixture . in the preferred embodiment , and as illustrated in fig4 and 5 , either the air flow rate or the hydrogen flow rate is modulated during a portion of the ignition sequence . the implementation of the modulation will differ slightly according to whether the embodiments of fig2 or fig3 are provided . because the flow through the solenoid valves shown in the configuration in fig2 can only be turned on or off , rather than varied continuously , a modulated flow is preferably achieved by cycling the appropriate valve ( valve 227v or fid , valve 226v for fpd ) on and off , starting at a low duty cycle and increasing it ( preferably at a fixed frequency ) until full flow is attained . in the configuration illustrated in fig3 the contemplated epc achieves a modulated flow by opening the appropriate valve ( valve 227v for fid , valve 226v or fpd ) in a continuous ramp , starting at a low value and increasing it until full flow is attained . in an instance of non - epc control , the second detector fluid flow is best modulated by a solenoid valve according to the practice of : a ) fixing the flow duty cycle and varying the frequency of modulation ; b ) fixing the frequency of modulation and varying the flow duty cycle ; or c ) varying both the flow duty cycle and the frequency of modulation . preferably , a fixed frequency option is selected because it is the easiest to implement in firmware resident in the computer 22 . the preferred frequency of modulation is chosen to offer : d ) for all operating conditions , a predetermined range of duty cycles that will result in ignition , and e ) for the most severe conditions ( such as may be found during a very high second detector fluid flow and when helium is used as the make - up gas ), the greatest span of duty cycles which will result in ignition . in another feature of the present invention , the aforementioned criteria may be applied to a particular chromatograph 10 such that a modulation envelope may be predetermined to provide the requisite flow modulation that will facilitate , if not ensure , a successful ignition even under worst case conditions . in a further aspect of the present invention , in the ignition of a fid , the make - up fluid flow is discontinued during a portion of the ignition sequence and then resumed after the flame is lit . in a still further aspect of the present invention , in the ignition of a fid , the first fluid flow is discontinued during a portion of the ignition sequence and then resumed after the flame is lit . in the preferred embodiment of the chromatograph 10 , detector 24 is provided as a plurality of separately located detectors , e . g ., a front detector and a back detector . also in the preferred embodiment , the first detector fluid is provided as hydrogen gas . fig4 illustrates a first preferred ignition sequence that is pertinent to the operation of the chromatograph 10 when one such detector 24 is provided in the form of an fid . in the preferred embodiment , each of the first , second , and third delay periods are approximately 2 - 3 seconds . fig5 illustrates a second preferred ignition sequence that is pertinent to the operation of the chromatograph 10 when one such detector 24 is provided in the form of an fpd . in the preferred embodiment , each of the first , second , and third delay periods are approximately 1 - 2 seconds . the advantages of the above - described embodiments were demonstrated in a series of ignition repeatability experiments performed on a test apparatus that included a fid mounted in a hewlett - packard hp5890 gas chromatograph . pneumatic control was provided according to the non - epc configuration illustrated in fig2 . consistent ignition was found to occur according to certain criteria , as will now be described . one modulation frequency that was found to satisfy these criteria in the chromatograph under test was 0 . 5 cycles / sec . a slow duty cycle was found to be preferable because the time demands on the firmware in the computer 22 are lessened and any differences in valve actuation speed are less likely to affect the success of the ignition . based on the test data , the preferred duty cycle started at 10 % and was stepped through several duty cycles until at least 60 %, at which point the relevant valve can remain full - on . adding a pneumatic volume between the valve 227v and the frit 227f was found to reduce the necessary frequency of actuation and , in addition , increase the range of duty cycling at which the flame will ignite . a volume of 1500 mm 3 was found to be the preferred amount . fig6 - 9 illustrate the test results that indicate the effect of certain operating conditions in the chromatograph upon ignition , according to a relationship between flow duty cycle and modulation frequency . in each instance , a successful ignition was found to occur within one or more particular modulation envelopes , each of which relate a range of flow duty cycles and modulation frequencies . the illustrated modulation envelopes are provided as examples of modulation envelopes that were particularly successful is achieving consistent ignition in the fid of the test apparatus , and in no way should be considered limiting . fig6 shows first ( a ), second ( b ), and third ( c ) modulation envelopes realized in the aforementioned test apparatus according to a variation in pneumatic volume . the response curves ( a ), ( b ), and ( c ) correspond to the pneumatic volume being implemented as 1500 mm 3 , 3000 mm 3 , and 785 mm 3 respectively . fig7 shows a modulation envelope realized in the aforementioned test apparatus according to an interruption in make - up gas during the ignition sequence . fig8 shows first ( a ) and second ( b ) modulation envelopes realized in the aforementioned test apparatus according to differing air flow rates during the ignition sequence . the first and second response curves ( a ) and ( b ) correspond to the air flow rates being implemented as 400 milliliters / minute and 650 milliliters / minute , respectively . fig9 shows first ( a ) and second ( b ) modulation envelopes realized in the aforementioned test apparatus according to differing jet orifice sizes that were used during the ignition sequence . the first and second response curves ( a ) and ( b ) correspond to the jet orifice being implemented as 0 . 030 inches and 0 . 011 inches , respectively . fig9 illustrates at least two worst case ignition conditions . by satisfying the ignition flow requirements via valve modulation rather than diverting fluid flow , the preferred embodiment may be constructed without a diverter valve and the associated costs of tubing and fittings , additional assembly labor , and machining of parts . reliability and ease of use are increased . the presence of make - up gas and / or carrier gas , each of which undermines successful ignition by diluting the hydrogen and oxygen in the fluid mixture and by cooling the igniter , may be eliminated during a portion of the ignition sequence . in contrast to systems constructed according to the prior art , a successful ignition in the preferred embodiment is not as subject to manufacturing production variations . heretofore , a normal variation in , for example , the gas source pressure , which may stray out of the range required by an operating condition for proper ignition would cause the operator to experiment with differing source pressures to try to find a reliable operating region . in the preferred embodiment , the first or second detector fluid flow is modulated during the ignition sequence and therefore will pass through the optimum fluid mixture that facilitates ignition . the modulation is automatically effected during the ignition sequence , in a manner not generally noticeable by the operator , thereby ensuring a reliable flame ignition . although the invention has been described with reference to the above - described preferred embodiments , variations and modifications are contemplated as being within the scope and spirit of the present invention .
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the present invention is hereinafter further described with reference to accompanying drawings by using embodiments . a method for identifying and extracting ideographic components is oriented to a bilingual sentence pair of same semantic content , where a sentence alignment operation is performed by using a software method and man - human interactions , and texts of languages a and b of same semantic content are stored in word fields of language a and word fields of language b in a sentence database ( this part is similar to translation memory in the prior art ). the present invention requires that samples of extracted ideographic components should be standard , for example , extracted from issued essays or works such as textbooks , model essays , and special reference documents . an operating principle is that a user who identifies and extracts ideographic components and a person who collates sentence pairs for semantic content alignment cannot modify content of an operated sentence pair . with reference to fig1 , which is a flowchart of extracting ideographic components , by using chinese and english languages as an example , the following further describes the method for extracting ideographic components . as shown in fig1 , this method includes the following four steps : herein concepts that have special meanings are defined and abstracted as follows : sentence : in a language text , a basic unit that expresses complete semantic content is a sentence . sentences in different language texts may express same semantic content . a sentence may include two parts : a sentence frame and a sentence cabin , where one sentence frame includes at least one sentence cabin . sentence frame : a residual part after sentence cabins are removed is a sentence frame . the sentence frame is the frame of a sentence . it is originated from abstraction of a type of sentence , is relatively stable in the sentence , and reflects the basic semantic content and type of the sentence . it constitutes the basic frame part of this type of sentence . the sentence frame reflects basic semantic content and type of the sentence and is oriented to the whole mankind and are language - independent , while the basic frame is oriented to a specific natural language . sentence cabin : the parts that are embedded in the sentence frame , namely , the basic frame , and are often replaced flexibly , are sentence cabins . the sentence frame plays a role in selecting and constraining sentence cabins . the sentence cabins may be filled or replaced with sense group strings and form specific diversified sentences . the quantity and semantic content of sentence cabins are oriented to the whole mankind and are language - independent , but positions and sequences of the sentence cabins in the sentence frame and sense group strings for filling therein are oriented to specific natural languages . idiom : an idiom is a sentence that cannot be divided into a sentence frame and a sentence cabin because it is too short , or is a sentence that cannot be divided into a sentence frame and a sentence cabin because of languages or customs . the idiom is a type of special sentence . for example , sentences that cannot be divided into sentence frames and sentence cabins because of languages or customs include : “ , , ”; “ one boy is a boy , two boys half a boy , three boys no boy .”; “ ” there can never be too much deception in war .” no word string has a same sense , and it is difficult to extract or label the sentence cabins . in chinese , some idioms , common sayings , proverbs , two - part allegorical sayings , and so on , are also idioms . the sentence frame and sentence cabin are like a blank filling question , where the sentence frame is a question stem and the sentence cabin is a blank . they are like a mathematical formula , where the sentence cabin is a variable and the sentence frame is an equation . the sentence cabin is filled with or composed of sense group strings led by sense groups . however , sizes of sentence cabins vary greatly . a smallest sentence cabin includes only one sense group string , while a largest sentence cabin may include a subordinate clause or a clause . sentence cabins are classed into two types : simple sentence cabin and complex sentence cabin . after a sentence pair is read into a bilingual sentence database ( 101 ), the sentence pair needs to be matched with a sentence frame . if there is a sentence frame , and after the sentence pair is integrated into the sentence frame , each sentence cabin and cabin eye are even and complete without stacking , the sentence pair is skipped . a sentence frame needs to be extracted only when the sentence pair does not match any sentence frame . first an operation of matching a sentence frame is performed . in matching a sentence frame , a sentence frame word string table is generated in advance according to a cavity between a sentence frame word string and a sentence cabin , and is indexed , for example , a sentence frame is “ i know +[ 1 ]+ got crush on +[ 2 ]+, +[ 3 ]+ you could +[ 4 ]+ . . . ”, “ +[ 1 ]+ +[ 2 ]+ , +[ 3 ]+ +[ 4 ]+ ”, so that it becomes a sentence frame word string “ i know . . . got crush on . . . , . . . you could . . . . ”, “ . . . . . . . . . . . . ”; they are jointly tabulated and indexed with a sentence frame code and a frame header . the sentence frame word string is divided by sentence cabins into sentence frame word segments , for example , “ i know ”, “ got crush on ”, “,”, “ you could ”, “.”; “ ”, “ ”, “ ,”, “,”, “ ”, “ ”. it is noted that “,” and “.”, like “ got crush on ”, are also a sentence frame word segment . sentence frame match operation : the machine generates and indexes a sentence frame word string table in advance according to a cavity between a sentence frame word string and a sentence cabin . when matching a sentence frame , the machine fetches english words and chinese characters one by one from a sentence example from left to right , searches for a frame header field ( in english , the first word or symbol of a sentence frame word string is included ; in chinese , the first word or punctuation is included ) in the sentence frame word string table , and saves a search result to a temporary table . then the machine fetches content of the temporary table from the records in succession , and inquires sentence pair examples by using sentence frame word segments . if each segment of the sentence frame word string may be found in the sentence pair examples and sequences thereof in sentence frames are the same , those sentence frames are matched sentence frames . then the machine fetches the sentence frame of the corresponding language according to a sentence frame code field of the sentence frame word string table . in the sentence frame match operation , a matched sentence frame is searched out , the current sentence pair example is integrated into the sentence frame , and “ cabin detection ” and “ search , match , and label ” buttons are displayed and provided . when a user considers , after reading , that each sentence cabin and cabin eye are even and complete without stacking ( this is an unexpected gain , because the user knows by a glimpse whether semantic content is appropriate ), and that the semantic content is correct , the user clicks the “ cabin detection ” button to indicate approval . the machine continues a cabin detection step . otherwise , the provided result is not approved , and the “ search , match , and label ” button is clicked . the machine performs a “ search , match , and label ” operation , and inquires , by using word strings of language a , a conventional electronic dictionary to see whether word strings of language b corresponding to the word strings of language a are included in the sentence of language b , and generates a semantic match table for the current sentence pair . “ search , match , and label ” operation : in a “ search , match , and label ” operation , the machine uses a match table including part - of - speech fields , word fields of language a , and word fields of language b , first performs segmentation in units of word strings of the sentence of language a and fills in the word fields of language a in the match table sequentially , then fetches the word strings from the records one by one and inquires the conventional electronic dictionary , and uses the obtained corresponding explanations of language b to search to determine whether the sentence of language b includes the explanations . if an explanation is included and is the longest string , the machine fills in the word field of language b with the string and fills in the part - of - speech field with the part of speech thereof . if no explanation is included , the word field of language b is empty . now a preparation is made for identifying and labeling sentence cabins . n is set to 0 , and a counter of sentence cabins is cleared . hereinafter concepts that have special meanings are defined and abstracted as follows : simple sentence cabin : if the count of word strings in a pinyin text in a sentence cabin is not greater than five original word strings or a sentence cabin includes not more than three sense group strings except non - ideographic function words , the sentence cabin is called a simple sentence cabin . repetitive sentence cabins : sentence cabins with completely same sentence cabin content and a same number are repetitive sentence cabins . in a sentence pair , the quantity and positions of repetitive sentence cabins in two sentences are not necessarily equal . continuous sentence cabins : two sentence cabins connected without a separating word string ( or character ) in between are continuous sentence cabins . the quantity of continuous sentence cabins in a sentence pair is strictly limited , and only two continuous sentence cabins are allowed . if three continuous sentence cabins appear in either of two sentences , the work and operation must be redone . complex sentence cabin : a sentence cabin that is greater than a simple sentence cabin is a complex sentence cabin . a sentence cabin including a cabin model is a sentence cabin with a model and is generally greater than or equal to eight original word strings . a group string sentence cabin generally includes a complex word string , and is greater than a simple sentence cabin but smaller than a sentence cabin with a model . cabin model and cabin eye : by further analyzing the complex sentence cabin , it is derived that a part like a frame part is called a cabin model and that a replaceable part embedded in the frame of the cabin model is called a cabin eye . the sentence cabin and cabin eye are a superordinate concept and a subordinate concept , but the size of the simple sentence cabin is equal to that of the cabin eye . automatic identification is oriented to the foregoing match table , and features of content of automatic identification are as follows : quantity string : all chinese and english word strings indicating “ number ” and “ quantity ” are collected and recorded in a quantity table . in the table , there are fields such as english quantity , chinese quantity , calculation value , and part of speech , where the part of speech includes “ calculation string ”, “ digital string ”, “ cardinal number ”, “ ordinal number ”, “ quantity ”, and so on . if calculation is required , a quantity string is segmented in words from left to right ; the table is inquired , and if the part of speech thereof is labeled with “ calculation string ”, it is added as a calculation value to result number a ; if it is a digital string , the digital string is multiplied by result number a and then is added to result number b after completion of the operation . in judging whether a string is a quantity string , a string recorded in the table is identified as a quantity string . if the quantity string in the match table is followed by a noun that is recorded and identified in the quantity table as a quantifier , the two are combined into a quantity string . proper noun string : by using english capital initials , all words beginning with a capital letter except in other capitalization cases are identified as proper noun strings . article noun string : an english article is used for identification . a noun following an article , or an “ article adjective noun ” inserted with an adjective is identified as an article noun string . zero - article noun string : a string that does not begin with an article but whose part - of - speech field is a noun and whose word field of language a and explanation field of language b are not empty , is identified as a zero - article noun string with equivalent semantic content . other match strings : other types of words , as long as their word fields of language a and explanation fields of language b are not empty , are identified as other match strings with equivalent semantic content . continuation : the machine identifies the bilingual quantity string , proper noun string , and article noun string sequentially simultaneously , and pre - labels them as sentence cabins according to a time sequence by using n = n + 1 . operation of automatically identifying the pre - labeled sentence cabins : for example , a sentence pair example is : “ in hengtung county , its per - mu_grain_yield surpassed 800 jin in 1970 , double that before 1965 . the machine inquires a semantic match table of the current sentence pair , first searches for and identifies quantity strings , and if quantity strings exist , simultaneously pre - labels the quantity strings with “ a , b , c . . . ” according to n = n + 1 . in this example , three pairs of quantity strings exist and are pre - labeled as three sentence cabins “ a , b , and c ”, for example , “ in hengtung county , its per - mu_grain_yield surpassed a { 800 jin } in b { 1970 }, double that before c { 1965 }. if no quantity string exists or after the machine identifies and searches for quantity strings in the whole sentence completely , the machine identifies and searches for proper noun strings . if proper noun strings exist , the machine also pre - labels them with “ a , b , c . . . ” according to n = n + 1 . in this example , one pair of proper noun strings exists and continues to be pre - labeled as a sentence cabin “ d ”, for example , “ in d { hengtung county }, its per - mu_grain_yield surpassed a { 800 jin } in b { 1970 }, double that before c { 1965 }. if no proper noun string exists or after the machine identifies and searches for proper noun strings in the whole sentence completely , the machine identifies and searches for article noun strings . if article noun strings exist , the machine also pre - labels them with “ a , b , c . . . ” according to n = n + 1 . no article noun string exists in this example . if no article noun string exists or after the machine identifies and searches for article noun strings in the whole sentence completely , the machine displays a symbol “|” and displays “←” and “→” command buttons on two sides respectively , calculates and displays a frame example percentage , and a “√” command button , and accepts the user &# 39 ; s correction or approval ; meanwhile displays the frame example percentage as “ 64 %”. the percentage does not reach a criterion 15 - 50 %. therefore , the machine needs to continue to identify and label sentence cabins , accepts the user &# 39 ; s click on the “√” button , and continues identification and labeling . quantity strings , proper noun strings , and article noun strings of two languages are simultaneously identified sequentially above . after the three types of word strings are identified , the machine calculates the frame example percentage , and displays and provides a pre - labeling result and some command buttons simultaneously . if a correction is required , the machine may accept a user &# 39 ; s ( namely , the user , same hereinafter ) correction . if no correction is required but the frame example percentage exceeds the criterion , as in this example , the machine continues identification and labeling . if the frame example percentage is higher than 15 - 50 %, the machine searches according to the match table , where those whose part - of - speech fields are nouns and whose word fields of language a and word fields of language b are not empty are semantic match zero - article noun strings , or those whose part - of - speech fields are not nouns but whose word fields of language a and word fields of language b are not empty are other semantic match word strings . meanwhile , the machine displays the semantic match table of the current sentence pair , “ hand ”, “ v ”, “& lt ;∩”, and “ format check ” buttons . in this example , the machine continues to identify zero - article noun strings and other semantic match word strings . it is noted that from now , the machine pauses every time when one sentence cabin is identified and pre - labeled and waits for interactive approval or correction . for example , the machine searches for zero - article noun strings from left to right and there are “ per - mu_grain_yield ” and “ ”, which are both separated from previous and next labeled sentence cabins by word strings , and therefore further pre - labels a sentence cabin “ e ”, for example , “ in d { hengtung county }, its e { per - mu_grain_yield } surpassed a { 800 jin } in b { 1970 }, double that before c { 1965 }. in this case , the frame example percentage “ 42 %” already reaches the criterion , but is not smaller than or equal to 15 %. therefore , the user may end identification according to the semantic case , and click the “ format check ” button ; or may perform identification and pre - labeling , and click the “√” button ; or may use other command buttons to make corrections . the correcting operation is associated with the foregoing displayed command buttons , which are enumerated as follows : “ ” buttons : when a sentence to be corrected is clicked , insert and display “|” at the clicked point , and then judge whether “←” and “→” buttons are clicked ; when “←” is clicked , move the left word string of “|” to the left : if “|” is in a sentence cabin , move the left word string of “|” out of the sentence cabin ; if “|” is out of the sentence cabin , move the left word string of “|” into the sentence cabin . when “|” is clicked , move the right word string of “|” to the right ; if “|” is in the sentence cabin , move the right word string of “|” out of the sentence cabin ; if “|” is out of the sentence cabin , move the right word string of “|” into the sentence cabin . thereby , content of the sentence cabin is increased or decreased . “√” button : approve the currently identified and pre - labeled sentence cabin , and continue to identify and pre - label a new sentence cabin . “| hand |” button : manually identify a sentence cabin , meanwhile respectively click the header and tail of each sentence cabin to be pre - labeled , in the sentences to be corrected of languages a and b , then click the “| hand |” button , pre - label them as a pair of sentence cabins , and automatically modify the frame example percentage . “& lt ;∩” button : click each time to draw back the last identified and pre - labeled sentence cabin , and restore to the state and frame example percentage before the last pre - labeling . this operation may be repeated until all sentence cabins are removed . “ format check ” button : end the correcting operation on the current sentence pair , and perform a format check operation . the format check includes three steps : redo check , label format check , and formal labeling . the specific operation is as follows : the length of a sentence frame is limited to be smaller than or equal to 200 characters for english sentences , and limited to be smaller than or equal to 150 characters ( one chinese character is counted as two bytes ) for chinese sentences ; the quantity of continuous sentence cabins is limited to two connected sentence cabins . once it is found that the sentence frame length exceeds the limit or that three sentence cabins are connected , a report is generated immediately , and work should be redone immediately . the automatic identification and pre - labeling of sentence cabins described above are performed according to the following “ rule for labeling sentence frames and sentence cabins ”. herein the label format check is also a check performed according to this rule . if there are incompliant parts , the incompliant parts are modified automatically if they can be modified automatically ; or the user is prompted to make modifications if they cannot be modified automatically . after completion of the check , a search is performed to determine whether continuous sentence cabins having same numbers simultaneously exist in sentences of languages a and b , and if so , a dialog box is displayed to obtain the user &# 39 ; s approval and then the continuous cabins are merged into one sentence cabin . the continuous sentence cabins having same numbers simultaneously , for example , connected sentence cabins “ c , d ” or “ d , c ” included in both sentences of languages a and b , should be merged after an interaction ( decided by the user certainly ). then the next step is performed . chinese and english are the first language pair extracted in the identification and comparison . according to the english sentence , numbers are arranged in an ascending order from left to right . the sentence cabins are formally labeled with numbers “ 1 , 2 , 3 . . . ”. starting from a third language , the labeled sentences are used as samples for replication , identification , and labeling , and no pre - labeling is required . { circle around ( 1 )} a sentence frame includes three types of components : sentence frame word , sentence cabin , and punctuation . “+” must be used for separation between a sentence cabin and the other two types of components , and between sentence cabins . punctuations are labeled in the same ways as sentence frame words . for example , { circle around ( 2 )} a punctuation is equivalent to a sentence frame word . the punctuation at the end or in the middle of the sentence is separated by a space in english , but not separated in chinese . for example , { circle around ( 3 )} the first word of the sentence frame in english is not capitalized ( except “|”), including an irregular word , inflectional ending , and so on ( should be consistent with the example ). for example , { circle around ( 4 )} all short forms are converted into full spellings regardless of whether they are in the sentence frame or sentence example . { circle around ( 5 )} chinese and english are the first language pair . according to the english sentence , sentence cabin numbers are arranged from left to right in an ascending order . those of chinese and other languages all correspond to the sentence cabin numbers of the english sentence according to the semantic content . there are two forms : a sentence frame form and a frame example form . the former uses square brackets , and the latter uses braces . ( a ) in the sentence frame form , such as a sentence frame 263 : ( b ) in the frame example form , the only difference lies in positions of numbers of sentence cabins . for example , the frame example form of the sentence frame 263 is : 1 { at_that_time they } could not afford 2 { the ordinary comforts of life }, not to speak of 3 { luxuries }. { circle around ( 6 )} repetitive sentence cabins have a same sentence cabin number and same sentence cabin content . they do not necessarily correspond each other between languages . their labels are also the same . for example , { circle around ( 7 )} the label of a cabin model is consistent with that of a sentence frame , and also has two corresponding forms . the cabin model number is placed in parentheses “( )” and located at the beginning of the sentence cabin , for example , the 1 { fisherman } consents to return 2 { the feather suit }, on condition that 3 {( 00205 ) 1 [ fairy ] 2 [ dance ] and 3 [ play heavenly music ] for him }. 3 {( 00205 ) 1 [ ] 2 [ ] 3 [ ]} , 1 { } 2 { }. { circle around ( 8 )} the foregoing parentheses , square brackets , and braces used for labeling all occupy a single byte for chinese , english , and other languages . continuation : for the current sentence pair example , identification and labeling of sentence cabins are all completed . for example , “ in 1 { hengtung county }, its 2 { per - mu_grain_yield } surpassed 3 { 800 jin } in 4 { 1970 }, double that before 5 { 1965 }. some content about identification and pre - labeling of sentence cabins of the current sentence pair example is still not involved . therefore , another example is provided for description . for example , a sentence pair is read : “ for three years , there is been a running fight between the tory and labour members of the housing committee about raising council ho house rents .”, “ 3 , ” as described above , a quantity string , a proper noun string , and an article noun string are automatically simultaneously identified sequentially . a prompt is displayed , saying “ the article noun string “ running ” does not match !” after the three types of word strings are identified and sentence cabins are pre - labeled , the frame example percentage is displayed as 59 %. the pre - labeling result is : “ for a { three years }, there is been a running fight between b { the tory } and c { labour members } of d { the housing committee } about raising council house rents .”: the content that is not involved in the previous example appears in this example . the processing is the same as above , and the machine additionally displays the semantic match table of the current sentence pair , “| hand |”, “ v ”, and “∩” buttons , and accepts the user &# 39 ; s modification of the match table or addition of semantic match word strings by using a sense group alignment method such as composing complex words , extending senses of words , or adding characters or words ahead or behind , and continues to pre - label sentence cabins . in the identification and pre - labeling of the quantity string , proper noun string , and article noun string , a prompt “ the article noun string “ running ” does not match !” is displayed . in the match table , a field of language b corresponding to “ running ” in language a is empty and therefore is not matched ; explanations about “ running ” in the conventional electronic dictionary include : “ n , ; ; ; ; adj , ; ; ; ; ;”. none of them is included in the sentence of language b during the search and therefore is not matched . according to semantic content of the current sentence pair example , the running expresses a sense of “ ”, which is an extension of the senses of “ ” and “ ”. it complies with the operation requirement of “ sense group alignment ” ( described in detail later ). therefore , “ ” is added to the field of language b ( the part - of - speech field is filled with “ t ”, indicating other supplementary word types , the same hereinafter ), so that “ running ” and “ ” are matched to form a sense group string . however , the article noun string “ a running fight ” and “ ” are matched , and are identified and pre - labeled as a sentence cabin “ e ”; the frame example percentage is 48 %. for example , “ for a { three years }, there is been e { a running fight } between b { the tory } and c { labour members } of d { the housing committee } about raising council house rents .”; 48 % no sentence cabin exists in the last part of the sentence pair , and the frame example percentage is 48 %. the machine may continue to pre - label sentence cabins . in the match table , “ council ” cannot be matched in the last “ raising council house rents ” and “ ”. in the conventional dictionary , senses of “ council ” include “ n , ; ; ; ; ; ; ; ; ”, and herein it expresses a sense of “ ”, and is an extension of the sense of the original word string . it complies with the operation requirement of “ sense group alignment ”. therefore , the explanation “ ” is added to the field of language b . when the user clicks the “√” button , automatic identification and pre - labeling are continued as follows : for a { three years }, there is been e { a running fight } between b { the tory } and c { labour members } of d { the housing committee } about f { raising council house rents }. a { 3 } , d { } b { } c { } f { } e { }. in this case , the frame example percentage is 26 %; and distribution of the sentence cabins is rational ( an interval between cabins is generally 1 - 5 strings ). the operation of identification and pre - labeling ends ; the click on the “ format check ” button is accepted . a format check operation is performed . then formal labeling is : for 1 { three years }, there is been 2 { a running fight } between 3 { the tory } and 4 { labour members } of 5 { the housing committee } about 6 { raising council house rents }. two sentence pair examples are provided above , and are both paused after formal labeling . continued from the foregoing sentence pair example 1 , after formal labeling , the sentence pair example is : 1 { in hengtung county }, 2 { its per - mu_grain_yield } surpassed 3 { 800 jin } in 4 { 1970 }, double that before 5 { 1965 }. in this case , the quantity of sentence cabins is 5 , which satisfies the “ n =& gt ; 1 ” requirement ; then the residual parts after content of the sentence cabins is removed are sentence frame components , for example , the sentence frame components are stored in corresponding language component fields of a sentence frame database respectively . herein , for example , the english sentence frame “ in +[ 1 ]+, its +[ 2 ]+ surpassed +[ 3 ]+ in +[ 4 ]+, double that before +[ 5 ]+.” is stored in the “ english sentence frame ” field of the sentence frame database ; and the chinese sentence frame “[ 1 ]+ +[ 4 ]+[ 2 ]+ +[ 3 ]+, +[ 5 ]+ ” is stored in the “ chinese sentence frame ” field of the sentence frame database . hereinafter , xxxx components are stored in corresponding language component fields in an xxxx database , and so on . there are sentence frame fields of multiple languages such as “ english sentence frame ”, “ chinese sentence frame ”, and “ russian sentence frame ” in a sentence frame database ( 105 ), which are respectively used to store sentence frames of corresponding languages . semantic content of sentence frames of multiple languages in a same record is the same . in the second round of semantic comparison and sentence frame extraction , the labeled language sentences are used as a template to identify and label the sentence cabins . after the sentence frame of the new language is obtained , the sentence frame database is searched by using the labeled language sentence frame , and the sentence frame is stored in the corresponding field of the new language in the same record . continued from the foregoing sentence pair example 2 , after formal labeling , the sentence pair example is : for 1 { three } years , there is been 2 { a running fight } between 3 { the tory } and 4 { labour } members of 5 { the housing committee } about 6 { raising council house rents }. in this case , the quantity of sentence cabins is 6 , which satisfies the “ n =& gt ; 1 ” requirement ; then the residual parts after content of the sentence cabins is removed are sentence frame components , for example , like the foregoing example , they are respectively stored in the “ english sentence frame ” and “ chinese sentence frame ” fields in the same record of the sentence frame database . many things grow in the garden that were never sown there . no sentence frame is matched in the operation of matching a sentence frame . then a “ search , match , and label ” operation is performed . there are 12 records in the match table after the “ search , match , and label ” operation . fields of language a are words and full stops of the english sentence . fields of language b are all empty . in the “ search , match , and label ” operation , no string is matched . then the operation of identifying and labeling sentence cabins is performed , but there is no sentence cabin that can be labeled . this satisfies n = 0 . they are idiom components . they are respectively stored in the “ english idiom ” and “ chinese idiom ” fields in a same record of an idiom database . there are idiom fields of multiple languages such as “ english idiom ”, “ chinese idiom ”, and “ russian idiom ” in an idiom database ( 104 ), which are respectively used to store the idioms of the corresponding languages . semantic content of idioms of multiple languages in a same record is the same . in the second round of semantic comparison and idiom extraction , the labeled language sentences are used as a template to identify and label the idioms . after the idiom of the new language is obtained , the idiom database is searched by using the labeled language idiom , and the idiom is stored in the corresponding field of the new language in the same record . the step of identifying and labeling the sentence cabins is completed . the obtained sentence frame components and idiom components are respectively stored in the sentence frame database and idiom database . ( iii ) detecting cabins and extracting a cabin model ( 106 ) sentence cabins are detected one by one sequentially . in the first round of comparison , word strings included in english sentence cabins are counted . if the quantity of word strings included in a sentence cabin is smaller than eight original word strings , complex words are composed according to requirements . if complex words do not need to be composed , this operation is skipped . if the quantity of word strings included in a sentence cabin is greater than or equal to eight original word strings , a “ search , match , and label ” operation is performed by using the current sentence cabin , and a semantic match table is generated for the current sentence cabin , so that a cabin model is further extracted as a sentence cabin with a model , for example , 1 { the american } 2 { economic } machine is , organized around 3 { a basically private - enterprise }, 4 { market - oriented economy } in which 5 { consumers } largely determine 6 { what shall be produced } by 7 { spending their money in the marketplace for those goods and services that they want most }. 1 { } 2 { } 3 { } 4 { } , 2 { } , 5 { } 7 { } 6 { }. 6 { }. the sentence cabins are detected one by one sequentially . none of the sentence cabins numbered 1 - 6 exceeds eight original strings . a sentence cabin 7 { spending their money in the marketplace for those goods and services that they want most } exceeds eight original word strings . a “ search , match , and label ” operation is performed and a semantic match table is generated for the current sentence cabin , so that a cabin model is further extracted as a sentence cabin with a model . the cabin model is extracted , and bilingual quantity strings , proper noun strings , and article noun strings are simultaneously identified sequentially and pre - labeled as cabin eyes . for example , the current cabin is labeled as : spending their money in a [ the marketplace ] for those goods and services that they want most in this case , the model example percentage is 81 %, greater than 50 - 70 %. then zero - article noun strings or other semantic match word strings are labeled as cabin eyes one by one under a prerequisite that spacing exists . the user can not only perform approval or correction , but also modify the match table by using a sense group alignment method such as composing complex words , extending senses of words , or adding characters or words ahead or behind , add a semantic match word string , and continue to pre - label cabin eye b . spending their money in a [ the marketplace ] for those b [ goods and services ] that they want most in this case , the model example percentage is 65 %, which is between 50 % and 70 %. the labeling operation may be ended or sentence cabin c may be further pre - labeled according to requirements of semantic content . spending their money in a [ the marketplace ] for those b [ goods and services ] that c [ they want most ] in this case , the model example percentage is 53 %, which is lower than 50 - 70 %. labeling cannot be performed any more . the previous labeling is drawn back and restored . eye labeling ends . the pre - labeled cabin eyes are modified into formally labeled cabin eyes for the english sentence cabins from left to right . for example , the current sentence cabin is formally labeled as : spending their money in 1 [ the marketplace ] for those 2 [ goods and services ] that 3 [ they want most ] the extracted cabin model of the current sentence cabin includes two cabin eyes , which satisfies the condition of the cabin model n =& gt ; 1 . residual parts after cabin eye content is removed are cabin model components . for example , the cabin models obtained in current extraction are saved to corresponding language component fields in a cabin model database ( 107 ). there are cabin model fields of multiple languages such as “ english cabin model ”, “ chinese cabin model ”, and “ russian cabin model ” in the cabin model database ( 107 ), which are respectively used to store the cabin models of corresponding languages . semantic content of cabin models of multiple languages in a same record is the same . in the second round of semantic comparison and cabin model extraction , the labeled language sentences are used as a template to identify and label the cabin models . after the cabin model of the new language is obtained , the cabin model database is searched by using the labeled language cabin model , and the cabin model is stored in the corresponding field of the new language in the same record . then the machine continues to detect other sentence cabins , until detection of sentence cabins of the whole sentence pair is completed . the current cabin model is the last sentence cabin of the current sentence pair example . therefore , detection of sentence cabins of the whole sentence pair is completed . the current sentence cabin is integrated back into the current cabin model . the frame example form of the whole sentence pair is as follows : 1 { the american } 2 { economic } machine is , organized around 3 { a basically private - enterprise }, 4 { market - oriented economy } in which 5 ( consumers ) largely determine 6 { what shall be produced } by 7 {( 2301 ) spending their money in 1 [ the marketplace ] for those 2 [ goods and services ] that 3 [ they want most ]}. 1 { } 2 { } 3 { } 4 { } , 2 { } , 5 { } 7 {( 2301 ) 1 [ ] 3 [ ] 2 [ ] } 6 { }. herein concepts that have special meanings are defined and abstracted as follows : sense group : a sense group is equivalence and unification of a “ sense ” of a character , a word , a word combination , or a phrase of a natural language and is a basic unit of human thinking activities . the sense group is not limited to languages but belongs to the whole mankind , and is also metabolized with development of the human society . sense group string : a corresponding expression of the sense group in a language text is called a sense group text string , sense group string for short . a sense group string in a pinyin text is classified into a single string and a complex string . a string including only one original word string is a single string . a string composed of two or more than two original word strings and connected with “ _ ” is a complex string . sense group alignment : the sense group alignment method uses the language - independent feature of the sense group to perform semantic alignment on the characters , words , word combinations , or phrases of multiple languages under the support of the current sentence pair example . after alignment , they become a sense group string and are eligible for being stored in a sense group database . mainly the following methods are available : { circle around ( 1 )} composing complex words : judgment is performed according to the semantic content of the current sentence pair and sentence cabin . if one of them requires that two or more original word entries should be merged , so that the semantic content is the same as that of another word entry , the original word entries are connected by using “-” and merged into one word entry , which is called a complex word . alternatively , when total semantic content of two or more original word strings cannot be obtained by addition of the semantic content of the word strings , the word strings are connected by using “ _ ” to form a complex word ( complex string ): with respect to “ works little ” “ ”, although a sense of “ works ” is “ ”, “ little ” does not have a sense of “ ”; the total semantic content of the two words cannot be obtained by addition of the word strings ; therefore , they are connected by using “ _ ” to compose a complex word . { circle around ( 2 )} according to the current sentence pair example , extending or supplementing semantic content of a word . the senses of “ useful ” include “ , ,”, and definitely the semantic content “ ” is expressed in the sentence pair ; in addition , senses of “ ” and “ ” are similar . therefore , the sense entry “ ” is added or extended . the sense entry “ ” is added for “ small ” according to the sentence pair example . { circle around ( 3 )} increasing or decreasing a string length under a prerequisite that the original characters and words are not changed , for ease of splicing . “ teach ” v has senses of “ , ”; the length of the word string is reduced to “ ”, and the sense entry “ ” is added . for example , words are added to change “ good ” into “ ”. for example , a word is added to change “ word ” into “ ”. { circle around ( 5 )} inflectional forms of words are recorded in the database as new word entries ( for semantic content expressed by participles and comparative degrees , new word entries and corresponding senses of the words ). for “ been ”, senses of “ ” are added . for “ punished ”, a sense of “ ” is added . the sense group alignment method is as important as the sentence frame match operation and “ search , match , and label ” operation , and is also indispensable to the method of the technology . the sense group database overlaps the conventional dictionary and electronic dictionary , and the original vocabulary is basically incorporated . a difference is related to sense group alignment . inflectional forms of words are recorded as new word entries . sense group alignment increases the relative quantity of word entries and makes great contributions to splicing . complex words and terms can all be covered . continuation : referring to the foregoing semantic match table after the identification and labeling of sentence cabins , bilingual word strings with aligned semantic content in the sentence cabins or cabin eyes are determined to be sense group strings , and are stored in pairs one by one in the corresponding language component fields in the sense group database ( 109 ). the operation of comparison and extraction of the current sentence pair ends , and s1 is continued to read a sentence and match a frame . according to an order of numbers of the sentence cabins and cabin eyes , the sentence cabins or cabin eyes are searched in pairs one by one . with reference to the semantic match table , if word fields of language a and word fields of language b are not empty in records of the match table of the corresponding content and semantic content of texts of languages a and b is aligned , the content has become sense group strings . the content is fetched from the records in succession , and respectively stored in the corresponding language fields of the same record in the sense group database ( 109 ). for example , a sentence pair example of the frame example form after the foregoing processing is : 1 { dyslexia } first was recognized in 2 { europe } and 3 { the united_states } more than 4 { 80 years } ago . the sentence cabins or cabin eyes are searched in pairs one by one . with reference to the semantic match table , if word fields of language a and word fields of language b are not empty in records of the match table of the corresponding content and semantic content of texts of languages a and b is aligned , the content is determined to be sense group string components . for example , “ dyslexia ”, “ europe ”, “ united_states ”, and “ years ” are expressions of sense groups in different language texts , and are equivalence and unification of “ senses ” of characters , words , word combinations , or phrases of natural languages ; therefore , they are sense group strings , namely , sense group string components . then the sense group strings are saved to the corresponding language component fields in the sense group database ( 109 ) in records ( pairs ) one by one . the sense group database ( 109 ) includes a corresponding single string database and complex string database because sense group strings of a pinyin text are classified into single strings and complex strings . an ideographic text is stored in the single string database or complex string database with the strings of the pinyin text according to semantic content . before the storing , first , a search is performed , and the ideographic text is added if it is not found in the database for avoiding repetitions . there are single string fields of multiple languages such as “ english single string ”, “ chinese single string ”, and “ russian single string ” in the single string database , which are respectively used to store sense group single strings of corresponding languages . semantic content of single strings of multiple languages in a same record is same . for example , “ dyslexia ” and “ europe ”. there are complex string fields of multiple languages such as “ english complex string ”, “ chinese complex string ”, and “ russian complex string ” in the complex string database , which are respectively used to store sense group complex strings of corresponding languages . semantic content of complex strings of multiple languages in a same record is same . for example , “ united_states ”, “ lose_touch_with ”, and “ strike_a_balance ”. in the second round of semantic comparison and sense group string extraction , the labeled language sentences are used as a template . after the sense group string of the new language is obtained , the single string database or complex string database is searched by using the labeled language sense group string , and the sense group string is stored in the corresponding single string or complex string field of the new language in the same record . after all sense group strings after the semantic match ( semantic alignment ) in the sentence cabins and cabin eyes of the current sentence pair example are stored in the sense group database , the operation of semantic comparison of the current sentence pair example and extraction of ideographic components ends . step ( i ) is continued : reading a sentence and matching a frame ; reading a next sentence pair example , and continuing the foregoing operation . the foregoing method for extracting ideographic components is performed in orientation to bilingual sentences by using chinese and english as an example . semantic comparison is performed , and several ideographic components are identified and extracted . in each round of comparison , identification , and extraction , two languages a and b are selected ; language a is allocated to pinyin texts or is a language that is already compared , identified , and extracted . language b is allocated to ideographic texts , or may be allocated to pinyin texts , or is a new language . in the first round of comparison , identification , and extraction , a chinese and english bilingual sentence pair is selected as a core pair ; language a is english and language b is chinese . starting from the second round , one new language is added in each round ; the other one must be a language that is already compared , identified , and extracted . however , starting from the second round , operations of comparison , identification , and extraction are different . language a that is already compared , identified , and extracted is used as a template to identify and label sentence cabins and obtain sentence frames , and so on . for example , the new language in the second round is russian , which is language b ; language a is chinese that is already compared , identified , and extracted . a chinese and russian sentence pair is extracted : however , the chinese sentence is used to search the sentence frame database to obtain a matched sentence frame “[ 1 ]+ +[ 4 ]+ +[ 3 ]+[ 2 ]+ ”; the chinese sentence example is integrated into the frame to become a frame example form , for example , then , content in sentence cabins is fetched in succession according to the match table after the corresponding “ search , match , and label ” operation , for example , “ ” of a sentence cabin 1 is fetched . corresponding “ ” in russian is found according to the match table , and is labeled as a sentence cabin 1 , for example , 1 ? in the same way , “ ” of a sentence cabin 4 is fetched . corresponding “ ” in russian is found according to the match table , and is labeled as a sentence cabin 4 , for example , 1 ? in the same way , “ ” of a sentence cabin 3 is fetched . corresponding “ ” in russian is found according to the match table , and is labeled as a sentence cabin 3 , for example , 1 ? finally , “ ” of a sentence cabin 2 is fetched . corresponding “ ” in russian is found according to the match table , and is labeled as a sentence cabin 2 , for example , however , residual parts after the sentence cabins are removed are sentence frame components . the sentence frame of the new language russian is obtained : the sentence frame database is inquired by using the sentence frame of language a “[ 1 ]+ +[ 4 ]+ +[ 3 ]+[ 2 ]+ ?”, and then the “ russian sentence frame ” field of the record where the sentence frame of language a is located is filled with the newly obtained russian sentence frame “[ 1 ]+[ 2 ]+ +[ 3 ]+ +[ 4 ]+?” sentence frames of the three languages “ english , chinese , russian ” in the current sentence frame database are respectively : does +[ 1 ]+[ 2 ]+ as +[ 3 ]+ as +[ 4 ]+? comparison , identification , and extraction of other ideographic components are inferred by analogy . in the foregoing operation process of the method for extracting ideographic components , four types of ideographic components , namely , sentence frames , cabin models , sense group strings , and idioms , are extracted , and are stored in the corresponding sentence frame database , cabin model database , sense group database , and idiom database respectively . their features are as follows : ( 1 ) sentence frame components are residual frame parts of the sentence after the sentence cabins are removed . the sentence frame database is configured to store sentence frame components and has sentence frame codes , english sentence frame fields , chinese sentence frame fields , and russian sentence frame fields , where sentence frame fields of each language in a same record store sentence frames of corresponding languages , they have same semantic content , and the sentence frame codes are expressions of their semantic content and position . sentence frames of each language in a same record have same semantic content , which is decided by use of a language pair in each round of comparison , identification , and extraction . starting from the second round , a language is added in each round , and corresponding language component fields are added to the sentence frame database . a new sentence frame that is compared , identified , and extracted is stored in the corresponding language component field . the comparison , identification , and extraction method and software operation ensure that ideographic components in a same record have same semantic content . due to the features of the database , components of a same record are mapped mutually , including component fields and sentence frame codes of each language , and as long as one of them is searched out , content of the corresponding language component field may be fetched . ( 2 ) cabin model components are residual frame parts of the sentence cabins after the cabin eyes are removed . the cabin model database is configured to store cabin model components and has cabin model codes , english cabin model fields , chinese cabin model fields , and russian cabin model fields , where cabin model fields of each language in a same record store cabin models of corresponding languages , they have same semantic content , and the cabin model codes are expressions of their semantic content and position . a feature of the cabin model database is that language component fields of a same record in a same sentence frame database have same semantic content and are mapped mutually . ( 3 ) sense group string components are components for filling sentence cabins or cabin eyes . the sense group database is configured to store sense group string components and has sense group codes , english group string fields , chinese group string fields , and russian group string fields , where sense group string fields of each language in a same record store sense group strings of corresponding languages , they have same semantic content , and the sense group codes are expressions of their semantic content and position . a feature of the sense group database is also that language component fields of a same record in a same sentence frame database have same semantic content and are mapped mutually . ( 4 ) idiom components are a type of special sentence that cannot be divided into sentence frames and sentence cabins . the idiom database is configured to store idiom components and has idiom codes , english idiom fields , chinese idiom fields , and russian idiom fields , where idiom fields of each language in a same record store idioms of corresponding languages , they have same semantic content , and the idiom codes are expressions of their semantic content and position . a feature of the idiom database is also that language component fields of a same record in a same sentence frame database have same semantic content and are mapped mutually . ( 5 ) ideographic components are specific reflections of associating different language texts by using ideographs , and are semantic blocks having different sizes and different forms and structures . they are also equivalence and unification of ideographs of multilingual texts . in addition , ideographic components are semantic blocks that have different sizes and different structures and may be disassembled , assembled , and spliced . the ideographic components include sentence frame components , cabin model components , sense group string components , and idiom components , where the sentence frame database , cabin model database , sense group database , and idiom database jointly constitute an ideographic component database . the four sub - databases are independent of each other . ( 6 ) in identification and extraction starting from the second round , component fields of a new language should be added to the four sub - databases respectively in advance . ( 7 ) language text information processing is supported by the ideographic components and database thereof ; therefore , beneficial effects of associating different language texts by using ideographs and overcoming “ semantic barriers ” by using language text information processing may be achieved . multiple scenarios of language text information processing may be supported . described by using a visualized language , sentence frame components are like a chassis of a car , and just enough space and connecting parts are reserved for the driver &# 39 ; s cab , wheels , power machine , oil supply machine , and so on . the cabin model components are like the driver &# 39 ; s cab , and further include other small machines and parts . the sense group string components are like wheels , other types of small machines , assemblies , components , and so on , and may be assembled in any position as required . the idiom is a special type of minicar having only features of a basic car , even a jinriksha and a handcart , and so on . ii . a method for performing interactive translation of machine translation and human proofreading based on ideographic components with reference to fig2 , which is a flowchart of interactive translation of machine translation and human proofreading , by using english - to - chinese translation as an example , the following further describes the method for performing interactive translation of machine translation and human proofreading . a source language file to be translated is read ( 201 ), and saved to a buffer . then steps of the following four modules are performed : ( i ) reading a sentence , matching a frame , and integrating a source language sentence into the frame ( 202 ). a source language sentence is read , a sentence frame database is searched by using the source language sentence , and a sentence frame match operation same as above is performed . oliver twist was born in workhouse ; there were no aunts , no sisters , no cousins , no grand_mothers . english words and chinese characters are fetched one by one from the current sentence example from left to right , a frame header field ( in english , the first word or symbol of a sentence frame word string is included ; in chinese , the first word is included ) in a sentence frame word string table ( including a frame header field , a sentence frame field , and a sentence frame code field ) is searched out , and a search result is saved to a temporary table . then content of the temporary table is fetched from the records in succession , and sentence pair examples are inquired by using sentence frame word segments . if each segment of the sentence frame word string may be found in the sentence pair examples and sequences thereof in sentence frames are the same , those sentence frames are matched sentence frames . then a sentence frame of the corresponding language is fetched according to the sentence frame code field of the sentence frame word string table . the sentence frame code is made up of a sentence frame database flag and a record number . other index tables are inferred by analogy . in this example , the source and target language sentence frames are fetched from a sentence frame database according to the sentence frame code field as follows : “[ 1 ]+ +[ 2 ]+; +[ 3 ]+, +[ 4 ]+, +[ 5 ]+, +[ 6 ]+.” then the source language sentence is integrated into the source language sentence frame strictly according to cabin numbers . “ integrating strictly according to cabin numbers ” means that the first sentence frame word segment “ was born in ” in the example matches the corresponding segment “ was born in ” in the sentence example , and that the sentence frame word segment “; there were no “ matches the corresponding segment ”; there were no ” in the sentence example , such as the “ bold ” parts : oliver twist was born in workhouse ; there were no aunts , no sisters , no cousins , no grand_mothers . other parts ( italic ) than the corresponding segments in the sentence example are respectively arranged in corresponding sentence cabins ( that is , in a frame example form ), for example , “ oliver twist ” is arranged in a sentence cabin [ 1 ], and “ workhouse ” is arranged in a sentence cabin [ 2 ], “ aunts ” is arranged in a sentence cabin [ 3 ], and so on , in a source language sentence frame example combination form . for example , 1 { oliver twist } was born in 2 { workhouse }; there were no 3 { aunts }, no 4 { sisters }, no 5 { cousins }, no 6 { grand_mothers }. after the source language sentence is integrated into the source language sentence frame strictly according to cabin numbers , cabin detection is performed . if a cabin is a sentence cabin with a model , a cabin model database is searched , the cabin is integrated into the cabin model and incorporated into the sentence frame , so that it is in a source language sentence frame example combination form . the step ends . ( ii ) transferring content of sentence cabins or cabin eyes ( 203 ). content of sentence cabins or cabin eyes is fetched in succession from the source language sentence frame example form , and transferred to corresponding sentence cabins or cabin eyes of a target language sentence frame to derive a source and target language transition form . using the foregoing sentence cabin including a model as an example , a source language frame example form thereof is as follows : 1 { the american } 2 { economic } machine is , organized around 3 { a basically private - enterprise }, 4 { market - oriented economy } in which 5 { consumers } largely determine 6 { what shall be produced } by 7 {( 2301 ) spending their money in 1 [ the marketplace ] for those 2 [ goods and services ] that 3 [ they want most ]}. corresponding sentence cabins or cabin models of a target language sentence frame are as follows : { 1 } { 2 } { 3 } { 4 } { 2 } , { 5 } 7 {( 2301 ) [ 1 ] [ 3 ] [ 2 ] { 6 }. then the content of the sentence cabins or cabin eyes is fetched in succession from the source language sentence frame example form , and transferred to the corresponding sentence cabins or cabin eyes of the target language sentence frame . for example , content “ the american ” of a sentence cabin 1 is fetched and transferred to a corresponding sentence cabin 1 “{ 1 }” of the target language sentence frame ; content “ economic ” of a sentence cabin 2 is fetched and transferred to a corresponding sentence cabin 2 “{ 2 }” of the target language sentence frame ; . . . ; content “ the marketplace ” of a cabin eye 1 in a sentence cabin 7 is fetched and transferred to a corresponding cabin eye 1 “[ 1 ]” of a sentence cabin 7 of the target language sentence frame , and so on , to derive a source and target language transition form : 1 { the american } 2 { economic }, 3 { a basically private - enterprise } 4 { market - oriented economy )} , 2 { economic } , 5 { consumers } 7 {( 2301 ) 1 [ the marketplace ] 3 [ ] 2 [ goods and services ] 6 { what shall be produced }. therefore , a source and target language transition form is derived . the step ends . ( iii ) saving inquiry items and pre - selecting and providing a target language sentence to be corrected ( 204 ). word strings of the source language are fetched one by one from the sentence cabins or cabin eyes in the source and target language transition form , and a sense group database is inquired . if no word spacing exists in an ideographic text , the sense group database is inquired by using possible left - to - right arrangements , and inquiry items of the word strings of the two languages are saved to a correcting table . the correcting table includes at least a word string segment field , a search string field , an explanation field , and a string header field . continued from the foregoing example , “ american ” is fetched , the sense group database is inquired , and “ ”, “ ”, “ ”, “ ”, and “ ” are obtained ; “ american ” is saved to the search string field ; “ ”, “ ”, and so on are saved to explanation fields : the word string segment field is filled with 1 ; and the string header field is filled with 8 ( including a space and occupying the eighth character position ). then “ economic ” is fetched and saved to the search string field , the sense group database is inquired , and “ ”, “ ”, “ ”, and so on are obtained and saved to explanation fields ( three records are added in the correcting table again ); the word string segment field is filled with 2 ( they are the second segment ); the string header field is filled with 22 , and so on . a search is performed by using a pre - selecting module ( 402 ). if a record is reselected , it is transposed to the header of the word string segment in the correcting table . in the foregoing example , before a machine operates the pre - selecting module , the target language sentence is as follows ( note italic words ): 1 { } 2 { } 3 { } 4 { } 2 { } , 5 { } 7 {( 2301 ) 1 [ ] 3 [ ] 2 [ ] } 6 { }. in the pre - selecting module ( 402 ), an experience - based word database ( 405 ) ( including english string fields and chinese explanation fields ) and a chinese word order database ( 408 ) ( including an original order field and a corrected order field ) need to be searched . the sentence cabin 1 “ american ” has a reselected record of “ ” in records of the experience - based word database ( 405 ). in this case , the fourth record at “ ” in the correcting table is the first word string segment , and the segment header is “ ”. therefore , “ ” is replaced with “ ” ( because only the segment header record is provided finally ). similarly , “ basically ” in a sentence cabin 3 has a reselected record of “ ”; content of a cabin eye 3 of a sentence cabin 7 has a record of a corrected order of “ ” in the chinese word order database ( 408 ); after the operation in the pre - selecting module and after the corresponding sentence cabins and cabin eyes are corrected automatically , a target language sentence to be corrected that reserves flags and numbers of sentence cabins and cabin eyes after the pre - selection is provided ; and the sentence to be corrected is displayed ( 416 ) as follows : 1 { } 2 { } 3 { } 4 { } , 2 { } , 5 { } 7 {( 2301 ) 1 [ ] 3 [ ] 2 [ ] } 6 { }. the corresponding source language reference sentence is : 1 { the american } 2 { economic } machine is , organized around 3 { a basically private - enterprise }, 4 { market - oriented economy } in which 5 { consumers } largely determine 6 { what shall be produced } by 7 {( 2301 ) spending their money in 1 [ the marketplace ] for those 2 [ goods and services ] that they want most }. while the sentence to be corrected is displayed and provided , command buttons “ return ”, “ follow - up ”, “ move left ”, “ move right ”, “▴”, “ λ ”, and “ rhetoric ”, and a corresponding source language reference sentence are displayed ; and a preparation is made for accepting a user &# 39 ; s correcting operation . the step of this module ends . all the steps in modules ( i ) to ( iii ) are completed in a completely automatic state , and are a “ machine translation ” part in the method title “ a method for performing interactive translation of machine translation and human proofreading ”. next , the step of module ( iv ) is a “ human proofreading ” part , where interactions in human proofreading ensure that a fast and convenient use effect is achieved . still as shown in fig3 , which is a flowchart of a semantic content correcting module , after the operation in the step of the foregoing module , the target language sentence to be corrected , button , and source language reference sentence are provided ( 301 ), and a preparation is made for correcting semantic content . when the user reads the target language sentence to be corrected and the corresponding source language reference sentence , a correcting operation is started . the correcting module of the machine performs a semantic content correcting operation by using the correcting table , and the self - leaming module ( 401 ) interacts with the correcting module to learn and memorize man - machine interactions in the correcting process and provide data for the pre - selecting module . ( a ) replacing impropriate word strings ( 302 ): for example , the sentence to be corrected that is read by the user and the corresponding source language reference sentence are as follows : when the user considers that a word string “ ” in the sentence to be corrected is appropriate , the user clicks it . the machine searches the correcting table , and displays a drop - down list providing all related inquiry items as options . the search string field and string header field are inquired according to a clicked word string and character positions in the sentence to be corrected , and compliant records such as “ , , , ” are provided in a drop - down list . when an option in the list is clicked by the user , for example , when “ ” is clicked , the current impropriate word string “ ” is replaced with “ ”; content of the two records “ ” and “ ” in the correcting table is interchanged ; because the length of “ ” is not equal to the length of “ ”, the value of the “ string header ” field needs to be recorded after the modification . after the “ return ” button is clicked , the foregoing correction information is recorded in the experience - based word database , so that it is used for a search by the pre - selecting module . finally , the machine returns and performs an operation of translating a next sentence . ( b ) segmenting continuous sentence cabins ( 303 ): when continuous sentence cabins that cannot be segmented automatically for lack of reference are encountered , the sentence cabins are provided for segmentation and the user &# 39 ; s intervention . for example , when continuous sentence cabins include two word strings , the two sentence cabins respectively take one word and are segmented automatically . for another example , two sentence cabins are continuous , and one of the sentence cabins is a repetitive sentence cabin . by referring to the other one of the repetitive sentence cabins , a same part in the repetitive sentence cabins is divided out of the continuous sentence cabins , and the residual part belongs to the other one of the continuous sentence cabins . for example , the operation on the sentence to be translated “ when will he go there , tomorrow or some_other_day ?” pauses , and continuous sentence cabins “ 1 { 2 { he go there }” appear and cannot be segmented for lack of reference ; therefore , “ continuous sentence cabins . please click a segmentation point :” is displayed : apparently , “ he go there ” should be segmented into “ he ” and “ go there ”, which are respectively put into [ 1 ]+ +[ 2 ]. when “ he go there ” is clicked , the clicked point is used as a segmentation point to separate content of the two sentence cabins , so that the sentence becomes : ( c ) intervening and selecting another sentence frame ( 304 ): when encountering an incorrect selection of a sentence frame , such as uneven , incomplete , or stacking sentence cabins or cabin eyes , or when the user does not approve the current translated sentence and clicks the “ follow - up ” button , the machine provides multiple matched sentence frames as options , reintegrates the sentence into a sentence frame selected by clicking , and continues to perform the operation in s6 . for example , a sentence to be translated is : all content of the reference sentence is stacked in one sentence cabin . at least “ one sentence includes two parts : a sentence frame and a sentence cabin ” is not supported . the sentence frame selected automatically is incorrect . the “ follow - up ” button is clicked by the user , and multiple matched sentence frames are provided as options . after the user selects another sentence frame , the operation is continued to provide the sentence to be corrected and the corresponding source language reference sentence : after the foregoing command button is clicked by the user , subsequent operations are judgment and follow - up ( 313 ). ( d ) adding a sense group string ( 305 ): when another word string is selected to replace an impropriate word string and the sentence becomes incomplete , the user &# 39 ; s addition of a sense group string by using a sense group alignment method such as extending senses of words or adding characters or words ahead or behind is accepted , and the added string is used to make a replacement , and added to a corresponding language component field of the sense group string . for example , a sentence to be translated is : when the user clicks “ doctors ”, no option is found in the correcting table . when the user selects doctors to inquire a dictionary , a prompt “ doctors is a plural noun or a third - person singular verb ” is provided . the method specifies that all inflectional forms of words are recorded as new words . a sense group string “ doctors ” and “ ” entered by the user is accepted as a new sense group string and saved to the sense group database . meanwhile , the sentence to be corrected is replaced with : after the foregoing command button is clicked by the user , subsequent operations are judgment and follow - up ( 313 ). ( e ) composing and selecting a complex word string ( 306 ): when another word string is selected to replace an impropriate word string and the sentence becomes incomplete , the user &# 39 ; s addition of a complex word string by using a method of composing a complex word or reselecting a complex word is accepted , and the added string is used to make a replacement , and added to a corresponding language component field of a complex word database of the sense group database . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : when the user clicks word strings in one of the two sentence cabins , the user does not select an option listed in the correcting table , but uses a drag method to select “ before eating ”. a complex string “ ” composed by using the word strings by using a method of composing a complex word by the user is accepted . herein the word strings “ ” are replaced and the complex string is added to the complex word database . then the user uses the drag method to select “ during the night ”, and a complex word “ during the night ” is automatically inquired and provided . the user &# 39 ; s click and selection are accepted . in this case , the sentence to be corrected is corrected as follows : after the foregoing command button is clicked by the user , subsequent operations are judgment and follow - up ( 313 ). ( f ) word order of a sentence cabin ( 307 ): when the word order of a sentence cabin of a translated sentence is incorrect , the user &# 39 ; s click on a string and click on the “ move left ” or “ move right ” button are accepted , and then the clicked string is shifted forward or backward by one string position . doctors have been able to help lessen the pain of ulcers . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : 1 { doctors } have been able to help 2 { lessen the pain of ulcers }. if the user clicks “ ” and then clicks the “ move right ” button twice consecutively , the word is shifted right twice , and the sentence to be corrected is changed to : then the user clicks the “ move right ” button after clicking “ ”, and the sentence to be corrected is corrected as follows : when the user clicks the “ return ” button , first it is determined that the user changes the word order by using the “ move left ” or “ move right ” button , and the self - learning module is started . content before and after the movement in the currently moved sentence cabin is saved to the “ chinese word order ” database . then the machine returns . ( g ) replacing words ( 308 ): when multiple continuous strings are impropriate and cannot be selected by clicking , when the user selects a string by using a drag operation , enters another word string in a word replacement position , or edits the string , or makes it empty , and then dicks the “ λ ” button , the machine replaces the former with the latter . alfred herman , he shared the 1911 nobel peace prize for his work toward world peace . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : 1 { }, 2 { } 4 { } , 3 ( 1911 peace prize }. 1 { alfred herman }, 2 { he } shared 3 { the 1911 nobel peace prize } for his work toward 4 { world peace )}. when the user considers that “ peace prize ” is inappropriate and selects them by using a drag operation , the machine displays them in a text box like “ string selection ” and “ word replacement ”, and accepts the edited “ ”. when the “ λ ” button is clicked , the former is replaced with the latter , and the sentence to be corrected is corrected as follows : after the foregoing command button is clicked by the user , subsequent operations are judgment and follow - up ( 313 ). ( h ) rhetoric ( 309 ): when a rhetoric phenomenon cannot be processed by using the foregoing listed steps , the user &# 39 ; s dick on the “ rhetoric ” button is accepted , and then the current sentence to be corrected is copied to an editing box , and the user &# 39 ; s rhetoric operation performed by using an editing method is accepted . for example , a sentence to be translated or a rhetoric phenomenon after processing in other listed steps is as follows : dickens &# 39 ; language , at once rich colourful and varied , is like fine and sensitive musical instrument . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : 1 { dickens &# 39 ; language }, at once 2 { rich colourful } and 3 { varied }, is like 4 { fine and sensitive musical instrument }. when the user clicks the “ rhetoric ” button , the sentence to be corrected is copied to the editing box , and the user &# 39 ; s rhetoric operation performed by using an editing method is accepted . after the operation , the target language sentence to be corrected is : in addition to the foregoing functions , the “ return ” command button is further used to scan an editing box that is specially set for rhetoric . when the editing box is not empty , content of the box is fetched and returned ; otherwise , the sentence to be corrected is fetched and returned . ( j ) adding a quantifier ( 311 ): in english - to - chinese translation , because there is no quantifier in english but there are quantifiers in chinese , when necessary , a quantifier needs to be added to the sentence to be corrected , and the machine accepts the user &# 39 ; s click in a position in which addition is needed in the sentence to be corrected , and searches for a central noun after a quantity string that is closest to the clicked point ; when the “▴” button is also clicked , the machine searches a quantifier database by using the central noun , fetches the corresponding quantifier , and adds it to the sentence to be corrected ; if no quantifier is found in the quantifier database , the machine provides a dialog box , accepts the entered quantifier , adds it to the sentence , and adds it to the quantifier database . for example , a sentence to be translated is : on apr . 24 , 1970 . china successfully launched its first man - made earth satellite . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : 1 { 24 }, 2 { 1970 , } 3 { }. 1 { on april 24 }, 2 { 1970 , china } successfully launched its 3 { first man - made earth satellite }. the user selects a central noun after a number string or a quantity string by using a drag operation . for example , the user selects “ , and the machine displays them in “ string selection ” and “ word replacement ”. when the user clicks the “▴” command button , the quantifier database is searched by using the central noun (“ ” herein ), and a corresponding quantifier “ ” is fetched and added to the sentence to be corrected . in this case , the sentence to be corrected is changed to : 2 { 1970 } 1 { 24 }, 3 { } 4 { }. if the quantifier is not found in the quantifier database , a dialog box is provided , saying “ the quantifier is not found . the quantifier may be added in a ‘ quantifier / noun ’ form in word replacement .” in this example , “ ” may be entered . after the foregoing command button is clicked by the user , subsequent operations are judgment and follow - up ( 313 ). the foregoing steps a - h are unrelated to the types of language texts and have common features , and may appear in a bidirectional translation process of multiple languages , for example , a bidirectional translation process of english - to - chinese translation or chinese - to - english translation . the step j are related to the types of language texts and used in translating english into chinese or translating other languages into chinese . hereinafter , the stepsl and k are further related to the types of language texts . the step i are used in translation of ideographic texts without word spacing , for example , chinese - to - english translation . the step k are used in chinese - to - english translation . j - k have individual features , which are set according to specific languages . english - to - chinese translation is used as an example for description above . hereinafter , i and k occur in a chinese - to - english translation process . therefore , chinese - to - english translation is hereinafter used as an example for description accordingly . ( 1 ) converting cabins ( 310 ): in chinese - to - english translation , the machine accepts the users click on content of a sentence cabin or a cabin eye , searches for all inquiry items included in the current sentence cabin or cabin eye in the correcting table , provides them in a list , waits for the user to sequentially click and select for multiple times , and uses them to replace the content of a corresponding sentence cabin or cabin eye in the sentence to be corrected . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : 1 { essentially }, a 2 { theory } is an 3 { abstract }, 4 { } of what is conceived to be 5 { reality }. the sentence to be corrected includes four sentence cabins , where three sentence cabins have been translated into english , and only a sentence cabin 4 reserves content “ 4 { }” of the source language sentence cabin . when the user clicks the cabin content “ ”, in the process of inquiring the sense group database and generating the correcting table , because possible left - to - right arrangements of an ideographic text without word spacing are used as word strings to inquire the sense group database , all inquiry items are saved to the correcting table . “ ” is segmented into chinese word strings such as “ ”, “ ”, “ ”, “ ”, and “ ”, and the inquiry items include them and english explanations related to them , so that the user selects them sequentially according to english habits . herein the user should first select “ symbolic ”, and then select “ representation ”. then processing of the current sentence cabin is completed . the current sentence to be corrected is : 1 { essentially }, a 2 { theory } is an 3 { abstract }, 4 { symbolic representation } of what is conceived to be 5 { reality }. regardless of whether there are other corrections , the machine detects whether the foregoing command button and the provided related box and table are clicked by the user , and determines whether to perform subsequent operations of judgment and follow - up ( 313 ) accordingly . ( k ) adding articles and other words ( 312 ): in chinese - to - english translation , because there are no articles in chinese and verbs to / be and to / have and so on are not distinguished , these words need to be added in chinese - to - english translation ; when the machine provides the target language sentence to be corrected that reserves flags and numbers of sentence cabins , the machine has displayed “ a / an ”, “ the ”, “ to / be ”, “ to / have ”. and “###”; when one of them is clicked ( except “###”, which is an end flag ) and the sentence to be corrected is also clicked , the machine uses one of them to add a word string of an appropriate form in the clicked position in the sentence to be corrected . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : the machine inquires the sense group database by using possible arrangements of “ ”, and saves all inquiry items to the correcting table for the user to make a selection . herein the user selects “ ” and “ tired ”. in this case , the sentence to be corrected is changed to : this obviously does not comply with requirements of english . the user clicks “ to / be ” in “ a / an the to / be to / have ###” listed under “ add articles and other words ”, and then clicks the space in “ we tired ”. the machine determines that an operation of “ adding articles and other words ” needs to be performed herein , and determines , according to a requirement of “ to / be ”, that a verb “ are ” should be inserted herein . then the current sentence to be corrected is changed to : regardless of whether there are other corrections , the machine detects whether the foregoing command button and the provided related box and table are clicked by the user , and determines whether to perform subsequent operations of judgment and follow - up ( 313 ) accordingly . the steps that need to be corrected are listed and described above . another case is that the provided sentence to be corrected is completely correct and that the user clicks the “ return ” button without clicking any one of the foregoing buttons and related displayed page controls , that is , in this case , the provided sentence to be corrected is completely correct and does not need to be corrected . with the use of the method , more and more such cases will occur . it should be noted additionally that , all the sentences to be corrected that are mentioned above are provided in forms of target language sentences to be corrected that reserve flags and numbers of sentence cabins and cabin eyes . when the “ return ” command button is clicked , the machine retums , and all these flags and numbers of sentence cabins and cabin eyes and unnecessary spaces are discarded , as in a conventional manner . for example , “ 1 { we are tired }, as anyone can see .”; “ 2 { 1970 } 1 { 24 }, 3 { } 4 { }.” is changed to : “ we are tired , as anyone can see ”. 1970 24 , , “ which is returned and provided in a translation text box . finally , a target language text is generated and output ( 206 ).” a software machine generated for implementing the present invention may be operated and implemented in stand - alone or networked computers such as an existing mid - range computer , a minicomputer , a microcomputer , a supercomputer , a notebook computer , and a palmtop computer . it may be operated and implemented in various computer networks , and in particular , on the internet . it may also be operated and implemented in apparatuses such as a “ personal digital assistant ” pda ( personal digital assistant ), a tablet computer , and a mobile phone . a product in which the present invention is implemented may be applied in scenarios of work , study , entertainment , tourism , and so on where communication with people of other languages is required ; and may be used in scenarios of homes , organizations , schools , and every industry or trade where foreign languages are involved .
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refer to fig1 , it is a flowchart showing a fabrication process according to a preferred embodiment of the invention . firstly , a metal - chalcogenide precursor containing benzyl or benzyl derivative is synthesized ( step s 101 ), wherein the metal - chalcogenide precursor containing benzyl or benzyl derivative has the general formula of ( r 1 r 2 r 3 r 4 r 5 — c 6 h 3 — ch 2 —) nh - 2i m h x i ; wherein r 1 , r 2 , r 3 , r 4 , and r 5 are each independently a functional group , m denotes an n - valent metal and n is an integer of 1 - 6 , x denotes a chalcogen element , h is an integer of 1 - 10 , and i is an integer of 0 - 30 ; wherein the r 1 - 5 groups are selected from hydrogen , aromatic , ester , ether , carboxylic acid , sulfonic acid , aldehyde , hydroxyl , ketone , imine , amide , methyl or ethyl group , and a branched or cyclic aliphatic group containing 3 to 6 carbons , and the metal is germanium ( ge ), antimony ( sb ), tin ( sn ), lead ( pb ), bismuth ( bi ), gallium ( ga ), indium ( in ), or thallium ( ti ). and then , the precursor is dissolved in a solvent to produce a precursor solution ( step s 103 ), wherein a chalcogen element or compound can be added to the precursor solution to adjust the molar ratio of metal ion to chalcogen therein ; wherein the chalcogen element is sulfur , selenium , or tellurium , or a mixture thereof , and the solvent may be selected from aromatics , aliphatics , esters , ketones , alcohols , amides , amines , imines , sulfonamides , or a mixture thereof . thereafter , the precursor solution is pattern - coated on a suitable substrate in a coating manner ( step s 105 ), such as roller coating , ink jet printing , screen printing , or imprinting , and the like . after the substrate is dried through a hot plate , a curing process is performed to form a patterned active layer film on the substrate ( step s 107 ) for use in a semiconductor element . the curing process can be performed by direct pattern , ultraviolet curing , or thermal curing to cure the existing patterned region ; and the semiconductor element may be , for example , an active element , thin film transistor , solar cell , radio - frequency identification element ( rfid ), integrated circuit , or optical communication element , and the like . refer to fig2 , it is a flowchart showing a fabrication process according to another preferred embodiment of the invention . firstly , a metal - chalcogenide precursor containing benzyl or benzyl derivative is synthesized ( step s 20 1 ), wherein the metal - chalcogenide precursor containing benzyl or benzyl derivative has the general formula of ( r 1 r 2 r 3 r 4 r 5 — c 6 h 3 — ch 2 —) nh - 2i m h x i ; wherein r 1 , r 2 , r 3 , r 4 , and r 5 are each independently a functional group , m denotes an n - valent metal and n is an integer of 1 - 6 , x denotes a chalcogen element , h is an integer of 1 - 10 , and i is an integer of 0 - 30 ; wherein the r 1 - 5 groups are selected from hydrogen , aromatic , ester , ether , carboxylic acid , sulfonic acid , aldehyde , hydroxyl , ketone , imine , amide , methyl or ethyl group , and a branched or cyclic aliphatic group containing 3 to 6 carbons , and the metal is germanium ( ge ), antimony ( sb ), tin ( sn ), lead ( pb ), bismuth ( bi ), gallium ( ga ), indium ( in ), or thallium ( ti ). and then , the precursor is dissolved in a solvent to produce a precursor solution ( step . s 203 ), wherein a chalcogen element or compound can be added to the precursor solution to adjust the molar ratio of metal ion to chalcogen therein ; wherein the chalcogen element is sulfur , selenium , or tellurium , or a mixture thereof , and the solvent may be selected from aromatics , aliphatics , esters , ketones , alcohols , amides , amines , imines , sulfonamides , or a mixture thereof . thereafter , the precursor solution is non - pattern - coated on a substrate in a coating manner ( step s 205 ), such as spin coating , roller coating , ink jet printing , slot die coating , screen printing , or imprinting , and the like . after the non - pattern coating , an active layer thin film can be formed , for example , through the following two ways . one is that after the substrate is dried through a hot plate , a curing process is performed by photo or thermal curing to directly cure the whole non - pattern coated region ( step s 207 ), and then photoresist and etching is utilized to remove unwanted metal - chalcogenide portion , forming a patterned active layer film ( step s 209 ). the other is that after the substrate is dried through a hot plate , a curing process is performed by a photo - mask in combination with laser or ultraviolet curing to only cure a desired pattern region ( step s 211 ), and then a developer is utilized to remove uncured metal - chalcogenide precursor portion , forming a patterned active layer thin film ( step s 213 ). finally , the patterned active layer thin film is applied to a semiconductor element , such as , active element , thin film transistor , solar cell , radio - frequency identification element ( rfid ), integrated circuit , or optical communication element , and the like . refer to fig3 , it is a sectional view showing the use in a bottom - gate thin - film transistor according to the invention . in a presently common bottom - gate thin - film transistor structure , an active layer thin film is formed by plasma enhanced chemical vapor deposition ( pecvd ) to deposit amorphous si on a gate insulator , and then coating photoresist is performed by spin coating , and after exposure and development , a pattern is obtained by etching . and in the present invention , a metal - chalcogenide precursor solution is pattern - coated on a gate insulator 3 formed on a substrate 1 , then a photo or thermal curing ( laser direct pattern ) is performed to fabricate a semiconductor layer 4 of an active layer thin film and a positively charged semiconductor layer 5 of an active layer thin film having material nature close to that of amorphous silicon , which are insulating for a first conductive layer 2 through the gate insulator 3 . a passivation layer 7 is further set on a second conductive layer 6 to insulate from outside , and a third conductive layer 8 is used to connect with outside . in addition , for the positively charged semiconductor layer 5 of an active layer thin film , after being non - pattern coated and cured , unwanted pattern region is removed by laser direct pattern . non - limiting exemplifications below are only used to further illustrate embodiment aspects of the present invention . refer to fig4 , it is a flowchart showing a synthesis process of a tin sulfide precursor containing benzyl group according to an embodiment of the invention . it can be seen in the fig4 that , a dibenzyl tin dichloride / thf solution ( step s 401 ) is firstly take , and then added drop - wise to anhydrous sodium sulfide / thf solution with magnetic stirring at 30 ° c ., and after this , the mixture solution is continually stirred for thorough mixing to react ( step s 403 ). subsequently , the reaction solution is poured into water , and extracted with diethyl ether ; repeat three times ( step s 405 ). the extract is concentrated under reduced pressure and filtrated to obtain a solid product ( step s 407 ). and then , the solid product is dried in vacuum at room temperature to synthesize the tin sulfide precursor containing benzyl group ( 2 , 2 , 4 , 4 , 6 , 6 - hexabenzyl cycloytristannasulfane , ( bn 2 sns ) 3 )( step s 409 ). refer to fig5 , it is a flowchart showing a preparation process of a tin - chalcogenide active - layer film according to an embodiment of the invention . firstly , the tin sulfide precursor synthesized in the fig4 is taken , mixed simultaneously with chalcogenide dibenzyl disulfide , dibenzyl diselenide , and pyridine as a solvent , and stirred on a hot plate at 60 ° c . until they are completely be dissolved . after that , the mixture solution is filtrate through a filter , obtaining a precursor solution ( step s 501 ). subsequently , the precursor solution is spin - coated on a substrate ( step s 503 ), dried with a hot plate ( step s 505 ), and charged into an oven under nitrogen to perform thermal curing ( step s 507 ). repeat ( steps s 503 to s 507 ) three times , to provide the tin - chalcogenide active - layer film ( step s 509 ). refer to fig6 , it is a flowchart showing a synthesis process of a tin sulfide precursor containing benzyl derivative according to another embodiment of the invention . it can be seen in the fig6 that firstly a di ( 4 - methylbenzyl ) tin dichloride )/ thf solution is taken ( step s 601 ), and then added drop - wise to anhydrous sodium sulfide / thf solution with magnetic stirring at 30 ° c ., and after this , the mixture solution is continually stirred for thorough mixing to react ( step s 603 ). subsequently , the reaction solution is poured into water , and extracted with diethyl ether ; repeat three times ( step s 605 ). the extract is concentrated under reduced pressure and filtrated to obtain a solid product ( step s 607 ). and then , the solid product is dried in vacuum at room temperature to synthesize the tin sulfide precursor containing benzyl derivative ( 2 , 2 , 4 , 4 , 6 , 6 - hexa ( 4 ′- methyl - benzyl ) cycloytristannasulfane , ( ch 3 — bn 2 sns ) 3 )( step s 609 ). refer to fig7 , it is a flowchart showing a preparation process of a tin - chalcogenide active - layer film according to another embodiment of the invention . firstly , the tin sulfide precursor synthesized in the fig6 is taken , mixed simultaneously with chalcogenide dibenzyl disulfide , dibenzyl diselenide , and pyridine as a solvent , and magnetically stirred until they are completely be dissolved . after that , the mixture solution is filtrate through a filter , obtaining a precursor solution ( step s 701 ). subsequently , the precursor solution is spin - coated on a substrate ( step s 703 ), dried with a hot plate ( step s 705 ), and charged into an oven under nitrogen to perform thermal curing ( step s 707 ), to provide the tin - chalcogenide active - layer film ( step s 709 ). in conclusion , with the technical approaches above , the present invention can not only achieve the purposes of reduced equipment cost and simplified process , but also further provide enhanced quality : in the precursor solution of the invention , various properties of the active layer thin film , such as band gap value and mobility etc ., can be adjusted by adding other compounds for doping ; and it can be well verified that these properties have favorable benefits for reducing starting voltage and improving whole quality . the invention is different from conventional technologies either in materials or in fabrication manner , is considerably valuable for industry application , and conforms to the requirements of novelty and inventive step . but , the foregoing general descriptions are only illustrative and not to limit the present invention . it will be apparent to those skilled in the art that various modifications and variations can be made without departing from the scope of the invention , which fall within the scope of the following claims .
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the present invention relates to the manipulation of pipettes , as well as a number of its applications . for the purpose of illustration , the drawings as well as the description will generally refer to the apparatus addressing this solution as a liquid handling android . however , the means disclosed in this invention are equally applicable to more general embodiments in the field of liquid handling . the global structure of a liquid handling android comprises few elements , all of which have a given functional role in the architecture . in essence , a liquid handling android operates above a certain deck , that could include or not the android base itself . the deck could either be a physical part , soft or rigid , either a virtual region without delimitations — for example belonging to a laboratory bench . the deck could also be the physical assembly of smaller units , called blocks , that combine together in order to form a larger operating surface . a liquid handling android body — also referred to as base — provides the physical support to the arm , and possibly may comprise additional hardware like power chord connector , general switch , illumination , twister , settings camera , arm fixation , usb hub , tip waste tray , pipette rack , lifting handle . most importantly , its purpose is providing a certain stable anchor to the arm movement . the arm constitutes the main electromechanical element : it generates movement of the hand in space , mainly moving over a two dimensional surface but also capable of lifting and descending the pipette in order to perform the desired pipette action . the arm is attached to the body and could either comprise a hand , or be connected to a hand . the hand constitutes the part of the body coming in contact with the pipette , and with the optional ability of grabbing and depositing pipettes onto the pipette rack . additionally , the hand may contain a hand camera , the functionality of manipulating the pipette knob for the purpose of aspiration and dispensing , the functionality of tip ejection and the functionality of actuating the pipette for the purpose of setting a desired volume . the system is complemented by a software interface , whose purpose comprises controlling the movements of the arm , the actions of the hand , communicating with the cameras and processing the images , and above all managing all the interaction with the user for programmability purposes and also for reporting purposes . a possible liquid handling android can be made as described in fig1 . the body 101 could be an injection moulded polymeric structure , either monolithic or in various parts , including active components ( like electronics and cameras ) and passive components like a weight ballast ( solid or liquid - filled ), preferably positioned in the lower part 104 . in some embodiments , the body could include a foot ( not shown ) meant to provide additional stability . in other embodiments the body could be positioned onto a laboratory bench but , by hosting batteries and interfaces , could also be designed to be used in other environments , like in the field or in portable implementations . in the figure , the body hosts a ballast 104 , a receptacle for a removable tip tray 103 , a body camera in location 102 with the purpose of volumetric setting and possibly with the purpose of deck area monitoring and inspection for intrusion detection , a plurality of pipette slots 121 , in the form of receptacles or hanging fixtures or magnetic holders or similar designed to host pipettes like the one indicated by 105 . the body can include a lifting handle like the one described in 108 , and mechanical elements like the one indicated in 109 making the interaction with the pipette easier , for example by allowing an easy access the ejection button for the tip . the body can include a twister 122 , defined as the actuator capable of setting the pipette volume . typically , this operation is performed by twisting the knob of the pipette , but it could also be achieved by electronic means for electronic pipettes — for example remote bluetooth communication or physical electrical links . it should be noted that additional electronics accessories could improve the advantages of the system : for example , a temperature or pressure or humidity sensor , possibly connected to a usb hub and read directly from the software interface , could allow improving the calibration of the pipettes by integrating and correcting for this information . the deck area 106 defines the operating surface of the liquid handling android , being larger , smaller or equal than the operating range of the arm . the deck area could have a circular shape , a rectangular shape or similar . preferably the deck has a shape making intuitive to the user the correct orientation . the deck could be a virtual region , for example delimited by simple illumination , but also a soft pad ( for example , a silicon pad that can be easily rolled above itself to reduce its size and recover a flat conformal shape when positioned onto a bench ), or a rigid metallic or polymeric plate , including wood or composite materials . it is important to emphasize the possible advantages of virtual or foldable decks , since portability of a liquid handling android constitutes a main advantage for service and support operations , making the shipment of the android more effective cost - wise . in addition , a foldable or virtual deck allows saving space when the android is not in use . the deck could contain a plurality of locations providing specific information , either to the user either to the system itself . for example , labels , warnings , instructions , precautions , and disclaimers addressed to the user , but also localization marks , barcodes , coded symbols , tags , fiducial spots , to improve the space localization of the pipette and the consumables by means of the cameras . a plurality of types of consumables , for example the microplates indicated as 107 , can be positioned onto the deck , either in a free format configuration , either in fixed or almost fixed format configuration . a fixed format configuration implies to precisely localize the consumable in a given position , without leaving an arbitrary choice for its orientation , while an almost fixed format configuration indicates an approximate region for the consumable , but leaving the option of rotations and displacements in proximity of the nominal position for the same . fixed format configurations may profit from slots , rails or similar solutions . in all configurations , the presence of serigraphic or printed graphics can facilitate the user job of positioning a plate , but also simplifying the function of consumable localization by the cameras and providing a sense of order to the user perception , making the repetition of the same protocol an easier task . optionally , the printed graphics and information could be performed in different colours , making the camera more selective to identify a part of the information hereby present . the arm , in this case defined as the structure between element 110 and element 113 , comprises a plurality of actuators or solutions with a similar functionality ( for example , a cable driven system where the motors are actually localized outside the arm , or a pneumatic system using cylinders as actuators ). in the present embodiment , actuators are chosen from the category of servo motors integrating gear reduction and angular feedback , allowing setting the actuator to a given angle between its body and the output axis . in a single unit , for example unit 110 , the provision of power and serial communication link ( for example based on the rs232 , rs485 or usb standards ) allows to input and output different information : examples of input are the desired position , the velocity profile for a movement , the maximum torque , the angular acceptance window ; examples of output are the current position , the current velocity , the unit temperature , the unit status , and possible faults . the motion of the arm occurs mainly in the horizontal plane , being typical biochemical operations performed on a planar and horizontal bench with consumables which have a marginally different height . however , the insertion of tips and the aspiration and dispensing of liquids , for example , also require vertical movements . in this specific embodiment , the arm operates mostly in the horizontal plane and it has a more limited excursion in the vertical plane . one way to achieve the required displacement , for example , would be relying on two angular actuators setting the position in the horizontal plane and a vertical linear actuator . in alternative , the weight and complexity of the linear actuator could suggest its replacement by two angular movements , for example the angular actuators 112 and 113 , allowing moving the pipette up and down by conserving its orientation in space through simultaneous movement . this feature can be important in consideration of the fact that the pipette verticality constitutes an important requirement for better volumetric performances of pipettes . for other reasons , it could be preferable to increase the number of angular actuators for a movement in the horizontal plane . for example , in some embodiments it could be desirable to define the orientation of the vertical pipette with respect to azimuthal rotations : this automatically implies at least three actuators for horizontal movements . the presence of obstacles or fixed structure could also require a larger number of actuators , for example four as depicted in fig1 . the choice of the arm configuration could follow good engineering practice and common sense , in view of the application and of the angular actuators performances . the hand design could exploit concepts and components similar to those applied to the arm . in the depicted embodiment , the hand starts from actuator 114 , which is actually the actuator taking care of the grabbing of the pipette . the grabber , not shown for clarity , can be a simple claw mechanism capable of exercising a pressure on the two sides of the pipette . it could also be a single claw mechanism , where the moving claw is opposite to a fixed claw which is conformal to the pipette . claws can have , in general , a conformal shape , a planar shape , or a limited number of contact points with the pipette . different design have different advantages : depending on the embodiment , the liquid handling android could be designed to deal with a single type of pipette , or with a multiplicity of models . it is obvious to those skilled in the art that claws have to be conceived accordingly , and their conception could be different for different pipettes . the hand may further comprise a camera 123 , to be oriented and moved in different directions , independently or dependently together with the pipette , with the purpose of identifying the consumable and its position in space but also the position of the tip 120 or the pipette 119 once it has been grabbed from the body slot 121 . it is important to realize that it is challenging to image , with a fixed camera , a typical deck surface characteristic of a biological or chemical test without going too far away from the deck . therefore , the suggested embodiment indicates a solution for the problem by imaging the deck area by a series of pictures individually covering a part of the useful surface . the image could be recomposed in a mosaic by suitable software , allowing having a synoptic view of the deck space and the consumable thereby contained . the composite imaging could also allow — by tilting or translation of the camera or of the hand — to have multiple images of the same deck or part of it . this feature could be easily exploited with the purpose of obtaining stereoscopic information in order to reconstruct at least part of the three - dimensional information . this feature is particularly relevant in order to extract information on the height of the consumable , possibly required for the correct setting of the pipette aspirating and dispensing position . three - dimensional information could also be achieved by means of using the focus information from the camera , provided that the camera has an adjustable focus and the optical configuration has a limited depth of focus . this method , would allow extracting depth information by simple scan of the object itself , and analysis of the spatial contrast of the image . a colour camera could also provide additional information , for example allowing identifying consumables and pipettes or other accessories based on the colour space distribution . the hand may include a thumb actuator 115 , whose purpose is to actuate the thumb 116 with functionality similar to the human thumb in the manipulation of a pipette . the thumb movement could be a simple partial rotation around the axis , but it is important to notice that improving the precision of the thumb action , for example in its speed , position , and pressure sensitivity with respect to a human thumb , could introduce various improvements in the pipette manipulation : for example , improved mixing of liquids by rapid aspiration / dispensing sequences through the excursion of knob 117 , improvements in the precision of dispensing by a reproducible position displacement or velocity profile , and an improved detection of the pipette stop by pressure feedback mechanisms . ultimately , the thumb action could also depend on the liquid properties — making the pipette working in optimal conditions with viscous liquids or heterogeneous samples . as another example , a fast and reproducible thumb action could improve the performances and the reliability for on - the - fly dispensing of liquids , defined as dispensing of liquids without physical contact with the recipient - contained liquid . this possibility would enable performances that are not possible to be achieved by manual pipetting operations , with significant savings in time and in the use of tips . a combination of a multiplicity of dispensing and aspirating methods , combined with the possibility of individually calibrate them for arbitrary liquids ( as described in a following section ) supports the evidence that a liquid handling android can outperform easily a manual operator , both in capacity and quality . a second embodiment of a liquid handling android is described in fig6 . a plastic enclose 601 constitutes and contains the main body , which is designed as a vertical structure mounted onto a baseplate 602 . the baseplate 602 has the purpose of providing stability to the system , and to make the system independent from possible vibrations and oscillations of the supporting bench — whether induced by the android itself or by external agents . the body 601 also include a rotating actuator 603 for the execution of the volume setting procedure . the rotating actuator is assisted by a camera 604 that , by means of the internal illuminator 605 , is capable if imaging the digital counter positioned onto the pipettes 606 . in this embodiment , the body 601 contains electronics and mechanics : in fact , the vertical movement of the arm is achieved by a linear actuator ( not visible in the picture ) that raises vertically the shoulder 607 , allowing for the required vertical excursion of the arm . as a consequence of this , the arm functionality is limited to the displacement of the hand 608 in the horizontal plane , being the vertical movements achieved inside the body 601 . differently from fig1 , the arm therefore contains only three servomotors 609 that allow for complete coverage of the intended area . details about the hand embodiment are shown in fig7 . two servomotors 701 and 702 assist the hand in manipulating the pipette , including grabbing , ejecting the tip , and actuating the pipette knob 705 for aspiration and dispensing of liquids . servomotor 701 has the double function of applying the required pressure on the pipette knob 705 , including the monitoring of the pressure feedback and the monitoring of the knob position in order to determine the pipette stop . the double functionality is achieved by means of cams , where cam 704 is always moving together with the servomotor 701 axis , while the cam 712 is actuated by the cam 704 only within a limited angular range . the pressure of cam 704 onto cam 712 actuates the button 706 on the pipette , inducing the ejection of tip 709 from the pipette . another cam is actuated by servomotor 702 : cam 703 actuates a lever ( not shown ) that slides on wedge 707 , which in its turn pushes the clamp 708 against the pipette body and results in the pipette grabbing . a symmetric mechanism is present on the other side of the pipette , resulting in a symmetric clamping force aligning the axis of the pipette with the axis of the hand . importantly , the hand hosts a camera 711 and an associated light source 710 . the purpose of the light is to apply uniform and constant illumination in the field of view of camera 711 , field of view comprising the bird flight view of the deck , the imaging of the tip 709 and in this case also of the pipette end 713 . having these elements within the field of view , allows measuring the relative position of these objects within the camera image . in fact , the correction of the optical distortion of the lens allows determining the radial line — passing through the objective of camera 711 — along which an object within the field of view lies . therefore , its transversal position can be reconstructed by estimating its vertical location . the vertical location of an element , for example the tip end , can be estimated in different ways : by means of the lens focus , by contact of the same object against a reference of known vertical position ( sensed through the pressure feedback of the vertical motion ), by multiple displaced images of an object which is not connected to the hand , by stereoscopic imaging of two cameras are mounted on the hand , by measurement of the apparent size of a 2 - dimensional barcode of known dimensions , and other methods . a possible embodiment describing methods and devices for the definition of the pre - set volume in an adjustable pipette is described in fig2 . in the picture , a camera 203 is located inside the body 201 , body already described in fig1 . the camera is positioned in such a way to be able to image the pipette display 215 ( not directly visible in the picture being covered by the pipette body but indicated for example in location 313 of fig3 ) indicating the dispensing / aspirating volume of pipette 204 . obviously , the arm which is partially visible ( actuators 213 and 214 ) has been suitably designed in order to allow this position to be reached . the camera could either image the display from the front , or from a certain angle in whatever direction and plane ( for example , from the top or from the bottom , from the left or from the right ). the camera could be assisted by artificial illumination , either from the environment or from sources contained in the liquid handling android , either from natural sources . it is useful to combine the display monitoring with the capability of adjusting the pipette volume setting . this is accomplished by the actuator 206 connected to the knob twister 207 . the actuator can be set either by its angular position , either by its angular velocity . the knob twister is an element , preferably of elastic material , which has been designed in order to be able , by simple pressure of the knob against the twister , of applying a torque on the knob therefore allowing — as done for the majority of pipette types — to perform the required pipette adjustment . in some embodiments , the twister could be a rubber based cylinder with a concave ( truncated ) cone carved into its body : the cone shape would allow to conformally adjusting to different sizes of pipette knobs . a possible embodiment describing apparatus and methods for the action of tip ejection is shown in fig3 . obviously , tip ejection in a liquid handling android is complemented by tip insertion onto the pipette . however , in most of the present pipettes the tip insertion is simply performed by applying a certain pressure when the pipette body has been inserted into the tip . clearly , this operation is feasible in an embodiment as described in fig1 . concerning the tip ejection , multiple solutions could be exploited , including the direct action of the ejection button by means of a dedicated actuator most probably located into the hand of the liquid android . however , there is an economical solution which doesn &# 39 ; t require an additional actuator , as shown in fig3 for the liquid handling android embodiment already described in fig1 . the arm allows localizing the pipette 303 in a configuration where the ejection button 305 of the same pipette is facing a fixed structure 306 , for example fixed with respect to the body structure 301 . the actuation of the ejection button is achieved by a force generated by the arm itself , for example by the action of the actuators 309 and 310 in order to have the fixed structure 306 and the ejection button 305 being pushed one against the other . this solution allows saving at least one actuator and a certain complexity in the hand , resulting in a lighter and more reliable solution . an appropriate choice of the shape of the structure 306 allows also ejecting the tip in different spatial position , something which is desirable to avoid the accumulation of tips into a limited area of the waste tray 103 shown in fig1 . a possible embodiment of methods and devices achieving volumetric monitoring and traceability of pipetting operations is shown in fig4 . the four images correspond to four different snapshots taken by a camera , which in the liquid handling android previously described could either be camera 123 or camera 102 of fig1 . for simplicity of description , the image is taken from a position which is orthogonal to the pipette axis : however , this is not strictly required and most angles of view are possible . the image can visualize in part or in full the pipette body 402 and the tip 401 . as it is visible in the leftmost image , a reference image of an empty pipette constitutes the reference and it could also be stored — temporarily or permanently . it is understood that the image could be taken in a reference position of the arm , so providing a uniform and constant background information and illumination . in the second picture from the left of fig4 , it is depicted a tip which has been loaded by a given amount of liquid , according to the volumetric settings of the adjustable pipette . it is obvious to those skilled in the art that every set volume corresponds , for a given tip , to a given location of liquid meniscus 403 . in this respect , therefore , the meniscus location constitutes an indicator that the pipette has aspirated correctly the desired amount of liquid . conversely , the reference image constitutes the logical reference after a dispensing operation , where the presence of droplets or liquid left - overs can also be detected in a similar way . in the third picture from the left in fig4 , it is shown a pathological case where the aspiration is not occurred correctly . visibly , a bubble of air 405 has been introduced in the pipette , modifying the actual liquid volume contained in the pipette with respect to the desired volume . according to the origin of the bubble , the meniscus 404 could be at the correct position ( defined according to the considerations done for the second picture from the left of the same figure ), therefore indicating that the actual liquid volume in the tip is lower than expected . the liquid meniscus could also be at a higher level , indicating for example that the bubble has been formed after aspiration , or could even be lower than expected — suggesting a serious problem in the liquid collection . a simple and practical case occurring in laboratory practice is shown in the rightmost picture of fig4 : a lack of liquid in the container where the pipette has aspirated the liquid , or the incorrect position of the tip with respect to the liquid level , has resulted in a partial aspiration of the liquid at the advantage of air contained in the pipette . the meniscus 405 is most probably in the correct position ; however a second liquid - air interface is visible in location 407 . all these undesirable behaviours can be made available to the user , significantly improving the interpretation of the data generated by the assay . in all cases , the image contains significant information that would be lost in manual operations . this useful information could either be processed online , in order to try recovering the process , either simply stored offline for operator monitoring and quality control purposes . overall , a similar imaging configuration could be used for controlling the position of a tip in a consumable with respect to the liquid level . the imaging of the consumable , and the identification of the liquid level , could allow determining the vertical distance between the liquid and the tip , allowing precise sipping or dispensing of liquids . similarly , the same procedure could be applied to aspirate liquid in particular vertical location of the liquid , for example in the case of separated blood and aspiration of buffy coat at the interface between plasma / serum and erythrocytes . a possible embodiment describing methods and apparatus for achieving vision assisted positioning of a tip is shown in fig5 . the image corresponds to the image taken by a camera which is preferably connected to the pipette hand , for example camera 123 described in fig1 . if the camera is connected to the pipette hand , grabbing the pipette 119 connected to tip 120 in fig1 will result in a reproducible and constant position of the pipette tip 504 visible in fig5 . therefore , this information constitutes already an important control on the proper grabbing of the pipette from the hand . it is understood that different pipettes and different tips could result in different images and shapes , so the tip imaging also represents a possible method for making sure that no misidentification has occurred . additionally , the image may contain — as in the case of fig5 — additional objects within the field of view . it is well known in the art that any object could be either in focus , either out of focus , accordingly to the type of optics and sensor utilized , and obviously their distance from the camera . the arm capability is such that it is possible to operate the arm at a desired height , which of course means that the distance between the consumable and the tip will be set to a desired value . in this conditions , it is possible to identify the lateral alignment of tip 504 with respect to the desired well position 507 according to the following method : the axis 504 of the tip 503 , when prolonged , will identify the trajectory that the tip will perform for a vertical movement ( in the example that the tip is vertical , as it should typically be ). however , a given and typical distance of the tip with respect to the consumable will define a single point in the image that the tip will intersect when localized at the same height of the identified well . therefore , the relative horizontal alignment of the tip can be achieved by imaging the same tip within the field of view , and applying an offset in the imaging plane : this point should be directly positioned onto the desired destination , by applying lateral movements of the arm without changing the distance of the tip from the consumable . it should be remarked that this method works also in presence of optical distortions , that can be corrected either in full by vision analysis method either by empirical alignment . in another implementation , as visible for example in fig7 , the camera can image the tip while the tip is approaching the liquid surface . with respect to an image where the tip is far away from the liquid , an image where the tip is in contact with the liquid will change the image of the tip , and therefore such change can be used to identify the position where the tip touches the liquid surface , for example with the purpose of aspirating or dispensing nearby the liquid surface . the difference in the images can be enhanced by suitable illumination of the tip or of the liquid : as soon as they come in contact , the refraction index of the tip polymer and the refraction index of a liquid are similar , and therefore light will channel through the other medium under the guidance of internal reflection along the materials surface . the change in the illumination configuration can be easily identified and lead to the detection of the tip - liquid contact . illumination conditions particularly suited to the internal reflection exploitation can be achieved by means of light emitting diodes or lasers , or under the guidance of light guides , like for example optical fibres . a possible embodiment of a deck configuration is shown in fig8 . differently from the deck described in fig1 , the consumables are organized in a geometrical manner by means of holders called blocks , defined as reusable or non - reusable supports capable of holding one or a plurality of consumables . a feature of the blocks is the possibility of assembling them into a larger structure called mosaic , which is a planar composition of blocks organized according to some pre - defined rules but with a certain pre - defined flexibility . in fig8 , different types of blocks are assembled together : for example , block 801 is intended for the collection of used tips , bock 802 is designed to contain and support different types of microtubes , block 803 is intended to hold and support tip racks , block 804 serves the support of larger tubes like for example 15 ml , 50 ml and blood tubes , and block 805 contains a microplate . these blocks are not exhaustively covering all possibilities . for example , a block could be designed to host simultaneously pre - loaded reagents , specific consumables like tips , barcodes for processing information , tubes and empty consumables for allowing the users providing their own samples . in this last configuration , it is possible to conceive a domino block as a single unit that doesn &# 39 ; t require external blocks for processing , making therefore the domino deck a collection of independent experiments that do not depend from each other . importantly , domino blocks can be complemented by information by means of nfc , rfids , linear barcodes , optical recognition marks and two - dimensional barcodes as indicated in 806 . the purpose of providing additional information reliefs the system in active and contact - less identification of the blocks , for example by means of the camera 711 described in fig7 . other ways of extracting the domino block information is by means of electrical contacts positioned on their sides and coming into contact with neighbouring blocks , and propagated to the other blocks by means of an electrical network . one important feature of a domino deck consists in the capability of adapting its configuration to the user needs , while simultaneously being able to organize and rule the assembly of the blocks . in fact , the domino block could present keys on the sides , for example mechanical keys or magnetic keys , preventing the user from assembling the domino block incorrectly , and also validating the choice of a configuration by some forces keeping the assembly all together . one embodiment for a key is a mechanical configuration , similar to those implemented in lego toys for the purpose of education and play . another mechanism consists in specific magnetic configuration : for example , along a side designed to be oriented in direction “ down ” the side could host a plurality of magnets presenting a suitable magnetic configuration . poles in the configuration sns ( south - north - south ) could be matched to sides presenting nsn ( north - south - north ) as a consequence of an attraction force , while sides nsn will be pushed away from a side nsn ( similarly to the repulsion force of a sns side when pushed against a sns side ). the advantage of a magnetic configuration consists in an attractive force validating an allowed configuration , while a repulsive force will prevent assembling blocks with the wrong orientation . these magnetic forces could also improve the overall organization of the domino deck by means of connecting to an external reference structure . for example , in fig8 the block 807 is magnetically attached to the base below the body of the android by means of a sns magnetic configuration facing a nsn magnetic configuration generated by magnets embedded on side 809 . similarly , block 808 is magnetically connected to magnets position on side 810 of the android base through an sns magnetic configuration facing a nsn magnetic configuration . in this example , what prevent to rotate by 90 degrees the block is the different pitch between magnets , shorter on side 810 with respect to side 809 . for the same reason , the blocks in the domino deck cannot be rotated by 180 degrees or by 90 degrees . one important advantage of a domino deck consists in an optimal space occupation of the laboratory bench , being external to the android body . in fact , the space occupied by the system is limited to the space required by a given experiment , contrarily to the configuration of today liquid handlers that occupy bench space irrespectively of the complexity of the experiment involved . additionally , it allows minimizing the occupied bench space when the system is not used , for example by storing the domino blocks elsewhere or by assembling them in a vertical pile occupying the footprint of a single domino block . in general , users can exploit different domino blocks according to their typical experiment , by varying the amount of blocks of the various types which are required and without using the blocks which are unnecessary . while multiple procedures and methods for positioning are known to those skilled in the art , including the use of precision mechanics and encoders and decoders of x - y - z cartesian robots , we describe a method which is particularly suited for the identification and localization of consumables by means of a simple camera mounted on the moving arm . the camera and arm geometry here described is the one shown in fig6 , the arm 609 holding a pipette 608 by means of the grabber 708 shown in fig7 together with camera 711 and related illumination 710 . fig9 represent a possible image taken by camera 711 while moving above a certain block , to be accessed precisely for the purpose of pipetting in one given position ( for example well 910 ). it should be noted it is critical to extract the relative position of the pipette axis in three dimensions with respect to the desired pipetting location . known the pipette tip length ( for example by the pipette model or by other techniques including the sensing of the pipette tip contact , stereoscopic imaging , external measurement by means of camera 604 of fig6 , and other methods ), and given the fact the pipette tip could be visible within the field of view of the camera ( as possible in fig7 for pipette 709 by exploiting a suitable objective for camera 711 ), it is evident that the lateral position of the pipette tip end with respect to the camera axis can be computed in the space of the image sensor coordinates ( pixels ) and converted in real space lateral displacement once the conversion scale is known for the plane where the pipette tip end resides . the conversion scale can be achieved in multiple ways , including the use of a two - dimensional barcode of known dimensions in the same plane . however , fig9 shows that knowing the relative position of the pipette tip end with respect to the camera is a partial solution to the problem addressing the positioning of the pipette tip end into a well 910 , since it is still required to move the camera axis ( shown by the hatched cross 901 ) at a given offset ( in the real space ) with respect to the consumable 902 . the following method shows a procedure which has the advantage of being rapid and robust , being capable of compensating any misalignments and locally adjusted for each individual block or small area of the deck . in fact , block 911 is equipped with different features . one feature is the presence of mirrors 903 , 904 , 905 , 906 positioned on planes which are at 45 degrees with respect to the horizontal plane , and reflecting in the upward direction the image from the side of the microplate . these mirrors allow the optical inspection of any user - labelled barcode put on the vertical sides of the microplates , that can be measured by the camera 711 easily irrespectively of the sides where the barcode is applied , and potentially detecting any microplate rotation if the user barcode should be in a given side of the microplate . the same barcode identification capability can be exploited to detect other barcodes implemented into the block 911 in positions 909 and 908 for example . it should be emphasized that the choice of two barcodes could be reduced to a single barcode and could be extended to a plurality of those , with the purpose of increasing the system robustness or the amount of information to be read by the camera . the two dimensional barcodes mounted in block 911 are positioned at about the same height of the wells , or at a known offset in the vertical plane . the reading of a barcode , for example of a qr barcode , also provides to the user information about its apparent size , which is the size measured by the camera in its space ( typically , measured in pixels along the directions of the dimensions of the sensor ). having barcodes of known dimensions , or of dimensions which are reported into the content of the barcode itself , allows therefore to define the spatial conversion scale to convert any distance measured by the camera in the same plane into real dimensions . alternatively , if the barcode is of unknown dimensions , two barcodes at a known distance can serve the same purpose , for example by knowing the distance between barcode 908 and barcode 909 . indeed , for the case of camera with unknown pixel shape the information about the barcode angle has to be used in order to extract the suitable conversion scale ( different in the two directions of the image sensor ). in summary , measuring the dimensions and the angle of a single two - dimensional barcode allows for measuring distances in the same plane of the barcode , or in its proximity . however , for a given camera and objective the conversion scale changes with the distance according to simple projective rules , once the camera images are corrected for the objective distortions . so , a vertical scan performed by moving vertically the camera at known steps ( for example , knowing the gear factor and the steps of a motor moving the arm vertically , allows to construct a curve that automatically provides the user , by interpolation and extrapolation , the vertical distance for a given camera and objective from the barcode itself . ultimately , the same curve can be used in a reverse manner to extract the actual distance of the camera from the barcode , and knowing the offset of the pipette tip end with respect to the camera : this inverse method allows solving the problem of vertical positioning of the pipette end tip with respect to well 910 . similarly , the lateral offset of the camera axis 910 with respect to well 910 can be computed by knowing the lateral offset of well 910 with respect to a barcode 909 in the reference frame described by arrows 912 and 907 . this offset is specific to each module , and can be stored into a suitable way externally or internally to the module ( for example , by means of a database , inside the barcode data , or by an rfid or nfc tag ). to achieve the target of relative positioning of the arm , it should be noted that the camera axis 901 is localized in the reference frame 912 and 907 by the measurement of the barcode angle , its position in the sensor image and the previously described spatial conversion scale : the transformation between the camera reference frame and the real space reference frame of the block become uniquely identified by a single image . so , putting all elements together , the present method allows precise relative positioning of a pipette with respect to a location in a given consumable by means of a camera mounted on a robotic arm , using the information provided by a barcode . in fact , the present method can be used also for precisely identify the parameters transforming the angles of the servomotors 609 of fig6 into relative coordinates within one block . this approach has the advantage of precisely refine the mechanical precision in presence of the arm twisting , bending , imperfections in the angular determination , inaccurate arm sizes and dimensions , assembly inaccuracies and in general improving the reproducibility . in summary , the non - linear , non - invertible transformation of the servomotors angles into the camera position in the real space depends on a large number of external parameters , but is a known analytical function following basic trigonometric rules . however , many of these parameters are more accurate when computed locally , for example the bending of the arm could vary as a function of the arm configuration ( its extension , for example ). the method here disclosed is based on multiple images of block 911 — similar to the image of fig9 — where the images are displaced by a known , local angular amount for any of the motors , allows creating a dataset of images where the barcode position and angle is measured within the camera image . using the arguments explained before for a single image , the distances between the theoretical positions of the camera in the barcode reference frame 912 and 907 and the actual distances can be minimized by means of a least squares minimization algorithm , and therefore an optimal local transformation can be created and used afterwards . this procedure can be repeated rapidly over time , for example triggered by a large discrepancy between theoretical positions and actual positions during the arm operations , in order to maintain the system highly reproducible . in fig1 , an example of the residuals that can be obtained by changing individually the angular position of the three servomotors 609 shown in fig6 , for a number of angular settings ( each of the intersecting lines corresponding to the modification of the angle of one individual motor , as indicated in the plot labels ). the arrows in the plot indicate the residuals , defined as the deviation of the expected position vs . the actual position measured by the camera , after having applied the previously mentioned minimization procedure . the size of the arrows ( magnified by a factor 5 × in order to make them visible in the plot ) indicates the error in positioning of the system . the method here described allowed improving the spatial precision of the system by a factor 6 ×, taking average residuals from 6 mm ( mainly given by the precision of the mechanical system and of the electronics ) to less than 1 mm . a problem specific to liquid handling instrumentation is the need of identify , localize , count and dispose the liquid handling consumable called tip . there many different types of tips — and typical liquid handling operations imply the disposal of the tip after each liquid dispensing step , to avoid further contamination . the consequence is a complex logistics even for relatively simple protocols , both in manual operations and liquid handling performed by automated systems . in particular , pipette tips in some disciplines have also strict requirements in terms of sterilization and contamination before operations actually have place : the consequence is that a typical laboratory has a very complex tip management logistics , induced by multiple tip types , compatibility of each tips for each equipment and manufacturer , and of the formats and packaging associated to those . essentially , all instrument manufacturers supply users with their own tip racks , tip rack being the name for a structure organizing tips in a regular array , and try to offer the widest choice possible in order to allow any operation on any instrument . consequently , tips supply becomes an expensive activity both for users and instrument suppliers . hereby , we describe a novel solution allowing our androids to use any tip which is already being used in the laboratory . the solution is totally independent from the tip rack , e . g . the holder containing the tips . the solution allows also to identify uniquely the tips , and to know which tips are usable in a rack without the requirement ( demanded by most instruments ) to start operations with unused and new tip racks . in this way , evident economy can be achieved by the customer , simultaneously obtaining the maximum flexibility in using high quality consumables on the android . the solution consists in identifying and localizing tips by means of top - view vision , for example the one achieved by means of camera 711 in picture 7 . any tip rack can be positioned in a domino block like the one shown in fig1 , the domino block essentially being a simple box ( possibly with a surface with an anti - slip pad to avoid undesired movement over time of the tip rack itself ) capable of hosting the vast majority of tip racks commercially available . it is very common to purchase tip racks that organize the tip consumables in the same geometrical configuration of microplate wells , e . g . a rectangular array of 12 × 8 tips which are spaced apart by 9 mm . assuming this configuration , in order to be able to use tips effectively we need to deal with various aspects : the identification of the type of tips , the identification of the available tips , the determination of the height of the tip upper part that will come in contact with the pipette end . even if these operations could be performed by direct image processing , e . g . vision - based algorithms identifying shapes and structures , it would be hard to be robust enough to be able to deal with hundreds of different configurations and designs which are not known a - priori . our vision - based solution consists in inserting into the tip racks two buttons 1101 and 1102 . the buttons could be either inserted by the user before executing an experiment , but also before autoclaving the tips for further reuse , or at manufacturing . the two buttons could be made in different ways : as a simple cork to be inserted into a tip of the corresponding type , or as a passive stub similar to the upper part of a tip and having about the same external diameter . buttons would require a barcode or similar optical mark at the top , the barcode being an easy and robust solution for identification and localization by the top - vision camera mounted on the arm . the advantage in using two - dimensional barcode consist in the fact that they will automatically provide the precise vertical position of the tip for grabbing , and also the correct transversal scale for identifying the conversion scale in the image allowing to reconstruct spatial dimensions . spatial coordinates are needed both for guiding the movement of the arm in order to grab a tip , but also to compute and determine the number of available tips , and their localization . in fact , barcodes 1101 and 1102 would be used to define the region of the tip rack where tips are present . in the example from fig1 , all the 34 tips localized in the matrix defined by the two buttons as corners would become a region from which the arm will pick the tips , region highlighted in the picture by means of the dashed rectangular perimeter 1103 . it is evident by anybody skilled in the art that the suitable choice of the corners would allow choosing the region of the tip rack to use , and allow counting ( by means of the known pitch among tips ) the number of tips available . similarly , the content of the barcode would provide to the system the information on the type of tips being hosted in the specific rack . the method here described by means of two barcodes , can be easily extended to a plurality of barcodes and different methods for indicating the usable sector of the rack for tips extraction . this method therefore provides the way of localize , identify and count tips in a substantially generic tip rack , and the same principle could be used for the extraction of partial information — for example in combination with tip recognition methods to discover possible holes in the tips formatting ( as an hypothesis , one tip being absent in location 1104 ). it should be noted that the same method can be applied to different types of consumables that imply picking operations : for example , needles for the purpose of liquid handling could be considered under the same methodology , with equivalent advantages . an important element of the liquid handling android is constituted by the software interface , a generic name including the package communicating with the camera , actuators and electronics , controlling and synchronizing their operations , processing the information to be sent and collected , but in particular interacting with the user and external sources of information ( websites and servers , for example ). the interaction with the user consists both on the system programmability and the provision of feedback related to the liquid handling process , including its execution performances , faults , checkpoints . in one possible embodiment , the cameras and the actuators of the liquid handling android are controlled by means of usb , and a usb hub is localized inside the body . in this embodiment , a single usb cable can connect the personal computer or the tablet constituting the user interface to the liquid handling android itself . in other embodiments , a wi - fi connection could serve for the purpose avoiding the necessity of a physical link . the controlling software could therefore exploit usb drivers and software development kits provided with the individual components with the purpose of minimizing the development , and similarly integrate existing packages for the vision processing and for the inverse transformation determining a set of actuators angles for a given position , in angle and space , of the pipette . an important aspect of software is constituted by the user interface . the availability of cameras capable of capturing real images of the process suggests using an approach based on virtual reality , where the user is provided with information — on the screen of the controlling system — which results partially from real images and partially from synthetic information . in this way , the adherence of the original protocol can be made in a more user - friendly way , improving the performances of the operator and reducing possible faults to minimum . the software interface could also interact with the user during the execution of liquid handling steps . for example , a protocol could require specific liquid handling steps — or operations like spectrophotometry , phase separation , microscope inspection or similar — which cannot be executed from the android itself . therefore , the software interface will trigger the user intervention ( or in alternative simply wait for it ) for example by means of visual indicators , hand waiving , acoustic signals , emails , sms or phone calls to the user . the purpose of the software is not limited to the execution of protocols , but it could also be extended to other operations having , for example , the purpose of improving the hardware performances . for example , it is well known in the art that accurate pipette performances require frequent calibration of the same , being the performances related to environmental parameters and also to their use . a liquid handling android could be controlled by software in such a way to execute pipette calibration procedures for example repeating a sufficient number of dispensing steps into a consumable , and monitoring ( by weight , colorimetry , fluorescence or similar techniques ) a physical parameter representative of the dispensed volume . it should be noted that — in a liquid handling android — there is no strict need of physically adjust the pipette calibration scale , since the software could automatically define the calibration table , and therefore the knowledge of the actual volume to be set in order to achieve a desired volume . having now described a few embodiments of the invention , it should be apparent to those skilled in the art that the foregoing is merely illustrative and not limiting , having been presented by way of example only . numerous modifications and other embodiments are within the scope of ordinary skill in the art and are contemplated as falling within the scope of the invention as defined by the appended claims and equivalents thereto . the contents of any references cited throughout this application are hereby incorporated by reference . the appropriate components , processes , and methods of those documents may be selected for the present invention and embodiments thereof .
| 1 |
this invention simplifies what has been attempted before in a very elegant aerodynamic execution of a device which not only distributes the fibers uniformly in the cross machine direction , but also allows them to be formed into a web . it is well known and published in the art what the key aerodynamic parameters for conveying solid particles in an air stream . the difficulty has been in developing a device that can maintain these conditions and distribute fibers onto a forming zone . a forming zone on most air laid machines is a foraminous screen supported over a vacuum table to consolidate the individual fibers into a web . other forming zones are rotary vacuum drums or condensers into which the air is blown into and the fibers are matted into a web on its surface later to be transferred to another process operation . other forming zones are composed by air conveying the individual cellulose fibers into a curtain of molten polymeric fibers as they are extruded from the die and later consolidated in a blended form onto a forming screen . fig6 shows a typical installation of this device , items 60 and 70 , with in association with a forming zone comprised of a forming vacuum box with a foraminous forming screen item 90 , as well as a meltblown extrusion die identified by item 80 . fibers or particles , because they are denser and consequently heavier than air , tend to follow their own trajectories due to the iso - kinetic forces exhibited in the air stream . therefore , it is imperative that air forming devices be designed to accommodate not only for the air characteristics required , but also accommodate the ability to uniformly convey and distribute particles or fibers in the cross direction , especially when a substrate or web is to be formed from the device . fibers , especially cellulose fluff fibers , need to be well defibrated into individual fibers . this process is . well understood in the industry , with several successful designs currently in the market place . companies like kamas , m & amp ; j , and famecannica have developed devices to defibrate pulp into individual fibers for many years now . the biggest use of these fibers is in absorbent cores for disposable products such as baby diapers and feminine care sanitary products . fibers from such devices can then be conveyed by air to their final fluff forming devices . in the case of forming absorbent batts in which the thickness or basis weight of the batt is large ( greater than 100 gsm ) the aerodynamic characteristics of the fluff forming devices are not as critical . the aerodynamic and design characteristics of the forming device become much more critical when the requirement is to form a substrate of less than 100 gsm and closer to the 20 gsm level . the challenge becomes on taking fibers that are being conveyed in a round duct at velocities that are typically in the 1000 to 10 , 000 fpm range and spreading these fibers to widths up to five meters wide while achieving a uniformity of the fibers or particles ranging under +/− 10 % by accepted standard test methods used in measuring this parameter . the present invention uses sound engineering principles in achieving this goal . the critical parameter of this invention is to take fibers from a circular duct and spread them to widths of approximately 1 . 5 to 3 . 2 meters or greater uniformly . fig1 shows the device which accomplishes this goal . it is a funnel like device which is fed by a round duct conveying fibers in an air stream . prior to the introduction of fibers into the air stream the spreading and forming device needs to provide air flows at the discharge which are extremely uniform in the cross direction . this is accomplished by maintaining constant or accelerating velocities through the funnel length , as the area at the discharge of the round duct is the same or slightly greater than the rectangular opening at the discharge of the funnel . this concept of maintaining constant or slightly accelerating air velocities through any cross sectional plane such that aa =& gt ; bb =& gt ; cc =& gt ; dd as shown in fig1 items 10 , 20 , 30 , and 40 of the spreading device is critical in achieving uniform cross direction air profiles at the discharge of the unit . fig4 shows the air profiles that are achieved applying these techniques to the forming device . this data was obtained from an unmodified discharge nozzle profile . it can be basically made flat when the profile control system shown in fig5 is implemented . the second key parameter is to have the fiber velocities which are equivalent to the air velocities of the conveying air stream be dissipated so that the iso - kinetic energy of the fiber is greatly reduced as it enters the spreading device . this is accomplished by the geometry of item 50 of fig2 , which shows the round duct entering the funnel at an angle , thus having the fibers hit the far wall of the spreading device . in this manner the velocity of the fibers and the momentum of the fibers are dissipated . this allows the fibers then to be re - aligned with the airflow profiles that will be developed by the geometries used in the design of the spreading device . if this step is not done , the fibers would have the tendency to stay in the center of the device creating a heavier center on the substrate formed . the angle of the circular duct can vary , as long as the fiber velocity is dissipated as they strike the back wall of the spreading and forming device . other means of conveying the fibers to the entrance of the forming device can be contemplated so that the velocities of the individual fibers align themselves with the velocities of the air stream . once the fibers are in the spreading and forming device , it is important that they have enough residence time in the device to streamline themselves to the airflows that have been developed within the device . this is accomplished by having the length of the device be at a minimum equivalent to ten times the diameter of the round feed duct for the fibers . lengths much shorter than 10 equivalent diameters will result in less efficient fiber spreading in the cross direction and worse profiles . the third key element of this invention is the ability to control the discharge of the fibers onto a foraminous forming screen or onto another fiber stream in order for the fibers to blend with these fibers forming a web . in this case the angle in which the fibers are directed onto either a forming zone , or is critical . this angle may require adjustment . item 60 in fig2 shows a device which is used at the discharge end of the spreading device to turn the fibers in the proper direction . the figure shows a nozzle with 90 ° turn . this angle is adjustable and can be adjusted to be whatever the application requires it to be . another method that can be used to adjust for the angle is to tilt the spreading and forming device to that angle which is also required for proper web forming . another advantage that this system has is the ability to have modular forming heads . thus , they can be combined individually in the cross machine direction making the formation width of the machine a non - issue . fig3 shows the advantage of this design by showing two side to side formers . there is no limitation to the number of formers that can be combined in the cross machine direction making it possible to achieve widths of five meters or more . for practical purposes the ideal width of the formers are in the range of 1 to 1 . 5 meters . even though the fiber formers are separate , the discharge portion , item 60 in the figures shown , is a continuous piece . in this manner , the fibers are air conveyed in a uniform cross direction manner to the forming zone without any separation as a result of the separate conveying funnels . furthermore , the discharge section as is shown in fig5 , item 60 , has an adjustable bottom plate , item 61 , which can be constricted in opening by adjustable screws to influence the trajectory of both the fiber and air stream . this added control system will guarantee a uniform profile of fibers into the forming zone .
| 3 |
preferred embodiments of the present invention will now be described in detail in accordance with the accompanying drawings . fig1 is a side sectional view depicting the structure of a thermal transfer printing apparatus ( to be referred to as a printing apparatus hereinafter ) as a typical embodiment of the present invention . the overall structure of the printing apparatus will be explained first . printing sheets p stacked in a paper cassette 2 are picked up and fed one by one to an apparatus main body 1 by a pickup roller 3 . a printing sheet p is clamped and conveyed by a pair of conveyance rollers 4 , so that the printing sheet p can be reciprocally moved relative to a printing unit . in the printing unit , a platen roller 5 and thermal head 6 that generates heat in accordance with information to be printed oppose each other to sandwich a printing sheet conveyance path therebetween . the thermal head 6 presses an ink sheet 8 , which is stored in an ink cassette 7 and has an ink layer applied with hot - melt or thermal sublimation ink , and an overcoat layer used to form an overcoat on the printing surface to protect the printing surface , against the printing sheet p , and selectively heats the ink sheet 8 , thus transferring a predetermined image onto the printing sheet p , and forming a protection layer that overcoats the printing sheet p . the ink sheet 8 is prepared by juxtaposing yellow ( y ), magenta ( m ), and cyan ( c ) ink layers and an overcoat ( op ) layer each having a size approximately equal to that of the printing region of the printing sheet p to cover the printing region . every time color ink for each layer is thermally transferred , the printing sheet p is returned to a print start position ( p 1 ), thus transferring the respective color inks on the printing sheet to overlap each other . in this way , the printing sheet p is reciprocally moved in correspondence with the total number of color ink and overcoat layers , and is finally guided to a pair of exhaust rollers 9 and is exhausted outside the apparatus housing , thus ending the printing operation . since the normal thermal transfer printing apparatus frame - sequentially prints three colors y , m , and c , control for accurately matching the printing leading ends of the respective colors is required . for this reason , the pair of conveyance rollers 4 must securely clamp and convey the printing sheet p without releasing it . as a result , unprintable margin portions must be required on the edge portions of the printing sheet p . in order to finally obtain a print without any extra - margins , as shown in fig2 the printing sheet p has perforations 22 formed by dotted - line pattern holes as cut - off portions that allow the user to easily manually cut off margin portions where no image can be printed since they are securely clamped by the pair of conveyance rollers 4 at the beginning of the print process . in this embodiment , an image is printed using such printing sheet p with perforations and the thermal transfer printing apparatus , and no overcoat agent is applied to the regions of the cut - off portions formed on the printing sheet p upon printing . the pair of conveyance rollers 4 include a pinch roller 42 and grip roller 41 , and the rotating shaft of a stepping motor ( not shown ) is directly coupled to the grip roller 41 via a reduction gear mechanism to freely drive the grip roller 41 in the forward / reverse direction under the rotation control of the stepping motor . since the printing sheet p is securely clamped and reciprocally conveyed by the pair of conveyance rollers 4 , it is conveyed while undergoing accurate position control by means of the rotation control of the stepping motor . if the printing pitch per line by the thermal head 6 is 85 μm , and the number of steps of the stepping motor required for conveying the printing sheet p by one line is 4 , the printing sheet p can be conveyed by one line ( i . e ., 85 μm ) by controlling rotation of the stepping motor to be four steps . furthermore , the printing apparatus 1 has a printing sheet leading end sensor 10 at a position immediately before the pair of conveyance rollers 4 when they are viewed from the pickup roller 3 . with this sensor , when a printing sheet p is fed from the paper cassette 2 or is conveyed toward the exhaust rollers 9 , the leading end ( or trailing end ) of the printing sheet p is detected , and after detection the printing sheet p is fed by the predetermined number of lines and is stopped within the range that the pair of conveyance rollers 4 can clamp it . in this embodiment , convey of the printing sheet is stopped after the stepping motor has rotated for 10 lines , i . e ., for 40 steps . this position corresponds to the aforementioned print start position ( p 1 ). such operation for stopping conveyance of the printing sheet at the print start position ( p 1 ) is made a total of four times upon transferring the y , m , and c color inks and overcoat layer . note that the distance between the printing sheet leading end sensor 10 and the position where the printing sheet p is pressed by the platen roller 5 and thermal head 6 is set at 10 mm in this embodiment in consideration of the parts layout in the apparatus . when the printing sheet p stops at the print start position ( p 1 ), it is conveyed toward the exhaust rollers 9 , the printing sheet leading end sensor 10 detects the leading end of the printing sheet again , the printing sheet is fed by the predetermined number of lines , and the thermal head is driven to generate heat in correspondence with information to be printed , thus printing predetermined images of the respective color inks and transferring the overcoat layer . on the other hand , a device such as a digital still camera , digital video camera , or the like is directly connected to the printing apparatus of this embodiment via a predetermined connection cable , and data of images captured by such device are input to the apparatus via an interface ( i / f ) 11 , and the apparatus can print an image on a printing sheet on the basis of such image data . for this purpose , the printing apparatus comprises a controller 12 that incorporates an mpu 13 for executing printing control . when the mpu 13 reads out and executes codes stored in the internal rom of the controller 12 , a predetermined image process and image print process are implemented . fig3 shows the image printing position and overcoat position together with the dimensions of a printing sheet . in fig3 hatched regions undergo only an image print process , and also correspond to perforation regions . on the other hand , cross - hatched regions undergo both an image print process and overcoating . since the image printing range shown in fig3 is around 144 mm wide in the conveyance direction , 1 , 694 lines can be printed , and the stepping motor can be rotated for 6 , 776 steps to convey the printing sheet by those lines . the printing method using the printing apparatus with the aforementioned arrangement will be explained in detail below . a conventional method will be explained first for the purpose of comparison . fig4 is a flow chart showing the conventional printing method . a printing sheet p is fed from the paper cassette 2 in step s 10 , and an initial value ( n = 1 ) is set in a control parameter variable ( n ) in step s 15 . the value of the control parameter variable ( n ) is checked in step s 20 . if n = 5 , it is determined that ink transfer and overcoat layer transfer are complete , and the flow jumps to step s 35 to exhaust the printing sheet p , then ending the processing . on the other hand , if n ≠ 5 , the flow advances to step s 25 . in step s 25 , the y , m , and c inks and overcoat agent are frame - sequentially transferred . upon completion of transfer of one of the y , m , and c inks and overcoat agent , the flow advances to step s 30 to increment the value of the control parameter variable ( n ) by “+ 1 ”. after that , the flow returns to step s 20 . as described above , according to the conventional method , the transfer print processes of the respective color inks and the overcoat layer transfer process are executed in the same processing sequence . by contrast , in the printing method according to this embodiment , as shown in the flow chart in fig5 color ink transfer processes and an overcoat agent transfer process are executed in different processing steps . note that the same step numbers in the flow chart in fig5 denote the same processes as those in the flow chart in fig4 and a detailed description thereof will be omitted . after the processes in steps s 10 and s 15 , the value of the control parameter variable ( n ) is checked in step s 20 a . if n = 4 , the flow jumps to step s 30 a ; if n ≠ 4 , the flow advances to step s 25 a . in step s 25 a , the respective color inks are transferred onto the printing sheet , and details of the process are as follows : ( 1 ) after the leading end of the printing sheet p is detected , the stepping motor 116 is rotated for 116 steps to start a print process . the print start position at that time is 12 . 465 mm from the leading end ( e ) of the printing sheet . ( 2 ) while rotating the stepping motor for four steps , the thermal head is driven to generate heat , thus printing an image for one line . this print process comes to an end after the stepping motor has rotated for a total of 6 , 776 steps ( 1 , 694 lines ). the print end position at that time is 156 . 455 mm from the leading end ( e ) of the printing sheet . ( 3 ) the stepping motor is rotated for about 10 lines ( 40 steps ) for the purpose of deceleration until conveyance of the printing sheet is stopped , thus stopping conveyance of the printing sheet . ( 4 ) the stepping motor is driven in the reverse direction from that state to convey the printing sheet p in a direction opposite to that upon printing . after the printing sheet leading end sensor 10 detects the leading end of the printing sheet again , the stepping motor is rotated for about 10 lines ( 40 steps ) for the purpose of deceleration . after that , conveyance of the printing sheet is stopped . ( 5 ) in order to print an image using another color ink , the stepping motor rotates again to convey the printing sheet p . in step s 30 , the control parameter variable ( n ) is incremented by “+ 1 ”, and the flow returns to step s 20 a . after such process is repeated three times , the print processes for three colors y , m , and c are complete , and a desired image is transferred and printed on the printing sheet p 1 . at this time , since the control parameter variable ( n ) becomes n = 4 , the flow advances to step s 30 a . in step s 30 a , the overcoat layer is transferred to protect the surface of the printed image . details of the overcoat layer transfer process will be explained below . ( 1 ) after the leading end of the printing sheet p is detected , the stepping motor 116 is rotated for 116 steps to start transfer of the overcoat agent . at this time , the coating start position is 12 . 465 mm from the leading end ( e ) of the printing sheet as that upon printing . ( 2 ) while rotating the stepping motor for four steps , the thermal head is driven to generate heat , thus transferring an overcoat agent for one line . the stepping motor is rotated for a total of 48 steps ( 12 lines ), thus ending transfer of the overcoat agent . the head position at that time is 13 . 485 mm from the leading end ( e ) of the printing sheet . ( 3 ) the stepping motor is rotated for 48 steps ( 12 lines ) without driving the thermal head . the head position at that time is 14 . 505 mm from the leading end ( e ) of the printing sheet . ( 4 ) the thermal head is driven again to generate heat to transfer an overcoat agent for one line while rotating the stepping motor for four steps , and this process proceeds over a total of 6 , 588 steps ( 1 , 647 lines ) until transfer of the overcoat agent is complete . the head position upon completion of transfer is 154 . 5 mm from the leading end ( e ) of the printing sheet . ( 5 ) the stepping motor is rotated for 48 steps ( 12 lines ) without driving the thermal head , thus conveying the printing sheet . the head position at that time is 155 . 52 mm away from the leading end ( e ) of the printing sheet . ( 6 ) the thermal head is driven again to generate heat , and the overcoat agent is transferred for one line while rotating the stepping motor for four steps . the stepping motor is rotated for a total of 48 steps ( 12 lines ), thus ending transfer of the overcoat agent . the head position at that time is 156 . 54 mm from the leading end ( e ) of the printing sheet . ( 7 ) the stepping motor is rotated for about 10 lines ( 40 steps ) for the purpose of deceleration until conveyance of the printing sheet is stopped , thus stopping conveyance of the printing sheet . in this manner , the transfer print process of the respective color inks and overcoat agent are complete . finally , the flow advances to step s 35 , and the printing sheet p is guided to the pair of exhaust rollers 9 and is discharged outside the housing , thus ending the print process . therefore , according to the aforementioned embodiment , since the overcoat agent is transferred so as not to form any overcoat layer on portions of the printing sheet where perforations as cut - off portions are present , even when the margin portions of the printing sheets are cut off along the perforations after the print process , the overcoat layer can be prevented from peeling , and a high - quality printed image can be stably preserved for a long period of time . since the overcoat layer never peels , neither fine dust nor powder dust are produced due to peeling of the overcoat layer , thus preventing environmental pollution and any causes of failures of the printing apparatus . in the above description , regions where no overcoat layer is formed have been explained as predetermined regions including the perforations as cut - off portions . for the purpose of protecting an image , the predetermined regions are preferably as small as possible , and can be set within the range in which the overcoat layer can be prevented from peeling . as described above , the present invention is characterized in that when an image is formed on a printing medium having cut - off portions that allow the user to easily cut off margin portions , a region on the printing medium where ink is applied during a print process , and a region on the printing medium where a protection agent is applied during a process for forming a protection layer by applying the protection agent are appropriately set to be different from each other , and no protection agent is applied to the cut - off portions on the printing medium . hence , upon cutting off margin portions from the printing medium along the cut - off portions , the protection agent is prevented from peeling , so that no dust or powder dust can be scattered . in the above embodiment , as shown in fig3 the overcoat agent is transferred onto the nearly entire image printing region except for perforation regions for the purpose of protection of a print . in general , portions cut off along the perforations are removed and discarded . hence , no overcoat layer need be formed on such portions which are to be discarded . this embodiment is made in consideration of such situation , and a print shown in fig6 is obtained . that is , an overcoat agent is transferred onto only a region bounded by perforations formed at the two sides of the printing sheet in the conveyance direction , thus obtaining an overcoated print . in fig6 hatched regions undergo only an image print process , and a cross - hatched region undergoes both the image print process and overcoat agent transfer process . operations for obtaining such print will be explained in detail below . a printing sheet and thermal transfer printing apparatus used in this embodiment are common to those in the aforementioned embodiment . a characteristic feature of this embodiment lies in the overcoat agent transfer process in step s 30 a shown in fig5 . this process is performed as follows . ( 1 ) the overcoat agent begins to be transferred by rotating the stepping motor 212 steps after detection of the leading end ( e ) of the printing sheet . the transfer start position at that time is 14 . 505 mm from the leading end ( e ) of the printing sheet . ( 2 ) while rotating the stepping motor for four steps , the thermal head is driven to generate heat , thus transferring an overcoat agent for one line . this process proceeds over 6 , 588 steps ( 1 , 647 lines ) of the stepping motor until transfer of the overcoat agent comes to an end . the head position at that time is 154 . 5 mm from the leading end ( e ) of the printing sheet . ( 3 ) the stepping motor is rotated for about 10 lines ( 40 steps ) for the purpose of deceleration until conveyance of the printing sheet is stopped , thus stopping conveyance of the printing sheet . according to the aforementioned embodiment , since the overcoat layer is formed on only a region slightly inside the perforations , the overcoat agent can be prevented from being wasted . in the aforementioned embodiments , the overcoat agent is transferred by only turning on / off the heat generation driving of the thermal head . in order to transfer the overcoat layer more stably , the heat amount may be controlled to gradually increase at the beginning of transfer of the overcoat agent , and to gradually decrease at the end of transfer of the overcoat agent , as shown in fig7 . in the above embodiments , heat generation driving of the thermal head is stopped to stop transfer of the overcoat agent . however , the present invention is not limited to such specific arrangement . for example , the thermal head clamps and presses the ink sheet and printing sheet in the transfer print process , and transfer of the overcoat layer may be stopped by releasing the pressing operation . in the aforementioned embodiments , in the transfer print process of the y , m , and c color inks and overcoat agent , the print position management is made by detecting the leading end of the printing sheet by the printing sheet leading end sensor and managing the number of steps of rotation driving of the stepping motor with reference to the leading end detection signal . however , the present invention is not limited to such specific arrangement . for example , the print position management may be made by managing the number of steps of rotation driving of the stepping motor throughout the print operation on the basis of the number of steps of the stepping motor and the positional relationship upon conveying the printing sheet p using the leading end detection signal of the printing sheet initially detected by the printing sheet leading end sensor when feeding the printing sheet p . note that the present invention is characterized in that no overcoat layer is formed on perforation regions formed on the printing sheet so as to easily obtain a print without any extra - margins . since the transfer print process at a desired position on the printing sheet is determined by the specifications of the thermal head and the arrangement of the conveyance means as described in the above embodiments , and can be achieved by managing them using predetermined means , modifications of the present invention can be applied to printing sheets with various sizes and perforation positions . furthermore , in the aforementioned embodiments , the thermal transfer printing apparatus has been exemplified . however , the present invention is not limited to such a specific apparatus , and a printing apparatus using other printing methods such as an ink - jet printing apparatus may be used as long as they print using printing media such as printing sheets with perforations . note that the present invention may be applied to either a system constituted by a plurality of devices ( e . g ., a host computer , an interface device , a reader , a printer , and the like ), or an apparatus consisting of a single piece of equipment ( e . g ., a copying machine , a facsimile apparatus , or the like ). the objects of the present invention are also achieved by supplying a storage medium ( or recording medium ), which stores a program code of a software program that can implement the functions of the above - mentioned embodiments to the system or apparatus , and reading out and executing the program code stored in the storage medium by a computer ( or a cpu or mpu ) of the system or apparatus . in this case , the program code itself read out from the storage medium implements the functions of the above - mentioned embodiments , and the storage medium which stores the program code constitutes the present invention . the functions of the above - mentioned embodiments may be implemented not only by executing the readout program code by the computer but also by some or all of actual processing operations executed by an os ( operating system ) running on the computer on the basis of an instruction of the program code . furthermore , the functions of the above - mentioned embodiments may be implemented by some or all of actual processing operations executed by a cpu or the like arranged in a function extension card or a function extension unit , which is inserted in or connected to the computer , after the program code read out from the storage medium is written in a memory of the extension card or unit . in the above embodiments , the perforations formed by dot - line pattern holes have been exemplified as cut - off portions that allow the user to easily cut off margin portions from a printing medium . however , the present invention is not limited to the printing medium with perforations , but can be applied to a printing medium in which the thickness of a portion to be cut off is set to be smaller than the remaining portion , and a printing medium in which cut - off portions are formed of a material that allows easy cutting . as many apparently widely different embodiments of the present invention can be made without departing from the spirit and scope thereof , it is to be understood that the invention is not limited to the specific embodiments thereof except as defined in the appended claims .
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the present invention now will be described more fully with reference to the accompanying drawings , in which preferred embodiments of the invention are shown . this invention may , however , be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein ; rather , these embodiments are provided so that this disclosure will be thorough and complete , and will fully convey the scope of the invention to those skilled in the art . like reference numerals refer to like elements throughout . it will be understood that when an element or layer is referred to as being “ on ,” “ connected to ” or “ coupled to ” another element or layer ( and variants thereof ), it can be directly on , connected or coupled to the other element or layer or intervening elements or layers may be present . in contrast , when an element is referred to as being “ directly on ,” “ directly connected to ” or “ directly coupled to ” another element or layer ( and variants thereof ), there are no intervening elements or layers present . like reference numerals refer to like elements throughout . it will be understood that , although the terms first , second , third , etc . may be used herein to describe various elements , components , regions , layers and / or sections , these elements , components , regions , layers and / or sections should not be limited by these terms . these terms are only used to distinguish one element , component , region , layer or section from another region , layer or section . thus , a first element , component , region , layer or section discussed below could be termed a second element , component , region , layer or section without departing from the teachings of the present invention . spatially relative terms , such as “ beneath ,” “ below ,” “ lower ,” “ above ,” “ upper ” and the like , may be used herein for ease of description to describe one element or feature &# 39 ; s relationship to another element ( s ) or feature ( s ) as illustrated in the figures . it will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures . for example , if the device in the figures is turned over , elements described as “ below ” or “ beneath ” other elements or features would then be oriented “ above ” the other elements or features . thus , the term “ below ” can encompass both an orientation of above and below . the device may be otherwise oriented ( rotated 90 degrees or at other orientations ) and the spatially relative descriptors used herein interpreted accordingly . the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the present invention . as used herein , the singular forms “ a ,” “ an ” and “ the ” are intended to include the plural forms as well , unless the context clearly indicates otherwise . it will be further understood that the terms “ comprising ”, “ including ”, “ having ” and variants thereof , when used in this specification , specify the presence of stated features , steps , operations , elements , and / or components , but do not preclude the presence or addition of one or more other features , steps , operations , elements , components , and / or groups thereof . in contrast , the term “ consisting of ” when used in this specification , specifies the stated features , steps , operations , elements , and / or components , and precludes additional features , steps , operations , elements and / or components . embodiments of the present invention are described herein with reference to cross - section and perspective illustrations that are schematic illustrations of idealized embodiments ( and intermediate structures ) of the present invention . as such , variations from the shapes of the illustrations as a result , for example , of manufacturing techniques and / or tolerances , are to be expected . thus , embodiments of the present invention should not be construed as limited to the particular shapes of regions illustrated herein but are to include deviations in shapes that result , for example , from manufacturing . for example , a sharp angle may be somewhat rounded due to manufacturing techniques / tolerances . unless otherwise defined , all terms ( including technical and scientific terms ) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs . it will be further understood that terms , such as those defined in commonly used dictionaries , should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein . fig1 a is a plan view illustrating a 3d semiconductor memory device according to an embodiment of the inventive concept . fig1 b is a cross - sectional view taken along line i - i ′ of fig1 a . fig1 c is a magnified view of a portion a of fig1 b . referring to fig1 a and 1b , a well region 102 doped with a first conductive dopant may be disposed in a semiconductor substrate 100 ( hereinafter referred to as a substrate ). the substrate 100 may be a silicon substrate , a germanium substrate or a silicon - germanium substrate , for example a common source region 105 doped with a second conductive dopant may be formed in the well region 102 . an upper surface of the common source region 105 may be disposed on the substantially same level as that of the upper surface of the substrate 100 . a lower surface of the common source region 105 may be disposed on a level higher than that of a lower surface of the well region 102 . one of the first and second conductive dopants may be an n - type dopant , and the other may be a p - type dopant . for example , the well region 102 may be doped with a p - type dopant , and the common source region 105 may be doped with an n - type dopant . a stack - structure , including insulation patterns 110 a and gate patterns 155 l , 155 a 1 , 155 a and 155 u that are stacked alternately and repeatedly , may be disposed on the common source region 105 . a plurality of the stack - structures may be disposed on the common source region 105 . as illustrated in fig1 a , the stack - structures may be extended side by side in a first direction . the stack - structures may be spaced apart in a second direction perpendicular to the first direction . the first and second directions may be parallel with the upper surface of the substrate 100 . a vertical active pattern 130 may pass through the stack - structure . the vertical active pattern 130 may be extended into a recess region 120 that is formed in the common source region 105 under the vertical active pattern 130 . therefore , the vertical active pattern 130 may be connected to the well region 102 under the vertical active pattern 130 . as illustrated in fig1 b , the recess region 120 may vertically pass through the common source region 105 . a bottom surface of the recess region 120 may be disposed on a level lower than that of the lower surface of the common source region 105 . the vertical active pattern 130 may contact the bottom surface of the recess region 120 . accordingly , the vertical active pattern 130 may contact the well region 102 . also , the vertical active pattern 130 may contact a sidewall of the recess region 120 . as a result , the vertical active pattern 130 may directly contact the common source region 105 . according to an embodiment of the inventive concept , a portion 122 of the well region 102 just under the bottom surface of the recess region 120 may have a high dopant concentration . in other words , the first conductive dopant concentration of the portion 122 of the well region 102 may be higher than the first conductive dopant concentration of another portion of the well region 102 . according to an embodiment of the inventive concept , the vertical active pattern 130 may have a hollow pipe shape or a macaroni shape . herein , the lower end of the vertical active pattern 130 may be in a closed state . the inside of the vertical active pattern 130 may be filled with a filling dielectric pattern 132 . a gate dielectric layer 150 may be disposed between a sidewall of the vertical active pattern 130 and each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . according to an embodiment of the inventive concept , as illustrated in fig1 b , the gate dielectric layer 150 may be extended to cover an upper surface and a lower surface of each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . that is , the extended portion of the gate dielectric layer 150 may be disposed between each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u and the insulation pattern 110 a adjacent to each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . the gate dielectric layer 150 will be described below in more detail with reference to fig1 c . referring to fig1 c , according to an embodiment of the inventive concept , the gate dielectric layer 150 may include a tunnel dielectric layer 141 , a charge storage layer 142 and a blocking dielectric layer 143 . the tunnel dielectric layer 141 may be adjacent to the sidewall of the vertical active pattern 130 , and the blocking dielectric layer 143 may be adjacent to each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . the charge storage layer 142 may be disposed between the tunnel dielectric layer 141 and the blocking dielectric layer 143 . according to an embodiment of the inventive concept , as illustrated in fig1 c , the entirety of the gate dielectric layer 150 ( i . e ., the tunnel dielectric layer 141 , the charge storage layer 142 and the blocking dielectric layer 143 ) may be extended to cover the upper and lower surfaces of each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . the tunnel dielectric layer 141 may include oxide and / or oxynitride . the tunnel dielectric layer 141 may be single - layered or multi - layered . the charge storage layer 142 may include a dielectric material having traps for storing electric charges , for example , the charge storage layer 142 may include nitride and / or metal - oxide . the blocking dielectric layer 143 may include a high - k dielectric layer having a dielectric constant higher than that of the tunnel dielectric layer 141 . for example , the high - k dielectric layer in the blocking dielectric layer 143 may include metal - oxide such as aluminum - oxide or hafnium - oxide . furthermore , the blocking dielectric layer 143 may further include a barrier dielectric layer . the barrier dielectric layer in the blocking dielectric layer 143 may include a dielectric material having a greater band gap than the high - k dielectric layer in the blocking dielectric layer 143 . for example , the barrier dielectric layer may include oxide . the barrier dielectric layer may be disposed between the high - k dielectric layer and the charge storage layer 142 . a lowermost gate pattern 155 l in the stack - structure may correspond to a ground selection gate . a ground selection transistor including the lowermost gate pattern 155 l may include a vertical channel region that is defined in the sidewall of the vertical active pattern 130 . as illustrated in fig1 a and 1b , the entire lower surface of the lowermost gate pattern 155 l may substantially overlap with the common source region 105 . an uppermost gate pattern 155 u in the stack - structure may correspond to a string selection gate . gate patterns 155 a 1 and 155 a between the uppermost gate pattern 155 u and the lowermost gate pattern 155 l may correspond to cell gates . a string selection transistor including the uppermost gate pattern 155 u and cell transistors including the cell gates may also include vertical channel regions that are defined in the sidewall of the vertical active pattern 130 a . the vertical channel regions of the ground selection transistor , the cell transistor and the string selection transistor configuring one cell string may be defined in the vertical active pattern 130 . according to an embodiment of the inventive concept , among gate patterns used as the cell gates in the stack - structure , a gate pattern most adjacent to the lowermost gate pattern 155 l may correspond to a dummy cell gate . for example , the gate pattern 1551 a disposed just on the lowermost gate pattern 155 l may be a dummy gate pattern . for example , the gate pattern 155 a 1 that is stacked secondly from the substrate 100 may be a dummy cell gate . naturally , one of the insulation pattern 110 a is disposed between the lowermost gate pattern 155 l and the secondly - stacked gate pattern 155 a 1 . for example , a dummy cell transistor including the secondly - stacked gate pattern 155 a 1 may have the same shape as that of a cell transistor storing data , but may not serve as the cell transistor . for example , the dummy cell transistor may perform only a turn - on / off function . thus , the secondly - stacked gate pattern 155 a 1 may be a second ground selection gate . in this case , the cell string may include a plurality of stacked ground selection transistors . a plurality of the vertical active patterns 130 may pass through each of the stack - structures . as illustrated in fig1 a , the vertical active patterns 130 passing though each of the stack - structures may be arranged in the first direction to form one column . alternatively , the vertical active patterns 130 passing though each of the stack - structures may be arranged in a zigzag shape in the first direction . the vertical active pattern 130 may include a semiconductor material . for example , the vertical active pattern 130 may include the same semiconductor material as that of the substrate 100 . the vertical active pattern 130 may have an undoped state , or may be doped with the first conductive dopant . the vertical active pattern 130 may have a poly - crystalline state or a single crystalline state . the gate patterns 155 l , 155 a 1 , 155 a and 155 u include a conductive material . for example , the gate patterns 155 l , 155 a 1 , 155 a and 155 u may include at least one of a doped semiconductor ( for example , doped silicon and others ), a metal ( for example , tungsten , aluminum , copper and others ), a transition metal ( for example , titanium , tantalum and others ) or a conductive metal nitride ( for example , a titanium nitride , a tantalum nitride and others ). the insulation patterns 110 a may include oxide . a device isolation pattern 160 a may be disposed between the stack - structures . an upper surface of the device isolation pattern 160 a and an upper surface of the stack - structure may substantially be coplanar . an interlayer dielectric 165 may be disposed on the substrate 100 . a contact plug 167 may be connected to an upper end of the vertical active pattern 130 through the interlayer dielectric 165 . a drain being doped with the second conductive dopant may be formed in the upper portion of the vertical active pattern 130 . a lower surface of the drain may be disposed on a level adjacent to an upper surface of the uppermost gate pattern 155 u . a bit line 170 may be disposed on the interlayer dielectric 165 , and may be connected to the contact plug 167 . the bit line 170 may be extended in the second direction and cross over the stack - structure . the interlayer dielectric 165 may include oxide . the contact plug 167 includes a conductive material . for example , the contact plug 167 may include tungsten . the bit line 170 also includes a conductive material . as an example , the bit line 170 may include tungsten , copper , aluminum or the like . according to the above - described 3d semiconductor memory device , the vertical active pattern 130 may be disposed in the recess region 120 passing though the common source region 105 and be connected to the well region 102 . moreover , the common source region 105 may be disposed under the lowermost gate pattern 155 l . therefore , a distance between the vertical active pattern 130 and the common source region can be minimized , and also the vertical active pattern 130 can be connected to the well region 102 . consequently , a current flowing through the vertical active pattern 130 can quickly flow to the common source region 105 . accordingly , the reduction of an amount of current in a cell transistor can be minimized . also , the vertical active pattern 130 is connected to the well region 102 , such that the erasing operation of cell transistors is very easy . as a result , the 3d semiconductor memory device can be implemented which has excellent reliability and is optimized for high integration . next , the modification examples of the 3d semiconductor memory device according to an embodiment of the inventive concept will be described below with reference to the accompanying drawings . in the modification examples , a description on the same elements as the above - described elements will be omitted for avoiding a repetitive description . fig2 a is a cross - sectional view taken along line i - i ′ of fig1 a for describing a modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig2 a and according to the modification example , protection dielectric patterns 173 a may be disposed between the insulation patterns 110 a and the vertical active pattern 130 and between the inner sidewall of the recess region 120 and the vertical active pattern 130 . the protection dielectric pattern 173 a may include a dielectric material for protecting the vertical active pattern 130 in a fabricating process . for example , the protection dielectric pattern 173 a may include oxide . according to the modification example , a capping semiconductor pattern 175 may be disposed on the vertical active pattern 130 . the capping semiconductor pattern 175 may also be disposed on the protection dielectric pattern 173 a that is disposed between an uppermost insulation pattern 110 a and the vertical active pattern 130 . the upper end of the vertical active pattern 130 may be disposed on a level lower than an upper surface of the uppermost insulation pattern 110 a . the upper surface of the capping semiconductor pattern 175 and the upper surface of the uppermost insulation pattern 110 a may be substantially coplanar . the capping semiconductor pattern 175 may include the same semiconductor material as that of the vertical active pattern 130 . the capping semiconductor pattern 175 may be doped with the second conductive dopant . the contact plug 167 may be connected to the capping semiconductor pattern 175 . fig2 b is a cross - sectional view taken along line i - i ′ of fig1 a for describing other modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig2 b and according to the modification example , a bottom surface of the recess region 120 may be disposed on a level higher than the lower surface of the common source region 105 . in this case , a region 122 a being counter - doped with the first conductive dopant may be disposed under the bottom surface of the recess region 120 a . the counter - doped region 122 a may contact the vertical active pattern 130 and the well region 102 . therefore , the vertical active pattern 130 may be connected to the well region 102 through the counter - doped region 122 a . fig3 a is a cross - sectional view taken along line i - i ′ of fig1 a for describing still other modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . fig3 b is a magnified view of a portion b of fig3 a . referring to fig3 a , a gate dielectric layer 150 a according to the modification example may be disposed between a vertical active pattern 130 a and each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . the gate dielectric layer 150 a may include a first sub - layer 147 and a second sub - layer 149 . the first sub - layer 147 may be substantially extended vertically and be disposed between the vertical active pattern 130 a and the insulation pattern 110 a . the second sub - layer 149 may be substantially extended horizontally and cover the lower surface and upper surface of each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . the gate dielectric layer 150 a may include the tunnel dielectric layer , the charge storage layer and the blocking dielectric layer . herein , the first sub - layer 147 may include at least a portion of the tunnel dielectric layer , and the second sub - layer 149 may include at least a portion of the blocking dielectric layer . one of the first and second sub - layers 147 and 149 may include the charge storage layer . in other words , a portion of the gate dielectric layer 150 a including the tunnel dielectric layer , the charge storage layer and the blocking dielectric layer may be extended vertically , and another portion of the gate dielectric layer 150 a may be extended horizontally . the vertical active pattern 130 a may include first and second semiconductor patterns 123 and 124 . the first semiconductor pattern 123 may be disposed between the second semiconductor pattern 124 and the first sub - layer 147 . the first semiconductor pattern 123 may contact the first sub - layer 147 . according to an embodiment of the inventive concept , the first semiconductor pattern 123 may have a macaroni shape or a pipe shape where an upper end and a lower end are opened . the first semiconductor pattern 123 may not contact the inner surface of the recess region 120 by the first sub - layer 147 . the second semiconductor pattern 124 may contact the first semiconductor pattern 123 and the inner surface of the recess region 120 . the second semiconductor pattern 124 may have a macaroni shape or a pipe shape where a lower end is closed . a filling dielectric pattern 132 may fill the inside of the second semiconductor pattern 124 . the first and second semiconductor patterns 123 and 124 may have an undoped state or be doped with a dopant ( i . e ., the first conductive dopant ) having the same type as that of the well region 102 . according to an embodiment of the inventive concept , as illustrated in fig3 b , the first sub - layer 147 of the gate dielectric layer 150 a may include a tunnel dielectric layer 141 , a charge storage layer 142 and a barrier dielectric layer 144 . in this case , the second sub - layer 149 may include a high - k dielectric material ( for example , metal - oxide such as aluminum oxide or hafnium oxide ) having a dielectric constant higher than that of the tunnel dielectric layer 141 . the barrier dielectric layer 144 may include a dielectric material having a greater band gap than that of the high - k dielectric material . for example , the barrier dielectric layer 144 may include oxide . the second sub - layer 149 and the barrier dielectric layer 144 , disposed between the charge storage layer 142 and each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u , may included in the blocking dielectric layer . in other words , the first sub - layer 147 may include the tunnel dielectric layer 141 , the charge storage layer 142 and a portion ( i . e ., the barrier dielectric layer 144 ) of the blocking dielectric layer , and the second sub - layer 149 may include another portion ( i . e ., the high - k dielectric layer ) of the blocking dielectric layer . however , an embodiment of the inventive concept is not limited thereto . the first and second sub - layers of the gate dielectric layer may be combined differently . fig3 c is a magnified view of a portion b of fig3 a for describing even other modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig3 c , a first sub - layer 147 a of a gate dielectric layer 150 b according to the modification example may include a tunnel dielectric layer 141 and a charge storage layer 142 , and a second sub - layer 149 a of the gate dielectric layer 150 b may include a barrier dielectric layer 144 and a high - k dielectric layer 146 . the high - k dielectric layer 146 may be formed of the same material as the high - k dielectric material that has been described above with reference to fig3 b . according to the modification example , the second sub - layer 149 b may correspond to a blocking dielectric layer . according to the modification example , the first sub - layer 147 a may include the tunnel dielectric layer 141 and the charge storage layer 142 , and the second sub - layer 149 a may include the blocking dielectric layer . fig3 d is a magnified view of a portion b of fig3 a for describing yet other modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig3 d , a first sub - layer 147 b of a gate dielectric layer 150 c according to the modification example may include the tunnel dielectric layer , and a second sub - layer 149 b of the gate dielectric layer 150 c may include the charge storage layer 142 and the blocking dielectric layer 143 . according to the modification example , the tunnel dielectric layer in the gate dielectric layer 150 c may be extended vertically and be disposed between the vertical active pattern 130 a and the insulation pattern 110 a , and the charge storage layer 142 and the blocking dielectric layer 143 in the gate dielectric layer 150 c may be extended horizontally and cover the upper surface and lower surface of each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . the first and second sub - layers according to an embodiment of the inventive concept are not limited to the modification examples that have been described above with reference to fig3 b , 3 c and 3 d . the first and second sub - layers may be combined differently . fig4 a is a cross - sectional view taken along line i - i ′ of fig1 a for describing further modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . fig4 b is a magnified view of a portion c of fig4 a . referring to fig4 a and 4b , the entirety of a gate dielectric layer 150 d between the vertical active pattern 130 a and each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u may be substantially extended vertically . that is , the tunnel dielectric layer 141 , charge storage layer 142 and blocking dielectric layer 143 of the gate dielectric layer 150 d may be substantially extended vertically . an extended portion of the gate dielectric layer 150 d may be disposed between the vertical active pattern 130 a and the insulation pattern 110 a . the stack - structure of fig1 a and 1b may have a line shape that is extended in the first direction . unlike this , the stack - structure may include gate patterns having a flat plate shape . this will be described below with reference to the accompanying drawings . fig5 a is a plan view illustrating still further modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . fig5 b is a cross - sectional view taken along line ii - ii ′ of fig5 a . referring to fig5 a and 5b , a stack - structure according to the modification example may include gate patterns 220 l , 220 a , 220 and 220 u and insulation patterns 210 and 210 u that are stacked alternately and repeatedly . a lowermost gate pattern 220 l in the stack - structure may be a ground selection gate , and an uppermost gate pattern 220 u in the stack - structure may be a string selection gate . the gate pattern 220 a just on the lowermost gate pattern 220 l may be used as a cell gate , a dummy cell gate or a second ground selection gate . the gate patterns 220 between the gate pattern 220 a just on the lowermost gate pattern 220 l and the upper gate pattern 220 u may be used as cell gates . the gate patterns 220 l , 220 a and 220 under a string selection gate , as illustrated in fig5 a and 5b , may have a flat plate shape . the uppermost gate pattern 220 u corresponding to the string selection gate may have a line shape that is extended in the first direction . the uppermost gate pattern 220 u may be provided in plurality , and the uppermost gate patterns 220 u may be extended side by side in the first direction . the bit line 170 may be extended in the second direction and cross over the uppermost gate pattern 220 u . like the uppermost gate pattern 220 u , an uppermost insulation pattern 210 u on the uppermost gate pattern 220 u may also be extended in the first direction . the vertical active pattern 130 a may pass through the stack - structure and be extended into the recess region 120 under it . the lowermost gate pattern 220 l corresponding to the ground selection gate may be disposed on the common source region 105 in the substrate 100 . the entire lower surface of the lowermost gate pattern 220 l may substantially overlap with the common source region 105 . according to the modification example , the gate dielectric layer 150 d may be disposed between the vertical active pattern 130 a and the inner sidewall of an opening 115 passing through the stack - structure . the gate dielectric layer 150 d may be substantially extended vertically . the opening 115 and the recess region 120 may be self - aligned . the gate dielectric layer 150 d may be extended into the recess region 120 . according to an embodiment of the inventive concept , the lower end of the gate dielectric layer 150 d in the recess region 120 may be disposed on a level higher than the lower surface of the recess region 120 . a lower interlayer dielectric 163 may be disposed between the uppermost gate patterns 220 u . an upper surface of the lower interlayer dielectric 163 may be coplanar with an upper surface of the uppermost insulation pattern 210 u . an upper interlayer dielectric 165 may be disposed on the lower interlayer dielectric 163 and the uppermost gate patterns 220 u . the insulation patterns 210 and 210 u may include oxide , nitride and / or oxynitride . the gate patterns 220 l , 220 a , 220 and 220 u may include at least one of a doped semiconductor ( for example , doped silicon ), a metal ( for example , tungsten and others ) or a conductive metal nitride ( for example , a titanium nitride , a tantalum nitride and others ). the elements of the above - described modification examples may be combined or replaced . for example , the capping semiconductor pattern 175 of fig2 a may be disposed on the vertical active pattern 130 or 130 a that has been disclosed in fig1 b , 3 a , 4 a or 5 b . fig6 a to 6h are cross - sectional views taken along line i - i ′ of fig1 a for describing a method of fabricating 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig6 a , a well region 102 may be formed by providing a first conductive dopant into the substrate 100 . a common source region 105 may be formed by providing a second conductive dopant into the upper portion of the well region 102 . insulation layers 110 and sacrificial layers 112 may be alternately and repeatedly stacked on the common source region 105 . for example , the insulation layers 110 may be formed as oxide layers . the sacrificial layers 112 may be formed of materials having an etch selectivity with respect to the insulation layers 112 . for example , the sacrificial layers 112 may be formed as nitride layers . referring to fig6 b , an opening 115 and a recess region 120 may be formed by sequentially patterning the insulation layers 110 , sacrificial layers 112 and the substrate 100 . the opening 115 may pass through the insulation layers 110 and sacrificial layers 112 , and the recess region 120 may be formed in the common source region 102 under the opening 115 ( i . e ., in a portion of the substrate 100 ). the recess region 120 is self - aligned in the opening 115 by sequentially patterning the insulation layers 110 and sacrificial layers 112 and the substrate 100 . the recess region 120 may pass through the common source region 105 , and the bottom surface of the recess region 120 may be disposed on a level lower than the lower surface of the common source region 105 . therefore , the well region 102 may be exposed to the bottom surface of the recess region 120 , and the common source region 105 may be exposed to the inner sidewall of the recess region 120 . a high concentration region 122 may be formed by providing the first conductive dopant into the well region 102 through the bottom surface of the recess region 120 . the high concentration region 122 of the first conductive dopant may be higher than another portion of the well region 102 . that is , due to the high concentration region 122 , the well region 102 may partially have a high dopant concentration . referring to fig6 c , a semiconductor layer may be conformally formed on the substrate 100 having the opening 115 and the recess region 120 . therefore , the semiconductor layer may be formed to have a substantially uniform thickness on the inner surface of the recess region 120 and an inner sidewall of the opening 115 . the semiconductor layer may contact the inner surface ( i . e ., an inner sidewall and a bottom surface ) of the recess region 120 . the semiconductor layer may be formed in a chemical vapor deposition process and / or an atomic layer deposition process . a filling dielectric layer may be formed on the semiconductor layer to fill the opening 115 . for example , the filling dielectric layer may be formed as an oxide layer . by planarizing the filling dielectric layer and the semiconductor layer until the uppermost insulation layer 110 is exposed , a vertical active pattern 130 and a filling dielectric pattern 132 may be formed in the opening 115 and the recess region 120 . referring to fig6 d , a trench 135 may be formed by sequentially patterning the insulation layers 110 and sacrificial layers 112 , such that insulation patterns 110 a and the sacrificial patterns 112 a being alternately and repeatedly stacked may be formed at a side of the trench 135 . the insulation patterns 110 a and sacrificial patterns 112 a may include the opening 115 . that is , the vertical active patterns 130 may sequentially pass through the insulation patterns 110 a and the sacrificial patterns 112 a being alternately and repeatedly stacked on the substrate 100 . sidewalls of the sacrificial patterns 112 a and the insulation patterns 110 a are exposed to the trench 135 . referring to fig6 e , empty regions 140 may be formed by removing the sacrificial patterns 112 a exposed to the trench 135 . each of the empty regions 140 corresponds to a region from which the each sacrificial pattern 112 a is removed . the empty regions 140 may expose some portions of the sidewall of the vertical active pattern 130 , respectively . referring to fig6 f , a gate dielectric layer 150 may be conformally formed on the substrate 100 having the empty regions 140 . therefore , the gate dielectric layer 150 may be conformally formed on the inner surfaces of the empty regions 140 . the gate dielectric layer 150 , as described above with reference to fig1 b and 1c , may include the tunnel dielectric layer , the charge storage layer and the blocking dielectric layer . a gate conductive layer 155 filling the empty regions 140 may be formed on the substrate 100 having the gate dielectric layer 150 . the gate conductive layer 155 may also be formed in the trench 135 . herein , the gate conductive layer 155 may partially fill the trench 135 . therefore , a space surrounded by the gate conductive layer 155 may be formed in the trench 135 . a bottom surface of the space may be lower than an inner - upper surface of the lowermost empty region 140 . referring to fig6 g , the gate patterns 155 l , 155 a 1 , 155 a and 155 u respectively filling the empty regions 140 may be formed by etching the gate conductive layer 155 . the gate patterns 155 l , 155 a 1 , 155 a and 155 u are separated by the etching process of the gate conductive layer 155 . according to an embodiment of the inventive concept , the etching process of the gate conductive layer 155 may be an isotropic etching process . the insulation patterns 110 a and the gate patterns 155 l , 155 a 1 , 155 a and 155 u , being alternately and repeatedly stacked on the substrate 100 , may be included in a stack - structure . subsequently , a device isolation insulation layer 160 may be formed to fill the trench 135 . referring to fig6 h , the device isolation insulation layer 160 and the gate dielectric layer 150 may be planarized until the uppermost insulation pattern among the insulation patterns 110 a is exposed . therefore , a device isolation pattern 160 a may be formed in the trench 135 . subsequently , by forming the interlayer dielectric 165 , contact plug 167 and bit line 170 of the fig1 b on the substrate 100 , the 3d semiconductor memory device that has disclosed in fig1 a , 1 b and 1 c may be implemented . according to the above - described 3d semiconductor memory device , the opening 115 and the recess region 120 can be formed in self - alignment by sequentially patterning the insulation layers 110 , the sacrificial layers 112 and the substrate 100 ( i . e . the common source region 105 ). therefore , the 3d semiconductor memory device can be implemented which has excellent reliability and is optimized for high integration . next , a method of fabricating the 3d semiconductor memory device that has been disclosed in fig2 a will be described below with reference to the accompanying drawings . the method may include the methods that have been described above with reference to fig6 a and 6b . fig7 a to 7d are cross - sectional views taken along line i - i ′ of fig1 a for describing a modification example of a method of fabricating 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig6 b and 7a , a protection dielectric layer 173 may be conformally formed on the substrate 100 having the opening 115 and the recess region 120 , and the protection dielectric layer 173 may be etched by a blanket anisotropic etching process until the bottom surface of the recess region 120 is exposed . as illustrated in fig7 a , therefore , the protection dielectric layer 173 may be formed on the sidewalls of the recess region 120 and the opening 115 . the protection dielectric layer 173 may include a dielectric material having an etch selectivity with respect to the sacrificial layer 112 . for example , the protection dielectric layer 173 may be formed of oxide . subsequently , a semiconductor layer may be formed , a filling dielectric layer may be formed on the semiconductor layer , and the filling dielectric layer and the semiconductor layer may be planarized . therefore , the vertical active pattern 130 and the filling dielectric pattern 132 may be formed in the opening 115 and the recess region 120 . the vertical active pattern 130 may contact the bottom surface of the recess region 120 . the protection dielectric layer 173 may be disposed between the vertical active pattern 130 and the inner sidewalls of the opening 115 and the recess region 120 . referring to fig7 b , the upper ends of the vertical active pattern 130 , filling dielectric pattern 132 and protection dielectric layer 175 may be recessed lower than the upper surface of the uppermost insulation layer 110 . subsequently , a capping semiconductor layer filling the opening 110 may be formed on the substrate 100 , and a capping semiconductor pattern 175 may be formed by planarizing the capping semiconductor layer until the uppermost insulation layer 110 is exposed . the capping semiconductor pattern 175 may cover the recessed upper ends of the vertical active pattern 130 , filling dielectric pattern 132 and protection dielectric layer 175 . subsequently , the trench 135 may be formed by sequentially patterning the insulation layers 110 and the sacrificial layers 112 . in this case , as described above , the insulation patterns 110 and the sacrificial patterns 112 a that are alternately and repeatedly stacked may be formed at a side of the trench 135 . referring to fig7 c , the sacrificial patterns 112 a exposed to the trench 135 may be removed . therefore , the empty regions 140 may be formed which respectively exposes some portions of the protection dielectric layer 173 disposed on the sacrificial patterns 112 a and the vertical active patterns 130 . as described above , the protection dielectric layer 173 has an etch selectivity with respect to the sacrificial patterns 112 a , and thus it can protect the vertical active pattern 130 from a process of removing the sacrificial patterns 112 a . the protection dielectric layer 173 may be used as an etch stop layer in the process of removing the sacrificial patterns 112 a . subsequently , the exposed portions of the protection dielectric layer 173 may be removed . therefore , the empty regions 140 may expose some portions of the side wall of the vertical active pattern 130 , respectively . when removing the exposed portions of the protection dielectric layer 173 , the protection dielectric patterns 173 a may be formed between the vertical active pattern 130 and the insulation patterns 110 a and between the vertical active pattern 130 and the inner sidewall of the recess region 120 . the protection dielectric patterns 173 a correspond to remaining portions of protection dielectric layer 173 . referring to fig7 d , the gate dielectric layer 150 may be conformally formed on the substrate 100 having the empty regions 140 , and the gate patterns 155 l , 155 a 1 , 155 a and 155 u respectively filling the empty regions 140 may be formed . afterwards , the device isolation pattern 160 a filling the trench 135 may be formed . subsequently , by forming the interlayer dielectric 165 , contact plug 167 and bit line 170 of fig2 a , the 3d semiconductor memory device of fig2 a can be implemented . the features of a method , that fabricates the 3d semiconductor memory device that has been disclosed in fig2 b , may have a process of forming the lower surface of the recess region 120 higher than the lower surface of the common source region 105 and a process of forming the counter - doped region 122 a by counter - doping the common source region 105 under the bottom surface of the recess region 120 with the first conductive dopant . other processes may be the same as the processes that have been described above with reference to fig7 a to 7d . next , a method of fabricating the 3d semiconductor memory device that has been disclosed in fig3 a will be described below with reference to the accompanying drawings . the method may include the methods that have been described above with reference to fig6 a and 6b . fig8 a to 8f are cross - sectional views taken along line i - i ′ of fig1 a for describing other modification example of a method of fabricating 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig6 b and 8a , a first sub - layer 147 may be conformally formed on the substrate 100 having the opening 115 and the recess region 120 . the first sub - layer 147 may be conformally formed on the inner sidewall of the opening 115 and the inner surface of the recess region 120 . a first semiconductor layer 121 may be conformally formed on the substrate 100 having the first sub - layer 147 . referring to fig8 b , portions of the first sub - layer 147 and the first semiconductor layer 121 disposed on the bottom surface of the recess region 120 may be removed . at this point , portions of the first sub - layer 147 and the first semiconductor layer 121 disposed outside opening 115 may also be removed . therefore , the first sub - layer 147 and the first semiconductor pattern 123 that are sequentially stacked on the sidewalls of the recess region 120 and opening 115 may be formed , the first semiconductor pattern 123 correspond to a portion of the first semiconductor layer 121 . according to an embodiment of the inventive concept , by blanket - anisotropic - etching the first semiconductor layer 121 and the first sub - layer 147 until the bottom surface of the recess region 120 is exposed , the first semiconductor pattern 123 may be formed . the first semiconductor pattern 123 may not contact the inner surface of the recess region 120 by the first sub - layer 147 . referring to fig8 c , subsequently , by isotropic - etching the first sub - layer 147 , at least one portion of the inner sidewall of the recess region 120 may be exposed . at this point , a portion of the first semiconductor pattern 123 in the recess region 120 may also be etched . referring to fig8 d , subsequently , a second semiconductor layer may be conformally formed on the substrate 100 , a filling dielectric layer filling the opening 115 may be formed on the second semiconductor layer . the second semiconductor layer may contact the first semiconductor pattern 123 , and also the second semiconductor layer may contact the bottom surface and exposed inner sidewall of the recess region 120 . by planarizing the second semiconductor layer and the filling dielectric layer , a second semiconductor pattern 124 and a filling dielectric pattern 132 may be formed in the opening 115 and the recess region 120 . the second semiconductor pattern 124 may contact the bottom surface and inner sidewall of the recess region 120 and the first semiconductor pattern 123 . the first and second semiconductor patterns 123 and 124 may configure a vertical active pattern 130 a . referring to fig8 e , subsequently , the trench 135 , the insulation patterns 110 a and the sacrificial patterns 112 may be formed by sequentially patterning the insulation layers 110 and the sacrificial layers 112 . the empty regions 140 may be formed by removing the sacrificial patterns 112 . at this point , the empty regions 140 may expose some portions of the first sub - layer 147 , respectively . referring to fig8 f , a second sub - layer 149 may be conformally formed on the substrate 100 having the empty regions 140 . the second sub - layer 149 may be conformally formed on the inner surfaces of the empty regions 140 . the second sub - layer 149 may contact the first sub - layer 147 exposed to the empty regions 140 . the first and second sub - layers 147 and 149 may be included in the gate dielectric layer 150 a . the first sub - layer 147 may include at least a portion of the tunnel dielectric layer , and the second sub - layer 149 may include at least a portion of the blocking dielectric layer . herein , one of the first and second sub - layers 147 and 149 may include the charge storage layer . according to an embodiment of the inventive concept , the first and second sub - layers 147 and 149 may be the same as the layers that have been described above with reference to fig3 b . unlike this , the first and second sub - layers 147 and 149 may be replaced with the first and second sub - layers 147 a and 149 a of the fig3 c , respectively . unlike this , the first and second sub - layers 147 and 149 may be replaced with the first and second sub - layers 149 b and 149 c of the fig3 c , respectively . subsequently , the gate patterns 155 l , 155 a 1 , 155 a and 155 u respectively filling the empty regions 140 may be formed , and the device isolation pattern 160 a filling the trench 135 may be formed . subsequently , the interlayer dielectric 165 , the contact plug 167 and the bit line 170 that have been disclosed in fig3 a may be formed . next , a method of fabricating the 3d semiconductor memory device that has been disclosed in fig4 a and 4b will be described below with reference to the accompanying drawings . the method may include the methods that have been described above with reference to fig6 a and 6b . fig9 a to 9d are cross - sectional views taken along line i - i ′ of fig1 a for describing still other modification example of a method of fabricating 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig6 b to 9a , a gate dielectric layer 150 d may be conformally formed on the substrate 100 having the opening 115 and the recess region 120 . a first semiconductor layer may be conformally formed on the gate dielectric layer 150 d . subsequently , the first semiconductor layer and the gate dielectric layer 150 d may be etched by a blanket - anisotropic - etching process until the bottom of the recess region 120 is exposed , such that a first semiconductor pattern 123 may be formed in the opening 115 and the recess region 120 . at this point , the gate dielectric layer 150 d may also be restrictively disposed in the opening 115 and the recess region 120 . the first semiconductor pattern 123 may not contact the side wall of the opening 115 and the inner surface of the recess region 120 by the gate dielectric layer 150 d . referring to fig9 b , subsequently , a second semiconductor may be conformally formed over the substrate 100 , and a filling dielectric layer may be formed on the second semiconductor layer . by planarizing the filling dielectric layer and the second semiconductor layer , a second semiconductor pattern 124 and a filling dielectric pattern 132 may be formed in the opening 115 and the recess region 120 . the first and second semiconductor patterns 123 and 124 may configure a vertical active pattern 130 a . subsequently , a trench 135 , insulation patterns 110 a and sacrificial patterns 112 a may be formed by sequentially patterning the insulation layers 110 and the sacrificial layers 112 . according to the modification example , a portion of the lowermost insulation layer among the insulation layers 110 may remain under the trench 135 . referring to fig9 c , empty regions 140 may be formed by removing the sacrificial patterns 112 a . the empty regions 140 may expose the gate dielectric layer 150 d . particularly , the blocking dielectric layer 143 ( see fig4 b ) in the gate dielectric layer 150 d may be exposed . subsequently , a gate conductive layer 155 filling the empty regions 140 may be formed on the substrate 100 . referring to fig9 d , by removing the gate conductive layer outside the empty regions 140 , gate patterns 155 l , 155 a 1 , 155 a and 155 u filling the empty regions 140 may be formed . subsequently , the device isolation pattern 160 a filling the trench 135 may be formed , and the interlayer dielectric 165 , contact plug 167 and bit line 170 of fig4 a may be formed . thus , the 3d semiconductor memory device of fig4 a and 4b can be implemented . next , a method of fabricating the 3d semiconductor memory device of fig5 a and 5b will be described below with reference to the accompanying drawings . fig1 a to 10c are cross - sectional views taken along line i - i ′ of fig1 a for describing even other modification example of a method of fabricating 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig1 a , insulation layers 210 and gate layers 220 may be alternately and repeatedly stacked on the common source region 105 in the substrate 100 . the insulation layers 210 and gate layers 220 l , 220 a and 220 may have a flat plate shape . referring to fig1 b , an uppermost gate pattern 220 u and an uppermost insulation pattern 210 u may be formed by patterning an uppermost insulation layer and an uppermost gate layer . the uppermost gate pattern 220 u and the uppermost insulation pattern 210 u may have a line shape that is extended in one direction as illustrated in fig5 a . a lower interlayer dielectric 163 may be formed on the substrate 100 , and the lower interlayer dielectric 163 may be planarized . an opening 115 and a recess region 120 may be formed by sequentially patterning the uppermost insulation pattern 210 u , the uppermost gate pattern 220 u , the insulation layers 210 , the gate layers 220 l , 220 a and 220 and the common source region 105 . the recess region 120 may be formed in self - alignment in the opening 115 . by providing a first conductive dopant through the bottom surface of the recess region 120 , a high concentration region 122 may be formed . subsequently , a gate dielectric layer 150 d may be conformally formed over the substrate 100 , and a first semiconductor layer may be conformally formed on the gate dielectric layer 150 d . by blanket - isotropic - etching the first semiconductor layer and the gate dielectric layer 150 d until the bottom surface of the recess region 120 is exposed , a first semiconductor pattern 123 may be formed in the opening 115 and the recess region 120 . referring to fig1 c , a second semiconductor layer may be conformally formed over the substrate 100 , and a filling dielectric layer may be formed on the second semiconductor . by planarizing the filling dielectric layer and the second semiconductor layer , a second semiconductor pattern 124 and a filling dielectric pattern 132 may be formed in the opening 115 and the recess region 120 . the first and second semiconductor patterns 123 and 124 may configure a vertical active pattern 130 a . subsequently , the tipper dielectric layer 165 , contact plug 167 and bit line 170 of fig5 b may be formed . thus , the 3d semiconductor memory device of fig5 a and 5b can be implemented . according to the above - described method , the uppermost gate pattern 220 u may be formed , and thereafter the vertical active pattern 130 a may be formed . unlike this , after the opening 115 , the recess region 120 and the vertical active pattern 130 a may be formed , and then the uppermost gate pattern 220 u may be formed . when forming the uppermost gate pattern 220 u , a stack - structure having a line shape may be formed by sequentially patterning the gate layers 220 , 220 a and 220 l and insulation layers 110 under the uppermost gate pattern 220 u . in this case , the 3d semiconductor memory device of fig4 a and 4b can be implemented . in other words , the 3d semiconductor memory device of fig4 a and 4b may be implemented in the method that has been described above with reference to fig9 a to 9d or a modified method of a portion of the fabricating method of fig1 a to 10c . fig1 is a cross - sectional view illustrating a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 , a well region 102 doped with a first conductive dopant may be disposed in a substrate 100 . a stack - structure may be disposed on the well region 102 . the stack - structure may include insulation patterns 110 a and gate patterns 155 l , 155 a 1 , 155 a and 155 u that are alternately and repeatedly stacked on the well region 102 . a plurality of the stack - structures may be disposed on the well region 102 . the stack - structures may be spaced apart from each other . as illustrated in fig1 a , the stack - structures may be extended in parallel . a vertical active pattern 280 may pass through the stack - structure . also , the vertical active pattern 280 may be extended into a recess region 120 that is formed in the substrate 100 under the vertical active pattern 280 . the vertical active pattern 280 may include a lower active pattern 250 and an upper active pattern 270 that are sequentially stacked . the lower active pattern 250 may fill the recess region 120 . the upper active pattern 270 may contact the inner surface ( i . e ., inner sidewall and bottom surface ) of the recess region 120 . the lower active pattern 250 is disposed in the recess region 120 and contacts the well region 102 . the upper surface of the lower active pattern 250 may be disposed on a level higher than that of the upper surface of the substrate 100 . according to an embodiment of the inventive concept , as illustrated in fig1 , the upper surface of the lower active pattern 250 may be higher than the lower surface of the lowermost gate pattern 155 l and lower than the upper surface of the lowermost gate pattern 155 l . however , the inventive concept is not limited thereto . the upper active pattern 270 contacts the upper surface of the lower active pattern 250 . according to an embodiment of the inventive concept , the lower active pattern 250 may have a pillar shape , and the upper active pattern 270 may have a pipe shape or a macaroni shape . in this case , the inside of the upper active pattern 270 may be filled with a filling dielectric pattern 132 . the lower and upper active patterns 250 and 270 may include a semiconductor material . for example , the lower and upper active patterns 250 and 270 may include the same semiconductor material as that of the substrate 100 . as an example , when the substrate 100 is a silicon substrate , the lower and upper active patterns 250 and 270 may include silicon . according to an embodiment of the inventive concept , the lower active pattern 250 may have a single crystalline state . the upper active pattern 270 may have a poly - crystalline state . the lower active pattern 250 may be doped with a dopant having the same type as that of the well region 102 . the upper active pattern 270 may be doped with a dopant having the same type as that of the well region 102 , or may have an undoped state . a high concentration region 122 may be disposed under the bottom surface of the recess region 120 . the high concentration region 122 may correspond to a portion of the well region 102 , and it may have a higher dopant concentration than another portion of the well region 102 . a gate dielectric layer 150 may be disposed between a sidewall of the vertical active pattern 280 and each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . as described above in first embodiment of the inventive concept , the gate dielectric layer 150 may be extended horizontally and cover the upper surface and lower surface of each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . according to an embodiment of the inventive concept , a common source regions 105 a may be disposed in the substrate 100 of the both sides of the stack - structure , respectively . the common source region 105 a may be laterally separated from the lower active pattern 250 . the common source region 105 a is doped with a second conductive dopant . a device isolation pattern 160 a may be disposed between the stack - structures . the common source region 105 a may be disposed under the device isolation pattern 160 a . in operating of the 3d semiconductor memory device , a horizontal channel may be generated in the well region 102 under the lowermost gate pattern 155 l . the common source region 105 a may be electrically connected to vertical channels that are formed in the vertical active pattern 280 by the horizontal channel in the well region 102 . a contact plug 167 passing through the interlayer dielectric 165 may be connected to the upper end of the upper active pattern 270 . a drain doped with the second conductive dopant may be disposed in the upper portion of the upper active pattern 270 . the lower surface of the drain may be disposed on a level adjacent to the upper surface of the uppermost gate pattern 155 u in the stack - structure . according to the above - described 3d semiconductor memory device , the lower active pattern 250 included in the vertical active pattern 280 fills the recess region 120 to contact the well region 102 . therefore , reliability for the operations of a vertical cell string can be improved . particularly , reliability for the erasing operation of cell transistors can be enhanced . also , the vertical active pattern 280 may be divided into the lower active pattern 250 and the upper active pattern 270 . accordingly , an independent and additional process may be performed in the lower active pattern 250 . for example , a dopant concentration may be adjusted in the lower active pattern 250 . thus , it is very easy to control the characteristic of the 3d semiconductor memory device . as a result , the 3d semiconductor memory device can be implemented which has excellent reliability and is optimized for high integration . next , the modification examples of the 3d semiconductor memory device will be described below with reference to the accompanying drawings . fig1 a is a cross - sectional view illustrating a modification example of a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 a , a common source region 105 may be extended to the substrate 100 under the stack - structures . for example , the entire lower surface of the lowermost gate pattern 155 l may substantially overlap with the common source region 105 . in this case , the bottom of the recess region 120 may be disposed on a level lower than the lower surface of the common source region 105 . the common source region 105 may contact a sidewall of the lower active pattern 250 . fig1 b is a cross - sectional view illustrating other modification example of a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 b , a vertical active pattern 280 a may include a lower active pattern 250 and an upper active pattern 270 a that are sequentially stacked . a gate dielectric layer 150 a may be disposed between the upper active pattern 270 a and each of the gate patterns 155 a 1 , 155 a and 155 u disposed next to the upper active pattern 270 a . the gate dielectric layer 150 a may include a first and a second sub - layers 147 and 149 . as described above in first embodiment of the inventive concept , the first sub - layer 147 may be extended vertically and be disposed between the upper active pattern 270 a and the insulation pattern 110 a . the second sub - layer 149 may be extended horizontally and cover the lower surface and upper surface of each of the gate patterns 155 a 1 , 155 a and 155 u . when the upper surface of the lower active pattern 250 is disposed on a level between the levels of the lower and upper surfaces of the lowermost gate pattern 155 l , the first sub - layer 147 may not exist between the lower active pattern 250 and the lowermost gate pattern 155 l . the upper active pattern 270 a may include a first semiconductor pattern 265 and a second semiconductor pattern 267 . the first semiconductor pattern 265 may be disposed between the first sub - layer 147 and the second semiconductor pattern 267 . the first semiconductor pattern 265 may be separated from the upper surface of the lower active pattern 250 by a portion of the first sub - layer 147 . the second semiconductor pattern 267 contacts the first semiconductor pattern 265 . also , the second semiconductor pattern 267 contacts the upper surface of the lower active pattern 250 . the upper surface of the lower active pattern 250 may be divided into a center portion 252 c contacting the second semiconductor pattern 267 and an edge portion 252 e contacting the first sub - layer 147 . herein , the center portion 252 c of the upper surface of the lower active pattern 250 may be disposed on a level lower than that of the edge portion 252 e . the upper active pattern 270 a including the first and second semiconductor patterns 265 and 267 may have a pipe shape or a macaroni shape . in this case , the inside of the upper active pattern 270 a may be filled with a filling dielectric pattern 132 . the first and second semiconductor patterns 265 and 267 may have a poly - crystalline state . in the modification example , the first and second sub - layers 147 and 149 may be replaced by the first and second sub - layers 147 a and 149 a of fig3 c or the first and second sub - layers 147 b and 149 b of fig3 c . unlike this , as described above in first embodiment of the inventive concept , the first and second sub - layers 147 and 149 may be formed by another combination of a tunnel dielectric layer , a charge storage layer and a blocking dielectric layer . fig1 c is a cross - sectional view illustrating still other modification example of a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 c , at least edge portion of the upper surface of the lower active pattern 250 may be disposed on a level higher than the upper surface of the lowermost gate pattern 155 l . in this case , an oxide layer 255 may be disposed between the sidewall of the lower active pattern 250 and the lowermost gate pattern 155 l . the oxide layer 255 may include oxide formed by oxidizing the sidewall of the lower active pattern 250 . therefore , the width of a first portion of the lower active pattern 250 next to the oxide layer 255 may be less than that of a second portion of the lower active pattern 250 disposed in the recess region 120 . when the gate dielectric layer 150 a includes the first and second sub - layers 147 and 149 , the oxide layer 255 and a portion of the second sub - layer 149 may be disposed between the sidewall of the lower active pattern 250 and the lowermost gate pattern 155 l . in other words , the first sub - layer 147 may not exist between the sidewall of the lower active pattern 250 and the lowermost gate pattern 155 l . according to an embodiment of the inventive concept , when the first sub - layer 147 includes a charge storage layer , the charge storage layer may not exist between the sidewall of the lower active pattern 250 and the lowermost gate pattern 155 l . therefore , the reliability of a ground selection transistor including the lowermost gate pattern 155 l can be improved . moreover , the lower active pattern 250 may have a single crystalline state . accordingly , the reliability of the ground selection transistor can be more enhanced . fig1 d is a cross - sectional view illustrating even other modification example of a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 d , at least the edge portion of the upper surface of a lower active pattern 250 may be disposed on a level higher than the upper surface of a gate pattern 155 a 1 that is stacked secondarily from the substrate 100 and lower than the lower surface of a gate pattern that is stacked thirdly from the substrate 100 . the secondarily - stacked gate pattern 155 a 1 and the thirdly - stacked gate pattern are disposed over the lowermost gate pattern 155 l . in this case , an oxide layer 255 may also be disposed between the secondarily - stacked gate pattern 155 a 1 and the side wall of the lower active pattern 250 . according to the modification example , a transistor including the secondarily - stacked gate pattern 155 a 1 may be used as a dummy transistor or a second ground selection transistor . in this case , a cell gate ( for example , the thirdly - stacked gate pattern 155 a ) adjacent to the secondarily - stacked gate pattern 155 a 1 may correspond to a dummy cell gate . as described above , a dummy cell transistor including the dummy cell gate has the same type as that of a cell transistor storing data , but it may not serve as a cell transistor . as an example , in operating of the cell string , the dummy cell transistor may perform only a turn - on / off function . however , the inventive concept is not limited thereto . the thirdly - stacked gate pattern may be used as a cell transistor . fig1 e is a cross - sectional view illustrating yet other modification example of a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 e , the entirety of a gate dielectric layer 150 d between the sidewall of the upper active pattern 270 a and each of the gate patterns 155 a 1 , 155 a and 155 u may be substantially extended vertically and be disposed between an upper active pattern 270 a and an insulation pattern 110 a . in this case , only an oxide layer 255 may be disposed between the sidewall of the lower active pattern 250 and the lowermost gate pattern 155 l . fig1 f is a cross - sectional view illustrating further modification example of a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 f , protection dielectric patterns 173 a may be disposed between the upper active pattern 270 a and the insulation patterns 110 a . in a fabricating process , the protection dielectric pattern 173 a may include a dielectric material for protecting the upper active pattern 270 . according to an embodiment of the inventive concept , the protection dielectric pattern 173 a may not exist between the lower active pattern 250 and the inner sidewall of the recess region 120 . the elements of the above - described modification examples may be combined without clash or replaced . for example , the common source region 105 a of fig1 may be replaced with the common source region 105 of fig1 b to 12f . for example , in the 3d semiconductor memory devices of fig1 and 12a to 12 f , the heights of the upper surfaces of the lower active patterns 250 may be replaced . fig1 a to 13e are cross - sectional views for describing a method of fabricating 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 a , a well region 102 may be formed by providing a first conductive dopant to the substrate 100 . insulation layers 110 and sacrificial layers 112 that are alternately and repeatedly stacked may be formed on the well region 102 . a recess region 120 and an opening 115 that are sequentially stacked may be formed by sequentially patterning the insulation layers 110 , the sacrificial layers 112 and the substrate 100 . the opening 115 may pass through the insulation layers 110 and the sacrificial layers 112 , and the recess region 120 may be self - aligned in the opening 115 and be formed in the substrate 100 . the recess region 120 may expose the well region 102 . referring to fig1 b , a high concentration region 122 may be formed by providing the first conductive dopant through the bottom of the recess region 120 . a lower active pattern 250 filling the recess region 120 may be formed . the upper surface of the lower active pattern 250 may be higher than the upper surface of the substrate 100 . therefore , a portion of the lower active pattern 250 may fill the lower portion of the opening 115 . the lower active pattern 250 contacts the well region 102 . the lower active pattern 250 may be formed in a selective epitaxial growth process that uses the substrate 100 exposed by the recess region 120 as a seed layer . therefore , the lower active pattern 250 may be formed in a single crystalline state . the lower active pattern 250 may be formed in a pillar shape . the lower active pattern 250 may be doped with the first conductive dopant . the lower active pattern 250 may be doped by an in - situ process when the selective epitaxial growth process is performed . unlike this , the lower active layer 250 may be doped by an ion - implanting process . referring to fig1 c , a semiconductor layer may be conformally formed on the substrate 100 having the lower active pattern 250 , and a filling dielectric layer filling the opening 115 may be formed on the semiconductor layer . the semiconductor layer may be conformally formed on the inner sidewall of the opening 115 and the upper surface of the lower active pattern 250 . the semiconductor layer may contact the lower active pattern 250 . the semiconductor layer may be formed in a chemical vapor deposition process and / or an atomic layer deposition process . therefore , the semiconductor layer may be formed in a poly - crystalline state . by planarizing the filling dielectric layer and the semiconductor layer , an upper active pattern 270 and a filling dielectric pattern 132 may be formed in the opening 115 . the lower and upper active patterns 250 and 270 may configure a vertical active pattern 280 . subsequently , a trench 135 , insulation patterns 110 a and sacrificial patterns 110 a may be formed by sequentially patterning the insulation layers 110 and the sacrificial layers 112 . the vertical active pattern 280 passes through the insulation patterns 110 a and the sacrificial patterns 112 a . subsequently , by providing a second conductive dopant into the well region 102 under the trench 135 , a common source region 105 a may be formed . referring to fig1 d , by removing sacrificial patterns 112 a exposed to the trench 135 , empty regions 140 may be formed . according to an embodiment of the inventive concept , at least a portion of an lowermost empty regions 140 may expose a portion of the sidewall of the lower active pattern 250 . a gate dielectric layer 150 may be conformally formed on the substrate 100 having the empty regions 140 , and a gate conductive layer 155 filling the empty regions 140 may be formed . referring to fig1 e , gate patterns 155 l , 155 a 1 , 155 a and 155 u , that are respectively disposed in the empty regions 140 , may be formed by etching the gate conductive layer 155 . subsequently , a device isolation pattern 160 a filling the trench 135 may be formed . the 3d semiconductor memory device of fig1 may be implemented by forming the interlayer dielectric 165 , contact plug 167 and bit line 170 of fig1 . according to the above - described 3d semiconductor memory device , the opening 115 and the recess region 120 are formed in self - alignment , and the lower active pattern 250 fills the recess region 120 to contact the well region 102 . after , the lower active pattern 250 is formed , and then the upper active pattern 270 may be formed . therefore , the doping concentration of the lower active pattern 250 may be independently adjusted . as a result , the 3d semiconductor memory device having superior reliability can be implemented . the features of the method of fabricating 3d semiconductor memory device that is illustrated in fig1 a will be described below with reference to fig1 . fig1 is a cross - sectional view illustrating a modification example of a method of fabricating 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 , a second conductive dopant is injected into a substrate 100 having a well region 102 , such that a common source region 105 may be formed . insulation layers 110 and sacrificial layers 112 that are alternately and repeatedly stacked may be formed on the common source region 105 . an opening 115 and a recess region 120 may be formed by sequentially patterning the insulation layers 110 , the sacrificial layers 112 and the substrate 100 . the recess region 120 may pass through the common source region 105 , and thus the bottom surface of the recess region 120 may be lower than the lower surface of the common source region 105 . the bottom surface of the recess region 120 may expose the well region 102 , and the inner sidewall of the recess region 120 may expose the common source region 105 . successive processes may be performed identically to the process that has been described above with reference to fig1 a through fig1 e . however , the process of forming the common source region 105 a that has been described above with reference to fig1 c may be omitted . fig1 a to 15f are cross - sectional views illustrating other modification example of a method of fabricating 3d semiconductor memory device according to another embodiment of the inventive concept . a fabricating method according to the modification example may include the method that has been described above with reference to fig1 . referring to fig1 and 15a , a lower active pattern 250 filling the recess region 120 may be formed on the substrate 100 having the opening 115 and the recess region 120 . the lower active pattern 250 may be formed identically to the process that has been described above with reference to fig1 b . the level of the upper surface of the lower active pattern 250 may be adjusted . in fig1 a , the upper surface of the lower active pattern 250 may be higher than the level of the upper surface of a lowermost sacrificial layer and lower than the level of the lower surface of a sacrificial layer just on the lowermost sacrificial layer . a first sub - layer 147 may be conformally formed on the substrate 100 having the lower active pattern 250 . a first semiconductor layer 264 may be conformally formed on the first sub - layer 147 . the first semiconductor layer 264 may be formed in a chemical vapor deposition process and / or an atomic layer deposition process . the first semiconductor layer 264 may be formed in a poly - crystalline state . referring to fig1 b , the first semiconductor layer 264 and the first sub - layer 147 may be blanket - anisotropic - etched until the upper surface of the lower active pattern 250 is exposed . therefore , a first semiconductor pattern 265 may be formed in the opening 115 . according to an embodiment of the inventive concept , the center portion of the exposed upper surface of the lower active pattern 250 may be recessed lower than the edge portion of the upper surface of the lower active pattern 250 . referring to fig1 c , a second semiconductor layer may be conformally formed on the substrate 100 having the first semiconductor pattern 265 , and a filling dielectric layer may be formed on the second semiconductor layer . the second semiconductor layer may contact the first semiconductor pattern 265 and the center portion of the upper surface of the lower active pattern 250 . by planarizing the filling dielectric layer and the second semiconductor layer , a second semiconductor pattern 267 and a filling dielectric pattern 132 may be formed in the opening 115 . the first and second semiconductor patterns 265 and 267 may configure an upper active pattern 270 a , and the lower and upper active patterns 250 and 270 a may configure a vertical active pattern 280 a . subsequently , a trench 135 , insulation patterns 110 a and sacrificial patterns 112 a may be formed by sequentially patterning the insulation layers 110 and the sacrificial layers 112 . referring to fig1 d , empty regions 140 may be formed by removing the sacrificial patterns 112 a . according to an embodiment of the inventive concept , the lowermost empty region of the empty regions 140 may expose the sidewall of the lower active pattern 250 , and empty regions on the lowermost empty region may expose the first sub - layer 147 . however , the inventive concept is not limited thereto . the number of empty regions for exposing the sidewall of the lower active pattern 250 may vary with the height of the edge portion of the upper surface of the lower active pattern 250 . referring to fig1 e , an oxide layer 255 may be formed by performing an oxidizing process in the exposed sidewall of the lower active pattern 250 . when the lower active pattern 250 is formed of silicon , the oxide layer 255 may be formed of a silicon oxide . the sidewall of the upper active pattern 270 a may not be oxidized by the first sub - layer 147 . referring to fig1 f , subsequently , a second sub - layer 149 may be conformally formed over the substrate 100 , and gate patterns 155 l , 155 a 1 , 155 a and 155 u respectively filling the empty regions 140 may be formed . subsequently , an isolation pattern 160 a , an interlayer dielectric layer 165 , a contact plug 167 and a bit line 170 may be formed . therefore , the 3d semiconductor memory device of fig1 c can be implemented . in the fabricating method of fig1 a to 15f , the level of the upper surface of the lower active pattern 250 may be higher than the level of the upper surface of a sacrificial layer that is stacked secondarily from the upper surface of the substrate 100 and lower than the level of the lower surface of a thirdly - stacked sacrificial layer . in this case , the 3d semiconductor memory device of fig1 d can be implemented . in the fabricating method of fig1 a to 15f , when the level of the upper surface of the lower active pattern 250 is disposed between the levels of the upper and lower surfaces of the lowermost sacrificial layer and the oxidizing process is omitted , the 3d semiconductor memory device of fig1 b can be implemented . in the fabricating method of fig1 a to 15f , when the first sub - layer 147 is replaced by the gate dielectric layer 150 d and forming of the second sub - layer 149 is omitted , the 3d semiconductor memory device of fig1 e can be implemented . next , a method of fabricating the 3d semiconductor memory device that is illustrated in fig1 f will be described below with reference to the accompanying drawings . the method may include the method that has been described above with reference to fig1 . fig1 a and 16b are cross - sectional views illustrating still other modification example of a method of fabricating 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 and 16a , after a lower active pattern 250 may be formed , a protection dielectric layer may be conformally formed on the substrate 100 . the protection dielectric layer may be blanket - anisotropic - etched until the upper surface of the lower active pattern 250 is exposed . therefore , a protection dielectric layer 173 may be formed to have a spacer shape in the sidewall of the opening 115 . subsequently , a semiconductor layer may be conformally formed , and a filling dielectric layer may be formed . the filling dielectric layer and the semiconductor layer may be planarized , such that an upper active pattern 270 and a filling dielectric pattern 132 may be formed in the opening 115 . subsequently , the upper ends of the protection dielectric layer 173 , upper active pattern 270 and filling dielectric pattern 132 may be recessed , and then a capping semiconductor pattern 175 may be formed . the capping semiconductor pattern 175 may be formed in the same process as the process that has been described above with reference to fig7 b . referring to fig1 b , a trench 135 , insulation patterns 110 a and sacrificial patterns 112 a may be formed by sequentially patterning insulation layers 110 and sacrificial layers 112 . empty regions 140 may be formed by removing the sacrificial patterns 112 a . at this point , the protection dielectric layer 173 may be used an etch stop layer . subsequently , by removing some portions of the protection dielectric layer 173 exposed to the empty regions 140 , some portions of the sidewall of the upper active pattern 270 may be exposed . subsequently , the 3d semiconductor memory device of fig1 f can be implemented by performing the method that has been described above with reference to fig1 d and 13e . according to an embodiment of the inventive concept , after forming the empty regions 140 of fig1 b and before forming a gate dielectric layer , an oxidizing process may be performed in the exposed sidewall of the lower active pattern 250 . the 3d semiconductor memory devices according to embodiments of the inventive concept may be implemented as various types of packages . for example , the 3d semiconductor memory devices according to embodiments of the inventive concept may be packaged in a package type such as package on package ( pop ), ball grid arrays ( bgas ), chip scale packages ( csps ), plastic leaded chip carrier ( plcc ), plastic dual in - line package ( pdip ), die in waffle pack ( diwp ), die in wafer form ( diwf ), chip on board ( cob ), ceramic dual in - line package ( cerdip ), plastic metric quad flat pack ( mqfp ), thin quad flat pack ( tqfp ), small outline package ( sop ), shrink small outline package ( ssop ), thin small outline package ( tsop ), thin quad flat pack ( tqfp ), system in package ( sip ), multi chip package ( mcp ), wafer level stack package ( wlsp ), die in wafer form ( diwf ), die on waffle package ( dowp ), wafer - level fabricated package ( wfp ) and wafer - level processed stack package ( wsp ). a package on which the 3d semiconductor memory device according to embodiments of the inventive concept is mounted may further include at least one semiconductor device ( for example , a controller , a memory device and / or a hybrid device ) performing another function . fig1 is a block diagram schematically illustrating an example of an electronic system including a 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig1 , an electronic system 1100 according to an embodiment of the inventive concept may include a controller 1110 , an input / output ( i / o ) unit 1120 , a memory device 1130 , an interface 1140 , and a bus 1150 . the controller 1110 , the input / output ( i / o ) unit 1120 , the memory device 1130 and / or the interface 1140 may be connected through the bus 1150 . the bus 1150 corresponds to a path for transferring data . the controller 1110 may include at least one of a microprocessor , a digital signal processor , a microcontroller , and logical devices for performing a function similar to the functions of the elements . the input / output unit 1120 may include a keypad , a keyboard , a display device and others . the memory device 1130 may store data and / or commands . the memory device 1130 may include at least one of the 3d semiconductor memory devices according to embodiments of the inventive concept . also , the memory device 1130 may further include another type of semiconductor memory device ( for example , phase - change random access memory ( pram ), magnetoresistive random access memory ( mram ), dynamic random access memory ( dram ) and / or static random access memory ( sram )). the interface 1140 may transmit data to a communication network or receive data from the communication network . the interface 1140 may have a wired type or a wireless type . for example , the interface 1140 may include an antenna or a wired / wireless transceiver . although not shown , the electronic system 1100 is a working memory device for improving the function of the controller 1110 , and may further include a high - speed dram and / or a high - speed sram . the electronic system 1100 may be applied to personal digital assistants ( pdas ), portable computers , web tablets , wireless phones , mobile phones , digital music players , memory cards , and all electronic devices for transmitting / receiving information at a wireless environment . fig1 is a block diagram schematically illustrating an example of a memory card including a 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig1 , a memory card 1200 according to an embodiment of the inventive concept may include a memory device 1210 . the memory device 1210 may include at least one of the 3d semiconductor memory devices according to embodiments of the inventive concept . also , the memory device 1210 may further include another type of semiconductor memory device ( for example , pram , mram , dram and / or sram ). the memory card 1200 may include a memory controller 1220 for controlling data exchange between a host and the memory device 1210 . the memory controller 1220 may include a processing unit 1222 for controlling the overall operation of the memory card 1200 . also , the memory controller 1220 may include an sram 1221 that is used as the working memory of the processing unit 1222 . furthermore , the memory controller 1220 may further include a host interface 1223 and a memory interface 1225 . the host interface 1223 may include a data exchange protocol between the memory card 1200 and the host . the memory interface 1225 may connect the memory controller 1220 and the memory device 1210 . in addition , the memory controller 1220 may further include an error correction block ( ecc ) 1224 . the error correction block 1224 may detect and correct the error of data that is read from the memory device 1210 . although not shown , the memory card 1200 may further include a rom that stores code data for interfacing with the host . the memory card 1200 may be used as a portable data memory card . on the contrary , the memory card 1200 may be implemented as a solid state disk ( ssd ) that may replace the hard disk of a computer system . according to the above - described 3d semiconductor memory device , the vertical active pattern can be disposed in the recess region of the common source region and be connected to the well region . therefore , the distance between the vertical active pattern and the common source region can be minimized , and also , the vertical active pattern can be connected to the well region . as a result , the 3d semiconductor memory device which has excellent reliability and is optimized for high integration can be implemented . the above - disclosed subject matter is to be considered illustrative and not restrictive , and the appended claims are intended to cover all such modifications , enhancements , and other embodiments , which fall within the true spirit and scope of the inventive concept . thus , to the maximum extent allowed by law , the scope of the inventive concept is to be determined by the broadest permissible interpretation of the following claims and their equivalents , and shall not be restricted or limited by the foregoing detailed description .
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the light wand of the present invention can be any shape or size . preferably , the wand is small enough to be carried . for example , the wand can be , but is not limited to the following dimensions : approximately 2½ inches × 7 inches × 1 inch . the light wand is shaped for ease of use . light emitting diodes ( leds ) are used to emit light energy for the promotion of tissue healing and other beneficial results . the light energy from leds can assist with various skin conditions , for example , acne , rosacea , and eczema and reduce inflammation in swollen gums associated with baby teething . monochromatic light from leds is focused light energy that isolates on the most potent frequencies for the relief of acute or chronic pain and wound healing . cell tissue responds best to certain frequencies that appear to be with the infrared spectrum , such as 660 nanometers ( nm ), 660 nm , 880 nm , 940 nm and 950 nm . the water and blood content within the body tissue restrict full absorption of light frequencies outside the range of 600 - 980 nm . one frequency of light may be a primary resonant frequency for the body , while the others may be wasted harmonics . a single wavelength within the middle of the spectrum ( e . g . 660 nm ) is the most resonant frequency to the human tissue . an application of a 660 nm light beam for several minutes to a wound approximately the size of a half of dollar every two hours can ( within a day or two ) stimulate the generation of new skin without scabbing or forming scar tissue . photons emitted by the monochromic leds are absorbed by the skin and underlying tissue , triggering biological changes within the body in a process know as “ photo - bio - stimulation .” monochromatic light increases oxygen and blood flow , wound healing and stimulates nerve functioning as well as facilitating pain reduction and muscular relaxation . light in the red spectrum and the infrared spectrum enhances and speeds up certain cellular metabolic processes , such as activity of mitochondria ( cellular organelles outside the nucleus that convert stored chemical energy into a more usable form ), charging the electrophysiological ( electrical aspect ) properties of the cell membrane and activating enzymes which turn into activate key chemical reactions . light energy is used as trigger for the rearrangement of cellular metabolism . there are photo acceptors at the molecular and cellular level that , when triggered , cause a series of biological actions . for example , dna and rna synthesis , protein and collagen synthesis and cellular proliferation are all increased when exposed to monochromatic light . the results of these biological actions are a rapid regeneration , normalization and healing of damaged cells tissue . exposure to monochromic led &# 39 ; s ( light ) energy is an effective therapy that works in harmony with the body &# 39 ; s own healing and pain relieving mechanisms . there are no known harmful side effects from the led &# 39 ; s light . light technology can also be used with hard - to - heal wounds , such as diabetic ulcers , serious burn and severe oral sores caused by chemotherapy and radiation . the light energy from monochromic leds stimulates the production of collagen , the most common protein found in the body . this essential protein is used to repair damaged tissues and replace old tissue . collagen is the substance that holds cells together and has a high degree of elasticity . by increasing collagen production , less scar tissue is formed at the site of injury . the led light energy also increases circulation by increasing the actual formation of the new capillaries , which are additional blood vessels that replace damaged ones . new capillaries that carry oxygen and nutrients are needed for healing and allow waste to be carried away for healthy skin to grow . led light energy using monochromic light also stimulates the lymphatic system , helping to eliminate toxins and excess fluids from the issue . the diameter of the lymph vessel ( a vascular duct ) accompanying lymph flow can be doubled with the use of light therapy that can increase the number of white blood cells in the blood circulation . monochromic led light therapy can also stimulate the release of adenosine triphosphate ( atp ). this chemical is the body &# 39 ; s major carrier of energy to the cells . increased amounts of this chemical allows cells to accept nutrients faster , and get rid of waste products faster by increasing the energy in the cell . increases of rna and dna synthesis also are available with light therapy that helps older or damaged cells to be replaced faster . further biological effects of led light therapy include the following . the led light can reduce excitability of the nerves tissue . the photon light energy enters the body as negative ions that require the body to send positive ions , calcium among others , to flow to the area being treated . these ions assist in regulating the nerves , thereby relieving pain . the led light can also stimulates the activity of the fibroblasts in the connective tissue . they are capable of forming collagen which aids in the repair process . led light stimulates proper tissue granulation , which is part of the healing process of inflamed tissue , such as acne breakouts . monochromic led light stimulates biological processes . just as plants are exposed to normal sunlight to synthesize carbohydrates in their chlorophyll - containing tissue ( photosynthesis ), light stimulates the formation and release of our own chemical compounds . in light therapy , the monochromic infrared light energy has a stimulating effect on the tissues because it increases cellular energy . the light energy becomes absorbed in the tissue , hence stimulating the metabolic process . the tissues exposed to monochromatic light increase blood flow , thus helping to carry vitamins and nutrients into the area where they are most needed with no damage to the surrounding tissues . as a result of increased blood flow , toxins and waste bi - products are taken away from the tissue . light therapy is also know as “ photo therapy ”. for instance , visible red light has a positive effect at a cellular level on living tissue . this type of light therapy is beneficial in treating conditions close to the surface . skin - layers because of their high blood and water content absorb red light readily . light and all electromagnetic energy travels as bundles of energy called photons . the center ( nucleus ) of the atom contains neurons and protons . the nucleus is surrounded by electrons moving in specific orbits . energy , in the form of photons , is released when the electrons change orbits . it is these bundles of energy that trigger biological changes within the body . we are constantly bombarded by photons from ordinary light sources including sunlight . monochromatic light created by the led &# 39 ; s of the present invention has the ability to control and concentrate these photons . to accomplish these benefits , the following example is given . this example is merely illustrative of the principles of the present invention and is not meant to limit the invention to embodiments given in this example . in fig1 , a top perspective view of a light wand 2 is shown . light wand 2 includes a lens cover 4 , which is used to protect the leds disposed underneath the cover . the lens cover can be clear or colored transparently , such as a blue transparent . the light wand further includes a handle 6 for gripping the wand . the wand can be any shape or design and does not necessarily require a handle to function within the scope of the present invention . the wand 2 further includes a battery cover 10 for protecting the power source disposed beneath cover 10 . preferably the power source is four aa batteries , however an ac adapter can be used and plugged into receptacle 12 . power switch 14 turns the light wand on and off . the power output for the light wand is preferably a steady power output of about 20 milliwatts to about 50 milliwatts . head 16 holds the circuitry for a control unit 22 as shown in fig2 and fig5 a and 5b . control unit 22 includes control switches 22 and 24 . in fig5 a and 5b theses switches are denoted by sw 2 , sw 3 . these control switches are for controlling the light delivery mode ( pulse or concentrated stream of light or both ), and the leds intensity level . the symbol sw 1 denotes power switch 14 . a microprocessor pic18c505c further provides control of the light mode and intensity of the leds . in fig5 b , the leds are denoted by led 1 - led 36 . in this example , there are ( 18 ) red leds and ( 18 ) red leds . it is preferred that the number of leds are even to provide a uniform distribution over the treatment site . however , it is within the scope of this invention to provide leds having a total amount that is an odd number . the distribution of the light energy will depend on the array of leds in the wand . for example , as shown in fig3 a and fig3 b , two different arrays of leds are shown . it is preferred that the led array is circular to allow uniform distribution of the light energy to the treatment site . shown in these figures are red led 30 and infrared led 32 . fig3 a illustrates a total number of leds of odd numbers ( 27 red , 25 infrared ). fig3 b illustrates a total number of leds of even numbers ( 18 red , 18 infrared ). again the even numbers are preferred to distribute uniform amounts of light energy ., both arrays are in a circular pattern to further the uniform emitting of the light energy . the leds are preferably red and / or infra red . the following illustration gives examples of the specifications of such leds . this illustration is not meant to limit the scope of the invention to this embodiment , but is merely given as an example of what leds can be used with the present invention for the advantages previously discussed . a light wand having 18 infrared and 18 red led typically provides an average light output energy density per minute of 1 . 46 joules / cm 2 . the total effective area of light out put is typically about 16 centimeters squared . again , the round shape of the led array assists in transmitting a uniform dosage of light energy to the treatment site without the need for a user to move the light wand back and forth to apply a uniform dosage of the led light energy . the light wand gives a user the ability to choose from at least 7 frequencies and at least 8 energy densities . the light frequencies are restricted to the range where body tissue can have full absorption , which is between about 600 nm to about 980 nm . preferably the frequencies are set at about 660 nm for red led and about 850 nm for infrared led . the control unit provides flexibility in led light delivery for the healing of tissue . again , cell tissue responds best to certain frequencies that appear to be with the infrared spectrum , such as 660 nanometers ( nm ), 660 nm , 880 nm , 940 nm and 950 nm . the water and blood content within the body tissue restrict full absorption of light frequencies outside the range of 600 - 980 nm . one frequency of light , a single wavelength that is preferably 660 nm is the most resonant frequency to the human tissue . an application of a 660 nm light beam for several minutes to a wound approximately the size of a half of dollar every two hours can ( within a day or two ) stimulate the generation of new skin without scabbing or forming scar tissue . fig4 illustrates a light wand having red leds only . in this illustration red leds 32 are mounted about head 4 in a circular array . the leds can have a total number that is odd or even . again , an even number of leds is preferred to assist in the uniform distribution of light energy . the energy intensity of the light wand has at least ( 8 ) settings . typical average energy light output per minute is estimated at about 1 . 3 joules / cm squared / minute . the following table illustrates and exemplary energy level settings of the present invention . this example is given for illustration purposes only and is not meant to limit the invention to this particular illustration . the above example demonstrates that the energy level settings may have a temporal relationship with the treatment time . for example , in this illustration there is an underlying constant level of light energy and the intensity is determined by the time of exposure . the exposure time is controlled by the control unit circuitry previously described above and shown in detail in fig5 a and 5b . an automatic shut off feature is included in the circuitry to avoid under and over exposure of the light energy . the automatic shut off feature is not a typical shut off circuit . through the microprocessor , the automatic shut off feature consistently provides control over the leds to emit the desired intensity and frequency of light energy . this feature prevents over or under exposure of the treatment site . light therapy from the light wand is emitted either in a pulsed or a constant light stream or beam or beams . the automatic shut off is provided in the control unit ( microprocessor circuitry ) to avoid over or under exposure of the treatment site . this automatic shut off turns the device off when the desired intensity is reached . this device is controlled by a microprocessor shown in fig5 b that prevents over and under exposure to the treatment site . the automatic shut off feature through the microprocessor adjusts the timing of exposure as the internal or external power source weakens or fluctuates . for example , with an internal battery source , as the battery weakens , the microprocessor adjusts the time of exposure so that the desired intensity of the leds is consistently achieved . if the power source is too weak to deliver the desired intensity , the device warns the user of this condition , and will prevent delivery of an undesirable dose . similarly , if the power source is too high , the control unit will decrease the time of exposure so that the desired frequency and intensity is achieved without over exposure to the treatment site . the present invention also has the ability to control time of light energy delivery and intensity of light energy delivery . the intensity of the light energy may be controlled by the control unit , in particular through sw 3 in fig5 b ( control switch 24 ) through a direct correlation in power available to the leds . for example , with this power supply method as the control switch 24 is increased , the power available to the leds is increased . this increase in power will increase the intensity of the treatment . the control unit will prevent any over or under exposure to the treatment site allowing consistent delivery of the desired joules of light energy . the description of operation includes turning on power switch 14 . either the ac adapter can be used or the battery pack located inside the light wand . the user then selects what mode to deliver . the mode refers to the type of light delivery , pulsed , constant stream of light or a combination of both . after the mode is selected , the intensity may be selected . there is no limitation in the order of using the control switches in the control unit . any sequence of steps can be used in the present invention . the user then applies the wand over the treatment site . the wand automatically shuts off after the selected treatment intensity is delivered . the automatic shut off protects the treatment site from being over exposed . an electric timer integrated in the microprocessor of the control unit prevents the treatment site from being under exposed . this feature provides consistent treatment exposure to the treatment site without the user induced error or speculation on how long to treat the treatment site . it should be understood that the above description is only representative of illustrative examples of embodiments . for the reader &# 39 ; s convenience , the above description has focused on a representative sample of all possible embodiments , a sample that teaches the principles of the invention . other embodiments may result from a different combination of portions of different embodiments . the description has not attempted to exhaustively enumerate all possible variations . furthermore , since numerous modifications and variations will readily occur to those skilled in the art , it is not desired that the present invention be limited to the exact construction and operation illustrated . accordingly , all suitable modifications and equivalents that may be resorted to are intended to fall within the scope of the claims .
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in the following description , for the purposes of explanation , numerous specific details are set forth in order to provide a thorough understanding of exemplary embodiments . it should be apparent , however , that exemplary embodiments may be practiced without these specific details or with an equivalent arrangement . in other instances , well - known structures and devices are shown in block diagram form in order to avoid unnecessarily obscuring exemplary embodiments . in addition , unless otherwise indicated , all numbers expressing quantities , ratios , and numerical properties of ingredients , reaction conditions , and so forth used in the specification and claims are to be understood as being modified in all instances by the term “ about .” the present disclosure addresses and solves problems of high power consumption , unnecessary pre - charging , and slow read cycle times . the present disclosure addresses and solves such problems , for instance , by , inter alia , providing a fuse state of a fuse unit cell based on a discharging of capacitors within a fuse sensing circuit that is coupled to the fuse unit cell . fig2 schematically illustrates a fuse sensing circuit that indicates a fuse state of a fuse unit cell based on a discharging of capacitors of the fuse sensing circuit , in accordance with an exemplary embodiment of the present disclosure . as shown , the circuit in fig2 includes fuse unit cell 201 coupled to sensing circuit 203 . fuse unit cell 201 includes fuse 205 having one end coupled to a power source ( e . g ., fsource ) and another end coupled to program transistor 207 . for example , while program transistor 207 is activated ( e . g ., based on inputs , fu_row_pg and fu_clm_pg , to and gate 209 ), a large current from fsource may go through fuse unit cell 201 , causing fuse 205 to become blown . to detect the fuse state ( e . g ., blown , unblown , etc .) of fuse 205 , fuse unit cell 201 includes reference resistor 211 along with transistors 213 and 215 that are connected to sensing circuit 203 . sensing circuit 203 includes two capacitors 217 a and 217 b that charge and discharge based on a sense input terminal of the sensing circuit 203 ( e . g ., based on the sense and inverted sense input signals at inverters 219 and 221 , respectively ). as shown , current from a power rail charges capacitor 217 a through charge path 223 a ( e . g ., that includes resistor 225 and pass - gate 227 a ) and capacitor 217 b through charge path 223 b ( e . g ., that includes resistor 225 and pass - gate 227 b ) when their respective pass - gates 227 a and 227 b are activated ( e . g ., sense =“ 0 ”). in addition , capacitor 217 a discharges current to fuse unit cell 201 ( e . g ., at its inverted / reference bitline ( blb )) through discharge path 229 a ( e . g ., that includes pass - gate 231 a and resistor 233 a ), and capacitor 217 b discharges current to fuse unit cell 201 ( e . g ., at its bitline ( bl )) through discharge path 229 b ( e . g ., that includes pass - gate 231 b and resistor 233 b ) when their respective pass - gates 231 a and 231 b are activated ( e . g ., sense =“ 1 ”). by way of example , at sense falling edge , the two capacitors 217 a and 217 b may start to charge . at sense rising edge , the two capacitors 217 a and 217 b may stop charging , and start to discharge . in sense mode , fsource may be fixed to a ground rail , and program transistor 207 may be switched off . if , for instance , fu_row_rd is selected , transistors 213 and 215 will be switched on . thus , when pass - gates 229 a and 229 b are activated , current will discharge from capacitor 217 a to the ground rail through transistor 213 and reference resistor 211 , and from capacitor 217 b to the ground rail through transistor 215 and fuse 205 . in one scenario , the resistance of reference resistor 211 may be 1 . 4 kiloohms , the resistance of unblown fuse 205 may be 140 ohms , and the resistance of blown fuse 205 may be 5 kiloohms . as such , regardless of the state of fuse 205 ( e . g ., blown , unblown , etc . ), the discharging rates with respect to the currents from capacitors 217 a and 217 b will not be the same and , thus , there will be a timing skew between the clock input and the d input at flip - flop 235 ( e . g ., based on inputs received at inverter 237 a and 237 b ). for example , the rise of the d input will occur before the rise of the clock input when fuse 205 is unblown ( e . g ., causing dout to be “ 0 ”), and the rise of the clock input will occur before the rise of the d input when fuse 205 is blown ( e . g ., causing dout to be “ 1 ”). in this way , the fuse state of fuse unit cell 201 ( and fuse 205 ) may be ascertained regardless of whether fuse 205 is blown or unblown . in addition , compared with the traditional circuit in fig1 , the circuit in fig2 may significantly reduce power consumption as a result of decreases in the minimum sensing supply voltage and the sensing current ( e . g ., there may only be transient current at sense clock &# 39 ; s rising edge and falling edge ). furthermore , the circuit in fig2 may increase read cycle times since read frequency can be increased ( e . g ., no need for unnecessary pre - charging ), and reduce chip area requirements for sensing purposes ( e . g ., no need for additional pre - charge pins ). fig3 schematically illustrates waveform diagrams of various signals based on a fuse state , in accordance with various exemplary embodiments of the present disclosure . for example , diagrams 301 and 303 may reflect signals with respect to the circuit of fig2 , where diagram 301 depicts a scenario with fuse 205 being unblown , and diagram 303 depicts a scenario with fuse 205 being blown . in the scenario associated with diagram 301 , capacitors 217 a and 217 b may start to discharge as a result of the rising edge of the sense input , sense , at time 305 . because the resistance of unblown fuse 205 is less than the resistance of reference resistor 211 , the discharge rate of capacitor 217 a is less than the discharge rate of capacitor 217 b ( e . g ., as illustrated by signals a and b ). thus , the rise of the d input at flip - flop 235 will occur before the rise of the clock input at flip - flop 235 ( e . g ., the rise of the clock input will occur at time 307 ). consequently , the dout signal ( e . g ., the sense output signal ) will be “ 0 ,” indicating that the fuse state of fuse unit cell 201 is unblown . similarly , in the scenario associated with diagram 303 , capacitors 217 a and 217 b may start to discharge as a result of the rising edge of the sense input , sense , at time 309 . however , because the resistance of blown fuse 205 is greater than the resistance of reference resistor 211 , the rise of the clock input at flip - flop 235 will occur before the rise of the d input at flip - flop 235 ( e . g ., the rise of the clock input will occur at time 311 ). accordingly , the dout signal will be “ 1 ,” indicating that the fuse state of fuse unit cell 201 is blown . in addition , as shown in diagrams 301 and 303 , the timing skews between the d input and the clock input may vary ( e . g ., having timing skews of 125 ps and 260 ps , respectively ). nonetheless , the reliability and the accuracy of the indicated fuse state may remain unaffected by such variations ( e . g ., the indicated fuse state may be detected even when timing skews of as little as 20 ps ). therefore , as compared with the traditional circuit of fig1 , variations of process , voltage , temperature , etc ., may not have as much effect on embodiments of the present disclosure . the embodiments of the present disclosure can achieve several technical effects , including power consumption efficiency , smaller device sizes , and faster read cycle times . embodiments of the present disclosure enjoy utility in various industrial applications as , for example , microprocessors , smart phones , mobile phones , cellular handsets , set - top boxes , dvd recorders and players , automotive navigation , printers and peripherals , networking and telecom equipment , gaming systems , digital cameras , or any other devices utilizing logic or high - voltage technology nodes . the present disclosure therefore enjoys industrial applicability in any of various types of highly integrated semiconductor devices . in the preceding description , the present disclosure is described with reference to specifically exemplary embodiments thereof . it will , however , be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the present disclosure , as set forth in the claims . the specification and drawings are , accordingly , to be regarded as illustrative and not as restrictive . it is understood that the present disclosure is capable of using various other combinations and embodiments and is capable of any changes or modifications within the scope of the inventive concept as expressed herein .
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generally , the present invention provides the ability to seal chip / structures / wafers which enables mechanical stability of critical joined components and protects from outside environmental damage . the sealing procedure of the present invention for sealing stacked wafer or chips enables structures to be hermetically sealed at a chip / die level and also allows wafer - level sealing which will enable downstream full - wafer processing . furthermore , the sealing solution can also be utilized for electrical signal propagation and thermal dissipation or as a thermal conductor ( through sealant material itself or using sealant as a thermal structure for dissipation ). materials that can be used to seal together chips or wafers include : metals ( for example : cu — cu , au — au , etc . ); alloys ( such as : cu — sn , ausn , etc . ); solders ; dielectrics ( oxide - oxide ); conductive adhesives ( cu - loaded pastes ) and any combination thereof ( example indium - oxide ). more specifically , referring to fig1 a , for illustrative purposes , two silicon wafers 10 are shown . a first silicon wafer 10 a is positioned over a second silicon wafer 10 b . each silicon wafer may include a plurality of electrical elements fabricated using known semiconductor fabricating techniques on a top surface and / or in an upper layer of the wafer or a chip . further , the electrical elements can be connected to each other and to electrically conductive vias extending throughout the wafer or chip and / or a substrate portion of the wafer or chip forming multiple circuits to provide , for example , power , connectivity , or circuit logic . the first silicon wafer 10 a includes a silicon layer 14 a and an oxide layer 18 a . similarly , the second silicon wafer 10 b includes a silicon layer 14 b and an oxide layer 18 b , in mirror image relationship to the first silicon wafer 10 a . further , the first silicon wafer 10 a includes a copper ( cu ) plated bond pad 22 a , and the second silicon wafer 10 b also includes a copper ( cu ) plated bond pad 22 b . the bond pads 22 a and 22 b are positioned in mating relationship to each other . referring to fig1 b , the first silicon wafer 10 a and second silicon wafer 10 b are bonded together at a bonded area 26 using the copper plated bond pads 22 a , 22 b of silicon layers 14 a , 14 b . the bonded area 26 formed by compressing the first and second silicon wafer 10 , 10 b together . heat is also applied to the bonded area 26 to form the bond and seal the wafers 10 a , 10 b together . thus , the first and second silicon wafers 10 a , 10 b are positioned in mating relation , as shown in fig1 a , and the cu plated bonding pads 22 a , 22 b are mated together and sealed by using compression and heat . the bonded structure is preferably hermetically sealed , i . e ., an airtight seal , which is intended to secure against the entry of unwanted particles and elements to maintain the quality of the electrical components and circuitry in the bonded structure . other material may be used other than cooper to accomplish the sealing bond . further , the seal prevents corrosion from atmosphere ( humidity or temperature ) or foreign materials ( contamination ) and wet chemistry reaction and plasma damage from beol / packaging processes . referring to fig2 , a silicon wafer 100 is shown having a plurality of integrated circuits ( ics or chips ) 104 positioned on a planar surface area 102 of the wafer 100 . each of the chips 104 includes a bonding material 108 forming a perimeter on a planar surface area 105 of the chip 104 . the wafer 102 also has bonding material 112 forming a perimeter on the planar surface area 102 . in the embodiment of the invention shown in fig2 , the bonding material is copper , however , other suitable electrically conductive or non - conductive materials may be used . it is understood , that the chip and wafer perimeters formed by the bonding materials 108 , 112 , respectively , may begin from outer edges 106 , 101 , respectively , and extend radially inwardly from the outer edges along the planar surface areas 105 , 102 , respectively , of the chips 104 and the wafer 100 . further , the chip and wafers perimeters formed by the bonding materials 108 , 112 can also be adjacent , offset , or in spaced adjacency from the outer edges 106 , 101 , respectively . the chips 104 also include dummy bonding pads ( pads , support columns / pillars ) 116 ( shown in fig2 ), which may be made of copper or other suitable materials . the pads or copper pad ( support columns / pillars ) 116 are structures without any electrical connection , but have a specified position on the planar surface area 105 of the chip 104 and a specified height to contact mating pads on a chip ( not shown ) to be fitted over the chip 104 shown in fig2 . the mating pads then form a structural column or support column ( or pillar ) in a sealed bonded structure of wafers or separate chips . the mating pads can also be bonded together when the wafer of chip is mated , thus forming a bonded support column . the mating pads 116 help support the wafer when stacked with other wafers , as will be discussed herein referring to fig3 c . referring to fig3 a and 3b , a pair of chips 200 are shown in mirror image relation . a first chip 200 a and second chip 200 b each have planar surface areas 204 a , 204 b , respectively . bonding materials 206 a , 206 b , respectively , define perimeters around the surface areas 204 a , 204 b , respectively , on the first and second chips 200 a , 200 b . as discussed in relation to fig2 , the bonding material may be cooper , as well , as other suitable materials . the perimeters defined by the bonding materials 206 a , 206 b extend inwardly along the planar surface areas 204 a , 204 b , respectively , from outer edges 202 a , 202 b , respectively . the chips 200 a , 200 b also include dummy bonding pads 208 a , 208 b , respectively ( similarly to the chips 104 shown in fig2 ), which may be made of copper or other suitable materials as discussed in regard to pads 116 on chip 104 in fig2 . similarly to chip 104 shown in fig2 , the pads 208 a , 208 b shown in fig3 a , 3 b are structures without any electrical connection , but have a specified position on the planar surface areas 204 a , 204 b of the chips 200 a , 200 b , respectively . the bonding pads 212 a , 212 b may be placed in a geometric pattern , as shown in fig3 a and 3b , but also may be placed in any pattern , or non - pattern desired , or in any quantity desired . each of the pads 208 a on chip 200 a have a specified height to contact mating pads 208 b on chip 200 b when the chips 200 a , 200 b are placed in overlapping relation and bonded as shown in fig3 c . the pads 208 a , 208 b coupled ( or bonded or fused ) together form mated pads 220 or structural columns , show in fig3 c , in the bonded chip structure 250 , as shown in fig3 c . further , the bonded chip structure 250 comprises a bonded perimeter 216 consisting of bonding material 206 a and bonding material 206 b mated together . in the bonded chip 250 ( shown in fig3 c ), the bonding material 206 a , 206 b shown in fig3 a and 3b are affixed together to form a seal 216 around the perimeter of the bonded chip 250 . the forming of the seal 216 includes compressing the bonding material together and heating the bonding material . other methods of forming the seal are also contemplated and within the scope of the present invention . the seal 216 stops unwanted entry of , for example , materials , substances , or debris into the bonded chip 250 , i . e ., between the chips 300 a and 300 b . referring to fig3 c , the wafers 200 a , 200 b are shown bonded together as a bonded chip structure 250 , in cross - section , so that the mated pads or structural columns 220 are shown . the mated pads or structural columns 220 are the pads ( or dummy pads ) 212 a on first wafer 200 a and second wafer 200 b mated together . the dummy pads mated together to form structural columns 220 provide strength to the bonded wafer 250 . the pads 220 help support the surface areas 204 a and 204 b of the first and second wafers 200 a , 200 b , respectively . the surface areas 204 a , 204 b have an inherent weight , and thus there are axial forces 252 across the surface areas 204 a , 204 b perpendicular to the “ x ” axis 253 a and along the “ y ” axis 253 b . more particularly , the axial forces 252 are from , for example , the inherent weight of the surface areas 204 a , 204 b of the first and second wafers 200 a , 200 b due to gravitation forces , or axial force ( or pressure ) from the weight of other chips ( or wafers ) stacked on the bonded chip 250 . the structural columns 220 provide support along the surface areas 204 a , 204 b of the first and second chips 200 a , 200 b , respectively , to support the axial forces . more specifically , when additional chips are stacked over each other , additional axial forces from the weight of additional chips bear down ( along the “ y ” axis 253 b ) on the outer top surface 256 of the bonded wafer 250 . further , the mated pads / structural columns 220 help to stabilize the bonded wafer 250 against torsional forces ( or stresses ), which may occur in the processing or fabricating of the wafer or from disproportionate weight distribution from stacking other chips ( or wafers ) over one another such that twisting or bending occurs along the surface areas 204 a , 204 b of the chips 200 a , 200 b . if torsional stresses are applied to the bonded chip 250 , the torsion causes twisting of the bonded chip 250 that may result in shearing stress which are perpendicular to surface areas 204 a , 204 b ( in the “ y ” direction 253 b ). thus , in one example , the structural columns may be positioned on the surface area of a chip or wafer in an area unpopulated by other components to effectively distribute axial and torsional forces throughout the chip or wafer during processing . distribution of forces throughout the chip or wafer lessens the force in one particular area and thereby reduces the stress in that area lessening the likelihood of a stress related fracture or break in the chip or wafer structure . also , the support columns reduce possible stresses from torsion and axial loads on the seal . further , an uncompromised seal ( preferably a hermetic seal ) about each chip or wafer prevents , for example , liquid and gas etchants / corrosives and particulate materials from ingressing into areas which will be damaged by such ingress . it is understood that a chip or wafer may have multiple electrical reference layers connected by vertical vias ( not shown ). the dummy pads , for example , as described in relation to fig3 a - 3c , can be positioned between layers in the chip or wafer to provide support between the layers , as well as providing support between the chips or wafers themselves . referring to fig4 a and 4b , wafers 300 a , 300 b , respectively , include a plurality of chips 304 positioned on surface areas 302 a , 302 b . the surface areas of the wafers 300 a , 300 b include bonding material 312 forming a perimeter around the wafers 300 a , 300 b with a thickness 320 ( shown in fig4 d ) starting from the edge of the wafers 301 a , 301 b and extending inwardly on the surface areas 302 a , 302 b of the wafers 300 a , 300 b . the chips 304 on the surface areas 302 a , 302 b of the wafers 300 a , 300 b include dummy pads 208 a , 208 b as depicted in more detail in fig3 a and 3b , and described above . further , the chips 304 on wafers 300 a , 300 b include bonding material 206 a , 206 b , respectively , defining a perimeter around the chip 304 as shown in more detail in fig3 a and 3b , and described above . wafers 300 a and 300 b are combined by positioning one wafer over the other to form bonded wafer 350 , shown in fig4 c . in the bonded wafer 350 , the bonding material 312 shown in fig4 a and 4b are affixed together to form a seal 312 around the perimeter of the bonded wafer 350 . the forming of the seal includes compressing the bonding material 312 between the wafers 300 a , 300 b and heating the bonding material 312 to form the bonded seal 316 . the bonded seal 316 stops unwanted entry of , for example , materials , substances , or debris into the bonded wafer 350 , i . e ., between the wafers 300 a and 300 b . referring to fig4 d , a cross - section of the combined wafers 350 is shown along line x - x to show the bonded seal 316 , resulting from bonding together of bonding material 312 on each wafer 300 a , 300 b , extending inwardly from the edges 301 a and 301 b of the wafers 300 a , 300 b . the bonded seal 316 around the perimeter of the wafer 350 is shown in fig4 d . while the present invention has been particularly shown and described with respect to preferred embodiments thereof , it will be understood by those skilled in the art that changes in forms and details may be made without departing from the spirit and scope of the present application . it is therefore intended that the present invention not be limited to the exact forms and details described and illustrated herein , but falls within the scope of the appended claims .
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referring to fig1 - 3 of the drawings , a welding assembly 10 can be seen having a mounting base 11 and a back plate 12 , shown in broken lines . a support carriage 13 is movably positioned on the block plate by multiple linear bearing assemblies 14 on respective bearing races 15 . the welding assembly has a power welder 16 secured within the support carriage 13 . the power welder 16 has a servo motor 17 , connected to a gear reducer 18 by a motor adapter 19 . the gear reducer 18 has a spindle assembly 20 with an attached driver 21 , best seen in fig1 and 2 of the drawings which will be discussed in greater detail hereinafter . the carriage 13 is movable in a vertical plane by a piston and cylinder assembly 22 secured to the back plate 12 . a piston rod 23 extends from the piston and cylinder assembly 22 and is secured to the movable carriage assembly as will be well understood by those skilled in the art . the servo motor 17 is of a three phase electrical servo positioning motor , the type manufactured by emerson under model no . dxm6200 having the ability to accelerate from a forced stop position to maximum r . p . m . in a fraction of a second and to de - accelerate to the force stop position just as rapidly . such servo motors 17 are characterized by their ability to constantly start and spin and stop within six arc seconds of a predetermined position which is critical to the method of the invention and weld characteristics of the thermoplastic parts disclosed herein . the output of the servo motor 17 is connected to the gear reducer 18 by the adapter 19 that mechanically interconnects therebetween . the gear reducer 18 is commercially available at model ato14 - 003 which is a 3 to 1 gear reduction manufactured by micron instrument corporation using multiple planet gears revolving around a single true &# 34 ; sun &# 34 ; gear well known to those skilled in the art . referring now to fig3 of the drawings , the driver 21 can be seen having a parts engagement fixture 24 secured thereto . the fixture 24 is simplified for illustration purposes and would be of a custom design for each part configuration to be joined as is typical in the art . a fixed base part fixture 25 is illustrated with pre - positioned thermoplastic parts 26 and 27 therein to be joined together . the parts 26 and 27 have abutting joining surfaces . in use , the power welder assembly 10 defines a unique welding method that first positions and holds the thermoplastic parts 26 and 27 together , then applies sufficient pressure to build up substantial energy in the process before the spindle 20 and associated driver 21 and fixture 24 actually turns . the position of the movable carriages 13 is physically controlled by the piston and cylinder assembly 22 in combination with carriage positioning sensors 28 and input control activation commands from a pre - programmed c . p . u . ( central processing unit ) interconnected to the power welder assembly 16 . torque is applied to the thermoplastic parts by the output of the servo motor 17 responding to the input control activation commands from the c . p . u . in accordance with its pre - programmed instructions in combination with input from the positioning sensor 29 within the driver 21 . referring now to fig5 of the drawings , a time line activation graph 30 is illustrated that indicates a typical activation time for the servo motor 17 to effect a power weld between the thermoplastic parts 26 and 27 as hereinbefore described . the graph 30 has time lines 31 and 32 in micro - seconds and second respectively with acceleration ( a ) indicated at 33 , and de - acceleration ( da ) illustrated at 34 ( in milliseconds ) and hold time ( h ) illustrated at 35 ( in seconds ) before joined parts are released . the critical element of thermoplastic welding is to achieve a weld temperature between the parts as rapidly as possible , illustrated by the acceleration bar 33 and the de - accelerate before the formed weld joint begins to set up ( cools ) that occurs as the parts de - accelerate illustrated by the de - acceleration bar 34 . the precise controlling of the acceleration and de - acceleration of the motor 17 is achieved by the hereinbefore described ability of the servo motor 17 that is controlled by the pre - programmed c . p . u . with feedback from positioning sensor 29 achieving &# 34 ; stop &# 34 ; position of the driver 21 and fixture 24 in a consistent and repeatable fashion . the resulting weld between the joined parts is characterized by high consistence with little or no flashing thereabout . referring now to fig4 of the drawings , a comparison graph of effective rotational duration of prior art spin welding to the method of the invention is illustrated . graphic arrows 36 illustrate the typical ( minimum ) rotational revolution required by prior art spin welding that is currently possible at three - quarter of a revolution to achieve welding . the graph arrow 37 illustrates the method of the invention where an efficient superior welding can be achieved in as little as one - third of a rotation . the rotational difference ( rotational time rt ) of less than half illustrated is demonstrative of other time rotational differences achieved in more than a full rotation in which the method of the invention will always achieve a reduced rotational difference and correspondingly reduced weld time ( t ) to achieve a superior quality weld , thus duration of weld cycle is reduced and production is increased . it will be apparent to those skilled in the art that various changes and modifications may be made therein without departing from the spirit of the invention .
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hereinafter , embodiments of the bump forming method and apparatus according to the present invention will be explained with reference to the drawings . [ 0036 ] fig1 is a plan view for showing a bump ball arranging and compression - bonding system for implementing the bump ( ball ) forming method as an embodiment of the present invention . in the figure , reference numeral 1 indicates a cassette platform , reference numeral 2 indicates a transfer robot , reference numeral 3 indicates a positioning table , reference numeral 4 indicates a cross arm , reference numeral 5 indicates an alignment unit , reference numeral 6 indicates a bonding head ( i . e ., a bump forming apparatus ), and reference numeral 7 indicates a control panel for controlling the above elements . the cassette platform 1 is a dedicated platform for setting a wafer cassette in which a plurality of silicon wafers ( i . e ., semiconductor substrates , where the silicon wafer may be simply called the wafer , hereinbelow ) are contained . the transfer robot 2 has a mechanism for extracting each wafer from the wafer cassette set on the cassette platform 1 in turn , inverting the position of the wafer by 180 ° in the vertical direction , and then setting this inverted wafer at a specific position on the positioning table 3 . the positioning table 3 is provided for defining the direction of an orientation flat or a notch of the wafer and for determining the position of the wafer to be held . the cross arm 4 has a rotation shaft 11 which is vertically positioned , four arms 12 a to 12 d horizontally and radially extending from the rotation shaft 11 , and wafer holding pads 13 a to 13 d , respectively attached to the heads of the arms 12 a to 12 d , each pad having an adjustment mechanism for attracting and holding a wafer and moving the wafer in the θ direction ( i . e ., the direction of the angle of rotation ) and in the z direction ( i . e ., the vertical direction ). the wafers , respectively held by the wafer holding pads 13 a to 13 d , are transferred by clockwise rotating the arms 12 a to 12 d around the rotation shaft 11 . the wafer holding pads 13 a to 13 d also function as a pressing device for compressing bump balls 22 ( explained below ) via a wafer . the alignment unit 5 is provided for performing alignment ( relating to parallelability and position ) of the wafer 17 transferred from the positioning table 3 by using the cross arm 4 . as shown in fig2 the bonding head 6 is a bump forming apparatus for forming bumps on pads provided at predetermined positions on a surface ( i . e ., a main surface ) of a wafer . the bonding head 6 has a double - plate structure consisting of a heater plate 21 ( i . e ., a heating device ) and a bump ball arrangement plate 23 ( i . e ., a positioning member ) for arranging bump balls 22 ( i . e ., bump materials ). the bonding head 6 also includes an ionizer 24 ( i . e ., an electrostatic charge dissipating device ), an ultrasonic generator 25 ( i . e ., an ultrasonic oscillating device ), and an air blower 26 ( i . e ., a bump ball arranging device ). the main body of the heater plate 21 is a flat plate 31 ( i . e ., a plate body ) made of , for example , ( i ) metal such as titanium ( ti ) or stainless steel , which has high heat resistance , or alloy of such metal , ( ii ) semiconductor material such as silicon ( si ), or ( iii ) ceramics such as silicon carbide ( sic ) or aluminum nitride ( aln ). the top face 31 a ( i . e ., a main surface ) of the plate 31 is polished so as to function as a heating surface for heating the bump balls 22 . in addition , a temperature sensor for measuring the temperature of the top face 31 a and a heater ( i . e ., a heating source ) are provided in the heater plate 21 , where this heater is controlled by using the control panel 7 . at each of the four corners of this plate 31 , a through hole 32 for inserting a movable shaft 35 ( explained below ) is formed in the vertical direction , where the diameter of the through hole 32 is slightly larger than that of the movable shaft 35 . the bump ball arrangement plate 23 is arranged above the heater plate 21 and in parallel to the heater plate 21 . the main body of the bump ball arrangement plate 23 is a flat plate 33 ( i . e ., a plate body ) which has substantially the same shape of the above - explained plate 31 and which is also made of , for example , ( i ) metal such as titanium ( ti ) or stainless steel , which has high heat resistance , or alloy of such metal , ( ii ) semiconductor material such as silicon ( si ), or ( iii ) ceramics such as silicon carbide ( sic ) or aluminum nitride ( aln ). the top face 33 a ( as a main surface ) of the plate 33 is polished , and holes 34 for positioning the bump balls 22 are formed at predetermined positions on the top face 33 a ( in fig2 only one hole 34 is shown ). the thickness of the plate 33 is less than the maximum diameter of the bump balls 22 , and the diameter of each hole 34 is slightly larger than the maximum diameter of the bump balls 22 . for example , when the maximum diameter of the bump balls 22 is 50 μm , the thickness of the plate 33 is 25 to 30 μm , and the diameter of the hole 34 is 55 μm . at each of the four corners of the plate 33 , the head of the movable shaft 35 is fastened by using a fastening member such as a bolt 36 . the space between the bottom face 33 b of the plate 33 and the top face 31 a of the plate 31 can be adjusted by moving the movable shaft 35 in the vertical direction . more specifically , a specific space such as 15 to 25 μm can be secured . the plate 33 also has a pull mechanism ( not shown ) for pulling the plate 33 from every corner and holding the plate so as to prevent the plate 33 from warping when the bump balls 22 are disposed on the plate 33 . in another method for preventing a warp of the plate 33 , the bump balls may be supplied little by little , that is , continuously or intermittently . the ionizer 24 is a device for dissipating electrostatic charge produced around the bump balls 22 , so as to prevent a small number of supplied bump balls from being attracted to each other due to electrostatic charge produced by the contact between the supplied bump balls . the ultrasonic generator 25 is used for generating ultrasonic waves at a contact surface between each bump ball 22 and the corresponding pad 37 on the wafer when the bump ball 22 is compression - bonded on the pad 37 . according to the generated ultrasonic waves , a resonant state is produced in the vicinity of the contact surface , thereby improving the contact strength between the bump ball 22 and the pad 37 . the air blower 26 is used for inserting bump balls 22 , supplied onto the top face 33 a of the plate 33 , into all the positioning holes 34 and collecting extra bump balls 22 which have not inserted into the holes 34 . these operations are performed by moving the shaft 27 of the air blower 26 in a direction above the top face 33 a of the plate 33 ( see the arrows in fig2 ). here , a dedicated brush or the like may be used instead of the air blower 26 , so as to insert the bump balls 22 into all the positioning holes 34 . below , the bump ball forming method as an embodiment of the present invention will be explained with reference to fig1 to 5 . first , a wafer cassette , in which wafers are contained , is set on the cassette platform 1 . in the next step , a wafer is extracted from the cassette stage by using the transfer robot 2 , which inverts the wafer by 180 ° in the vertical direction and transfers the inverted wafer onto the positioning table 3 , so as to set the wafer at a predetermined position on the positioning table 3 . on the positioning table 3 , the direction of an orientation flat or a notch of the wafer is defined , and the position of the wafer to be held is determined . each wafer , whose direction of an orientation flat or a notch has been defined , is held by the wafer holding pads 13 a to 13 d of the cross arm 4 in turn . the cross arm 4 can efficiently transfer the wafers by clockwise rotating the arms 12 a to 12 d around the rotation shaft 11 . for example , the wafer held by the wafer holding pad 13 a is transferred and set to the alignment unit 5 by clockwise rotating the arm 12 a around the rotation shaft 11 . the alignment unit 5 performs alignment ( relating to parallelability and position ) of the wafer . during the alignment , bump balls 22 are arranged at the bonding head 6 , so that the bump balls 22 are in a stand - by state . the method of arranging the bump balls 22 will be explained below . first , as shown in fig2 the bump ball arrangement plate 23 is moved upward by moving upward the movable shafts 35 attached at the four corners of the plate 33 , so that the space between the bottom face 33 b of the plate 33 and the top face 31 a of the plate 31 is set to a predetermined value , for example , 15 to 25 μm . in the next step , the bump balls 22 are supplied onto the bump ball arrangement plate 23 . here , in order to prevent the bump balls 22 from being attracted to each other by electrostatic charge , the electrostatic charge produced around the bump balls 22 is dissipated in advance by using the ionizer 24 . next , the shaft 27 of the air blower 26 ( or a dedicated brush or the like ) is moved along a direction ( see the arrows in fig2 ) above the top face 33 a of the plate 33 , so that the bump balls 22 , from which electrostatic charge has been dissipated , are inserted into all the positioning holes 34 , and simultaneously , extra bump balls 22 on the plate 33 are collected at the edge of the plate 33 . in the next step , the movable shafts 35 are moved downward so as to move the bump ball arrangement plate 23 downward , thereby making the bottom face 33 b of the plate 33 contact the top face 31 a of the plate 31 . accordingly , an upper end portion ( as a face to be compressed and bonded ) of each bump ball 22 , inserted in the positioning hole 34 , protrudes from the upper end of the hole 34 ( see fig3 ). in the following step , as shown in fig4 the cross arm 4 is operated so as to attract a wafer , for which the alignment ( relating to parallelability and position ) has been completed , by the wafer holding pad 13 a . the attracted wafer 17 is moved to the origin ( i . e ., defined as the home position ) above the top face 33 a of the plate 33 and is then lowered so as to make each bonding pad 37 , which is attached to the bottom face 17 a of the wafer 17 , contact the upper end of the corresponding bump ball 22 . in the next step , as shown in fig5 the plate 31 is heated to , for example , 150 to 250 ° c . by using the built - in heater while the wafer 17 is pressed with a predetermined pressure by the wafer holding pad 13 a . accordingly , each bump ball 22 is softened and simultaneously pressed and deformed so that the bump ball 22 is transformed into a bump 38 which has a specific shape matching the shape of the corresponding hole 34 . accordingly , bumps 38 are compression - bonded onto the bonding pads 37 provided on the bottom face 17 a of the wafer 17 by a single compressing and heating operation . when ultrasonic waves are generated at a contact face between each bump ball 22 and the bonding pad 37 by using the ultrasonic generator 25 in the compressing and heating operation , a resonant state can be produced in the vicinity of the contact face , thereby improving the contact strength between the bump ball 22 and the bonding pad 37 . the wafer 17 , on which the bumps 38 are bonded , is returned to the origin position by raising the wafer holding pad 13 a and is then transferred to the positioning table 3 by rotating the cross arm 4 . the wafer holding pad 13 a is then lowered so that the wafer 17 is put on the positioning table 3 . the wafer 17 is held by the transfer robot 2 again . this wafer 17 is inverted by 180 ° in the vertical direction and is then stored into the wafer cassette set on the cassette platform 1 . as explained in detail above , according to the bump ball forming method of the present embodiment , the bump balls 22 , from which electrostatic charge has been dissipated , are inserted into the positioning holes 34 on the bump ball arrangement plate 23 . therefore , in comparison with the conventional case of attracting bump balls , holding and positioning of the bump balls can be more easily performed . in addition , the plate 31 is heated to a predetermined temperature by using a built - in heater while the wafer 17 is pressed with a predetermined pressure by using the wafer holding pad 13 a , so that each bump ball 22 is softened and simultaneously pressed and deformed and that the bump ball 22 is transformed into a bump 38 having a specific shape . therefore , the bumps 38 , each having a specific shape , can be formed by a single compressing and heating operation ; thus , no bump ball 22 has an abnormal shape which requires an operation for correcting the shape . accordingly , it is possible to reduce the time for performing the bump forming process and also reduce the manufacturing cost . according to the bump ball arranging and compression - bonding system in the present embodiment , the bonding head 6 has a double - plate structure consisting of the heater plate 21 and the bump ball arrangement plate 23 for arranging the bump balls 22 . therefore , the holding and positioning operation of the bump balls can be easily performed , thereby reducing the time necessary for the bump forming process and also reducing the manufacturing cost . in addition , the ionizer 24 is provided . therefore , when the bump balls 22 are supplied onto the bump ball arrangement plate 23 , electrostatic charge produced by the contact between the bump balls 22 can be dissipated . accordingly , it is possible to prevent the bump balls from being attracted to each other . additionally , the ultrasonic generator 25 is provided . therefore , ultrasonic waves can be generated at a contact face between each bump ball 22 and the bonding pad 37 , thereby producing a resonant state in the vicinity of the contact face and improving the contact strength between the bump ball 22 and the bonding pad 37 . furthermore , in another method of securing a predetermined space between the bump ball arrangement plate 23 and the heater plate 21 , the bump ball arrangement plate 23 has a first magnetic material and the heater plate 21 has a second magnetic material , so that a predetermined space is secured between the bump ball arrangement plate 23 and the heater plate 21 which face each other , according to repulsive force produced by the first and second magnetic materials .
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[ 0023 ] fig1 a to 1 c are three perspective views 10 a , 10 b and 10 c , respectively , of a portion of a telescoping tip electrode catheter 11 with a steerable portion 14 of the main catheter body 16 just proximal of the telescoping tip portion 18 according to an embodiment of the present invention . more particularly , fig1 a shows the catheter 12 including a main body portion 16 and a telescoping tip portion 18 . the telescoping tip portion of this fig1 a also shows the tip electrode 20 . fig1 b shows the steerable portion 14 of the main catheter body 16 just proximal of the telescoping tip portion 18 . the portion 18 includes a partially extended mandrel 22 which extends from and retracts to the main catheter body 16 and to which the telescoping tip electrode 20 attaches . fig1 c shows the steerable portion 14 engaged in a curve with a greater degree of curvature than the catheter portion 10 b and the mandrel 22 extended to a greater length than the mandrel 22 in the catheter portion 10 b . in alternative embodiments of the present invention , the tip electrode 22 can be retracted inside the catheter main body 16 rather than being external to the catheter main body 16 when the mandrel 22 is retracted to its full extent . [ 0024 ] fig2 is a side view of the handle portion 30 and the distal portion of the catheter main body 16 including the telescoping tip electrode 20 and the steerable portion 14 of the catheter main body 16 according to the fig1 a to 1 c embodiments . the handle portion 30 includes a slider mechanism 32 which operates the telescoping tip 18 . the mechanism 32 moves in increments along the longitudinal axis of the catheter 10 and is connected in the interior ( not shown ) of the catheter 10 to the mandrel 22 for the telescoping tip 20 . movement of the slider mechanism 32 in either direction similarly causes the mandrel 22 to move in the same direction in order to extend or retract the tip electrode 20 . for example , movement of the slider mechanism 32 proximally causes the mandrel 22 and the tip electrode 20 to retract and movement of the slider mechanism 32 distally causes the mandrel 22 and the tip electrode 20 to extend . the mechanism 32 can also be manipulated to cause partial movement of the mandrel 22 and tip electrode 20 so that partial extension at varying lengths of the tip electrode 20 can be achieved . a slider mechanism which can be used for an embodiment of the present invention is also disclosed in u . s . pat . no . 6 , 178 , 354 , to charles gibson arid issued on jan . 23 , 2001 , which is incorporated herein in its entirety by reference . the handle portion 30 also includes a thumbwheel 34 which operates the steerable portion 14 of the catheter main body . the thumbwheel 34 and operation of the steerable portion 14 is described in u . s . pat . no . 5 , 611 , 777 , to bowden et al . and issued on mar . 18 , 1997 , which is incorporated herein in its entirety by reference . the handle portion 30 also connects to a generator device 36 which is proximal of the portion 30 . the generator device portion 36 is used in a conventional manner to connect to a wire which carries power to the tip electrode 20 . such device 36 and operation is well known to those of ordinary skill in the art and therefore will not be further described herein . [ 0025 ] fig3 is an exploded perspective view of the telescoping tip electrode 20 according to the fig1 a to 1 c embodiments . in this embodiment , a bipolar electrode 20 is used , including three interlocking portions 38 , 40 and 42 . portions 38 and 42 provide an elliptical shape to the electrode 20 and are the conducting portions . portion 40 can be an electrical insulation . exemplary materials for the construction of the electrode 2 are platinum , platinum / iridium or gold , etc . an exemplary size of the electrode 20 is 9 french with a length which can vary between about 4 to 8 mm . in alternative embodiments , the electrode 20 size can be smaller than the outer diameter of the main catheter body 16 so that the electrode 20 can retract inside the catheter 10 . in further alternative embodiments , the electrode 20 can be a split electrode or any other type of shape ( e . g ., square , rectangular or circular ) electrode 20 operable to treat tissue in a cardiac or arterial passageway . [ 0026 ] fig4 is a first partial cross sectional view of the telescoping tip electrode 20 according to the fig1 a to 1 c embodiments . the electrode 20 includes conductors 44 and 46 which provide power to the portions 38 and 42 . conductors 44 and 46 extend through the mandrel 22 to the generator device 36 ( shown in fig2 ). also shown is a soldering bonding junction 48 between the electrode 20 and the mandrel 22 . [ 0027 ] fig5 is a second partial cross sectional view of the telescoping tip electrode 22 according to the fig1 a to 1 c embodiments . shown are a temperature sensor 50 and circumferential grove 52 around the electrode 20 for sensor placement . the soldering junction 48 is also shown between the electrode 20 and the mandrel 22 . referring also to fig1 c and 2 , an exemplary material for the mandrel 22 is nitinol , mp35n and sst . in alternative embodiments , where the mandrel 22 is not the electrical conductor , the material choices can be expanded to include non - conductive plastics that are durable but flexible , such as polyimide , peek or nylon , etc . in one embodiment , the length of the mandrel 22 and telescoping tip 20 portion 18 which extends or retracts from the main catheter body 16 can range in length from greater than 0 cm to about 6 cm or more in length . the diameter of the mandrel 22 can be 7 french for example . in alternative embodiments , the mandrel 22 diameter can be just smaller than the inner diameter of the main catheter body 16 shaft . [ 0028 ] fig6 is a side view of the telescoping tip portion 18 including the mandrel 22 on which the telescoping tip electrode 20 is mounted ( not shown ) and the portion of the catheter main body 16 just proximal of the telescoping tip portion 18 according to the fig1 a to 1 c embodiments . the portion of the main catheter body 16 includes a bonding area 60 in which the mechanisms to add in the steerability of the catheter 10 reside . also shown in this embodiment is a ring electrode 62 for use in bipolar recordings , as is conventional . fig7 is a partial cross section of the proximal portion of the main catheter body 16 according to the fig1 a to 1 c embodiments which shows the bonding area 60 in more detail . more particularly , the area 60 includes a steering anchor 64 and a threaded core assembly 66 for use in controlling the steerable portion 14 of the main catheter body 16 . [ 0029 ] fig8 is a partial cross section of the telescoping tip electrode catheter 10 showing the steering cables 70 and 72 for the steerable catheter portion 14 . in this embodiment , the steerable portion 14 is located proximal of the distal end of the main catheter body 16 . however , in alternative embodiments , the steerable portion 14 can extend to the distal end of the catheter main body 16 . curve directional arrows 74 show the potential direction of curvature for the steerable portion 14 in this embodiment . also shown is mandrel 22 extending through the main catheter body 16 to connect to the slider mechanism 32 , as described in u . s . pat . no . 6 , 178 , 354 , as cited above . [ 0030 ] fig9 is a partial cross section of the telescoping tip electrode catheter 10 showing the steering cables 70 and 72 and the steerable catheter portion 14 engaged in a curve 76 according to the fig1 a to 1 c embodiments . [ 0031 ] fig1 is a perspective view of the telescoping tip electrode catheter 10 with the steerable portion 14 engaged in a curve and the telescoping tip 20 being extended and contacting a treatment site 78 according to the fig1 a to 1 c embodiments . as a result of the curvature in the steerable portion 14 , additional pressure is applied to the electrode 20 to improve the contact between the electrode 20 and the treatment site 78 .
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reference will now be made in detail to the preferred embodiments of the present invention , examples of which are illustrated in the accompanying drawings . fig5 a is a plan view of an exemplary laser head according to the present invention , and fig5 b is a plan view showing an exemplary laser pixel of the laser head of fig5 a according to the present invention . in fig5 a and 5b , a laser head 160 may have about 224 laser pixels 162 arranged along a line , wherein each of the laser pixels 162 may have a length l of about 5 μm to about 20 μm and a width w of about 3 μm to 5 μm . of course , the laser pixel 162 may have a different size , i . e ., larger or smaller , than the laser pixels 162 when the power of each of the laser pixels 162 is considered . for example , an entire size of the laser pixels 162 within the laser head 160 may be about 4480 μm by about 31 m , and a scan width of the laser head 160 may be about 4480 μm . the laser pixels 162 of the laser head 160 may be automatically operated by a computer system such that each of the laser pixels 162 turn on and off according to red , green , and blue color filter patterns . fig6 is a cross sectional view of an exemplary color transcription film according to the present invention . in fig6 , a color transcription film 110 may include three layers : a supporting film 110 a ; a light - to - heat conversion ( lthc ) layer 110 b ; and a color filter layer 110 c . the supporting film 110 a , which may support the lthc layer 110 b and the color filter layer 110 c , may include a high molecular substance , such as polyester and polyethylene , having transparent and high transmittance characteristics in order to transmit a laser beam to the lthc layer 110 b . the lthc layer 110 b may be formed on the supporting film 110 a and may be made of a material that can efficiently convert light into heat energy . accordingly , the lthc layer 110 b may convert light energy from a laser head into heat energy . the lthc layer 110 b may include an organic material , such as carbon black and ir ( infrared ) pigments , or an inorganic material , such as a metal material ( i . e ., aluminum ( al ), metallic oxide , or alloy of the above materials ). the color filter layer 110 c , which may be the layer to be transferred , may be formed on the lthc layer 110 b and may include one of red , green , and blue colors . fig7 a to 7 e are cross sectional views of an exemplary method of fabricating a color filter substrate according to the present invention . here , a color filter substrate of fig7 a to 7 e shows pixels along a line having the same color , for example red , and for convenience of explanation , a laser head may be illustrated to be shortened as compared with a region between black matrixes of a substrate . in fig7 a , a black matrix 105 may be formed on an insulating substrate 100 by depositing a metal material , such as chromium ( cr ), or coating a resin , such as an epoxy . then , the metal material or resin may be patterned through photolithographic processes . in fig7 b , a first color transcription film 120 , which may include a supporting film 120 a , a light - to - heat conversion ( lthc ) layer 120 b , and a color filter layer 120 c , may be disposed over the substrate 100 including the black matrix 105 with the color filter layer 120 c facing the substrate 100 . the first color transcription film 120 may be adhered to the substrate 100 without bubbles , and a laser head 160 may be disposed at a distance over the first color transcription film 100 . then , a laser beam of the laser head 160 may be applied to the first color transcription film 120 in a portion where a first color filter pattern will be formed later as the laser head 160 scans the substrate 130 by reciprocating the laser head 160 along a straight line or moving a stage fixing the substrate 100 thereon along a straight line . in the first color transcription film 120 exposed to the laser beam , the lthc layer 120 b may transform light absorbed from the laser beam into thermal energy , thereby emitting thermal energy . then , the color filter layer 120 c may be transferred onto the substrate 100 due to the emitted thermal energy . in fig7 a to 7 e , the color filter substrate may be a stripe - type , wherein color filter patterns along a line may have the same color . accordingly , a first line may be exposed to the laser beam by moving the laser head along a straight line . however , second and third lines may be skipped . similarly , a fourth line may be exposed to the laser beam . in this manner , all the lines of the first color filter pattern may be exposed . after a first scan , one of the substrate 100 and the laser head 160 is transferred , and the second , third , and fourth scans may be sequentially performed . in fig7 c , the first color transcription film 120 ( in fig7 b ) may be removed after the whole substrate 100 is scanned . here , the color filter layer 120 c corresponding to the lthc layer 120 b exposed to the laser beam may be transferred onto the substrate 100 , while the color filter layer 120 c corresponding to the lthc layer 120 b not exposed to the laser beam may be removed together with the color transcription film 120 ( in fig7 b ). accordingly , a first color filter pattern 125 may be formed both between the adjacent black matrixes 105 on the substrate 100 and on the black matrixes 105 . in the example shown , the first color filter pattern 125 may be a red color filter . scanning traces 130 may be formed along borders between the first , second , third , and fourth scans on the color filter pattern 125 . the scanning traces 130 protrude over the color filter pattern 125 . next , although not shown in the figures , a second color filter pattern and a third color filter pattern may be formed through the same process shown in fig7 b and 7c . the second and third color filter patterns may be green and blue color filters , respectively . next , the substrate 100 having the color filter pattern 125 may be placed into a hardening furnace , and the color filter pattern 125 may be hardened under temperatures within a range of about 200 degrees of celsius to about 300 degrees of celsius . in fig7 d , the substrate 100 including the hardened color filter pattern 125 may be situated onto a stage ( not shown ), and the surface of the color filter pattern 125 may be polished by a chemical mechanical polishing ( cmp ) process using a polisher 150 moved along the surface of the color filter pattern 125 or by moving the stage . accordingly , the scanning traces 130 may be removed and the surface of the color filter pattern 125 may be flattened ( or planarized ). in addition , a surface roughness of the color filter pattern 125 may be improved . the polishing process may be accomplished along an entire surface of the color filter pattern 125 , or may be performed within specified portions of the color filter pattern 125 . in fig7 e , a common electrode 140 may be formed on the color filter pattern 125 by depositing a transparent conductive material , such as indium - tin - oxide and / or indium - zinc - oxide . thus , an overcoat layer may be formed between the color filter pattern 125 and the common electrode 140 may be omitted since the color filter pattern 125 has a flat surface due to the polishing process . according to the present invention , since the scanning traces formed along a border between adjacent scans may be removed through a polishing process , such as a cmp process , a liquid crystal display device having high quality images may be provided . in addition , manufacturing costs may be reduced since the overcoat layer may be omitted . it will be apparent to those skilled in the art that various modifications and variations can be made in the color filter substrate and method of fabricating a color filter substrate of the present invention without departing from the spirit or scope of the invention . thus , it is intended that the present invention cover the modifications and variations of this invention provided that they come within the scope of the appended claims and their equivalents .
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aspects of the present invention are directed to systems and methods which take into account multiple preemption events . in some embodiments , the invention adjusts to changing backfill window conditions caused by multiple preemption events and canceling low priority jobs which may have advantageously backfilled into the system due to past high priority work . that is , a backfilled job that is low priority , if it needs to be preempted by a high priority job , will be returned to the job queue in its original location . operating in this manner preserves the intent of classic preemption rules : to allow higher priority jobs to run immediately even if low priority work is presently using them . in addition , aspects of the present invention prevent previously preempted low priority work from excessive restart delays due to low priority backfill in the event of high priority preemption . as a further advantage high system utilization is preserved because low priority work may still be advantageously backfilled in the event of a high priority preemption . systems and methods according to the present invention subject low priority backfill to rules that prevents the problems experienced in the current backfill and preemption implementations . fig1 shows an example of a computing system 100 according to an embodiment of the present invention . the computing system 100 may be any type of computing system and may be , for example , a mainframe computer or a personal computer . in some embodiments , the computing system 100 includes a plurality of node clusters 102 . for instance , and as shown in fig1 , the computing system 100 includes node clusters 102 a , 102 b . . . 102 n . each of the node clusters 102 may include a plurality of processing nodes therein . in one embodiment each node cluster 102 includes 16 nodes . it should be understood that the number of nodes per cluster and the number of nodes clusters themselves is not limited in any manner . the term “ node ” as used herein shall refer to an element capable of processing a job either independently or in combination with other nodes . examples of nodes include , but are not limited to , microprocessors , integrated circuits , and the like . in some embodiments , a node cluster may be a cluster of personal computers where the each personal computer may include one or more processing nodes . each of the node clusters 102 may be coupled to a scheduler 104 . the scheduler 104 may , in some embodiments , be a parallel job scheduler such as a tivoli workload scheduler loadleveler from ibm . in general , the scheduler 104 determines how to distribute the jobs contained in a job queue 106 amongst the node clusters 102 in order to efficiently utilize the resources of the computing system 100 . the computing system 100 receives jobs to be performed from a system user 108 and these jobs are placed in the job queue 106 in the order they are received . of course , more than one system users 108 could be connected to the computing system 100 . the job queue 106 and the operation of the scheduler 104 are described in greater detail below . fig2 shows an example of a job queue 106 . the job queue 106 includes , in this example , four jobs , 202 ( referred to as job 1 or j 1 ), 204 ( referred to as job 2 or j 2 ), 206 ( referred to as job 3 or j 3 ), and 208 ( referred to as job 4 or j 4 ). each of these jobs includes a priority rating contained in a priority rating ( or class ) column 210 . for instance , j 1 has a lowp ( low priority ) rating , j 2 has a hip ( high priority ) rating , j 3 has a lowp rating and j 4 has a hip rating . according to classic preemption rules , a hip job will always preempt a lowp job . that is , even if a hip job is received from a user after a lowp job , the computing system will halt ( suspend ) the lowp job and run the hip job if there are not enough nodes to process both jobs simultaneously . in such a case , the lowp is suspended and put on hold until the nodes it was running on become available ( i . e ., after the hip job finishes ). such a preemption rule may be established in the configuration files of the scheduler . as one of skill in the art will realize , different configurations could exist but the following discussion that the above preemption rule is applied . the job queue 106 may also include a state column 212 indicating whether a job is running ( r ) or idle ( i ). the job queue 106 may also include a nodes required column 214 . the values in the node required column 214 represents the number of nodes ( or processors ) in a node cluster that will be needed for a particular process to run . the job queue 106 may also include a time required column 216 indicating how long the job will take to run and a time in column 218 that represents a time that a particular job was submitted to the queue . as shown , the time in column 218 is just an ordered list for ease of explanation but any type of representation of the time a job came in may be utilized . alternatively , the time in column 218 could represent an order that jobs are to be completed or any other type of ordering for jobs to be completed . it should be understood that the job queue 106 shown in fig2 is by way of example only . the job queue may have the same or different columns than those shown in fig2 . the only column that may be needed is one that indicates the priority of a particular job . of course , this information could be in any form and need not necessarily exist in a column as long as it is otherwise associated with a particular job . in general , the job queue is utilized by the scheduler 104 ( fig1 ) to schedule the processing of jobs to be run by the system . fig3 a - 3 f show the usage of particular nodes in a single node cluster . as depicted , the node cluster includes 16 nodes . of course , the node cluster could include any number of node clusters . the description of fig3 a - 3 f below describes the utilization of particular nodes during operation of a computing system that may accept jobs having hip and lowp and references jobs having attributes as shown in fig2 . in particular , jobs 1 - 4 from fig2 are referenced in the following description . in fig3 a - 3 f a node with no shading is idle and shaded node is processing a job . furthermore , a black shaded node is running a hip job and a grey shaded node is running a lowp job . fig3 a shows an example of job 1 running in a 16 node system . each node 301 is shown in grey meaning that it is being utilized by a lowp job . consulting again fig2 , job 1 is rated as a lowp job and its state is running ( r ). further , job 1 is utilizing 16 nodes and has an estimated run time of four hours . job 2 is a hip job and come in after job 1 and requires 1 node . according to classic preemption rules , job 2 preempts job 1 and the nodes take on the state shown in fig3 b . that is , job 1 is not running ( suspended ) and job 2 is running on 1 node , node 1 leaving 15 nodes unutilized . the scheduler attempts to achieve maximal efficiency and , therefore , maximal usage of the nodes . as shown in fig3 b the condition of 15 unused nodes is not consistent with such an operating procedure . thus , the scheduler attempts to utilize the unused nodes for another process . one way in which this may be done is to backfill the unused nodes with another job from the job queue 106 . examining the job queue 106 shown in fig2 , it can be seen that the job 3 will require 8 nodes and may run in one hour . assuming that job 3 comes in at a time less than or equal to one after hour job 2 has begun , job 3 could be run on eight of the 15 available nodes and complete before job 2 does . alternatively , if j 2 and j 3 were placed on the queue simultaneously ( where j 1 was already running on the machine ), in the order indicated in fig2 , j 3 can be started as a backfill event . because j 2 will take 2 hours to complete , the 15 free nodes are available for 2 hours . since j 3 will complete in 1 hour , it is well within the backfill window . as time progresses , this backfill window will become shorter . as long as j 3 is started when the backfill window is 1 hour ( or greater ), j 3 runs as a backfill job with no impact on either j 2 or the planned restart of suspended job j 1 . in such a situation , job 1 would then be able to restart when job 2 completed and the standard procedure of having hip jobs preempt lowp jobs would be met with the added benefit that job 3 also was completed . fig3 c shows hip job job 2 running on node 1 and the backfill job job 3 running on nodes 9 - 16 . having job 3 run in the time available nodes while job 2 was running is referred to herein as “ backfilling ” and any job so running is referred to herein as a “ backfill job .” backfill jobs run in what are referred to herein as “ backfill windows ” which represent a period of time that a certain number of nodes may be available to receive a backfill job . the backfill window may have two dimensions , a temporal dimension representing the amount of time the nodes will be available and a physical dimension representing the number of available nodes . as shown in fig3 d , assume that a new hip job job 4 is submitted a few minutes after jobs 1 - 3 and requires 10 nodes for 10 hours . job 4 preempts job 3 and runs on ten of the free nodes ( nodes 7 - 16 ) while job 2 is processing . the reason that job 4 preempts job 3 is there are only 7 free nodes and job 4 requires 10 nodes , thus , in order for job 4 to run as soon as possible it needs to preempt job 3 . at this time a so called multi - layer preemption event has occurred . in particular , job 1 was preempted by job 2 and job 3 was preempted by job 4 . in order for job 1 to resume it must wait for all the high priority jobs job 2 and job 4 to complete and , under certain conditions , for j 3 to complete as well . fig3 e shows the state of the nodes after job 2 finishes , thus , closing the original backfill window that allowed job 3 to start . job 3 remains suspended because of job 4 . because job 2 now finishes the backfill window that allowed j 3 to start is now void . given the current machine state , job 3 would not be able to backfill since there are six free nodes available for the remainder of the run time of job 4 . in ten hours job 4 finishes and job 3 restarts from suspension . this restart blocks the restart of job 1 until job 3 completes . the restart of job 3 is based on the backfill window established when the high priority job , job 2 , ran . job 1 finally gets to run after all of jobs 1 - 3 are completed . fig3 f shows job 3 running and , as discussed above , job 1 will not be restarted until job 3 is completed . as can be seen from this brief example , in the case where multiple preemptions occur in systems where backfilling is allowed , situations could exist where job 1 never gets completed . aspects of the present invention may ensure that this will not happen . fig4 shows an example of a method by which aspects of the present invention may be implemented . this method may be implemented in the scheduler 104 ( fig1 ) or in any other location in the computer system that has access to allocation of jobs to the nodes contained therein . at a block 402 it is determined if it is acceptable to backfill a job from a job queue . if so , at a block 404 the backfill job is started . that is , as is described above , the job may be placed on nodes that are currently idle , yet protected by a backfill window as the result of a high priority job preempting a previously running low priority job . at a block 406 a higher priority job is received and causes , at a block 408 , the backfill job to be returned to the queue in the location it originally had . returning the backfill job to the job queue at block 408 accomplishes the goal of ensuring that low priority backfill jobs do not end up taking on a higher priority than previously started low priority jobs . in this manner the present invention helps alleviate the problems associated with backfilling that may exist when multilevel preemption events occur . fig5 shows a more detailed depiction of the process of block 408 of fig4 where a backfill job is returned to the job queue . it should be understood that the process shown in fig5 is optional . in the event that the process of fig5 is not implemented the backfill job is merely replaced in the job queue when a hip job preempts it . the process begins at a block 510 where the status of the backfill job is checked . it is then determined , at a block 510 , whether a particular processing threshold has been exceeded . this threshold is based on how much of the backfill job has been completed . in some instances it may be advantageous to store all of the processing that has been performed on the backfill job in a storage location ( available disk space or memory ) so that when the job is restarted this information may be retrieved . of course , in certain instances the job may not have progressed far enough such that the amount of time taken to store the information and then recall when the backfill job restarts results in any advantage . that is , it may take longer to “ checkpoint ” the job than to just restart it when the job reappears at the top of the job queue . the threshold that is checked may be a time running or amount of processing completed and is configurable by a user of the system . if the threshold has not been exceeded , processing progresses to a block 514 where the backfill job is returned to the job queue . if the threshold has been exceeded processing progresses to a block 516 where the processing that has been performed on the job is stored . after the processing of the backfill job has been stored , at a block 518 , the job is returned to the job queue and , in some instances may include an indication of the memory locations where the checkpoint information has been stored . in some embodiments , certain jobs may not be checkpointable . for instance , in the example above , assume job 3 is not checkpointable and it has run for a certain portion of its run time . in some embodiments , jobs that are not able to be checkpointed are tagged as such and the system would not save any job state if the job is placed back onto the job queue . in addition , another class of jobs may also impact storage in such a way that , if they are cancelled after a partial run , there would be undesired side effects . jobs in this category are tagged as not checkpointable , and not able to be backfilled in the case where a preempted backfill window becomes available . these special situations can be handled by flags within the jobs to indicate which different categories the job belongs to . fig6 shows an example of a scheduler 104 according to an embodiment of the present invention . the scheduler 104 shown in fig6 may include a resource manager 602 . the resource manager keeps track of which resources are currently being utilized . for instance , the resource manager may keep a list of machines in the form of a machine list 604 indicating which machines are being used by which jobs and the time requirements associated therewith . for instance , the machine list 604 could include a listing of the node clusters and which nodes within them are being used . fig7 shows an example of a method that may be performed by the resource manager utilizing the machine list . the process begins at a block 702 where a particular machines status is examined . at a block 704 , the machines are ordered based on preemption issues discovered . for instance , a machine ( node cluster ) that does not have a preemption job will be listed higher than one that does . at a block 706 , the list may then be made available to the scheduler . in some embodiments , nodes may be ordered such that free nodes are at the top of the list , busy nodes come next and then preempted nodes are ordered from a lowest to highest level of preemption . referring again to fig6 , the resource manager may perform the steps shown in fig7 and release the information to the scheduler 104 . fig8 shows a process by which the scheduler may operate in order to carry out the multi - level preemption according to the present invention . the process shown in fig8 assumes that a machine is currently running with a number of jobs already being processed . at a block 802 a request for a hip job is received . at a block 804 it determined if any of the node clusters , considered either alone or in combination , include enough open nodes to run the hip job . if so , at a block 818 the hip job has nodes in one of the node clusters allocated for it and it is run . the allocation of nodes may include updating the status of particular nodes within a node cluster in the machine list as described above . if there are no nodes available , or not enough nodes available to run the hip job , then the node clusters are examined to see if any have lowp jobs running on them that may be preempted at a block 806 . the determination made in block 806 may include scanning the machine list which contains the status of the nodes in node clusters of the computing system . it will be understood that a hip job may run on a combination of free nodes and nodes that previously had lowp job running on them . in other words , to the extent additional nodes beyond available free nodes are needed , those nodes may be made available by preempting lowp jobs . in the event that no lowp jobs are running that may be preempted , i . e ., all of the nodes are running high priority jobs , the current scheduler pass moves to the next job and processing returns to block 804 . that is , if a job cannot be scheduled , it is skipped and the scheduler considers other jobs in the list . at the next pass , all idle jobs are again checked to see if they can now run ( due to changes in node availability ). in the event that there is a lowp job running on a particular node in certain clusters that may be preempted ( i . e ., the lowp job is utilizing the same or more nodes than are needed by the hip job ), at a block 810 it is determined whether this lowp is a backfill job . in some embodiments , the probability that a node having a backfill job running on it will be selected may be reduced by placing nodes having backfill jobs running on them at the bottom of the machine list and scanning the machine list from top to bottom when searching for nodes having lowp jobs in block 808 . if the lowp job is not a backfill job , at a block 820 the job is preempted . in some instances , preempting the job may cause the node or node cluster the job was running on to be placed at the bottom of the machine list . the hip job is then allocated and run at a block 818 . of course , as one of skill in the art will realize , multiple lowp jobs may need to be preempted in order to free up the required resources . as such , the process performed in block 820 may involve preempting multiple lowp jobs . if the lowp was a backfill job , a checkpointing routine may be run . that is , if the lowp job is a backfill job as determined at block 810 , at a block 812 it is determined if the backfill job should be checkpointed . if so , at a block 814 the processing that has been performed on the backfill job is saved . regardless of whether checkpointing is required , at a block 816 the backfill job is returned to the job queue . as discussed above , returning the backfill job to the job queue ensures that a lowp backfill job will not , by virtue of being a backfill job , achieve a status that is higher than a lowp job that was previously started but is suspended because it was preempted . as described above , embodiments can be embodied in the form of computer - implemented processes and apparatuses for practicing those processes . in exemplary embodiments , the invention is embodied in computer program code executed by one or more network elements . embodiments include computer program code containing instructions embodied in tangible media , such as floppy diskettes , cd - roms , hard drives , universal serial bus ( usb ) flash drives , or any other computer - readable storage medium , wherein , when the computer program code is loaded into and executed by a computer , the computer becomes an apparatus for practicing the invention . embodiments include computer program code , for example , whether stored in a storage medium , loaded into and / or executed by a computer , or transmitted over some transmission medium , such as over electrical wiring or cabling , through fiber optics , or via electromagnetic radiation , wherein , when the computer program code is loaded into and executed by a computer , the computer becomes an apparatus for practicing the invention . when implemented on a general - purpose microprocessor , the computer program code segments configure the microprocessor to create specific logic circuits . while the invention has been described with reference to exemplary embodiments , it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention . in addition , many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof . therefore , it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention , but that the invention will include all embodiments falling within the scope of the appended claims . moreover , the use of the terms first , second , etc . do not denote any order or importance , but rather the terms first , second , etc . are used to distinguish one element from another . furthermore , the use of the terms a , an , etc . do not denote a limitation of quantity , but rather denote the presence of at least one of the referenced item .
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various details of the state of the art in the area of sequencing - by - synthesis caused us to re - think the approach . we first considered the size of the 3 ′- cap in light of the crystal structures of various polymerases . both the mom and allyl groups , although small , are still too large to fit comfortably into the active site based on crystallographic analysis ( see [ eva00 ] and papers cited therein ). these groups each contain three heavy atoms , defined here to be non - hydrogen atoms , in addition to the 3 ′- oxygen being protected . the essence of the instant invention is that a 3 ′- blocking group that has fewer than three heavy atoms is required for an efficient sequencing by synthesis architecture , either with natural polymerases or with polymerases in which one of the amino acids in contact with the ribose ring is mutated . to implement this invention , the 3 - o - amino group is used as a removable protecting group for the sequencing - by - synthesis scheme ( fig1 ). the 3 ′- o - amino group is chosen because it is as small a moiety as can be imagined to form a stable 3 ′- o blocking group . the small size of the 3 ′- modification makes it most likely to be accepted by dna polymerases during template - directed dna polymerization [ hen04 ]. further , contact by dna polymerases with the 3 ′- end of the incoming triphosphate is frequently made with an amino acid with an aromatic side chain ( phe or tyr ) [ gar99 ]. the size of this can be reduced ( to his ), generating the possibility that if any particular natural polymerase does not work , then these can be mutated , followed by a round of in vitro directed evolution [ gha01 ], to generate polymerases that accept 3 ′- o - amino triphosphates with acceptable specifications . a working sequencing - by - synthesis system that permits parallel ( for example , a 100 × 100 array ) sequencing or single nucleotide sequencing would be extremely useful , provided that the reads are & gt ; 25 nucleotides in length ). even if the reads are short , sequencing - by - synthesis could be very useful in the laboratory and , perhaps , in personalized medicine . for example , one can imagine the use of a sequencing - by - synthesis chip for resequencing a specific locus within a genome to identify polymorphisms in a population . the hydroxylamine functionality is stable in water , and displays several other advantages : ( a ) a set of 3 ′- o - amino - 2 ′- deoxynucleosides ( fig2 ) is already known in the literature [ dec90 ][ kon85 ][ bur94 ][ coo94 ]. they are directly synthesizable from the xylo - 2 ′- deoxyribonucleosides via a mitsunobu reaction with n - hydroxyphthalimide ( fig2 ). from this work , we know that the o — nh 2 group is compatible with dna bases ( pace the ability of hydroxylamine and methoxyamine to be mutagenic ; see below ). ( b ) the 3 ′- o - amino - 2 ′- deoxynucleoside blocking group is small , even smaller than the speculative — osh unit ( which was considered ) and the azido unit ( which is incorporated by reverse transcriptases when they accept azidothymidine triphosphate , for example ). ( c ) the 3 ′- o - amino - 2 ′- deoxynucleoside functionality has much of the hydrogen bonding potential of the 3 ′- oh group . while not wishing to be bound by theory , these derivatives may form a network of hydrogen bonds to the catalytic magnesium ion , as suggested by crystallography for the natural substrate , and therefore fitting into the active site of various polymerases . ( d ) in some cases , a polymerase can be improved by replacing the phe or tyr ( depending on the polymerase ) [ eva00 ] [ gar04 ] that blocks the 3 ′- position of the incoming triphosphate with a slightly smaller aromatic group , h is or phe ( respectively ). ( e ) a large number of reagents are known that cleave the n — o linkage in hydroxylamines and o - alkoxyamines . these are discussed in greater detail below . oxidative conditions are provided by bleach , nitroso compounds , iodate , or potassium ferrate in 1 m nacl , 50 mm potassium phosphate buffer , 25 ° c . ; this generates the free — oh group and n 2 o , which is trapped . reducing agents include catalytic hydrogenation . the preferred approaches include addition - elimination cycles where the amino group of the alkoxyamine adds to an electrophile ( such as maleimide or a naphthoquinone ) and then ejects the alcohol as a leaving group . ( f ) the 3 ′- o - amino - 2 ′- deoxynucleosides offer a handle that can permit the selection of polymerases that incorporate them , should mutagenesis studies not succeed . the water - oil emulsion system [ gha01 ] to select for thermostable polymerases is used to select polymerases that incorporate 3 ′- o - amino - 2 ′- deoxynucleosides to their own gene where the genes are recovered by an aldehyde column that captures 3 ′- o - amino - 2 ′- deoxynucleosides as oximes . with this 3 ′- o blocking group , other features of the architecture of the state - of - the - art sequencing - by - synthesis approach could be adopted . in particular , the same cleavable linkers that hold the fluorescent labels to the nucleobases would be used . these linkers might also be designed such that they can be cleaved by whatever reagent was used to remove the amino group from the terminal 3 ′- o - amino - 2 ′- deoxynucleoside . using the o - amino 3 ′- blocking group in a sequencing - by - synthesis strategy is not constrained by the reactivity of n - alkoxyamines . these are nucleophiles , and simple members of this class of compound ( hydroxylamine and methoxyamine in particular ) are known to react with dna , predominantly by replacing the exocyclic amino groups of cytosine and , to a lesser extent adenine , with the alkoxyamine to generate 4 - methoxycytosine and 4 - methoxyadenine [ koc69 ]. this is not a serious problem here . first , the reaction of alkoxyamines with cytidine proceeds slowly at neutral ph , even when the concentration of alkoxyamines is high . the reaction is slower with methoxylamine than hydroxylamine , and it is still slower with the secondary n - alkoxyamines , such as a 3 ′- onh 2 unit on a nucleoside derivative . while not wishing to be bound by theory , it appears that these structural features explain why the 3 ′- o - amino unit does not react rapidly with cytosine and adenosine nucleosides [ dec90 ]. for a typical alkoxyamine , pk a ≈ 4 . 6 . the 3 ′- o - amino group is neutral at physiological ph . the triphosphates of the 3 ′- o - amino - 2 ′- deoxyribonucleosides are prepared using the ludwig - eckstein synthetic procedure [ lud89 ] ( fig3 ). our preferred route for generating triphosphates applies the ludwig - eckstein procedure to the precursor where the o — nh 2 group is protected as an fmoc amide , a trifluoroacetyl amide , or transiently as an oxime with acetone . less preferably , but as an alternative , is to use the ludwig - eckstein procedure with the unprotected 3 ′- o - amino - 2 ′- deoxynucleoside . a variety of reagents and conditions cleave n — o bonds . the instant invention offers a number of these , so that chemists can chose a procedure to fit the particular side chain chemistry that is used to append a readable tag to the nucleobases . most preferably , the reaction that removes the 3 ′- oh amino group is done in water . this is desired so that the integrity of the double helix is retained . it is possible , in a sequencing - by - synthesis architecture , to re - anneal following a treatment by a reagent that denatures the double helix , making the requirement for aqueous chemistry not absolute . this is less preferable , however , for practical use . therefore , most preferable is an aqueous deblocking chemistry , with organic co - solvents present to less than 50 % of the total by volume , under conditions where the double helix does not disassociate or precipitate . for example ( depending on the salt concentration ), solvents such as methanol or ethanol ( to ca . 50 %), tetrahydrofuran or dioxane ( to 40 %), or denaturants ( e . g ., dimethylformamide , dimethylsulfoxide to ca . 25 %) may be used . a substantial literature covers a large number of procedures to cleave the n — o bond of an r — onh 2 unit . as summarized below , the instant invention offers ca . two dozen different reagents that might be used to cleave the n — o bond under conditions sufficiently mild that they will not degrade dna , and not denature the primer - template duplex . most of these rely on the unique reactivity of the pair of heteroatoms ( o — n ), both having unshared pairs of electrons , reactivity that is not found elsewhere in dna . thus , the o — n unit has particularly low basicity , particularly good electron donation properties , and particularly high nucleophilicity . it shares these features with hydrazine and peroxide , as is well known in the art under the rubric of the “ alpha effect ”. this means that against a variety of reagents , both electrophilic and oxidizing , the alkoxyamine group reacts first , before other parts of the dna molecule . this suggests that competing reactivity is easily managed , using conditions that are beneficial in general for other reasons , including low reagent concentrations , low temperatures , rapid treatments , and rapid quenches . these conditions are desired by most sequencing - by - synthesis architectures . the species that is being deblocked is known as an o - alkylhydroxylamine . reagents are known for the cleavage of the n — o bond many other derivatives , including o - acyl hydroxylamines , n - acyl hydroxylamines , and oximes ( where the o is — oh ) ( fig4 ). these substrates have been chosen because they are intermediates in natural product syntheses of various types . many of these are homogeneous , and many are known to work in aqueous media . however , it may be necessary to transform the 3 ′- terminally blocked — o — nh 2 unit into one of these derivatives . for example , preparing an oxime from the 3 ′- o — nh 2 unit is direct ; one simply stirs with an aqueous solution of the appropriate ketone or aldehyde . the nature of the ketone or aldehyde can be adjusted to adjust the reactivity of the species . preparing the o - alkylhydroxamic acid requires acylation . here , mild acylation reagents in aqueous media are expected to prefer the hydroxylamine , with its enhanced nucleophilicity over the exocyclic amino groups of the nucleobases . thus , reagents that cleave all three are considered here . the nh 2 group is susceptible to oxidation that leads to fragmentation . the simplest reagent is dilute hypochlorite in a process that has been known for half a century [ ril54 ]. in addition , nitric oxide and other nitrosating agents may be used . these have been reviewed recently by corsano et al . [ cor01 ]. in particular , the reaction of o - alkoxyamines with nitroso compounds ( e . g ., nitrosobenzene ) generates the diazo compound ( in this case ph — n ═ n — or ), which can be fragmented to give the alcohol roh [ mas88 ][ mas90 ][ pat77 ][ ver91 ]. dna is not easily degraded by hypochlorite and other oxidizing agents ( see literature in this area [ ber90 ] [ hay71 ] [ hoy73 ] [ pat72 ] [ whi97 ] [ whi99 ]). hypochlorite is a product of biological systems ( through the reaction of hydrogen peroxide and chloride catalyzed by myeloperoxidase in mammalian neutrophils ), as well as being ubiquitous in the environment ( in swimming pools , food sanitizers , and the paper industry ). in a relatively thorough recent study , whiteman et al . [ whi97 ] exposed calf thymus dna to hypochlorite at 37 ° c . for one hour at ph 7 . 4 , and quantitated various oxidation products of dna . they found pyrimidine oxidation products ( thymine glycol ( cis / trans ), 5 - hydroxycytosine , 5 - hydroxyuracil , 5 - chlorouracil , and 5 - hydroxyhydantoin ), but not purine oxidation products ( 8 - hydroxyguanine , 2 - and 8 - hydroxyadenine , fapy guanine , fapy adenine ). conversion was strongly dependent on concentration . at 0 . 1 mm hocl concentrations , total modified base concentrations are between 1 and 5 nanomoles per mg of dna . thus , this represents a conversion of ca . 0 . 1 %, in one hour at 37 ° c . as the alkoxylamine reaction is complete in seconds at lower temperature , this reaction has utility . other oxidizing agents are reported to cleave the n — o bond in oximes . these include caro &# 39 ; s acid [ mov00 ] and iodate [ mah97 ]. iodate and dna are quite compatible , as is well known from the fact that iodate is a product in the periodate - mediated cleavage of rna , a process that is widely used in nucleoside chemistry . in these cases , the reaction appears to be done under aqueous conditions . in general , however , the procedure is well documented for oximes having a free oh group ( see review in [ cor0 ]. n - bromosuccinimide and n - bromoacetamide were also found to be efficient and selective reagents for the mild oxidative cleavage of oximes . perchlorate and periodate are also able to convert a variety of oximes into the corresponding carbonyl compounds . these reactions are reported at 0 ° c ., leaving alkaloid nitrogens untouched . but many of these reagents ( such as the dess - martin periodinane ) require a free oh on the oxime . our presently preferred method for oxidative cleavage is treatment with nitrous acid at ph 4 - 5 , which cleaves the onh 2 group at a rate over 100 times faster than it deaminates guanine , or treatment with a nitrite ester ( e . g ., ethyl nitrite ) at ph 7 - 8 . the classical way in synthetic organic chemistry to cleave the n — o bond is to treat the linkage with dihydrogen in the presence of a pt or pd catalyst [ cor83 ] [ nai94 ]. this reaction proceeds quantitatively , can occur in aqueous solvents , and leaves dna undamaged . the primary disadvantage of this process is that catalytic hydrogenation requires a heterogeneous catalyst which may not be accessible to dna immobilized on a chip . no work has evidently been done to identify soluble catalysts that achieve the same end . a variety of reagents have been used to reductively cleave n — o bonds under mild conditions . these are reviewed in [ khl03 ]. one of the earliest of these , introduced by keck [ kec79 ], involves sodium amalgam . the reaction is reported in ethanol as solvent . best results are obtained when the reaction mixture was buffered with four equivalents of sodium hydrogen phosphate . several low oxidation states metal cations that dissolve in water cleave n — o bonds . these were discovered in the late 1960 &# 39 ; s and early 1970 &# 39 ; s in programs to synthesize antibiotics where oximes were precursors . many of these work in water under conditions where duplex dna is expected to be stable . one of these was provided by timms and wildsmith in a process that cleaved the n — o bond of an oxime in a precursor for the synthesis of erythromycin [ tim71 ]. here , heterogeneous catalysts were explicitly not desired ( as is the case in sequencing - by - synthesis ), and special effort was made to obtain a reagent that could exist in homogeneous solution with the reactant . clean and quantitative conversion was obtained using a 15 % solution of ticl 3 in water buffered with sodium acetate . two equivalents of the reagent were required , and the reaction was easily followed by the loss of the characteristic color of titanium ( iii ). conversion was complete within five minutes at room temperature . the only negative feature of this reaction is the fact that it is reported for a free oxime , rather than an o - alkyloxime . timms and wildsmith also report two other low valent metals suitable for reduction of an oxime in aqueous solution . these are divalent vanadium ( prepared by zn / hg reduction of vanadyl sulfate ), samarium [ chi96 ] and divalent chromium ( where acetate buffer was not used ). molybdenum hexacarbonyl mo ( co ) 6 is widely used in synthesis , as it cleaves the o — n bond where both the oxygen and the nitrogen have substitutents . this reagent is used in water - acetonitrile mixtures [ nit85 ] [ khu04 ] [ maro5 ] [ you06 ]; the species is not soluble in pure water . active agents having the formula mo ( co ) n ( ncr ) 6 - n , which are more soluble in water , may also be used . the fact that ticl 3 works directly on an oxime was cited by [ tim71 ] as an advantage over other procedures that use low valent metals as reducing agents , but are reported for o - acylated oximes . the procedure of corey and richman [ cor70 ], which involves the treatment of an o - acyl oxime with chromium ( ii ) cleaves the n — o bond of o - acetyl oximes in aqueous solution . the reaction is reported to proceed in high yield at room temperature over 24 hours . only incomplete experimental details are provided in the original paper ; in particular , the paper does not report whether the reaction also works with o - alkylated oximes . another potentially suitable method was offered by keck [ kec95a , b ] using smi 2 . some of these reagents may have utility to regenerate the 3 ′- hydroxyl group , allowing the next cycle in the sequencing - by - synthesis strategy to occur . in these procedures , the first step involves the reaction of a carbonyl compounds with the nh 2 group to create an oxime . acetone appears to be perfectly acceptable for this purpose . this creates 2 ′- aminopropane as a side product , which is innocuous . a larger aldehyde having fluorescence can also be used . this generates the corresponding amine , which can be detected as a way to monitor the progress of the reaction . in the second step , the trivalent cation is introduced as its chloride salt in dilute aqueous solution . a third approach , which is presently preferred , involves neither oxidation nor reduction , but rather an addition / elimination sequence . this can be done with a wide range of electrophiles . the general strategy involves the attack of the amino group of the alkoxylamine upon an electrophilic molecule that , after the appropriate arrowisms , produces a push of electrons that ejects the oxygen of the alkoxylamine as a leaving group . a schematic for these is shown in fig5 . the electrophile can be maleimide [ sek97 ] [ sek99 ], nitrobenzene [ nik00 ], or nitroolefins [ ima96 ] [ ima97 ]. one method potentially involves the reaction of the o - alkoxylamine with a quinone , preferably a 1 , 4 - naphthoquinone [ bit94 ], and more preferably a 1 , 4 - naphthoquinone that carries on the second ring an ionic group ( such as a sulfonate or carboxylate group ) that makes the quinone soluble in aqueous media . the reactions leading to the removal of the amino group from the oxygen all proceed under mild conditions ( fig5 ). while not wishing to be bound by theory , the utility of this reagent may be diminished by the presence of multiple electrophilic sites in the species , which creates dead - end products that are not easily converted to the desired product . while the reagents described give the new compositions utility in a variety of settings , the instant application discloses additional reagents for cleaving a 3 ′- onh 2 blocking group . these fall into two classes . class 1 . reagents that react directly with the 3 ′- onh 2 blocking group , and generates the 3 ′- oh unit without the isolation of an intermediate , or the addition of a subsequent reagent in a second step . these include reagents shown in fig1 . while not wishing to be bound by theory , these figures also illustrate mechanisms by which these reagents are presumed to act . class 2 . reagents that react directly with the 3 ′- onh 2 blocking group to form an intermediate , which then generates the 3 ′- oh unit . these include reagents shown in fig1 . while not wishing to be bound by theory , these figures also illustrate mechanisms by which these reagents are presumed to act . we next consider fluorescent tags that might be used in conjunction with a 3 ′- onh 2 reversible blocking group . classically , fluorescent groups are appended to the five position of pyrimidines , or to the 7 - position of 7 - deaza purines . many groups have developed chemistry for preparing these classical derivatives ( see for example [ hob91 ], see also our work [ hel02 ] [ roy04 ] and references cited therein for a “ two moving target ” optimization of polymerases and the 5 - position linker ). tags at this position are accepted by polymerases [ hel02 ], and fluors at this positions are combined with modifications in the sugar to do dideoxy sequencing . in practice , any linker that can be cleaved to release the fluorescent product allows the loss of the fluor prior to the next extension reaction , preventing the fluor from cycle n from confusing the signal from the fluor appended at cycle n + 1 . alternatively , with strategic choice of the fluor , the fluor can itself be destroyed by chemical transformation , including by reduction ( e . g . of cyanine fluors ) or by bleach . a second consideration reflects the fact that the rule - based molecular recognition properties displayed by dna and rna are unique in chemistry , and easily disrupted . as was demonstrated in earlier work [ hel02 ], addition of extensive functionality to every nucleobase may disrupt the rule based molecular recognition . therefore , the preferred strategy removes as much of the tag as possible at each cycle , and arranges to have what is left behind be as hydrophilic as possible . this is , of course , in addition to the need to have inexpensive and readily accessible linkers . the presently preferred linker , after cleavage , leaves behind a — ch ═ ch — ch 2 oh group . this is preferable to the — ch ═ ch — ch 2 — nh 2 group , which places a positive charge on the side chain . it is also preferable to the — cc — ch 2 — oh , — c — ch 2 — sh , and — cc — ch 2 — nh 2 units , for reasons of record [ hel02 ], although these may also be used . last , the longer linkers — cc — ch 2 — ch 2 — oh , — cc — ch 2 — ch 2 — sh , — cc — ch 2 — ch 2 — nh 2 , — ch ═ ch — ch 2 — ch 2 — nh 2 , h ═ ch — ch 2 ch 2 — oh , and — ch ═ ch — ch 2 — ch 2 — sh linkers , which have enhanced stability , although they each leave an extra atom once cleavage is complete . each of these linkers can carry a fluorescent tag appended by an ester , amide , or disulfide linkage , appropriately . the presently preferred — ch ═ ch — ch 2 oh linking group has certain advantages , however . first , the allyl group stabilized duplexes when attached to the 5 - position of pyrimidines . further , the — oh terminus is uncharged , yet hydrophilic . most significantly , however , the — oh terminus can be left behind with the reagent that cleaves the 3 ′- onh 2 group , if the fluor is attached to the linker via the — o — nh - tag unit . this can be coupled to the 5 - iodopyrimidine and the 7 - iodo - 7 - deazapurine units using the synthetic intermediate where the boc - nh — ch 2 — ch 2 — n - fmoc unit , which is then attached to a standard fluor ( a cyanine dye for single molecule sequencing , or a rhodamine , bimane , dyes with large stokes shift , and other molecules ). these are the presently preferred linkers in large part because they can be cleaved from the nucleobase using the reagent that is used to cleave the 3 ′- o blocking group . kondo et al . nearly two decades ago reported the synthesis of the first 3 ′- o - amino - 2 ′- deoxynucleoside [ kon85 ]. subsequently , de clerq prepared a complete set of 3 ′- o - amino - 2 ′- deoxynucleosides , and reported their syntheses in the european patent literature [ dec90 ]. the team at isis led by cook also generated these as well as part of their program in antisense nucleic acid analogs [ coo94 ]. finally , in 1994 , burgess and his coworkers reported the synthesis of dinucleotides joined via an n — o linker in a synthesis that began with the 3 ′- o - amino - 2 ′- deoxynucleoside [ bur94 ] ( fig2 , see also [ oga98 ]). these research groups prepared these compounds because they were seeking to generate nucleic acid analogs where the anionic phosphodiester bond was replaced by an uncharged linker . it does not appear that they considered the possibility of using the 3 ′- o - amino moiety as a blocking group for a sequencing - by - synthesis architecture . the uncharged n - o linker was viewed as a useful replacement for the charged phosphodiester linker . coupling could be easily achieved via reaction of the 3 ′- o - amino - 2 ′- deoxynucleoside with an aldehyde on the next nucleotide building block . these and other uncharged dna analogs were hoped to be able to passively enter cells , and to continue to bind to natural dna and rna following watson - crick pairing rules . the antisense strategy fell out of favor when this was found not to be the case . nevertheless , the activity left behind a rich literature , which makes the synthesis of the needed 3 ′- o - amino - 2 ′- deoxynucleosides well precedented . this notwithstanding , no route was available for preparing the triphosphates , which are new compounds disclosed in the instant invention for the first time . these can be prepared by the route disclosed in fig3 ). the xylo - nucleoside analogs are synthesized under mild conditions from the 5 ′- trityl - or 5 ′- dimethoxytrityl - nucleoside derivatives by mitsunobu reaction with benzoic acid , followed by aminolysis of the resulting benzoate with nh 4 oh . representative procedures are given below : 5 ′- o - trityl - xylothymidine . thymidine ( 4 . 8 g ; 20 mmol ), dmap ( 1 . 2 g ; 10 mmol ) and triethylamine ( 5 . 6 ml ; 40 mmol ) are dissolved in anhydrous pyridine ( 70 ml ) at room temperature . tritylchloride ( 11 . 2 g ; 40 mmol ) is added and the mixture is stirred at room temperature , leading to the precipitation of hcl salts . after 3 days , tlc ( ch 2 cl 2 : meoh = 10 : 1 ) is used to show ca . 90 % conversion . the mixture is then cooled to 0 ° c . methanesulfonyl chloride ( 1 . 9 ml ; 25 mmol ) and triethylamine ( 3 . 5 ml ; 25 mmol ) are added and the mixture is stirred at room temperature for 2 h . the hcl salts are removed by filtration , and the filtrate is concentrated in vacuo . ethanol ( 130 ml ) and aqueous naoh ( 1 . 5 m ; 65 ml ) are added and the mixture is heated at reflux for 2 h . the reaction is quenched by the addition of aqueous hcl ( 1 m ; 80 ml ) and the solvents are removed in vacuo . aqueous work - up ( ch 2 cl 2 ) and flash liquid chromatography ( silica , eluent ch 2 cl 2 : meoh = 30 : 1 to 10 : 1 ) gives 5 ′- o - trityl - xylothymidine ( expected 5 . 9 g ; 61 % overall ) as a colorless foam . 1 h - nmr ( cdcl 3 ; 300 mhz ): δ ( ppm )= 1 . 74 ( d , j = 0 . 8 hz , 3h ); 2 . 22 ( dd , j = 1 . 9 , 15 . 0 hz , 1h ); 2 . 46 - 2 . 59 ( m , 1h ); 3 . 28 ( br s , 1h ); 3 . 45 - 3 . 68 ( m , 2h ); 4 . 02 - 4 . 08 ( m , 1h ); 4 . 40 - 4 . 44 ( m , 1h ); 6 . 17 ( dd , j = 2 . 2 , 8 . 0 hz , 1h ); 7 . 20 - 7 . 50 ( m , 15h ); 7 . 60 ( d , j = 1 . 0 hz , 1h ); 9 . 59 ( br s , 1h ). 5 ′- o - trityl - 3 ′- o - phthalimido - thymidine . 5 ′- o - trityl - xylothymidine ( 1 . 9 g ; 4 mmol ), triphenylphosphine ( 1 . 3 g ; 5 mmol ) and n - hydroxyphthalimide ( 815 mg ; 5 mmol ) are dissolved in thf ( 60 ml ) at 0 ° c . diisopropylazodicarboxamide ( diad , 965 / l ; 5 mmol ) is added drop wise , and the reaction mixture is stirred as the temperature rises from 0 ° c . to room temperature . after 15 h , the reaction was quenched by the addition of h 2 o ( 100 μl ), and the reaction mixture is concentrated in vacuo . flash liquid chromatography ( silica , eluent etoac : hexanes = 1 : 1 to 3 : 1 ) gives 5 ′- o - trityl - 3 ′- o - phthalimido - thymidine ( expected 3 . 4 g ; ca 3 . 5 mmol nucleoside ; 88 %) as a colorless foam . the material may be contaminated with ph 3 p ═ o , but is used for the next step without further purification . 1 h - nmr ( cdcl 3 ; 300 mhz ): a ( ppm )= 1 . 48 ( d , j = 0 . 9 hz , 3h ); 2 . 34 - 2 . 42 ( m , 1h ); 2 . 84 ( ddd , j = 1 . 7 , 4 . 8 , 14 . 0 hz , 1h ); 3 . 48 ( ddd , j = 3 . 2 , 10 . 0 , 35 . 0 hz , 2h ); 4 . 50 - 4 . 54 ( m , 1h ); 5 . 07 - 5 . 13 ( m , 1h ); 6 . 60 ( dd , j = 5 . 6 , 8 . 0 hz , 1h ); 7 . 16 - 7 . 85 ( m , 38h ); 9 . 08 ( br s , 1h ). 3 ′- o - amino - thymidine . hydrazine monohydrate ( 7 ml ) is added to a suspension of 5 ′- o - trityl - 3 ′- o - phthalimido - thymidine ( 2 . 9 g ; ca . 3 mmol nucleoside , contaminated with some ph 3 p ═ o ) in ethanol ( 30 ml ), and the solution is heated under reflux for 2 h . the ethanol is removed in vacuo and the resulting mixture is partitioned between ch 2 cl 2 ( 100 ml ) and aqueous nacl ( 50 % sat . ; 100 ml ). the organic phase is separated and concentrated in vacuo to give a colorless foam , which is redissolved in anhydrous dichloromethane ( 20 ml ). a solution of zinc chloride etherate ( 1 m in et 2 o ; 30 ml ; 30 mmol ) is then added . after a few minutes , the product starts to precipitate . after 30 minutes , the solution is diluted with ch 2 cl 2 ( 100 ml ) and the precipitate removed by filtration . the solids are partitioned between water ( 20 ml ) and ch 2 cl 2 ( 20 ml ). the aqueous phase is separated and lyophilized . the crude product is purified by reverse phase hplc ( c 18 , gradient 0 - 5 % acetonitrile in water over 20 minutes ) to give 3 ′- o - amino - thymidine ( expected 340 mg ; 44 % overall ) as a colorless foam . 1 h - nmr ( dmso - d 6 ; 300 mhz ): δ ( ppm )= 1 . 77 ( d , j = 0 . 7 hz , 3h ); 1 . 97 - 2 . 07 ( m , 1h ); 2 . 29 ( ddd , j = 0 . 7 , 5 . 9 , 13 . 7 hz , 1h ); 3 . 50 - 3 . 66 ( m , 2h ); 3 . 99 - 4 . 03 ( m , 1h ); 4 . 16 - 4 . 20 ( m , 1h ); 5 . 08 ( t , j = 5 . 1 hz , 1h ); 6 . 10 - 6 . 16 ( m , 3h ); 7 . 73 ( d , j = 1 . 0 hz , 1h ); 11 . 27 ( br s , 1h ). 13 c - nmr ( dmso - d 6 ; 75 mhz ): a ( ppm )= 12 . 3 , 35 . 7 , 62 . 1 , 83 . 7 , 83 . 7 , 83 . 9 , 109 . 5 , 136 . 0 , 150 . 5 , 163 . 7 . triphosphates are synthesized using an adaptation of the ludwig - eckstein procedure . the amino group is first protected by fmoc to prevent phosphorylation of this amine . the protection also enhances the solubility of the nucleoside . 3 ′- o -( fmoc ) amino - thymidine . 3 ′- o - amino - thymidine ( 129 mg ; 0 . 5 mmol ) and sodium carbonate ( 53 mg ; 0 . 5 mmol ) are dissolved in water ( 1 . 5 ml ). fmoc - osucc ( 202 mg ; 0 . 6 mmol ) is dissolved in dioxane ( 1 . 5 ml ). the two solutions are then mixed , and the mixture is stirred at room temperature for 3 h . the mixture is partitioned between etoac ( 20 ml ) and aqueous nacl ( 50 % sat ., 20 ml ). the organic phase is concentrated in vacuo and the residue purified by flash liquid chromatography ( silica , eluent etoac : hexanes = 1 : 1 to pure etoac ) to give 3 ′- o -( fmoc ) amino - thymidine ( expected 122 mg ; 52 %) as a colorless solid . 1 h - nmr ( cdcl 3 ; 300 mhz ): δ ( ppm )= 1 . 92 ( d , j = 1 . 0 hz , 3h ); 2 . 45 ( m , 1h ); 2 . 62 ( m , 1h ); 3 . 75 ( m , 1h ); 3 . 92 ( m , 1h ); 4 . 16 ( d , j = 2 . 4 hz , 1h ); 4 . 24 ( t , j = 6 . 0 hz , 1h ); 4 . 57 ( t , j = 5 . 7 hz , 2h ); 6 . 06 ( dd , j = 6 . 4 , 8 . 8 hz , 1h ); 7 . 29 - 7 . 48 ( m , 4h ); 7 . 58 ( d , j = 7 . 8 hz , 2h ); 7 . 77 ( d , j = 7 . 5 hz , 2h ); 8 . 13 ( br s , 1h ). 3 ′- o -( fmoc ) amino - thymidine - 5 ′- triphosphate . following the ludwig - eckstein procedure , 3 ′- o -( fmoc ) amino - thymidine ( 111 mg ; 0 . 23 mmol ) is rendered anhydrous by coevaporation with pyridine . the residue is redissolved in anhydrous pyridine ( 230 μl ) and anhydrous dioxane ( 690 μl ). a freshly prepared solution of 2 - chloro - 4h - 1 , 2 , 3 - dioxaphosphorin - 4 - one ( 73 mg ; 0 . 36 mmol ) in anhydrous dioxane ( 210 μl ) is then added at room temperature under stirring . after 10 minutes , a mixture of bis ( tributylammonium ) pyrophosphate ( 127 mg ; 0 . 27 mmol ; 1 . 6 eq . bu 3 n per pyrophosphate ) and tributylamine ( 212 μl ; 0 . 89 mmol ) in anhydrous dmf ( 640 μl ) was added . after a further 10 minutes , a solution of diiodine in pyridine / water ( 98 / 2 , v / v ; 1 % iodine ; 4 . 5 ml ) is added . after 15 minutes , excess diiodine is reduced by the addition of a few drops of aqueous na 2 so 3 ( 5 %; ca 0 . 3 ml ). the mixture is then concentrated in vacuo . the residue is redissolved in water ( 2 ml ) and purified by rp - hplc ( c 18 , gradient 0 - 35 % acetonitrile in 10 mm triethylammonium acetate over 37 minutes ) to give 3 ′- o -( fmoc ) amino - thymidine - 5 ′- triphosphate as a colorless foam . 1 h - nmr ( d 2 o ; 300 mhz ): a ( ppm )= 1 . 72 ( s , 3h ); 1 . 81 - 1 . 91 ( m , 3h ); 3 . 91 ( m , 3h ); 4 . 01 ( m , 1h ); 4 . 29 ( m , 1h ); 4 . 41 ( m , 1h ); 5 . 89 ( m , 1h ); 7 . 11 - 7 . 20 ( m , 4h ); 7 . 39 - 7 . 57 ( m , 5h ). 31 p - nmr ( d 2 o ; 162 mhz ): δ ( ppm ; h 3 po 4 = 0 )=− 12 . 4 ( br s , 1p ); − 13 . 3 ( br s , 1p ); − 24 . 9 ( br s , ip ). 3 ′- o - amino - thymidine - 5 ′- triphosphate . 3 ′- o -( fmoc ) amino - thymidine - 5 ′- triphosphate is dissolved in 20 % piperidine in dmf ( 0 . 5 ml ). the mixture is stirred at room temperature for 30 minutes and then concentrated in vacuo . the residue is redissolved in triethylammonium acetate buffer ( aqueous , 10 mm ; ph 7 ; 2 ml ) and purified by rp - hplc ( c 18 , gradient 0 - 21 % acetonitrile in 10 mm triethylammonium acetate over 27 minutes ) to give 3 ′- o - amino - thymidine - 5 ′- triphosphate as a colorless foam . the purity of the product is confirmed by analytical ion - exchange chromatography ( deae , gradient 0 - 1 m triethylammonium bicarbonate in water over 30 minutes ). 1 h - nmr ( d 2 o ; 300 mhz ): δ ( ppm )= 1 . 80 ( s , 3h ); 2 . 18 ( m , 1h ); 2 . 34 - 2 . 39 ( m , 1h ); 4 . 03 - 4 . 09 ( m , 2h ); 4 . 25 ( m , 1h ); 4 . 45 ( m , 1h ); 6 . 17 ( dd , j = 6 . 0 , 9 . 1 hz , 1h ); 7 . 66 ( s , 1h ). 31 p - nmr ( d 2 o ; 162 mhz ): δ ( ppm ; h 3 po 4 = 0 )=− 14 . 1 ( br s , ip ); − 16 . 3 ( br s , ip ); − 27 . 7 ( br s , 1p ). ms - esi − : [ m - h ] − calcd . for c 10 h 17 o 14 n 3 p 3 , 496 . 0 ; found , 496 . 4 . classically , fluorescent groups are appended to the 5 - position of pyrimidines , or the 7 - position of 7 - deaza purines . a variety of chemistry is available for preparing these classical derivatives ( see for example [ hob91 ]. work in the benner group ( see [ hel02 ] [ roy04 ] and references cited therein ) describe the “ two - part ” ( or perhaps better named , the “ two moving target ” optimization of polymerases and the 5 - position linker . tags at this position are accepted by polymerases [ hel02 ], and fluors at this positions are combined with modifications in the sugar to do dideoxy sequencing . disclosed here is one of several orthogonal protection strategies that allow for the attachment of the fluorescent tag onto the triphosphate without interference of the nucleophilic alkoxylamines ( fig8 ). other strategies are easily envisioned by those skilled in the art . the nucleosides bearing an iodo substituent at the 5 - position ( pyrimidines ) or 7 - position ( 7 - deazapurines ) are either commercially available or well documented in literature [ hob91 ]. first , the 3 ′- o - amino group is introduced by the procedure outlined above . next , the linker for the fluorophore or other tag is attached via a heck coupling reaction [ dey01 ]. the linker contains an olefin to allow the heck coupling to proceed , a base - labile boc protected n — o bond that is susceptible to cleavage by the naphthoquinone ( or its derivatives , or other reagents that cleave the n — o bond used to deblock the 3 ′- o group ), and a ( acid - labile protected ) primary amine for attachment of the fluorophore . the same linker is therefore used for all four nucleosides . the third step is the introduction of the triphosphate group , in analogy to the procedure outlined above . the boc protection of the linker amine is selectively removed by short treatment with trifluoroacetic acid , reportedly without cleaving either the triphosphate or the glycosidic bond [ sto99 ]. the attachment of the fluorophore to this amine via an activated ester is a broadly established procedure . final cleavage of the fmoc group yields the target compounds . the synthesis of the linker ( fig9 ) starts with dess - martin oxidation [ des91 ] of commercially available boc - aminoethanol to yield the corresponding aldehyde , which is captured with o - allylhydroxylamine to give the corresponding oxime . reduction with cyanoborohydride gives the amine which is protected with fmoc to give the target compound . several details are described below . oxime . tert - butyl n -( 2 - hydroxyethyl ) carbamate ( 900 mg ; 5 . 5 mmol ) is dissolved in anhydrous dichloromethane ( 40 ml ) at room temperature . dess - martin periodinane ( 2 . 12 g ; 5 . 0 mmol ) is added . the solution is stirred at room temperature for 2 h during which it turned into a milky suspension . aqueous nahco 3 / na 2 s 2 o 3 ( sat ., 40 ml ) is added and the mixture stirred for an additional 30 minutes . the organic phase is separated and the aqueous phase is extracted with dichloromethane ( 2 × 50 ml ). the combined organic phase is dried with brine ( 30 ml ) and na 2 so 4 and concentrated in vacuo , to give a yellow slime . the crude aldehyde is taken up in acetonitrile ( 30 ml ) and thf ( 20 ml ). o - allylhydroxylamine hydrochloride hydrate ( 720 mg ; ca . 6 . 5 mmol ) and potassium carbonate ( 900 mg ; 6 . 5 mmol ; powdered ) are added and the suspension is stirred at room temperature for 30 minutes . the solids are removed by filtration , and the filtrate is concentrated in vacuo . aqueous work - up ( dichloromethane ) and flash liquid chromatography ( silica ; eluent etoac / hexanes , 1 : 4 to 1 : 2 ) gives the oxime ( expected 670 mg ; 63 %) as a colorless oil which solidifies at − 20 ° c . 1 h - nmr ( cdcl 3 ; 300 mhz ): δ ( ppm )= 1 . 45 ( s , 9h ); 3 . 89 ( t , j = 5 . 0 hz , 1 . 2h ); 4 . 01 ( t , j = 4 . 9 hz , 0 . 8h ); 4 . 53 ( dt , j = 5 . 7 , 1 . 4 hz , 1 . 2h ); 4 . 58 ( dt , j = 5 . 7 , 1 . 4 hz , 0 . 8h ); 4 . 94 ( br s , 1h ); 5 . 19 - 5 . 33 ( m , 2h ); 5 . 90 - 6 . 04 ( m , 1h ); 6 . 74 ( t , j = 4 . 3 hz , 0 . 4h ); 7 . 44 ( t , j = 4 . 8 hz , 0 . 6h ). 13 c - nmr ( cdcl 3 ; 75 mhz ): δ ( ppm )= 28 . 6 , 36 . 8 , 40 . 0 , 75 . 0 , 75 . 3 , 80 . 1 , 117 . 8 , 118 . 2 , 134 . 1 , 134 . 3 , 146 . 8 , 149 . 9 , 155 . 8 . hrms - ei : [ mh + ] calcd for c 10 h 19 o 3 n 2 , 215 . 1396 ; found , 215 . 1486 . amine . the oxime ( 428 mg ; 2 mmol ) and methyl orange indicator ( ca . 1 mg ) are dissolved in methanol ( 10 ml ) at 0 ° c . a solution of methanolic hcl ( 6 n aqueous hcl : methanol , 1 : 1 ). a solution of sodium cyanoborohydride ( 150 mg ; 2 . 4 mmol ) in methanol ( 2 . 4 ml ) is slowly added as needed to maintain ph ≈ 3 . 5 and ice cold temperature . the final solution is stirred at 0 ° c . and ph 3 . 5 for an additional 30 minutes . the reaction is quenched by the addition of aq . nahco 3 ( sat ., 5 ml ) and aq . naoh ( 2 n , 200 μl ) and the methanol is removed in vacuo . aqueous work - up ( etoac ) and flash liquid chromatography ( silica ; eluent etoac / hexanes , 1 : 2 ) gives the amine ( expected 420 mg ; 97 %) as a colorless oil . 1 h - nmr ( cdcl 3 ; 300 mhz ): a ( ppm )= 1 . 45 ( s , 9h ); 2 . 99 - 3 . 04 ( m , 2h ); 3 . 27 - 3 . 33 ( m , 2h ); 4 . 18 ( dt , j = 5 . 9 , 1 . 3 hz , 2h ); 4 . 97 ( br s , 1h ); 5 . 18 - 5 . 32 ( m , 2h ); 5 . 71 ( br s , 1h ); 5 . 86 - 6 . 00 ( m , 1h ). 13 c - nmr ( cdcl 3 ; 75 mhz ): δ ( ppm )= 28 . 6 , 38 . 8 , 51 . 7 , 75 . 4 , 79 . 4 , 118 . 2 , 134 . 5 , 156 . 2 . hrms - ei : [ mh + ] calcd for c 10 h 21 o 3 n 2 , 217 . 1552 ; found , 217 . 1620 . final linker . the amine ( 216 mg ; 1 mmol ) is added to a solution of sodium carbonate ( 106 mg ; 1 mmol ) in water ( 2 . 5 ml ). fmoc - osucc ( 337 mg ; 1 mmol ) is dissolved in dioxane ( 2 . 5 ml ) and added . the mixture is stirred vigorously at room temperature for 2 h . the reaction is quenched by the addition of etoac ( 40 ml ) and aq . nacl ( 50 % sat ., 40 ml ). aqueous work - up and flash liquid chromatography ( silica ; eluent dichloromethane / methanol , 100 : 0 to 60 : 1 ) gives the target compound ( expected 130 mg ; 30 %) as a colorless oil . 1 h - nmr ( cdcl 3 ; 300 mhz ): a ( ppm )= 1 . 41 ( s , 9h ); 3 . 24 - 3 . 32 ( m , 2h ); 3 . 55 - 3 . 60 ( m , 2h ); 4 . 22 - 4 . 38 ( m , 3h ); 4 . 54 ( d , j = 6 . 4 hz , 2h ); 4 . 75 ( br s , 1h ); 5 . 22 - 5 . 32 ( m , 2h ); 5 . 81 - 5 . 95 ( m , 1h ), 7 . 28 - 7 . 43 ( m , 4h ); 7 . 60 - 7 . 63 ( m , 2h ); 7 . 74 - 7 . 78 ( m , 2h ). 13 c - nmr ( cdcl 3 ; 75 mhz ): δ ( ppm )= 28 . 6 , 38 . 7 , 47 . 4 , 49 . 8 , 67 . 8 , 76 . 2 , 79 . 6 , 120 . 2 , 120 . 4 , 125 . 2 , 127 . 4 , 128 . 0 , 132 . 3 , 141 . 6 , 143 . 9 , 156 . 0 , 157 . 6 . hrms - ei : [ mh + ] calcd for c 25 h 31 o 5 n 2 , 439 . 2233 ; found , 439 . 2244 . reverse transcriptase ( rt ) and a variety of dna polymerases of microbial origin are able to incorporate 3 ′- o - aminonucleoside triphosphates opposite their watson - crick pair in a complementary strand acting as a template for primed dna synthesis . reverse transcriptase is the ideal polymerase for direct sequencing of messenger rna . as rt also accepts dna templates , the enzyme can also be used in the sequencing - by - synthesis architectures being developed that amplify a small number of dna / rna molecules to give sequencable dnas ( in polonies , for example ). rt as well as other dna polymerases that accept 3 ′- o - aminonucleoside triphosphates are also useful for single molecule sequencing by synthesis strategies , if the 3 ′- o - aminonucleoside triphosphates carry a label that can be visualized at the single molecule level ( a fluorescent species such as rhodamine , cy3 and / or cy5 , a species that can be visualized by atomic force microscopy , or a species that can be visualized by stem , for example ). this notwithstanding , it is conceivable that mutant polymerases will be needed to accept to 3 ′- o - aminonucleoside triphosphates to meet the specifications of specific architectures . to obtain these , polymerases may be mutated , as has been done for other substrate analogs , guided by crystal structures for dna polymerases and reverse transcriptases [ eom96 ][ liy98 ][ kie98 ][ fra01 ][ hop99 ]. these crystal structures show a relatively tight packing between the enzyme and the 3 ′- hydroxyl group . as with the polymerases engineered to incorporate 2 ′, 3 ′- dideoxy nucleosides , the size of the amino acid residues in contact with the 3 ′- hydroxyl group is diminished . this disclosure teaches that replacing a phenylalanine in contact with the 3 ′- oh group by histidine , or a tyrosine in contact with the 3 ′- oh group by phenylalanine , improves the performance of polymerases for certain assay architectures . for site directed mutagenesis , the preferred protocol exploits the stratagene “ quik change ” kit . the process begins with a vector containing the inserted gene between strategically chosen restriction sites . this is transformed into an e . coli strain that is dam + . the colonies are grown , picked , and the subsequently extracting the plasmid with a miniprep or phenol - chloroform procedure . the vector is then used as a template for rolling circle replication where the primers bind to the desired mutation site on the gene of interest and introduce the desired mutation . both primers are designed to contain the desired mutation flanked by 15 nucleotides on each end , and the pcr is cycled for 18 rounds ( t denaturation : 30 sec ; t annealing : 60 sec . ; t extension : 1 min / kb plasmid ) with pfu turbo . the reaction is then treated with the dpni restriction nuclease to degrade the methylated and hemi - methylated dna of the original plasmid , thus leaving only the mutated dna produced in the pcr . the nicked product from the rolling circle replication is then transferred into a carrier cell line xl - 21 blue ( stratagene ). this method gives an 80 % mutation rate , making isolation of the correct variant trivial it is possible that rationally designed mutants of some ( or all ) of these polymerases may well prove to accept 3 ′- o - amino - 2 ′- deoxyribonucleoside triphosphates with the high rate and fidelity that meets the specifications for the sequencing - by - synthesis strategy . if this is the case , then work to develop polymerases will be done . recognizing that most site - directed mutagenesis is in fact site - directed damage , however , an alternative approach for obtaining polymerases that incorporate 3 ′- o - amino - 2 ′- deoxyribonucleoside triphosphates to specifications is preferred . this exploits a strategy , called compartmentalized self - replication ( csr ), for the evolution of polymerases [ gha01 ]. in csr , individual polymerase variants are isolated in water droplets that are suspended in oil . these droplets provide separate compartments into which are put single e . coli cells containing a clone for a single polymerase variants , together with nucleoside triphosphates and other appropriate reagents . within the drop , each polymerase replicates only its own encoding gene to the exclusion of genes in other compartments . consequently , only genes encoding active polymerases are manipulated , while inactive variants fail to amplify their own genes and disappear from the gene pool . among differentially active variants , the more active can be expected to produce proportionally more “ offspring ,” correlating post replication copy number with enzymatic turnover . as was shown in earlier work by tawfik and griffiths [ taw98 ], the individual drops in a water - in - oil emulsion are stable for prolonged periods at temperatures exceeding 90 ° c . this approach allows selection for enzymatic activity under a wide range of conditions . using this approach , holliger selected for variants of the taq dna polymerase with 11 - fold higher thermostability than the wild - type enzyme or with a & gt ; 130 - fold increased resistance to the inhibition by heparin [ gha01 ]. selection for a polymerase that incorporates 3 ′- o - amino - 2 ′- deoxynucleotides is done using this system with some minor adaptations . as with holliger &# 39 ; s experiment , the polymerase variants are carried on a pask75 plasmid . the gene lies after an xbai site and before a sali site ( c * aattg ) and a tli site ( c * tcgag ) site . the expression of the polymerase variant is done inside the cell . the solution outside the cell , however , contains tli endonuclease , a thermostable restriction enzyme , as well as a 3 ′- o - amino - 2 ′- deoxynucleoside triphosphate . in the first heat cycle , the cell breaks open and the plasmid is delivered to the restriction endonuclease outside the cell . the restriction enzyme cleaves the plasmid at the single tli site , generating a sticky end with a 3 ′- overhang that can serve as a polymerization template . the thermostable polymerase variant released from the cell then has the opportunity to add a single 3 ′- o - amino - 2 ′- deoxynucleotide to the 3 ′- end of the sticky end in a template - directed fashion . polymerases that can do so will tag their own gene with a 3 ′- onh 2 unit . work up of the emulsion in ether / water mixtures generates a pool of dna that encodes variants of taq . those variants that were able to add a 3 ′- o - amino - 2 ′- deoxynucleotide will be tagged with a 3 ′- onh 2 unit . these will be retained on an aldehyde column through the formation of an oxime . those that failed to add a 3 ′- onh 2 unit will be washed from the column , as the only other amine groups in the dna structure ( the exocyclic nucleobase amines ) are shielded from reaction by hydrogen bonding interactions and the phosphodiester backbone . due of the presence of a sali site between the gene and the 3 ′- o - amino - 2 ′- deoxynucleotide , the 3 ′- cap can be cleaved with sali , the encoding region of the gene can be recovered by cleaving with xbai . the genes are then shotgun cloned back into the plasmid between the xbai and sali sites , ready for another cycle of selection or for analysis . the tli site is especially convenient , as it creates a sticky end having one of each of the four nucleotides . if the 3 ′- o - amino - 2 ′- deoxynucleoside bears a thymine , then termination occurs at the first nucleotide , and one selects for polymerases that incorporate a t - bearing 3 ′- o - amino - 2 ′- deoxynucleoside opposite a . to select for polymerases that incorporate 3 ′- o - amino - 2 ′- deoxynucleotides bearing c , we add this triphosphate as well as dttp . the polymerase will add the first ( natural ) da , and then will be challenged to complement the next nucleotide in the template ( a g ). this process can be completed to screen for polymerases that incorporate all nucleotides . conversely , the procedure is reversed to exclude polymerases that incorporate the wrong nucleotide . thus , the first cycle can include the 3 ′- o - amino - 2 ′- deoxynucleoside triphosphate carrying a c . a faithful polymerase will not incorporate it opposite the first a in the template . here , the affinity column cycle is reversed , where the undesired genes are retained on the column , and the desired genes are eluted . these water - in - oil emulsions are simple to make . briefly , 0 . 2 ml of csr mix [ the required 3 ′- o - amino - 2 ′- deoxynucleoside triphosphate and any required dntp &# 39 ; s ( 0 . 2 mm for taq , 0 . 8 mm for vent and 9 ° n variants ), 50 μm tetramethylammonium chloride , and 0 . 05 % ( vol / vol ) dnase - free pancreatic rnase ( roche ) in 1 × taq buffer , as well as the tli enzyme and induced taq expresser cells ) are added drop wise to 0 . 4 ml of the organic phase [ 4 . 5 % ( vol / vol ) span 80 ( fluka ), 0 . 4 % ( vol / vol ) tween 80 , and 0 . 05 % ( vol / vol ) triton x - 100 in light mineral oil ( all sigma )] under constant stirring ( 1 , 000 rpm ). after addition of the aqueous phase , stirring is continued for 5 minutes more before thermocycling . compartment dimensions are determined by light microscopy and by laser diffraction spectroscopy . compartments had average diameters of 15 μm and proved heat - stable , with no coalescence or changes in compartment size after 20 cycles of pcr as judged by laser diffraction and light microscopy . for recovering polymerase genes , emulsions are quenched with ether and the phases are separated . the aqueous phase was extracted with ether , and the dna mixture is passed through an aldehyde affinity column and washed thoroughly . the captured dna is then removed either by washing with acetone - water mixtures , or by direct cleavage with sali . a working prototype for a sequencing by synthesis is built on a glass slide that uses dna molecules that are mobilized in the form of a hairpin , and are therefore able to self - prime . the slide is dipped into a solution containing the four 3 ′- o - amino - 2 ′- deoxynucleoside triphosphates and the polymerase . one fluorescently labeled , capped nucleotide is incorporated on each spot , selected to be the one that is complementary to the next nucleotide on the template . the excess reagents are removed by washing , and a four color fluorescence imager is used to image the surface of the chip . the color of each spot reveals the identity of the nucleotide that was added . after imaging , any unreacted 3 ′- oh groups on the self - primed template are capped by adding ddntps and dna polymerase . the 3 ′- oh cap and the fluorescent label are then removed by adding a solution containing the napthoquinone reagent , and the chip is washed again . the process is repeated . a fluorimeter that is equipped with an accessory to detect fluorescence from a glass slide is used to image the fluorescence emission in our proposed dna sequencing system . for large scale tests , a multi - color scanning system able to detect four different fluorescent dyes ( 500 nm - 700 nm ) ( gsi lumonics scanarray 5000 standard biochip scanning system ) is used . for both proof - of - concept and more advanced work , two - dimensional arrays of hairpin dna are used . these synthetic templates for evaluating the technique of sequencing by synthesis are immobilized on 96 - well plates with well coated with streptavidin . biotin attachment strategies are preferably replaced by a covalent immobilization chemistry . such chemistry provides the chip with greater stability and a longer shelf life ( fig1 ). 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| 2 |
referring initially to fig1 , a syringe device for expelling a fluid through a needle mounted on a hub is shown and generally designated 10 . as shown in fig1 , the device 10 includes a substantially cylindrical syringe body 12 that is centered on an axis 14 and formed with a finger grip 16 at its proximal end . fig1 further shows that the device 10 includes an adapter 18 sized to fit within the syringe body 12 . the adapter 18 includes a cylindrical portion that is also centered on the axis 14 . for the device 10 , a substantially cylindrical needle guard 20 is provided and positioned co - axially with both the syringe body 12 and adapter 18 . the guard 20 is sized to fit within the adapter 18 . it can be further seen that the device 10 includes a plunger 22 that is formed with a grip flange 24 at its proximal end . referring to fig2 , a straight , elongated hypodermic needle 26 is shown extending from a sharp needle tip 28 to a needle hub 30 . as best seen in fig3 a , the needle 26 may be mounted to the passively guarded , fillable injection device 10 . specifically , the device 10 includes a luer member 32 that receives and engages the needle hub 30 . the luer member 32 has a proximal portion or head 34 . extending distally from the head 34 is a substantially cylindrical shaft 36 centered on the axis 14 . the needle hub 30 is mounted to the luer member 32 at the shaft &# 39 ; s distal portion or distal shaft end 38 . additionally , the head 34 has a proximal side 33 and a distal side 35 that engages the adapter 18 . circumferentially - spaced truss - like webs 40 are provided on the luer member 32 to reinforce the connection between the shaft 36 and the head 34 . furthermore , the luer member 32 includes a pipe - like conduit 39 that extends from the proximal side 33 of the head 34 to the shaft end 38 . when the needle hub 30 is frictionally mounted on the shaft end 38 , the needle hub 30 and luer member 32 are sealed together to establish fluid communication between the needle 26 and the conduit 39 . as shown in fig3 a , the adapter 18 engages the luer member 32 about the webs 40 thereby preventing rotational movement therebetween . the adapter 18 includes a substantially cylindrical wall 42 that is centered on the axis 14 and forms a cavity 43 . the wall 42 extends from a proximal end 44 substantially covered by a base 45 to an open distal end 46 . at its proximal end 44 , the adapter 18 has a narrow circumference and is designed to engage the distal side 35 of the head 34 of the luer member 32 . at its distal end 46 , the adapter 18 has a broad circumference and is designed to engage the plunger 22 and receive the guard 20 . as can be seen in fig3 a , the adapter 18 also includes two oppositely positioned , axially aligned slits 48 . as best seen in fig3 a , the adapter 18 is sized to allow the cylindrical guard 20 to move along the axis 14 into and out of the adapter cavity 43 . specifically , the guard 20 may be moved between an extended position 49 ( shown in fig3 a and 4a ) to a retracted position 53 ( shown in fig3 b and 4b ). structurally , the guard 20 is a shell forming a lumen 51 that extends between an open proximal end 50 and an open distal end 52 . the guard 20 includes abutments 54 that extend radially outward from the proximal end 50 . also in fig3 a , it can be seen that the inverted plunger 22 has a substantially cylindrical side member 56 that extends from a closed proximal plate member 58 to an open distal edge 60 . structurally , the cylindrical side member 56 surrounds a fluid chamber 62 and is slidingly mounted on the proximal end 44 of the adapter 18 . fig3 a further shows that the plunger 22 is formed with tangs 64 that extend radially inward ( i . e . toward the axis 14 ) and distally from the cylindrical side member 56 of the plunger 22 . it can be seen in fig3 a , that the device 10 includes an elastomeric seal 66 that is attached onto the proximal end 34 of the luer member 32 . specifically , the seal 66 is press fitted onto the proximal end 34 of the luer member 32 . as shown , the seal 66 has a generally fusiform or spindle - like shape and is formed with a through - hole 68 . when the open distal edge 60 of the plunger 22 is slid over the luer member 32 and adapter 18 , the seal 66 compresses between the luer member 32 and the cylindrical side member 56 of the plunger 22 to establish sealed fluid communication between the fluid chamber 62 and the conduit 39 of the luer member 32 . when the needle hub 30 is mounted on the luer member 32 to establish fluid communication between the needle 26 and the conduit 39 , the plunger 22 can be moved to a withdrawn position 61 ( shown in fig3 b and 4b ) to draw fluid through the needle 26 and into the chamber 62 . furthermore , the plunger 22 can be moved to an advanced position 63 ( shown in fig3 c and 4c ) to expel fluid from the chamber 62 through the needle tip 28 . as further shown in fig3 a , the syringe body 12 extends from an open proximal end 70 to an open distal end 71 . positioned at the proximal end 70 , the finger grip 16 includes a recess 72 sized to receive the grip flange 24 of the plunger 22 . functionally , the plunger 22 can be advanced distally after an injection until the grip flange 24 is positioned in the recess 72 . once the grip flange 24 is positioned in the recess 72 it cannot be removed ; therefore , subsequent movement of the plunger 22 relative to the syringe body 12 is effectively prevented . turning to fig4 a , other features of the device 10 may be seen . specifically , the adapter 18 is shown having cam levers 74 positioned at its distal end 46 . the cam levers 74 are in a biased position 76 in which the plunger 22 forces them to be coincident with the rest of the cylindrical wall 42 . however , the cam levers 74 mechanically prefer a relaxed position 78 ( shown in fig4 b ) in which the distal ends 80 of the cam lever 74 extend radially outward from the cylindrical wall 42 . as shown in fig4 a , the guard 20 has hinges 82 . similar to the cam levers 74 of the adapter 18 , the hinges 82 of the guard 20 have a relaxed position 84 in which the proximal ends 86 of the hinges 82 extend radially outward from the rest of the guard 20 . the biased position 88 of the hinges 82 is shown in fig4 b . as further shown in fig4 a , the syringe body 12 can also include flanges 90 at its distal end 71 . the flanges 90 extend distally and radially inward from the cylindrical portion 92 of the syringe body 12 . their purpose is discussed below . by cross - referencing fig3 a - d and 4 a - d , it can be seen that the device 10 includes a mechanism to lock the guard 20 in an extended position 49 covering the needle tip 28 prior to an injection procedure . once locked , the guard 20 can only be unlocked by movement of the plunger 22 . as previously discussed , the adapter 18 is formed with cam levers 74 having distal lever ends 80 . comparing fig4 a with fig4 b , it can be seen that the cam levers 74 are deflectable by the cylindrical side member 56 of the plunger 22 from a relaxed position 78 ( fig4 b ) to a biased position 76 ( fig4 a ). in the relaxed position 78 ( fig4 b ), the cam levers 74 extend radially outward from the remaining cylindrical section of the adapter 18 . on the other hand , as shown in fig3 a , in the biased ( i . e . deflected ) position 76 , the cam levers 74 are coincident with the remaining cylindrical wall 42 of the adapter 18 . when the plunger 22 is in the advanced position 63 shown in fig4 a , the cylindrical side member 56 of the plunger 22 contacts the cam levers 74 and deflects them into the biased position 76 . as shown in fig4 a , when the cam levers 74 are in the biased position 76 , the lever ends 80 engage the proximal ends 86 of the hinges 82 of the guard 20 and prevents proximal movement of the guard 20 . when the plunger 22 is in its withdrawn position 61 as shown in fig3 b and 4b , the cam lever 74 relaxes into its undeflected , outward position 78 ( as shown in fig4 b ) and allows the guard 20 to move proximally . as an additional locking mechanism , the syringe body 12 may be moved relative to the adapter 18 to deflect the cam levers 74 of the adapter 18 with its flanges 90 . as shown in fig4 d , the flanges 90 are moved toward the adapter 18 when the plunger 22 and adapter 18 are fully pushed into the syringe body 12 . as a result , the flanges 90 contact and force the cam levers 74 of the adapter 18 to the biased position 76 to lock the device 10 to prevent any further proximal movement of the needle guard 20 . this prevents inadvertent reuse of the device 10 . initially , the device 10 is provided without a needle 26 . to mount a needle 26 on the device 10 , the needle guard 20 is first moved to the retracted position 53 by withdrawing the plunger 22 . then the needle hub 30 is frictionally engaged with the shaft end 38 of the luer member 32 as can be understood from fig3 b and 4b . after mounting the needle hub 30 on the shaft end 38 , the needle guard 20 is allowed to move to its extended position 49 to cover the needle 26 by moving the plunger 22 to its advanced position 63 as shown in fig3 a . as further shown in fig3 a the tangs 64 of the plunger 22 extend through the slits 48 in the adapter 18 to engage the abutments 54 and retract the guard 20 when the plunger 22 is withdrawn . from fig4 a , it can be seen that the cylindrical side member 56 of the plunger 22 holds the cam levers 74 deflected inward to lock the guard 20 and prevent proximal movement of the guard 20 . as illustrated by fig3 a - b and 4 a - b , use of the device 10 begins by withdrawing the plunger 22 . such proximal movement of the plunger 22 has several effects . specifically , as shown in fig4 a and 4b , initial proximal movement of the plunger 22 allows the cam levers 74 to relax outwardly from the axis 14 and unlock the guard 20 for proximal movement . as shown in fig3 a and 3b , additional proximal movement of the plunger 22 engages the tangs 64 with the abutments 54 , causing the guard 20 to be retracted with the plunger 22 . also , withdrawal of the plunger 22 draws air ( or other fluid ) through the needle 26 and into the fluid chamber 62 . once the guard 20 has been retracted as shown in fig3 b and 48 , the next step is to insert the exposed distal needle tip 28 into a medicament vial ( illustrated by surface 94 in fig3 c and 4c ). at this point , the plunger 22 can be depressed as shown in fig3 c and 4c to expel air into the vial and void the fluid chamber 62 . comparing fig3 b and 4b with fig3 c and 4c , it can be seen that during its advance the plunger 22 disengages the guard 20 . thus , as illustrated by fig3 c and 4c , after advancing the plunger 22 , distal movement of the guard 20 is only prevented by the contact between the distal end 52 of the guard 20 and the surface 94 . next , the plunger 22 can be withdrawn to fill the chamber 62 with medicament fluid 95 ( note fig3 b and 4b are representative of the configuration of the device 10 after the chamber 62 is filled with medicament 95 ). from fig3 b , it can be seen that during withdrawal of the plunger 22 , the tangs 64 reengage the abutments 54 . the result is that the plunger 22 engages the guard 20 and prevents distal advancement of the guard 20 . as illustrated by fig3 b and 4b , when the needle 26 is removed from the vial , the distal tip 28 of the needle 26 remains unguarded and exposed . the device 10 is now ready for an injection . as illustrated by fig3 c and 4c , to inject a medicament into a patient , the distal tip 28 of the needle 26 is inserted into the patient ( represented by surface 94 ) and the plunger 22 is depressed . as shown in fig3 c , the distal advancement of the plunger 22 releases the guard 20 . once released , the guard 20 is free to move distally under the influence of a coil spring 96 that is interposed between the guard 20 and the adapter 18 . thus , as the needle 26 is withdrawn from the patient , the needle 26 retracts proximally into the guard 20 which remains in contact with the patient &# 39 ; s skin ( represented by surface 94 ). fig3 a and 4a are representative of the device 10 after the needle 26 has been withdrawn from the patient and the needle 26 has passively retracted into the guard 20 . once the device 10 has been removed from the patient , the plunger 22 and the adapter 18 can be advanced distally relative to the syringe body 12 to lock the guard 20 in place ( fig4 d ). fig3 d and 4d also show that this places the grip flange 24 of the plunger 22 in the recess 72 formed in the syringe body 12 . functionally , once the device 10 is in the configuration shown in fig3 d and 4d , the plunger 22 is disabled and the guard 20 completely covers the hollow needle 26 to protect the user from unwanted needle sticks and prevents inadvertent reuse of the device 10 . while the particular devices and methods as herein shown and disclosed in detail are fully capable of obtaining the objects and providing the advantages herein before stated , it is to be understood that they are merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims .
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fig1 shows a settling tank 1 of the present invention in an assembled configuration . the constituent components are best shown in the exploded view of fig2 . the portable settling tank 1 is comprised of a portable open - top container 40 , a disposable watertight liner 3 , a disposable coarse granular material 10 , a disposable filter cloth 20 , and a drain port 2 . the cross - section view of fig4 shows how the components are layered and overlapped to form a vessel for receiving a thin slurry 30 . the slurry 30 , comprised of particulate 32 ( not shown ) suspended in water , is introduced by pump action into the vessel through a deeply - drafted inlet port 5 . the particulate 32 settles therein by gravity segmentation to leave a floating layer of substantially clean water 31 . filtration through the filter cloth 20 into an interstitial space 14 in the coarse granular material 10 results in a filtrate 22 ( not shown ), which is also substantially void of particulate 32 . filtrate 22 is removed by pump or gravity action through the drain port 2 . clean water 31 is removed by pump action through a shallowly - drafted exit outlet port 6 . the resulting residue , consisting essentially of dewatered particulate 32 , is discarded along with all contents of the vessel , including the watertight liner 3 , the coarse granular material 10 , and the filter cloth 20 . the watertight liner 3 assures that the open - top container 40 is left in its original state and precludes any need for cleaning or decontamination . referring to fig2 , portable open - top container 40 has a bottom 41 and four sides 42 enclosing a volume . the volume may be of any size appropriate for the amount of slurry to be processed . in the preferred embodiment , the volume is defined by the dimensions is of 22 feet long by eight feet wide by four and a half feet deep . while any portable rigid or semi - rigid container is suitable , preferably the open - top container 40 is a roll - on waste container 43 , typically available by rental from a local waste - disposal company . because the open - top container 40 is portable , a transportation means for hauling purposes is also comprehended . the watertight liner 3 is draped over the bottom 41 and four sides 42 of the open - top container 40 to shield the interior surfaces of the container . the watertight liner 3 may lap over the top edges of the container , or otherwise be fixed thereto , so that the liner cannot be caused to expose the interior surfaces . the watertight liner 3 is preferably a film with a gauge of 5 - 10 mils . while any waterproof film is suitable , a preferred choice would be one of bio - degradable or recycled resin composition , in order of preference . the preferred resins are those comprising polyethylene , polypropylene , or a mixture thereof , or polyolefin , which may be a blend of those resins . a layer of coarse granular material 10 is laid over the bottom of the watertight liner 3 to effectively provide a reservoir for drainage by means of interstitial space 14 . interstitial space 14 is comprised of all space within the boundaries of the layer which is not filled with the material of the coarse granular material 10 . preferably , the layer is 6 - 12 inches in depth , but may be any depth consistent with the volume of drainage desired . the coarser the consistency , the larger the interstitial space 14 for a given volume of the layer ; consequently , therefore , coarsening provides a means for optimization . the coarse granular material 10 may be anything disposable which has the property of maintaining is interstitial space therein , as , for example , pine cones , or discarded bricks arrayed in a jumble . it may also be discarded old pallets , or broken up construction materials , although not granular in the same sense . in the preferred embodiment , the coarse granular material 10 is stones 11 , and in a particularly preferred embodiment , the stones are river rock 12 . the drain port 10 vents the watertight liner 3 and ducts into the interstitial space 14 to drain said space . in the preferred embodiment , an intermittent pump provides the means for draining . the intermittent pump should be of a peristaltic , or otherwise of a self - priming , type because the pump may outstrip the flow of drainage . in an alternate embodiment , shown in fig3 , gravity may provide the means for draining . in order to facilitate this means , a side opening 44 is provided in at least one of the sides 42 to permit a gravity flow there through . in a particular alternate embodiment , the side opening 44 is a doorway 45 , which may otherwise provide access to the interior of open - top container 40 . if there is a door 47 in the doorway 45 , and if there are gaps around the periphery thereof , the gaps may present sufficient opening for leaching purposes . otherwise , a false wall 46 may be constructed adjacent to the doorway 45 to function as a supporting wall and prevent collapse of the vessel when door 47 is positioned open . false wall 46 may have an aperture 48 , which is in fluid communication with the drain port 2 , to facilitate gravity drainage . false wall 46 may be guyed to one or more sides 42 by rope or cabling to thereby support it upright . it is intended that false wall 46 be discarded with the contents of the open - top container 40 . false wall 46 may be comprised , for example , of an old sheet of plywood . the disposable filter cloth 20 is draped over the watertight liner 3 and the layer of coarse granular material 10 . the filter cloth 20 may lap over the top edges of the container , or otherwise be fixed proximate thereto , so that the filter cloth remains at all times above the liquid surface level . the filter cloth 20 is a woven or nonwoven textile having a sieve matched to the tiniest allowable particle in the filtrate . in the preferred embodiment , the filter cloth 20 is a geotextile cloth , or equivalent , fabricated with polyester or polypropylene yarns , or , otherwise laid up with polypropylene fibers . such a material is sometimes used in road construction or for environmental stabilization . the preferred sieve size is in the 100 - 200 micron range , and a particular preference requires 150 microns or less to trap seeds . the filter cloth 20 is designed to substantially trap the particulate 32 and separate it from the filtrate 22 by filtering action . this filtering action may or may not be assisted by pump suction through the drain port 2 . applying pump suction before the particulate 32 has had a chance to naturally settle , however , might clog the filter cloth 20 prematurely by driving particles into the pores of the cloth . in a similar way , slurry maintained at full tank capacity , or in other words , with a full “ head ”, would hydraulically pressurize the sediment layer on the bottom . a means for reducing water in the slurry while substantially avoiding clogging of the filter cloth 50 ( fig5 ), hereinafter “ a means for reducing water 50 ”, therefore , would comprise the procedural steps of adding the slurry 30 and pumping the clean water 31 in staggered cycles that would result in minimizing the head . a staggered cycle would involve , for example , pumping in slurry , waiting for is settlement to vacate a thin top layer , and then pumping clean water out of the thin top layer . the means for reducing water 50 would further comprise cyclically pumping the filtrate 22 to maintain the filtrate level just above the bottom of the filter cloth 20 ; or , otherwise , allowing gravity drainage of the filtrate 22 . these cyclical steps of pumping , both of clean water and of filtrate , if applicable , would continue until a preferred buildup of settled particulate 33 ( not shown ) is achieved . it is recognized that the stratification of particulate 32 within the pool of slurry 30 is in the form of a gradient , rather than discrete in the form of layers . that is to say , there is a distribution of particulate 32 decreasing from bottom to top over any relatively short period of time , such that a “ clean ” top layer is only an approximation . it is further recognized that the addition of more slurry 30 will inevitably disturb this distribution . the preferred means for reducing water 50 , therefore , further comprises pumping in slurry at one end of the open - top container 40 and pumping out clean water at the opposite end . the preferred means still further comprises locating the distal end of the inlet port 5 at or near the top of the bottom settlement and the distal end of the outlet port 6 at or near the top of the clean water layer . as the bottom settlement collects over time and rises in level , the distribution will cause more and more of the particulate 32 to remain present in the clean water layer . when a recognizable amount of particulate is pumped out with the clean water , it is either a signal that the current pumping cycle is excessive ; or , otherwise , that the preferred buildup of settled particulate 33 has been reached . the latter will be hallmarked by shorter and shorter pumping cycles . an amount of particulate 32 in the clean water 31 which is recognizable might be that is amount clogging a filter to the pump , for example . when the preferred buildup of settled particulate 33 has been reached , the pumping of filtrate 22 may proceed unrestricted until all water is substantially removed and an essentially dry residue remains . fig5 shows an alternate embodiment , wherein a method for dewatering a slurry 100 comprises the following process : step 101 . providing the portable open - top container 40 having the bottom 41 and four sides 42 . step 102 : covering the bottom 41 and the four sides 42 with the disposable watertight liner 3 . step 103 : covering the bottom of the watertight liner 3 with the coarse granular material 10 having the interstitial space 14 therein . step 104 : layering the filter cloth 20 over the coarse granular material 10 and the watertight liner 3 . step 105 : providing the drain port 2 through the watertight liner 3 and into the interstitial space 14 . step 106 : pumping the slurry 30 containing the particulate 32 into one end of the open - top container 40 through the open top , whereby settlement produces relatively clean water 31 at the top of container and settled particulate at the bottom , and filtering through the filter cloth 20 produces the filtrate 22 in the interstitial space 14 . step 107 : using the means for reducing water 50 , whereby room is provided for the cyclical addition of more slurry 30 . step 108 : deciding whether or not the preferred buildup of settled particulate 33 has been achieved ; and , if not , repeating steps 106 and 107 . step 109 : draining any remaining filtrate 22 through the drain port 2 . step 110 : transporting the open - top container 40 and its residual contents to a disposal site . step 111 : discarding the watertight liner 3 , the coarse granular material 10 , the filter cloth 20 and the residue by dumping the contents to leave the container in its original state . it is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the preceding description or illustrated in the drawings . the means for reducing water 50 might be carried out by evaporation in place of pumping clean water , for example . also , it is to be understood that the phraseology and terminology employed herein are for the purpose of the description and should not be regarded as limiting .
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the present invention relates to an apparatus and method for the treatment of stimulation fluid . when describing the present invention , all terms not defined herein have their common art - recognized meanings . to the extent that the following description is of a specific embodiment or a particular use of the invention , it is intended to be illustrative only , and not limiting of the claimed invention . the following description is intended to cover all alternatives , modifications and equivalents that are included in the spirit and scope of the invention , as defined in the appended claims . fig1 illustrates a schematic depiction of one embodiment of the present invention . the treatment of the stimulation fluid is carried out in a tank ( 1 ) having a first end ( 30 ) and a second end ( 32 ) and that is sectioned . as shown in fig1 , in a preferred embodiment , the tank ( 1 ) has three sections , a primary agitation section ( 2 ) into which the stimulation fluid is initially charged through the fluid inlet ( 25 ), an intermediate settling section ( 3 ) and a final settling section ( 4 ). however the tank ( 1 ) may have any number of intermediate sections to optimize the process as required . the final settling section ( 4 ) has a fluid outlet ( 6 ) for the removal of treated fluid . the sections are separated by substantially vertical barriers ( 22 ) that extend from the floor of the tank ( 26 ) upwards towards the roof of the tank ( 27 ). the transfer of fluid from one section to another occurs by primarily or solely by flowing over the top of the barriers ( 22 ) when the level of the fluid in the section reaches the level of the top of the vertical barrier ( 22 ). solids and denser fluids remain trapped behind the barrier while lighter fluids forming the upper layers pass over the barrier . as the stimulation fluid is pumped into the tank ( 1 ) through the fluid inlet ( 25 ), reagents including , but not limited to , liquefied clay and acidified water are added from separate storage vessels ( 10 , 11 ). the mixture of reagents and stimulation fluid enters the tank through the fluid inlet ( 25 ) and fluid flows in a direction from the first end of the tank ( 30 ) towards the second end of the tank ( 32 ). as more of the stimulation fluid and reagent mixture is added , any reagent , such as clay or aqueous acid and having a density greater than the density of the stimulation fluid settles to the bottom of each section , while the lighter hydrocarbon - based stimulation fluid forms an upper layer . some of the heavier density reagent may overflow into the intermediate ( 3 ) or final settling section ( 4 ); however , the amount settling in the bottom of the sections decreases in going from the primary ( 2 ) to the final section ( 4 ). the primary agitation section ( 2 ) may be provided with a baffle ( 24 ) to direct the flow of the mixture of stimulation fluid and reagent mixture downwardly towards the floor of the tank ( 26 ). as more of the mixture is added and is agitated by re - circulation ( as described below ) in the primary agitation section ( 2 ), the primary section ( 2 ) becomes filled and the stimulation fluid and some reagent and entrained solids may overflow into the adjacent intermediate section ( 3 ). operation in this manner continues until the level of fluid in the intermediate section ( 3 ) reaches a level whereby it spills over into the final settling section ( 4 ). as shown in fig1 , in one embodiment , the tank further comprises a fluid agitation system that can be coupled to the primary agitation section ( 2 ), or to any of the other sections to promote the mixing of the reagents and the stimulation fluid . in this manner , the lower phases of a section may be selectively removed and mixed and agitated and then reintroduced to the primary section ( 2 ) through the fluid inlet ( 25 ). the system consists of a loop containing a mixing pump ( 8 ) and optionally a jet mixer ( 14 ) as well . fluid is extracted from the bottom of the sections through a section outlet ( 34 ) positioned at the lowest point of the floor of each section . the extracted fluid is mixed and agitated using the mixing pump ( 8 ) and then reintroduced to the tank ( 1 ) through the fluid inlet ( 25 ). the jet mixer ( 14 ) may be additionally used to introduce powdered additives such as clay . agitation in this manner promotes thorough and complete mixing of the reagents and the stimulation fluid . agitation in the primary and intermediate sections may also be achieved using such other suitable agitation means as would be selected by one skilled in the art including use of a mechanical agitator ( not shown in the figures ) and baffles ( not shown in the figures ). the sections of the tank are connected such that they share a common vapour space towards the roof of the tank ( 27 ). the tank ( 1 ) has a vapour outlet ( 36 ) to facilitate the removal of vapor build up . in one embodiment , a vapour transfer line having an associated pump ( 5 ) is coupled to the vapour outlet ( 36 ) for the avoidance of pressure build - up . in one embodiment , after the stimulation fluid and regent mixture has been thoroughly mixed for sufficient amount of time in a section , the entire section containing the reagent - fluid mixture may be transferred to the next section , analogous to a batch process , or alternatively , the operation can be carried out as a continuous process , where portions of a section are transferred to the adjacent section and so on . the intermediate and final settling sections allow for separation of the hydrocarbon phase from the aqueous phase in the case of acid treatment , or separation of the hydrocarbon phase from the settling agent for removal of the gelling agent . complete separation is not necessarily required and may be monitored by means of a sight - tube ( not shown ) or the like . any of the sections may include a sloping floor to assist in collection and removal of solids , or denser fluids . in one embodiment , each of the sections comprises a floor which slopes upwards towards the second end of the tank ( 32 ), as shown in fig1 . as already discussed , a section outlet ( 34 ) is situated in a lower portion of each section . in one embodiment the section outlet ( 36 ) comprises a collection tube placed transversely within each section , at the bottom of the sloping floor . the section outlets ( 36 ) may be attached to a suction manifold ( 7 ) as described below . a fluid outlet ( 6 ) is connected to the final settling section ( 4 ) for removal of the treated stimulation fluid and , transfer and storage to a product return vessel or barrel ( 16 ) assisted by a product return pump ( 9 ). the sections outlets ( 36 ) are also connected to a tank suction manifold ( 7 ) via appropriate valves . at one end , the tank suction manifold ( 7 ) is connected to a suction point for a vacuum truck ( 15 ) that may be used to clean out the unit when operations has been completed or to change chemicals during operation , and at the other end to the previously described agitation and mixing system . the tank suction manifold ( 7 ) allows for recirculation of the stimulation fluid and more complete treatment of the fluid , which may be tested using appropriate sensors within each section . in one embodiment , the primary agitation section ( 2 ) has a volume approximately one - half of the intermediate settling section ( 3 ) and a final settling section ( 4 ), which may have approximately equal volume . relative residence time in each section may be manipulated by providing different volume capacity in each section , or by varying the height of the barriers ( 22 ) which separate the sections , or both . overall residence time in the tank ( 1 ) may be varied by altering the flow rate into the fluid inlet ( 25 ). fig1 also discloses a heat exchange system ( 13 ) with appropriate connections , valves , pumps and controls connected to two fluid storage vessels ( 12 and 16 ). the fluid storage vessels ( 12 and 16 ) may be used to store untreated stimulation fluid and to receive treated fluid from the fluid outlet ( 6 ). the heat exchange system ( 13 ) is used to preheat the stimulation fluid prior to introduction to the tank ( 1 ) which promotes reactivity with the reagents . various modifications can be made to the heat exchange system without departing from the scope of the invention . in addition , although glycol has been indicated as the fluid for heat exchange , a skilled artisan would recognize that other fluids have heat exchange capacity , such as , for example , thermaoil ™, dowtherm ™ or silitherm ™ can also be used , where appropriate . the setup disclosed in fig1 has a common pathway , which is preferred but not essential , for the two fluid storage vessels ( 12 , 16 ) for receiving and heating the fluid . the outlet from the heat exchanger is set up so that the product may be returned to the originating vessel or can be used to transfer the fluid from one product vessel to another . in addition , appropriate connections and valves have been provided to re - direct the stimulation fluid from either storage vessel ( 12 , 16 ) for treatment to the inlet on the tank ( 1 ). the size of the apparatus for treatment of the fluid can vary depending upon the objective for use of it , as would be known to a skilled artisan . in addition , the apparatus can be setup near a site of operation or can be mounted and operated on a moving vehicle , as shown in fig2 - 6 , or may be skid - mounted . fig2 - 6 disclose an embodiment with additional intermediate settling sections , which may be added as required , for optimization of the process . various other modifications and amendments may be made to the apparatus disclosed and discussed herein , without departing from the scope of the invention , as defined by the appended claims .
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fig1 shows the cross section of a typical optical mouse . shown is a light source ( led or vcsel ) 100 , from which light is directed / focused onto an object ( table , desk , paper , mouse mat ) 110 , and the resulting image observed on an optical sensor 120 which tracks movement . typically there are low - friction pads 130 mounted on the optical mouse to reduce friction and allow the mouse to move smoothly over the surface . typically there are one or more buttons on the top of the mouse ( not shown ), and usually a scroll wheel or tilt wheel 140 . fig2 shows a cross section of a mouse device according to one embodiment of the invention . this mouse includes a second optical sensor unit 250 and associated light source 260 . preferably the “ mouse surface ” 270 provided by this second sensor arrangement 250 , 260 is positioned directly underneath the position of the index finger when it is in a relaxed or comfortable state . consequently the sensor unit 250 may receive an image based on light reflected off an object , such as a finger , on the mouse surface 270 . the first optical sensor 220 and light source 200 are located on a first , main substrate ( printed circuit board , pcb ) 280 . the second optical sensor ( and associated light source ) is mounted on a second substrate ( pcb ) 290 . as an alternative to the arrangement depicted , the mouse surface could be on a side of the device ( with a plane approximately perpendicular to that depicted ) for manipulation by a thumb . fig3 shows an improved mouse from that of fig2 . by careful design of the mouse housing , the second optical sensor 250 and associated light source 260 has been mounted on the same substrate 280 as the first optical sensor 220 . this reduced the thickness and provides greater comfort to the user and also decreases the manufacturing cost . fig4 illustrates one of a number of exemplary implementing architectures according to an embodiment of the invention . it shows the first motion sensor ( looking down ) 220 , the second motion sensor ( looking up ) 250 and the controller 400 , which may be an i2c or spi or similar control interface . in particular , the connections of the “ control ,” “ motion ,” ( used to signal if the sensor has detected movement ) and ( optionally ) “ shutdown ,” ( used by a host to power down a sensor to save energy ) pins are shown for the sensors 220 , 250 and controller 400 . in this example “ motion ” and “ shutdown ” are independently connected to the controller device 400 . the output from the controller 400 is preferably a usb ( universal serial bus ) output or may even be a signal suitable for rf ( radio frequency ) modulation , in the case of a wireless mouse . the disadvantage of this system is the extra wires and input pins used add to the complexity and cost of the mouse . fig5 shows an optimized system where the controller device 400 is connected to only one sensor 250 . due to size constraints , the down - facing sensor { desk } 250 has more space available than the up - facing { finger } sensor 220 . therefore , the down - facing sensor 250 would typically receive the inputs from the up - facing sensor 220 and modify / relay these to the controller 400 . in the arrangement of fig4 , the decision to use either the down - facing sensor or up - facing sensor is made by the controller device 400 . in the arrangements of fig5 & amp ; 6 , the up facing sensor 220 would be programmed ( typically via the control interface ) with the speed threshold and the switching between the sensors being made by up facing sensor 220 . fig6 shows a more efficient system architecture which may be possible , depending on the control bus uses . for example , if an i2c bus is used , there is no need to have a control input on the down - facing sensor 220 , thus dispensing with the need of two extra pads / connections on the device . furthermore , the i2c bus supports multiple ( slave ) devices , which means that the two sensors 220 , 250 can be connected in parallel . in a main embodiment , an aspect to the invention is the operation of the device , in that the device operates by using the two control signals from the two optical sensors in a co - operative manner so as to output a single navigation output . for large movements and high speed operation , the mouse itself is moved across the surface below it , and motion data from the down - facing sensor 220 is used . for high precision movements , the mouse is kept largely stationary and the finger ( typically index ) is moved over the mouse surface 270 of the device . as the human body possesses fine motor control on the fingers , this operation results in a device which provides increased accuracy control . in order to best achieve this operation , data from the down facing sensor 220 should be ignored for the purposes of control when the mouse is largely stationary , or its speed is below a threshold level . as noted above , the output from the two sensors provides for a single navigational output . this is as opposed to an output that comprises two separate positional signals as is the case with a mouse and scroll wheel , where the mouse controls a cursor and the scroll wheel controls the scrolling in a window . in the present embodiment , the two control signals would , for example , control the same cursor , providing a coarse control and fine control of the cursor . clearly , control is not limited to that via a cursor , and the control method could be any other suitable method , including scroll , zoom etc . fig7 shows a plot of the speed of the mouse as detected by the down - facing sensor 220 against its actual speed for a mouse configured in this way . when the detected speed of the mouse is above a certain threshold t , for example , 2 - 5 mm / sec , the navigation data from the down - facing sensor 220 is used , and the reported speed increases linearly with increase in actual speed ( of course , this relationship does not need to continue in a linear fashion but instead may “ accelerate ” as is known in the art ). during this second period , data from the up facing sensor 250 is being ignored , and the sensor 250 and corresponding light source 260 may in fact be switched off . when the speed drops below the threshold t , the data from the down - facing sensor 220 is disregarded and the reported speed drops to zero ( first period on graph ). during this period data from the up - facing sensor 250 is used instead . this technique avoids small nudges in the mouse when a user is sliding a finger on the top surface from being used as valid cursor movement data . optionally , the output resolution ( counts per inch ) from the two sensors can be made different , such that the down - facing sensor outputs 800 cpi , i . e . one inch of travel outputs 800 counts , while the up facing sensor outputs 200 cpi . therefore , in the latter case , the finger has to move further to output the same number of counts . this decrease of sensitivity increases the positional accuracy of the system . the different output counts may be achieved either by changing the motion gain on the sensor or by varying the magnification in the optics (× 0 . 5 vs × 0 . 25 ) or by using sensors with different array sizes ( 20 * 20 pixels vs 40 * 40 pixels ). fig8 shows a graph similar ( axes are scaled the same ) to that of fig7 for the up facing sensor 250 during the first period of graph 7 . it can be seen that the reported speed increases linearly with actual speed of the finger on the sensor , but with a different slope than that of fig7 , representing the difference in output resolution . of course , the reported speed on this graph drops to zero should the mouse speed recorded by the down facing sensor 220 pass the threshold value t . it should be noted that the output from a mouse is rarely the actual “ speed ,” but is usually measured in counts . the speed is deduced by the controller , pc or mobile phone handset by monitoring the speed and time , i . e . speed = distance / time . speed is used on fig7 and 8 as it clearly explains the operation of the device . the above embodiments are for illustration only and other embodiments and variations are possible and envisaged without departing from the spirit and scope of the invention .
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fig1 a is a top perspective view and fig1 b is a bottom perspective view of a trading card 10 having features of the present invention with the trading card 10 in a folded configuration 12 . as provided herein , the trading card 10 can easily be moved between the folded configuration 12 and an unfolded configuration 14 illustrated in fig2 a - 2c . the trading card 10 , for example , can be a collectible item or can be used is sports or entertainment games . in one embodiment , the trading card 10 includes a viewing lens 16 , one or more images 18 ( illustrated as an “ x ”), a front wall 20 , a back wall 22 , a bottom wall 24 , and a top wall 26 . in this embodiment , when the trading card 10 is in the unfolded configuration 14 , a user ( not shown ) can view the image 18 through the viewing lens 16 . alternatively , when the trading card 10 is in the folded configuration 12 , the user is not able to view the image 18 through the viewing lens 16 . the size and shape of the components of the trading card 10 can be varied to suit the desired design requirements of the trading card 10 . the design of the viewing lens 16 can be varied pursuant to the teachings provided herein . for example , the lens 16 can be a piece of glass , plastic , or other transparent material . in one embodiment , the lens 16 is a magnifying glass that enlarges the image 18 on the piece of film 18 . the image 18 for example , can include one or more characters , sports athletes , celebrities , an entertainers , statistics , information , instructions , a game field or arena , an image used in a game , data , a character , an autograph , an animal and / or landscape . in one embodiment , the image 18 is positioned on a piece of rectangular film 28 . the film 28 can be at least partly transparent . alternatively , the image 18 can be positioned on another medium and / or the film 28 could have another shape . additionally , in one embodiment , the film 28 is fixedly secured to the trading card 10 . alternatively , for example , the film 28 could be selectively removable from the back wall 22 . with this design , the film 28 could be interchangeable . the front wall 20 retains the viewing lens 16 . the back wall 22 retains the image 18 . the bottom wall 24 and the top wall 26 each extend between and maintain the front wall 20 and the back wall 22 spaced apart when the trading card 10 is the unfolded configuration 14 . in one embodiment , each wall 20 , 22 , 24 , 26 is generally rectangular shaped and each wall 20 , 22 , 24 , 26 includes a first connected edge 30 a , a second connected edge 30 b that is opposite the first connected edge 30 a , and a pair of opposed unconnected edges 30 c . in one embodiment , ( i ) the first connected edge 30 a of the front wall 20 is secured to the first connected edge 30 a of the top wall 26 ; ( ii ) the second connected edge 30 b of the front wall 20 is secured to the first connected edge 30 a of the bottom wall 24 ; ( iii ) the first connected edge 30 a of the back wall 22 is secured to the second connected edge 30 b of the top wall 26 ; and ( iv ) the second connected edge 30 b of the back wall 22 is secured to the second connected edge 30 b of the bottom wall 24 . in one embodiment the trading card 10 can be slightly weakened ( e . g . embossed , scored , or crimped ) at the connections between the walls 20 , 22 , 24 , 26 to facilitate relative movement of the walls 20 , 22 , 24 , 26 so that the trading card 10 can be easily moved between the configurations 12 , 14 . in one embodiment , the trading card 10 is perforated , e . g . including a line of holes , at the connections between the walls 20 , 22 , 24 , 26 to facilitate relative movement of the walls 20 , 22 , 24 , 26 . additionally , as illustrated in fig1 a and 1b , in the folded configuration 12 , ( i ) the walls 20 , 22 , 24 , 26 are all substantially parallel to each other , and ( ii ) the viewing lens 16 and the film 28 are substantially parallel to each other . further , in the folded configuration 12 , ( i ) the front wall 20 and the top wall 26 are substantially coplanar , and ( ii ) the bottom wall 24 and the back wall 22 are substantially coplanar . in one embodiment , in the folded configuration 12 , the trading card 10 is generally flat , rectangular shaped and has a length of between 2 and 6 inches , a width of between approximately 1 . 5 and 4 . 0 inches , and a thickness of between approximately 0 . 0625 and 0 . 25 inches . for example , in the folded configuration 12 , the trading card 10 can be similarly sized and shaped as a standard trading card having a length of approximately 3 . 5 inches , a width of approximately 2 . 5 inches , and a thickness of between approximately 0 . 06 and 0 . 2 inches . fig2 a is a top , front perspective view of the trading card 10 in an unfolded configuration 14 with a pair of tabs 34 ( only one is illustrated in fig2 a ) in an unlocked position 36 , fig2 b is a top , front perspective view of the trading card 10 in the unfolded configuration 14 with the tabs 34 ( only one is illustrated in fig2 a ) in a locked position 38 , and fig2 c is a bottom , rear perspective view of the trading card 10 in the unfolded configuration 14 with the tabs 34 in the locked position 38 . in the unfolded configuration 14 , the user can easily view the image 18 through the viewing lens 16 . fig2 a - 2c illustrate that in the unfolded configuration 14 , the trading card 10 ( i ) is now generally rectangular tube shaped having open sides ; ( ii ) the front wall 20 and the back wall 22 are substantially parallel and spaced apart ; ( iii ) the bottom wall 24 and the top wall 26 are substantially parallel and spaced apart ; ( iv ) the film 28 and the viewing lens 16 are substantially parallel , space apart , and are aligned so that the film 28 can be viewed through the viewing lens 16 ; ( v ) the bottom wall 24 extends between the front wall 20 and the back wall 22 ; and ( vi ) the top wall 26 extends between the front wall 20 and the back wall 22 . fig2 a also illustrates a portion of the trading card 10 in the folded configuration 12 ( illustrated in phantom ). in fig2 a , arrow 40 illustrates movement of the trading card 10 from the folded configuration 12 to the unfolded configuration 14 . more specifically , three of the walls move relative to the other wall during movement between configurations 12 , 14 . for example , during movement from the folded configuration 12 to the unfolded configuration 14 , ( i ) the front wall 20 has pivoted relative to the bottom wall 24 from being substantially parallel to the bottom wall 24 in the folded configuration 12 to being substantially perpendicular to the bottom wall 24 in the unfolded configuration 14 ( approximately 90 degrees rotation ); ( ii ) the back wall 22 has pivoted relative to the bottom wall 24 from being substantially parallel to and in substantially the same plane as the bottom wall 24 in the folded configuration 12 to being substantially perpendicular to the bottom wall 24 in the unfolded configuration 14 ( approximately 90 degrees rotation ); ( iii ) the front wall 20 has pivoted relative to the top wall 24 from being substantially parallel to and in substantially the same plane as the top wall 26 in the folded configuration 12 to being substantially perpendicular to the top wall 26 in the unfolded configuration 14 ( approximately 90 degrees rotation ); ( iv ) the back wall 22 has pivoted relative to the top wall 26 from being substantially parallel to the top wall 26 in the folded configuration 12 to being substantially perpendicular to the top wall 26 in the unfolded configuration 14 ( approximately 90 degrees rotation ); and ( v ) the top wall 26 has moved relative to the bottom wall 24 from being substantially parallel and adjacent to the bottom wall 24 in the folded configuration 12 to being substantially parallel and spaced apart from the bottom wall 24 in the unfolded configuration 14 . it should be noted that movement from the unfolded configuration 14 to the folded configuration 12 results in the opposite motion described above . as mentioned previously , the trading card 10 includes one or more tabs 34 that are moved between the unlocked position 36 ( illustrated in fig2 a ) and the locked position 38 ( illustrated in fig2 b and 2c ). arrow 42 in fig2 a and 2b illustrate movement of one tab 34 from the unlocked position 36 to the locked position 38 . with the tabs 34 in the unlocked position 36 , the trading card 10 is free to move between configurations 12 , 14 . however , when the tabs 34 are in the locked position 38 , the tabs 34 inhibit movement of the trading card 10 from the unfolded configuration 14 back to the folded configuration 12 . stated in another fashion , the tabs 34 in the locked position 38 hold and maintain the trading card in the unfolded configuration 14 . the design , number , and location of the tabs 34 can vary . in the embodiment illustrated in fig2 a - 2c , the tabs 34 are a portion of the bottom wall 24 that has been partly cut from the bottom wall 24 and rotated . in the unlocked position 36 , the tab 34 is generally parallel and coplanar with the rest of the bottom wall 24 . in this position , the trading card 10 is free to move between configurations 12 , 14 . in the locked position 38 , each tab 34 ( i ) has been rotated 90 degrees relative to the rest of the bottom wall 24 , ( ii ) is adjacent to the front wall 20 , and ( iii ) extends generally perpendicular to the front wall 20 and the rest of the bottom wall 24 . with this design , an edge of the tab 34 engages the inside of the front wall 20 to inhibit movement of the trading card 10 from the unfolded configuration 14 to the folded configuration 12 and to stabilize the trading card 10 in the unfolded configuration 14 . additionally , in certain embodiments , the notches in the bottom wall 24 and the tabs 34 provide a convenient position to hold the trading card 10 in the unfolded configuration 14 . it should be noted that the notches and tabs 34 can be wider so that larger fingers can fit in the notches and tabs 34 . it should be noted that in one embodiment , opposite walls are generally the same size and configuration . for example , the front wall 20 and the back wall 22 have substantially the same size and configuration . further , the top wall 26 and the bottom wall 24 have substantially the same size and configuration . additionally , in one embodiment , the bottom wall 24 includes an arch shaped wall opening 46 located near the back wall 22 . in certain embodiments , in the folded configuration 12 , before the trading card 10 has ever been moved to the unfolded configuration 14 , the scored or weakened areas can be relatively stiff . the wall opening 46 can provide a finger hole , e . g . a place to push , to start to move the trading card 10 from the folded configuration 12 to the unfolded configuration 14 for the first time . after the trading card 10 has been moved between the configurations 12 , 14 a number of times , the wall opening 46 may not be necessary . fig3 a is an exploded view of the beginning components , and fig3 b is an exploded perspective view of one non - exclusive , embodiment of the trading card 10 . fig3 a illustrates that in this embodiment , the trading card 10 can be made out of the viewing lens 16 , the piece of film 28 , and multiple cards 48 . in fig3 a , the trading card 10 includes a first card 48 a , a second card 48 b , and a third card 48 c . in one embodiment , each of the cards 48 a , 48 b , 48 c is generally rectangular shaped and the same size . for example , each of the cards 48 a , 48 b , 48 c can be a piece of card stock . in one embodiment , each of the cards 48 a , 48 b , 48 c is made of 24 points card stock . in fig3 a and 3b , each of the card stocks 48 a - 48 c includes a distal end 48 d and a proximal end 48 e . fig3 b illustrates that the card 48 a - 48 c have been die - cut and scored prior to assembly . more specifically , fig3 b illustrates that ( i ) a lens aperture 50 has been die cut from the first card 48 a ; ( ii ) a first cut 52 ( illustrated as dashed line ) was made in the first card 48 a across a portion of the first card 48 a to provided a weakened area for the front wall 20 to bend relative to the top wall 26 ; ( iii ) a lens aperture 54 has been die cut from the second card 48 b ; ( iv ) a rectangular shaped intermediate aperture 56 has been die cut from the second card 48 b ; ( v ) a pair of cuts 58 have been made at the proximal edge of the intermediate aperture 56 ; ( vi ) a rectangular shaped film aperture 62 has been die cut from the second card 48 b ; ( vii ) each of the tabs 34 is made with a pair of spaced apart , cuts 64 made in the third card 48 c ; ( viii ) a second cut 66 ( illustrated as dashed line ) was made in the second card 48 b across a portion of the second card 48 b to provided a weakened area for the rear wall 22 to bend relative to the bottom wall 26 ; ( ix ) the semicircular wall opening 46 has been die cut from the third card 48 c ; and ( x ) a rectangular shaped film aperture 68 has been die cut from the third card 48 c . as mentioned above the three card 48 a - 48 c are assembled together to form the trading card 10 . referring to fig3 b , ( i ) the viewing lens 16 is secured to the second card 48 b over the lens aperture 54 , ( ii ) the lens aperture 50 of the first card 48 a is positioned around the viewing lens 16 , and ( iii ) the proximal end 48 e of the first card 48 a is secured with an adhesive 70 to second card 48 b at a location that is slightly spaced apart from the proximal end 48 e of the second card 48 b . with this design , a portion of the first card 48 a and a portion of the second card 48 b cooperate to form the front wall 20 . additionally , the first card 48 a defines the top wall 26 . further , ( i ) the distal end 48 d of the first card 48 a is secured with an adhesive 72 to the distal end 48 d of the second card 48 b , ( ii ) the distal end 48 d of the third card 48 c is secured with an adhesive 74 to second card 48 b at a location that is slightly spaced apart from the distal end 48 d of the second card 48 b with the piece of film 28 positioned therebetween aligned with the film apertures 62 , 68 , and ( iii ) the second card 48 b is separated at the cuts 58 . with this design , a portion of the second card 48 b and a portion of the third card 48 b cooperate to form the rear wall 22 . further , the third card 48 c defines the bottom wall 24 . finally , the proximal end 48 e of the second card 48 b is secured with an adhesive 76 to the proximal end 48 e of the third card 48 b . it should be noted that the adhesives 70 , 72 , 74 , 76 can be replaced with another type of fastener . it is to be understood that the trading cards 10 disclosed herein is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims .
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the presently disclosed subject matter provides a decision support software system that predicts potential disruptive events , contingencies , in a distribution system before they happen based on , for example , machine learning , and computes and communicates contingency and real - time management decisions to most efficiently allocate available resources ( e . g ., electricity ) to carry out pre - emptive actions ( e . g . preventative maintenance , curtailment of load , etc .) in order to prevent resource shortfalls ( e . g ., electricity outages ), additional infrastructure harm or failure , and associated harm to the public . referred to herein as the dynamic contingency avoidance and mitigation system ( dcams ), the system simultaneously estimates future needs and interactions and responds to real - time events to provide accurate , controller - based costing and pricing of the commodity ( e . g ., reliability based pricing of electric service in a micro - load pocket ), curtailment actions , and management mechanisms in order to prevent outages , equipment failure , emergencies , and contain events that have already taken place . in various embodiments of the presently disclosed subject matter , dcams communicates contingency and real - time management decisions to utilities and dr owned and operated by their customers . this optionally , combined with lean management principles , provides a dcams that both estimates future needs and interactions and responds to real - time events to provide accurate , preventive maintenance , controller - based pricing , curtailment and load pocket management mechanisms . dcams can recommend additions from dr , load shedding and other operations such as switching , crew deployment , and improved work processes to reduce the risk of power disruptions , equipment failure , and harm to people . the dcams enhances the safety and security of the distribution system ( e . g ., an electrical grid ) by improving reliability and safety on at least two fronts : the first is through the use of the simulation component to predict the effects of possible control actions , thereby permitting both human and computer decisions to be made with a better understanding of the ramifications of a particular sequence of actions ( e . g ., an electrical simulation component ). the simulation can also be used to monitor the effects of a sequence of actions in order to detect and warn of anomalous behavior . the second is through the use principles to detect those longer - term infrastructure enhancements that are most likely to have the greatest positive impact on performance and to then recommend the stronger more successful enhancements . in this regard , the methods disclosed in u . s . published application no . wo 2009 / 117742 , hereby incorporated by reference in its entirety , can be used in conjunction with the presently disclosed dcams . in the context of an electrical grid , dcams manages additions from distributed resources such as power supply storage and generation , load shedding and other operations such as switching , crew deployment , and improved work processes to alleviate risks of power disruptions and equipment failure , and to distribute power more effeciently . dcams also allows utilities to prepare in advance and to respond in real - time to detailed customer issues such as load pocket constraints ( e . g ., low voltage condition ). by implementation of reliability based pricing and curtailment strategies , made possible via dcams , the need to build additional distribution feeders in this load pocket or build additional generating resources can be reduced or rendered unnecessary . dcams receives real - time measured load and supply modulations such as from electric vehicles , building loads , and supplies like energy storage and distributed generation and predicts future response and availability of these dr . verification of the effects of curtailment orders and pricing and cost changes is a part of the controller &# 39 ; s decision - making process . dcams is also used by transmission and distribution engineering personnel to accurately evaluate capital asset upgrade options within high risk load pockets ( e . g ., from the micro level of a large customer to the area substation level ). embodiments of the presently disclosed subject matter utilize the stochastic controller technology disclosed in u . s . pat . no . 7 , 395 , 252 , granted jul . 1 , 2008 and hereby incorporated by reference in its entirety . a machine learning system can be used to train power control system operators , for example , to take suitable actions to respond quickly to fluctuations or interruptions in electricity flow anywhere in the power grid . the controller can be configured as a computer - based simulation and training tool that learns the “ best response scenarios ” to specific events on the grid , which for example , can lead to critical failure cascades across integrated generation , transmission , and distribution grids such as the eastern north american inter - connected grid , if not controlled . for example , the subject regional and distribution power grids can be modeled using commercially available power flow and short - circuit modeling tools ( such as distribution engineering works station ( dew ), sold by edd , inc . blacksburg , va ., and epri solutions , inc . palo alto , calif .). dew can , for example , model inverter and synchronous distributed generation power flow , as well as multiple - source fault analysis . dew is in use in the power industry as a real - time simulator of a utilitys &# 39 ; distribution system , for example , in conjunction with the utilitys &# 39 ; supervisory control and data acquisition ( scada ) systems and / or its energy management systems ( ems ) and their associated data historians . dew also can be used to model regional grid behavior using , for example , federal energy regulatory commission ( ferc ) data . various types of powerflow models exist that can be used for analysis in connection with peak load leveling , peak shaving , voltage correction , right sizing of equipment , and machine learning . one embodiment of the presently disclosed subject matter provides a web service for initiation of , interactive adjustments to , historian recording of , and human and machine training in the operation of the dcams . this can be achieved through access to the outputs of an integrated workflow of a plurality of analytical computer applications for characterization and analysis of operational traits , improved management of capital and human resource allocation for maintenance and operational response , and commodity or energy transaction decisions for infrastructure - based businesses such as water , electric , oil , and gas companies . the dcams is ideal in electric economies of now and in the future , such as new york which is , or can be , dominated by electric vehicles , electric trains , subways , buses and other energy sources such as alternative wind , solar and other distributed energy generation and storage resources ( dr ). the presently disclosed subject matter can improve and account for operational responses of the workforce to events in a seamless and remotely accessible package . problems caused by the disparate nature of business , regulatory , and engineering requirements and techniques are solved through software wrappers to allow specific rules and regulations written into scripts to be read into the dcams . the presently disclosed subject matter advances the current state of the art to utilize market and dispatch mechanisms to solve congestion of energy or commodity flow and human resource allocation with the least risk and cost possible . the dcams also permits the simulation and record keeping necessary to plan for and implement new operational strategies that can in turn permit the incorporation of alternative energy sources . smart feedback from the power consumers , both large and small , to the dcams allows it to anticipate demand and demand response potential , and coordinate the operations of diverse drs and other supply to produce the least pollution and lowest carbon dioxide emissions at the lowest cost while maintaining reliability expectations . such feedback can include how much dr can respond in a given time interval in terms of reduced load and over what time frame and when such capability would be available from that dr . the dcams predicts future disruptive events in the distribution system before they happen based on , for example , machine learning , and communicates contingency and real - time management decisions to utilities and dr ( distributed energy generation and storage resources ) owned and operated by their customers . see u . s . pat . no . 7 , 395 , 252 , granted jul . 1 , 2008 and hereby incorporated by reference in its entirety . in one embodiment , machine learning ranking algorithms such as , for example , support vector machines and boosting and adaboosting for ranking of susceptibility to failure of electrical components based on predicted levels of attributes versus what is observed in real time . see , generally u . s . published application no . 2009 / 0157573 and t . zhang , “ convex risk minimization , annals of statistics , 2004 , each of which is hereby incorporated by reference its entirety . through this ranking mean time between failure ( mtbf ) is approximated for failure of assets in a predicted or forecasted future state . through a topological model of the electric distribution grid , algorithms performing sequential monte carlo analysis can be used where mean time to repair ( mttr ) of various responses that are available for restoration improvement are included in the sequential or non sequential monte carlo analysis . the mttr for these actions can be learned through experience from past directed actions first as averages and then moving to the application of prediction algorithms , as disclosed , for example , in international published application no . wo 2009 / 1177421 ( hereby incorporated by reference in its entirety . in one embodiment , the dcams employs the on - policy monte carlo control method in order to improve methods to evaluate or improve on the policy that is used to make decisions on actions such as adding electric supply from distributed generation or reducing loads at specific nodes to reduce vulnerabilities or risk . one advantage of using monte carlo methods is that it provides an alternative policy evaluation process . rather than use a model to compute the value of a state , the monte carlo methods average many options for returning to the start state . the monte carlo method can be combined with dynamic programming or adp to find policies on top of monte carlo . an overview of the dcams system , according to one non - limiting , exemplary embodiment ( 300 ), is represented in fig3 . the dcams system incorporates both predictive models ( shown in fig3 in ovals ) and real - time data from the field ( shown in rectangles ). in this embodiment , the system includes a planning system and a real world system , which receives output from the planning system to assist in controlling the electrical grid in view of real - time information from the field . the planning system is described first below . as shown in fig3 , independent system operator ( iso ) market data ( 310 ) is sent to , and processed within a predicted supply model ( 320 ) that anticipates the amount of supply needed and to be made available based on historical matches to coming weather conditions , contractual agreements of supply availability ( e . g ., interconnected electric vehicles and / or distributed generation at a specific location ), and daily and seasonal usage patterns . power flow algorithms ( 330 ) in concert with forecasted ami / cis ( automated meter intelligence / customer information system ) load data ( 340 ) is sent to a predictive model to estimate predicted loads ( 350 ) at critical locations ( e . g ., load pockets ). cis and interconnection data ( 360 ) on predominately weather dependent generation ( e . g ., solar , wind ) is sent to a weather dependent generation predictive model ( 370 ) to estimate , for example , the availability of solar and / or wind power available to supplement centralized power plant supply of electricity for a specific location . output from high resolution and low resolution weather bureau predictions such as from dtn weather forecasts and deep thunder ( dtn ) ( 380 ), a service available from ibm to provide local , high - resolution weather forecasts specific to neighborhoods , is also sent as an input to the weather dependent generation predictive model and also to a weather forecast predictive model ( 390 ). output from these weather bureau forecasts is also sent to a predictive model used to predict and display known system failures ( 400 ) some of which are highly weather likely under adverse weather conditions ( e . g ., wind fallen on overhead power lines ). the predicted and known system failures model ( 400 ) also receives real - time data from gis ( geographic information systems ) ( 410 ), vegetation management history ( 420 ), feeder management system , supervisory control and data acquisition system ( scada ) outage management system ( 430 ) and data output from the contingency analysis program ( 440 ), which is disclosed in international published application no . wo 2009 / 117741 , hereby incorporated by reference in its entirety . a scorecard system ( 450 ) sends data to a financial predictive model ( 460 ). the financial predictive model quantifies the value of smart grid technologies , which in turn relies upon measuring the cost and customer convenience of the specific use of these technologies . in addition , the scorecard system tracks outages and equipment failures . exemplary scoreboard systems according to one embodiment of the presently disclosed subject matter is described in greater detail below . a work management system or scheduler ( wms ) ( 470 ) that includes , among other things , warehouse supplies , worker availability , tool availability , vehicle availability and shop management information to send data to a model used to estimate logistical capacity ( 480 ). each of the predictive models discussed above and as shown in fig3 are transmitted to the dcams , along with information about curtailment contracts ( 490 ) and managed energy storage ( 500 ). the dcams outputs sources of predicted loads ( 520 ), predicted supply ( 510 ) and predicted risks and costs ( 530 ) for better dcams decisions . in one emodiment , dcams uses such technologies as described in u . s . pat . no . 7 , 395 , 252 , which is hereby incorporated by reference in its entirety . in the embodiment represented in fig3 , the dcams also submits recommended actions to a control center operator , or alternatively , implements those actions with electronic messages via the response manager ( 630 ). examples of recommended actions during a time of tight period of tight power supply can include , for example , instructions to add battery sources or distributed generation , instructions to stop the charging of electrical vehicles or energy storage ( 500 ) and / or to withdraw current from the electrical vehicles and / or energy storage , and to cut power to other curtailable loads ( 490 ) under contract . the system configuration ( 540 ) also receives input from real - time data from managed energy sources ( 550 ), system failures ( 560 ), actual capacity ( 570 ) and actual load ( 580 ), actual weather ( 590 ), weather dependent generation ( 600 ), actual supply ( 610 ) and realized curtailment ( 620 ) to provide real time evaluation of the state of the system at specific locations for mitigation , containment , and restoration purposes . in this example , the dcams uses a monte carlo control method in order to compute methods to evaluate or improve on the policy that is used to make decisions on actions such as adding electric supply from dr sources or reducing loads at specific nodes to reduce vulnerabilities and risk . control strategies facilitate efficient distribution of electricity by applying curtailment , by moving portable sources , by prioritizing maintenance and emergency response , as well as directing surgical replacements and upgrades to the points of greatest vulnerability . the price responsiveness of curtailable customer &# 39 ; s behavior and the times needed to deploy resources , such as batteries , is also learned by the dcams . in one embodiment , the dcams employs a data historian to record the configuration of dcams by time and date , so that any previous date and time can be recalled from memory to see the data , systems configuration , recommended actions and results of those action recommended by the dcams at that past time . the presently disclosed subject matter contains decision aids that utilize the contingency calculations to provide transparency to stakeholders . the assumptions , analytic processes , input and output data used for each analysis can be readily retrieved and re - evaluated for future auditing , training , and / or effort justification . thus , access to , input and output from all workflows , present or past , and analytical tracking of decisions made in the field is provided . it is often desired in the execution of science and engineering computations to keep a notebook with a record of all experiments and the trail and errors and successes , as well as observations and analyses of events occurring during the experiment . in performing complicated tasks such as evaluation of decision processes between various resource requirements and asset allocations in complex infrastructure systems , and design basis decisions such as improving or optimizing how electrical equipment and computational software are configured , records must be kept of all decisions so that it can later be established that they were carefully made based upon the best information available at the time . the presently disclosed subject matter can use the notebook and historian technologies disclosed , for example , in u . s . pat . no . 6 , 826 , 483 , hereby incorporated by reference in its entirety . an exemplary integrated system model notebook ( 400 ) is shown in fig4 . in this embodiment , a display layer ( 410 ) is provided that includes drill down access to a network distribution layer ( 420 ), a bulk power system layer ( 430 ) and a layer detailing connection to other large sources of electricity ( e . g ., other generating systems or connection to other systems ) ( 440 ). in this embodiment , the dcams provides the ability to , for example , control asset deployment within the smart grid ( e . g ., maintenance crews in the field , or maintenance crews working in connection with capital improvement projects based on the design model ( 450 ). power routing and virtual scada ( supervisory control and data acquisition system ) functionalities are provided within the control system ( 460 ). for example , the system can use data coming in from the remote monitoring system ( rms ) to sense the electrical load on transformers in the streets and feeders at each substation . this embodiment of the present application also provides decision support ( 470 ) of , for example , electric operations , such as decisions regarding power restoration and information about customer operations and load projections in connection thereto . also provided is the ability to provide condition - based maintenance ( 480 ) based on real - time conditions and machine learning . for example , through the use of machine learning , future events can be predicted and prevented , workflow can be dispatched to replace susceptible equipment before it breaks and maintenance scheduling can be coordinated . see u . s . published application no . 2009 / 0157573 for disclosure regarding machine learning that can be used in conjunction with this embodiment . this reference is hereby incorporated by reference in its entirety . the non - limiting embodiment shown in fig4 also receives input and facilitates process control via price signals ( 490 ) regarding the commodity or resource at issue ( e . g ., the cost of electricity ). the ability to have access to , and incorporate price signals into the calculus of process control provides for energy and asset improvement , efficiency in usage and increased customer focus and satisfaction . various embodiments of the presently disclosed subject matter allows , for example , a utility to prepare in advance and to respond in real - time to detailed customer issues such as load pocket constraints at transformer high tension vaults ( htv ) for large customers such as that in fig5 or in overhead loop feeders . this level of granularity results from accurate measurement and prediction of curtailable loads such as electric vehicles , building loads , and supplies like energy storage . verification of curtailment is a part of the controller &# 39 ; s decision - making process . the same dcams can be used by distribution engineering to accurately evaluate capital asset upgrade options within high risk load pockets ( e . g ., at the micro level of a htv ) all the way through to the area substation level . fig1 - 18 provide screenshots from a display , coupled to one or more processors , that visually presents a depiction of a portion of an electrical grid according to a non - limiting embodiment of the disclosed subject matter . an area substation is depicted to provide transmission power flow contingency models that interface with scada systems . as shown in fig1 , the user has the capability of changing the configuration of the particular portion of the electrical grid that is analyzed . for example , a transformer can be added to the system model . the user can also specify the failure of a component , and the system outputs how the other components will react . as shown in fig1 , the system incorporates design basis limitations into the model . as shown in fig1 , the system can output load shifts and how much supply ( e . g ., supply from dr ) or load reduction is required in response to a failure of a user - specified component . as shown in fig1 , the system allows for the input of load forecasts . as shown in fig1 , prospective equipment violations can also be specified based on the user - specified contingency . embodiments of the presently disclosed subject matter also provides improved infrastructure response to storms . through actual vegetation management actions and locations of electric equipment , machine learning algorithms , such as but not limited to svm and / or boosting , rankings of equipment susceptibility for a given type of storm ( e . g ., high temperature storms with strong winds from the east versus cold temperature storms with high soil moisture , with winds from the north ). in one embodiment , a machine learning system employs svm or boosting to determine the ranking and subsequent mtbf of tree - lined versus non tree lined electric equipment . vegetation management history is used within the machine learning system to predict susceptibility to impending feeder outages , given a specific type and severity of approaching storm , to drive storm anticipation and response systems . the dcams system can include software modules running on a computer , one or more processors , or a network of interconnected processors and / or computers each having respective communication interfaces to receive and transmit data . alternatively , the software modules can be stored on any suitable computer - readable medium , such as a hard disk , a usb flash drive , dvd - rom , optical disk or otherwise . the processors and / or computers can communicate through tcp / ip , udp , or any other suitable protocol . conveniently , each module is software - implemented and stored in random - access memory of a suitable computer , e . g ., a work - station computer . the software can be in the form of executable object code , obtained , e . g ., by compiling from source code . source code interpretation is not precluded . source code can be in the form of sequence - controlled instructions as in fortran , pascal or “ c ”, for example . various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein . for example , hardware , such as firmware or vlsics ( very large scale integrated circuit , can communicate via a suitable connection , such as one or more buses , with one or more memory devices . a load pocket “ a ” in an urban area is fed by a four transformer htv “ b ” as shown in fig5 . the utility is supplying power from four medium voltage feeders from a single substation separately to each transformer . there are various dr sources and sinks owned by a large customer inside the load pocket , which can provide additional load or nega - watts in case of needed local curtailment . there is a ‘ plug and play ’ capability of the dr to communicate presence and demand of the grid , and a combination of old and new technologies for communication in the event that curtailed load can be necessary . in order for a utility to leverage the value of dr in combination with its own distribution assets , a high fidelity control system is desirable to predict future outcomes , continously evaluate the risks to reliability and efficiency , and act on those issues that could put the system in jeopardy of failure . dcams provides granular modulation of dr in addition to load curtailment verification and control . as shown in fig6 , the load pocket information is projected coming into the dcams from the load pocket a &# 39 ; s several different dr sources that are processed in addition to the htv b load and distribution grid scada coming in from the utility &# 39 ; s equipment . without an intelligent decision support system , a utility would have to ignore the dr in the load pocket a and build out more costly capital infrastructure such as an additional feeder and transformer for htv b to supply peak load contingency supplies even though these additional dr assets exist in the local area . there is a forecast for a hot summer day in a large northeastern city in the u . s . the utility plans ahead for each specific load pocket level in its region , based on predicted weather conditions , load estimates , and availability of supply . with the addition of a new generation of electric vehicles , it is desirable that the utility knows how these dr impact its system and its load pockets . at 4 pm on the day before the predicted hot day , the utility would look to one of the dcams control consoles ( fig6 ) to plan the purchase of tomorrow &# 39 ; s power . there is a potential of supply not meeting the required load in load pocket a given the future load required to be delivered to the the four transformers in htv b . in fig6 , any load below zero balance means the utility cannot meet demand if a single emergency event of say the loss of one transformer in the htv b via an open auto outage anywhere along the length of the 4 feeders from the substation to the htv b . the dcams prediction of what might happen tomorrow is based on the weather forecast and predictions of loads and supplies associated with load pocket a in view thereof . through simulation , the controller would compute recommended actions to relieve this perceived crisis period when the load pocket a is near zero balance , this time through suppression of load by increasing the local price in load pocket a and curtailing load in htv b . as shown in fig6 , the day ahead price ( 710 ) and modified day ahead price ( 720 ) are computed given the changes made by the operator , or machine , to price setpoints of electricity . load mw ( 730 ), supply mw ( 740 ), balance mw ( 750 ) are predicted for hours after 6 am ( vertical dashed line ), modified load mw ( 760 ), modified supply mw ( 770 ) and modified balance mw ( 780 ) are also computed as a result of changes made to electricity price setpoints offered to the dr at this specific location . the decision aid recommends an announcement be sent to the customer of htv b that 1 mw of curtailable load may be required in this micro load pocket the next day from 10 am to 5 pm . in response thereto , the dcams alerts customers of large energy sinks in load pocket a , such as electric billboard customers , customers in large skyscrapers or facilities for charging electric vehicles , that voltage can be temporarily reduced . the dcams recommends to the customers that load be diverted to time periods when demand is not likely to be as high . note the “ no change in scheduling of crews ,” in the recommended actions box at the bottom of fig6 , which indicates that this decision aid also recommends that no worker actions need be taken at this time based on the risk ranking of severity of an additional contingency situation actually occurring during the curtailment event . this recommendation is evaluated using data on the availability of crews as well as on the potential of remedying the grid overloads through such actions like changes in the position of electric switches within the area &# 39 ; s electric system should an additional event happen . in this example , the dcams uses a continuously updating machine learning evaluation of the multi - objective function required to maintain sufficient levels of reliability and efficiency of the smart grid . in fig6 , the dashed lines are the predicted responses of the electric grid if the recommended changes to the pricing signals are acted on by the customers for this load pocket a as predicted or contractually obligated by agreements such as curtailment . the dcams learns the extent that load in the load pocket would change due to price responsive load ( prl ) responses in the past , and / or knowledge from previous testing that a certain number of electric vehicles can decide to become suppliers and add to capacity capability within this micro load pocket . the system operator would either accept these recommendations or perform more simulations using dcams to decide what works best to meet the next day &# 39 ; s forecasts . it is now the day the hot weather arrives in load packet a , and suddenly there is a medium voltage feeder that open auto fails , causing one transformer out of the four in fig5 to go out of service in this customer htv b . the load falls below the zero balance level load pocket a and voltage is reduced . the utility must quickly act to get the system back to above zero balance to prevent loss of power to the customers or damage to the other three transformers in htv b due to overload . in real - time , the dcams instantly and automatically curtails the charging of electric vehicles in all parking lots in load pocket a ( fig7 ). it recommends the utility also raise real - time market prices in the local area of load pocket a to entice price responsive load like electric billboards on buildings and non - emergency lighting to shut off . there is a switch that ties in more supply from nearby feeders at the substation , and dcams suggests this move after automatically performing model simulations that indicate that such a load transfer would not adversely affect other parts of the electric system . the dcams also re - dispatches crews to the location of the failed feeder as a result of detection of an additional transformer overload in htv b that places the transformer at high risk of failure at the htv b . as can be seen , the dcams , through model simulation and learning of demand and supply curves in this load pocket , makes recommendations to utilize the various levers available to the utility to maintain reliability . other potential actions that dcams might recommend to operators for field crew deployment include , but are not limited to , those set forth in the table below : one of the three remaining operational transformers in htv suddenly presents an overload anomaly , as shown in fig8 . in fig8 , the vertical axis is load . the lower line ( 810 ) is predicted load on one transformer in the htv . the upper line ( 820 ) indicates that this transformer is in danger of overheating because its load ( 820 ) has jumped from 45 % to 75 % of maximum safe operation rating ( 830 ). a transformer load variance detection system alerts operators at the utility control center when more load than expected goes to the other than planned transformers during load shifting caused by feeder outages because of open main low voltage feeders . the dcams also presents the system operator with additional curtailment recommendations to shed tranche a curtailable load customers as a result of this transformer anomaly , as indicated by the recommended actions box at the bottom of fig7 . through smart management by the dcams of dr , such as curtailing charging on electric vehicles , turning off billboards and escalators , load relief via utility switching , and crew actions , a day that is disrupted by an emergency outage and overload is managed in real time , and the system is prevented from dropping below zero balance , and a blackout in load pocket a is averted . the margin between supply and load rises above zero as indicated by the dotted line in fig7 and the transformer in htv b &# 39 ; s return to normal % of safe operational rating as seen in fig8 . a prototype of the dcams is developed , complete with a weather - driven , software simulation of test cases like the above load pocket aihtv b example with the various dr like electric vehicles , solar power , price responsive load , and curtailable loads . this example shows how the dcams would meet real field example requirements of an electrical utility company . a power utility real - time integrated operations , control management , and design architechture for dcams with loads and dr is modeled in fig9 . this model , based on graph trace analysis ( gta ), can be used as both an engineering model and an operational tool . the prototype uses model - based generic algorithms for design and control of reconfigurable interdependent systems . it &# 39 ; s use eliminates the need for large matrix solvers , using instead compositions to implement polymorphism and simplify management using dependency components to structure analysis across different systems types using an implementation of hot - swappable algorithms . the iterative nature of gta provides distributed computation that allows convergence and solution of the multi - million node models conducive for an integrated systems model of large urban utilities in seconds . having this model as a base for the controller framework provides high potential for fast simulation for operator decision support that is fast enough for real - time grid control . fig1 provides a representation of the gta algorithms acting on the system model . the integrated system model allows system operations personnel to take field actions such as automatically opening or closing breakers through use of this model . this system model platform has allowed the same algorithms , such as dew , to be used simultaneously by engineers in planning and for troubleshooting , by operators in the control room , and by crews in the field . in one embodiment , the dcams grid controller of fig9 can piggyback on the real time servers of power flow and contingency analysis algorithms , such as dew &# 39 ; s gta - based power flow algorithm shown in fig1 . the dcams can be positioned in study mode servers to map out the dynamics of the electric grid for each tomorrow through use of data from existing scada and automated meter infrastructure . upon fully learning tomorrow &# 39 ; s optimal states and control policies , the dcams controller can then be used to control all facets of electric grid operations , from management of phase angle regulators , to breakers , to load shedding , to driving energy pricing based on system constraints . the contingency analysis program tool , disclosed in international published application no . wo 2009 / 117741 and hereby incorporated by reference , can be used in conjunction with the presently disclosed subject matter , and can provide system operators with decision support and assistance in identifying operational variances , measuring risks of future outages , and providing prioritized capabilities to modulate equipment , supply , crews , and current usage to prevent impending contingency emergencies from happening . fig1 provides a summary of the stochastic controller platform disclosed in u . s . pat . no . 7 , 395 , 252 , which is hereby incorporated by reference . this stochastic controller platform can be used alone , or coupled with the dew model , described above , and used as the algorithmic computational engine in accordance with the methods and systems of the presently disclosed dcams . the stochastic controller uses approximate dynamic programming ( adp ), combined with mixed - integer nonlinear programming solvers . adp is used as a decomposition strategy that breaks the problem of continuous grid management , with its long time horizon , into a series of shorter problems that the mixed - integer nonlinear programming solver can handle . the adp framework also provides a way of treating uncertainty from both operational and financial standpoints , simultaneously . to achieve this , the stochastic controller has combined real option valuation with operational policy and action determination using the same adp algorithms within the adaptive stochastic controller . the result is maximization of real option value as a control objective that are merged control objectives driven efficient and safe operations . the adp adaptive stochastic controller optimizes by solving the hamilton - jacobi - bellman equation using a unique formulation of adp interacting with the integrated system model ( ism ) via feedback loops and a critic function , similar to the way models are used in model predictive control ( mpc ). this approach is considerably different from prior work in transmission control using dynamic programming ( i . e ., approximate dynamic programming is not equivalent to dynamic programming ). fig1 shows the system architecture and the operation of an exemplary learning system 1400 , used for a critical feature of the stochastic controller , which can be set up for training operators of a distributed electrical power grid 1600 . learning system 1400 includes a reinforcement - learning controller 1002 , optional learning matrices 1004 that are used within critic function 1003 , and a model 1006 of power flow within the utility electric grid 1600 . the subject power grid can include regional power generation , transmission , and distribution grids as well as integrated transcontinental power grids ( e . g ., the eastern interconnect f the north american power grid ). the integrated system controller approach that the dcams uses employs simultaneous modeling of business processes and scheduling of three things : assets , energy ( in the form of curtailment and supply of integrated dr and distribution grid processes ), and field crew deployment . the best use of business process modeling ( bpm ) in the dispatch and monitoring of crews via the dcams is analyzed . designing and constructing a simulation environment to test and verify the dcams is thus provided . a region within an electric utility &# 39 ; s territory is isolated so that the utlity can explore how various dr sources and sinks react under abnormal circumstances such as emergency situations . responses to dr related pricing signals is also studied . the cause and effect between the distribution grid and the charging and discharging of electric vehicles and other dr tools such as storage and generation into and out of the load pocket test sites are also analyzed . the scheduling of curtailable load , coupled with feedback by way of verification mechanisms that can eventually learn how to successfully predict how to manage loads during curtailment obligations for the entirety of the utility operating region . the dcams system can be used in concert with ami and past metering of building loads and unique supplies ( e . g , solar ) to determine the confidence of loads and supplies for a large building . predicted day ahead electric load fro a skyscraper or manufacturing facility is calculated with possible variances to this load ( top three lines in fig1 ( 110 )). with the addition of predicted solar supply for the day at this building with its expected variance ( 2σ ), the load on the grid can be lowered even though predicted load variance can widen significantly ( 120 ). energy storage ( 130 ) can be manually manipulated by the building manager , or utility if under its control , to supply dr energy into the building load to further offset requirements of the grid . alternatively , the dcams can operate the bms ( building management system ). in one embodiment , dcams can operate the bms using real options valuation based on either historical or predicted outcomes of energy market pricing or additional pricing provided by the utility in this specific location for improvements in reliability and efficiency . in addition to all the above , the dcams can provide a suggestion of resources required to respond to predicted outages during severe weather events hitting overhead utility systems . as shown in fig1 , the following attributes are input into a machine learning system to predict the resources required to respond to the coming storm emergency : soil type in the immediate area of each pole , pole design , pole digging type ( rock bore versus dug soil ), wind direction , wind speed , amounts of precipitation predicted , land gradients ( e . g ., proximity to mountains or hills ), location of trees in relation to transmission and distribution lines and roads , size of trees , elevation of equipment , in view of historical data regarding past momentary outages based on observed wind and speed . deployment strategies are then sent to the storm emergency team so that they can most effectively respond to the coming damage . assuming looking at the red ( 110 ) and blue ( 120 ) dash curves at 0800 the morning before a major storm event . the capability of determining when to actually call in additional crews , when to have called in five crews for 1600 hours and to call in other utilities for a 2300 start with an understanding in advance of when they will most like be released is very valuable planning tool . most scheduling of crews must be done many hours in advance to get them available in time to respond to outages . if one waited until all the failures already took place , then outage durations would be significantly longer than if crews were prepared and prepositioned at the right time to respond to predicted levels of storm damage . just as important is when you should start releasing crews or deciding that they not respond for the next shift do to reductions in additional storm damage . through predictions of dcams of expected damage based on storm formation and severity , there are significant reductions in the cost of responding to storms . if one were to look at the actual solid blue line ( 130 ), the actual damage can be seen , which was closely predicted at 0800 . as the storm unfolds , obviously , more accuracy at the moment will allow changes to actions to further refine the response . the presently disclosed subject matter is not to be limited in scope by the specific embodiments described herein . indeed , various modifications , in addition to those described herein , will become apparent to those skilled in the art from the foregoing description and the accompanying figures . such modifications are intended to fall within the scope of the appended claims . it is further to be understood that all values are approximate , and are provided for description . patents , patent applications , publications , product descriptions , and protocols are cited throughout this application , the disclosures of each of which is incorporated herein by reference in its entirety for all purposes .
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details of the objects and technical configuration of the present invention and operational effects according thereto will be more clearly understood by the detailed description described below based on the accompanying drawings attached in the specification of the present invention . a first keypad and a second keypad described hereinafter may be referred to as a real keypad and a virtual keypad , respectively . the second keypad is virtually created on the first keypad , and the first keypad and the second keypad are respectively configured of an independent character key structure and independent codes and provided with an independent character input mode . in addition , character input on the first keypad is accomplished by a tapping action , and character input at the second keypad is accomplished by a touch move action such as sliding ( pushing ), flicking or the like . fig1 is a block diagram schematically showing the configuration of a character input device according to an embodiment of the present invention , fig2 is an exemplary view showing the structure of a first keypad information database according to an embodiment of the present invention , fig3 is an exemplary view showing the structure of a second keypad information database according to an embodiment of the present invention , fig4 is an exemplary view showing a first keypad according to an embodiment of the present invention , fig5 is an exemplary view showing forms of second keypads visibly created on a first keypad according to an embodiment of the present invention , fig6 is an exemplary view showing forms of character keys created by a second keypad creation unit according to an embodiment of the present invention , and fig7 is an exemplary view showing forms of character keys and assignment of codes on a second keypad according to an embodiment of the present invention . referring to fig1 , a character input apparatus 100 includes a touch screen 110 , a storage unit 120 , a database 130 , a first keypad creation unit 140 , a first key touch recognition unit 150 , a second keypad creation unit 160 and a second key touch recognition unit 170 . the touch screen 110 includes a display unit 112 and a touch panel 114 . the display unit 112 displays a state of the character input apparatus 100 . at this point , the display unit 112 may be implemented in a liquid crystal display ( lcd ) or the like . the touch panel 114 is mounted on the display unit 112 and provided with a touch sense unit ( not shown ) and a signal conversion unit ( not shown ). the touch sense unit is an element for sensing whether or not a touch device touches the touch screen and senses generation of touch by detecting changes of , for example , resistance , capacitance or the like . here the touch device may include a hand of a user , a touch pen , a stylus pen , a mouse and the like . the signal conversion unit converts changes of physical quantity into a touch signal . although the touch sense unit may be configured of a touch sensor of a capacitive overlay , a resistive overlay , an infrared beam or the like or configured of a pressure sensor , it is not limited thereto and may include all kinds of sensors capable of sensing touch or pressure of an object . the touch screen 110 may also include an apparatus having an interface capable of character input only through a touch action on a specific character key , without directly touching the character key . the storage unit 120 performs a function of storing programs and data needed for operation of the character input apparatus 100 . the database 130 includes a first keypad information database 132 and a second keypad information database 134 . the first keypad information database 132 stores a coordinate value according to the form and size of each of character keys configuring the first keypad , a center point coordinate value or a center point color value of each of the character keys arranged on the first keypad , a character code and a character label corresponding to the center point coordinate value or the center point color value , and the like . here , a form of a character key configuring the first keypad may be a rectangle , a circle , a straight line , a dot , a character , a color or the like , and the form or size of a character key may be arbitrarily determined and visibly or invisibly expressed . a character key of a color form is configured in a photo , a picture or the like . the first keypad information database 132 stores information on the first keypad in the form of a character key layout table as shown in fig2 . referring to fig2 , a center point coordinate value “( 30 , 40 )” of a first key arranged on the first keypad , a center point color value ( color code ) “ red ( 02 )” of the first key , a character code “ 0041 ” of the first key , a character label “ a ” of the first key and the like are stored in the first keypad information database 132 . information on the first keypad stored in the first keypad information database 132 is provided to the first keypad creation unit 140 in the case of character input mode . the second keypad information database 134 stores a coordinate value according to the form and size of second keypad corresponding to each of the keys arranged on the first keypad , a center point coordinate value or a center point color value of each of the character keys arranged on the second keypad , a character code and character label on the second keypad corresponding to the center point coordinate value or the center point color value , a character code and a character label on the second keypad corresponding to the character code of the first key and a touch move direction and the like . here , a form of a character key configuring the second keypad may be a rectangle , a circle , a straight line , a dot , a character , a color or the like , and the form or size of a character key may be arbitrarily determined and visibly or invisibly expressed . the coordinate value of a character key arranged on the second keypad may be expressed as a single coordinate value in the case of a character key of a dot form and as a plurality of coordinate values in the case of a character key having an area formed as a straight line , a rectangle , a polygon or a circle . for example , the coordinate value may be previously determined as one or more coordinate values in the case of a character key of a dot form , coordinate values of about three points ( three pixels ) in the case of a character key of a straight line form , or less than the number of coordinate values expressing an area in the case of a character key having an area . in addition , if a representative coordinate value of a character key is selected among the plurality of coordinate values allocated to each character key as a center point coordinate value and the center point coordinate value is defined in the second keypad information database 134 in advance , the center point coordinate value of a corresponding character key is obtained when a specific character key is touched . since the second keypad information database 134 stores information on the second keypad for each of the keys arranged on the first keypad and a corresponding character code is assigned to a character key arranged on the second keypad , the second keypad can input character keys . the second keypad information database 134 stores information on the second keypad in the form of a character key layout table as shown in fig3 . fig3 a shows a case of storing a center point coordinate value of a character key arranged on the second keypad and a character code and a character label on the second keypad corresponding to the center point coordinate value . in this case , a center point coordinate value “( 40 , 50 )” of a character key arranged on the second keypad , character code “ 0042 ” of the character key , a character label “ b ” of the character key and the like are stored in the second keypad information database 134 as information on the second keypad . fig3 b shows a case of storing a center point color value of a character key arranged on the second keypad and a character code and a character label corresponding to the center point color value . in this case , a center point color value “ red ” of a character key arranged on the second keypad , a center point coordinate value “( 50 , 50 )” of the character key , a character code “ 0043 ” of the character key , a character label “ c ” of the character key and the like are stored in the second keypad information database 134 as information on the second keypad . fig3 c shows a case of storing a character code and a character label on the second keypad corresponding to a character code of a first key and a touch move direction . in this case , a code value “ 0043 ” of the first key , a touch move direction “ right ”, a character code “ 0044 ” of a character key arranged on the second keypad , a character label “ f ” of the character key and the like are stored in the second keypad information database 134 as information on the second keypad . here , a value of the character code of a character key arranged on the second keypad may vary according to combination of the code value of the first key and the touch move direction . the character key layout table of the second keypad as shown in fig3 is stored in the system as a character array and character code format file of the second keypad using a program . character keys belonging to the second keypad may be used by previously marking together with the first key on the first keypad . that is , a predetermined number of character keys around the first key may be displayed on the second keypad , or a predetermined number of character keys highly probable to be used may be displayed on the second keypad based on a character key use pattern . in the case of character input mode , the first keypad creation unit 140 displays the first keypad configured of at least one or more character keys on the touch screen 110 . at this point , the first keypad creation unit 140 creates the first keypad configured of character keys having at least one of the forms including a dot , a straight line , a curved line , a polygon , a circle and a color . the first keypad created by the first keypad creation unit 140 may be set in advance , and it may be a keypad having a general qwerty type key array as shown in fig4 a , a character keypad based on twelve keys as shown in fig4 b , or a keypad having its own structure as shown in fig4 c . that is , the first keypad or the second keypad may be configured in the form of allocating and arranging character keys of each country on a standard key array of a computer such as qwerty or may be configured in the form of allocating character keys of each country to be overlapped with a key on a keypad having a key array of a small number of keys . in addition , the first keypad or the second keypad may be a keypad configured of character keys designed in a unique structure such as a color picture or the like . in addition , the first keypad or the second keypad may be implemented in a keypad configured of a subset of character keys in the rows and columns of a keyboard having a character array the same as that of a computer keyboard , a keypad configured of some character keys of the characters on a standard 10 - key array of a telephone , or a keypad configured of character keys configured in a unique structure such as a color or figure type keypad . the first keypad creation unit 140 performs a function of providing the first keypad to the display unit 112 of the character input apparatus 100 in response to a request from a user . if touch of the first key is sensed on the first keypad , the first key touch recognition unit 150 acquires a character code corresponding to the value of the first key from the first keypad information database 132 and calls the second key touch recognition unit 160 . here , the first key is a key initially input by touch among the character keys on the first keypad , and it may perform a function of starting creation and display of the second keypad when the first key is input . the first key touch recognition unit 150 acquires the center point coordinate value or the center point color value of the initially touched first key among the character keys arranged on the first keypad . since a touch panel is basically provided with pixel data , the first touch key recognition unit 150 may acquire the center point coordinate value ( x , y ) of the key at the touch start point . in addition , if the first keypad is created on a specific picture , the first key touch recognition unit 150 may also acquire the center point color value of the key at the touch start point . if the center point coordinate value or the center point color value of the initially touched first key is acquired , the first key touch recognition unit 150 may acquire a character code corresponding to the center point coordinate value or the center point color value by searching the first keypad information database 132 . since character codes corresponding to center point coordinate values or center point color values of the character keys arranged on the first keypad are stored in the first keypad information database 132 , the first key touch recognition unit 150 may acquire a character code of the first key from the first keypad information database 132 . in response to the call of the first key touch recognition unit 150 , the second keypad creation unit 160 creates a second keypad including character keys in the neighborhood of the first key and virtually display the second keypad on the touch screen 110 . in addition , the second keypad creation unit 160 may create a second keypad including a predetermined number of character keys highly probable to be used together with the first key and virtually display the second keypad on the touch screen 110 . the second keypad creation unit 160 virtually create and display a second keypad arranging character keys which can be input , in at least one of the upward , downward , leftward , rightward and diagonal directions . at this point , the second keypad creation unit 160 may visibly or invisibly create the virtual second keypad inside or outside of the first key of the first keypad . in addition , the second keypad is created around the first key , and it is sufficient if the position of displaying the second keypad is inside the touch screen , and the second keypad does not need to be necessarily displayed around the touch point where a first key touch input is received . a case of creating and displaying a second keypad on the first keypad by the second keypad creation unit 160 will be described with reference to fig5 . first , fig5 a is a view showing a case of displaying a second keypad 520 on a first keypad 510 based on an english qwerty keyboard . referring to fig5 a , if a user inputs ‘ d ’ as a first key 512 , the second keypad creation unit 160 creates and displays the second keypad 520 on the first keypad 510 around the center point of the first key 512 as soon as the first key is input . at this point , character keys arranged up and down and left and right of ‘ d ’ are displayed on the second keypad 520 . next , fig5 b is a view showing a case of displaying a second keypad 560 on a first keypad 550 based on a character array abc of a telephone keypad . referring to fig5 b , if a user inputs ‘ a ’ as a first key 552 , the second keypad creation unit 160 creates a second keypad 560 around the center point of the first key 552 as soon as the first key is input and displays the second keypad 560 on the first keypad 550 . at this point , character keys arranged together with ‘ a ’ are displayed on the second keypad 560 . the second keypad creation unit 160 creates a layout of the second keypad in the form of various character keys . for example , the second keypad creation unit 160 may configure the second keypad by expressing a character key as a polygonal character key , a dot , a straight line , a curved line , a circle , a colored figure or the like having an area the same as or smaller than that of a key of the first keypad . at this point , the character key boundaries on the first keypad may be different from or the same as the character key boundaries on the second keypad . the character keys of the second keypad created in a variety of forms by the second keypad creation unit 160 will be described with reference to fig6 . fig6 a is a view expressing character keys of the second keypad by the unit of a dot ( corresponding to a pixel on a touch panel ) and displaying the second keypad expressed as dot form character keys around the first key on the first keypad . a coordinate value or a color value on a second keyboard (→ the second keypad ) is assigned to each of the dots displayed around the first key . fig6 b is a view expressing character keys of the second keypad as polygonal small keys around the center point of the first key and displaying the second keypad expressed as polygonal small keys around the first key on the first keypad . a coordinate value or a color value on a second keyboard (→ the second keypad ) is assigned to each of the polygonal keys displayed around the first key . fig6 c is a view expressing character keys of the second keypad as rectangular small keys and displaying the second keypad expressed as rectangular small keys around the first key on the first keypad . a coordinate value or a color value on a second keyboard (→ the second keypad ) is assigned to each of the rectangular keys displayed around the first key . fig6 d is a view expressing character keys of the second keypad as small keys of a straight line and displaying the second keypad expressed as small keys of a straight line around the first key on the first keypad . a coordinate value or a color value on a second keyboard (→ the second keypad ) is assigned to each of the straight lines displayed around the first key . as described above with reference to fig6 , a character key of the first keypad or the second keypad may be configured in the form of a rectangle , a circle , a straight line , a dot , a character , a color or the like , and a form or a size of a character key may be arbitrarily determined and visibly or invisibly expressed . in addition , a fingering distance of a key touch can be reduced as the size or the number of the character keys on the second keypad is reduced to be smaller than the size or the number of the character keys on the first keypad , and the distance between character keys can be optimized . the character key boundaries on the first keypad may be different from or the same as the character key boundaries on the second keypad . since the character keys of the second keypad have a variety of forms , the second keypad creation unit 160 implements the character keys of the second keypad by selecting a form from the character keys of various forms , and the implemented virtual second keypad is visibly or invisibly provided on the first keypad . in addition , a unique character code is assigned to each character key of the second keypad , and the character code is used by the second key touch recognition unit 170 on the second keypad . that is , if touch of a first key begins on the first keypad , character keys of the second keypad are created around the center point of the first key , and it becomes a state capable of character input . the forms of character keys and assignment of character codes on the second keypad will be described with reference to fig7 . fig7 a is a view showing character keys of the second keypad configured in a dot form around the first key a of the first keypad , and a unique character code such as b or c is assigned to each dot formed key . fig7 b is a view showing character keys of the second keypad configured in a rectangular form around the first key a of the first keypad , and a unique character code such as b or c is assigned to each of the rectangular keys . fig7 c is a view showing character keys of the second keypad configured in a polygonal form around the center point of the first key d of the first keypad , and a unique character code such as e or f is assigned to each of the polygonal keys . fig7 d is a view showing character keys of the second keypad configured in a straight line form around the center point of the first key d of the first keypad , and a unique character code such as e or f is assigned to each of the keys formed in a straight line . here , the center point of a character key arranged on the first keypad or the second keypad has a specific coordinate value within the character key assigned according to the form of the character key on the first keypad or the second keypad , and it is stored in the database 130 . the second key creation unit 160 may provide an interface capable of easily recognizing a character key which can be input on the second keypad by displaying a figure of the second keypad having a configuration the same as that of the second keypad in a character input window , as soon as creating the second keypad on the first keypad . at this point , the second keypad may be provided in a configuration independent from the first keypad , in which boundaries of the character keys on the second keypad are different from boundaries of the character keys on the first keypad , and a character code value assigned to each of the characters of the second keypad is also different from the those of the first keypad . if a touch move action is sensed on the second keypad , the second key touch recognition unit 170 acquires a character corresponding to the touch move action from the second keypad information database 134 and displays the character on the touch screen 110 . here , the touch move action includes dragging , flicking , sliding and the like and can be an action continued from a first key touch action . character input of a user on the second keypad virtually created on the first keypad is accomplished by a touch move action of the user , and if the touch action is completed without a touch move action , a character corresponding to the character code of the first key is output in the character input window of the touch screen 110 . assignment of an input character key according to a touch move action of a user on the second keypad may vary according to the method of implementing a character key configuring the second keypad . a character key configuring the second keypad can be implemented in an arbitrary form and size , such as a rectangle , a circle , a straight line , a dot , a character , a color or the like . a touch move direction of a user on the second keypad is the upward , downward , leftward , rightward or diagonal direction from inside or outside of the first key , and it can be any direction in which a character key of the second keypad is set . the second key touch recognition unit 170 displays a character on the touch screen 110 using at least one of the coordinate value , the color value and the touch move direction information according to the touch move action . hereinafter , a case of displaying a character using a coordinate value or a color value according to a touch move action and a case of displaying a character using touch move direction information will be described separately . first , a case of displaying a character using a coordinate value or a color value according to a touch move action will be described . in this case , the second key touch recognition unit 170 acquires a coordinate value or a color value according to a touch move action on the second keypad , extracts a character code corresponding to the acquired coordinate value or color value from the second keypad information database 134 , and displays a character corresponding to the extracted character code on the touch screen 110 . finally , a case of displaying a character using touch move direction information will be described . in this case , the second key touch recognition unit 170 acquires a coordinate value according to a touch move action on the second keypad , detects touch move direction information through an operation on the center point coordinate value of the first key and the coordinate value according to the touch move action , extracts a character code corresponding to a combination of the character code of the first key and the touch move direction information by searching the second keypad information database 134 , and displays a character corresponding to the extracted character code on the touch screen 110 . at this point , the second key touch recognition unit 170 detects the touch move direction information through a subtraction operation on the center point coordinate value of the first key and the coordinate value of the touch end point . for example , when the coordinate value of the touch end point is ( x2 , y2 ) and the center point coordinate value of the first key , which is the touch start point , is ( x1 , y1 ), the second key touch recognition unit 170 calculates x2 − x1 = dx , y2 − y1 = dy . the touch move direction information is created as move left if dx is a negative value as a result of the calculation , move right if dx is a positive value , move downward if dy is a negative value , and move upward if dy is a positive value . at this point , if the dx and dy values are the same , any one of them may have priority over the other . then , the second key touch recognition unit 170 may combine the touch move direction information with the character code of the first key , extract a character code on the second keypad corresponding to a set of the combined character code and touch move direction information from the second keypad information database 134 , and display a character corresponding to the extracted character code . the second key touch recognition unit 170 functions only in a corresponding input mode as far as a key touch is not released in the input mode of the second keypad . since a touch movement can be made in the upward , downward , leftward , rightward or diagonal direction from the first key of the user while the character key input mode of the second keypad is maintained , the second key touch recognition unit 170 may detect and recognize a coordinate value of a specific position having a code value when a touched position is moved . the character input apparatus 100 configured as described above may input a character in six combinations based on the center point of the first key , information on the character keys on the second keypad and a touch move action . specifically , the character input apparatus 100 may input a character using at least one of ( 1 ) a combination of the center point coordinate value of the first key and a coordinate value of a character key on the second keypad , ( 2 ) a combination of the center point coordinate value of the first key and a color value of a character key on the second keypad , ( 3 ) a combination of the center point color value of the first key and a coordinate value of a character key on the second keypad , ( 4 ) a combination of the center point color value of the first key and a color value of a character key on the second keypad , ( 5 ) a combination of the center point coordinate value of the first key and touch move direction information on the second keypad , and ( 6 ) a combination of the center point color value of the first key and touch move direction information on the second keypad . the character input apparatus 100 as described above may be applied to any user device provided with a touch screen . for example , the character input apparatus 100 may be applied to various devices such as a notebook computer , a mobile communication terminal , a smart phone , a portable media player ( pmp ), a personal digital assistant ( pda ), a tablet pc , a set - top box , a smart tv and the like . fig8 is a flowchart illustrating a method of inputting a character in a character input apparatus according to an embodiment of the present invention . referring to fig8 , if a character input mode is executed ( step s 802 ), the character input apparatus displays a first keypad configured of one or more character keys on a touch screen ( step s 804 ). if a first key touch is sensed on the first keypad ( step s 806 ), the character input apparatus acquires a character code corresponding to the center point coordinate value of the first key ( step s 808 ). that is , if touch of an initially touched first key is sensed , the character input apparatus acquires the center point coordinate value of the first key and acquires a character code corresponding to the center point coordinate value of the first key by searching a first keypad information database provided in advance . then , the character input apparatus creates a second keypad including character keys in the neighborhood of the first key and displays the second keypad on the touch screen ( step s 810 ) and determines whether or not a touch move action is sensed on the second keypad ( step s 812 ). at this point , the character input apparatus displays the second keypad on the first keypad and senses a touch move action such as dragging , flicking , sliding or the like . if a touch move action is sensed on the second keypad as a result of the determination at step s 812 , the character input apparatus acquires a center point coordinate value or a center point color value of a character key according to the touch move action ( step s 814 ) and extracts a character code corresponding to the acquired center point coordinate value or center point color value by searching a second keypad information database ( step s 816 ). then , if the touch movement is completed ( step s 818 ), the character input apparatus displays a character corresponding to the character code extracted at step s 816 on the touch screen ( step s 820 ). if a touch move action is not sensed on the second keypad as a result of the determination at step s 812 , the character input apparatus displays a character corresponding to the character code acquired at step 3808 on the touch screen ( step s 822 ). hereinafter , an embodiment of a case in which the center point coordinate value of the first key is ( 33 , 33 ) and a code value of character is previously assigned to a coordinate value ( 44 , 44 ) will be described . in this case , if the touch movement is completed at a coordinate value ( 44 , 44 ), the character input apparatus acquires a code value of character ‘ a ’ corresponding to the coordinate value ( 44 , 44 ) by searching the second keypad information database and displays a character corresponding to the code value on the touch screen . through the procedures described above , input of a character is completed by one touch input . fig9 is a flowchart illustrating a method of inputting a character in a character input apparatus according to another embodiment of the present invention . referring to fig9 , if a character input mode is executed ( step s 902 ), the character input apparatus displays a first keypad configured of one or more character keys on a touch screen ( step 3904 ). if an initial first key touch is sensed ( step s 906 ), the character input apparatus acquires a center point color value of the first key and acquires a character code corresponding to the center point color value of the first key by searching the first keypad information database provided in advance . then , the character input apparatus creates a second keypad including character keys in the neighborhood of the first key and displays the second keypad on the touch screen ( step s 910 ) and senses a touch move action on the second keypad ( step s 912 ). at this point , the character input apparatus displays the second keypad on the first keypad and senses a touch move action such as dragging , flicking , sliding or the like . if a touch move action is sensed on the second keypad as a result of the determination at step s 912 , the character input apparatus acquires a coordinate value or a color value according to the touch move action ( step s 914 ) and extracts a character code corresponding to the acquired coordinate value or color value ( step s 916 ). then , if the touch movement is completed ( step s 918 ), the character input apparatus displays a character corresponding to the character code extracted at step s 916 on the touch screen ( step s 920 ). if a touch move action is not sensed on the second keypad as a result of the determination at step s 912 , the character input apparatus displays a character corresponding to the character code acquired at step s 908 on the touch screen ( step s 922 ). as described above , the character input apparatus may input a character key on the second keypad by assigning a character code to a color after classifying and defining the character keys on the first keypad or the second keypad by color and individually expressing the characters in color . that is , if character keys of the second keypad existing at a position to which a touch movement can be applied from the center point of the first key are assigned with a distinguishable color such as red , blue , yellow , purple , greed or the like , these character keys can be distinguished by the value of a color . in addition , first keys on the first keypad may also be expressed in colors described above . accordingly , if a color of a touch start point , i . e ., the center point coordinates of the first key , and a color of the coordinates of the move end point are specified , the character input apparatus may acquire , output and display a character code value assigned to the color of a corresponding point . the character input apparatus may input or output a character using a character key expressed only in color without a special form . if a character key is implemented by assigning a color value as shown in fig9 , a keyboard of a special form which sets a character code to a specific color in a sheet of picture or an image can be designed and configured , and it can be utilized as a character input keyboard appropriate to a special purpose . for example , as a character input keyboard of a special purpose , it can be utilized as an id or pw ( password ) input keyboard used for a locking mechanism of a smart phone . fig1 is a flowchart illustrating a method of inputting a character in a character input apparatus according to still another embodiment of the present invention . referring to fig1 , if a character input mode is executed ( step s 1102 ), the character input apparatus displays a first keypad configured of one or more character keys on a touch screen ( step s 1104 ). if a first key touch is sensed on the first keypad ( step s 1106 ), the character input apparatus acquires a character code corresponding to the center point coordinate value or the center point color value of the first key ( step s 1108 ) and acquires a character code corresponding to the center point coordinate value or the center point color value of the first key by searching the first keypad information database provided in advance . then , the character input apparatus creates a second keypad including character keys in the neighborhood of the first key and displays the second keypad on the touch screen ( step s 1110 ) and senses a touch move action on the second keypad ( step s 1112 ). if a touch move action is sensed on the second keypad , the character input apparatus acquires a coordinate value of the touch move point ( step s 1114 ) and detects a touch move direction using the acquired coordinate value ( step s 1116 ). at this point , the character input apparatus calculates x2 − x1 = dx , y2 − y1 = dy using the coordinate value ( x2 , y2 ) of the touch end point and the center point coordinate value ( x1 , y1 ) of the first key , which is the touch start point . the touch move direction information is created as move left if dx is a negative value as a result of the calculation , move right if dx is a positive value , move downward if dy is a negative value , and move upward if dy is a positive value . at this point , if dx and dy values are the same , the dx value has priority . that is , the horizontal and vertical values are the same , the horizontal direction has priority . if step s 1116 is performed , the character input apparatus extracts a character code corresponding to a combination of the character code of the first key and the touch move direction information from the second keypad information database ( step s 1118 ). here , a combination value of the character code of the first key and the touch move direction information may be configured in the form of a set of ( character code of first key , touch move direction information ). for example , if the character code of the first key is ‘ a ’ and the touch move direction information is right , it can be configured in the form of a set like ( a , right ). in this case , the character code of the first key , the coordinate value or the color value of the center point of the first key , touch move direction information , a character code and a character label on the second keypad corresponding to the character code of the first key and the touch move direction information and the like are stored in the second keypad information database as shown in fig3 c . if the touch movement is completed ( step s 1120 ) after step s 1118 is performed , the character input apparatus displays a character corresponding to the character code extracted at step s 1118 on the touch screen ( step s 1122 ). if a touch move action is not sensed on the second keypad as a result of the determination at step s 1112 , the character input apparatus displays a character corresponding to the first key of the first keypad ( step s 1224 ). as described above , the character input apparatus may input a character using touch move direction information . that is , using the coordinate value and the color value of the center point of the first key on the first keypad , the character input apparatus may acquire a corresponding character code from the first keypad information database , detect a touch move direction according to an upward , downward , leftward or rightward touch move action , and then acquire a character code corresponding to a combination of the character code of the first key and the upward , downward , leftward or rightward touch move direction information from the second keypad information database and display a character corresponding to the acquired character code . fig1 is an exemplary view showing screens for illustrating a method of inputting a character using a qwerty keypad as a first keypad according to an embodiment of the present invention . referring to fig1 , if ‘ e ’ 1112 , which is the first key , is touched on the first keypad 1110 while a qwerty keypad is created as a first keypad 1110 as shown in fig1 a , the character input apparatus informs that it is the character key input mode of the second keypad and displays a second keypad 1130 including character keys in the neighborhood of the first key in a character input window area 1120 as shown in fig1 b . if the user performs a touch move action on the second keypad 1130 and releases the touch on a desired character key , the character input apparatus displays a corresponding character in the character input window area 1120 . fig1 is an exemplary view showing screens for illustrating a method of inputting a character using a 12 - key alphabet keypad as a first keypad according to an embodiment of the present invention . referring to fig1 , if the ‘ abc ’ key 1212 , which is the first key , is touched on the first keypad 1210 while a 12 - key alphabet keypad is created as a first keypad 1210 as shown in fig1 a , the character input apparatus informs that it is the character key input mode of the second keypad and displays a second keypad 1230 including character keys included in the first key 1212 in a character input window area 1220 as shown in fig1 b . if the user performs a touch more action on the second keypad 1230 and releases the touch on a desired character key , the character input apparatus displays a corresponding character in the character input window area 1220 . fig1 is an exemplary view showing screens for illustrating a method of inputting a character using a keypad arranging korean consonants and vowels as a first keypad according to an embodiment of the present invention . referring to fig1 , if the ‘ l ’ ( , , ) key 1312 is touched as a first key on the first keypad 1310 as shown in fig1 a , the character input apparatus informs that it is the character key input mode of the second keypad and displays a second keypad 1330 including character keys included in the first key 1312 in a character input window area 1320 as shown in fig1 b . if the user moves the touch in the direction to the point of key ‘ ’, the character input apparatus acquires a coordinate value of key ‘ ’, acquires a character code corresponding to the acquired coordinate value and displays the character ‘ ’ corresponding to the acquired character code in the character input window area 1320 if the user releases the touch at the same point . fig1 is an exemplary view showing screens for illustrating a method of inputting a character using a picture as a first keypad according to an embodiment of the present invention . referring to fig1 , if a sunflower picture as shown in fig1 a is used as a first keypad 1410 , character keys are assigned on the first keypad 1410 according to colors or positions . if the user touches area ‘ a ’ 1412 on the first keypad 1410 , the character input apparatus informs that it is the character key input mode of the second keypad and displays a second keypad 1430 including character keys assigned to the area ‘ a ’ 1412 in a character input window area 1420 as shown in fig1 b . then , if the user performs a touch move action on the second keypad 1430 and releases the touch on a desired character key , the character input apparatus displays a corresponding character in the character input window area 1420 . this corresponds to a case in which the second keypad 1430 and the character keys are invisibly created on the first keypad 1410 . according to the present invention , characters can be input rapidly and conveniently and , furthermore , error input can be reduced by doubly providing keypads in a touch or non - touch action type character input apparatus of various materials and forms . in addition , a character can be input more correctly and flexibly by virtually providing a second keypad , on which characters that can be input by touch movement of a user are displayed , when a touch start of a first key is sensed on a first keypad which is provided basically . in addition , since nine or more characters can be input through a first key touched on the first keypad when the keys of the second keypad virtually displayed on the first keypad are arranged in upward , downward , leftward , rightward and diagonal directions , a user can input a character more conveniently and correctly . in addition , a new user experience can be provided by providing a character input apparatus of various forms invisible to other people , such as an idle screen of a smart phone , a background picture of an application or web , a figure and the like . in addition , efficiency of character input can be improved by reducing a fingering distance required for character input in the character input environments of various users , improving correctness of character key touch and minimizing movements of a hand . in addition , a plurality of characters can be input through a touch start character key without pressing keys several times in inputting characters using a touch screen . in addition , speed of character input can be improved by displaying a complete character on a screen through one touch and touch move action on a touch - type keypad . while the present invention has been described with reference to the particular illustrative embodiments , it is not to be restricted by the embodiments but only by the appended claims . it is to be appreciated that those skilled in the art can change or modify the embodiments without departing from the scope and spirit of the present invention . embodiments of the subject matter and the functional operations described in this specification can be implemented in digital electronic circuitry , or in computer software , firmware , or hardware including the structures disclosed in this specification and their structural equivalents , or in combinations of one or more of them . embodiments of the subject matter described in this specification can be implemented as one or more computer program products , i . e ., one or more modules of computer program instructions encoded on a tangible program carrier for execution by or to control the operation of a data processing apparatus . the tangible program carrier can be a computer readable medium , which can be a machine - readable storage device , a machine - readable storage substrate , a memory device , a composition of matter effecting a machine - readable propagated signal , or any combination thereof . the term “ data processing apparatus ” encompasses all apparatus , devices , and machines for processing data , including by way of example a programmable processor , a computer , or multiple processors or computers . the apparatus can include , in addition to hardware , code that creates an execution environment for the computer program in question , e . g ., code that constitutes processor firmware , a protocol stack , a database management system , an operating system , or any combination thereof . while this specification contains many specifics , these should not be construed as limitations on the scope of an invention that is claimed or of what may be claimed , but rather as descriptions of features specific to particular embodiments . certain features that are described in this specification in the context of separate embodiments can also be implemented in combination in a single embodiment . conversely , various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable sub - combination . moreover , although features may be described above as acting in certain combinations and even initially claimed as such , one or more features from a claimed combination can in some cases be excised from the combination , and the claimed combination may be directed to a sub - combination or a variation of a sub - combination . similarly , while operations are depicted in the drawings in a particular order , this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order , or that all illustrated operations be performed , to achieve desirable results . in certain circumstances , multi - tasking and parallel processing can be advantageous . moreover , the separation of various system components in the embodiments described above should not be understood as requiring such separation in all embodiments and it should be understood that the described program components and systems can generally be integrated together in a single software product or packaged into multiple software products . as described above , this specification is not intended to limit the present invention to the presented specific terms . while the present invention has been described in detail with reference to the particular illustrative embodiments , those skilled in the art can alter , change or modify the embodiments without departing from the scope and spirit of the present invention . the scope of the present invention is defined by the accompanying claims , rather than the above detailed description , and the meaning and scope of the claims and all changes and modifications derived from equivalents thereof should be interpreted as being included in the scope of the present invention .
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the matrix 1 depicted in fig1 within its central area , is provided with a positioning portion 2 which , on both sides , is followed by two terminal areas 3 which , with respect to the positioning part 2 , are stepped in such a way that the positioning part 2 projects with a section from the plane formed by the upper edges of the two terminal areas 3 . the matrix 1 is provided with two stamped - out windows 5 ; it is preferably constructed in two layers , in which case the one supporting layer comprises a thin steel band of e . g . 0 . 05 mm thickness , upon which an equally thin , transparent strip of plastic , by way of preference of cellulose acetate , is attached . the two layers may be bonded to each other , be thermally sealed by warmth or heat or be joined together in some other way ; when in use , they form a unit , in which case the plastic strip rests against the dental filling and the steel band is at a distance from said filling , as is illustrated e . g . in fig5 . the fig2 and 3 show , in a top view and in a side view , a dental group 7 comprising three teeth , of which the center tooth has a cavity 8 which has to be filled with a plastic while the original shape of the tooth is adhered to . within the area of the dental neck 9 , as is apparent from fig3 the circumference of the tooth decreases . it is for this reason that the matrix , when engaging around the tooth to be treated and when the matrix is contracted at its two ends 3 , has to produce a conical shape in order to encircle the dental configuration tightly which , at the point of contact , is broader . that is why the wall edge towards the cervical area is shorten than the edge which faces the marginal strip of the filling , as is disclosed by fig3 . the matrix 1 reproduces the anatomical configuration of the tooth within the cervical area , i . e . within the area of the dental neck , as accurately as possible . it thereby prevents the excessive filling with filling material within this area and thus protects the marginal parodontium . in order to resist the lateral forces occurring during the insertion of the filling material , the matrix 1 is equipped with the steel band . the fig4 to 6 depict analogous representations as do the fig1 to 3 , but of closely set teeth and with a small diameter of the dental neck of the tooth to be tretaed . in this embodiment , the matrix band should likewise project cervically only a little above the approximal box in order to be wedged there . this wedging is shown particularly in fig7 on an enlarged scale . the fig4 shows a matrix 12 having a curvature 13 which is greater than that of the matrix 1 according to fig1 as well as with two windows 5 , 5 &# 39 ; and a pronounced conical stepping 15 which corresponds to the smaller circumference of the dental neck . this matrix 12 is intended to be used on a dental group 18 in which the center tooth has a cavity and a , in diameter , relatively small dental neck 20 . the matrix according to fig4 allows for this configuration by the relatively large conical stepping 15 . in fig7 two teeth are illustrated in a side view , viz . a sound tooth 25 and a tooth 26 with a cavity provided with a plastic filling 27 which is indicated in a dash - dotted manner . a matrix 28 of the type described has an externally located steel band 30 with one or several windows 31 and a plastic band 32 resting against the tooth to be treated 26 . an illuminating wedge 34 is inserted between the dental necks of the teeth 25 and 26 . the fig8 shows the top view of the teeth according to the arrangement according to fig7 in which case the two matrix ends 35 of the matrix laid around the tooth to be treated 26 are tightened with the aid of a matrix tightener 36 around the tooth by the matrix ends being seized and whereby the filling is imparted the shape desired in the fig7 and 8 . the lighting of the illuminating wedge 34 by means of an external light source permits , in this position of the parts , to cure the critical area where plastic and dental material meet as the first within the primary curing area 37 and to thereby prevent the feared shrinkage interstices between the plastic and the dental material . the areas of the plastic material which are located at the top are cured subsequently in such a way that the shrinkage of the curing manifests itself only on the free areas of the plastic and , basically , the entire plastic material can be cured so as to be devoid of the formation of any cracks or interstices . the matrix has , dependent upon the application indication , one ( for single approximal fillings ) or two windows ( for double approximal fillings ) of cellulose acetate within the approximal area . the windows make a perfect light curing within the approximal area possible . the action of the light is not restricted . the matric band is retained in position with the aid of matrix tighteners , such as the toffel wire system , the uhm system or the nystrom i and ii system . the fig9 a to 9e and 10 , 10a to 10e show premolar matrix bands , while the fig1 , 12a to 12k show molar matrix bands . the bulges 40 are clearly perceptible . the fig1 and 14 show the basic form of double - bulge matrix bands , while fig1 discloses a single - bulge embodiment . in this case the window sizes of molar bands are approximately 5 × 10 mm and the premolar bands possess a window size of approximately 4 × 8 mm . the fig1 shows a cellulose acetate strip 42 , such as is applied prior to the stamping out of the matrix with the steel band and subsequent to the windows being stamped out . fig1 shows a tooth 45 in perspective representation provided with a filling 46 which is schematically boldly framed and identified with zones 48 , 49 and 50 . an illuminating wedge 52 is acted upon by a light source with light beams 55 which , owing to the construction of the wedge , are deflected and thus cure the lowermost zone 48 when light is incident . subsequently the two zones 49 and 50 , as is apparent in a diagrammatically shown manner , are finally cured , in which case the matrices shown in the various figures appropriately encircle the plastic filling 46 so that the same can be subjected to the curing process in a geometrically correct manner . in fig1 , a device 60 for the fabrication of matrix bands is diagrammatically illustrated which comprises a plastic band roll 61 and a metal band roll 161 . the metal band of the steel band roll 161 is passed through a stamping means , by means 64 of which the pertinent number of windows is stamped out . the plastic band is removed from the roll and the stamped - out metal bands are laminated to each other in the joining station 65 by heat , adhesive or suchlike so that they are able to form an inseparable unit . the two combined bands are conveyed into a matrix punch 67 , with the aid of which the matrices 68 are fabricated and ejected possesing a form in which they are ready for use . the metal band imparts the requisite rigidity to the window matrices , which again is of advantage when the band is laid as well as in the shaping the filling . according to one of the embodiments , the matrix 1 is comprised of a thin band - shaped blank of steel or some other suitable material , it being also possible to employ plastics which do not react with the dental filling . in this band - like metallic blank , one or several window - like perforations 5 are formed which , by means of a strip - shaped blank , are covered by means of a transparent , more particularly , crystal - clear plastic , said plastic strip possessing a design which corresponds to the shape and dimensions of the steel band of the matrix 1 so that the plastic strip coincides fully with the steel band . however , the possibility also exists of disposing blanks of transparent plastic solely within the area of the window 5 in the steel band , in which case these plastic bands are dimensioned in such a way that the windows 5 are covered and that they rest with a section against the wall area of the steel band so as to make it possible to attach the plastic blanks to the steel band . as covering for the windows 5 , transparent plastic are employed , such as e . g . plastics having a cellulose base , such as cellulose acetate , or vinyl polymerisates , ps , pmma and pc . according to a further embodiment , the matrix provided with at least one window 5 is comprised of a blank constructed according to the configuration of the matrix fabricated from a transparent , crystal - clear plastic , e . g . possessing a cellulose base , such as cellulose acetate , or a vinyl polymerisate , ps , pmma and pc , in which case especially such plastics are employed as are used for optical purposes , in which a certain elasticity has to be present so as to enable one to lay the matrix around a tooth . for the formation of windows 5 , the matrix of the plastic strip is provided with a metallic coating which may e . g . be vapor - deposited while window - like areas are formed . metallized plastics of this type are produced by non - galvanic or by galvanic processes . consequently , the fabrication may be effected in accordance with the metallization process , in which low - melting metals are applied to the plastic in the form of a mist or according to the metal reduction method , in which metal salt solutions , e . g . gold , silver or copper salt solutions are reduced with the aid of formaldehyde . the materials then precipitate onto the plastic . a metal coating is also possible to effect in accordance with the vacuum deposition method . in the present case , as plastics are employed those which neither combine with the dental fillings nor are partially or completely dissolved by the latter . the advantage of using metal coated matrices resides in the simplified fabrication . large - surface blanks of a suitable plastic are coated with the aid of metals while , at the same time , a number of uncoated surface sections are formed whose number corresponds to that of the matrices then to be stamped out from the blank , which subsequently form the windows 5 . following the coating , the matrices are then stamped out of the metal - coated blank , in which case each matrix is provided with a window - like area that - is transparent . if it is intended that every matrix is to possess several windows 5 , in that case the coating process , per matrix to be stamped out , a corresponding number of transparent areas are left blank . the fig1 shows a matrix 1 of a carrier or supporting material 80 of a transparent plastic which is provided with a metallic coating 81 in which one window 5 has been left blank . it is furthermore possible for the matrix 1 to be comprised of a glass metal which is inserted in the form of a thin band or film or sheet , from which the matrix 1 is fabricated while windows 5 are produced . the number of the windows 5 constructed in the matrix 1 may be arbitrarily selected , in which case , apart from one window , the matrix 1 may be provided with two or even more than two windows disposed in side - by - side - arrangement . especially advantageous in this connection is also a latticed construction of the metallic part of the matrix so that a plurality of windows 5 is formed which are disposed in a side - by - side arrangement or on top of each other . the inherent stability of the matrix 1 is improved by means of this design while an adequate flexibility is maintained at the same time . the windows 5 possess a square , rectangular , circular or some other geometric configuration .
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with reference initially to fig1 a triple ripple airlock is illustrated , the triple ripple airlock being indicated generally at 10 . this airlock consists of a molded clear plastic member indicated generally at 12 , the plastic member including an “ s ” shaped passageway which will be described later . extending downwardly from the “ s ” shaped passageway is a mounting stem 14 which is inserted into the rubber bung or cork 16 of a fermenting vessel 18 so as to be an airtight fit . the airlock is provided with a dust cap 20 at its upper end . the “ s ” shaped passageway includes an upwardly extending portion 22 which is in direct communication with the stem 14 , the portion 22 being essentially cylindrical in cross section . a “ u ” shaped member 24 having a circular cross section connects the portion 22 with a downwardly extending portion 26 having upper , intermediate , and lower bulbs 26 . 1 , 26 . 2 , and 26 . 3 , respectively . a further “ u ” shaped member 28 having a circular cross section connects the lower end of the downwardly extending portion 26 with an upwardly extending portion 30 provided with upper , intermediate and lower bulbs 30 . 1 , 30 . 2 , and 30 . 3 , respectively . an upwardly extending member 32 is provided with a bulb 34 at its top end , which bulb receives the dust cap 20 . a clear plastic web or flashing 36 extends between the downwardly extending portion 26 and the upwardly extending portion 30 , and also between the downwardly extending portion 26 and the upwardly extending portion 22 to keep the various parts in fixed relationship to each other . after the liquid to be fermented is placed in the vessel , which liquid may be a wine must , the vessel is sealed with an airlock at the commencement of anaerobic fermentation . to this end , a sterilizing liquid is placed in the “ s ” shaped airlock , the sterilizing liquid filling the “ u ” shaped member 28 and ½ of each of the lower bulbs 26 . 3 and 30 . 3 , the sterilizing liquid being indicated generally at sl in fig2 . the sterilizing liquid typically contains either sodium or potassium metabisulfite , although other sterilizing agents may be used . during anaerobic fermentation the yeast is less active than during the initial aerobic fermentation , and the co 2 produced with escape through the sterilizing liquid one bubble at a time . with reference to fig2 it can be seen that the “ s ” type airlock of the present invention is provided with two electrodes 40 , 42 . electrode 40 is embedded in the flashing 36 which extends between the downwardly extending portion 26 and the upwardly extending portion 30 . additional flashing 44 is provided to one side of the upwardly extending portion 30 for the receipt of electrode 42 . as can be seen from fig2 the electrodes have lower terminal ends that extend into the passageway 28 . normally the ends of the electrodes are covered with the sterilizing liquid , which conducts electricity . thus , when a voltage is applied between them , current flows between the electrodes . however , when a bubble passes through the tube 28 , the current flow between the electrodes is interrupted . dust cap 20 , shown in fig3 prevents dust from settling into the airlock when it is engaged with the top of airlock 12 . conducting members 21 connect to electrodes 40 and 42 . as illustrated in fig4 electrodes 40 and 42 are connected to control means 60 through conducting members 21 . control means 60 comprises control buttons 65 a , 65 b , 65 c , 65 d , and 65 e , and a display 70 . bottle 18 contains wine must w . control means 60 counts the number of times the current between electrodes 40 and 42 is interrupted . control means 60 determines the status of the fermenting liquid based on the history of bubbles detected . control means 60 displays the status of the fermenting liquid on display 70 . the interruption of the current between the electrodes is illustrated in fig5 . bubble 50 , created by the production of co 2 during fermentation , envelops the exposed conductive material of both electrodes . thus , with a low voltage drop across the electrodes , the gas does not conduct electricity between the electrodes . a preferred voltage drop across the electrodes is approximately 5 v , although other voltage drops might be suitable . the control means of the apparatus records each interruption in the current as a bubble event . [ 0029 ] fig6 is a schematic of an embodiment of the electrical circuit of the control means . the circuit shown comprises electrodes 40 and 42 , a 5 v source , resistor 85 , operational amplifier ( op amp ) 87 , positive and negative power supplies v + and v − to power the op amp , and processor 90 . processor 90 is a conventional microprocessor , well known to those in the electronics art . the 5 v source is connected across electrodes 40 and 42 through resistor 85 . when current exists between the electrodes , v in − is 0 v . ( the 5 v source is shorted to ground .) however , when a bubble interrupts the current through the electrodes , v in − is no longer zero . ( ground is separated from v in − by an open circuit .) v in + is connected to ground . thus processor 90 can determine the presence of a bubble between electrodes 40 and 42 from the output of operational amplifier 87 . [ 0030 ] fig7 shows a second possible embodiment of control means 60 . this embodiment comprises a plurality of control buttons 65 a , 65 b , 65 c , 65 d , 65 e , and 65 f , electrodes 40 and 42 , a 5 v source , resistor 89 , pin 88 of processor 90 , audio alarm 92 , and visual alarm 94 . pin 88 of processor 90 is connected to electrode 40 and to a 5 v source through resistor 89 . electrode 42 is connected to ground . when current exists between the electrodes , pin 88 is shorted to ground . when the current is interrupted by a bubble , pin 88 will be lifted to a non - zero voltage . ( the voltage level will depend on the resistance value of resistor 89 ). in this manner , processor 90 can determine the presence of bubbles between electrodes 40 and 42 . to use the above - described device , a measure volume of a liquid subject to fermentation , such as a wine - must , is placed in a container . ( this is typically done after a period of aerobic fermentation and a hydrometer measurement to determine the proportion of sugar remaining .) the airlock of the present invention is inserted in the neck of the container . the user programs the volume of liquid present in the container using the control buttons . in a preferred embodiment , control means 60 are configured as follows . first , the batch size must be set . button 65 a increases the batch size by 10 liters each time it is pushed . button 65 b increases the batch size one liter each time it is pushed . button 65 c accepts the batch size when it is pushed , if the batch size is non - zero . ( buttons 65 d and 65 e have no function in setup mode ). after the batch size is set , the user can enter a user specified time alarm , to be activated when the enter amount of time passes without a bubble being detected . button 65 a increases this alarm time by one hour each time it is pushed . button 65 b increases this alarm time by one minute each time it is pushed . button 65 c accepts the current alarm time . ( zero may be entered if no user specified time alarm is desired .) when the user specified alarm is set , the user can then enter an alcohol alarm level . button 65 a increases the alcohol level alarm by one percent each time it is pushed . button 65 b increases the alcohol level alarm by one tenth of one percent each time it is pushed . button 65 c accepts the current alcohol level . after the alcohol level alarm is set , the user can activate the 24 hour alarm . button 65 a enables the 24 hour alarm . button b disables the 24 hour alarm . button 65 c accepts the current 24 hour alarm status . the control means then detects the bubbles of gas escaping from the airlock and displays the status of the liquid on display 70 . the status is determined based on the history of bubbles detected by control means 60 . in one embodiment , airlock 12 is configured such that the escaping bubbles have a volume at room temperature and 1 atmosphere of pressure of 1 . 7 ml . ( it is assumed that the fermentation is done at a constant temperature , thus an equal amount of gas is contained in each bubble ). thus , by counting the number of bubbles , control means 60 can determine the amount of gas to escape from the airlock . according to calculations known in the art , the amount of alcohol generated during anaerobic fermentation can be determined based on the volume of co 2 generated ( assuming substantially all of the escaping gas is co 2 generated by fermentation ) and the amount of liquid present in the container ( input using the control buttons , as discussed above ). accordingly , control means 60 can calculate the volume of alcohol generated and display this amount on display 70 . in a preferred embodiment the buttons of the control means function as follows . button 65 a scrolls the display of the bubble events towards the most current event . button 65 b scrolls the display of the bubble events towards the least recent event . button 65 c deletes the display of the displayed event if pressed alone . button 65 d caused the control means to reenter setup mode . button 65 e silences current alarms and calls up a screen to review past alarms . display 70 is set to the most recent event when button 65 e is released . when buttons 65 c and 65 e are pressed simultaneously , past alarms are cleared . as discussed above , a user can preprogram a percentage of alcohol desired with the control buttons . in this case , control means 60 displays a countdown of the amount of alcohol still to be generated . control means 60 can include an audible alarm 94 and / or visual alarm 96 to signal a user when the desired amount of alcohol has been produced . this can be especially useful in making beverages wherein some fermentation is desired after the liquid is bottled . the alarm can be set to alert the user when a portion of the desired alcohol has been produced . the user can then transfer the beverage to individual bottles for the remaining fermentation . this is also useful for the production of a sweet beverage . the user can stop fermentation before all the sugar has been consumed by the yeast . control means 60 also includes timing means to determine the amount of time between each bubble . counting means displays the amount of time since the last bubble on display 70 . audible and / or visible alarms can be activated to alert the user after a specified time without a bubble has been reached . in one embodiment , this time period is 24 hours . in another embodiment , this time period is set by the user using the control buttons ( the user specified alarm discussed above ). a potential problem with fermentations that can take a long period of time is the evaporation of the sterilizing liquid . if the sterilizing liquid evaporated to the point wherein outside air may pass into vessel 18 , then the fermentation may be spoiled . the present invention warns a user when the level of the sterilizing liquid is low . electrodes 40 and 42 are placed in member 28 such that they are exposed to air before the liquid level drops to an extent that air could reenter vessel 18 , as shown in fig2 . control means 60 times the length of the bubbles . if the sterilizing liquid has partially evaporated , then the electrodes will be exposed to air continuously . thus , when control means 60 detects an interruption of the current that lasts an extended period of time ( in one embodiment 1 hour ), it displays a low liquid level warning on display 60 . audible and / or visible alarms may also be activated . in addition , bubble detection indicator 92 is lit when a bubble is being detected ( when current is not flowing between electrodes 40 and 42 .) this can also allow a user to determine there is a problem if the bubble detection indicator remains lit for an extended period of time . the low liquid level warning and bubble detection indicator allow a user to replace the lost sterilizing liquid before the fermenting liquid is spoiled . [ 0038 ] fig2 , and 5 show the present invention being practiced with an “ s ” type airlock . however , it should be readily apparent to one skilled in the art that other airlocks or valves may be modified to practice the present invention . fig8 - 10 illustrate several valves known in the art . fig8 shows a flapper check valve 110 . electrodes 140 and 142 contact conducting strip 145 on flapper 115 when the valve is closed . thus , when the valve is closed , current flows from electrode 140 to electrode 142 through strip 145 . when flapper 115 is forced open by gas pressure , the current flowing between electrode 140 and electrode 142 is interrupted . thus , the number of times gas escapes from the valve can be counted . the amount of gas that escapes each time is measured and programmed into control means 60 . in this manner , a fermentation process can be monitored as described above . in a similar manner , fig9 shows a piston check valve 210 comprising electrodes 240 and 242 , and valve member 215 having conducting strip 245 on a surface thereon . when the valve is closed , current flows from electrode 240 to electrode 242 through strip 245 . when member 215 is forced open by gas pressure , the current flowing between electrode 240 and electrode 242 is interrupted . fig1 shows ball check valve 310 comprising electrodes 340 and 342 and conducting ball 345 . when the valve is closed , current flows from electrode 340 to electrode 342 through conducting ball 345 . when ball 345 is forced up by gas pressure , the current flowing between electrode 340 and electrode 342 is interrupted . the amount of gas released each time the valve opens is used to determine how much gas is produced during fermentation , in the manner described above . these modifications , including the use of the practicing of the present invention with other valves not shown , is intended to be within the spirit and scope of the invention as claimed . in the present specification and claims , the word “ airlock ” is intended to mean any airlock or valve known in the art or hereafter developed that can be modified as described herein to practice the present invention . while a preferred form of this invention has been described above and shown in the accompanying drawings , it should be understood that applicant does not intend to be limited to the particular details described above and illustrated in the accompanying drawings , but intends to be limited only to the scope of the invention as defined by the following claims . in this regard , the term “ means for ” as used in the claims is intended to include not only the designs illustrated in the drawings of this application and the equivalent designs discussed in the text , but it is also intended to cover other equivalents now known to those skilled in the art , or those equivalents which may become known to those skilled in the art in the future .
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referring now to the figures , wherein like reference numerals refer to like elements throughout the figures , there is shown in fig1 a telescoping anti - rotation attachment system 10 constructed in accordance with the principles of the present invention . the system 10 comprises a backup frame 12 , a pair of external anti - rotation support tubes 14 , and an internal telescoping support tube 16 . anti - rotation support pads 18 are disposed on the distal end of each of the external anti - rotation support tubes 14 , and an adjustable eye assembly 20 is disposed on the distal end of the internal telescoping support tube 16 . the trailer attachment system 10 , in a preferred embodiment , is made of a - 36 steel and weights approximately 660 lbs . the overall dimensions are approximately 25 in .× 54 3 / 16 in .× 74 in . during normal operation , the system 10 attaches to a pintle hook on a truck , using the eye assembly 20 , which in one embodiment comprises a 3 in . lunette eye . this eye is a standard component for trailers where the truck pintle hook is connected for attenuator transport . this eyelet should be a 20 , 000 lb . minimum standard trailer eyelet . again , referring to a preferred embodiment , the telescoping tube 16 is preferably ½ in .× 5 in .× 5 in . for an internal fixed tube 16 a and ½ in .× 6 in .× 6 in . for an external telescoping tube 16 b . the external support tubes 18 are also preferably ½ in .× 6 in .× 6 in . the anti - rotation support pads 18 preferably comprise a - 36 steel plate , preferably ½ in . thick . in the embodiment illustrated in fig1 , the pad size is approximately 6 in .× 6 in ., but it is preferably preferred that the pads 18 be larger , as shown , for example in fig1 and 12 . the two external support tubes 14 are substantially shorter than the internal telescoping tube 16 , as shown in fig1 , so that the vehicle , when traveling , can freely negotiate a complete 90 degree turn if necessary . of course , while presently preferred materials and dimensions have been disclosed herein , for the purpose of thoroughness and to ensure an enabling disclosure , those of ordinary skill in the art will recognize that alternative materials and dimensions may be selected , depending upon desired application and performance criteria , without departing from the basic principles of the invention . with respect now to fig1 - 7 , more details of the system 10 and its engagement with a truck or other suitable vehicle will become apparent . as shown in fig4 , on the rear end of the internal telescoping tube 16 is installed a stop plate 22 , which closes the end of the tube 16 . this plate acts as a stop when the trailer attenuator is being towed . when the tow vehicle is pulling the trailer attenuator , the plate 22 is larger than the outside dimension of the external telescoping tube 16 b . the stop plate 22 and the pintle hook of the tow vehicle share the load during transport of the trailer attenuator . as shown in fig4 - 7 , a cross - bar 24 is disposed across the system 10 , extending through the internal tube 16 and connecting the two external tubes 14 . a spring - loaded friction brake or lock 26 is disposed on the internal tube 16 , wherein the cross - bar intersects the internal tube 16 . a shear pin 28 is disposed in the internal fixed tube 16 a and the external telescoping tube 16 b of the internal tube 16 , and is arranged to slide down vertically between both tubes . during normal operational use , with the system 10 connected to a truck frame 30 , by attachment of the eye hook 20 to a pintle hook 32 on the truck frame 30 , the shear pin 28 is not under load . loads during operation are distributed between the pintle hook and a stop plate 34 on the truck . this condition , prior to impact , is illustrated particularly in fig2 . however , during an impact , the shear pin 28 undergoes double shear . once the pin has sheared , as shown in fig3 , the system 10 slides forwardly against the plate 34 on the truck . the anti - rotation arms 14 slide forwardly , and the anti - rotation support pads 18 on those arms 14 bump up against the truck plate 34 , thus preventing the attenuator from rotation around the end of the truck . at the point at which the system 10 bumps up against the truck plate , the system is converted from a uni - attachment to a tri - support system , with two outward support arms 14 preventing angular rotation and the central pintle hook attachment providing direct central support . to reduce rotation of the attenuator in angled impact situations , the telescoping anti - rotation attachment system 10 has an anti - rotation locking mechanism . the anti - rotation locking mechanism is a one - direction friction lock 26 incorporated into the internal and external telescoping tubes 16 a and 16 b , respectively . in an impact of sufficient force to shear the shear pin 28 , the inner support tube 16 is released to telescope to a collapsed orientation , so that the system 10 is allowed to slide up to the truck frame unrestricted , as shown in fig3 . the anti - rotation locking system then restricts the system 10 from moving away from the truck frame 30 . in normal operation of the trailer , the anti - rotation lock is set in the ready position . the anti - rotation locking mechanism has no effect during normal operation of the trailer . in a direct impact , the anti - rotation lock provides no restriction to the system 10 sliding forward , allowing the anti - rotation arms 14 to contact the truck plate 34 . when the anti - rotation arms 14 have contacted the truck plate 34 , the locking mechanism 26 holds the system 10 in plate against the plate 34 . during an angled impact , when the system 10 slides forwardly , the anti - rotation arms 14 contact the frame 30 . the direction of the impact creates an angular moment , putting one of the anti - rotation arms 14 in compression and one in tension . the locking action restricts the rotation of the attenuator by placing the pintle hook attachment in tension . with the pintle hook attachment in tension , and one of the anti - rotation arms in compression , rotation of the attenuator is restricted . post impact , the lock can be easily released , allowing the system 10 to be moved back from the end structure of the truck . now with reference to fig8 - 10 , a crash attenuator unit 36 has been attached to the telescoping anti - rotation attachment system 10 . the unit 36 is attached to the backup frame 12 in known fashion . in the illustrated embodiment , the attenuator unit 36 is mounted on wheels 38 disposed on a standard axle assembly 40 , as shown . in preferred embodiments , the crash attenuator unit 36 is essentially the same as an existing scorpion tma available from the assignee traffix devices , inc . and shown and described in u . s . pat . no . 6 , 581 , 992 , already incorporated herein by reference . components of the crash attenuator unit 36 include a strut portion 42 and a cartridge portion 44 . the strut portion 42 comprises a frame 46 , preferably comprised of aluminum tubing , and the cartridge portion 44 comprises a frame 48 , also comprised of aluminum tubing . energy absorbent cartridges 50 , 52 , and 54 are disposed within the unit 36 . fig1 and 12 are somewhat similar to fig2 and 3 , in that they illustrate a pre - impact condition position for the inventive system 10 , in fig1 , and a post - impact condition position for the inventive system , in fig1 , in somewhat more detail than is shown in fig2 and 3 . in particular , in this embodiment , larger anti - rotation support pads 18 are shown than in the fig2 and 3 embodiment , which provides a better support contact between the system 10 and the stop plate 34 . fig1 - 15 illustrate a somewhat modified embodiment of the present invention , wherein an arrowboard 56 has been installed on the crash attenuator unit 36 , specifically on the backup frame 12 . the arrowboard unit 56 includes support posts 58 which engage the back up frame to mount the arrowboard 56 onto the crash attenuator . this embodiment is also different , in that the wheels 38 and axle assembly 40 are disposed in the rear of the unit 36 , rather than the center thereof . this embodiment offers some advantages , in that it makes the unit simpler , lighter , more stable , and easier to produce . still another modified embodiment , of the telescoping anti - rotation attachment system 10 , is illustrated in fig1 . this embodiment features a single point attachment between the tma and the host vehicle , as in previous embodiments , by means of a ring hook 60 or the like , suitable for attachment using a conventional hitch system or other desired means . aft of the ring hook 60 are a plurality of telescoping sliders 62 , which function to collapse upon vehicular impact with the tma , in order to prevent rotation of the trailer ( tma ) upon impact . this embodiment differs from that shown in the prior embodiments , for example , in that the center support tongue 64 for supporting the ring 60 is rigid , rather than telescoping , as in the prior embodiment . on the other hand , the two supports 62 are telescoping , rather than rigid , as in the prior embodiment . the important concept is that , in either embodiment , there is a single - point connection between the tma and the vehicle , in conjunction with structure to prevent rotation of the tma upon impact by a vehicle . within this parameter , the structure may include one or more slides , one or more telescoping tubes , and / or one or more collapsing tubes , used in conjunction with one or more stops that move into contact with the host vehicle , in order to resist rotation of the trailer attenuator . some of the advantages of the present invention , and , particularly , these additional embodiments , are that it can be used in connection with a lighter host vehicle than the federal standard 19 , 600 lb . host vehicle currently necessary for tma &# 39 ; s . the inventors have determined that the present invention may successfully be used with a host vehicle as light as 10 , 000 lb , and perhaps lighter . the rams prevent rotation of the trailer with respect to the host vehicle . a torsion axle is preferably employed instead of leaf springs . the embodiments with rear - mounted wheels allow for elimination of a relatively incompressible center axle accordingly , although an exemplary embodiment of the invention has been shown and described , it is to be understood that all the terms used herein are descriptive rather than limiting , and that many changes , modifications , and substitutions may be made by one having ordinary skill in the art without departing from the spirit and scope of the invention .
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referring to the drawings , fig1 schematically illustrates a method for directing lubricating material through an automatic planetary transmission to sufficiently cool the pinion gears of the planetary carrier . first , the lubricating material ( oil or other reasonably appropriate transmission fluids ) is supplied to the transmission at step 110 through an inlet on the exterior of the transmission housing where the lubricating material is then directed from the supply to the inner diameter of the main shaft at step 112 . next , the lubricating material is directed from the main shaft to the interior of the sun gear shaft at step 114 where the oil travels along the sun gear and its neighboring components . from the sun gear the oil is directed to the spider section of the planetary carrier at step 116 . the planetary carrier , being configured with machined and formed grooves , receives the lubricating material and directs the lubricating material into the grooves of the spider section at step 118 . next , the oil is directed into the axial slots ( 56 shown in fig1 and 3 ) of the first thrust washer ( 50 ) at step 120 . from the first thrust washer the lubricating material is directed axially and radially to the pinion bearings and the spindle of the pinion gear to specifically cool that area of the planetary carrier at step 122 . the oil is then directed to a second thrust washer ( 62 ) at step 124 , which directs the oil axially through axial slots 56 in the thrust washer to the flange section ( 28 shown in fig1 , 4 a and 4 b ) of the planetary carrier at step 126 . the oil is then directed radially outward , at step 127 , through grooves ( 65 shown in fig4 a ) in the flange section 28 . finally , the oil is dispersed to components adjacent to the planetary carrier ( 16 ) at step 128 and directed back to the sump ( or supply ) to repeat the process at 112 . the lubricating material 10 is directed through the transmission by pressurizing the inner cavity of the transmission . in the preferred embodiment , a pump ( not shown ) sends the lubricating material 10 , as shown in fig2 , from a source at 30 p . s . i . to the inner diameter of the main shaft 12 . to maintain the desired pressure level , the transmission components are designed to nest substantially close with respect to each another . this significantly seals the connection between the components and prevents the lubricating material 10 from flowing in unintended areas . for example , in fig2 , the sun gear 14 — adjacent to the planetary carrier 16 — rests on a bushing 18 and steel sleeve 20 that substantially prevent the lubricating material 10 from flowing away from the planetary carrier 16 . therefore , the bushing 18 and steel sleeve 20 help to maintain the desired pressure level in the vicinity of the planetary carrier 16 so that the lubricating material 10 can successfully reach the pinion bearings 22 of the pinion gears 24 . the planetary carrier 16 consists of at least one pinion gear 24 ( three of the five are shown in fig4 b ) and a two - piece housing defined by a spider section 26 and a flange section 28 which are sintered brazed together . the face of the spider section 26 of the planetary carrier 16 is shown in fig4 c . the spider section 26 contains cylindrical openings 29 to receive posts 30 which add stiffness and strength to the planetary carrier 16 to react the pinion bearing 22 loading . fig4 a shows the face of the flange section 28 , which is the more frontward portion of the planetary carrier 16 . the flange section 28 contains splines 32 , which connect the planetary carrier 16 to the main shaft 34 , as shown in fig2 , and transmit power to the rear of the transmission ( not shown ). as shown in fig2 , the planetary carrier 16 is designed so that the pinion gears 24 are in a drivable relationship with a sun gear 14 and ring gear 36 . together , the three gear types ( 14 , 24 and 36 ) encircle the main shaft 34 of the transmission and through engagement with clutches ( not shown ) determine the output speed of the transmission . one technical advantage of this invention is in the redesign of the spider section 26 and flange section 28 of the planetary carrier 16 . the spider section 26 of the planetary carrier 16 has five grooved areas , each having a first and second groove formed therein ( 38 and 40 respectively ). the grooves 38 , 40 have several functions including , directing the lubricating material 10 from the inner diameter of the planetary carrier 42 to the pinion bearings 22 at the inner diameter of the pinion gears 44 . each first groove 38 , as shown in fig4 c , is concave , facing the inner diameter of the planetary carrier 42 so as to receive lubricating material 10 from the sun gear 14 and sun gear shaft 15 . the first groove 38 is also segmentally annular , extending about the inner diameter of the planetary carrier 42 in each first groove . the first groove 38 is intersected by a second groove 40 , which extends radially to intersect the first groove 38 and radially along the grooved spider section 26 of the planetary carrier 16 to transfer the lubricating material 10 into a first pocket 46 . in the preferred embodiment , the second groove 40 is formed in the spider section 26 of the planetary carrier 16 by an alteration to the die ( not shown ) of the planetary carrier 16 . formed by a powder metallurgy process , the planetary carrier 16 is constructed with a die having a protrusion defining the second formed groove 40 . powder metallurgy was chosen because the process is ideal for parts with irregular curves or for small recesses that are difficult to machine . moreover , the process reduces the amount of material waste since the intricacies of the part can be included in the die instead of being sculpted from a blank through a series of machining processes . still , powder metallurgy has its limitations . the intricacies of the die must be such that the part is removable from the die . for this reason , in the preferred embodiment , the first groove 38 was machined into the spider section 26 of the planetary carrier 16 . the first groove 38 was designed to intersect the second groove 40 ( as shown in fig4 c ) and transfer the lubricating material 10 radially into the first pocket 46 where a first thrust washer 50 will aid in directing the lubricating material 10 into the pinion bearings 22 . the intersection between the first groove 38 and second groove 40 forms a shoulder at 52 , which acts as a dam to substantially prevent oil from escaping the pinion area of the spider section 26 of the planetary carrier 16 . the second groove 40 leads to and defines the first pocket 46 that extends radially to the inner diameter the pinion gear 44 where an axial slot 56 in the first thrust washer 50 receives the lubricating material 10 . adjacent to the first pocket 46 is the first thrust washer 50 , which is better shown in fig3 . the first thrust washer 50 has radially extending slots 54 ( or conned depressions ) spanning across the face of the first thrust washer 50 . the radially extending slots 54 in the first thrust washer 50 serve to direct the lubricating material 10 toward the first pocket 46 , as shown in fig2 . in the preferred embodiment , the thrust washer 50 also has axial slots 56 ( or notches ), shown in fig2 and 3 , which , along with groove 40 , carry the lubricating material 10 to the spindle 58 and bearings 22 of the pinion gear 24 where the spindle 58 is supported or press fit into the carrier bore 59 . moreover , the first thrust washer 50 also has a flanged edge 60 . the flanged edge 60 extends axially into the radially extending flange slots 61 of the spider section 26 and functions to keep each washer from rotating with respect to the spider section 26 of the planetary carrier 16 by nesting in the spider section 26 at 61 ( as shown in fig2 and 4 c ). from the first thrust washer 50 , the lubricating material 10 is directed to the pinion bearings 22 . the pinion bearings 22 , as shown in fig2 , are aligned axially along the spindle 58 . the pinion bearings 22 act to provide support for the pinion gear 24 . since the pinion gears 24 are in a drivable relationship with the ring gear 36 as well as the sun gear 14 , the pinion bearings 22 see a substantial amount of loading during operation of the transmission . therefore , this area requires lubrication for cooling to enhance the lifecycle of the pinion bearings 22 . also shown in fig2 , a second thrust washer 62 is attached to the pinion gear 24 . each second thrust washer 62 has radially and axially extending slots similar to 54 and 56 shown in fig3 . the slots of the second thrust washer 62 are operative to direct the lubricating material 10 axially away from the spindle 58 of the pinion gear 24 through axial slot 56 and towards a third groove 64 formed in the flanged section 28 of the planetary carrier 16 . the second thrust washer 62 also has a flanged edge 60 which nests in the flange section 28 at 65 ( as shown in fig4 a ). from each third groove 64 , the lubricating material 10 exits the planetary carrier 16 and is directed to other transmission components ( not shown ) for cooling and is eventually returned to the transmission sump for reuse . the configuration of transmission components adjacent to the planetary carrier 16 also assists in directing the lubricating material 10 to the spider section 26 of the planetary carrier 16 and into the pinion bearings 22 . the sun gear shaft 15 for example , which encircles the main shaft 34 , has at least one radially extending aperture 68 to direct the lubricating material 10 from the inner diameter of the main shaft 12 to the sun gear 14 and eventually the spider section 26 of the planetary carrier 16 . the sun gear shaft 15 is attached to the sun gear 14 by a section of splines 70 between the sun gear 14 and sun gear shaft 15 . the sun gear 14 is adjacent to a thrust bearing 72 , which further restricts the passage of the lubricating material 10 away from the planetary carrier 16 and its pinion gears 24 . moreover , the main shaft 34 is fitted with apertures like 74 that extend radially and direct the lubricating material 10 from the inner diameter of the main shaft 12 to the outer diameter of the main shaft 76 . the apertures — 68 and 74 — are designed to be large enough to permit the passage of the lubricating material 10 but small enough to maintain the pressure in the cavity of the planetary carrier 16 . lastly , the ring gear 36 also has a radially extending aperture 78 to permit the lubricating material 10 to exit the planetary carrier 16 . while the best modes for carrying out the invention have been described in detail , those familiar with the art to which this invention relates will recognize various alternative designs and embodiments for practicing the invention within the scope of the appended claims .
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reference will now be made in detail to the present preferred embodiments of the invention , examples of which are illustrated in the accompanying drawings . wherever possible , the same reference numbers are used in the drawings and the description to refer to the same or like parts . fig2 is a diagram showing the circuit structure of a scanner according to one preferred embodiment of this invention . as shown in fig2 , the scanning circuit 200 is responsible for controlling the entire process of scanning a document . the scanning circuit 200 includes a main circuit module 210 and an optical sensor circuit module 220 . the main circuit module 210 and the optical sensor circuit module 220 are linked together through a connection cable 230 such as a flat cable . the flat cable carries both scan control signals and digital image data . the main circuit module 210 further includes a main control logic unit 270 , a memory unit 280 and a memory control logic unit 275 . the optical sensor circuit module 220 further includes an optical sensor 240 , an analog front - end processor ( afe ) 250 , an analog / digital converter 260 and a timing signal generator 265 . the main control logic unit 270 in the main circuit module 210 connects with the human / machine interface of a personal computer ( not shown ) through a communication interface 285 . here , the communication interface 285 can be a universal serial bus ( usb ) interface or an enhanced parallel port ( epp ) interface , for example . the communication interface 285 receives important scanning instructions regarding image resolution , brightness level and scanning range and converts the scanning instructions into scanning control signals that pass along the connection cable 230 . when the optical sensor circuit module 220 receives scanning control signals from the main circuit module 210 , the timing generator 265 produces the required timing control signals for extracting an analog image signal from the optical sensor 240 . the optical sensor 240 is a charge - coupled device ( ccd ) or a cmos image sensor , for example . the captured analog image signal is preprocessed by the analog front - end preprocessor 250 . thereafter , the pre - processed analog image is transmitted to the analog / digital converter 260 and converted to digital image data . the digital image data is subsequently transmitted to the main circuit module 210 through the connection cable 230 . at this moment , the data transmitted on the connection cable 230 is no longer the analog signal that easily has the distortion but is the digital image data that can be easily transmitted in a fast speed . as a result , it can effectively solve the issue about difficulty on maintaining the scanning quality when the scanning process is operated in the fast speed . on receiving the digital image data , the main circuit module 210 transfers the data to the memory unit 280 via the memory controller 275 . the memory unit 280 may contain conventional types of memory such as synchronous or non - synchronous dynamic random access memory ( dram ) or static random access memory ( sram ). obviously , the main control logic unit 270 may incorporate an image preprocessor ( not shown ) for compensating and adjusting the captured digital image data so that the scanned image can have better quality . in addition , timing signals may have to be adjusted due to the change in connection between the communication interface of various integrated circuits ( ics ). 1 . since the flat cable transmits digital data instead of easily distorted analog image signals , a clearer image can be obtained at a higher scanning speed . 2 . since the flat cable transmits scanning control signals between conventional ic communication interfaces instead of timing control signals , the effect due to electromagnetic interference is greatly minimized . it will be apparent to those skilled in the art that various modifications and variations can be made to the structure of the present invention without departing from the scope or spirit of the invention . in view of the foregoing , it is intended that the present invention cover modifications and variations of this invention provided they fall within the scope of the following claims and their equivalents .
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fig1 shows a typical wellhead structure that is used in connection with an oil and / or gas well , where a wellhead 1 , at its upper end , is connected to a riser 2 which extends between a floating structure ( not shown ), for example , a platform or the like , and the wellhead 1 . a first casing 3 extends a distance down into a surface formation and is cemented to the surface formation o . the upper end of the first casing 3 is suitably suspended from the wellhead 1 , sealing devices 4 in the form of one or more packers being arranged between an exterior surface of the first casing 3 and an interior surface of the pressurised housing h of the wellhead 1 . within the first casing 3 there is arranged another , second casing 5 , which will then extend through the first casing 3 and a longer distance down into the surface formation o than the first casing 3 . the second casing 5 will , like the first casing 3 , be cemented to the surface formation o . the second casing 5 will in addition be partly supported by ( suspended in ) the first casing 3 . in order to obtain a tight connection between an interior surface of the first casing 3 and the exterior surface of the second casing 5 , sealing devices 4 are provided between the first and the second casing 3 , 5 . as the second casing 5 has a smaller diameter than the first casing 3 , a space will be formed between the first and the second casing 3 , 5 , which space is called an annulus . the space that is delimited by the interior surface of the first casing 3 , the second casing 5 and the casing hanger in the first and the second casing 3 , 5 will define a first annulus a . as described above for the first and the second casing 3 , 5 , a third casing 6 will run internally through the second casing 5 , and will be supported by ( suspended in ) the second casing 5 . the third casing 6 will have a diameter that is smaller than the diameter of the second casing 5 . here , the second and the third casing 5 , 6 , together with the casing hanger in the second and the third casing 5 , 6 , will define a second annulus b . within the third casing 6 there is arranged a last and fourth casing 7 , through which fourth casing 7 a production tubing ( not shown ) will run when the oil and / or gas well is in production . the fourth casing 7 will have a diameter that is smaller than the diameter of the third casing 6 . the space that is formed between the third and the fourth casing 6 , 7 and the casing hanger in the third and the fourth casing 6 , 7 will form a third annulus c . to obtain a tight connection between an interior surface of the second and the third casing 5 , 6 and the exterior surface of the third and the fourth casing 6 , 7 , sealing devices 4 are provided between the second and the third casing 5 , 6 and the third and the fourth casing 6 , 7 . the wellhead 1 may furthermore be connected to a blow - out valve ( not shown ), a so - called bop ( blow out preventer ). the above wellhead structure will provide a fluid and pressure - tight system , but conditions in the oil and / or gas well might mean that the sealing devices 4 , owing , for example , to large pressure build - ups in the well , temperature variations , or their service life , might begin to “ leak ”, such that a pressure leak occurs in the well , where this is not desirable . in order to prevent such undesired pressure leaks , a plurality of apparatus for measuring different parameters 8 , which will be explained in more detail in connection with remaining fig2 to 4 , will be arranged along the length of the wellhead 1 , such that measurement and monitoring of different parameters , for example , pressure and / or temperature , can be carried out in each of the annuli a - c in the well . the wellhead 1 will then be configured with a plurality of through holes ( not shown ), to which holes the apparatus 8 can suitably be connected . the measurements made in each of the annuli a - c may be suitably transmitted to , for example , a floating structure for processing and monitoring . fig2 shows a first embodiment of a measuring or monitoring apparatus 8 according to the present invention , where the apparatus 8 is shown partly from the side and in a cross - section , when connected to the wellhead 1 . the wellhead 1 will then be configured with a plurality of through holes or passages , 9 , which passages 9 will then be so positioned as to lead in to each of the annuli a - c . the apparatus 8 comprises a sensor 10 and a flange assembly 11 , which are fixedly connected to each other . the flange assembly 11 is constituted of a front flange portion 12 and a rear flange portion 13 , which via a plurality of bolts 14 or the like are connected to each other . an end of the rear flange portion 13 will then be so configured that it overlaps an end of the front flange portion 12 when the front and the rear flange portion 12 , 13 are assembled . both the front and the rear flange portion 12 , 13 will furthermore be configured with a groove or recess 16 , in which recess 16 an o - ring 17 is arranged when the front and the rear flange portion 12 , 13 are connected to each other , so as to provide a fluid - tight connection between them . the flange assembly 11 is further configured with a through bore 14 , in which bore 14 the sensor 10 and the associated electronics 15 are arranged . a second end ( opposite the end that is connected to the rear flange portion 13 ) of the front flange portion 12 will then be configured with a contact face 18 for the sensor 10 , the said contact face 18 forming a stop edge for the sensor 10 . the sensor 10 will then similarly be configured with a face 19 that will bear against the contact face 18 in the front flange portion 12 , such that the sensor 10 is positioned correctly in relation to the wellhead 1 . the sensor 10 will furthermore , along a part of its length , be configured with a threaded portion 20 , such that the sensor 10 can be screwed into the passage 9 in the wellhead 1 . the passage 9 in the wellhead 1 will then be configured with a complementarily threaded portion ( not shown ). the sensor 10 comprises a first electronic circuitry , e . g . in the form of an electronic printed circuit board 21 , which via wires 22 is connected to a second electronic circuitry in the form of a separate main printed circuit board 23 arranged in the bore 14 in the front flange portion 12 . through this configuration , the sensor 10 , comprising the electronic printed circuit board 21 , will be separated from the main printed circuit board 23 , the sensor 10 being arranged at the end of the front flange portion 12 which lies closest to the wellhead 1 , whilst the separate main printed circuit board 23 will be arranged at an opposite end of the front flange portion 12 , adjacent to the rear flange portion 13 . between the sensor 10 and the separate main printed circuit board 23 there is disposed a pressure - tight element 24 , for instance a ceramic element with wires 22 connecting the sensor 10 and the separate main printed circuit board 23 extending through the ceramic element . in one embodiment , the wires 22 will , however , not run through the whole of the ceramic element 24 , only a certain length into the ceramic element 24 , such that wires 22 from sensor 10 and wires 22 to the main printed circuit board 23 , when arranged in the ceramic element 24 , will be located at a distance from each other . the ceramic element 24 is however so configured that through at least one through - going portion or area through the ceramic element 24 there is arranged a mixture of a ceramic material and an electrically conducting material ( for example , platinum ). this will mean that the ceramic element 24 will form a pressure - tight barrier in the apparatus 8 . the ceramic element 24 is in a fluid and / or pressure - tight way connected to a sleeve 25 . the sleeve 25 is further configured with a threaded portion ( not shown ) and a varying cross - section along its length . the current passage through the ceramic element 24 may however be achieved by , for example , using metallic or other electrically conducting materials . the pressure - tight element 24 has been described above , by example , as a ceramic element . in this case the pressure - tight element 24 may be provided as a ceramic feedthrough disc , wherein wires or other electrical conductors may be embedded in the ceramic element . the ceramic material may be chrystalline or non - chrystalline . the ceramic material may , e . g ., include aluminium oxide . alternatively , the pressure - tight element 24 may be a glass element , or as another alternative , the pressure - tight element 24 may include a metallic disc ( e . g ., made of steel or titanium ), and the transmission devices may be electrical conductors ( e . g ., made of platinum ) passed through bores in the metallic disc . further , a glass , sapphire or a ceramic material may surround each conductor and fluidly seal the space between each conductor and the corresponding bore in the metallic disc . the pressure - tight element 24 may be located in a portion of the bore 14 where the diameter is reduced . the pressure - tight element 24 is shown fitted into a portion of the bore having a diameter corresponding to the diameter of the pressure - tight element 24 . a sleeve 25 is located in the bore 14 in engagement with a first side of the pressure - tight element facing the passage 9 . the sleeve 25 in this position exerts pressure to the isolation element 24 . the sleeve may be configured with threads , provided for engagement with threads in the bore 14 , and may be provided with a diameter enlarged portion 25 b arranged to fit with a restriction of the bore 14 which may provide an end stop for the sleeve 25 . by engaging the threads of the sleeve 25 with the threads of the bore 14 , the sleeve may be screwed into a position exerting a pressure to the pressure - tight element 24 . a second side of the isolation element 24 , which faces away from the passage 9 , rests against a restriction in the diameter of the bore providing a contact portion 26 . in between the contact portion 26 and a portion of the second side of the isolation element a seal , for instance a metallic seal , may be provided . by moving the sleeve 25 relative to the bore 14 , for instance by screwing the sleeve 25 relatively to the bore 14 the isolation element 24 exerts a force to the seal of a size which provides an isolation engagement between the contact portion 26 , the seal and the isolation element 24 . this arrangement may enable or further improve the pressure tight properties of the apparatus . the through bore 14 in the front flange portion 12 will along a part of its length be configured with a varying cross - section , which varying cross - section will be complementarily configured with the varying cross - section of the sleeve 25 . a rear edge 26 of the varying cross - section in the through bore 14 will , when the sleeve 25 with the pressure - tight element 24 , e . g . ceramic element , is arranged in the varying cross - section of the through bore 14 , together with an end of the sleeve 25 , form a tight connection between the front flange portion 12 and the sleeve 25 . this arrangement may form a fireproof connection in the apparatus 8 . the rear flange portion 13 is configured with a through and threaded hole 27 , so as to enable a cable lead - in 28 , comprising a tensioning nut 29 , to be connected to the threaded hole 27 . between the contact faces of the rear flange portion 13 and the cable lead - in 28 there is arranged a seal 30 in the form of an o - ring . an electric cable e is then passed through the cable lead - in 28 and connected to a connecting printed circuit board 31 in the though bore 14 in the flange assembly 11 . the separate main printed circuit board 23 and connecting printed circuit board 31 are , by means of a securing device 32 , connected to a rear wall 33 of the front flange portion 12 . the securing device 32 will further ensure that the main printed circuit board 23 and the connecting printed circuit board 31 are arranged at a distance from each other . signals received from the sensor 10 will then be wirelessly transmittable from the main printed circuit board 23 to the connecting printed circuit board 31 , in order thus , through the electric wire e , to be transmitted for processing on a floating structure ( not shown ). the rear flange portion 13 , which is an “ open ” sleeve , is , at an end opposite the end overlappingly connected to the front flange portion 12 , configured for being connected to an end termination 34 , such that the apparatus 8 can be closed or sealed at the end opposite the connection to the wellhead 1 . the end termination 34 is then configured with a plurality of through openings 35 , which through openings 35 are used for passage of bolts 36 . an end termination in the rear flange portion 13 will then be configured with a plurality of threaded holes 37 for receipt and screw fastening of bolts 36 . the end termination 34 will on one side be configured with a projection 38 , which projection 38 will be such that it essentially corresponds to the through bore 14 , such that the projection 38 will extend a certain distance into the rear flange portion 13 when the end termination 34 , via the bolts 36 , is connected to the rear flange portion 13 . a seal 39 in the form of an o - ring is arranged between the interior surface of the rear flange portion 13 and the exterior surface of the projection 38 , one or both of these surfaces then being configured with a groove for receiving the seal 39 . furthermore , the front flange portion 12 , in a face a which forms contact with the wellhead 1 , is configured with a plurality of holes 41 , such that bolts and nuts 42 can be used to fixedly connect the apparatus 8 to the wellhead 1 . face a is further configured with a recess 43 for receiving a sealing element 44 such that a tight connection is provided between the apparatus 8 and the wellhead 1 when they are connected to each other . fig3 shows another embodiment of the apparatus 8 according to the present invention , where the apparatus 8 is now configured so as to be able to transmit signals from the sensor 10 wirelessly . with the exception of how the transmission of signals takes place according to this embodiment , the general component composition of the apparatus 8 and its operating principle are the same as described for the first embodiment of the invention as shown in fig2 , and so for the sake of simplicity they are not described again . the embodiment shown in fig3 uses a wireless transmission of signals from the sensor 10 , where the rear flange portion 13 will be configured with a through and threaded hole 27 , so as to enable a wireless antenna 44 to be connected to the through and threaded hole 27 . a securing device 32 is also used in this embodiment to connect the separate main printed circuit board 23 and the connecting printed circuit board 31 to the rear wall 33 of the front flange portion 12 . however , the distance between the main printed circuit board 23 and the connecting printed circuit board 31 will now be greater than in the embodiment described with reference to fig2 , seen in relation to the fact that a part of the wireless antenna 44 will extend a distance into the through bore 14 in the flange assembly 11 . signals received from the sensor 10 will then be wirelessly transmittable from the main printed circuit board 23 to the connecting printed circuit board 31 , so as to be further transmittable wirelessly from the connecting printed circuit board 31 to the wireless antenna 44 , in order to be further transmitted wirelessly for processing on a floating structure ( not shown ). for signal amplification , a plurality of signal amplifying units ( not shown ) may be provided between the wellhead and the floating structure . to operate the sensor 10 and / or the wireless antenna 44 in the apparatus 8 , a battery or a battery pack 45 is provided in the apparatus 8 when the apparatus 8 is assembled . this embodiment will mean that the battery or battery pack 45 can easily be replaced by unscrewing bolts 36 in the end termination 34 and removing the end termination 34 from the rear flange portion 13 . the battery or battery pack 45 can in a suitable manner , for example , by means of wires etc . ( not shown ), be connected to the connecting printed circuit board 31 . the battery or battery pack 45 may also be connected to , or comprise a device ( not shown ) capable of ensuring that the battery or battery pack 45 is turned off and on at certain time intervals . the device can then turn the battery or battery pack 45 on for a pre - specified time unit ( minutes , hours or days ), so as to allow the desired number of measurements of , for example , pressure and temperature to be carried out , after which the device will turn the battery or battery pack 45 off . however , it should be understood that such a device must also comprise the possibility of being overridden , seen in relation to the fact that measurements with the apparatus 8 may also be carried out outside the pre - specified time units . fig4 shows an additional embodiment of the apparatus 8 according to the present invention , where the rear flange portion 13 in the apparatus 8 is configured with several through and threaded holes 27 . the general component composition of the apparatus 8 and its operating principle are the same as described for the first embodiment of the invention as shown in fig2 , and so for the sake of simplicity they are not described again . configuring the rear flange portion 13 with several through and threaded holes 27 , will enable the apparatus 8 to be connected to two electric cables e , an electric cable e and a wireless antenna 44 , or even two wireless antennas 44 . alternatively , one of the through and threaded holes 27 can initially be closed by a stop plug 46 . if , for example , the electric wire e or the wireless antenna 44 for some reason is knocked off or damaged there will be the possibility of connecting to the apparatus 8 by removing the stop plug 46 and , for example , coupling a wireless antenna 44 to the other through and threaded hole 27 . in addition , this embodiment will also permit several similar apparatus to be connected on the same line , where the apparatus will then be able to communicate with each other digitally . the invention has now been explained by referring to some non - limiting examples . a person of skill in the art will understand that it will be possible to make a number of variations and modifications to the temperature and pressure monitoring system as described within the scope of the invention as defined in the attached claims .
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here we describe an editing tool for affect in speech . we describe its architecture and an implementation and also suggest a set of transformations of f 0 contours , energy , duration and spectral content , for the manipulation of affect in speech signals . this set includes operations such as selective extension , shrinking , and actions such as ‘ cut and paste ’. in particular , we demonstrate how a natural expression in one utterance by a particular speaker can be transformed to other utterances , by the same speaker or by other speakers . the basic set of editing operators can be enlarged to encompass a larger variety of transformations and effects . we describe below the method , show examples of subtle expression editing of one speaker , demonstrate some manipulations , and apply a transformation of an expression using another speaker &# 39 ; s speech . the affect editor , shown schematically in fig1 , takes an input speech signal x , and allows the user to modify its conveyed expression , in order to produce an output signal { tilde over ( x )}, with a new expression . the expression can be an emotion , mental state or attitude . the modification can be a nuance , or might be a radical change . the operators that affect the modifications are set by the user . the editing operators may be derived in advance by analysis of an affective speech corpus . they can include a corpus of pattern samples for concatenation , or target samples for morphing . a complete system may allow a user to choose either a desired target expression that will be automatically translated into operators and contours , or to choose the operators and manipulations manually . the editing tool preferably offers a variety of editing operators , such as changing the intonation , speech rate , the energy in different frequency bands and time frames , or the addition of special effects . this system may also employ an expressive inference system that can supply operations and transformations between expressions and the related operators . another preferable feature is a graphical user interface that allows navigation among expressions and gradual transformations in time . the preferred embodiment of the affect editor is a tool that encompasses various editing techniques for expressions in speech . it can be used for both natural and synthesized speech . we present a technique that uses a natural expression in one utterance by a particular speaker for other utterances by the same speaker or by other speakers . natural new expressions may be created without affecting the voice quality . this system may also employ an expressive inference system that can supply operators and transformations between expressions and the related operators . another preferable feature is a graphical user interface that allows navigation among expressions and gradual transformations in time . the editor employs a preprocessing stage before editing an utterance . in preferred embodiments post - processing is also necessary for reproducing a new speech signal . the input signal is preprocessed in a way that allows processing of different features separately . the method we use for preprocessing and reconstruction was described by slaney ( slaney m ., covell m ., lassiter b . : automatic audio morphing ( icassp96 ), atlanta , 1996 , 1001 - 1004 ) who used it for speech morphing . it is based on analysis in the time - frequency domain . the time - frequency domain is used because it allows for local changes of limited durations , and of specific frequency bands . from human computer interaction point of view , it allows visualization of the changeable features , and gives the user graphical feedback for most operations . we also use a separate f 0 extraction algorithm , so a contour can be seen and edited . these features also make it a helpful tool for the psycho - acoustic research of features &# 39 ; importance . the pre - processing stages are described in algorithm 1 : 2 . calculating the smooth spectrogram using mel - frequency cepstral coefficients ( mfcc ). the coefficients are computed by re - sampling a conventional magnitude spectrogram to match critical bands as measured by auditory perception experiments . after computing logarithms of the filter - bank outputs , a low dimensional cosine transform is computed . the mfcc representation is inverted to generate a smooth spectrogram for the sound which does not include pitch . 3 . divide the spectrogram by the smooth spectrogram , to create a spectrogram of f 0 . 4 . extracting f 0 . this stage simplifies the editing of f 0 contour . 5 . edge detection on the spectrogram , in order to find significant patterns and changes , and to define time and frequency pointers for changes . edge detection can also be done manually by the user . the pre - processing stage prepares the data for editing by the user . the affect editing tool allows editing of an f 0 contour , spectral content , duration , and energy . different implementation technique can be used for each editing operation , for example : 1 . changing the intonation . this can be implemented by mathematical operations , or by using concatenation . another method for changing intonation is to borrow f 0 contours from different utterances of the same speaker and other speakers . the user may change the whole f 0 contour , or only parts of it . 2 . changing the energy in different frequency ranges and time - frames . the signal is divided into frequency bands that relate to the frequency response of the human ear . a smooth spectrogram that represents these bands is generated in the pre - processing stage . changes can then be made in specific frequency bands and time - frames , or over the whole signal . 3 . changing the speech rate . extend and shrink the duration of speech parts by increasing and decreasing the overlap between frames in the inverse short time fourier transform . this method works well for the voiced parts of the speech , where f 0 exists , and for silence . the unvoiced parts , where there is speech but no f 0 contour , can be extended by interpolation . these changes can be done on parts of the signal or on all of it . as will be shown below , operations on the pitch spectrogram and on the smooth / spectral spectrogram are almost orthogonal in the following sense . if one modifies only one of the spectrograms and then calculate the other from the reconstructed signal it will have minimal or no variations compared to the one calculated from the original signal . the editing tool has built - in operators and recorded speech samples . the recorded samples are for borrowing expression parts , and for simplifying imitation of expressions . after editing , the system has to reconstruct the speech signal . post - processing is described in algorithm 2 . 6 . regeneration of the new full spectrogram by multiplying the modified pitch spectrogram with the modified smooth spectrogram . 7 . spectrogram inversion , as suggested by griffin and lim [ 2 ]. algorithm 2 : post - processing for reconstruction of a speech signal after editing . spectrogram inversion is the most complicated and time - consuming stage of the post - processing . it is complicated because spectrograms are based on absolute values , and do not give any clue as to the phase of the signal . the aim is to minimize the processing time in order to improve the usability , and to give direct feedback to the user . this is just one example of many editing techniques that can be integrated in the speech editor tool , as provided for example by text and image processing tools . in this section we show some of the editing operations , with a graphical presentation of the results . we were able to determine that an affect editor is feasible with current technology . the goals were to determine whether we could obtain new speech signals that sound natural and convey new or modified expressions , and to experiment with some of the operators . we examined basic forms of the main desired operations , including changing f 0 contour , changes of energy , spectral content , and speech rate . for our experiment we used recordings of 15 people speaking hebrew . each speaker was recorded uttering repeatedly the same two sentences during a computer game , with approximately a hundred iterations each . the game elicited natural expressions and subtle expressions . it also allowed tracking of dynamic changes among consecutive utterances . fig2 presents features of the utterances ‘ sgor de - let ’ which means in hebrew ‘ close the door ’, uttered by a male speaker . fig2 a represents the fundamental frequency curves of two original utterances . the higher curve shows the expression of uncertainty , and the lower curve shows determination . the uncertainty curve is long , high , and has a mildly ascending slope , while the determination curve is shorter and has a descending slope . fig2 b represents the curve of the edited utterance of uncertainty , with the combined f 0 curve generated from the two original curves , after reconstruction of the new edited signal . the first part of the original uncertainty curve , between 0 . 25 sec and 0 . 55 sec , was replaced by the contour from the determination curve . the location of the transformed part and its replacement were decided using the extracted f 0 curves . the related parts from the f 0 spectrograms were replaced . a spectrogram of the new signal was generated by multiplying the new f 0 spectrogram by the original smoothed energy spectrogram . the combined spectrogram was then inverted . the energy and spectral content remained as in the original curve . this manipulation yields a new and natural - sounding speech signal , with a new expression , which is the intended result . we have intentionally chosen an extreme combination in order to show the validity of the editing concept . an end - user is able to treat this procedure similarly to ‘ cut and paste ’, or ‘ insert from file ’ commands . the user can use pre - recorded files , or can record the required expression to be modified . fig3 presents another set of operations , this time on the utterance ‘ ptach de - let zo ’, which means ‘ open door this ’ ( open this door ) in hebrew . we manipulated local features of the fundamental frequency , as shown . we took an utterance by a male speaker , and replaced part of its f 0 contour with a contour of an utterance by a female speaker with a different expression , using the same technique as in the previous example . the pitch of the reconstructed signal is shown in crosses . as can be seen , both the curve shape and its duration were changed . the duration was extended by inverting the original spectrogram with a smaller overlap between frames . the sampling rate of the recorded signals was 32 khz ; the short - time fourier transform , and the f 0 extraction algorithm used frames of 50 ms with original overlap of 48 ms , which allowed precision calculation of low f 0 and flexibility of duration manipulations . after changing the intonation , we took the edited signal and changed its energy by multiplying it by a gaussian , so that the center of the utterance was multiplied by 1 . 2 and the sides the beginning and the end of the utterance , were multiplied by 0 . 8 . the new signal sounds natural , with the voice of the male speaker . the new expression is a combination of the two original expressions . the goal here was to examine editing operators to obtain natural - sounding results . we employed a variety of manipulations , such as replacing parts of intonation contours with different contours from the same speaker and from another speaker , changing the speech rate , and changing the energy by multiplying the whole utterance by a time dependent function . the results were new utterances , with new natural expressions , in the voice of the original speaker . these results were confirmed by initial evaluation with hebrew speakers . the speaker was always recognized , and the voice sounded natural . on some occasions the new expression was perceived as unnatural for the specific person , or the speech rate too fast . this happened for utterances in which we had intentionally chosen slopes and f 0 ranges which were extreme for the edited voice . in some utterances the listeners heard an echo . this occurred when the edges chosen for the manipulations were not precise . using pre - recorded intonation contours and borrowing contours from other speakers enables a wide range of manipulations of new speakers &# 39 ; voices , and can add expressions that are not part of a speaker &# 39 ; s normal repertoire . a relatively small reference database of basic intonation curves can be used for different speakers . time - related manipulations , such as extending the shrinking durations , and applying time dependent functions , extend the editing scope even farther . the system allows flexibility and a large variety of manipulations and transformations and yields natural speech . gathering these techniques and more under one editing tool , and defining them as editing operators creates a powerful tool for affect editing . however , to provide a full system which is suitable for general use the algorithms benefit in being refined , especially synchronization between the borrowed contours and the edited signal . special consideration should be given to the differences between voiced ( where there is f 0 ) and unvoiced speech . usability aspects should also be addressed , including processing time . we have described a system for affect editing for non - verbal aspects of speech . such an editor has many useful applications . we have demonstrated some of the capabilities of such a tool for editing expressions of emotion , mental state and attitudes , including nuances of expressions and subtle expressions . we examined the concept using several operations , including borrowing f 0 contours from other speech signals uttered by the same speaker and by other speakers , changing speech rate , and changing energy in different time frames and frequency bands . we managed to reconstruct natural speech signals for speakers with new expressions . these experiments demonstrate the capabilities of this editing tool . further extensions could include provision for real - time processing input from affect inference systems and labeled reference data for concatenation , an automatic translation mechanism from expressions to operators , and a user interface that allows navigation among expressions . the method chosen for segmentation of the speech and sound signals into sentences was based on the modified entropy - based endpoint detection for noisy environments , described by shen ( zwicker , e ., “ subdivision of the audible frequency range into critical bands ( frequenzgruppen )”, journal of the acoustical society of america 33 . 248 , 1961 ). this method calculates the normalized energy in the frequency domain , and then calculates entropy , as minus the product of the normalized energy and its logarithm . in this way , frequencies with low energy get a higher weight . it corresponds to both speech production and speech perception , because higher frequencies in speech tend to have lower energy , and require lower energy in order to be perceived . in order to improve the location of end - points a zero - crossing rate calculation ( zwicker , e ., flottorp g . and stevens s . s ., “ critical bandwidth in loudness summation .” journal of the acoustical society of america 29 . 548 - 57 , 1957 ) was used at the edges of the sentences identified by the entropy - based method . it corrected the edge recognition by up to 10 msec in each direction . this method yielded very good results , recognizing most speech segments ( 95 %) for men but it requires different parameters for men and for women . the signal is divided into frames x of 512 samples each , with overlap of 10 msec . the length of overlap in frames is : overlap = 10e − 3 · f sampling the parameters that affect the sensitivity of the detection are : μ — the entropy threshold , and the overlap between frames . a speech segment is located in frames in which the entropy & gt ; entropy th . locate all short speech segment candidates and check if the can be unified with their neighbours . otherwise , a segment shorter than 2 frames is not considered a speech segment . a short segment of silence in the middle of a speech segment becomes part of the speech segment . check that the length of the segment is longer than the minimum sentence length allowed ; 0 . 1537 sec . define threshold of zero crossing as 10 % of the average zc : zc th = 0 . 1 · average ( zc ) for each of the identified speech segment , check if the there are adjacent areas in which zc & gt ; zc th . if there are , the borders of the segments move to the beginning and end as defined by the zero - crossing . psychological and psychoacoustic tests have examined the relevance of different features to the perception of emotions and mental states using features such as pitch range , pitch average , speech rate , contour , duration , spectral content , voice quality , pitch changes , tone base , articulation and energy level . the features most straightforward for automatic inference of emotions from speech are derived from the fundamental frequency , which forms the intonation , energy , spectral content , and speech rate . however additional features such as loudness , harmonies , ( jitter , shimmer and rhythm may also be used . jitter and shimmer are fluctuations in f 0 frequency and in amplitude respectively ). however the accuracy of the calculation of these parameters is highly dependent on the recording quality , sampling rate and the time units and frame length for which they are calculated . alternative features from a musical point of view are , for example , tempo , harmonies , dissonances and consonances ; rhythm , dynamics , and tonal structures or melodies and the combination of several tones at each time unit . other parameters include mean , standard deviation , minimum , maximum and range ( equals maximum - minimum ) of the pitch , slope and speaking rate , statistical features of pitch and of intensity of filtered signals . our preferred features are set out below : the central feature of prosody is the intonation . intonation refers to patterns of the fundamental frequency , f 0 , which is the acoustic correlate of the rate of vibrations of the vocal folds . its perceptual correlate is pitch . people use f 0 modulation i . e . intonation in a controlled way to convey meaning . there are many different extraction algorithms for the fundamental frequency . i examined two different methods for calculating fundamental frequency f 0 , here referred to as pitch , an autocorrelation method with inverse linear prediction code ( lpc ) and a cepstrum method . both methods of pitch estimation gave very similar results in most cases . paul boersma &# 39 ; s algorithm was used by him in the tool praat which in turn is used for emotions analysis in speech and by many linguists for research of prosody and prosody perception . this was adopted to improve the pitch estimation . paul boersma pointed out that sampling and windowing cause problems in determining the maximum of the autocorrelation signal . his method therefore includes division by the auto - correlation of the window , which is used for each frame . the next stage is to find the best time - shift candidates in the autocorrelation , i . e . the maximum values of the autocorrelation . different weight with strength , and given to voiced candidates and to unvoiced candidates . the next stage is to find an optimal sequence of pitch values for the whole sequence of frames , i . e . for the whole signal . this uses the viterbi algorithm with different costs associated with transitions between adjacent voiced frames and with transitions between voiced and unvoiced frames ( these weights depend partially on the shift between frames ). it also penalises transitions between octaves ( frequencies twice as high or low ). the third method yielded the best results . however , it still required some adaptations . speaker dependency is a major problem in automatic speech processing as the pitch ranges for different speakers can vary dramatically . it is often necessary to clarify the pitch manually after extraction . i have adapted the extraction algorithm to correct the extracted pitch curve automatically . the first attempt to adapt the pitch to different speakers included the use of three different search boundaries , of 300 hz for men , 600 hz for women and 950 hz for children , adjusted automatically by the mean pitch value of the speech signal . although this has improved the pitch calculations , the improvement was not general enough . the second change considers the continuity of the pitch curves . it comprises several observed rules . first , the maximum frequency value for the ( time shift ) candidates ( in the autocorrelation ) may change if the current values are within a smaller or larger range . the lowest frequency default was set to 70 hz , although automatic adaptation to 50 hz was added , for extreme cases . the highest frequency was set to 600 hz . only very few sentences in the two datasets required a lower minimum value , mainly men who found it difficult to speak ; a higher range , mainly children who were trying to be irritating . second the weights of the candidates are changed if using other candidates with originally lower weights can improve the continuity of the curve . several scenarios may cause such a change : first , frequency jumps between adjacent frames that exceed 10 hz : in this case candidates that offer smaller jumps should be considered . second , candidates exactly one octave higher or lower from the most probable candidate , with lower weights . in addition , in order to avoid unduly short segments , if voiced segments comprise no more than two consecutive frames , the weights of these frames are reduced . correction is also considered for voiced segments that are an octave higher or lower than their surrounding voiced segments . this algorithm can eliminate the need of manual intervention in most cases , but is time consuming . algorithm 4 describes the algorithm stage by stage . fig4 shows two fundamental frequency curves , one as extracted by the original algorithm of the praat , and the other with the additional modifications . another way used to describe the fundamental frequency at each point is to define one or two base values , and define all the other values according to their relation to these values . this use of intervals provides another way to code a pitch contour . divide the speech signal signal into overlapping frames y of frame length , framelength , which allows 3 cycles of the lowest allowed frequency · f s is the sampling rate of the speech signal . i also tried shifts of 1 , 2 and 10 msec . a shift of 5 msec gives a smoother curve than 1 msec and 2 msec , with less demands on memory and processing , while still being sufficiently accurate . ( the window specified in the original paper does not assist much , and should be longer than the length stated in the paper . it is not implemented in praat ). calculate c wn , the normalized autocorrelation of the window . c w is the autocorrelation of the window ; fft length was set to 2048 . b . c w = real ( ifft ( abs ( x w ) 2 )) short - term analysis . for each signal frame y of length framelength and step of frameshift calculate : 1 . subtract the average of the signal in a frame from the signal amplitude at each sampling point . y n = y − mean ( y ) 2 . apply a hanning window w to the signal in the frame , so that the centre of the frame has a higher weight than the boundaries . c a = real ( ifft ( abs ( x ) 2 )) 4 . normalize the autocorrelation function : 6 . find candidates for pitch from the autocorrelation signal — the first n max maxima values of the modified autocorrelation signal ; n was set to 10 . 7 . for each of the candidates , calculate parabolic interpolation with the autocorrelation points around it , in order to find more accurate maximum values of the autocorrelation . 9 . check if the candidates &# 39 ; frequencies are within the specified range , and their weight is positive . if not , they become unvoiced candidates , with value 0 . 10 . define the strength of a frame as the weight of the signal in the current frame relative to all the speech signal ( calculated at the beginning in the program ) calculate an optimal sequence of f 0 ( pitch ), for the whole utterance . calculating for every frame , and every candidate in each frame , recursively , using m iterations ; m = 3 . the cost for transition from voiced to voiced , and among octaves is : ii . calculate range , median , mean and standard deviation ( std ) for the extracted pitch sequence ( the median is not as sensitive as mean to outliers ). a . consider frequency jumps to higher or lower octaves ( f * 2 or f / 2 ), by equalizing the candidates &# 39 ; weights , if these candidates exist . b . if the best candidate creates a frequency jumps of over 10 hz , consider a candidate with jump smaller than 5 hz , if exists , by equalizing the candidates &# 39 ; weights . iv . adapt to speaker . change maxpitch by factor 1 . 5 , using the median , range and standard deviation of the pitch sequence : v . for very short voiced sequences ( 2 frames ), reduce the weight by half vi . if the voiced part is shorter than the n th part of the signal length then : ; n = 1 / 3 if equalize weights for consecutive voiced segments in the utterance , among which there is an octave jumps after m iterations , the expectation is to have a continuous pitch curve . in the second stage a more conservative approach was taken , using the bark scale with additional filters for low frequencies . the calculated feature was the smoothed energy , in the same overlapping frames as in the general energy calculation and the fundamental frequency extraction . in this calculation the filtering was done in the frequency domain , after the implementation of short - time fourier transform , using slaney &# 39 ; s algorithm ( slaney m ., covell m ., lassiter b . : automatic audio morphing ( icassp96 ), atlanta , 1996 , 1001 - 1004 . another procedure for the extraction of the fundamental frequency , which includes an adaptation to the boersma algorithm in the iteration stage ( stage 10 ), is shown in algorithm 5 below . 2 . apply a hamming window to the signal in the frame , so that the centre of the frame has a higher weight then the boundaries . 5 . find candidates for the pitch from the normalised autocorrelation signal — the first n maxima values . calculate parabolic interpolation with the autocorrelation points around it , in order to find more accurate maximum values of the auto correlation . keep all candidates for harmonic properties calculation algorithm 6 & gt ;& gt ;& gt ; calculate in iteration an optimal sequence of f 0 ( pitch ), for the whole utterance . calculate for every frame , and every candidate in each frame , recursively , using the viterbi algorithm . in each iteration , adjust the weights of the candidates according to : 6 . check if the candidates &# 39 ; frequencies are within the specific range , and their weights are positive . if not , they become unvoiced candidates , with frequency value 0 . 7 . define the strength as the relation between the average value of the signal in the frame and the maximal value of the entire speech signal . calculate weights according to pre - defined threshold values and frame strengths for voiced and unvoiced candidates . 8 . the cost for transition from voiced to unvoiced or from unvoiced to voiced . 9 . the cost of transition from voiced to voiced , and among octaves 10 . the continuity of the curve ( adaptations to boersma &# 39 ; s algorithm ): the adaptation is achieved by adapting the strength of a probable candidate to the strength of the leading candidate . a . avoid frequency jumps to higher or lower octaves b . frequency changes greater than 10 hz c . eliminate very short sequences of either voiced or unvoiced signal . d . adapt to speaker by changing the allowed pitch range . & gt ;& gt ;& gt ; after m iterations , the expectation is to have a continuous pitch curve . referring again to fig4 the upper pitch extraction has ringed regions indicating outliers that require correction , the lower is after modification using algorithm 5 . the second feature that signifies expressions in speech is the energy , also referred to as intensity . the energy or intensity of the signal x for each sample i in time is : the smoothed energy is calculated as the average of the energy over overlapping time frames , as in the fundamental frequency calculation . if x1 . . . xn defines the signal samples in a frame then the smoothed energy in each frame is ( optionally , depending on the definition , this expression may be divided by frame_length ): the first analysis stage considered these two representations . in the second stage only the smoothed energy curve was considered , and the signal was multiplied by a window so that in each frame a larger weight was given to the centre of the frame . this calculation method yields a relatively smooth curve that describes the more significant characteristics of the energy throughout the utterance ( w i denotes the window ; optionally , depending on the definition , this expression may be divided by frame_length ): another related parameter that may also be employed is the centre of gravity : referring to fig5 this shows a speech signal and the results of different energy calculations ; the speech signal is shown in ( a ), its energy ( b ), the smoothed energy ( averaged ) ( c ) and smoothed energy with a window ( d ). it can be seen that the smooth curves ( c and d ) give the general behaviour of the energy , or the contour of the energy , rather than rapid fluctuations that are more sensitive to noise , as in the energy calculation for each sample ( b ). the application of a window ( d ), emphasises the local changes in time , and follows more closely the original contour , as of the signal itself ( a ). features related to the spectral content of speech signals are not widely used in the context of expressions analysis . one method for the description of spectral content is to use formants , which are based on a speech production model . i have refrained from using formants as both their definition and their calculation methods are problematic . they refer mainly to vowels and are defined mostly for low frequencies ( below 4 - 4 . 5 khz ). the other method , which is the more commonly used , is to use filter - banks , which involves dividing the spectrum into frequency bands . there are two major descriptions of frequency bands that relate to human perception , and these were set according to psycho - acoustic tests — the mel scale and the bark scale , which is based on empirical observations from loudness summation experiments ( zwicker , e . “ subdivision of the audible frequency range into critical bands ( frequenzgruppen )”, journal of the acoustical society of america 33 . 248 , 1961 ; zwicker , e ., flottorp g . and stevens s . s . “ critical bandwidth in loudness summation .”, journal of the acoustical society of america 29 . 548 - 57 , 1957 ). both correspond to the human perception of sounds and their loudness , which implies logarithmic growth of bandwidths , and a nearly linear response in the low frequencies . in this work , the bark scale was chosen because it covers most of the frequency range of the recorded signals ( effectively 100 hz - 10 khz ). bark scale measurements appear to be robust across speakers of differing ages and sexes , and are therefore useful as a distance metric suitable , for example , for statistical use . the bark scale ranges from 1 to 24 and corresponds to the first 24 critical bands of hearing . the subsequent band edges are ( in hz ) 0 , 100 , 200 , 300 , 400 , 510 , 630 , 770 , 920 , 1080 , 1270 , 1480 , 1720 , 2000 , 2320 , 2700 , 3150 , 3700 , 4400 , 5300 , 6400 , 7700 , 9500 , 12000 , 15500 . the formula for converting a frequency f ( hz ) into bark is : in this work , at the first stage , 8 bands were used . the bands were defined roughly according to the frequency response of the human ear , with wider bands for higher frequencies up to 9 khz . fig6 shows the energy in different bands of a speech signal using the eight bands . in the second stage the bark scale up to 9 khz was used . one of the parameters of prosody is voice quality . we can often describe voice with terms such as sharp , dull , warm , pleasant , unpleasant , and the like . concepts that are borrowed from music can describe some of these characteristics and provide explanations for phenomena observed in the autocorrelation of the speech signal . we have found that calculation of the fundamental frequency using the autocorrelation of the speech signal usually reveals several candidates for pitch , they are usually harmonies , multiplications of the fundamental frequency by natural numbers , as can be seen in fig7 and 8 . in expressive speech , there are also other maximum values , which are considered for the calculation of the fundamental frequency , but are usually ignored if they do not contribute to it . interestingly , in many cases they reveal a behaviour that can be associated with harmonic intervals , pure tones with relatively small ratio between them and the fundamental frequency , especially 3 : 2 , as can be seen in fig7 ( the line indicated by b ). other intervals , such as 4 : 3 and more complicated patterns also appear , as can be seen for example in fig8 . these candidates do not exist in all speech signals , and can appear only in parts of an utterance . it seems as if these relations might be associated with the musical notations of consonance . in other cases , the fundamental frequency is not very ‘ clean ’, and the autocorrelation reveals candidates with frequencies which are very close to the fundamental frequency . in music , such tones are associated with roughness or dissonance . there are other ratios that are considered unpleasant . the main high - value peaks of the autocorrelation correspond to frequencies that are both lower and higher than the fundamental frequency , with natural ratios , such as 1 : 2 , 1 : 3 and their multiples . in this work , these ratios are referred to as sub - harmonies , for the lower frequencies , and harmonies for the higher frequencies , intervals that are not natural numbers , such as 3 : 2 and 4 : 3 are referred to as harmonic intervals . sub - harmonies can suggest how many precise repetitions of f 0 exist in the frame , which can also suggest how pure its tone is . ( the measurement method limits the maximum value of detected sub - harmonies for low values of the fundamental frequency ). i suggest that this phenomenon appears in the speech signals and may be related to the harmonic properties , although the terminology which is used in musicology may be different . one of the first applications of physical science to the study of music perception was pythagoras &# 39 ; discovery that simultaneous vibrations of two string segments sound harmonious when their lengths form small integer ratios ( e . g . 1 : 2 , 2 : 3 , 3 : 4 ). these ratios create consonance , blends that sound pleasant . galileo postulated that tonal dissonance , or unpleasant , arises from temporal irregularities in eardrum vibrations that give rise to “ ever - discordant impulses ”. statistical analysis of the spectrum of human speech sounds show that the same ratios of the fundamental frequency are apparent in different languages . the neurobiology of harmony perception shows that information about the roughness and pitch of musical intervals is present in the temporal discharge patterns of the type i auditory nerve fibres , which transmit information about sound from the inner ear to the brain . these findings indicate that people are built to both perceive and generate these harmonic relations . the ideal harmonic intervals , their correlate in the 12 tones system of western music and their definitions as dissonances or consonances are listed in table 1 . the table also shows the differences between the values of these two sets of definition . these differences are smaller than 1 %. the different scales may be approximations . when two tones interact with each other and the interval or ratio between their frequencies create a repetitive pattern of amplitudes , their autocorrelation will reveal the repetitiveness of this pattern . for example , minor second ( 16 : 15 ) and tritone ( 7 : 5 = 1 . 4 , 45 : 32 = 1 . 40625 or 1 . 414 , the definition depends on the system in use ) are dissonances while perfect fifth ( 3 : 2 ) and forth ( 4 : 3 ) are consonances . minor second is an example of two tones of frequencies that are very close to each other , and can be associated with roughness , perfect fourth and fifth create nicely distinguishable repetitive patterns , which are associated with consonances . tritone , which is considered a dissonant , does not create such a repetitive pattern , while creating roughness ( signals of too close frequencies ) with the third and fourth harmonies ( multiplications ) of the pitch . consonance could be considered as the absence of dissonance or roughness . dissonance as a function of the ratios between two pure tones can be seen in fig9 . the curve of the dissonance perception has a minimum at unison , rises fast to maximum and decays again . it rises faster as the lower frequency in the ratio is higher . however , there seem to be well - known and robust results regarding the perceived sense of intervals when two pure tones of different frequencies interact with each other . two tones are perceived as pleasant when the ear can separate them clearly and when they are in unison , for all harmonies . relatively small intervals ( relative to the fundamental frequency ), are not well - distinguished and perceived as ‘ roughness ’. the autocorrelation of expressive speech signals reveals the same behaviour , therefore i included the ratios as appeared in the autocorrelation to the extracted features , and added measures that tested their relations to the documented harmonic intervals . the harmonies and the sub - harmonies were extracted from the autocorrelation maximum values . the calculation of the autocorrelation follows the sections of the fundamental frequency extraction algorithm ( algorithm 4 , or preferably algorithm 5 ), that describes the calculation of candidates . the rest of the calculation , which is described in algorithm 6 is performed after the calculation of the fundamental frequency is completed : if candidate & gt ; f 0 then it is considered as harmony , with ratio : else , if candidate & lt ; f 0 then it is considered as sub - harmony , with ratio : for each frame all the candidates and their weights , candidatew eights , are kept . the next stage is to check if the candidates are close to the known ratios of dissonances and consonances ( table 1 ), having established the fact that these ratios are significant . i examined for each autocorrelation candidate the nearest harmonic interval and the distance from this ideal value . for each ideal value i then calculated the normalised number of occurrences in the utterance , i . e . divided by the number of voiced frames in the utterance . the ideal values for sub - harmonies are the natural numbers . unfortunately , the number of sub - harmonies for low values of the fundamental frequencies is limited , but since the results are normalised for each speakers this effect is neutralised . these features can potentially explain how people can distinguish between real and acted expressions , including the distinction between real and artificial laughter , including behaviour that is subject to cultural display rules or stress . the distance of the calculated values from the ideal ratios may reveal the difference between natural and artificial expressions . the artificial sense may be derived from inaccurate transitions while speakers try to imitate the characteristics of their natural response . i have determined that the harmonic related features are among the most significant features for distinguishing between different types of expressions . time variations within utterances serve various communication roles . linguists and especially those who investigate pragmatic linguistics use sub - units of the utterance for observations . speech signals ( the digital representation of the captured / recorded speech ) can be divided roughly into several categories . the first is speech and silence , in which there are no speech or voice . the difference between them can be roughly defined by the energy level of the speech signal . the second category is voiced , where the fundamental frequency is not zero , i . e . there are vibrations of the vocal folds during speech , usually during the utterance of vowels , and unvoiced , where the fundamental frequency is zero , which happens mainly during silence and during the utterance of consonants such as / s /,/ t / and / p /, i . e . there are no vibrations of the vocal folds during articulation . the linguistic unit that is associated with these descriptions is the syllable , in which the main feature is the voiced part , which can be surrounded on one or both sides by unvoiced parts . the pitch , or fundamental frequency , defines the stressed syllable in a word , and the significant words in a sentence , in addition to the expressive non - textual content . this behaviour changes among languages and accents . in the context of non - verbal expressiveness , the distinction among these units allows the system to define characteristics of the different speech parts , and their time - related behaviour . it also facilitates following temporal changes among utterances , especially in the case of identical text . the features that are of interest are somewhat different from those in the purely linguistic analysis , such features may include , for example the amount of energy in the stressed part compared to the energy in the other parts , or the length of the unvoiced parts . two approaches to parsing were tried . in the first i tried to extract these units using image processing techniques from spectrograms of the speech signals and from smoothed spectrograms . spectrograms present the magnitude of the short time fourier transform ( stft ) of the signal , calculated on ( overlapping ) short time - frames . for the parsing i used two dimensional ( 2d ) edge detection techniques including zero crossing . however , most of the utterances were too noisy , and the speech itself has too many fluctuations and gradual changes so that the spectrograms are not smooth enough and do not give good enough results . 2 . locate peaks ( location and value ) of energy maximum value in the smoothed energy curve ( calculated with window ), that are at least 40 msec apart . 3 . delete very small energy peaks that are smaller than the silence threshold . 4 . beginning of sentence is the first occurrence of either the beginning of the first voiced part ( pitch ), or the point prior to an energy peak , in which the energy climbs above the silence threshold . 5 . end of sentence is the last occurrence of either pitch or of the energy getting below the silence threshold . 6 . remove insignificant minimum values of energy between two adjacent maximum values ( very short — duration valleys without a significant change in the energy . in a ‘ saddle ’ remove the local minimum and the smaller peak .) 7 . find pauses — look between two maximum peaks and find if the minimum is less than 10 percent of the maximum energy . if it is true then bracket it by the 10 percent limit . do not do it if the pause length is less than 30 msec or if there is a pitch in that frame . the second approach was to develop a rule based parsing . from analysis of the extracted features of many utterances from the two datasets in the time domain , rules for parsing were defined . these rules follow roughly the textual units . several parameters were considered for their definition , including the smoothed energy ( with window ), pitch contour , number of zero - crossings , and other edge detection techniques . algorithm 7 ( above ) describes the rules that define the beginning and end of a sentence , finds silence areas and significant energy maximum values and locations . the calculation of secondary time - related metrics is then done on voiced part , where there are both pitch and energy , places in which there is energy ( significant energy peaks ) with no pitch , and on durations of silence or pauses . the vocal features extracted from the speech signal reduce the amount of data because they are defined on ( overlapping ) frames , thus creating an array for each of the calculated features . however , these arrays are still very long and cannot be easily represented or interpreted . two types of secondary metrics have been extracted from each of the vocal features . they can be divided roughly into statistical metrics which are calculated for the whole utterance , such as maximum , mean , standard deviation , median and range , and to time - related metrics , which are calculated according to different duration properties of the vocal features and according to the parsing , and their statistical properties on occasions . it can be hard to find a precise manner to describe these relations mathematically as done in western music , and therefore it is preferable to use the extreme values of pitch at the locations of extreme values of the signal &# 39 ; s energy , the relations between the values , durations and the distances ( in time ) between consecutive extreme values . i have examined mainly two sets of features and definitions . the first set , listed in table 2 ( below ) was used for initial observations , and it was improved and extended to the a final version listed in table 3 ( below ). the final set includes the following secondary metrics of pitch : voiced length — the duration of instances in which the pitch is not zero , and unvoiced length , in which there is no pitch . statistical properties of its frequency were considered in addition to up and down slopes of the pitch , i . e . the first derivative or the differences in pitch value between adjacent time frames . finally , analysis of local extremum ( maximum ) peaks was added , including the frequency at the peaks , the differences in frequency between adjacent peaks ( maximum - maximum and maximum - minimum ), the distances between them in time and speech rate . similar examination was done for the energy ( smoothed energy with window ), including the value , the local maximum values , and the distances in time and value between adjacent local extreme values . another aspect of the energy was to evaluate the shape of the energy peak , or how the energy changes in time . the calculation was to find the relations of the energy peaks to rectangles which are defined by the peak maximum value and its duration or length . this metric gives a rough estimate for the nature of changes in time and the amount of energy invested . temporal characteristics were estimated also in terms of ‘ tempo ’, or more precisely in this case , with different aspects of speech rate . assuming , based on observations and music related literature that the tempo is set according to a basic duration unit whose products are repeated throughout an utterance , and this rate changes between expressions and different speech parts of the utterance . the assumption is that different patterns and combinations of these relative durations play a role in the expression . the initial stage was to gather the general statistics and check if it is enough for inference , which proved to be the case . further analysis should be done for accurate synthesis . the ‘ tempo ’ related metrics used here include the shortest part with pitch , that is the shortest segment around an energy peak that includes also pitch , the relative durations of silence to the shortest part , the relative duration of energy and no pitch and the relative durations of voiced parts . the harmonic related features include a measure of ‘ harmonicity ’, which in some preferred embodiments is measured by the sum of harmonic intervals in the utterance , the number of frames in which each of the harmonic intervals appeared ( as in table 1 ), the number of appearances of the intervals that are associated with consonance and those that are associated with dissonance and the sub - harmonies . the last group includes the filter bank and statistic properties of the energy in each frequency band . the centres of the bands are at 101 , 204 , 309 , 417 , 531 , 651 , 781 , 922 , 1079 , 1255 , 1456 , 1691 , 1968 , 2302 , 2711 , 3212 , 3822 , 4554 , 5412 , 6414 and 7617 hz . although the sampling rate in both databases allowed for frequency range that reaches beyond 10 khz , the recording equipment not necessarily does , therefore no further bands were employed . no doubt many other effective alternatives will occur to the skilled person . it will be understood that the invention is not limited to the described embodiments and encompasses modifications apparent to those skilled in the art lying within the spirit and scope of the claims appended hereto .
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referring to fig1 , a cryptographic system is shown generally by the numeral 10 . a pair of correspondents 12 , 14 , referred to as alice and bob , communicate over a network 16 . each correspondent has an arithmetic logic unit ( alu ) 18 , 20 . the alu can be a general - purpose computer , with a cryptographic unit , which implements cryptographic protocols from instructions provided by software . the software may be provided on a data carrier or in memory . each correspondent has a long - term private key a , b and a corresponding long - term public key y a , y b . each correspondent has access to an authentic copy of the other correspondent &# 39 ; s long - term public key . it is desired to share a key between the correspondents using the mqv protocol . it is recognized that the mqv equations can be reorganized to provide efficient computations without necessarily using the truncation operation . the reorganization proceeds as follows . the formula k =( r b ( y b ) r b ) s a that is used to determine the key can be rearranged as k =( r b ( y b ) r b ) s a = r b s a y b s a r b , using the notation above . this rearrangement allows the key to be computed by using a technique known as simultaneous multiple exponentiation , which uses only one set of squares . to compute the multiple r b s a y b s a r b , two tables of small exponents of r b and y b respectively of a predetermined width are first established . the scalars s a and s a r b are then examined using windows of the predetermined width . the multiples of r b and y b corresponding to each window are retrieved from each respective table . the product of the table entries from the two windows is multiplied into an accumulator . the accumulator is then squared in accordance with the width of the window , and then the next window is examined . this process is repeated until each window has been examined , and therefore terminates with the accumulator holding the value of k . referring to fig2 , a method of computing a shared secret key is shown generally by the numeral 100 . alice selects an ephemeral private key x at random from the interval 1 to q − 1 ( 102 ). alice computes the corresponding ephemeral public key g x and sends it to bob ( 104 ). similarly , bob selects an ephemeral private key y at random from the interval 1 to q − 1 ( 106 ). bob computes the corresponding ephemeral public key g y and sends it to alice ( 108 ). alice computes s a =( x + ar a ) mod q and the shared secret k = r b s a y b s a r b ( 110 ) using simultaneous multiple exponentiation , as described below . bob computes s b =( y + br b ) mod q and the shared secret k = r b s a y b s a r b ( 112 ) using simultaneous multiple exponentiation . referring fig3 , a method of computing a simultaneous multiple exponentiation is shown generally by the numeral 300 . a window width of a predetermined number of bits w is first established ( 302 ). then , a table of small exponents α of r b is established ( 304 ) and a table of small exponents β of y b is established ( 306 ). the table entries consist of a column of possible bit combinations ( e . g . α = 1001 2 ), and a column of corresponding exponentiations ( e . g . r b 1001 2 ). then , the scalars s a and s a r b are examined using windows of the window width w ( 308 ). the powers of r b and y b corresponding to each window are retrieved from each respective table ( 310 ). the product of the table entries from the two windows is multiplied into an accumulator ( 312 ). the accumulator is then squared w times in accordance with the width w of the window ( 314 ), and then the next window is examined ( 316 ). the scalars are repeatedly examined and table entries multiplied into the accumulator and the accumulator squared w times for each repetition as described above ( 318 ) until the shared secret k is computed ( 320 ). it will be noted that in this embodiment one simultaneous multiple exponentiation is used instead of two separate exponentiations . accordingly , the number of squaring operations required corresponds to the number required for one exponentiation instead of that required for two separate exponentiations . it will be recognized that using the method of this embodiment , truncating the first exponent in an attempt to save squarings is not effective , since these squaring can be shared with the second multiplication . the truncation then saves only multiplications , not squarings , when applied to this embodiment since this embodiment uses simultaneous multiple exponentiation . referring to fig4 , an alternate embodiment is shown generally by the numeral 200 . in this embodiment , alice uses the improved method of computing the shared key , while bob can compute the shared key by any method . alice selects ( 202 ) x at random from the interval 1 to q − 1 . then , alice computes ( 204 ) g x and makes it available to bob ( 206 ). alice then obtains ( 208 ) g y from bob . alice computes ( 210 ) s a =( x + ar a ) mod q and then computes ( 212 ) the shared secret k = r b s a y b s a r b using simultaneous multiple exponentiation . referring to fig5 , an alternate embodiment is shown generally by the numeral 500 . in this embodiment , the correspondents of fig2 are shown carrying out the method in parallel . alice selects an ephemeral private key x at random from the interval 1 to q − 1 ( 502 ). bob selects an ephemeral private key y at random from the interval 1 to q − 1 ( 106 ). alice computes the ephemeral public key g x corresponding to the ephemeral private key x ( 504 ). similarly , bob computes his ephemeral public key g y ( 514 ). alice sends g x to bob and bob sends gy to alice . after alice receives bob &# 39 ; s ephemeral public key , she computes s a =( x + ar a ) mod q ( 506 ). then alice computes the shared secret k as before ( 508 ). after bob receives alice &# 39 ; s ephemeral public key , he computes s b as before ( 516 ). then bob computes k as before ( 518 ). thus , it will be understood that the order of the computations is not critical and it is only necessary that a correspondent have both its own private key and the other correspondent &# 39 ; s , ephemeral public key before computing s and k . referring to fig6 , an alternate method of computing a simultaneous multiple exponentiation is shown generally by the numeral 600 . the exponent s a is shown stored in a register 602 . the exponent s a r b is shown stored in a register 604 . each register has an associated pointer 603 , 605 . the pointers are aligned to designate corresponding bits in each exponent . a pair of switches 606 , 608 are provided . two multipliers 610 , 612 are shown , although their functionality could be performed by one multiplier . an accumulator 614 , a squaring operation 616 , and a control 618 are provided . in use , the pointer 603 is an input to the switch 606 which controls multiplier 610 so that when the corresponding bit of s a is set , the quantity r b is multiplied into the accumulator 514 . similarly , the pointer 605 is an input to the switch 608 which operates the multiplier 612 . the quantity y b is multiplied into the accumulator 614 when the corresponding bit of register 604 is set . after considering each exponent , the accumulator is squared 616 , and the control 618 operates to set the pointers 603 , 605 to the next bits of registers 602 , 604 . the process repeats until all the bits have been considered . in this way , the bits of the two exponents are considered simultaneously , and only one set of squares is performed . the above methods can be implemented in any group where the discrete logarithm problem is believed to be intractable . one example of such a group is an elliptic curve group , where the method is very similar however , the additive notation is usually used instead of multiplicative notation . in the elliptic curve setting , group multiplication corresponds to addition of elliptic curve points , and group exponentiation corresponds to scalar multiplication . in this case , the tables will contain a column possible bit combinations of the scalar ( e . g . 1001 2 ), and a column of corresponding point multiplications ( e . g . 1001 2 p ). referring therefore to fig7 , the method of fig5 is shown in an elliptic curve setting by the numeral 700 . the correspondents have common elliptic curve parameters comprising an elliptic curve , a finite field , a base point p of order q , and a function π to convert elliptic curve points to integers , each correspondent has a long term private key a , b and a corresponding long term public key y a = ap , y b = bp . alice selects an ephemeral private key x at random from the interval 1 to q − 1 ( 702 ). bob selects an ephemeral private key y at random from the interval 1 to q − 1 ( 712 ). alice computes the ephemeral public key xp corresponding to the ephemeral private key x ( 704 ). similarly , bob computes his ephemeral public key yp ( 714 ). alice sends xp to bob and bob sends yp to alice . after alice receives bob &# 39 ; s ephemeral public key , she computes s a =( x + aπ ( r a )) mod q ( 706 ). then alice computes the shared secret k = s a r b + s a π ( r b ) y b ( 708 ) using simultaneous multiple scalar multiplication ( fig8 ). after bob receives alice &# 39 ; s ephemeral public key , he computes s b =( y + bπ ( r b )) mod q ( 716 ). then bob computes k = s b r a + s b π ( r a ) y a ( 718 ) using simultaneous multiple scalar multiplication ( fig8 ). referring to fig8 , a method of performing simultaneous multiple scalar multiplication used in this embodiment is shown generally by the numeral 800 . a window width of a predetermined number of bits w is first established ( 802 ). then , a table of small exponents a of r b is established ( 804 ) and a table of small exponents β of y b is established ( 806 ). the table entries consist of a column of possible bit combinations ( e . g . α = 1001 2 ), and a column of corresponding scalar multiples ( e . g . 1001 2 r b ). then , the scalars s a and s a π ( r b ) are examined using windows of the window width w ( 808 ). the scalar multiples of r b and y b corresponding to each window are retrieved from each respective table ( 810 ). the sum of the table entries from the two windows is added into an accumulator ( 812 ). the accumulator is then doubled w times in accordance with the width w of the window ( 814 ), and then the next window is examined ( 816 ). the scalars are repeatedly examined and table entries added into the accumulator and the accumulator doubled w times for each repetition as described above ( 818 ) until the shared secret k is computed ( 820 ). although the invention has been described with reference to certain specific embodiments , various modifications thereof will be apparent to those skilled in the art without departing from the spirit and scope of the invention as outlined in the claims appended hereto .
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hereinafter , the first embodiment of the present invention will be described with reference to fig1 a through 1g and fig2 a and 2b . fig1 a through 1g are cross - sectional views illustrating the flow of a process for fabricating a semiconductor device in this embodiment . first , as shown in fig1 a , an insulating film 102 ( thickness : 0 . 8 μm ), a first metal layer 103 formed by alternately stacking aluminum and a titanium alloy ( thickness : 0 . 5 μm ) and a first interlevel dielectric film 104 ( thickness : 1 . 0 μm ) are deposited in this order on a semiconductor substrate 101 on which a semiconductor active element ( not shown ) has been formed beforehand . thereafter , an interconnecting resist pattern 105 is formed thereon and an interlevel contact hole 106 is opened by dry etching . next , as shown in fig1 b , the interconnecting resist pattern 105 is removed , and an adhesion layer 107 made of tin / ti , for example , is deposited over the entire surface of the substrate as well as over the inside of the interlevel contact hole 106 . then , an interconnecting material 108 such as tungsten is further deposited thereon by a blanket w - cvd technique . and the adhesion layer 107 and the interconnecting material 108 are removed by a dry etching or cmp technique except for the respective portions existing inside the interlevel contact hole 106 . the respective portions of the adhesion layer 107 and the interconnecting material 108 , existing only in the interlevel contact hole 106 , constitute an interconnecting metal 109 altogether . then , as shown in fig1 c , a first - interconnect resist pattern 110 is formed over the first interlevel dielectric film 104 and the interconnecting metal 109 . assume the first - interconnect resist pattern 110 has been formed with an alignment error 111 . if the diameter of the interlevel contact hole 106 is 0 . 3 μm and the line width of a recess in the first - interconnect resist pattern 110 is also 0 . 3 μm , then the maximum permissible alignment error 111 between the interconnecting metal 109 filled in the interlevel contact hole 106 and the first - interconnect resist pattern 110 is 0 . 1 μm . [ 0034 ] fig2 a is a plan view illustrating how the positional relationship between the first - interconnect resist pattern 110 and the interconnecting metal 109 changes with the mask - to - mask placement error . in the lower part under the wave line in fig2 a , the position of the first - interconnect resist pattern 110 is misaligned with that of the interconnecting metal 109 . on the other hand , in the upper part over the wave line in fig2 a , the position of the first - interconnect resist pattern 110 matches with that of the interconnecting metal 109 . next , as shown in fig1 d , the layers on the surface of the substrate , which are exposed through the first - interconnect resist pattern 110 , are sequentially dry - etched by using a cf - based etching gas used for removing an oxide film and a cl - based etching gas used for removing aluminum . first , parts of the first interlevel dielectric film 104 , exposed through the openings of the first - interconnect resist pattern 110 , are removed by dry etching using the cf - based etching gas at a low temperature . in this case , part of the interconnecting metal 109 corresponding to a misaligned portion 112 is not etched by the cf - based etching gas . then , parts of the first metal layer 103 , exposed through the openings of the first - interconnect resist pattern 110 , are removed by dry etching using the cl - based etching gas until the insulating film 102 is exposed . the part of the interconnecting metal 109 corresponding to the misaligned portion 112 is not etched by the cl - based etching gas , either . [ 0036 ] fig2 b is a perspective view illustrating how the positional relationship between lines in the first interconnect layer 113 and the interconnecting metal 109 changes with the mask - to - mask placement error . first , as to a line 113 b that has been formed out of the first metal layer 103 by dry etching without having been misaligned , the interconnecting metal 109 having a diameter equal to the width of the line 113 b is formed on the upper surface of the line 113 b . on the other hand , as to a line 113 c that has been formed out of the first metal layer 103 by dry etching with an alignment error , part of the first metal layer 103 located under the interconnecting metal 109 is not etched during the dry etching . accordingly , the part of the first metal layer 103 located under the interconnecting metal 109 is not etched but left in a self - aligned manner in the misaligned portion 112 shown in fig1 d . as a result , a line 113 c is shaped as shown in fig2 b . therefore , the line 113 b or 113 c ( both identified by 113 a in fig1 d ) of the first interconnect layer 113 is formed without fail under the entire bottom of the interconnecting metal 109 . also , since the portions under the first - interconnect resist pattern 110 are not etched , the first interlevel dielectric film 104 remains as it is in the portions over the lines 113 a in the first interconnect layer 113 where the interconnecting metal 109 does not exist . that is to say , either the first interlevel dielectric film 104 or the interconnecting metal 109 always exists over the lines 113 a in the first interconnect layer 113 . accordingly , portions of the first metal layer 103 existing under the interconnecting metal 109 and the first interlevel dielectric film 104 constitute the lines 113 a in the first interconnect layer 113 . the total thickness of the lines 113 a in the first interconnect layer 113 , formed out of the first metal layer 103 , and the first interlevel dielectric film 104 is 1 . 5 μm . thus , the aspect ratio of a recess 115 formed in a line - to - line space 114 , which is a region between adjacent lines in the first interconnect layer 113 and has the minimum width of 0 . 3 μm , is about five . it is noted that a dummy interconnect pattern may be formed in a field portion 116 where the lines of the first interconnect layer 113 do not exist . next , as shown in fig1 e , the first - interconnect resist pattern 110 is removed . then , a second interlevel dielectric film 117 is deposited over the insulating film 102 , the first interlevel dielectric film 104 and the interconnecting metal 109 on the semiconductor substrate 101 by using a plasma cvd apparatus . part or all of a recess formed in a line - to - line space 114 is not filled in with the second interlevel dielectric film 117 , but forms an air gap 118 . in a recess having a high aspect ratio , in particular , the entire region of a line - to - line space 114 is turned into an air gap 118 . subsequently , as shown in fig1 f , the surface of the second interlevel dielectric film 117 is planarized by a cmp technique such that the respective surfaces of the first interlevel dielectric film 104 , the interconnecting metal 109 and the second interlevel dielectric film 117 form a single plane . in this embodiment , the first and second interlevel dielectric films 104 and 117 are made of different materials and the etching rate of the first interlevel dielectric film 104 is set smaller than that of the second interlevel dielectric film 117 during the cmp process . in this manner , the first interlevel dielectric film 104 is used as an etching stopper . even in a recess having a high aspect ratio , the upper part thereof is filled in with the second interlevel dielectric film 117 to a certain degree . accordingly , no opening is formed over any air gap 118 through the surface of the second interlevel dielectric film 117 after cmp is finished . then , as shown in fig1 g , a metal layer formed by alternately stacking aluminum and a titanium alloy is deposited thereon and subjected to photolithography and dry etching , thereby forming a second interconnect layer 119 . as described above , in this embodiment , part or all of a line - to - line space 114 is turned into an air gap 118 . accordingly , the relative dielectric constant between adjacent lines 113 a in the first interconnect layer 113 can be reduced at the line - to - line space 114 . in particular , when a recess 115 formed in a line - to - line space 114 has a high aspect ratio , the entire region of the line - to - line space 114 is turned into an air gap 118 . as a result , the relative dielectric constant between adjacent lines 113 a in the first interconnect layer 113 can be minimized . in addition , since the first interconnect layer 113 is formed after the interconnecting metal 109 has been formed , the first interconnect layer 113 exists without fail under the entire bottom of the interconnecting metal 109 . accordingly , it is possible to prevent a contact failure from being caused between the first interconnect layer 113 and the interconnecting metal 109 . moreover , after the interconnecting metal 109 has been filled in the interlevel contact hole 106 provided in the first interlevel dielectric film 104 , the first interconnect layer 113 and the second interlevel dielectric film 117 are formed in this order . accordingly , even if a mask - to - mask placement error has been caused during the formation of the first interconnect layer 113 , either the interconnecting metal 109 or the first interlevel dielectric film 104 always exists on the upper surface of the first interconnect layer 113 . and the interconnecting metal 109 is never filled in any air gap 118 formed simultaneously with the second interlevel dielectric film 117 . accordingly , it is possible to prevent a shortcircuit failure from being caused between adjacent lines 113 a in the first interconnect layer 113 or between a line 113 a and the semiconductor substrate 101 through the interconnecting metal 109 . hereinafter , the second embodiment of the present invention will be described with reference to fig3 a through 3c illustrating the flow of a process for fabricating a semiconductor device in this embodiment . the same process steps as those illustrated in fig1 a through 1d are also performed prior to the process step shown in fig3 a . thus , the same components as those used in the first embodiment will be identified by the same reference numerals and the description thereof will be omitted herein . unlike the first embodiment in which the second interlevel dielectric film 117 is deposited by using a plasma cvd apparatus , a second interlevel dielectric film 217 is formed in this embodiment by using an applicator . the second interlevel dielectric film 217 may be an organic film made of organic poly - siloxane or an organic material containing fluorine , or an inorganic porous film , for example . many of these materials have fluidity . first , as shown in fig3 a , the material is applied onto the first interlevel dielectric film 104 , the interconnecting metal 109 and the line - to - line spaces 214 . in this manner , the recesses in the line - to - line spaces 214 are filled in with the fluid material , thereby forming the second interlevel dielectric film 217 without any air gap . as the material of the second interlevel dielectric film 217 , a material having a lower relative dielectric constant than that of the first interlevel dielectric film 104 is selected . accordingly , the relative dielectric constant between adjacent lines 113 a in the first interconnect layer 113 can be reduced at the line - to - line spaces 214 . subsequently , as shown in fig3 b , the surface of the second interlevel dielectric film 217 is planarized by a cmp technique such that the respective surfaces of the first interlevel dielectric film 104 , the interconnecting metal 109 and the second interlevel dielectric film 217 form a single plane . in this embodiment , the first and second interlevel dielectric films 104 and 217 are made of different materials and the etching rate of the first interlevel dielectric film 104 is set smaller than that of the second interlevel dielectric film 217 during the cmp process . in this manner , the first interlevel dielectric film 104 is used as an etching stopper . then , as shown in fig3 c , a metal layer formed by alternately stacking aluminum and a titanium alloy is deposited thereon and subjected to photolithography and dry etching , thereby forming a second interconnect layer 219 . as described above , in this embodiment , the line - to - line spaces 214 are entirely filled in with the second interlevel dielectric film 217 made of a material having a lower relative dielectric constant than that of the first interlevel dielectric film 104 . thus , the relative dielectric constant between adjacent lines 113 a in the first interconnect layer 113 can be reduced at the line - to - line spaces 214 . in addition , the relative dielectric constant can be determined based on the material of the second interlevel dielectric film 217 . in addition , since the first interconnect layer 113 is formed after the interconnecting metal 109 has been formed , the first interconnect layer 113 always exists under the entire bottom of the interconnecting metal 109 . accordingly , it is possible to prevent a contact failure from being caused between the first interconnect layer 113 and the interconnecting metal 109 . moreover , after the interconnecting metal 109 has been filled in the interlevel contact hole 106 provided in the first interlevel dielectric film 104 , the first interconnect layer 113 and the second interlevel dielectric film 217 are formed in this order . accordingly , even if a mask - to - mask placement error has been caused during the formation of the first interconnect layer 113 , either the interconnecting metal 109 or the first interlevel dielectric film 104 always exists on the upper surface of the first interconnect layer 113 . and the second interlevel dielectric film 217 always exists in the line - to - line spaces 214 . accordingly , it is possible to prevent a shortcircuit failure from being caused between adjacent lines 113 a in the first interconnect layer 113 or between a line 113 a and the semiconductor substrate 101 through the interconnecting metal 109 . hereinafter , the third embodiment of the present invention will be described with reference to fig4 a through 4d and fig5 . fig4 a through 4d are cross - sectional views illustrating the flow of a process for fabricating a semiconductor device in this embodiment . the same process steps as those illustrated in fig1 a through 1f are also performed prior to the process step shown in fig4 a , except that the thickness of a first interlevel dielectric film 304 is set larger ( e . g ., at 2 . 5 μm ). thus , the same components as those used in the first embodiment will be identified by the same reference numerals and the description thereof will be omitted herein . first , as shown in fig4 a , a second - interconnect inverted resist pattern 320 is formed by photolithography over the first interlevel dielectric film 304 , an interconnecting metal 309 and a second interlevel dielectric film 317 . assume the second - interconnect inverted resist pattern 320 has been formed with an alignment error 311 . if the diameter of the interlevel contact hole is 0 . 3 μm and the line width of a recess in the second - interconnect inverted resist pattern 320 is also 0 . 3 μm , then the maximum permissible alignment error 311 between the interconnecting metal 309 filled in the interlevel contact hole and the second - interconnect inverted resist pattern 320 is 0 . 1 μm . next , as shown in fig4 b , the first and second interlevel dielectric films 304 and 317 are etched , thereby forming interconnect recesses 321 a having a depth of 0 . 5 μm . then , as shown in fig4 c , an adhesion layer ( not shown ) made of a titanium alloy is deposited on the recesses and a second metal layer 322 made of aluminum , an aluminum / copper alloy or copper is formed by vacuum evaporation , cvd or the like . subsequently , as shown in fig4 d , the second metal layer 322 is removed by a cmp technique except for the portions existing in the interconnect recesses 321 a to form a second interconnect layer 323 . next , it will be described with reference to fig5 and fig4 b through 4d how the positional relationship between the second interconnect layer 323 and the interconnecting metal 309 changes owing to the misalignment of the second - interconnect inverted resist pattern 320 . fig5 is a perspective view illustrating how the positional relationship between the interconnect recesses 321 a , where the second interconnect layer 323 is to be formed , and the interconnecting metal 309 changes with the mask - to - mask placement error . first , as to an interconnect recess 321 b that has been formed by dry etching without having been misaligned , the interconnect recess 321 b has a width equal to the diameter of the interconnecting metal 309 . since a line of the second interconnect layer 323 is formed inside the interconnect recess 321 b , the interconnecting metal 309 and the line are in contact with each other over substantially the entire side face of the interconnecting metal 309 . on the other hand , as to an interconnect recess 321 c that has been formed by dry etching with an alignment error , the interconnect recess 321 c , having a width equal to the diameter of the interconnecting metal 309 , is formed with an alignment error 311 shown in fig4 b . since the interconnecting metal 309 is not etched , the side face of the interconnecting metal 309 is exposed in the interconnect recess 321 c except for the portion of the interconnecting metal 309 ingrown into the first interlevel dielectric film 304 by the alignment error 311 . accordingly , most of the side face of the interconnecting metal 309 comes into contact with the second metal layer 322 shown in fig4 c , and with the second interconnect layer 323 shown in fig4 d after cmp has been performed . as described above , in this embodiment , even if the second - interconnect inverted resist pattern 320 used for forming the second interconnect layer 323 has been misaligned , most of the side face of the interconnecting metal 309 is in contact with the second interconnect layer 323 . accordingly , in this embodiment , not only the same effects as those of the first embodiment can be attained , but the reliability in connecting the interconnecting metal 309 to the second interconnect layer 323 can also be improved , even if the second - interconnect inverted resist pattern 320 has been misaligned . hereinafter , a method for fabricating a semiconductor device in the fourth embodiment of the present invention will be described with reference to fig6 a through 6i . first , as shown in fig6 a , an insulating film 102 ( thickness : 0 . 8 μm ), a first metal layer 103 formed by alternately stacking aluminum and a titanium alloy ( thickness : 0 . 5 μm ) and a first interlevel dielectric film 104 ( thickness : 1 . 0 μm ) are deposited in this order on a semiconductor substrate 101 on which a semiconductor active element ( not shown ) has been formed beforehand . thereafter , an interconnecting resist pattern 105 is formed and an interlevel contact hole 106 is opened by dry etching . next , as shown in fig6 b , the interconnecting resist pattern 105 is removed , and an adhesion layer 107 made of tin / ti , for example , is deposited over the entire surface of the substrate as well as over the inside of the interlevel contact hole 106 . then , an interconnecting material 108 such as tungsten is further deposited thereon by a blanket w - cvd technique . and the adhesion layer 107 and the interconnecting material 108 are removed by a dry etching or cmp technique except for the respective portions existing inside the interlevel contact hole 106 . the portions of the adhesion layer 107 and the interconnecting material 108 , existing only in the interlevel contact hole 106 , constitute an interconnecting metal 109 altogether . subsequently , as shown in fig6 c , the first interlevel dielectric film 104 is etched by about 0 . 5 μm to adjust the thickness of the residual portion of the first interlevel dielectric film 104 at 0 . 5 μm . as a result , the interconnecting metal 109 protrudes upward from the surface of the first interlevel dielectric film 104 . then , as shown in fig6 d , a first - interconnect resist pattern 110 is formed over the first interlevel dielectric film 104 and the interconnecting metal 109 . assume the first - interconnect resist pattern 110 has been formed with an alignment error 111 . if the diameter of the interlevel contact hole 106 is 0 . 3 μm and the line width of a recess in the first - interconnect resist pattern 110 is also 0 . 3 μm , then the maximum permissible alignment error 111 between the interconnecting metal 109 , filled in the interlevel contact hole 106 , and the first - interconnect resist pattern 110 is 0 . 1 μm . [ 0057 ] fig2 a is a plan view illustrating how the positional relationship between the first - interconnect resist pattern 110 and the interconnecting metal 109 changes with the mask - to - mask placement error . in the lower part under the wave line in fig2 a , the position of the first - interconnect resist pattern 110 is misaligned with that of the interconnecting metal 109 . on the other hand , in the upper part over the wave line in fig2 a , the position of the first - interconnect resist pattern 110 matches with that of the interconnecting metal 109 . next , as shown in fig6 e , the layers on the surface of the substrate , which are exposed through the openings of the first - interconnect resist pattern 110 , are sequentially dry - etched by using a cf - based etching gas used for removing an oxide film and a cl - based etching gas used for removing aluminum . first , parts of the first interlevel dielectric film 104 , exposed through the openings of the first - interconnect resist pattern 110 , are removed by dry etching using the cf - based etching gas at a low temperature . in this case , part of the interconnecting metal 109 corresponding to a misaligned portion 112 is not etched by the cf - based etching gas . then , parts of the first metal layer 103 , exposed through the openings of the first - interconnect resist pattern 110 , are removed by dry etching using the cl - based etching gas until the insulating film 102 is exposed . in this manner , the first interconnect layer 113 is formed . the part of the interconnecting metal 109 corresponding to the misaligned portion 112 is not etched by the cl - based etching gas , either . [ 0059 ] fig2 b is a perspective view illustrating how the positional relationship between lines in the first interconnect layer 113 and the interconnecting metal 109 changes with the mask - to - mask placement error . first , as to a line 113 b that has been formed out of the first metal layer 103 by dry etching without having been misaligned , the interconnecting metal 109 having a diameter equal to the width of the line 113 b is formed on the upper surface of the line 113 b . on the other hand , as to a line 113 c that has been formed out of the first metal layer 103 by dry etching with an alignment error , part of the first metal layer 103 located under the interconnecting metal 109 is not etched during the dry etching . accordingly , the part of the first metal layer 103 located under the interconnecting metal 109 is not etched but left in a self - aligned manner in the misaligned portion 112 shown in fig6 e . as a result , a line 113 c is shaped as shown in fig2 b . therefore , the line 113 b or 113 c ( both identified by 113 a in fig6 e ) of the first interconnect layer 113 is formed without fail under the entire bottom of the interconnecting metal 109 . also , since the portions under the first - interconnect resist pattern 110 are not etched , the first interlevel dielectric film 104 remains as it is in the portions over the first interconnect layer 113 where the interconnecting metal 109 does not exist . that is to say , either the first interlevel dielectric film 104 or the interconnecting metal 109 always exists over the first interconnect layer 113 . next , as shown in fig6 f , the insulating film 102 is etched by about 0 . 5 μm in accordance with a dry etching technique using the cf - based etching gas . in this manner , the first interconnect layer 113 is formed to be sandwiched by upper and lower insulating films 102 and 104 . in fig6 f , the non - etched portions of the insulating film 102 immediately under the lines 113 a in the first interconnect layer 113 are identified by 112 a . accordingly , the first metal layer 103 , existing under the interconnecting metal 109 or the first interlevel dielectric film 104 , constitutes the first interconnect layer 113 . the total thickness of the first interconnect layer 113 , formed out of the first metal layer 103 , the first interlevel dielectric film 104 and the insulating film 112 a is 1 . 5 μm . thus , the aspect ratio of a recess 115 formed in a line - to - line space 114 , which is a region between adjacent lines 113 a in the first interconnect layer 113 and has the minimum width of 0 . 3 μm , is about five . it is noted that a dummy interconnect pattern may be formed in a field portion 116 where the first interconnect layer 113 does not exist . next , as shown in fig6 g , the first - interconnect resist pattern 110 is removed . then , a second interlevel dielectric film 117 is deposited over the insulating film 102 , the first interlevel dielectric film 104 and the interconnecting metal 109 on the semiconductor substrate 101 by using a plasma cvd apparatus . a recess 115 formed in a line - to - line space 114 is partially or entirely not filled in with the second interlevel dielectric film 117 , but turned into an air gap 118 . in a recess having a high aspect ratio , in particular , the entire region of the line - to - line space 114 is turned into an air gap 118 . subsequently , as shown in fig6 h , the surface of the second interlevel dielectric film 117 is planarized by a cmp technique such that the respective surfaces of the interconnecting metal 109 and the second interlevel dielectric film 117 form a single plane . even in a recess having a high aspect ratio , the upper part thereof is filled in with the second interlevel dielectric film 117 to a certain degree . accordingly , no opening is formed over any air gap 118 through the surface of the second interlevel dielectric film 117 after cmp is finished . then , as shown in fig6 i , a metal layer formed by alternately stacking aluminum and a titanium alloy is deposited thereon and subjected to photolithography and dry etching , thereby forming a second interconnect layer 119 . hereinafter , it will be described with reference to fig7 a and 7b and fig8 a and 8b how the shape of an air gap changes with the manner in which the second interlevel dielectric film 117 is deposited . first , fig7 a will be referred to . fig7 a illustrates an ideal state where the second interlevel dielectric film 117 has not ingrown into the recesses 115 at all and the recesses 115 are entirely occupied by air gaps . in this case , since no dielectric exists between adjacent lines 113 a , the line - to - line capacitance cl is very small . also , in fig7 a , the upper end of an air gap is not higher than the upper surface of the first interlevel dielectric film 104 . accordingly , even after the surface of the second interlevel dielectric film 117 has been polished by cmp , the air gaps are less likely to be exposed . if the air gaps communicate with the outside through the polished surface of the second interlevel dielectric film 117 subjected to the cmp process , then the function of the interlevel dielectric film 117 is lost and shortcircuit possibly happens between lines . [ 0065 ] fig7 b illustrates a state where the second interlevel dielectric film 117 has been deposited on the bottom and side faces of the recesses 115 and a small part of each recess 115 is occupied by an air gap . such a state is established if the second interlevel dielectric film 117 has been deposited with satisfactory step coverage . for example , in performing plasma cvd using teos as a source material , before the upper part of a recess 115 is completely filled in with the second interlevel dielectric film 117 being deposited , the interlevel dielectric film having a certain thickness is deposited on the bottom and side faces of the recess 115 . as a result , the capacitance c 2 between adjacent lines 113 a adversely increases . [ 0066 ] fig8 a illustrates a state where the second interlevel dielectric film 117 has not ingrown into the recesses 115 at all and the upper part 118 of an air gap reaches a higher level than the upper surface of the first interlevel dielectric film 104 . such a state is established if the second interlevel dielectric film 117 has been deposited with poor step coverage and high directivity . for example , if the second interlevel dielectric film 117 is a so - called “ high - density plasma ( hdp ) film ”, the air gaps such as those shown in fig8 a are obtained . in this case , since no dielectric is deposited inside the recesses 115 , the capacitance c 3 between adjacent lines 113 a is smaller . an hdp film is formed by using an hdp apparatus . if an hdp film is deposited in an hdp apparatus with a bias voltage applied to the substrate , an etching phenomenon also happens in competition with the deposition . as a result , the dielectric film is deposited on the bottom of the recesses and the upper end of an air gap does not exceed the upper surface of the first interlevel dielectric film 104 . the air gaps in such a shape are shown in fig8 b . if the hdp film , which has been deposited with a bias voltage applied to the substrate , is used as the second interlevel dielectric film , only a small amount of dielectric is deposited on the bottom of the recesses . however , if the insulating film , which is an underlying layer of the first interconnect layer , has been etched , the deposited dielectric is located at a lower level than that of the first interconnect layer . accordingly , the capacitance between the lines 113 a remains low . thus , if the process step of etching the insulating film 102 has been performed as shown in fig6 f , the capacitance c 4 between the lines 113 a is kept low , even though a small amount of dielectric has been deposited on the bottom of the recesses . this point will be further described with reference to fig9 a and 9b . fig9 a illustrates the shape of air gaps where the process step of etching the insulating film 102 has not been performed , while fig9 b illustrates the shape of air gaps where the process step of etching the insulating film 102 has been performed . in fig9 a , if a dielectric has been deposited on the bottom of the recesses , then the capacitance c 5 is larger than the capacitance c 4 because the dielectric exists between adjacent lines . accordingly , in forming the second interlevel dielectric film in accordance with a deposition method for forming the air gaps in such shapes as those shown in fig7 b and 8b , it is preferable to make the bottom of the recesses lower than the first interconnect layer 113 by performing the process step of etching the insulating film 102 . in order to reduce the line - to - line capacitance , the air gaps of such a shape as shown in fig8 b are most preferable . however , if such air gaps are formed , it is highly probable that the second interlevel dielectric film is planarized and etched by cmp to the level on which the upper end of the air gaps is located . nevertheless , if the interconnecting metal 109 is formed to protrude upward from the upper surface of the first interlevel dielectric film 104 , the chemical / mechanical polishing can be stopped at the level of the upper surface of the interconnecting metal 109 . that is to say , the interconnecting metal 109 can function as a kind of etching stopper layer . in such a case , it is easy to control the cmp process such that the polished and etched surface is located higher than the upper end of the air gaps . accordingly , even if the air gaps of the shape shown in fig8 a have been formed , problems are less likely to happen . also , if the air gaps of the shape shown in fig8 a are formed , the necessity of etching the insulating film 102 is relatively low . however , if the insulating film 102 has been etched , the line - to - line capacitance c 3 can be lower as compared with the case where the insulating film 102 has not been etched at all . the reason is as follows . the line - to - line capacitance is determined by the physical properties of a space of a certain dimension located between two adjacent lines . accordingly , since the line - to - line capacitance is also affected by the relative dielectric constants of spaces over and under the space adjoining the lines , the insulating film is preferably etched . considering these points , it can be understood that partially etching the insulating film 102 at the spaces between adjacent lines 113 a is advantageous in reducing the line - to - line capacitance for various shapes of air gaps . as described above , in this embodiment , part or all of a line - to - line space 114 is turned into an air gap 118 . accordingly , the relative dielectric constant between lines 113 a in the first interconnect layer 113 can be reduced at the line - to - line space 114 . in particular , when a recess 115 formed in a line - to - line space 114 has a high aspect ratio , the entire region of the line - to - line space 114 is turned into an air gap 118 . as a result , the relative dielectric constant between the lines 113 a can be minimized . in addition , since the first interconnect layer 113 is formed after the interconnecting metal 109 has been formed , the first interconnect layer 113 always exists under the entire bottom of the interconnecting metal 109 . accordingly , it is possible to prevent a contact failure from being caused between the first interconnect layer 113 and the interconnecting metal 109 . moreover , after the interconnecting metal 109 has been filled in the interlevel contact hole 106 provided in the first interlevel dielectric film 104 , the first interconnect layer 113 and the second interlevel dielectric film 117 are formed in this order . accordingly , even if a mask - to - mask placement error has been caused during the formation of the first interconnect layer 113 , either the interconnecting metal 109 or the first interlevel dielectric film 104 always exists on the upper surface of the first interconnect layer 113 . and the interconnecting metal 109 is never filled in any air gap 118 formed simultaneously with the second interlevel dielectric film 117 . accordingly , it is possible to prevent a shortcircuit failure from being caused between adjacent lines 113 a in the first interconnect layer 113 or between a line 113 a and the semiconductor substrate 101 through the interconnecting metal 109 . hereinafter , the fifth embodiment of the present invention will be described with reference to fig1 a through 10d illustrating the flow of a process for fabricating a semiconductor device in this embodiment . the same process steps as those illustrated in fig1 a through 1d and fig6 e and 6f are also performed prior to the process step shown in fig1 a . thus , the same components as those used in the first embodiment will be identified by the same reference numerals and the description thereof will be omitted herein . unlike the first embodiment in which the second interlevel dielectric film 117 is deposited by using a plasma cvd apparatus , a second interlevel dielectric film 212 is formed in this fifth embodiment by using an applicator . the second interlevel dielectric film 212 may be an organic film made of organic poly - siloxane or an organic material containing fluorine , or an inorganic porous film , for example . many of these materials have fluidity . first , as shown in fig1 a , the material is applied onto a first interlevel dielectric film 204 , an interconnecting metal 208 and the line - to - line spaces 215 formed on the semiconductor substrate 201 . in this manner , the recesses in the line - to - line spaces 215 are filled in with the fluid material , thereby forming the second interlevel dielectric film 212 without any air gap . as the material of the second interlevel dielectric film 212 , a material having a lower relative dielectric constant than that of the first interlevel dielectric film 204 is selected . accordingly , the relative dielectric constant between adjacent lines in the first interconnect layer 203 can be reduced at the line - to - line spaces 215 . subsequently , as shown in fig1 b , the surface of the second interlevel dielectric film 212 is planarized by a cmp technique such that the respective surfaces of the first interlevel dielectric film 204 , the interconnecting metal 208 and the second interlevel dielectric film 212 form a single plane . in this embodiment , the first and second interlevel dielectric films 204 and 212 are made of different materials and the etching rate of the first interlevel dielectric film 204 is set smaller than that of the second interlevel dielectric film 212 during the cmp process . in this manner , the first interlevel dielectric film 204 is used as an etching stopper . then , as shown in fig1 c , only the second interlevel dielectric film 212 is selectively etched in the depth direction by about 0 . 3 μm , and a third interlevel dielectric film 214 is deposited to be about 0 . 5 μm thick . and then the surface of the third interlevel dielectric film 214 is planarized again by a cmp technique such that the respective surfaces of the first interlevel dielectric film 204 , the interconnecting metal 208 and the third interlevel dielectric film 214 form a single plane . next , as shown in fig1 d , a metal layer formed by alternately stacking aluminum and a titanium alloy is deposited thereon and subjected to photolithography and dry etching , thereby forming a second interconnect layer 216 . as described above , in this embodiment , the line - to - line spaces 215 are entirely filled in with the second interlevel dielectric film 212 made of a material having a lower relative dielectric constant than that of the first interlevel dielectric film 204 . thus , the relative dielectric constant between adjacent lines in the first interconnect layer 203 can be reduced at the line - to - line spaces 215 . in addition , the relative dielectric constant can be determined based on the material of the second interlevel dielectric film 212 . in addition , since the first interconnect layer 203 is formed after the interconnecting metal 208 has been formed , the first interconnect layer 203 always exists under the entire bottom of the interconnecting metal 208 . accordingly , it is possible to prevent a contact failure from being caused between the first interconnect layer 203 and the interconnecting metal 208 . moreover , after the interconnecting metal 208 has been filled in the interlevel contact hole provided in the first interlevel dielectric film 204 , the first interconnect layer 203 and the second interlevel dielectric film 212 are formed in this order . accordingly , even if a mask - to - mask placement error has been caused during the formation of the first interconnect layer 203 , either the interconnecting metal 208 or the first interlevel dielectric film 204 always exists on the upper surface of the first interconnect layer 203 . and the second interlevel dielectric film 212 always exists in the line - to - line spaces 215 . accordingly , it is possible to prevent a shortcircuit failure from being caused between adjacent lines in the first interconnect layer 203 or between a line and the semiconductor substrate 201 through the interconnecting metal 208 . in this embodiment , parts of the insulating film 202 located in the line - to - line spaces between adjacent lines in the first interconnect layer 203 are also etched . accordingly , the line - to - line capacitance is substantially determined by the relative dielectric constant of the second interlevel dielectric film 212 . if the parts of the insulating film 202 located in the line - to - line spaces between adjacent lines in the first interconnect layer 203 are not etched , then the parts of the insulating film 202 located in the vicinity of the line - to - line spaces between adjacent lines in the first interconnect layer 203 increase the line - to - line capacitance to a certain degree . moreover , in this embodiment , the third interlevel dielectric film 214 is formed . accordingly , even if a material poorly resistant to etching or plasma is used for the second interlevel dielectric film 212 , the second interlevel dielectric film 212 is not damaged during the process step of forming the second interconnect layer 216 . thus , the third interlevel dielectric film 214 is preferably made of a material highly resistant to etching or plasma . even if the relative dielectric constant of the third interlevel dielectric film 214 increases because of the selection of such a material , the line - to - line capacitance of the first interconnect layer 203 is not increased . in the embodiment illustrated in fig1 a through 10d , no air gaps are formed in the line - to - line spaces 215 . alternatively , air gaps may be formed in the line - to - line spaces 215 . in the sixth embodiment , the same process steps as those of the fifth embodiment are performed before the second interlevel dielectric film is formed . the sixth embodiment is characterized by the process step of forming the second interlevel dielectric film . hereinafter , the process step of forming the second interlevel dielectric film will be described in detail with reference to fig1 a through 11c . [ 0085 ] fig1 a through 11c illustrate a region where a relatively narrow recess 115 a having a width of 0 . 5 μm or less and a relatively broad recess 115 b having a width larger than 0 . 5 μm ( e . g ., 0 . 8 μm or more ) have been formed . in particular , fig1 a and 11b show the cross sections , in each of which the second interlevel dielectric film 117 is made of a single type of film . in the example shown in fig1 a , an insulating film with relatively poor step coverage has been deposited . examples of such films with poor step coverage include a plasma - oxidized film formed in a parallel - plate plasma cvd apparatus by using silane / n 2 o - based gas plasma . if such a film is used , then air gaps are formed in both of the recesses 115 a and 115 b . in the relatively broad recess 115 b , a large air gap is formed . accordingly , the upper end of the air gap in the recess 115 b possibly exceeds the resulting level of the second interlevel dielectric film 117 at which cmp is to be stopped ( in this specification , such a level will be called a “ cmp target level ”). if such a large air gap has been formed , the air gap is possibly exposed through the polished surface after the cmp process is finished . in such a case , a disconnection or shortcircuit failure of the second interconnect layer may happen . on the other hand , in the example shown in fig1 b , a dielectric film , which can generally fill in a gap rather satisfactorily , has been deposited as the second interlevel dielectric film 117 . examples of such a film include a plasma - oxidized film formed by using high - density plasma ( hdp ). if such a film is used , then the second interlevel dielectric film 117 is deposited on the bottom and side faces of the relatively narrow recess 115 a . as a result , an air gap of the size smaller than that of the recess 115 a is formed in the recess 115 a . on the other hand , the relatively broad recess 115 b is filled in with the second interlevel dielectric film 117 and no air gap is observed therein . the hdp film is formed by using - an hdp apparatus . if the hdp film is deposited in the hdp apparatus with a bias voltage applied to the substrate , an etching phenomenon also happens in competition with deposition . as a result , the dielectric film is deposited on the bottom of the recess and the gap can be filled in with the film more satisfactorily . in this case , the upper end of an air gap does not reach the cmp target level . however , since a smaller air gap is formed in the recess 115 a , the line - to - line capacitance is not reduced so much . in the embodiment shown in fig1 c , in order to attain the advantages of these two types of films at the same time , the second interlevel dielectric film 117 is made up of dielectric layers formed by at least two different methods . specifically , first , the upper part of the relatively narrow recess 115 a is substantially covered with a first interlevel dielectric layer 117 a and then the other relatively broad recess 115 b is filled in with a second interlevel dielectric layer 117 b . in particular , the first interlevel dielectric layer 117 a is formed in a parallel - plate plasma cvd apparatus by using silane / n 2 o - based gas plasma and then the second interlevel dielectric layer 117 b is deposited in an hdp apparatus with a bias voltage applied to the substrate . the first and second interlevel dielectric layers 117 a and 117 b are made of silicon dioxide , for example . alternatively , the second interlevel dielectric layer 117 b may be an organic coating film ( made of polyarylether , for example ) having a low relative dielectric constant . the first interlevel dielectric layer 117 a may be formed using silane , oxygen and argon gases at a pressure of 5 mtorr . if the width of an air gap ( i . e ., the ratio of the air gap to a line - to - line space ) is increased , the upper end of the air gap becomes higher . the width and height of an air gap can be optimized by adjusting the thicknesses of the first and second interlevel dielectric layers 117 a and 117 b . next , the results of evaluation performed on the multilevel interconnect structure formed in this embodiment will be described . first , fig1 a through 12c will be referred to fig1 a illustrates a positional relationship between a line - to - line space and an air gap . in fig1 a , h denotes a distance between the upper surface of the first interconnect layer and the top of the air gap , and d denotes a distance between the lower surface of the first interconnect layer and the bottom of the air gap . the occupancy ratio r is the ratio of the width w of the air gap to the line - to - line space s . [ 0091 ] fig1 b illustrates the dependence of the occupancy ratio r of the air gap on the line - to - line space s . if s is equal to or smaller than 0 . 8 μm , the occupancy ratio r of the air gap is a positive value larger than zero . the smaller the line - to - line space s is , the larger the occupancy ratio r is . when s = 0 . 3 μm , the occupancy ratio r is about 0 . 9 . [ 0092 ] fig1 c illustrates the dependence of the distances h and d on the line - to - line space s . the value of h never exceeds 500 nm at any value of the line - to - line space s , and never reaches the cmp target level ( in the range from 800 nm to 1000 nm above the interconnect layer ). in other words , even after the interlevel dielectric film 117 has been planarized by a cmp technique , the air gap is not exposed . thus , the yield of the second interconnect layer does not decrease . next , it will be described with reference to fig1 how the line - to - line capacitance is effectively reduced in the multilevel interconnect structure formed in this embodiment . in fig1 , data about a conventional multilevel interconnect structure in which no air gaps are formed between adjacent lines is represented by open circles as a comparative example . in the comparative example , the smaller the line - to - line space is , the larger the line - to - line capacitance per unit length is . however , in this embodiment , as the line - to - line space decreases , the line - to - line capacitance also decreases to the contrary . the line - to - line capacitance decreases presumably because the occupancy ratio r of the air gap to the line - to - line space increases as the line - to - line space decreases . next , with reference to fig1 a and 14b , the reduction of the line - to - line capacitance in accordance with this embodiment will be compared to the reduction of the line - to - line capacitance accomplished by the use of an interlevel dielectric film having a low relative dielectric constant . [ 0095 ] fig1 a is a cross - sectional view illustrating the configuration of a model used for calculation ( or simulation ). fig1 b illustrates the dependence of an effective relative dielectric constant on a line - to - line space . the effective relative dielectric constant is determined by calculating the line - to - line capacitance ( per unit length ) generated when a uniform medium having a certain relative dielectric constant is used as the interlevel dielectric film and then by comparing the capacitance to the actually measured capacitance . as represented by the open squares in fig1 b , in this embodiment , the smaller the line - to - line space is , the smaller the effective relative dielectric constant is . if the line - to - line space is 0 . 8 μm or less , an air gap is formed in the line - to - line space . and if an air gap is formed , the effective relative dielectric constant drastically decreases . when the line - to - line space is 0 . 3 μm , the effective relative dielectric constant is as low as about 1 . 8 . [ 0096 ] fig1 illustrates a relationship between the resistance of an interconnecting metal ( i . e ., via resistance ) and the diameter of the interconnecting metal ( i . e ., via diameter ). as can be understood if this embodiment is compared to the comparative example in which no air gaps are formed , via resistance values are not different so much in both cases . [ 0097 ] fig1 illustrates the dependence of a via resistance value on an alignment error between the first interconnect layer and the interconnecting metal . the “ alignment error ” herein denotes the magnitude of the misalignment between the interconnecting metal and the first interconnect layer . since the width of a line - to - line space in the first interconnect layer is equal to the via diameter in the pattern used for measurement , there is no overlap margin between the first interconnect layer and the interconnecting metal . as can be understood from fig1 , in the conventional example , the larger the alignment error is , the higher the via resistance is . by contrast , in this embodiment , the via resistance remains substantially the same irrespective of the via resistance . the reason is as follows . even if misalignment has been caused , the contact area between the first interconnect layer and the interconnecting metal is kept at a maximum value , because the interconnecting metal always exists on the upper surface of the first interconnect layer . since the second interlevel dielectric film 117 is deposited after the interconnecting metal 109 has been formed , the air gaps , formed simultaneously with the deposition of the second interlevel dielectric film 117 , do not come into contact with the interconnecting metal 109 . accordingly , neither a shortcircuit failure between adjacent lines 113 a in the first interconnect layer 113 nor a shortcircuit failure between a line 113 a and the semiconductor substrate 101 is caused through the interconnecting metal 109 . the material of the first interconnect layer is not limited to al . alternatively , the first interconnect layer may be made of cu , for example . instead of a plasma oxide film , an applied insulating film , which can fill in a gap satisfactorily , may also be used as the second interlevel dielectric layer of the second interlevel dielectric film 117 . also , desirable effects can be attained even if the method for forming the second interlevel dielectric film , described with reference to fig1 c , is applied to any other embodiment of the present invention . according to the present invention , the first interconnect layer always exists under the entire bottom of the interconnecting metal . accordingly , even if misalignment has been caused during the formation of the first interconnect layer , it is possible to prevent a contact failure from being caused between the first interconnect layer and the interconnecting metal . in addition , the interconnecting metal is not filled into the air gaps that are formed simultaneously with the second interlevel dielectric film . thus , it is possible to prevent a shortcircuit failure from being caused between adjacent lines in the first interconnect layer or between a line and the semiconductor substrate through the interconnecting metal . if part or all of a line - to - line space is turned into an air gap or if the line - to - line space is entirely filled in with a material having a low relative dielectric constant , the relative dielectric constant between adjacent lines can be reduced at the line - to - line space . as a result , a semiconductor device , which operates with a larger margin and is less likely to operate erroneously , is realized by reducing a signal delay between the lines in the first interconnect layer . moreover , since most of the side face of the interconnecting metal is in contact with the second interconnect layer , reliability in connecting the interconnecting metal to the second interconnect layer can also be improved even if misalignment has been caused during the formation of the second interconnect layer . furthermore , even if misalignment has been caused during the formation of the first interconnect layer , either the interconnecting metal or the first interlevel dielectric film always exists on the upper surface of the first interconnect layer . in addition , the interconnecting metal is not filled into the air gaps that are formed simultaneously with the second interlevel dielectric film . thus , it is possible to prevent a shortcircuit failure from being caused between adjacent lines in the first interconnect layer or between a line and the semiconductor substrate through the interconnecting metal .
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the present invention will be discussed hereafter in detail in terms of the preferred embodiment of the present invention with reference to the accompanying drawings . in the following description , numerous specific details are set for the in order to provided a thorough understanding of the present invention . it will be obvious , however , to those skilled in the art that the present invention may be practiced without these specific detail . in other instances , well - known structures are not shown in detail in order to avoid unnecessary obscurity of the present invention referring to fig1 , an electrical equipment ( not labeled ), such as a computer , according to the present invention comprises a motherboard and an electrical connector 100 mounted on the motherboard and exposed to access network through telephone line . the electrical connector 100 performs partial functions of an exiting modem card assembly . as best showing in fig2 in conjunction with fig1 , in the preferred embodiment of the invention , a digital insulation barrier ( combination of a safety insulation barrier and digital filters ) and a modem controller b are combined inside the electrical connector 100 . for convenience , such digital insulation barrier and the modem controller b integrated in the electrical connector 100 are referred to hereafter as modem components 33 ( shown in fig1 ). it should be noted that the existing modem card assembly is eliminated . the electrical connector 100 is mounted on the motherboard . at the same time functions of the modem controller a are moved onto the motherboard and associated with the modem components 33 of the electrical connector 100 . therefore , the main processor on the motherboard can access network directly through the electrical connector 100 and the telephone line . as a result the need in motherboard connectors is eliminated , additional significant cost reduction is achieved by reducing the size of the motherboard . it also should be noted that the digital insulation barrier and the modem controller a may selectively both be incorporated onto the motherboard , while only the controller b is integrated into the electrical connector 100 . referring to fig3 and 5 , the electrical connector 100 includes an insulative housing 1 , a plurality of conductive contacts 2 retained in the housing 1 , an electrical element 3 containing the modem component 33 performing partial functions of the existing modem card assembly , a connector module 4 ( shown in fig4 ), a plastic rear cover 5 and an outer shell 6 substantially surrounding and shielding the housing 1 . referring to fig6 and 7 , the insulative housing 1 includes a mating face 11 , an upper wall 12 , two sidewalls 13 and a rear opening 14 . the mating face 11 provides upper and lower cavities 111 , 112 extending rearwardly thereinto . the rear opening 14 shares a panel 15 with the lower cavity 112 . in the embodiment illustrated , the upper cavity 111 is a modular plug - receiving cavity for mating with a modular plug connector , and the lower cavity 112 is provided for receipt thereinto of the connector module 4 . the upper cavity 111 provides a plurality of barriers 113 projecting inwardly from the mating face 11 , and a number of ramps 115 essentially aligned with and spaced from corresponding barriers 113 in a longitudinal direction , thereby forming a plurality of parallel slots 114 between the adjacent barriers 113 and the ramps 115 in a front - to - rear direction for receiving corresponding contacts 2 . a plurality of grooves 117 are dimensioned to be positioned proximate the panel 15 and communicating with the rear opening 14 for receiving the contacts 2 . the housing 1 further includes a plurality of comb passages 116 extending into the upper cavity 111 and communicating with the rear opening 14 . the upper wall 12 defines a pair of locking holes 121 far from the mating face 11 . each sidewall 13 has a shaft 131 projecting inwardly from a bottom portion thereof for engaging with the plastic rear cover 5 . as best shown in fig8 , the conductive contacts 2 are initially attached to a carrier strip 24 . each conductive contact 2 includes a base portion 21 having a front nose 211 on a front section thereof , a contacting portion 22 upwardly and rearwardly extending from the front nose 211 of the base portion 21 and a tail portion 23 connected to the carrier strip 24 . the base portion 21 has a pair of shoulders 212 adjacent to the front nose 211 and extending transversely from opposite sides thereof . the base portion 21 further has an enlarged section 213 apart from the front nose 211 and extending transversely and outwardly . the tail portion 23 is integrally attached to the enlarged section 213 by a transition bight 24 . the tail portion 23 downwardly offsets from the transition bight 24 and is parallel to the base portion 21 . the tail portion 23 has a positioner section 231 extending from opposite sides thereof adjacent to the transition bight 24 . referring to fig1 and 12 , the electrical element 3 includes an internal circuit board 31 carrying the modem components 33 and a plurality of footer contacts 32 thereon . the internal circuit board 31 provides a plurality of pinouts 311 on a substantial middle portion thereof for respectively receiving the contacts 2 and a plurality of footer holes 312 in a lower portion thereof . each footer contact 32 has a latch beam 321 extending horizontally from a top portion thereof and interferentially fitted in the corresponding footer holes 312 . it should be noted that the footer contacts 32 are initially attached to a carrier strip 34 . the carrier strip 34 is removed from the footer contacts 32 after or before the footer contacts 32 are installed in the internal circuit board 31 and soldering thereto . the internal circuit board 31 further has a number of signal conditioning components mounted thereon ( not labeled ). such signal conditioning components can be passive electrical components such as transformers , resistors , capacitors and as such , and active components such as varistors , thyristors , transistors and integrated circuits , and electromechanical components such as switches , relays , indicators and transient voltage suppressors . referring to fig4 and 5 , the plastic rear cover 5 includes a vertical portion 51 and a horizontal portion 52 extending forwardly from a bottom side of the vertical portion 51 . the vertical portion 51 includes a pair of projections 53 extending from a top end thereof and a pair of fixing portions 54 formed near opposite sides of a bottom end thereof . the projections 53 are provided for latching within the locking holes 121 of the housing 1 , respectively . the fixing portions 54 are provided for engaging with the corresponding shafts 131 of the housing 1 . the outer shell 6 is stamped from a sheet of conductive material and includes a front shell 61 and a rear shell 62 which mount together to define an interior space for enclosing the housing 1 . the front shell 61 includes a front plate 611 providing two windows ( not labeled ) respectively corresponding to the upper and lower cavities 111 , 112 , and two side plates 612 . each side plate 612 has a plurality of embossments 613 and a plurality of grounding tabs 614 extending downwardly from a bottom end thereof . the rear shell 62 has a number of apertures 621 corresponding to and engaging with respective ones of the embossments 613 . referring to fig9 and 10 in conjunction with fig8 , in assembly , the conductive contacts 2 are installed in the housing 1 from the rear opening 14 . the front nose 211 of each contact 2 extends through respective one of the passages 116 and is received in the corresponding slot 114 . the contacting portion 22 of each contact 2 is exposed in the upper cavity 111 with a free end deflected by the corresponding passage 116 , thereby having a preload force . the base portion 21 and the front nose 211 of each contact 2 are held in the slot 114 . the shoulders 212 of each contact 2 are latched with the raised ramps 115 , in conjunction with the contact preload force which keeps a constant downward force on the contacts 2 , thereby assuring that the contacts 2 don &# 39 ; t lift off the shoulders at the end of the ramps . the positioner sections 231 of the contacts 2 are received in the grooves 117 . therefore , the contacts 2 are securely embedded in the housing 1 . after installation , the carrier strip 24 is removed from the contacts 2 . referring to fig4 and 5 in conjunction with fig3 , the electrical element 3 is attached to the housing 1 from the rear opening 14 . the tail portion 23 of each contact 2 extends beyond the grooves 117 and into the respective one of the pinout 311 of the internal circuit board 31 . the plastic rear cover 5 is coupled to the housing 1 . the shafts 131 of the housing 1 are installed in the fixing portion 54 of the plastic rear cover 5 . the projections 53 of the plastic rear cover 5 are received in the corresponding locking holes 121 of the housing 1 , thereby stabilizing the connection between the contacts 2 and the internal circuit board 31 . the connector module 4 such as a dual usb module for mating with usb type plugs , is assembled to the lower cavity 112 of the housing 1 from the mating face 11 . the structure and the function of the connector module 4 is well known to those skilled in the art , a detailed description thereof is omitted herefrom . the outer shell 6 substantially surrounds the housing 1 . the front plate 611 of the front shell 61 affixes along the mating face 11 of the housing 1 . the embossments 613 are interference fitted in the respective one of the apertures 621 . the grounding tabs 614 are soldered to the corresponding grounding holes ( not shown ) of the motherboard . it is to be understood , however , that even though numerous , characteristics and advantages of the present invention have been set fourth in the foregoing description , together with details of the structure and function of the invention , the disclosed is illustrative only , and changes may be made in detail , especially in matters of shape , size , and arrangement of parts within the principles of the invention to the full extent indicated by the broad general meaning of the terms in which the appended claims are expressed .
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in accordance with the invention , a composition for deicing or inhibiting the formation of ice comprises ( a ) between about 1 . 0 and about 99 % by weight waste material from a fermentation process for producing an amino acid from a carbohydrate source used as an anti - freezing and deicing agent ; ( b ) between about 0 . 0 and about 99 % by weight of a second anti - freezing and deicing agent ; and ( c ) between about 0 . 0 and about 60 % by weight of a carrier . the fermentation process relies upon the use of microbes that synthesize the desired amino acid from the carbohydrate source . the microbes may be genetically altered to better perform this function and include bacteria from various genera . in one particularly useful embodiment of the present invention , the amino acid is selected from a group consisting of glutamic acid and lysine . glutamic acid may be produced by bacteria from the genera bacillus , micrococcus , brevibacterium microbacterium , corynebacterium anthrobacter and the like . corynebacterium glutamicum and related strains are useful in producing lysine . it should be appreciated , however , that other microorganisms useful in producing glutamic acid of lysine by means of fermentation of a carbohydrate source may be used . the carbohydrate source may be any such source known to be useful in the production of the desired amino acid by means of microbial fermentation . carbohydrate sources include , but are not limited to , cassava , raw sugar , starch , starch hydrolysate , molasses , desugared molasses , corn sugar molasses , sugar beet molasses , sugar cane molasses , desugared sugar beet molasses and mixtures thereof . in one possible production process known in the art , a starch from cassava is hydrolized . after the starch processing stage , molasses is added during a syrup refining stage . after this stage , glucose syrup is added and the mixture proceeds to a fermentation stage . during the fermentation stage , ammonia and micro - organisms , in this case bacteria , are added for microbial fermentation . the bacteria are grown in a liquid medium containing molasses as the fermentation substrate . glutamic acid producing bacteria produce and excrete glutamic acid into the medium . alternatively , lysine producing bacteria may be used to produce and excrete lysine into the medium . as a consequence of fermentation , all or substantially all of the sugar in the substrate is used . subsequently , the glutamic acid / lysine is separated from the medium by evaporation and neutralization ( addition of sodium hydroxide and hydrochloric acid ). the glutamic acid / lysine then goes through another stage of neutralization , followed by filtration and crystallization . the glutamic acid / lysine is then dried , sieved and packaged . the leftover byproduct or waste material from the fermentation process , sometimes referred to as condensed molasses fermentation solubles ( cms ), is an active ingredient in the deicing composition of the present invention . the waste material of the fermentation process exhibits enhanced deicing properties and is non - corrosive . the waste material is approximately sixty percent ( 60 %) solids , but may vary depending on the process . the carrier is typically water although any other appropriate carrier suitable for use in a deicing composition including fermentation waste material may be used . the resulting composition is easily sprayed or applied to surfaces in need of deicing or where there is a desire to prevent freezing ( such as roads , bridges , sidewalks , vehicles , machines , crops , aggregate piles , or the like ). the second anti - freezing and deicing agent may , for example , be selected from a group of material consisting of sugar cane molasses , sugar beet molasses , desugared sugar beet molasses , or organic agricultural byproducts . alternatively , the second anti - freezing and deicing agent may be selected from a group consisting of calcium chloride , magnesium chloride , sodium chloride , potassium chloride , sodium formate , sodium acetate , potassium acetate , ethylene glycol , diethylene glycol . the second anti - freezing and deicing agent may be in solid form ( granular ) or solution brine ) form . the first deicing agent serves to enhance the deicing properties and reduce the corrosive nature of these second anti - freezing and deicing agents . the weight percentages of the various ingredients of the composition are selected and mixed as desired in order to tailor the deicing properties of the composition to any particular application . in accordance with yet another aspect of the present invention , it should be appreciated that the fermentation waste material deicing agent , can be used without further additions ( 100 % or neat ), which is desirable in terms of providing a completely natural deicing product . alternatively , the fermentation waste material may be mixed with additional materials including , for example , water , anti - skid agents such as sand , cinders , etc . forming a composition in the range of 1 - 80 % solids by weight , depending on the application . the following detailed examples illustrate experiments which demonstrate the improved properties and characteristics of the compositions of the present invention . of course , these examples are provided for purposes of illustration only and are not intended to be limiting . the objective of the first experiment was to determine the corrosiveness of various fermentation waste materials on metals . initially , used steel nails were cleaned with an aqueous solution of muriatic acid ( better known as hydrochloric acid , hcl ). subsequently , the steel nails were inserted into different solutions of fermentation waste materials ( fwm ) for thirty days to study the corrosive effects the solution had upon the steel nails . the results of the experiment of displayed in the table below : as shown in the table , the 10 %, 20 % and 30 % fwm solutions by weight did not show any corrosive effect on the steel nails in thirty days . the objective of the second experiment was to determine whether various fmw solutions would freeze under freezing conditions . fmw solutions ranging between 10 % and 50 % solids by weight were placed into freezing conditions . in particular , these solutions were placed into a freezer at 32 ° f . ( 0 ° c .) to study whether the solutions would freeze . the 10 % and 20 % solids by weight fmw solutions froze the first day . the 30 % solids by weight fmw solution by weight became “ slushy ” on the first day . specifically , some freezing was observed , but the solution remained primarily in its liquid state . the 40 % and 50 % solids by weight fmw solutions did not freeze over the thirty day period . based upon the experimentation , no increase in freeze point of the various fmw solutions was observed . further , no dilution of the fmw solutions was observed throughout the testing . the foregoing description of a preferred embodiment of the invention has been presented for purposes of illustration and description . it is not intended to be exhaustive or to limit the invention to the precise form disclosed . obvious modifications or variations are possible in light of the above teachings . the embodiment was chosen and described to provide the best illustration of the principles of the invention and its practical application to thereby enable one of ordinary skill in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated . all such modifications and variations are within the scope of the invention .
| 2 |
in the following description , numerous specific details are set forth to provide a more thorough understanding of the present invention . however , it will be apparent to one of skill in the art that the present invention may be practiced without one or more of these specific details . in other instances , well - known features have not been described in order to avoid obscuring the present invention . fig1 illustrates a system 100 configured to implement one or more aspects of the present invention . the system 100 includes , without limitation , a central processing unit ( cpu ) 130 , a system memory 110 , a graphics processing unit ( gpu ) 115 , a device / memory bridge 105 , a network interface 145 , a digital pen 135 , and a spatially - aware projector 132 . the spatially - aware projector 132 is configured to be grasped by a non - dominant human hand while the digital pen 135 is configured to be grasped by a dominant human hand . the cpu 130 communicates with the system memory 110 via the device / memory bridge 105 , which may be , e . g ., a northbridge device or subsystem . system memory 110 is configured to store application programs , as well as data used by or generated by the cpu 130 . in particular , system memory 110 is configured to store design data 150 , such as computer - aided design drawings and information that is accessed by the application program 112 . system memory 110 is also configured to store image data 155 for display by the spatially - aware projector 132 . the image data 155 may be produced by the cpu 130 or a discrete gpu 115 based on design data 150 and / or data received via the spatially - aware projector 132 and the digital pen 135 . system memory 110 is coupled to the device / memory bridge 105 via a system memory bus 150 . the device / memory bridge 105 may be coupled to the gpu 115 that incorporates real - time image rendering means for rendering both three - dimensional ( 3d ) and two - dimensional ( 2d ) images . the cpu 130 or gpu 115 delivers pixel data to the spatially - aware projector 132 . in some embodiments , the integrated circuit implementing the cpu 130 may incorporate additional functional blocks , such as the device / memory bridge 105 and gpu 115 . the device / memory bridge 105 is also coupled to the network interface 144 , the digital pen 135 , and the spatially - aware projector 132 . the network interface 144 provides network connectivity to other computers in local or remote locations using any suitable technology , preferably a wireless technology . in particular , portions of design data 150 and image data 155 may be output to remote users via the network interface 144 . similarly , data received from a remote user via the network interface 144 may be displayed and / or stored as design data 150 or image data 155 . other components ( not explicitly shown ), including usb or other port connections , cd drives , dvd drives , film recording devices , and the like , may also be connected via network interface 145 . communication paths interconnecting the various components in fig1 may be implemented using any suitable protocols , such as pci ( peripheral component interconnect ), pci express ( pci - e ), agp ( accelerated graphics port ), hypertransport , quick path interconnect , or any other bus or point - to - point communication protocol ( s ), and connections between different devices may use different protocols as is known in the art . in one embodiment , system memory 110 is configured to store a graphics modeling or authoring application program 112 that is configured to access the design data 150 to provide image data 155 for display via spatially - aware projector 132 and use information acquired by the digital pen 135 and the spatially - aware projector 132 to display a user - interface or image data . fig2 illustrates a detailed view of the digital pen 135 according to one embodiment of the present invention . as shown , the digital pen 135 includes a force sensor 202 , which indicates when the tip of the digital pen 135 is in contact with a display surface 208 and may be used to record pen strokes . an ink reservoir may be configured to deposit physical ink on the display surface when the tip of the digital pen 135 is in contact with a surface . a camera 204 is also included in the digital pen 135 and is positioned to enable 2d tracking using patterns printed on the display surface 208 . in one example , dot - pattern technology is used to provide the 2d tracking , where a unique dot pattern 212 is identified by camera 204 while scanning area 210 . the camera 204 may also be used to enable 3d optical tracking using traceable patterns to retrieve camera calibration parameters to determine 3d location and orientation . the patterns may also represent a hierarchical encoding pattern which allows the camera to cover a wide range of distances from the display surface 208 . additional patterns may be printed on the display surface 208 in infrared ink to be less distracting to the user . in other embodiments , the digital pen 135 may include alternative tracking mechanisms to the camera 204 . for example , any type of proximity sensor , e . g ., electromagnetic sensors may be included in the display surface 208 to detect a location of digital pen 135 . this configuration would advantageously enable the spatially aware projector 132 to be lifted a substantial distance from the display surface 208 while maintaining overall functionality and providing a larger projected image onto the display surface 208 . an input mechanism 206 is further included in digital pen 135 and may be implemented using a button that is configured to be activated and / or deactivated by a user , as described in further detail herein . fig3 a - 3b illustrate a detailed view of the spatially - aware projector 132 according to one embodiment of the present invention . in order for the spatially - aware projector 132 to display the design data 150 and / or image data 155 as a visual overlay in the context of a paper document , the application program 112 needs to be aware of the spatial location of the spatially - aware projector 132 and the digital pen 135 relative to the display surface 208 . capturing the location of the spatially - aware projector 132 and / or the spatially - aware pen 135 on the display surface 208 allows the spatially - aware projector 132 to display virtual information which is relevant to the existing physical content on the paper . the virtual information may be read from design data 150 or information previously captured by digital pen 135 from pen strokes stored as image data 155 . the digital pen 135 increases the user &# 39 ; s ability to work with functionality that requires visual feedback , such as viewing the results of computations , and overlaying contextual information onto the digital paper 208 via spatially - aware projector 132 . in one embodiment , the spatially - aware projector 132 includes a handle 302 , a scroll wheel 304 , a digital pen 135 1 , a digital pen 135 2 , a micro - projector 306 , a small mirror 308 , a swivel handle 310 , and a large mirror 312 . the handle 302 may be grasped by a hand of the user to navigate the spatially - aware projector 132 across the display surface 208 . the scroll wheel 304 may be implemented using a scroll wheel of a mouse , and is used to , e . g ., cause elements included within a projected image 314 to be scaled up or down . the projected image is dynamically updated to display virtual layers , as described in further detail below in conjunction with fig6 . input received via digital pens 135 1 and 135 2 provides both a position and angle of the projector with respect to the display surface 208 . in other embodiments , alternative tracking mechanisms may be included within the spatially - aware projector 132 , such as the proximity sensors described above in conjunction with fig2 . projected image 314 is displayed via micro - projector 306 , small mirror 308 and large mirror 312 . the angle of large mirror 312 is adjustable via the swivel handle 310 to increase or decrease the size of the projected image 314 . in this way , a user of system 100 is advantageously able to focus his or her work across a small or large portion of display surface 208 , as illustrated in fig3 b . note that the position of micro - projector 306 and small mirror 308 are not fixed and may also be adjusted , either alone or in combination , to influence projected image 314 . in addition , if a laser - based pico projector is used , the scanning pattern produced by the pico projector may be modified to reduce artifacts that are often visible when the large mirror 312 is angled to increase the size of the projected image 314 . for example , the spatially - aware projector 132 may include a mechanical controller , that , when adjusted , changes the spread between each raster line that is produced by the laser - based pico projector . this may be accomplished , for example , by modulating x and y axis - based oscillating mirrors that relay the laser beam to different x , y coordinates of the large mirror 312 . moreover , the oscillating frequency of these can be modified on demand using acousto - optic modulators . as a result , the artifacts may either be reduced or eliminated entirely . fig4 illustrates an independent input / output technique 400 according to one embodiment of the present invention . as shown , the spatially - aware projector 132 produces a projected image 402 on display surface 208 . the location and orientation of the spatially - aware projector 132 and the digital pen 135 with respect to display surface 208 is carefully considered , since they affect the overall operation of the system in several ways . digital pen 135 3 provides a direct link between input , e . g ., pen strokes , illustrated as virtual input 404 , and output , e . g ., projected image 402 . importantly , decoupling the digital pen 135 and spatially - aware projector 132 allows for independent input and output . for example , the projected image 402 can be stationary while the digital pen 135 is used . in other words , the digital pen 135 and the spatially - aware projector 132 can be operated simultaneously and independently from one another . additionally , multiple users may share the same display surface 208 and collaborate by each providing input via additional spatially - aware digital pens 135 4 - x . remote users may also provide input and see the same projected image 402 on a remote display surface 208 . fig5 illustrates a displaced input technique 500 according to one embodiment of the present invention . another property resulting from decoupling the digital pen 135 and spatially - aware projector 132 is the capability to provide input via the digital pen 135 outside of the projected image 402 . for example , the user can write a “ search ” keyword via displaced virtual input 502 outside the projected image 402 on a separate display surface 208 2 and the search results can be included in the projected image 402 . furthermore , users can interact with the projected image 402 on a separate display surface 208 to interact with virtual display elements located thereon . fig6 illustrates different virtual layers , according to one embodiment of the present invention . the display layers include the physical display layer 260 and the virtual display layer ( s ) 265 . the virtual display layers 265 may include multiple separate virtual layers that are overlaid . each virtual layer may include one or more of user printout database layers 270 , user database layer 275 , and / or viewport layer 280 . the physical display layer 260 is the layer which physically exists on the display surface 208 and may include a variety of different elements . examples of elements include printed content , such as a diagram or two - dimensional building layout , ink created by the user , and user interface elements , such as menus and icons , preprinted on the physical display layer 260 . above the physical display layer 260 are one or more virtual display layers 265 that may be combined to produce the projected image 402 . a variety of display elements may be projected onto the virtual display layers 265 . printout database layer 270 contains auxiliary data that is displayed in the context of the printed content . for example , if a map is printed on a piece of paper , the printout database consists of vector images and text labels of either printed content or electronically stored content . display elements within the printout database layer are locked on - surface and aligned with the underlying printout . printout database layer 270 may be useful for displaying aspects of the design data 150 that are not included in the physical display layer 260 . for example , when multivalent documents that consist of multiple abstract layers of distinct — but closely coupled content — are used , then only some of the abstract layers may be included in physical layer 260 . multivalent documents are especially prevalent in the application domain of architecture and three - dimensional modeling , e . g ., different floor plans , section views , and additional metadata to describe materials and processes . user database layer 275 includes any new virtual display element , which is added by the user . for example , when a user creates ink ( annotation or sketching ) on top of the paper , the stroke is inserted into this layer . the contents of this layer are also locked on - surface . the most basic functionality of the digital pen 135 is creating virtual and / or physical ink . the digital pen 135 enables users to create and manage virtual ink that users can then make use of in different functions , such as tracing and drawing virtual guides . in some embodiments , the input mechanism 206 is used to change from a pen tip with physical ink to a pen tip using virtual ink that is displayed within the projected image 402 . when virtual ink is enabled , all pen strokes are added to the virtual ink display layer 265 , in the location of the display surface in which they are created . the user database layer 275 may be stored in image data 155 or design data 150 . hence , the annotations are added to only the virtual display layer 265 . this allows a user to annotate a blueprint without altering the original document . users can trace over both physical and virtual content within projected image 402 to produce trace data that is captured and stored in image data 155 . the trace data may be applied to different special locations within the display surface 208 . users may also load existing virtual templates to trace out with physical ink input . the resolution and size of the virtual content being traced may be adjusted via , e . g ., the scroll wheel 304 , or by displaying a virtual menu in projected image 402 that may be navigated using a digital pen 135 . instead of tracing , virtual guides may be created to aid in generating a physical sketch . such grids and guides are widely used in image editing applications , but unavailable when working on physical paper . to create a geometric guide , the user can select the line circle , rectangle , or grid menu display element , as described in further detail below in conjunction with fig7 . instead of entering points that define the geometry , the user may draw a similar shape and the digital pen 135 will approximate the selected shape . for example , the user can draw a circle using the digital pen 135 on the display surface 208 , and the location of digital pen 135 relative to the display surface 208 determines the center point and the radius . in grid mode , users may draw a rectangle that serves as the unit rectangle shape of the grid . once the digital pen 135 is lifted , the entire virtual layer is covered with a self replicating grid layout . viewport layer 280 contains global user - interface controls that enable a user to change the settings of the printout database layer 270 and the user database layer 275 . to keep these elements available at all times , viewport layer . 280 is not bound to a specific location of the display surface 208 but instead locked in - hand . note that the printout database layer 270 and user database layer 275 are page - dependent while the viewport layer is application - dependent . hence , when the digital pen 135 and / or spatially - aware projector 132 are placed on a different page , the spatially - aware projector 132 displays different content , but the same user - interface controls . an exemplary user - interface is described in detail below in conjunction with fig7 . fig7 illustrates a user interface 700 that is projected onto display surface 208 according to one embodiment of the present invention . as shown , user interface 700 is included in projected image 402 and allows for display , combination , and / or manipulation of the virtual display layers 265 displayed within the interaction region 706 . to access and control system features , the spatially - aware projector 132 displays the user interface 700 . to manipulate virtual content displayed within projected image 402 , contextual marking menus can be displayed within the viewport layer 280 , thereby providing the user with a diverse set of command execution options . the user interface 700 includes one or more database layer toolbar 702 icons 704 in the top border of the projected image 402 , and one or more icons 710 in the toolbar 708 included in the bottom border of the projected image 402 . the database layer toolbar 702 allows users to toggle the visibility of the printout database layer 270 and the user database layer 275 . additionally , touching and holding the digital pen 135 to the display surface 208 causes a marking menu ( not shown ) to be displayed within interaction region 706 and enables selection of various menu display elements , as described in further detail below in conjunction with fig8 a - 8b . for example , if working with a college campus map , layers such as “ library ”, “ dining ”, and “ overview ” could be menu display elements in the marking menu that could be activated or deactivated . icons 710 included in toolbar 708 may be used to , e . g ., modify colors of virtualized data , copy and paste virtualized data , perform search functions , enable camera view , and / or operate drafting tools , as described in further detail below . fig8 a illustrates a dominant hand menu selection 800 performed via a radial menu 802 that is included in projected image 402 according to one embodiment of the present invention . the radial menu 802 may be implemented using hierarchy to access various functions of the system . the radial distribution of menu display elements in regions 802 , 804 , 806 , and 808 that are separated by region boundaries , e . g ., region boundary 810 , simplifies use of the radial menu 802 since users only need to remember what direction to move towards . here , a virtual cursor is bound to the tip of the digital pen 135 , and is used to control the selection of regions 802 , 804 , 806 and 808 . users can access the radial menu 802 , e . g ., by activating the input mechanism 206 on digital pen 135 to cause the top level of the radial menu 802 to be displayed in virtual display layers 265 . in contrast , conventional digital pen menu systems rely on menus that are preprinted on the display surface . the user can select a menu display element in two ways , as illustrated in fig8 a - 8b . the first method involves a dominant hand menu selection technique 800 , where the user can use a traditional method of moving the digital pen 135 in the direction of the menu display element , as illustrated in fig8 a . alternatively , the user can use a non - dominant hand menu selection technique 850 , illustrated in fig8 b . here , user instead moves the spatially - aware projector 132 with the non - dominant hand ( i . e ., the hand that is not holding the digital pen 135 ) in the opposite direction of the menu display element while keeping the digital pen 135 fixed and pressed against the display surface 208 , thereby repositioning the menu display element under the pen tip . advantageously , the non - dominant hand menu selection technique 850 allows users to perform menu display element selections without leaving a physical ink trail on the display surface 208 . fig9 illustrates a display surface 208 that includes a floorplan that is overlaid with a projected image 900 that displays virtual content according to one embodiment of the present invention . the projected image 900 includes electrical components 902 . note that the electrical components 902 are only visible within the projected image 900 . in other embodiments , the projected image 900 may include additional components or additional layers , e . g ., heating , ventilation , mechanical , lighting , and the like . the overlaid content or the original physical content may be copied to another location on display surface 208 to be overlaid . the user enters a copying mode using the radial menu 802 and indicates an area using the digital pen 135 to specify a contextual parameter of the projected image 900 or the image printed on the display surface 208 . the user then enters a pasting mode using the radial menu 802 , and the copied content is displayed using the locked in - hand metaphor and copied when the user engages the input mechanism 206 . fig1 illustrates a display surface 208 that includes a floorplan that is overlaid with a projected image 1000 that hints at virtual content according to one embodiment of the present invention . the virtual display layers 265 enable computations to be performed and the results displayed in the contexts of the user &# 39 ; s workspace . the user may perform a measurement query by selecting a particular element to be measured using the spatially - aware projector 132 and / or digital pen 135 and engaging a dimension tool to overlay the measurement information . using the radial menu 802 , the user can choose to measure a distance , path length , area , or volume . alternatively , the user may create a line or bounding box using the digital pen 135 , where the measurements of the line or bounding box are displayed in the projected image 1000 . the measurement computation is displayed by the spatially - aware projector 132 within the projected image 1000 . a search command may allow users to search for elements that exist within the virtual display layers 265 . the user can perform the query in two ways . first , they can choose from a list of query elements , e . g ., sprinklers , outlets , and the like , in the search menu provided by the radial menu 802 as described above . alternately , the user can directly select an instance of an element on display surface 208 or within projected image 1000 using the digital pen 135 . for example , the user may perform a query to search for electrical outlets . in response , the outlets 1002 — which are outside of the projected image 1000 — are hinted to by halos 1004 , where each halo corresponds to an outlet that is nearby , but not within , the projected image 1000 . halos 1004 may guide the user to additional instances of the element that was searched , allowing the user to find elements of interest faster . the user can also adjust the swivel handle 310 to increase the size of the projected image 1000 to navigate toward or to display the elements corresponding to one or more of the halos 1004 . alternatively , the user can relocate the spatially - aware projector 132 perform the navigation . fig1 illustrates a display surface 208 that is overlaid with a projected image 1100 that includes a color palette 1104 according to one embodiment of the present invention . here , each section of the color palette 1104 includes a unique border color . to change the property of a virtual display element , e . g ., an electrical component 1102 , the user first aligns the color palette 1104 on top of a display element included in printout database layer 270 . then , the user can tap on the electrical component 1102 through the color palette 1104 to change the color of the electrical component 1102 . to simplify the manipulation , the color palette 1104 can be resized via scroll wheel 304 . the color palette 1104 can also be relocated within projected image 1100 via a handle attached to the color palette 1104 . fig1 illustrates a display surface 208 that is overlaid with a projected image 1200 that includes a stencil 1202 according to an embodiment of the present invention . here , the stencil 1202 is representative of any drafting tools that are used to guide a user when he or she is drawing across the display surface 208 using a digital pen 135 . like the color palette 1104 , the stencil 1202 is resizable via the scroll wheel 304 . in addition to the virtual ink that can be used to trace drawings , drafting and measurement palettes can also be used as virtual “ stencils ” that help users guide their physical pen strokes ( i . e ., ink strokes ). in one embodiment , these stencils include rectangle and circle shape tools , a protractor , and french curves . fig1 illustrates generating a video walk - through of an environment based on strokes generated by a user via a digital pen 135 according to one embodiment of the present invention . the user may draw a path , such as walkthrough path 1300 , on the display surface 208 with the digital pen 135 . frames of the two - dimensional walk - through represented as pixel data , as viewed from a viewpoint moving along the walkthrough path 1300 , are generated by the cpu 160 or the gpu 115 and stored in the image data 155 for playback as a walk - through animation . the playback may be projected onto the display surface 208 by the spatially - aware projector 132 and / or played back on alternative output devices , e . g ., a liquid crystal display ( lcd ) monitor . as the frames are being displayed via spatially - aware projector 132 , the position 1302 indicates the position along the walkthrough path 1300 that corresponds to the current frame that is displayed . additionally , the walkthrough path 1300 and position 1302 may be used as a slide bar and slide bar position interface element , respectively , for the user to navigate a corresponding frame that he or she desires to view . fig1 illustrates an in - place copy / paste technique 1400 according to one or more embodiments of the invention . as described above in conjunction with fig4 , independent input and output allows users to select different parts of the viewport layer 280 and to easily select menu display elements . when the copy and paste feature is activated , the user can use the viewport layer 280 as a clipboard to copy a display element , e . g ., an electrical component 902 , from one location to another within a display surface 208 that includes electrical component 902 , or in another display surface 208 . there are two steps involved when copying an display element from one location of a display surface 208 to another location . the user first copies the display element from the database layer 275 to the viewport layer 280 . then , users paste the display element into the desired location of the user database layer 275 by using in - place copy / paste technique 1400 or displaced copy / paste technique 1500 described in further detail below in conjunction with fig1 . when performing an in - place copy / paste technique 1400 , the object selection occurs within the viewport layer 280 , and the in - place paste can occur from the database layer 275 to the viewport layer 280 thereby , which creates a hyperlink between the virtual display elements . the spatially - aware projector 132 is then repositioned to a desired paste location , whereupon the user can paste the copied display element from the viewport layer 280 to the database layer 275 . fig1 illustrates a displaced copy / paste technique 1500 according to one or more embodiments of the invention . as illustrated , when a display element that lies outside of the projected image 402 is selected , the displaced copy / paste technique 1500 is used . when the display element is selected and copied with the digital pen 135 , its virtual representation is copied to the viewport layer 280 , and an active hyperlink is created as described above . this active hyperlink enables the user to select the display element again using the dominant hand to access a contextual marking menu for the copied display element , where the contextual marking menu is displayed in the viewport layer 280 . selecting a paste submenu display element will paste the display element to the user database layer 275 . display elements can be copied from one layer to another because different contextual marking menus are shown depending on the underlying information layer . for example , if display elements are located in the user database layer 275 , then a menu containing “ copy ” pops up so that the printout database layer 270 can be used as source of copy . similarly , if a display element is located inside the viewport layer 280 , a menu containing “ paste ” pops up . when the user transfers display elements to the viewport layer 280 or to the user database layer 275 , different types of representations can be selected . the user may copy its raw digital representation using a “ shape ” submenu . if the user wants to copy an iconic representation that displays meta - data such as the direction to its original location within the display surface 208 , the user can select an “ icon ” submenu . for error management , users can correct and undo their copy and paste operation using different techniques . in one example , users can select a “ delete ” submenu on display elements in user database and viewport layers . in another example , the user can reposition display elements within the viewport layer using the “ move ” submenu . note that users can either move the digital pen 135 , or move the spatially - aware projector 132 to change the relative location of the display element in the viewport coordinate system . in - place and displaced manipulations are also available in the search functions described herein . when the search feature is activated , the user can execute a search by either writing or clicking the display element to be searched inside the projection area ( in - place ) or outside the projection area ( displaced ). when the user writes the display element to be searched , the pen strokes are gathered and translated into text that the cpu 130 is able to interpret . for example , if the user writes “ wireless ” on a separate display surface 208 , and the projector is placed on top of a display surface 208 that corresponds to a college campus , then buildings with wireless support will be highlighted . if the projector is placed on top of a document , a text bounding box of the search results will be highlighted . if the result is inside the viewport , then the result is simply highlighted with an outline . if the result is outside the viewport , the halo technique may be used as described above in conjunction with fig1 . there are a variety of ways to initiate a search . for example , users can write a keyword , or lasso a phrase already written as part of an annotation , or lasso printed text . the search considers not only the printout database layer 275 but also display elements on the user database layer 275 that the user may have added while during previous interactions with a corresponding display surface 208 . fig1 illustrates a flow diagram of method steps 1600 for performing a copy and paste function according to one embodiment of the invention . the method begins with step 1602 where the user selects the overlay data to be displayed in the projected image 402 . the data may be selected using the projected radial menu 802 . at step 1604 , the application program 112 updates the overlay data in the projected image 402 via the spatially - aware projector 132 . at step 1606 , the user activates a copy mode . at step 1608 , the user selects a region or an element within the display surface 208 or the projected image 402 . at step 1610 , the application program 112 stores in memory within image data 155 an image of the copied region or element . at step 1612 the user selects a paste position within the display surface 208 using the spatially - aware projector 132 . at step 1614 , the application program 112 updates the overlay image to include the copied region or element . at step 1618 the updated overlay image is displayed via the spatially - aware projector 132 , whereupon the user is able to complete the paste function as described above . fig1 illustrates a flow diagram of method steps 1700 for displaying overlay data for a computation according to one embodiment of the invention . the method begins at step 1702 where the user selects a region or element on display surface 208 or within projected image 402 using the digital pen 135 . at step 1704 , the application program 112 obtains the data corresponding to the selected region or element . at step 1706 , the application program 112 performs one or more computations specified by the user . at step 1708 , the application program 112 updates the overlay image to include the computation result . at step 1710 , the updated overlay image is displayed via the spatially - aware projector 132 . the printed content that is visible on the display surface is only one abstract view of a larger electronic file that is stored in the design data 150 within system memory 110 . for example , when a two - dimensional floor plan is printed on the display surface 208 , the digital pen 135 may directly access a highly detailed three - dimensional model that is stored as the design data 150 or image 155 or generated by the cpu 130 or gpu 115 using the design data 150 . a view of the three - dimensional model may be displayed within the projected image 402 that is output by the spatially - aware projector 132 . the printed content that is visible on the display surface is only one abstract view of a larger electronic file that is stored in the design data 150 within system memory 110 . for example , when a two - dimensional floor plan is printed on the display surface 208 , the digital pen 135 may directly access a highly detailed three - dimensional model that is stored as the design data 150 or image 155 or generated by the cpu 130 or gpu 115 using the design data 150 . a view of the three - dimensional model may be displayed within the projected image 402 that is output by the spatially - aware projector 132 . in sum , the spatially - aware projector and digital pen enable the use of virtual ink in addition to conventional physical ink . the virtual ink may be used to capture commands , annotate an existing design , and communicate with a remote user . the virtual ink may be displayed as a projected image on a display surface by the spatially - aware projector . auxiliary design information and rendered images may also be displayed in the projected image . the spatially - aware feature of the projector and digital pen allows for gestures to be interpreted differently based on the position of the spatially - aware projector and digital pen in a given space . as a result , paper is no longer just a static source of data , but it is also used as the display surface and a dynamic workspace . virtual ink benefits the user by providing visual feedback without permanently modifying the physical display surface . the spatially - aware projector and digital pen enable a user to interact with the design more efficiently and intuitively . while the foregoing is directed to embodiments of the present invention , other and further embodiments of the invention may be devised without departing from the basic scope thereof . for example , aspects of the present invention may be implemented in hardware or software or in a combination of hardware and software . one embodiment of the invention may be implemented as a program product for use with a computer system . the program ( s ) of the program product define functions of the embodiments ( including the methods described herein ) and can be contained on a variety of computer - readable storage media . illustrative computer - readable storage media include , but are not limited to : ( i ) non - writable storage media ( e . g ., read - only memory devices within a computer such as cd - rom disks readable by a cd - rom drive , flash memory , rom chips or any type of solid - state non - volatile semiconductor memory ) on which information is permanently stored ; and ( ii ) writable storage media ( e . g ., floppy disks within a diskette drive or hard - disk drive or any type of solid - state random - access semiconductor memory ) on which alterable information is stored . such computer - readable storage media , when carrying computer - readable instructions that direct the functions of the present invention , are embodiments of the present invention . in view of the foregoing , the scope of the present invention is determined by the claims that follow .
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referring now to the drawing , and in particular to fig1 to 4 , there is illustrated a protective shield assembly of the present invention , generally indicated as 10 , and comprised of semicylindrically - shaped half sections or sleeve members 12 and 14 hingeably mounted to one another by hinge members , generally indicated as 16 . the hinge members are comprised of half hinge elements 18 and 20 mounted , such as by welding , to the respective semicylindrically - shaped half sections or sleeve members 12 and 14 and maintained in hinged relationship by hinge pin 22 . the protective shield assembly 10 is formed with a securing assembly , generally indicated as 24 , and comprised of a looped strap 26 including a buckle 28 , mounted such as by rivets 30 to the member 12 , and by a strap 32 mounted , such as by rivets 34 to the member 14 . proximate the ends of the protective shield assembly 10 and mounted to inner surfaces of the members 12 and 14 , such as by welding , there are provided inwardly - extending arm members 36 . a semicircularly - shaped support member 38 is mounted to paired arm members 36 in a manner to engage the leg of the animal , such as illustrated in fig4 . the semicircularly - shaped support members 38 are preferably formed of a metal or plastic overlayed with a protective outer layer of a resilient material , such as rubber , foamed rubber of the like . the members 12 and 14 may be formed of a metal , such as aluminum or stainless steel , or may be formed of a thermoplastic material , such as polycarbonate or like plastic material having physical properties to withstand the effects of gnawing or chewing by the animal . it will be understood by one skilled in the art that the hinge assemblies 16 , buckle assembly 24 , arm members 26 , etc . are secured to the members 12 and 14 by means compatible with the materials of construction of the members 12 and 14 . additionally , while the semicylindrically - shaped members are illustrated as being formed of a curved surface , the surface may be corrugated or formed of a plurality of planar surfaces . still further , while a universal protective shield assembly would be desirable for any size animal , the protective shield assemblies of the present invention are made in varying lengths and of varying spacial distances between the support member 38 and the members 12 and 16 . in operation , the injury to the animal is first cleaned and treated with an antiseptic material and a normal active treatment protocol performed whereupon the protective shield assembly 10 of the present invention is caused to be encircled about the treated area of the leg of the animal in a manner such that the treated area is positioned between the semicircularly - shaped support members 38 , i . e . out of contact with the treated area to minimize aggravation to the injury wound . the strap 32 is positioned within the buckle 28 and drawn fast to a point whereby the force between the support elements 38 and the leg of the animal is sufficient to maintain the protective shield assembly 10 of the present invention at the desired position but with a support force that is insufficient to cause discomfort to the animal or to aggravate the treatment protocol by reducing circulation to the injury or wound . while the invention has been described in connection with an exemplary embodiment thereof , it will be understood that many modifications will be apparent to those of ordinary skill in the art and that this application is intended to cover any adaptation or variation thereof ; therefore , it is manifestly intended that this invention be only limited by the claims and the equivalent thereof .
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in various embodiments as illustrated in fig1 - 5 , a distributed system of sensor elements , communication nodes , and a central reporting application server communicate to monitor statistics of electrical conductors . in one embodiment , an electrical conductor is a transformer or a power line ; however , it should be appreciated that an electrical conductor is any suitable electrical device . a sensor element is a device that connects to an electrical conductor to be monitored . a communication node is a device that receives messages and data from the sensor elements , aggregates the data , and relays it to either another communication node , out to a network connection ( e . g , a lan or wan network ), or broadcasts an alert if needed . the central reporting application server receives messages from the communication nodes directly , or through an intermediate network connection ( e . g ., a lan or wan connection ). it should be appreciated that the above elements are not required and / or can be replaced by any suitable element configured for any suitable purpose . referring to fig1 , in one embodiment , a plurality of sensor elements 100 a - 100 c are each connected to an electrical conductor to capture and record at least one statistic of the monitored electrical conductors 105 a - 105 c ( e . g ., peak voltage of the electrical conductors 105 a - 105 c or any other suitable function or operating characteristic of the monitored electrical conductors 105 a - 105 c ). the sensor elements 100 a - 100 c are also configured to communicate with a communication node 110 ; however , it should be appreciated that the sensor element can be configured to communicate with any suitable device . more specifically , the sensor elements 100 a - 100 c are configured to transmit at least one message to the communication node 110 regarding the at least one recorded statistic of the monitored electrical conductors 105 a - 105 c . the communication node 110 is configured to transmit any received messages from the sensor elements 100 a - 100 c to a central reporting application server 120 . in one embodiment , as illustrated in fig2 , sensor element 200 includes a plurality of components . in one embodiment , sensor element 200 includes a processor 210 component for handling computing tasks such as processing captured data of a monitored electrical conductor and writing the captured data to a storage device . the processor 210 can also handle or assist in other processing tasks of the sensor element 200 such as communicating with a communication node . it should be appreciated that the processor can be configured to process any suitable task or assist other sensor element 200 components in completing processing tasks . in one embodiment , sensor element 200 includes data storage 220 for storing collected electrical conductor data for long term and / or short term storage . the data storage 220 can be static ram , dynamic ram , optical storage , or any other suitable storage component . it should be appreciated that sensor element 200 may not include any long term storage and immediately forward any captured statistical data to a communication node . in one embodiment , sensor element 200 includes and energy collection component 230 and an energy storage component 240 . the energy collection component 230 and energy storage component 240 can harvest electrical energy from the electrical conductor being monitored for data collection purposes and to provide at least part or all of the power requirements of the sensor element 200 . alternatively , sensor element 200 can receive electrical power from electrical outlets , solar panels , or from any other suitable source . in one embodiment , sensor element 200 includes an electrical conductor monitoring interface component 250 . the electrical conductor monitoring interface component 250 enables the sensor element to connect to the electrical conductor to measure at least one statistic of the electrical conductor ( e . g ., temperature or peak voltage ). sensor element 200 may also use the electrical conductor monitoring interface component 250 to draw electrical power to provide the power requirements for sensor element 200 . it should be appreciated that electrical conductor monitoring interface component 250 can include any number of suitable components for measuring any desired feature of the connected electrical conductor . it should also be appreciated that electrical conductor monitoring interface component 250 may include a plurality of different components for measuring a plurality of features of the connected electrical conductor simultaneously or asynchronously . in one embodiment , sensor element 200 also includes a communication interface component 260 . the communication interface 260 may include hardware or software to connect to a local wireless network or to a hard wired ethernet connection , enabling communication with a communication node . however , it should be appreciated that the communication interface 260 can be any suitable network interface for connecting to any suitable network . it should also be appreciated that communication interface 260 can also be configured to connect to any suitable device ( e . g ., devices other than a communication node in one embodiment ). in one embodiment , the communication node may comprise an ibm or macintosh compatible personal computer that includes components ( e . g ., a general purpose cpu , data storage , graphics card , os , application programs , etc .) that enable it to function as a general purpose personal computer in addition to performing functions of the communication nodes . however it should be appreciated that the communication node may include any suitable set hardware and software components that are focused on receiving and forwarding sensor element messages to a central reporting application server to minimize the cost of the communication node . in one embodiment the central reporting application server may comprise an ibm or macintosh compatible personal computer , a workstation , a mini - computer , a mainframe , or other types of computers having at least a microprocessor , disk storage and some memory for processing . in one embodiment , the central reporting application server may also comprise a nc ( network computer ) in which there is no disk for storage , or a nc operating in a cloud computing environment where data computation and analysis tasks are distributed and shared over a plurality of computers of the same or different configuration . in one embodiment , when current is flowing through the monitored conductors , the sensor elements each harvest electrical energy , and periodically transmit a short status message to a nearby communication node ( e . g ., a communication node with communication range ). the status message may be as short as an identifier , or it may also include information such as a peak or real - time current reading , conductor temperature , etc . the communication node receives these messages , and relays them to other nodes , relays them back to the receiving central reporting application server through a lan / wan interface , or broadcasts an alert . in one embodiment , a broadcasted alert can be sent directly to a user ( e . g ., a technician ) through email , sms , audio voice alerts sent through the pstn or cellular networks , or through any suitable communications method . alternatively , the communication node may aggregate the status reports , and transmit a single status message or measurement , instead of transmitting each individual message or reading . one process for monitoring electrical conductors is illustrated in fig3 . at step 300 a sensor element monitors a connected electrical conductor and captures at least one statistic of the connected conductor ( e . g ., the conductor &# 39 ; s peak voltage , open circuit conditions , etc .). at step 310 , the sensor element transmits the at least one captured statistic to communication node located with communication range after a predetermined amount of time . at step 320 , the communication node receives the at least one transmitted electrical conductor statistic from the at least one sensor element . at step 330 , the communication node transmits the at least one received electrical conductor statistic to a central reporting application server after a predetermined amount of time . in one embodiment , the communication node may transmit the at least one received electrical conductor statistic to a central reporting application server after collecting a predetermined amount of electrical conductor statistical data . in one embodiment , the sensor elements are self - contained , and powered by the current flowing through the monitored electrical conductor . in this embodiment , the power may be harvested by using a magnetic coupling , or through a rogowski coil and specialized power harvesting circuitry . alternatively , the ambient electric field may be used with capacitive coupling , or with a mechanical harvesting system to utilize the 60 hz vibration of the conductor . a battery or line powered version is also possible , or even an rfid - style system where the communication node broadcasts a burst which powers the sensor element during the sensor read and transmission . a hybrid or mixed approach is also possible . in one embodiment wherein the sensor element is self powered , the sensor element accumulates energy from the monitored electrical conductor . when enough energy for a transmission has been gathered ( or the periodic transmit time has occurred ), the element broadcasts a short status message to all available communication nodes in range . this broadcast can be a low power rf or vlf burst , but can also be another communication means , such as power line carrier , infrared , sonic , or any other suitable device or method . in one embodiment , the status message can minimally contain enough information for the communication node to determine that the monitored conductor has not failed ( e . g . just the sensor unique identifier , either a globally unique identifier , or unique within range of the communication node ); however , the status message is not required to include such minimal information and can include any suitable information . if the sensor element is powered by drawing power from the current through the conductor , then the reception of the signal itself is an indication that the conductor is still functioning . additionally , the sensor element may harvest enough energy to actually measure the electrical current through the conductor , or may be able to estimate this current based on the energy level harvested , or the time required to harvest a certain amount of energy . this information may also be sent to the communication node , or the communication node may be able to estimate this based on a received signal power level , a time between message bursts , or other signal characteristics which may be correlated ( intentionally or as a side - effect of the sensor element operation and construction ) with the electrical conductor current . in various embodiments , the minimum energy harvest time or the received signal strength is highly correlated with the monitored current , and can be used to estimate the conductor current . the conversion to actual amperes of current may occur later , based on after - the - fact conversion factors , or may be used to indicate changes in current , rather than absolute current levels ( e . g . to indicate increased conductor loading over a period of time ). in one embodiment wherein the sensor element is self - powered , a failure to receive a sensor element status message in a predetermined amount of time indicates a likely monitored conductor failure , and would generate an alarm condition . additionally , in one embodiment , either the communication node or the central reporting application server can track the periods of time between receipt of the sensor element status message . in one embodiment , a single sensor element can be configured to monitor multiple electrical conductors . in one such embodiment , any one or more of the electrical conductors may provide power for the element , but each individual electrical conductor is monitored for current flow or any other desired statistic as discussed above . in one embodiment , to increase redundancy and reliability , multiple sensor elements may be used to monitor the same electrical conductor . in one such embodiment , the communication node may be programmed to declare an alert if all sensors on the same conductor indicate a conductor failure ; however , the communication node can be programmed in any suitable manner . in another such embodiment , a first sensor element can be configured to monitor a first electrical conductor ; however , the first sensor element can be connected to a second electrical conductor to serve as a backup sensor element for the second electrical conductor . if a second sensor element monitoring the second electrical conductor malfunctioned or failed , the first sensor element can be configured to monitor both the first electrical conductor and the second electrical conductor . in one such embodiment , a sensor element can be configured to serve as a backup monitor for any suitable number of electrical conductors . the sensor element broadcast times are timed to optimally reduce interference from each other in various embodiments . in one embodiment wherein the sensor element is self - powered , the energy harvest time can factors into the broadcast timing , since enough energy must be harvested to transmit a message . however , it should be appreciated that the sensor element can be configured to communicate with communication nodes and / or the central reporting application server using any suitable communication protocol . thus , in some embodiments , a communication protocol can eliminate or reduce the need to configure the timing of the sensor elements broadcasts . in one embodiment , the communication node contains suitable circuitry and hardware components to send and receive messages from one or more types of sensor elements . these messages may be sent directly through a network or other concentrator device , where they eventually end up at the central reporting application server . alternatively , the communication node may rebroadcast received messages and electrical conductor statistics data to other nearby communication nodes ( e . g . communication nodes within range of bluetooth , wifi , a direct ethernet connection , or any other known short range communication protocols ), distant communication nodes ( e . g ., communication nodes beyond the range of bluetooth / wifi / ethernet that may require longer range communication protocols such as wimax , ppp , atm , fddi , various cellular standards , or any other suitable long range communication protocols ), or broadcast using low - power fm / am broadcast bands or other suitable communication protocols directly to users . in one embodiment where the communication node includes features of a general purpose personal computer , the communication node can be configured for tasks beyond aggregating data and routing the data to the central reporting application server . in one such embodiment , the communication node can be configured to aggregate electrical conductor statistics received from one or more sensor elements and analyze the data for more specific reporting purposes . for example the communication node can be configured to generate a report that the average temperature over a period of time is greater than the tolerances of the electrical conductor which requires the electrical conductor to be replaced because failure is imminent due to the environment conditions . thus , in one such embodiment , reporting and analysis of the electrical conductor data can be shared with central reporting application server . it should be also appreciated that the communication node can also be configured to directly send alerts to end users ( e . g ., technicians ) detailing the communication node &# 39 ; s analysis of the electrical conductor data . in one such embodiment , the communication node can be configured to communicate with end users through a pstn , sms , cellular links , email , or any other suitable communication channel . in one embodiment as illustrated in fig4 , the monitoring system is deployed in an underground network grid . in one such embodiment , a vault such as vault 400 a or vault 400 b is positioned underground at least at every city block . each vault 400 a and 400 b includes a plurality of sensor elements 405 a - 405 f , wherein each sensor element 405 a - 405 f is connect to at least one electrical conductor ( not shown ). in one embodiment , due to the self - contained nature of the sensor elements 405 a - 405 c located in vault 400 a , sensor elements 405 a - 405 c do not require wiring for communicating with communication node 410 a , which is a significant advantage over other methods due to shorter installation times and reduced material costs . in one embodiment , each vault can be configured with wireless communication between sensor elements and the communication node . however , as illustrated in vault 400 b , sensor elements 405 d - 405 f can be hard wired to communication node 410 b for communication purposes . thus , it should be appreciated different vaults can be configured with different communication methods as is deemed appropriate based on costs and engineering requirements . furthermore , in one embodiment , each vault can be configured with at least one communication node ; however any suitable number of communication nodes can be present in a vault . in one embodiment , within the vault , sensor elements 405 a - 405 c and 405 d - 405 f send messages to the communication nodes 400 a and 400 b respectively . the communication nodes 400 a and 400 b relay the messages upstream to a central reporting software application server 430 . the relay communications method may be powerline carrier based ( e . g . hazeltine , turtle , opera , homeplug , insteon , etc . ), rf ( e . g . bluetooth , wifi , etc . back to a lan ), or any other suitable method . in one embodiment , additional reporting software application servers may be incorporated into the system depending on the number of vaults being monitored . thus , different vaults may be configured to send messages to different central reporting application servers . in one embodiment as illustrated in fig5 , communication nodes can be connected to other communication nodes to form a mesh network . in one embodiment , a communication node may monitor different numbers of sensor elements at different monitored sites . in one such example as illustrated in fig5 , communication node 510 a receives messages from sensor elements 500 a - 500 c ; communication node 510 b receives messages from sensor elements 500 d and 500 e ; communication node 510 c receives messages from sensor element 500 f ; and communication node 510 d receives messages from sensor elements 500 g - 500 j . in this embodiment , communication node 510 a is connected to the central reporting application server 520 and to communication node 510 d ; communication node 510 b is connected to central reporting application server 520 and to communication node 510 c ; communication node 510 c is connected to communication node 510 b and communication node 510 d ; and communication node 510 d is connected to communication node 510 c , communication node 510 a , and to central reporting application server 520 . in this example configuration , communication nodes 510 a - 510 d can be configured to transmit the received messages ( or aggregated messages ) to other nearby communication nodes that are then relayed to the central reporting application server 520 forming a mesh network ( e . g ., any one or more of the communication nodes 510 a - 510 d can serve as a message aggregator that communicates directly with the central reporting application server 520 ). in one example of the mesh network , if the link between communication node 510 a and central reporting application server 520 becomes unusable , communication node 510 a can route messages through communication 510 d to central reporting application server 520 . in one embodiment , the underground vault communication nodes ( as described in connection with fig4 ) can also be configured to form a mesh network . in one embodiment , certain vaults also optionally contain more advanced communication nodes , or other communication / data concentrators , that relay messages out of the mesh and onto a lan / wan for transmission back to the central reporting application server . optionally , programming / configuration data for any of the communication nodes 510 a - 510 d and / or the sensor elements 500 a - 500 j may be sent through the mesh network to change at least one device parameter , programming setup , silence alarms , etc . it should also be appreciated that each communication node 510 could be connected to the central reporting application server 520 and each communication node 510 could be connected to one or more communication nodes , or not connected to any communication nodes . sensor element and communication node parameters may be programmable in various embodiments . for example , the sensor element status message contents , energy harvesting / collection parameters , etc . may be software or hardware selectable . the communication node relay and aggregation logic , etc . may also be programmable . additionally , the communication node may log all received sensor element transmissions , especially if they contain measurement data such as current level , or log date / time stamps of alert conditions ( e . g . failure of sensor element to broadcast , which indicates that a monitored conductor failed ). the recording parameters may also be set in the communication node . the communication nodes may be programmed with information about the sensor elements within range ( e . g . in the same vault ), or preferably , it may automatically add sensor elements . in the latter case , when the communication node receives messages from a sensor element , it automatically adds the transmitting sensor element to an internal list of monitored sensor elements . thus , once the sensor element is added to the list of monitored sensor elements , if the communication node fails to receive a timely status message from the sensor element , an alert condition is triggered . alternatively , the communication nodes may not relay messages / data to other communication nodes . in one such embodiment , the communication nodes are normally silent , and only broadcast a message if a conductor has failed ( typically indicated by the failure of a sensor element to send a message within a specified amount of time ), or a limit has been reached . this broadcast may be through a low power radio transmitter , or indicated by some other suitable alert or annunciator mechanism ( e . g . visible strobe light , etc .). if low - power fm / am broadcast bands are used , users may use a standard broadcast fm / am radio receiver or other suitable receiver for “ drive - by ” reception of vault communication node prerecorded or constructed voice messages . in various such embodiments , there may not be a central software system . status data may be automatically recorded during the drive - by a suitable receiver system , and transmitted to the central software when back in the office , or relayed immediately by an in - vehicle system such as cell phone or other wan connection . a combination of communication node types may be used , or a single node may incorporate more than one of these methods . it should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art . such changes and modifications can be made without departing from the spirit and scope of the present subject matter and without diminishing its intended advantages . it is therefore intended that such changes and modifications be covered by the appended claims .
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the process according to the invention and certain aspects of its industrial application are described in the following examples . however , the process according to the invention is by no means restricted to these examples . thus , the strains according to the invention can be cultured on low - cost media , in particular using as carbon - containing culture substrate hexadecanes or gas oils ( which enables paraffin to be extracted from gas oils ) or even using lactoserum as the complete medium . these examples illustrating the application of the process according to the invention were all carried out with the strain r 312 lodged in the collection de la chaire de genetique de l &# 39 ; ecole nationale superieure agronomique de montpellier , and also at the centraal bureau voor schimmelcultures ( holland ) under the number cbs 717 - 73 . these examples are particularly intended to illustrate the non - specificity of the strains selected , and it is for this reason that they were all carried out with the strain r 312 , although almost all the strains selected are capable of the hydrolyses described hereinafter . the strain r 312 is cultured on a medium containing glucose as carbon source . after culture , the cells are centrifuged , washed with a physiological salt solution and then suspended in the reaction medium consisting of a 10 % by weight solution of lactonitrile obtained by chemical synthesis . the ph - value is adjusted to 8 with potash or ammonia . the bacterial cells , representing approximately 20 to 40 g of dry material per liter , completely hydrolyzed the nitrile over a period of 2 to 3 hours with stirring at a temperature of 25 ° c . they are then eliminated by centrifuging . the supernatant liquid contains ammonium lactate which can be recovered in a quantitative yield by drying . this product may be used as such , because its applications are numerous , for example as an antiscaling agent in washing solutions . the lactic acid can also be recovered in a quantitative yield by methods known per se . for example , acidification may be followed by continuous extraction with ethyl ether or with any other suitable organic solvent . the lactic acid thus recovered is suitable for use , for example in the food industry and in the chemical or pharmaceutical industry . in this process , lactonitrile is synthesised in situ by the action of an aqueous acetaldehyde solution on an aqueous solution of hydrocyanic acid in exactly the same molar concentrations as above . the ph - value of the solution is adjusted to approximately 5 by the addition of concentrated ammonia in order to start the reaction . in a second stage , the ph - value of the solution is adjusted to 8 by the addition of ammonia , the bacterial cells are suspended in the medium in a quantity of 20 to 40 g of dry material per liter , and hydrolysis carried out over a period of 2 to 3 hours in the manner described in the preceding example . as in the preceding examples , the strain r 312 is cultured on a medium containing glucose as carbon source . after culture , the cells are centrifuged , washed with a physiological salt solution and then suspended in the reaction medium which is a 6 % aqueous solution of glycinonitrile ( in hydrochloride form ). the ph - value of the solution is adjusted to approximately 8 by adding potash or ammonia . the bacterial cells , representing from 60 to 80 g of dry material per liter , completely convert the nitrile into acid over a period of about 5 hours at a temperature of 25 ° c . the ph - value is kept at about 8 for the first hour and at ph 7 for the next 4 hours . the cells are then eliminated by centrifuging . glycine is then precipitated from the solution obtained by reducing the solution to 1 / 5th of its volume and by adding methanol in the absence of heat . the strain r 312 is cultured on a medium containing glucose as carbon source . after culture , the cells are centrifuged , washed with a physiological salt solution and then suspended in a reaction medium consisting of a 5 % by weight aqueous solution of α - aminopropionitrile hydrochloride . the ph - value is adjusted to 8 and kept at that level for 2 hours . the bacterial cells , representing 20 to 40 g of dry material per liter , completely hydrolyze the solution over a period of 2 to 3 hours with stirring at a temperature of 25 ° c . after the cells have been eliminated by centrifuging , the solution contains approximately 40 g of α - alanine per liter which is recovered by known techniques . the strain r 312 is cultured and recovered in the same way as described above . it is suspended in a reaction medium consisting of a 5 % by weight aqueous solution of amino - 3 - propionitrile . the ph - value is adjusted to 8 and is kept at that level for 30 minutes . the ph - value is then reduced to 7 and kept at that value for 5 hours with stirring at a temperature of 25 ° c . the bacterial cells , representing 60 to 80 g of dry material per liter , completely hydrolyze the solution under these conditions . after the cells have been eliminated by centrifuging , the solution contains approximately 60 g per liter of β - alanine which is recovered by known techniques . the strain r 312 is cultured and recovered in the same was as described above . it is suspended in a reaction medium consisting of a 6 % by weight solution in water of α - amino - γ - methyl thiobutyronitrile sulphate . the ph - value is adjusted to 8 . the bacterial cells , representing 20 to 40 g of dry material per liter , completely hydrolyze the solution after 3 hours with stirring at a temperature of 25 ° c . after the cells had been eliminated by centrifuging , the solution is reduced to 1 / 3rd of its volume and adjusted to ph 7 . the methionine precipitates . the yield is of the order of 80 %. as in example 2 , α - amino - γ - methyl thiobutyronitrile can be prepared in situ from methylmercapto propion aldehyde , ammonia and alkali cyanide used in stoichiometric proportions . on completion of the reaction , the bacteria are suspended . the further procedure is then as in example 6 . some remarks should be made on the reaction equilibria prevailing in view of the toxicity of the cyanides . in cases where hydrolyzed nitrile participates in an equilibrium with hydrocyanic acid : on the one hand , the constants measured are very favorable to the nitrile in every case . on the other hand , the hydrolysis reaction displaces the equilibrium towards the disappearance and complete utilisation of the cyanide present in the medium . nevertheless , the concentration of cyanide in the starting products has to be finally checked in order to avoid any accidents ( unfavorable stoichiometric proportions at the outset always being possible ). accordingly , it is possible by this process to hydrolyzed a large number of nitriles under mild conditions from a simple reaction medium , and to obtain extremely pure compounds in substantially quantitative yields .
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the novel administration and treatment means of the invention results from knowledge of a parasitic nematode , the ascaris roundworm life cycle in human beings , as detailed below . ascaris lumbricoides is one of the largest and most common parasites found in humans . the adult females of this species can measure up to 18 inches long ( males are generally shorter ), and it is estimated that 25 % of the world &# 39 ; s population is infected with this nematode . the adult worms live in the small intestine and eggs are passed in the faeces . a single female can produce up to 200 , 000 eggs each day . about two weeks after passage in the faeces the eggs contain an infective larval or juvenile stage , and humans are infected when they ingest such infective eggs . the eggs hatch in the small intestine , the juvenile penetrates the small intestine and enters the circulatory system , and quickly the juvenile worm makes its way to the capillaries of the lungs . in the lung capillaries the juvenile worm secrets proteolytic enzymes from its mouth . these enzymes act upon the cells of the capillary wall . the wall ultimately breaks down and the worm is able to move across the blood - air barrier into the lung . the juvenile worm then migrates up the air passages into the pharynx where it is swallowed , and once in the small intestine the juvenile grows into an adult worm . examples of specific worm proteases include the strongyloides stercoralis — the larvae of this nematode parasite can move through tissue at speeds of up to 10 cm per hour . this nematode larvae secrete a potent histolytic metalloprotease to facilitate the rapid migration . this protease has elastase activity and catalyses the degradation of a model of dermal extracellular matrix . ascaris suum , in the tissue - invasive infective and lung stage larvae release proteinases . specifically , this activity contained multiple proteolytic enzyme activities , particularly chymotryptic , tryptic collagenolylic and elastolytic activities . the novel administration means of the invention employs the method of blood - air barrier movement exhibited by the worm . the active agent , which in the examples considered here , is useful in treatment of cystic fibrosis , is brought into the vicinity of the lung capillary and , with the excretion or otherwise application of proteases , is able to cross the boundary into the lung . it will be appreciated by one skilled in the art that although this discussion is primarily concerned with cystic fibrosis the novel administration method of the invention may well be used to treat other lung conditions as it allows a cell or a treatment species access to the lung . in the case of cystic fibrosis the “ treatment species ” is one or more cells having normal cftr production . in other applications the treatment species may be other drugs ( anticancer , asthma drugs etc ) or other chemical or biological bio - actives for which will have some effect in the lung . an essential process in the invention is access of the treatment species into the lung via access to the lung epithelia . the result could be incorporation of the treatment species ( or a derivative ) into the epithelial layer as is the case with cftr functioning cells . alternatively access to the lung epithelia of the treatment species could result in access through the epithelia by disruption or otherwise , of the treatment species into the lung itself . the “ active agent ” contemplated here is cellular material from a suitable mammal donor . more specifically it may take one of ( but is not restricted to ) three forms : i ) human cells in which the cftr protein is present ( in other words , the chloride pump is functioning ); ii ) porcine cells in which the cftr protein is present ; iii ) human stem cells . the cells are administered in the form of a biological delivery device . this is more specifically encapsulated cells , or encapsulated cell clusters . the following outlines our preferred methodology for creation of the device but it will be appreciated other known variations or alternatives for this methodology may also be included without departing from the scope of the invention . cells taken from healthy humans ( not having cystic fibrosis ) cells taken from other suitable mammalian species ( such as pigs ) cells taken from transgenic species not having the defective gene . human stem cells . in our preferred method we prepare clusters of cells which will then be encapsulated . as the size of the overall device is crucial in the method of the invention ( ultimately a device in range 20 - 80 micrometers is desired ) then a cluster of & lt ; 70 micrometers is ( pre - encapsulation ) required to provide this size . we have prepared micro clusters of porcine lung epithelia according to the following method . i . dissection of parenchyma from large vessels and airways of the donor species ii . removal of red blood cells iii . digestion with liberase or similar iv . addition of nutrient media ( including rpmi , nicotinamide , human serum albumin , pig serum , aproxin ) v . removal of gross clumps by filtration vi . segmentation and resuspension in the nutrient medium vii . culture in non - adherent culture dishes ( up to one month ) an example lung cluster prepared by such a method is shown in fig1 . the image is a uv / phase contrast the spheroid being some 60 micrometers in diameter . fig2 illustrates a number of such clusters . our cell transplant work has shown that transplanted cells even from foreign species can be protected from rejection after transplantation without the need to use severe immune suppressing drugs . this is done by coating the cells or clusters of such cells with ‘ micro - capsules ’, which allow the required cell secretion out , and nutrients in but excludes the larger components of the immune system . smaller components can be neutralised by use of nicotinamide - a harmless vitamin derivative . one particular encapsulation process ( as an example ) follows . it employs alginate as an encapsulation material but equally other in vivo similarly behaving materials may be employed . take a population of cells ( or cell clusters ) to be transplanted encapsulate or encase in an alginate coating apply polyornithine coat once more in alginate the proteolytic enzyme may be inserted on top of the polyornithine before application of the second coating of alginate . alternatively it may be mixed with the final alginate coating in the form , for example as gelatin ( or other suitable ) microcapsules . the outermost alginate coating will dissolve relatively quickly in blood of the patient ( for example within 2 days ) to expose the proteolytic enzyme . with particular reference to fig3 , a form of preferred device of the invention is illustrated . in particular we have shown preparation of triple - layered encapsulation lung epithelial structures , as organotypic structures with beaded protease clusters . ( a ) porcine lung epithelia are prepared in modified cell culture media as spheroidal organotypic structures , the spheroid having an outer layer of epithelial cells a lumen filled with liquid . ( b ) a first layer of alginate outside the cells is deposited by calcium gelation . ( c ) the outer surface of the alginate is stabilised with a layer of poly - l - ornithine . preferably the beaded clusters of proteases are deposited with the poly - l - ornithine layer . ( d ) there is an option for a third layer of alginate to cover the protease beads in order to conserve their activity . the delivery mode takes advantage of the circulation system , in particular the venous system . the delivery device is injected into a vein and then moves through the system until it reaches the smaller diameter capillaries of the lungs . as a result of the decreasing capillary size the device will eventually get “ jammed ” or impact in the vessel in the lung . the impaction may also cause compaction of the device . the size of the device is crucial to the working of the invention . it must be large enough to impact in the capillary system within the lung but small enough not to lodge earlier in the venous system . lung capillaries are approximately 7 - 13μ diameter . this lung microvasulative has a diameter less than 100μ . once the device is impacted , via the structure of the outer wall of the device is destabilised and the proteases released such that they come into contact with the capillary wall . the capillary wall will then breakdown admitting the ( residue of ) the device , and specifically the treatment cells . the treatment cells then , come into contact with the epithelial cells inside the lung surface . as has been known in the prior art the similar properties of the treatment cells allow merging of the treatment cells with the epithelial cells to form micro chimaeric clusters within the lung ( a mixture of the two cells types ). ultimately , the human capillary wall reorganises itself whilst the epithelial cells now include treatment cells with a healthy chloride pump activity on the lung wall . with particular reference to fig4 we have illustrated an example of impaction of encapsulated lung structures through blood - air barrier and integration into the patient &# 39 ; s airway structure . in stage one the capsules are injected into a suitable vein , travel in the venous blood to the lung where the narrow capillaries prevent onward movement and the structure is impacted and compressed and the capsule structure compromised . in stage two the outer surface of the capsule structure is sufficiently compromised to release the protease beads that degrade the capillary wall and the basal layer of the airway epithelium , releasing epithelial cells in a focal area in stage three the encapsulated cells are released from the capillary into the epithelial layer where they integrate as a micro - chimaeric group of cells capable of expressing cftr and promoting chloride transport and water secretion . the assimilated cells should start to cause water transport into the lung linings via the chloride pumping system . cystic fibrosis studies have shown you only need & lt ; 1 % of total chloride pumping ability to significantly decrease cystic fibrosis symptoms . administration is via the venous system thus the administered devices may proceed via the capillary system to all areas of the lung . this is an advantage over prior art treatment methods which generally only allow treatment in one specific area . where in the foregoing description reference has been made to elements or integers having known equivalents , then such equivalents are included as if they were individually set forth . although the invention has been described by way of example and with reference to particular embodiments , it is to be understood that modifications and / or improvements may be made without departing from the scope or spirit of the invention .
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persons of ordinary skill in the art will realize that the following description of the present invention is illustrative only and not in any way limiting . other embodiments of the invention will readily suggest themselves to such skilled persons . fig6 shows an embodiment of an inverting flip - flop of the present invention . a function generator circuit is coupled to the data input of the flip - flop via a programmable routing element . the inverting flip - flop includes an inverting multiplexer ( a multiplexer with one of its inputs logically inverted ) in series with its data input signal . the inverting multiplexer causes the output signal from the flip - flop to have the opposite logical polarity from the data input signal . the inverting multiplexer also buffers the data input signal , providing a faster data input signal path than non - inverting flip - flops of the prior art . present in fig6 are function generator 10 , flip - flop 12 , and multiplexers 14 , 16 , 18 , 20 , 22 , 24 , 26 and 30 previously discussed . also present in fig6 is inverting multiplexer 58 which replaces multiplexer 28 of fig4 and complex flip - flop 60 which replaces complex flip - flop 32 of fig4 . the output y of the logic module 10 and the output q of the flip - flop 60 are coupled to programmable routing elements not shown in the drawing figure . inverting multiplexer 58 is shown having an inversion on its data input that is coupled to the output of multiplexer 26 . this indicates a logical inversion in the signal path . correspondingly the input to the data input of complex flip - flop 60 is labeled db in the diagram . fig7 shows exemplary circuit details of complex flip - flop 60 . present in fig7 is flip - flop 12 comprising transmission gates 40 , 46 , 50 and 56 and inverters 42 , 44 , 48 , 52 and 54 previously discussed . also present in fig7 is inverting multiplexer 58 comprising tri - state inverter 62 , transmission gate 64 , and inverter 66 . tri - state inverter 62 has a data input coupled to the db input of complex flip - flop 60 , a non - inverting enable input coupled to the en input of complex flip - flop 60 , an inverting enable input coupled to the output of inverter 66 ( labeled enb in the figure ), and an output coupled to the output of transmission gate 64 and the input of transmission gate 40 ( labeled di in the figure ). transmission gate 64 has a data input coupled to the output of inverter 52 , the input of inverter 54 , and the output of complex flip - flop 60 ( labeled q in the figure ), an inverting enable input coupled to the en input of complex flip - flop 60 , a non - inverting enable input ( labeled enb in the figure ) coupled to the output of inverter 66 , and an output coupled to the input of transmission gate 40 ( labeled di in the figure ) and the output of tri - state inverter 62 . inverter 66 has an input coupled to the en input of complex flip - flop 60 and an output coupled to the internal enb signal . when the en signal is at logic - 0 , inverter 66 drives the enb signal to logic - 1 . this causes tri - state inverter 62 to present high - impedance to node di and causes transmission gate 64 to be open presenting the logic value on the node q to the node di . this corresponds to complex flip - flop 60 being disabled . when the en signal is at logic - 1 , inverter 66 drives the enb signal to logic - 0 . this causes tri - state inverter 62 to drive the complement of the logic value on the node db to node di and causes transmission gate 64 to be closed presenting high impedance to the node di . this corresponds to complex flip - flop 60 being enabled . the presence of tri - state inverter 62 breaks the long chain of pass transistors and transmission gates that can create a substantial amount of rc delay discussed in conjunction with fig5 . tri - state inverter 62 acts as a buffer while only costing the delay of a single gain stage instead of the two gain stages required by a non - inverting buffer . this increases the speed of signal propagation through multiplexers 20 , 26 and 58 and into flip - flop 12 in fig6 relative to the analogous path through multiplexers 20 , 26 and 28 and flip - flop 12 in fig4 . however , tri - state inverter 62 inverts the logical polarity of the complex flip - flop 60 which requires that the design software for an fpga implementing such a circuit have the ability to compensate for the logic inversions that it introduces . persons skilled in the art will realize that many different flip - flop circuits are known in the art and will understand that the choice of the exemplary circuits shown in fig7 is in no way limiting . fig8 a shows , as indicated generally by reference number 62 - a , a first exemplary implementation of the tri - state inverter 62 of fig7 . circuit 62 - a comprises pmos transistors 68 and 70 and nmos transistors 72 and 74 . pmos transistor 68 has a source node coupled to vcc , a gate node coupled to the enb signal , and a drain node coupled to the source node of pmos transistor 70 . pmos transistor 70 has a source node coupled to the drain node of pmos transistor 68 , a gate node coupled to the gate node of nmos transistor 72 and the input node db , and a drain node coupled to the drain node of nmos transistor 72 and the output node di . nmos transistor 72 has a source node coupled to the drain node of nmos transistor 74 , a gate node coupled to the gate node of pmos transistor 70 and the input node db , and a drain node coupled to the drain node of pmos transistor 70 and the output node di . nmos transistor 74 has a source node coupled to ground , a gate node coupled to the en signal , and a drain node coupled to the source node of nmos transistor 72 . when en is at logic - 1 and enb is at logic - 0 , the transistors 68 and 74 are both on and the transistors 70 and 72 act as a cmos inverter passing the logical complement of the signal on db to the node di . when en is at logic - 0 and enb is at logic - 1 , the transistors 68 and 74 are both off and high impedance is presented to the node di . fig8 b shows , as indicated generally by reference number 62 - b , a second exemplary implementation of the tri - state inverter 62 of fig7 . circuit 62 - b comprises inverter 76 and transmission gate 78 . the input of inverter 76 has an input node that is coupled to the db signal and an output node that is coupled to the input of transmission gate 78 . transmission gate 78 has a input node coupled to the output of inverter 76 , a non - inverting enable input coupled to the en signal , an inverting enable input coupled to the enb signal , and an output node coupled to the di signal . when en is at logic - 1 and enb is at logic - 0 , transmission gate 78 is open and passes the logical complement of the signal on db at the output of inverter 76 to the node di . when en is at logic - 0 and enb is at logic - 1 , transmission gate 78 is closed and high impedance is presented to the node di . persons of ordinary skill in the art will realize there are other ways to implement tri - state inverter 62 and the examples chosen in fig8 a and fig8 b are exemplary only and in no way limiting . since the use of inverting fpga flip - flops is unknown in the prior art , it is required that the design software for an fpga implementing such a circuit be adapted to have the ability to compensate for the logic inversions that it introduces . one possible solution would be to let users design using the inverting flip - flop . unfortunately , virtually all fpga designers ( and logic designers in general ) think in terms of non - inverting flip - flops , and trying to force customers to think in an unfamiliar manner is commercially unwise . a more practical approach is to hide the use of the inverting flip - flops inside the design software and then compensate for the logic inversion in the flip - flops while post - processing the end user design . fig9 a shows an illustrative portion of a typical end user logic design to be implemented in an fpga . logic module 80 is shown implementing boolean function a with its output coupled to an input on logic module 82 . logic module 82 is shown implementing boolean function b with its output coupled to the data input of a standard non - inverting flip - flop 84 . flip - flop 84 has a data output coupled to an input on logic module 86 shown implementing boolean function c . fig9 b shows the transformation of the logic design of fig9 a into a logically identical representation . logic modules 80 , 82 and 86 are still present and still implementing boolean functions a , b and c respectively . inverting flip - flop 88 is shown replacing non - inverting flip - flop 84 . the input inversion ( like that of complex flip - flop 60 of fig6 and fig7 ) is indicated by inversion bubble 90 . in order to keep the logic identical , a compensating inversion bubble 92 is shown on the output of logic module 82 . the logical representation of fig9 b is an abstraction created in the design software to realize the end user design in physically available programmable elements . unless , for example , logic module 82 has an inverting output that the interconnect between logic module 82 and inverting flip - flop 88 can be rerouted to , further transformation of the representation of fig9 b is required . fig9 c shows the transformation of the representation of fig9 b into a form that can be physically realized in an fpga . logic modules 80 , 82 and 86 and inverting flip - flop 88 with its inverting data input 90 are still present . however , the boolean function implemented in logic module 82 is now ˜ b which is the logical complement of the original boolean function b . in an fpga which uses look - up tables for function generators this is a very simple transformation . in some fpgas , where different sorts of function generators are used , the transformation can be more complicated if the function ˜ b is not available from logic module 82 . in such cases , the entire logic function implemented by logic modules 80 , 82 and any other logic modules and flip - flops ( not shown ) can be transformed into a boolean equivalent function of a different topology . when designing an fpga with an inverting flip - flop , it is highly desirable to incorporate function generators that work conveniently with the sorts of transformations necessary in the design software used for programming it . fig1 a shows another illustrative portion of a typical end user design . logic module 94 is shown implementing boolean function d with its output coupled to an input on logic module 96 . logic module 96 is shown implementing boolean function e with its output coupled to the data input of a standard non - inverting flip - flop 98 . flip - flop 98 has a data output coupled to an input on logic module 100 shown implementing boolean function g . fig1 b shows the transformation of the logic design of fig1 a into a logically identical representation . logic modules 94 , 96 and 100 are still present and still implementing boolean functions d , e and g respectively . inverting flip - flop 104 is shown replacing non - inverting flip - flop 98 . the input inversion ( like that of complex flip - flop 60 of fig6 and fig7 ) is indicated by inversion bubble 106 . in order to keep the logic identical , a compensating inversion bubble 108 is shown on the output of inverting flip - flop 104 . the logical representation of fig1 b is an abstraction created in the design software to realize the end user design in physically available programmable elements . unless , for example , flip - flop 104 has an inverting output that the interconnect between flip - flop 104 and logic module 100 can be rerouted to , further transformation of the representation of fig1 b is required . fig1 c shows the transformation of the representation of fig1 b into a second logically identical representation . logic modules 94 , 96 and 100 are still present and still implementing boolean functions d , e and g respectively . inverting flip - flop 104 is shown replacing non - inverting flip - flop 98 . the input inversion ( like that of complex flip - flop 60 of fig6 and fig7 ) is indicated by inversion bubble 106 . in order to keep the logic identical , a compensating inversion bubble 110 is shown on the input of logic module 100 replacing the compensating inversion bubble 108 . the logical representation of fig1 c is also an abstraction created in the design software as a means towards realizing the end user design in physically available programmable elements . unless , for example , logic module 100 has an inverting input that the interconnect between flip - flop 104 and logic module 100 can be rerouted to , further transformation of the representation of fig1 c is required . fig1 d shows the transformation of the representation of fig1 c into a form that can be physically realized in an fpga . logic modules 94 , 96 and 100 and inverting flip - flop 104 with its inverting data input 106 are still present . however , the boolean function implemented in logic module 100 is now g ′ which is the logical equivalent of the original boolean function g with an inversion on the input coupled to inverting flip - flop 104 . in an fpga which uses look - up tables for function generators this is a very simple transformation . persons of ordinary skill in the art will appreciate that the examples shown in fig9 a through fig1 d are exemplary and in no way limiting . when transforming boolean functions many different approaches can be taken and other such transformations will readily suggest themselves to such skilled persons . some fpgas have probe circuits which can be used by the end user to monitor logic signals internal to the fpga , primarily for debugging a design . such a scheme is shown in fig1 . shown in fig1 are function generator 10 , complex flip - flop 60 , and multiplexers 14 , 16 , 18 , 20 , 22 , 24 , 26 and 30 previously discussed . the probe circuit comprises nmos transistors 112 and 114 , sense amplifier 116 , probe control circuit 118 , xnor gate 120 , output buffer 122 , and bond pad 124 . nmos transistors 112 and 114 are used to sense the output node q of complex flip - flop 60 . since the gate of nmos transistor 112 is coupled to q , it will be either turned on when q is at logic - 1 or turned off when q is at logic - 0 . signal pen ( for probe enable ) is coupled to the gate of nmos transistor 14 providing the means to enable or disable the probe circuit . nmos transistors 112 and 114 are local to the flip - flop 60 while all other circuits are shared amongst many different flip - flops . sense amplifier 116 is coupled to the drain of nmos transistor 114 . it may be directly coupled to a sense amp at the top of a column of flip - flops , or there may be multiplexing transistors ( not shown ) present to allow sharing the sense amp 116 with many different columns . xnor - gate 120 has a first input coupled to the output of sense amplifier 116 , a second input coupled to an output of probe control circuit 118 , and an output coupled to the input of output buffer 122 . output buffer 122 has an output coupled to bond pad 124 for driving signals off of the fpga integrated circuit device . when the probe circuit is enabled , sense amplifier 116 will amplify the current supplied ( or not supplied ) by nmos transistors 112 and 114 . xnor - gate 120 is used to control the polarity of the signal being sent off chip by output buffer 122 through bond pad 124 . probe control circuit 118 is coupled to a computer running the design software ( through another off - chip connection not shown ) that controls which flip - flop is being probed . since the design software has the programming data available to it , it knows if the polarity of the output signal q of the flip - flop being probed is inverted or not due to the transformations needed to compensate for the use of inverting flip - flops . when using a probe for debugging purposes , the signal stored in a register is a very common thing for the end user to examine . if the flip - flop does not have the expected logic polarity at its output inverted , this can create a very confusing situation for the end user . the most expedient approach is to cancel out the inversions before they leave the fpga at bond pad 124 . in a presently preferred embodiment , all the flip - flop logic modules in the fpga have probe circuits ( though this is not true in all embodiments ). thus the flip - flop 60 is representative of all the flip - flop logic modules in the fpga including flip - flops 84 and 88 in fig9 a through 9c and flip - flops 98 and 104 in fig1 a through 10d . in the example of fig9 a , 9 b and 9 c , the logic sense of the flip - flop 88 is exactly the same as the output of the original flip - flop 84 and no inversion in xnor - gate 120 is needed for probing . however , in the example of fig1 a , 10 b , 10 c and 10 d , the output of the flip - flop 104 is inverted relative to flip - flop 98 and needs to be inverted again in xnor - gate 120 to restore the correct polarity for probing . persons skilled in the art will realize that there are many different ways to build a probe system for an fpga , and that the choice of the circuit presented in fig1 is exemplary only and in no way limiting . while embodiments and applications of this invention have been shown and described , it would be apparent to those skilled in the art that many more modifications than mentioned above are possible without departing from the inventive concepts herein . the invention , therefore , is not to be restricted except in the spirit of the appended claims .
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the present invention will now be described more fully hereinafter with reference to the accompanying drawings , in which preferred embodiments of the invention are shown . unless otherwise defined , all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains . although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention , suitable methods and materials are described below . any publications , patent applications , patents , or other references mentioned herein are incorporated by reference in their entirety . in case of conflict , the present specification , including any definitions , will control . in addition , the materials , methods and examples given are illustrative in nature only and not intended to be limiting . accordingly , this invention may be embodied in many different forms and should not be construed as limited to the illustrated embodiments set forth herein . rather , these illustrated embodiments are provided so that this disclosure will be thorough and complete , and will fully convey the scope of the invention to those skilled in the art . other features and advantages of the invention will be apparent from the following detailed description , and from the claims . with the foregoing in mind , an in vitro dormancy model that can be adapted to drug screening would help to discover antilatency drug candidates . in vitro models suitable for such screening are urgently needed . a number of different stresses have been applied to mtb in vitro in an attempt to generate a dormant state and gene expression changes have been investigated . most of these models involve single stress factors such as oxygen depletion , nutrient deprivation , no treatment and acidic conditions . the gene expression changes during combined nutrient deprivation and 10 % and 0 . 2 % oxygen stress on stationary phase cultures were investigated . some of these stress conditions such as prolonged nutrient starvation caused mtb to become highly rif - resistant but accumulation of storage lipids was not tested . on the other hand hypoxic conditions we used that caused tg accumulation did not develop resistance to 5 μg / ml rif ( unpublished ). the nrp - 1 condition was reported to cause resistance to a lower concentration of rif ( 1 μg / ml ) but lipid accumulation was not tested . we suggest that both rif - resistance and lipid storage are hallmarks of dormancy . since individual stress conditions do not allow the pathogen to fully meet these criteria , we attempted to mimic the in vivo conditions by applying multiple stresses thought to be encountered in vivo by mtb and tested whether the pathogen would accumulate storage lipids and develop rif - resistance . bacilli within granulomas encounter low oxygen ( 5 %) but not hypoxia , high co 2 ( 10 %) concentrations , low nutrient levels and acidic ph . based on these reports , we used 5 % o 2 , 10 % co 2 , ph 5 . 0 and 10 % dubos medium in a multiple stress in vitro model . our preliminary results show that the combination of the four stress factors leads to accumulation of storage lipids ( tg and we ), development of rif - resistance and gene expression changes thought to be associated with dormancy . some of the gene expression changes are similar to those found in the pathogen from infected lungs of hosts , including primates and a human tb patient . both rif - resistance and storage lipid accumulation are associated with dormancy . however , the commonly used in vitro hypoxia model , does not show both of these characteristics . therefore we developed a novel multiple stress model that applies four different stresses that the pathogen is thought to encounter in the host . we grew mtb cultures in low ph ( ph 5 . 0 ), low nutrient ( 10 %) dubos medium without glycerol , with high ( 10 %) co 2 and low ( 5 %) oxygen gas phase . mtb cultures in 10 % dubos ( difco ) medium at ph 5 . 0 at an od 600 of 0 . 2 were maintained under 5 % o 2 + 10 % co 2 + 85 % n 2 by replacing the air phase every other day ; oxygen levels did not change significantly during the two day period . after monitoring the progressive changes that happened to the pathogen , we chose to harvest cells at 3 , 9 and 18 days under such conditions for more detailed studies . these studies included examination of storage lipids , antibiotic ( rif and inh )- resistance , gene expression changes directly relevant to storage lipid synthesis by quantitative real time pcr ( qpcr ), and gene expression profiles by microarray analyses . tlc showed that we and tg accumulated under the multiple stress conditions reaching near maximal levels by 9 days fig1 . the major wax ester was oleyl oleate and the major fatty acids in the tg were c16 and c18 with less c26 ( data not shown ). under these conditions more we accumulated than tg in absolute amounts . control samples at ph 7 . 0 or ph 5 . 0 without additional stress showed no increase in storage lipids . nile red staining revealed storage lipid accumulation under the multiple stress conditions . it is well known that mtb cultures contain a heterogeneous population of cells under different physiological states . as the culture was subjected to multiple stress factors we observed decrease in acid fast staining cells with increasing lipid body staining cells from a barely detectable level to a significant percentage of the total cells by 18 days ( fig2 , 3 ). drug resistance was tested by treatment with 5 μg / ml rif for 5 days followed by serial dilution and plating . by 9 days about 10 % of the cells were found to be rif resistant whereas the starting culture contained about 0 . 03 % rif - resistant cells . rif - resistance increased up to 18 days , sometimes reaching up to 25 % at 5 μg / ml rif . the tgs1 ( rv3130c ) disruption resulted in the loss of rif - resistance which was restored in the complemented mutant ( table 1 ). hypoxic conditions , that were previously found to cause accumulation of storage lipids , did not cause the cells to develop detectable rif - resistance at 5 μg / ml . the tgs1 ( rv3130c ) disruption resulted in loss of tg accumulation under multiple stress . however the complemented mutant showed a level of tg accumulation comparable to the wild type ( fig4 ). gene expression changes directly relevant to storage lipid accumulation were examined by real - time pcr . among all the tgs genes , induction of tgs1 ( rv3130c ) was by far the highest at 9 days under the multiple stress condition , followed by rv3371 and rv3088 ( fig5 ). microarray analysis also indicated upregulation of rv3371 under multiple stress condition ( data not shown ). upregulation of rv3088 probably resulted from the low ph as it has been previously reported to be induced under acidic stress . up - regulation of rv3371 is noteworthy as it was also shown to be up - regulated in human lung granuloma by microarray analysis . the degree of induction of tgs1 ( rv3130c ) was comparable to that of icl and acr ( hspx ), genes previously reported to be induced during persistence . our preliminary experimental results raise the possibility that lipid accumulation under different stress conditions might use different sets of tgs genes . the tigr pathogen functional genomics resource center provided the mtb genome microarray for this study . under our multiple stress condition , genes that encode enzymes involved in glyoxylate cycle such as isocitrate lyase ( acea ) and citrate synthase ( glta1 ) showed significant increase in expression for all time points examined ( fig6 ). from these data we infer that the metabolic regulation of cells adapting to the multiple stresses was similar to that observed in persistent bacilli adapting to the phagosomal environment of a macrophage . under multiple stresses , mtb showed shutdown of both atp / nad energy regeneration systems . while gene expression for anaerobic respiration was continuously increased at the later time points , the aerobic respiration was significantly repressed at all the time points . all the subunits encoding nadh dehydrogenase and the ubiquinol - cytochrome c complex were repressed more than 2 - fold . in addition , the expression of the genes encoding atp synthase subunits was repressed . slowdown of the transcription / translation apparatus was evident during the multiple stresses . many genes related to transcription and translation apparatus were all consistently repressed . genes involved in modification of chromosome and cell division were repressed by the multiple stresses . the expression level of the gene cluster , mas , fad28 , mmpl7 , and ppsa - e , associated with phthiocerol dimycocerosate ( pdim ) synthesis and transport , that was repressed at the beginning of the multiple stress treatment , gradually increased more than two - fold and remained high throughout the period of in vitro multiple stress . further , the mas - like gene pks2 , which is responsible for encoding a hepta / octa - methyl branched fatty acid synthase , was highly expressed . these changes are consistent with the report that dormant cells have thickened walls . we also found significant induction of the genes classified as the stress response genes ( eg . hspx ) that has been suggested to play a role in maintaining long term survival within the host . the gene array analysis results were verified by qpcr analysis of selected test genes . repressed and induced gene transcript level changes indicated by microarray analysis were found to be consistent with the changes indicated by the qpcr method ( data not shown ). we investigated whether the lipid accumulation that occurs as a result of multiple stresses might be reflected in changes in buoyant density . we fractionated the culture on a percoll ® gradient in 10 ml seton easy - seal polyallomer centrifuge tubes with seton noryl crown assembly . this procedure resolved cells based on buoyant density ( fig7 ). the banding pattern changed as the cultures were subjected to multiple stresses for increasing duration . these changes are consistent with the conclusion that application of multiple stresses caused progressive changes in lipid accumulation resulting in increasing percentages of cells in the lighter fractions . auramine - o / nile red staining of the different fractions showed that with increasing periods under the multiple stresses , increasing percentage of cells became lipid - loaded and lost acid - fast staining ( presumably dormant cells ). staining of percoll ® fractions from 18 day stressed cultures showed that the lighter fractions were more enriched in , lipid loaded cells that lost acid - fastness . after this long stress period most cells were in the lighter fractions ( fig7 ). upon percoll ® density gradient fractionation of the 18 - day multiple - stressed culture , the great majority of the cells were distributed in the lighter fractions . when rif - resistance was assessed by the alamar blue dye method the lighter fractions showed a higher percentage of rif - resistant cells ( data not shown ). the small number of heavier cells present in this culture showed rif - susceptibility comparable to that of the starting culture . recent meta - analysis of mtb microarray data from many in vitro and in vivo conditions that are thought to induce dormancy ( murphy and brown , bmc infect . dis . i , 84 - 100 , 2007 ) indicated that a set of genes possibly involved in lipid storage and utilization are highly upregulated . we have determined the transcriptional profile of the genes , selected on the basis of the meta - analysis by real - time pcr using 7500 fast system ( applied biosystem ). detection of transcriptional upregulation of the known dormancy - responsive genes such as hspx , icl and dosr ( fig1 ) is consistent with our conclusion that the multiple stress conditions induce dormancy . seven of the 10 genes in the first priority group , such as rv3130c along with a few other tgs genes ( rv3371 , rv1760 ), a few genes encoding potential hydrolases ( lipx lipy , cut3 ), and fatty acyl - coa reductase gene ( rv3391 ) showed upregulation . three of the 21 genes in the next priority group showed upregulation under the multiple stress condition . one of them showed surprisingly high induction . the other two upregulated genes in this group were cut2 and lipz . only one gene ( rv2285 , a tgs ) in the third priority group showed upregulation . among the tgs products that showed the highest enzymatic activity ( when expressed in e coli ) only this tgs showed a preference for oleoyl - coa . we already have mutant for this gene and this mutant showed the second most impaired ability to accumulate tg under hypoxia as indicated in the preliminary results presented in the application . it is noteworthy that 7 of the 10 genes in the first priority group and 3 out of 21 genes from the second priority group and only one out of 17 in the third priority group showed upregulation . since the prioritization is based on meta - analysis of the degree of their upregulation under a variety of conditions thought to induce dormancy , our results suggest that the multiple stress model reflects real dormancy and adds validity to our approach . the tuberculous granuloma , which is thought to be a hypoxic environment , consists of a core of mtb - infected macrophages surrounded by lipid - loaded macrophages , mononuclear phagocytes and lymphocytes enclosed by a fibrous cuff . the differentiation of macrophages into lipid - loaded macrophages in tuberculous granulomas is a well - documented observation and the secretion of cytokines by the infected lipid - loaded macrophages probably helps to maintain the granuloma . histological studies revealed the presence of lipid - loaded macrophages in the granulomas of immunocompetent and hiv - 1 infected patients with tb . lipid - loaded macrophages contain abundant cytosolic stores of tg and cholesterol esters . a recent study showed that exposure of human macrophages to hypoxia ( 1 % o 2 ) converted them into lipid - loaded cells and m . bovis bcg infection induced the conversion of macrophages into lipid - loaded cells but the nonpathogenic mycobacterium smegmatis failed to induce lipid body formation . thus lipid bodies within mtb - infected macrophages may have important roles in pathogenesis and possibly in latency . human thp - 1 monocytic cell line - derived macrophages ( tdm ) are known to be converted into lipid - loaded macrophages . therefore they can serve as a more convenient experimental model for studies on mtb mutants , because their use can avoid the variability in responses encountered in the use of human peripheral blood monocyte - derived macrophages and provide a readily available uniformly reproducible cell model suitable for high throughput screening of drug candidates . lipid bodies have been found in mtb obtained from patients with active disease . however , the origin of these lipids remains unknown . the pathogen inside the lipid - loaded macrophages might utilize fatty acids derived from the lipid bodies in the host cells to store lipids within mtb for later use . such a possibility was raised by the recent finding that adipocytes might be a home for dormant mtb in humans . in fact , mtb inside adipocytes were found to accumulate lipid bodies while becoming dormant , as indicated by their resistance to killing by drugs . the lipid bodies found in the pathogen from patients probably originate from the lipid bodies in the macrophages . our results indicate that mtb within lipid - loaded macrophages can use the host &# 39 ; s tg to accumulate tg within the pathogen and this mtb becomes rif resistant meeting our criteria for dormancy . herein we disclose a newly developed thp - 1 derived macrophage ( tdm ) system for infection with mtb . thp - 1 cells , differentiated into macrophages by treatment with 100 nm pma for 3 days , were incubated for 3 days in 1 % o2 and 5 % co2 . oil red - o staining revealed lipid droplet accumulation in such macrophages ( fig2 ). when the tdm were infected with mtb at a multiplicity of infection ( moi ) of 1 . 0 for 4 hr and incubated in 1 % o 2 / 5 % co 2 for 3 days , lipid bodies accumulated in the host cells ( fig3 ). mtb cells within the macrophages showed nile red stained lipid bodies ( fig4 ). most mtb cells showed loss of acid fast staining and thus stained only red ; a few showed some acid fast and lipid staining ( yellow ). we modified our experimental protocol to allow for longer incubation of infected macrophages . we infected tdm with mtb at an moi of 0 . 1 ( 1 bacillus per 10 macrophages ) and extended the incubation of the infected tdm to 7 days under hypoxia . after 7 days , infected tdm were lysed and the cell debris was removed by centrifugation at 300 g for 10 min . the mtb cells were pelleted by centrifugation at 3000 g for 10 min and washed . lipids from the host - lipid bodies were extracted from the supernatant and the lipids from the pelleted to analyze fatty acid composition , host or mtb tg was purified by preparative tlc and the methyl esters generated by bf3 / methanol transesterification , were analyzed by capillary gc . the amount of fatty acids from the tg isolated from mtb , recovered for tdm , is more than enough for such gc analysis ( fig6 ) pathogens were extracted . tlc analysis of the lipids revealed that tg in the host cells was markedly increased by incubation under hypoxia for 7 days and the levels of tg were lower in infected tdm under hypoxia ( fig5 a ). lipids extracted from mtb recovered from infected tdm were also analyzed by tlc . we detected increased tg level in mtb cells recovered from tdm incubated under hypoxic conditions ( fig5 b ). the fatty acid composition of the tg from the pathogen was not identical to that of the host tg . c16 : 0 , c18 : 0 and c18 : 1 fatty acids were the dominant components in both the pathogen and the host . longer chain saturated fatty acids ( c24 , c26 and c28 ) that were present in the pathogen tg were absent in the host tg . we conclude that the tg that accumulated in the pathogen probably consisted of fatty acids from the host and some fatty acids generated within the pathogen . gene expression changes occurring in the pathogen within tdm were examined using a two - step real time pcr method . briefly , total rna was isolated and purified from a mixture of mtb - infected tdm using trizol ( invitrogen ) and qiagen rneasy column purification method . total rna was dnase treated twice , purified through qiagen mini elute rneasy column , purity of rna was checked at every step . controls without reverse transcription ( rt ) verified lack of dna contamination . first - strand cdna , synthesized with exo - resistant random hexamers and superscript iii reverse transcriptase ( invitrogen ) was used for multiplex pcr using many mtb gene specific primer sets . all primers and taqman probes were designed using visualomp6 software from dna software , inc ( ann arbor , mich .). the taqman probes have a fluorescein reporter dye ( fam ) at 5 ′- end and a black hole quencher ( bhq ) at 3 ′- end . each multiplex and real - time pcr primer was checked for specificity and efficiency . differences in mtb specific gene transcripts were quantified by real - time pcr on generated multiplex - pcr products with nested taqman primers and probes . the overall reliability and sensitivity of the two - step rt - pcr method to quantify gene expression profiling has been discussed in detail elsewhere . we have thus far done only a subset of genes thought to be relevant to lipid storage and metabolism ( fig7 ); icl was by far the most induced gene , consistent with the idea that the pathogen in tdm grows on fatty acids . it is noteworthy that lipy , that was previously shown by us to be involved in tg mobilization , was highly induced and some of the other lip genes also showed induction . dosr and tgs genes were also induced probably indicating their involvement in the storage of fatty acids derived from host - lipids as tg resynthesized within the pathogen , consistent with our hypothesis . fatp , that might be involved in fatty acid transport into the pathogen was also induced . putative fabp genes also showed some induction . these results indicate that our hypothesis concerning storage and mobilization of host lipids by the pathogen has real validity . we analyzed the resistance of mtb recovered from tdm after a 7 day incubation under 20 % o 2 or 1 % o 2 to rif and inh by cfu determination . tdm were infected with mtb at an moi of 0 . 1 . mtb cells inside tdm were exposed to antibiotic for 2 days prior to lysis of tdm and recovery of the bacilli . the recovered mtb cells were diluted and plated on agar plates without antibiotic and incubated for 4 weeks after which cfus were enumerated . antibiotic resistance is expressed as percentage of control without antibiotic . as indicated in table 2 , mtb recovered from tdm incubated under 20 % o 2 showed resistance to both antibiotics . others have found development of rif resistance in host cells . we found that rif resistance increased significantly in mtb recovered from tdm incubated under 1 % o 2 for 7 days compared to normoxic conditions . these results indicate support for our hypothesis that lipid - loading of macrophages favor the entry of mtb into dormancy . in making further progress developing the macrophage dormancy model , we tested different moi in the lipid loaded macrophage system . we assessed the viability of mtb - infected lipid - loaded macrophages under hypoxia under different moi . at moi 1 . 0 or higher the host cell viability was seriously compromised . at moi 0 . 1 , after 7 days under 1 % o 2 , 40 % of the original tdm population remained intact as an adhered monolayer and were loaded with lipid droplets . about 94 % of these lipid - loaded tdm cells in the adhered monolayer were viable . these results support the notion that these lipid - loaded tdms provide a tg - enriched sanctuary for mtb , favoring its entry into dormancy . we originally suspected that mtb utilizes the macrophage lipid bodies to acquire fatty acids and store them as tg within the pathogen to enable it to go through dormancy . to test this hypothesis , we labeled tdm lipids by incubating the cells with [ 14 c ] acetic acid or [ 14 c ] oleic acid , under 1 % o 2 for 2 days . these cells were washed three times with sterile phosphate - buffered saline ( pbs ) to remove unincorporated radiolabel . thin - layer chromatographic ( tlc ) analysis of the labeled lipids extracted from tdm showed that major part ( about 60 %) of the radioactivity in the lipids derived from labeled acetate and oleate was in tg that accumulated in tdm under 1 % o 2 . these pre - labeled cells were infected with mtb at an moi of 0 . 1 for 4 h under 1 % o 2 . following infection , extracellular mtb were removed by thoroughly washing the tdm monolayer with sterile pbs . infected tdm were incubated for 5 more days under 1 % o 2 . the host lipids and lipids from mtb recovered from the host cells were obtained and the lipids were analyzed by tlc . the fatty acid composition of the mtb and host tg was analyzed by resolving the intact tg and fatty acid methyl esters derived from tg on reversed - phase silica - tlc and argentation - tlc . analysis of intact tg from [ 14 c ] acetate in tdm was composed of saturated and unsaturated fatty acids . however , the tg of mtb was predominantly composed of saturated fatty acids as indicated by greater mobility on agno 3 - impregnated tlc ( fig8 a ). analysis of fatty acid methyl esters prepared from tg isolated from tdm and mtb indicated that the tg of mtb , recovered from tdm labeled with [ 14 c ] acetate , was composed primarily of saturated fatty acids , mostly 14 c - 16 : 0 and a very small quantity of 14 c - 18 : 0 fatty acids ( fig8 b , c ). see also table 3 , below . mtb recovered from [ 14 c ] oleic acid - labeled tdm had tg that was distinctly different in fatty acid composition from the tg in tdm . while the 14 c in tdm tg was predominantly in 18 : 0 ( about 81 % of total fatty acids ), 14 c in mtb tg was mainly in unsaturated fatty acids ( about 70 % of total fatty acids ). the identity of these fatty acids is to be determined . these results clearly indicate that mtb acquires fatty acids from tdm lipid bodies for synthesizing tg as a potential energy source . the tg stored within the pathogen probably includes the fatty acids from the host lipids and fatty acids generated by modification and / or catabolism and resynthesis . the biochemical processes involved can be deduced only after further characterization of the tg that accumulates in the host and in the pathogen . we also postulated that the mtb tgs gene products may be pivotally involved in synthesizing tg within the mtb cell from fatty acids acquired from host tg . to test this hypothesis , we infected the pre - labeled tdm with wild - type mtb and tgs1 ( rv3130c ) deletion mutant ( δrv3130c ) as described in the methods section . about 1 % of the radiolabel in the tg in tdm was found in the tg isolated from mtb . we quantitated the radioactivity in the tg of mtb and δrv3130c recovered from tdm . the results indicate that tg accumulation by the δ3130c was decreased by 90 - 95 % when compared to the wild - type ( table 3 ). these results additionally suggest that rv3130c plays an essential role in the accumulation of tg by mtb within lipid - loaded macrophages . in order to visualize the mtb inside lipid - loaded host cells , infected tdm after 7 days under hypoxia were fixed with 4 % paraformaldehyde and stained for mtb with carbolfuschin followed by methylene blue or hematoxylin and eosin to stain the host cell . mtb inside tdm were also stained with the mycolic acid - specific fluorescent dye auramine - o followed by nile red which stains neutral lipids . interestingly , as seen in fig9 , the mtb - infected tdm which were incubated under hypoxia for 7 days appeared to be fusing together . it is probable that these tdm are in the process of forming multinucleate giant cells ( asterisk in fig9 a ) which are known to be present in the hypoxic environment of the granuloma in close vicinity to lipid - loaded macrophages . these observations support the hypothesis that this lipid - loaded macrophage system is a good model for in vivo latency . individual mtb cells inside tdm that accumulated neutral lipids , as indicated by nile red staining , lost acid - fastness as shown by weak or total loss of auramine - o staining ( fig1 ). conversely , mtb cells which stained strongly with auramine - o did not accumulate neutral lipids . this accumulation of neutral lipids and loss of acid - fastness by a subset of mtb cells within lipid - loaded tdm under hypoxia , correlates well with our data in the preliminary results , that demonstrated the development of rif resistance by about 25 % of the mtb population and increase in tg within mtb from tdm under the same conditions . since then , we have reconfirmed these results with additional experiments . based on these results , the multiple stress in vitro latency model disclosed herein appears to be the best one available for screening chemicals to discover drug candidates that can eliminate latent pathogen . accordingly , in the drawings and specification there have been disclosed typical preferred embodiments of the invention and although specific terms may have been employed , the terms are used in a descriptive sense only and not for purposes of limitation . the invention has been described in considerable detail with specific reference to these illustrated embodiments . it will be apparent , however , that various modifications and changes can be made within the spirit and scope of the invention as described in the foregoing specification and as defined in the appended claims .
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fig1 is a general view of xerographic copier 10 incorporating the present invention ; for example , a copier of the type which is designated as the ibm series iii copier / duplicator . in fig1 fuser assembly 12 is shown in its extended or pulled - out position in front of the copier , and is slidably supported within copier 10 by apparatus shown for purposes of simplicity . this is a nonoperating position adapted to facilitate inspection , cleaning , repair and / or sheet jam clearance . the slidably supported fusing assembly 12 includes a hot roll 14 and a backup roll 16 . generally , hot roll 14 is heated to an accurately controlled temperature by an internal heater 15 , as seen in fig2 and an associated temperature control system which is not shown . hot roll 14 preferably includes a deformable external surface formed as a thin elastomeric surface . this surface is designed to engage the toned side of a copy sheet which has a latent image formed thereon which was first located on a photoconductor surface ( not shown ). this image is transferred from the photoconductor to the copy sheet by first placing toner on the imaged surface of the photoconductor , with the toner adhering to the image formed thereon . next , a suitable transfer means is used to transfer this toned image to the copy sheet . hot roll 14 , acting in concert with backup roll 16 , fuses the image onto the copy sheet and readily releases the sheet with minimum adherance of residual toner to the hot roll . as is conventional in hot roll fusers , the sheet &# 39 ; s toned side faces the hot roll . backup roll 16 is preferably a relatively cool and rigid roll . both rolls 14 and 16 are circular cylinders and the fusing nip formed thereby defines a line ( of some width due to deformation of hot roll 14 ) parallel to the axis of rolls 14 and 16 . the fusing nip formed by rolls 14 and 16 may be opened and closed in synchronism with the arrival and departure of copy sheet leading and trailing edges , respectively . this synchronism is achieved by a drum position sensing means which responds to the position of the photoconductor drum and effects opening and closing of the nip by means of a copier control system ( not shown ). in the alternative , for a multi - copy run , the fusing nip may continuously remain closed until the trailing end of the last sheet has passed therethrough . fig2 shows the fusing nip closed . rigid backup roll 16 is shown to be in contact with resilient hot roll 14 , thereby deforming the surface of hot roll 14 so as to form a fusing nip 18 of a certain width , measured in the direction of sheet movement 19 . feed roller 20 cooperating with idler roller 21 continues sheet movement 19 until a copy passing therethrough is free of fusing nip 18 and has passed through fuser exit - way 22 . in fig3 hot roll 14 is removably , rotationally mounted on a fixed position axis in mounting blocks 23 which are supported by way of positioning surfaces 24 formed in the ends of a single piece mounting main frame member 26 . this main frame member 26 includes a hanger which supports the fuser assembly by way of telescoping rails 30 . frame member 26 also includes rollers 32 , or equivalent sliding bearings , which cooperate with a copier frame member to stabilize the fuser assembly position within the copier . as seen in fig3 and 13 , roll 16 is rotationally supported , on axis 34 , by way of pivoting cradle arms 36 at each end of frame member 26 . these cradle arms are pivoted on the frame member at axis 38 . pivot arms 40 , at each end of main frame member 26 , are pivotably mounted to the frame member by way of pivot 42 . pivot arms 40 have downwardly extending projections 41 which support rollers 44 which cooperate with nip opening and closing cams 46 . the other ends of pivot arms 40 have mounted thereon ends 48 of compressible force - cells 50 . the other ends 52 of force - cells 50 operate on cradle arms 36 to cause arms 36 to rotate clockwise about axis 38 , force cells 50 provide controlled pressure to backup roll 16 through axis 34 , and consequently the pressure to fusing nip 18 is controlled . springs 53 , positioned between hanger 28 and pivot arms 40 , provide an additional opening force to fuser nip 18 . the closing of fusing nip 18 is achieved by cams 46 which are rotationally mounted on axis 38 . these cams include a low point 54 which , when positioned to cooperate with roller 44 , establish a nip - open condition . to close the nip , solenoid 56 is energized and clutch 58 , shown in fig4 - 6 , operates to rotate cams 46 , in fig3 clockwise 235 ° ( counterclockwise if observing fig4 ) to the position shown , causing nip 18 to close . during nip closure , pivot arms 40 ( see fig3 ) rotate counterclockwise causing fixed - position pivot 42 , force - cell pivot 60 and axis 34 to come into substantial alignment . however , pivot point 60 does not move overcenter . thus , subsequent rotation of cams 46 , back to the nip open cam position 54 , as a result of the deenergization of solenoid 56 , allows force - cell 50 to rotate pivot arms 40 clockwise ( when observed on fig3 ) about pivot 42 , opening fusing nip 18 . cams 46 are connected to rotate on axis 38 as long as clutch member 58 ( fig5 and 6 ) is free to rotate . in the deenergized position of solenoid 56 , dog 62 is held against rotation by tab 70 on pivoting link 66 . link 66 is pivoted at fixed position pivot 68 . when solenoid 56 is energized , clutch member 58 and cam 46 are driven 235 ° until dog 62 engages tab 64 . fusing nip 18 is now closed . subsequently , when it is desired to open the fusing nip , solenoid 56 is deenergized , link 66 returns to its deenergized position , and clutch member 58 rotates until it is stopped by tab 70 . fusing nip 18 is now opened . the above - described means for opening and closing the fusing nip is more specifically described and claimed in a copending application , entitled &# 34 ; hot roll fuser roll closure apparatus &# 34 ;, ser . no . 826 , 619 , filed aug . 22 , 1977 , and assigned to the same assignee as the instant invention . in the fragmented portion of fig4 a folded hot roll handle 72 , for manually removing hot roll 14 , is shown . the use of this handle for removing hot roll 14 from the fusing assembly will be explained hereinafter . in fig1 , a manually movable , rod - like handle 74 extends the length of the fuser assembly , parallel to axis 34 . opposite ends of this handle are attached to movable links 76 , at each end of the fuser assembly . in fig7 and 8 it is seen that these links are pivoted on fixed - position axis 78 . both of the links have a notch 80 , and a pivot point 82 for one end of a drive arm 84 . in fig7 links 76 are shown in their operative positions , wherein the hot roll detach bar , 101 of fig2 and the fuser &# 39 ; s output sheet transport channel or exit - way , 22 of fig2 are located closely adjacent the downstream portion of fusing nip 18 , shown closed in fig2 . u . s . pat . no . 3 , 955 , 813 , commonly assigned and incorporated herein by reference , describes this sheet output channel and describes and claims and detach bar . fig1 is similar to fig7 of u . s . pat . no . 3 , 955 , 813 , and shows the pneumatic detach means incorporated within detach bar 101 . fig1 is a view of bar 101 with the leading edges 188 of a copy sheet 189 emerging from fusing nip 18 . the flow of air from nozzle 182 , into the gap formed by hot roll 14 and backup roll 16 , is complex and not completely understood . however , it is believed that air begins to flow tangent to the hot roll , as shown at 190 . it then follows the roll &# 39 ; s contour , rather than flowing in a straight line , due to the well known coanda flow effect . this flow pattern continues until the flow reaches the obstruction created by the fusing nip . this obstruction causes stagnation and lateral division of the airflow . in this stagnation process some of the jet &# 39 ; s kinetic energy is converted to an increase in pressure which propogates upstream toward orifice 182 and causes the jet to separate as shown at 194 . as a result , pressure differentials are created above the sheet . as the leading edge 188 of the copy sheet enters this flow , it is subjected to a force lifting it off roll 14 . in addition , the forward facing step created by the sheet &# 39 ; s leading edge , due to the paper &# 39 ; s thickness , aids in separation of the leading edge by presenting another obstacle to jet flow . in fig7 and 13 , links 88 are pivoted on fixed - position axis 90 . each of links 88 has a projection 92 thereon for holding mounting blocks 23 securely within main frame 26 . links 88 carry locking pins 96 which lock links 88 , and the detach bar 101 , in operative position by virtue of an interface at 98 between pin 96 and pivotable link 100 . links 100 are pivoted on fixed - position axis 102 . the ends of output sheet transport channel 22 are attached to links 106 . these links are pivoted on backup roll axis 34 . axis 34 is not a fixed - positioned axis because during nip closure , axis 34 moves a slight distance downward , as represented by arrow 108 in fig7 . the upper end of links 106 carry a locking pin 110 , cooperating with notch 80 formed in links 76 . the lower end of links 106 carry lower pivot axis 112 for the end of drive arm 84 that is opposite pivot point 82 . in fig8 two tension springs 114 extend between pins 116 carried by links 76 and pins 118 carried by links 100 . the springs provide a closing force between links 76 and links 100 . in addition to providing a closing force between links 76 and links 100 , springs 114 provide a contacting force between pins 96 and pivotable links 100 . the above - mentioned interface 98 is created by these latter two sets of links . in order to move the above - mentioned detach bar and output sheet transport channel out of the way for jam clearance and / or to remove hot roll 14 , the above - mentioned rod - like handle 74 is lifted up and rotated counterclockwise about fixed - position axis 78 , to the position shown in fig8 . this causes the detach bar to generally rotate clockwise about hot roll 14 away from fusing nip 18 , and the output sheet transport channel to generally rotate counterclockwise about backup roll 16 . during such movement , pins 116 on links 76 engage links 100 and cause these links to pivot counterclockwise about their fixed - position axis 102 . as a result , interface 98 , as seen in fig7 created by contact between pins 98 and pivoted links 100 is broken . in fig8 as handle - actuated links 76 continue to rotate counterclockwise , notches 80 free pins 110 . counterclockwise rotation of links 76 transmits counterclockwise rotation to links 106 by virtue of drive arms 84 . as pivot axis 112 moves counterclockwise as represented by arrow 120 in fig7 to its position in fig8 links 106 are pivoted clear of fusing nip 18 . as counterclockwise rotation of links 76 continues , surfaces 122 formed thereon engage locking pin 96 , causing links 88 to rotate clockwise about their fixed - position axis 90 . the detach bar and output sheet transport channel have now been moved out of the fusing nip for manual sheet jam clearance . in addition , link 88 has been pivoted clockwise , eliminating the interface between projection 92 on links 88 and mounting blocks 23 . links 88 can now be manually rotated clockwise , as represented by arrow 124 in fig8 in order that hot roll 14 can be removed from main frame 26 . in summary , interface 98 locks the detach bar in operative position , notch 80 and pin 110 lock the output sheet transport channel in operative position , spring 114 maintains interface 98 , pin 116 lifts link 100 to interrupt interface 98 , counterclockwise rotation of link 76 frees pin 110 and rotates link 106 by virtue of drive arm 84 , and counterclockwise rotation of link 76 rotates link 88 clockwise as a result of interference with locking pin 96 . a jam clearance means of the above - mentioned generic type is described and claimed in copending application ser . no . 771 , 126 , filed feb . 22 , 1977 , now u . s . pat . no . 4 , 110 , 068 , and assigned to the assignee of the instant invention . fig9 shows the fixed center drives for ( 1 ) producing rotation of the fuser &# 39 ; s backup roll 16 , ( 2 ) producing oscillatory movement of the backup roll &# 39 ; s scraping blade cleaner 126 , and ( 3 ) producing rotation fo the fuser &# 39 ; s paper exit guide transport roller 20 . roller 20 is supported by the exit paper transport guides , and engages the non - toner side of a sheet , as the sheet emerges from fusing nip 18 . additional information pertaining to the blade cleaner 126 appears in ibm technical disclosure bulletin , volume 18 , no . 2 , july 1975 , pages 326 - 327 . counterclockwise rotation of backup roll 16 is produced by gear 132 which meshes with continuously driven gear 134 . gear 132 is connected to the backup roll &# 39 ; s axis 34 and causes counterclockwise rotation of this roll . when the fusing nip is being closed or opened , the backup roll &# 39 ; s rotational axis 34 moves in an arc about axis 38 . thus , gear 132 merely rolls about its meshing gear 134 . cleaner 126 is supported by double helix lead screw 138 . this lead screw is driven in a counterclockwise direction by virtue of gears 140 - 142 with gear 140 being fixedly mounted on an end of lead screw 138 , gear 141 being rotatively mounted on fixed axis 144 and gear 142 being fixedly mounted on axis 34 . since all of these gears are carried by cradle arm 36 , a fixed center relationship is maintained during nip opening and closing . as a sheet of newly fused copy paper emerges from the fusing nip , and as it is driven by counterclockwise rotation of backup roll 16 , its leading edge is guided into the output sheet transport channel ( not shown in fig9 ). this sheet channel is supported by pivoting links 106 . links 106 supported at the rear end of the fuser , and shown in fig9 and 13 , carry a pair of gears 146 , 148 which mesh with a gear 150 which is integral with backup roll 16 . counterclockwise rotation of sheet transport roller 20 by gears 146 , 148 and 150 transports the copy paper out of the fusing nip . roller 20 cooperates with idler roller 21 , shown in fig2 to trap the copy sheet therebetween . the idler roller engages the toned side of the copy sheet . when the fuser &# 39 ; s sheet detach bar and output sheet transport channel are manually moved out of the way , as for jam clearance , links 106 rotate in a counterclockwise direction as discussed above with reference to fig7 and 8 . since link 106 pivots about the backup roll &# 39 ; s rotational axis 34 , a fixed center is maintained for gears 146 - 150 , and gears 146 and 148 merely rotate in a circle about gear 150 . consequently , a constant center distance between the gears is maintained and transport roller 20 is driven with minimum backlash by the gearing . the fuser &# 39 ; s main frame member 26 , shown in fig1 and 11 , comprises a central portion surrounding , but spaced from , the surface of hot roll 14 and having upstanding end flanges establishing the various rotational axes of the backup roll and its associated structure . these end flanges include u - shaped slots or positioning surfaces 24 adapted to receive the ends of the reversible hot roll . with reference to fig1 , hot roll 14 is rotationally mounted in rigid u - shaped subframe member 152 which is symmetrically located between positioning surfaces 24 . subframe 152 is locked to main frame 26 and is unlocked therefrom by rotation of rotatable handle 74 . a handle 154 shown folded in fig1 and shown extended in fig1 , is mounted on the central portion of subframe member 152 . each end of the not roll is supported for substantially frictionless rotation in metal end blocks 23 . end blocks 23 each have a stub shaft which fits into bearings at both ends of hot roll 14 . hot roll 14 is easily replaceable because metal end blocks 23 are removable from subframe 152 . these end blocks are substantially identical , the only exception being that one end block cooperates with a helix compression spring 160 which axially biases hot roll 14 towards the other end block for retention purposes . end blocks 23 nonrotationally support heating element 15 , as also seen in fig2 on the hot roll &# 39 ; s axis of rotation . a hot roll core temperature sensor ( not shown ) is mounted on main frame 26 under and in contact with hot roll 14 . hot roll 14 is driven in a clockwise ( fig2 ) direction by frictional engagement with counterclockwise rotating backup roll 16 when the fusing nip is closed . as seen in fig1 , both end blocks 23 have a mounting channel 164 . channels 164 are of uniform cross - section and run perpendicular to the hot roll &# 39 ; s axis of rotation . as shown in fig1 and 11 , the back mounting channel only of main frame member 26 includes a positioning pin 166 adapted to mate with channel 164 in the end block adjacent helix compression spring 160 . the front positioning channel of main frame member 26 , however , does not include such a positioning pin . each end of the reversible subframe member 152 , in fig1 , includes an electrical connector portion 168 , one of which is exploded and separated from end block 23 to illustrate electrical connector 170 . connector 172 is insulatively mounted on the main frame member &# 39 ; s forward end flange . the rear one of these connectors 168 is maintained in a fixed position by virtue of locking engagement between channel 164 and pin 166 . electrical connector 170 experiences movement along the axis of the hot roll as the temperature of the hot roll &# 39 ; s u - shaped subframe member 152 changes . metallic u - shaped subframe member 152 expands and contracts with temperature changes . however , since connector member 172 has a channel extending in a direction parallel to the axis of the hot roll , sliding movement of connector 170 within the channel of member 172 is accommodated . paper is fed through the copier with its long dimension parallel to the hot roll &# 39 ; s rotational axis , and with sheets of various sizes referenced to a common rear side edge ( corresponding to the common corner registration for all original documents to be copied on the master document support glass ). this rear edge is indicated by broken line 174 in fig1 . the forward edge of an 81 / 2 × 11 inch sheet of paper would reside at broken line 176 , whereas the forward edge of and 81 / 2 × 14 inch sheet of paper would reside at broken line 178 . the hot roll &# 39 ; s variable forward working area 176 - 178 makes it desirable to reverse hot roll 14 , end - for - end , periodically to distribute wear on the hot roll . before removing subframe 152 and hot roll 14 out of the fuser assembly 12 , subframe 152 is unlocked from main frame 26 by actuating rotatable handle 74 and movable links 76 which rotate links 88 clear of mounting blocks 23 . a shroud ( not shown ) which overlies hot roll 14 is pivoted clear of the roll and foldable handle 154 is unfolded to allow for the lifting of hot roll 14 , including subframe 152 , out of main frame 26 . with reference to fig1 , as subframe 152 is lifted , the connection between positioning pin 166 and channel 164 in end block 23 is broken . the electrical connection between the male and female connectors on the other end block 23 and main frame 26 respectively , is also broken . the upward motion of subframe 152 continues and end blocks 23 continue sliding until free of positioning surfaces 24 . once out of main frame 26 and the fusing area , subframe 152 is reversed , end for end . after reversal of subframe 152 , the above steps are reversed until subframe 152 is again locked to main frame 26 . even though the handle for lifting subframe 152 out of the copier is shown and described as being permanently attached to subframe 152 , it should be understood by those having skill in the art that modifications to the handle - subframe configuration can be made . for example , handle 154 could be detachable and stored until needed to remove subframe 152 from the copier . these simple manual steps allow hot roll reversal to be accomplished within a short period and also reduce the risk of component damage due to handling . additionally , the hot roll core temperature sensor is not disturbed during reversal of the hot roll . the use of handle 154 for removing hot roll 14 from the fusing assembly is more specifically described and claimed in a copending application , entitled &# 34 ; apparatus for the reversal of a hot roll in a fusing assembly &# 34 ;, ser . no . 820 , 272 , filed july 29 , 1977 , now u . s . pat . no . 4 , 121 , 089 , and assigned to the same assignee as the instant invention . while the invention has been shown and described with reference to a preferred embodiment thereof , it will be appreciated by those of skill in the art that variations in form may be made therein without departing from the spirit and scope of the invention .
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fig1 illustrates a first embodiment of a medical shaft - type instrument 1 . it comprises an instrument handle 2 on its proximal end . in brief , the instrument handle 2 may also be referred to as a handle . the handle may be designed in the manner of a “ challenger handle ”. an instrument head 3 is formed on the distal end of the medical shaft - type instrument 1 . arranged between the instrument handle 2 and the instrument head 3 is an instrument shaft 4 connecting the two components to each other . the instrument shaft 4 comprises an external outer tube 5 . the outer tube 5 may have an annular cross - section and be formed in the manner of a hollow cylinder . the instrument handle 2 acting as a contact area for a hand forwards an instruction of an operating surgeon to the instrument shaft 4 in order to actuate the instrument head 3 by means of it . a clip magazine 7 is present within the outer tube 5 functioning as a housing 6 . the clip magazine 7 is a magazine for storing clamps , clips , brackets or other clamping configurations suitable for ligature use . such clamps , in particular ligature clamps or clips are provided for being plastically deformed or locked in place , in order to stanch an organ of a mammalian , for instance a blood vessel of a human , in the deformed state . a plurality of such clamps 8 is represented in fig2 . fig2 shows the individual parts of the medical shaft - type instrument 1 , without the instrument handle 2 . in particular , an upper jaw part / an upper jaw part branch 9 , a lower jaw part / a lower jaw part branch 10 , a slider 11 which may be referred to as a cam carrier component and a retaining rail 12 can be seen . in the embodiment illustrated there , twenty clamps 8 are utilized in total . it would also be possible , however , to use a higher or smaller number of said clamps 8 . a tongue 13 which may also be referred to as a feed tongue , a feed divider 14 , a spring support 15 and a transport and entraining rail 16 which may also be referred to as a feed rail , are also included . further , a feed spring 17 , a sealing disc 18 , a feed rod / pusher rod 19 and a feed rod end piece 20 are used . a pusher tube 21 adjoins a sealing ring 22 . the sealing ring 22 is a distal limitation of a compression spring 23 which is adjacent to a spring flange 24 . the compression spring 23 is supported on the spring flange 24 . the compression spring 23 is responsible for a return motion of the jaw parts 9 and 10 , hence for moving the upper jaw part 9 away from the lower jaw part 10 . the components 9 to 24 are provided for being inserted within the outer tube 5 . the outer tube 5 is inserted in a handle flange 25 after the assembly process . the handle flange 25 for its part is in a force - fitting , form - fitting and / or material - bond type contact with a handle piece / handle coupling component 26 in order to connect to the instrument handle 2 . a hollow cylinder end piece 27 is arranged proximally with respect to the spring flange 24 . said hollow cylinder end piece 27 as well as the feed rod end piece 20 can be seen as proximally protruding from the handle piece 26 . fig3 illustrates the components known from fig2 in the assembled state . fig4 to 6 suggest the assembly unit made up of the upper jaw part branch 9 and the lower jaw part branch 10 for receiving the most distal clamp 8 within a shell form 28 . a retaining rail 12 formed as a metal retaining plate is arranged below the transport and entraining rail 16 . fig7 allows to clearly see the guidance of the clamps 8 in a cross - sectional view . as can be seen , the clamp 8 illustrated there has its four clamp webs 29 supported on the retaining rail 12 as well as on the outer tube 5 . the clamp webs 29 may be briefly referred to as webs . in this arrangement , the outer tube 5 comprises contact surfaces / abutment surfaces 30 for contacting the upper clamp webs 29 of the clamp 8 . the clamp 8 is designed here in the manner of a double - web clip . the tongue 13 is provided for ejecting the foremost , first clamp 8 , i . e . the most distal clamp 8 , whereas the transport and entraining rail 16 is provided in the manner of a metal feed plate for moving all the clamps 8 in the clip magazine 7 . the contact surfaces / abutment surfaces 30 are designed such that they allow a sliding motion of the clamps 8 along it . optionally , but not illustrated , the outer tube 5 — in the area of the contact surface 30 intended for being contacted by the clamp webs 29 — may be provided with recesses such as slots , grooves , serrations or through - holes , through which the clamps 8 may project outwards to the outer side of the outer tube 5 , i . e . so as to penetrate the outer tube 5 . this allows to achieve a particularly compact configuration of the shaft - type instrument 1 . the clamps 8 also rest on the retaining rail 12 with their clamp webs 29 , in fact in such a manner that a compression / deflection of the clamps 8 is forced in cooperation with the support on the outer tube 5 . the clamps 8 do not contact each other here . the tongue 13 is fed through the double - web clip - like clamps 8 , resulting in a sort of threading of the clamps 8 . in this arrangement , the clamp webs 29 form leg portions . the feed motion of the clamps 8 is effected by a forward and rearward movement of an elongated component comprising lugs in the style of protrusions , lamellas or barbs . the clamps 8 are exclusively guided on an inner wall 31 of the outer tube 5 and on a sheet - metal type retaining rail 12 . this results in an effective use of the installation space . noises , in particular rattling noises , are prevented . this results in a precise guidance . a compensation of the tolerances is achieved as well . a separate channel is not required . a channel - like construction as shown in fig7 is sufficient here , and the use of metal sheets has advantages in terms of dimensioning the stiffness . the retaining rail 12 comprises retaining lugs 32 . these can be clearly seen in fig1 to 16 , for instance . in said figures , a butterfly - type segmentation of the retaining lugs 32 into a first retaining lug portion 33 and a second retaining lug portion 34 can be seen as well . thus , these two retaining lug portion 33 and 34 constitute a kind of butterfly lug . the wings of a butterfly lug may also be referred to as first and second retaining lug portions 33 and 34 . the clamp webs 29 , which may also be designated as legs , slide / slip over the retaining lug portions 33 and 34 and result in the retaining lug portions 33 and 34 folding along a swivel or bending line 35 . the swivel or bending line 35 may also be referred to as a bending axis or swivel axis . as can be clearly seen especially in fig1 and 16 , a movement of the clamps 8 in proximal direction is prevented by a proximal end of the clamp 8 resting against a distal edge 36 of the retaining lug 32 . as can be clearly taken from fig1 and 16 , the shape of the lugs is also implemented in a butterfly - type shape . the protruding lugs including wings having the largest possible edge / area for supporting the clamps 8 on the clamp &# 39 ; s back should offer a high rigidity . the geometry of the retaining lugs is designed such that it can get out of the way during the run - over process , without going below the level of the metal sheet . in other words , the retaining lugs 32 lay down flat . in the erected state , side edges 37 of the retaining lugs 32 form lines which are almost parallel . they extend predominantly in the longitudinal direction . at least an angle from proximal larger than 0 ° is acceptable . this provides for minimum friction . if the clamp 8 runs over the retaining lug 32 from proximal , this angle will be enlarged . looking ahead to fig1 , it is mentioned that also the transport and entraining rail 16 comprises lugs , namely clamp entraining elements or clamp entraining lugs 38 . increments and distances of the lugs are important for the limitation of the length of the component , in particular for the length of the magazine . they dictate the work of friction . they have to be arranged in a skillful way with respect to their position in relation to the feed hub which may also be referred to as a delivery stroke . they can be formed in a simple manner if a shaped metal strip or a plastic component is used as a starting base for them . they should be arranged preferably in the style of springy lugs with precisely defined distances . the mutual distances between the retaining lugs 32 may be variable along the length of the sheet metal , i . e . does not have to be kept constant . the distances of the clamp entraining elements / lugs 38 relative to each other should also be variable along the length of the sheet metal , i . e . should not remain constant . the spacing increments of the lugs should be selected such that a sequential collecting of the clamps 8 is carried out starting from a rest position of the clamps 8 , resulting from non - constant distances . this has the effect of a continuous increase of force . in that case , a predetermined amount of a force to be applied will not be exceeded . the spacing increments of the lugs should be selected such that the length of the magazine is minimized . the spacing increments of the lugs are selected here such that the collecting process occurs sequentially from distal to proximal depending on the rest position of the clamps in order to avoid a mutual collision of the clamps or counteract it . the following relationship is suitable for the determination of the spacing a : the spacing ( a ) is referred to as the spacing between the j th and the ( j − 1 ) th lug either of the retaining rail 12 or of the feed rail / transport and entraining rail 16 , with j specifying the position of the lug starting from distal and n corresponding to the total number of the clips in the applicator . spacing of the retaining lug ( arhl )= constant spacing ( ak )+ incremental spacing rhl ( ajrhl ) incremental spacing rhl ( ajrhl )= increment rhl ikrhl ·( n − j ) spacing of the feed lug ( avsl )= constant spacing ( ak )+ constant ( k )+ incremental spacing vsl ( ajvsl ) incremental spacing vsl ( ajvsl )= increment vsl ikvsl ·( n − j ) however , the constant spacing ( ak ) depends on the clamps , their size and their geometry and amounts to approximately 8 . 5 mm , for example . it is also possible to provide a constant increment ( ik ) and a variable increment ( iv ). the total increment i is then calculated as follows : i = ik + iv . this allows to determine the location of the occurring maximum force and hence the buckling of the sheet metal . fig8 illustrates the friction - related behavior as a function of the position where the clamp 8 runs over one of the lugs 32 and 38 . the abscissa shows the length of the lugs in mm , whereas the ordinate shows the total force f ges in newton . in fig9 is an illustration of the increase in force during “ collecting ” the clamps 8 in the course of a delivery stroke , on the one hand , and in the course of a return stroke on the other hand , due to the friction when all the clamps 8 run over all the lugs ( retaining lugs 32 and clamp entrainment lugs 38 ). here , the solid line represents the increase in force / force progression during the feed motion / delivery stroke , and the broken line represents the increase in force / force progression during the return stroke . the abscissa shows the feed travel in mm , whereas the ordinate shows the need of physical force in newton . returning to fig1 and 18 , reference is made to the sandwich - like arrangement of the transport and entraining rail 16 above the tongue 13 which for its part is situated above the retaining rail 12 . thus , the retaining rail 12 , the transport and entraining rail 16 and the tongue 13 are arranged one above the other and so as to be axially movable . the lug heights of at least some of the lugs 32 and / or 38 are dimensioned here such that they guide the tongue 13 situated in the middle . in consideration of the fig1 to 21 , it should be obvious that it is desirable to achieve a feed motion division by means of an elongated hole 39 which is engaged by a cam 40 . the cam 40 protrudes from a feed divider 41 which may be designed so as to be separate from a spring support 42 . the cam 40 may be an integral constituent part of the spring support 42 . in any case , the feed rod 19 extends through the spring support 42 and is connected to the feed divider 41 in an axially fixed manner . the cam 40 of the feed divider 41 extends through the elongated hole 39 of the transport and entraining rail 16 . the tongue 13 is connected to the feed rod 19 in an axially fixed manner , so that any movement transferred from the feed rod 19 is directly imparted to the tongue 13 and passed on to the transport and entraining rail 16 not until the cam 40 impinges on a stop edge 43 . in this way , two engaging components are configured such that a pin , a cam or any other protrusion engages in a hole , a groove or a recess such that an axial relative movement of the two parts with respect to each other by a specific amount is allowed , but a combined movement is caused upon reaching a stop . as can be seen particularly well in fig1 and 20 , the spring support comprises recesses 44 which can be engaged by protrusions or lugs of the outer tube 5 in order to bring about an axial fastening . the fig2 and 23 show a variant differing therefrom , namely a variant in which the pusher rod 19 is directly connected to the tongue 13 . to this end , the tongue 13 is crimped around a distal end of the pusher rod 19 in the manner of a folded sheet . it goes without saying that the tongue 13 may also be an integral constituent part of the pusher rod 19 . with the configuration of fig2 and 23 , there is no separate feed divider 41 . however , said folded sheet 45 which provides for the connection between the tongue 13 and the pusher rod 19 vertically engages an elongated hole 39 provided in the transport and entraining rail 16 , in order to come in contact with a stop edge 43 — similar to the exemplary embodiment as described above — to bring about the initiation of the delivery stroke on the transport and entraining rail . whereas fig2 illustrates a perspective view predominantly from below , fig2 shows a longitudinal section . it is possible that the tongue 13 is glued to the pusher rod 19 , welded to it or crimped with it . in the end , two very precise stops are made available , allowing a very accurate working with the medical shaft - type instrument 1 . the retaining rail 12 does not only have a retaining function for the clamps 8 , namely the prevention of the return motion of the clamps 8 during the return stroke into the neutral position of the transport and entraining rail 16 , but ( as seen in cross - section ) also defines the lower limitation of the clip line formed by the clamps 8 . further , the retaining lugs 35 should be realized in the manner of barbs which can be run over in one direction by the clamps 8 and can also be displaced by the latter . the retaining rail 12 is also supposed to be fixed on the tube wall of the outer tube 5 by means of retaining rail mounting lugs 46 which can be seen in fig2 to 27 . to this end , a mounting hole 47 is provided in the outer tube 5 . the mounting hole 47 is worked into the material in the form of a slit for instance by means of a laser cutting procedure . an outer tube fold area 48 , provided in the manner of a lug and comprising an inspection window 49 , is bent radially inwards and offers sufficient space so that the retaining rail mounting lug 46 can engage below a lower edge 50 limited by the outer tube fold area 48 . this results in an axial stop toward the proximal end , provided with the reference symbol 51 , and an axial stop toward distal , provided with the reference symbol 52 . a height fixation means 53 is realized by the lower edge 50 . the mounting hole 47 is shaped in the manner of a window . the inspection window 49 is for checking purposes during the assembly process . in this way , a self - catching system is realized . the outer tube fold area 48 , which acts as a lug and is formed in one piece on the outer tube 5 , catches the retaining rail mounting lug 46 which is a single constituent part of the retaining rail 12 formed as a metal retaining plate and fixes the metal retaining plate at a predetermined level and in an axial position . the sequence during the assembly process is apparent from the fig2 to 27 which show the assembly protrusions of the retaining rail 12 from proximal to distal , caught under / caught by the outer tube fold area 48 with the retaining rail mounting lug 46 . fig2 shows the completely assembled state . a modified exemplary embodiment is shown in fig2 in which the retaining rail 12 is fixed on the spring support 42 by means of cut - outs . the spring support 42 for its part is already immobilized on the outer tube 5 in radial and axial direction . in this arrangement , the spring support 42 comprises cams 54 , which penetrate the retaining rail 12 and fix both components to each other in a form - and / or force - fitting manner . here too , a cam 40 enters an elongated hole 39 , so that a limitation of the delivery stroke is reached if the cam 40 hits the stop edge 43 , which is advantageous with a force - controlled use of the handle . in fact , the handle switches over the direction of movement as from a specific limit value on . an active retraction of the transport and entraining rail 16 and of the tongue 13 is then possible . fig2 to 31 have their focus on a distal end of the retaining rail 12 . at this place , a bridge / abutment plate 55 is formed which facilitates the gliding of the clamp 8 into the shell forms 28 of the upper jaw part branch 9 and the lower jaw part branch 10 . the bridge / abutment plate 55 may also be referred to as a cover for the lower jaw part 10 . in addition , a retaining rail mounting hole 56 is provided , which is arranged between the bridge / abutment plate 55 and a kicker - or ski jump - like deflector 57 . this deflector 57 serves in the manner of a kicker for lifting the clamp 8 at its tail , i . e . at its proximal end , so that the clamp 8 slides better into the upper and lower jaw part branch 9 and 10 , respectively . the deflector 57 also serves for stiffening purposes . during the assembly process , the retaining rail mounting hole 56 is used by an assembly tool ( not shown ), in order to be hooked in place there . in fig3 , laterally protruding retaining rail mounting lugs 46 offset in longitudinal direction are connected to each other by a ( theoretical ) asymmetrical bending line 58 , so that the ( theoretical ) direct bending line 59 provided with the reference symbol 59 does not occur . such a direct bending line 59 orthogonal relative to the longitudinal direction is avoided , as asymmetrical bending lines 58 are preferred in the event of the occurrence of critical torsional forces , because torsional forces do not occur here . spring lugs 60 which serve for supporting the retaining rail 12 on the pusher tube 21 can be seen in fig3 . thus , a residual force is made available which tries to decrease the clip channel into which the clamps 8 are directed . this results in a mutual stabilization of all components and prevents the clamps 8 from missing the retaining lugs 32 upon retraction . otherwise , retaining lugs 32 having a larger height and requiring more power would then be necessary , which would result in higher friction , entailing an increased physical effort during the feed motion process . in the end , a compensation of tolerances is also achieved by the spring lugs . as an alternative or in addition , the spring lugs 60 could rest on the upper and / or lower jaw part branch 9 and 10 , respectively . fig3 to 43 have their focus on the tongue 13 and its special configuration . the tongue 13 has its distal end provided with a tissue - protecting protrusion 61 which prevents that any tissue of the organ to be treated enters the area between the clamp webs / legs 29 of the clamp 8 and is pinched here unintentionally . the tissue - protecting protrusion 61 may also be referred to as a tissue spacer 61 . at a site proximal relative thereto , a notch 62 is provided which forms an insertion opening 63 . the insertion recess may be synonymously referred to as insertion opening 63 . as can be seen particularly clear in fig4 and 41 , this insertion opening 63 allows the proximal portion of the clamp 8 , namely the clamp web / leg 29 , to swivel or enter into the free zone provided by the notch 62 . the insertion opening 63 may also be referred to as an insertion recess and makes it possible that a portion of the clamp 8 projects from below into the notch 62 at least by some extent or even right through it . further , a protrusion in the manner of a movement - guiding element 64 is formed on the underside of the tongue 13 . this movement - guiding element 64 is formed in the manner of a deflector 65 or pilot bead 66 . it has the effect of increasing the flexural rigidity and at the same time provides for a catching protection . the catching protection prevents the clamp 8 from undesirably contacting the tongue 12 in the area of impact edges 67 , as otherwise the clamp 8 would be moved in axial direction ahead of time or in the wrong sense . abutment edges 68 for providing a targeted pushing effect on the clamp 8 are provided as well . this abutment edge 68 may also be referred to as a pushing edge or thrust lug . this is why it is provided with the reference symbol 69 . the tongue rests against a part of a clamp web 29 over the length designated with the reference line 70 . in this context , the insertion opening 63 also enables that the contact between the tongue 13 and the clamp 8 is maintained during the tilting of the clamp 8 . the tissue - protecting protrusion 61 with its protective function for animal or human tissue can be clearly deduced from fig3 . the guiding effect of the movement - guiding element 64 / deflector 65 / pilot bead 66 can be clearly taken from fig3 to 39 and 43 . here , it can also be clearly seen that the pilot bead 66 prevents the clamp 8 from getting caught . the movement - guiding element 64 also enhances the stiffness of the tongue 13 . in this way , a catching protection and an edge shielding function are provided in addition to an anti - bulging function . this is why the clamp 8 cannot get caught on a folded sheet metal portion of the tongue 13 . this may also be referred to as “ edge shielding ”. the tongue 13 is threaded through several clamps 8 without taking the function of guiding it . it is an elongated element with a high proneness of kinking in the course of advancing and guiding the most distal clip / the most distal clamp 8 , with smallest tolerances . a lengthwise flange 71 prevents the tongue 13 from buckling . longitudinal beads as shown in fig3 to 43 also have an anti - buckling effect . the point of the tongue 13 allows to reliably grasp the clamp 8 , and the transmission of forces onto the clamp 8 in the event of an angular or positional change is achieved just as the compensation of tolerances . implementing the tip as a flexible portion , for instance by using a material with smaller thickness , by the provision of elasticity holes , by means of cut - outs for reducing the bending forces , allows to achieve an advantageous embodiment . all those special lug or tip shapes are advantageous which prevent the thrust lugs 69 from getting levered out . the situation of the tongue 13 slipping off from a clamp web / leg 29 is effectively prevented in the manner described above . the tissue - protecting protrusion 61 protrudes beyond the sheet metal at the tip of the tongue and is in abutment on the inner side of a clamp 8 in the leg fillet provided there . it is to be noted that the deflector 65 / the pilot bead 66 has the same depth as the flange 71 of the tongue 13 , to prevent any thrust transmission to the clamp 8 . in the following fig4 to 51 , the spring support 42 is illustrated and explained in more detail . the spring support 42 comprises a holding catch / a cam 72 provided for being hooked into the retaining rail 12 in order to establish an axial and / or radial fixation . further , the spring support 42 comprises a cam / a lug 73 for immobilizing the spring support on the outer tube 8 . said cam 73 is surrounded by a sealing surface 74 . the latter serves for sealing off the recess in the outer tube 5 , so that no fluid can escape from the shaft - type instrument towards outside , and fluids from outside the shaft - type instrument 1 should not reach its interior either . the area which forms the sealing surface 74 is designed in the manner of a dome spring which is provided with the reference symbol 75 . thus , the wedge - shaped cam 73 lies within the sealing surface 74 of the dome spring 75 . this dome spring 75 gets caulked radially in one direction , because it is arranged so as to be off - center . the holding catch 72 and a recess accommodating it may be designed such that the respective fixations of the metal retaining plate 12 on the spring support 42 in radial and axial direction are effected separate from each other . in this case , the tolerances can be better used as if this was performed on a component in both directions . this is why a protrusion 76 is provided which is only designed for axially supporting the retaining rail 12 , whereas the holding catches 72 are designed for the radial fixation . thus , the spring support 42 has shell design having a positive effect on the elasticity . the spring support 42 serves for the fixation on the outer tube 5 . it may be implemented as an injection - molded part comprising a central feed - through for guiding the pusher rod / feed rod 19 . it may be designed in the manner of an integrated annular spring and comprise a springy , thin - walled oversize bulge . an extensive contact around the cam 73 , being configured in the manner of a retaining cam , is advantageous in terms of producing tightness . a protrusion / retaining cam having a centering effect engages in the outer tube 5 easier if it has chamfered edges . such chamfered edges may be provided on all protrusions or lugs . the spring support 42 is firmly clipped in place on the retaining rail 12 . thus , the spring support 42 comprises a through - hole 77 provided in the longitudinal direction and having the function of guiding the feed rod 19 . fig5 shows the state of the spring support 42 in the state when clipped in place in the metal retaining plate forming the retaining rail 12 . this situation is also illustrated in fig5 . the bridge / abutment plate 55 may also be referred to as an abutment plate . further , the retaining rail mounting hole 56 may be briefly referred to as a mounting hole .
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according to one embodiment of this invention , a ruthenium complex photosens tizer dye is represented by the following general formula ( i ): where z 1 and z 2 individually represent hydrogen atom ( h ), lithium ( li ), sodium ( na ), or tetra - alkyl ammonium group represented by the following formula ( a ), where x 1 to x 4 individually represent c m h 2m + 1 ( m is an integer from 1 to 6 ), in formula ( i ), a is one of the followings : h , or c m h 2m + 1 ( m is an integer from 1 to 15 ), or ch 2 [ oc 2 h 4 ] p oc m h 2m + 1 ( p is an integer from 1 to 30 , m is an integer from 1 to 15 ); in the formulae ( 110 ) to ( 132 ), n is zero or an integer from 1 to 15 , in formula ( i ), b , c , and d are individually one of the followings : h , or c m h 2m + 1 ( m is an integer from 1 to 15 ), or ch 2 [ oc 2 h 4 ] p oc m h 2m + 1 ( p is an integer from 1 to 30 , m is an integer from 1 to 15 ); where r 3 , r 4 , r 7 , r 9 , r 10 , r 21 , r 22 , r 24 , r 26 , r 27 , and r 39 to r 43 represent c m h 2m + 1 ( m is zero or an integer from 1 to 15 ); r , r 12 to r 15 , r 19 , r 28 to r 33 , r 37 , and r 44 to r 48 represent c m h 2m + 1 ( m is an integer from 1 to 15 ); r 1 , r 11 , r 17 , and r 35 represent c m h 2m + 1 ( m is an integer from 1 to 15 ) or phenyl ; r 2 , r 16 , and r 34 represent ch 2 [ oc 2 h 4 ] p oc m h 2m + 1 ( p is an integer from 1 to 30 , m is an integer from 1 to 15 ); r 18 , r 20 , r 36 , and r 38 represent ch 2 [ oc 2 h 4 ] p oc m h 2m + 1 or c m h 2m + 1 ( p is an integer from 1 to 30 , m is an integer from 1 to 15 ). in formulae 123 , 125 , 147 , 148 , 150 , 170 , 172 , 173 and 175 , x represents se , s or o . in formulae 110 to 115 and 134 to 138 , x represents f , cl , br , i or c m h 2m + 1 ( m is an integer from 1 to 15 ). several exemplary embodiments will be described below to illustrate the processes of synthesis of the ruthenium complex photosensitizer dyes 1 , 2 and 3 of this invention . the structures of the ruthenium complex photosensitizer dyes 1 , 2 and 3 are showed below . it must be understood that the exemplary embodiments should be regarded as illustrative rather than restrictive . put 20 ml of polyphosphoric acid ( ppa ) into a double - necked flask , stir and preheat the solution to about 90 ° c . then , slowly add about 2 . 46 g ( about 0 . 02 mol ) of 2 - picolinic acid into the double - necked flask , and keep stirring the mixture evenly for about 30 minutes . afterwards add about 2 . 16 g ( about 0 . 02 mol ) of o - phenylenediamine , then raise temperature to about 150 ° c . and keep stirring evenly the mixture for about 4 hours . when the reaction ends , lower the temperature of the mixture to about 100 ° c . then , carefully and rapidly pour the reactant into iced water , and neutralize the mixture to weak alkalinity ( about ph 9 ) with 1m sodium hydroxide ( naoh ) solution . a pinkish purple color solid product is precipitated now . the solid is filtered out by suction , then it is dried by heat and purified by column chromatograph using a hexane / ethyl acetate ( ea ) solution ( 1 : 2 ) as eluent . about 2 . 21 g of white color solid is obtained with the yield of about 56 . 7 %. the white solid product is 2 -( pyridin - 2 - yl )- 1h - benzimidazole . mix about 0 . 195 g ( about 1 mmol ) of the white solid product obtained in step 1 , about 0 . 276 g ( about 2 mmol ) of k 2 co 3 , and about 15 ml of n , n ′- dimethylformamide ( dmf ) in a reaction vessel and keep stirring for about 10 minutes . then , carefully inject about 0 . 385 ml ( about 3 mmol ) of 2 , 4 - difluorobenzyl bromide into the mixture by a syringe and let the mixture react for about 3 hours at room temperature . when the reaction ends , pour the reactant into iced water and extract using ea . then collect and dehydrate the organic layer using anhydrous sodium sulfate . after filtration and concentration , a yellow color viscous liquid is obtained . then purify the yellow viscous liquid by column chromatograph using a hexane / ea solution ( 3 : 1 ) as eluent . then , dry it by vacuum suction and collect about 0 . 242 g of beige - white color solid ( i . e . the ligands l1 ) . the yield is about 75 . 3 %. the steps of synthesis of ruthenium complex photosensitizer dye 1 are shown below . ( 1 ) in the environment of dmf and argon ( ar ), two equivalents of the ligand l1 ( about 0 . 257 g , about 0 . 8 mmol ) are reacted with one equivalent of [ rucl 2 ( p - cymene )] 2 ( about 0 . 244 g , about 0 . 4 mmol ) at a temperature of about 70 ° c . for about 4 hours to form [ ru ( l1 )( p - cymene )] c1 coordination from broken dichloride - bridged structure . ( 2 ) then , add two equivalents of 4 , 4 ′- dicarboxy - 2 , 2 ′- bipyridine ( dcbpy , l ) ( about 0 . 195 g , about 0 . 8 mmol ) and raise the temperature to about 140 ° c . for reaction for about 4 hours , resulting in [ ru ( l )( l1 )( c1 ) 2 ]. ( 3 ) finally , add excess amount of potassium thiocyanate ( kscn ) and let the mixture react at about 140 ° c . for about 5 hours . after that , remove residual dmf from the reaction vessel using a distillation apparatus and kscn residuals by water ( h 2 o ) . after suction filtration , about 0 . 563 g of the ruthenium complex photosensitizer dye 1 is obtained . the yield is about 90 %. put 20 ml of polyphosphoric acid ( ppa ) into a double - necked flask , stir and preheat to about 90 ° c . then , slowly add about 2 . 00 g ( about 0 . 02 mol ) of 4 - bromopyridine - 2 - carboxylic into the flask , and keep stirring the mixture evenly for about 30 minutes . afterwards , add about 1 . 08 g ( about 0 . 01 mol ) of o - phenylenediamine and raise the temperature to about 150 ° c . and keep stirring the mixture evenly for about 4 hours . when the reaction ends , lower the temperature to about 100 ° c . then , carefully and rapidly pour the reactant into iced water , and neutralize it to weak alkalinity ( about ph 9 ) with 1m sodium hydroxide solution . a pinkish purple color solid product is precipitated . the solid product is filtered by suction and dried by heat , then purified by column chromatograph using a hexane / ea solution ( 1 : 3 ) as eluent . about 1 . 47 g of white color solid is obtained with the yield of about 53 . 8 %. the white solid product is 2 -( 4 - bromopyridine - 2 - yl )- 1h - benzimidazole . mix about 0 . 273 g ( about 1 mmol ) of the white solid product obtained in step 1 , about 0 . 276 g ( about 2 mmol ) of k 2 co 3 , and about 15 ml of dmf in a reaction vessel and stir for about 10 minutes . then , carefully inject about 0 . 385 ml ( about 3 mmol ) of 2 , 4 - difluorobenzyl bromide into the mixture by a syringe and keep at room temperature for about 3 hours . when the reaction ends , pour the reactant into iced water and extract using ea . collect the organic layer and dehydrate it using anhydrous sodium sulfate . after filtration and concentration , a yellow color viscous liquid is obtained . then purify the yellow viscous liquid by column chromatograph using a hexane / ea solution ( 2 : 1 ) as eluent . then , after vacuum suction , about 0 . 273 g of beige - white color solid is obtained with the yield of about 68 . 3 %. the beige - white solid product is 1 -( 2 , 4 - difluorobenzyl )- 2 -( 4 - bromopyridin - 2 - yl )- benzimidazole . mix about 0 . 24 g ( about 0 . 6 mmol ) of the beige - white solid product obtained in step 2 , about 0 . 092 g ( about 0 . 72 mmol ) of thiophen - 2 - yl - 2 - boronic acid , about 0 . 0462 g ( about 0 . 04 mmol ) of pd ( pph 3 ) 4 , and about 20 ml of tetrahydrofuran ( thf ) in a reaction vessel . in the environment of nitrogen gas , add about 2 ml of 2m k 2 co 3 , then the mixture is heated and refluxed for about 8 hours . when the reaction ends , pour the reactant into iced water and extracte using ch 2 cl 2 . collect and dehydrate the organic layer using anhydrous magnesium sulfate . after filtration and concentration , a light yellow color viscous liquid is obtained . purify the light yellow viscous liquid by column chromatograph using a hexane / ea solution ( 10 : 1 ) as eluent . then , about 0 . 22 g of beige - white color solid ( i . e . the ligands l2 ) is obtained with the yield of about 91 %. the steps of synthesis of ruthenium complex photosensitizer dye 2 are shown below . ( 1 ) in the environment of dmf and argon , two equivalents of the ligand l2 ( about 0 . 322 g , about 0 . 8 mmol ) are reacted with one equivalent of [ rucl 2 ( p - cymene )] 2 ( about 0 . 244 g , about 0 . 4 mmol ) at a temperature of about 70 ° c . for 4 hours to fog in [ ru ( l2 )( p - cymene )] cl coordination from broken dichloride - bridged structure . ( 2 ) then add two equivalents of 4 , 4 ′- dicarboxy - 2 , 2 ′- bipyridine ( dcbpy , l ) ( about 0 . 195 g , about 0 . 8 mmol ) and raise the temperature to about 140 ° c . for reaction for about 4 hours , resulting in [ ru ( l )( l2 )( c1 ) 2 ]. ( 3 ) finally , add excessive amount of potassium thiocyanate ( kscn ) into the mixture and let it react at about 140 ° c . for about 5 hours . after that , remove residual dmf in the reaction vessel using a distillation apparatus and kscn residuals using water . after suction filtration , about 0 . 612 g of ruthenium complex photosensitizer dye 2 is obtained with the yield of about 88 . 5 %. mix about 0 . 96 g ( about 0 . 03 mol ) of sulfur ( s ) powder , about 1 . 07 g ( about 0 . 01 mol ) of 2 , 4 - lutidine , and about 1 . 08 g ( about 0 . 01 mol ) of o - phenylenediamine in a single - necked flask . then , raise the reaction temperature to about 160 ° c . and keep stirring evenly for about 6 hours till the yellow brown liquid turn into yellow solid . finally , the reaction is terminated by addition of methanol . after filtering out the sulfur powder , the collected liquid is evaporated by a rotary concentrator . about 1 . 3 g of light yellow color solid is obtained with the yield of about 62 . 2 %. the light yellow solid is 2 -( 4 - methylpyridin - 2 - yl ) benzimidazole . mix about 0 . 209 g ( about 1 mmol ) of the light yellow solid product obtained in step 1 , about 0 . 276 g ( about 2 mmol ) of k 2 co 3 , and about 15 ml of dmf in a reaction vessel and keep stirring for about 10 minutes . then , carefully inject about 0 . 385 ml ( about 3 mmol ) of 2 , 4 - difluorobenzyl bromide into the mixture by a syringe , and let it react for about 3 hours at room temperature . when the reaction ends , pour the mixture into iced water then extracte using ea . collect and dehydrate the organic layer using anhydrous sodium sulfate . after filtration and concentration , a yellow color viscous liquid is obtained . purify the yellow viscous liquid by column chromatograph using a hexane / ea solution ( 4 : 1 ) as eluent . then , after vacuum suction , about 0 . 23 g of beige - white color solid is obtained with the yield of about 68 . 7 %. the beige - white solid product is 1 -( 2 , 4 - difluorobenzyl )- 2 -( 4 - methylpyridin - 2 - yl ) benzimidazole . put about 0 . 335 g ( about 0 . 001 mmol ) of the beige - white solid product obtained in step 2 in a 100 ml double - necked flask . then , the flask is alternately evacuated then filled with nitrogen gas for three times . after that , add 10 ml of anhydrous thf into the flask . then slowly add 2m lithium diisopropylamide ( lda , about 0 . 0012 mol , about 0 . 6 ml ) at a temperature of − 20 ° c . keep stirring the mixture for about 30 minutes at above temperature . add about 0 . 17 g ( about 0 . 0015 mol ) of thiophene - 2 - carbaldehyde dissolved in anhydrous thf into the flask . keep stirring the mixture for about 10 minutes at above temperature then move to room temperature for reaction for about 2 hours . the reaction is terminated by addition of methanol ( meoh ). next , after thf is removed , the residue was extracted three times using ch 2 cl 2 . collect and dehydrate the organic layer using anhydrous magnesium sulfate . after filtration and concentration , about 0 . 172 g of light yellow color viscous liquid is obtained . place the light yellow viscous liquid in a 100 ml single - necked flask then add about 10 ml of pyridine . under ice bath condition , add poc1 3 ( about 0 . 0012 mol / 0 . 11 ml ). then put the mixture in room temperature for reaction for about 10 minutes . terminate the reaction by adding meoh . next , after pyridine was removed , the residue was extracted three times using ch 2 cl 2 ( about 10 ml ) and saline water . collect and dehydrate the organic layer using anhydrous magnesium sulfate . then , after vacuum suction , a yellow color liquid is obtained . purify the yellow liquid by column chromatograph using a hexane / ea solution ( 2 : 1 ) as eluent . about 0 . 17 g of beige - white color solid ( i . e . the ligands l3 ) is obtained with the yield of about 39 . 6 %. the steps of synthesis of ruthenium complex photosensitizer dye 3 are shown below . ( 1 ) in the environment of dmf and argon , two equivalents of the ligand l3 ( about 0 . 343 g , about 0 . 8 mmol ) is reacted with one equivalent of [ rucl 2 ( p - cymene )] 2 ( about 0 . 244 g , about 0 . 4 mmol ) at a temperature of about 70 ° c . for about 4 hours to form [ ru ( l3 )( p - cymene )] cl coordination . from the broken dichloride - bridged structure . ( 2 ) then add two equivalents of 4 , 4 ′- dicarboxy - 2 , 2 ′- bipyridine ( dcbpy , l ) ( about 0 . 195 g , about 0 . 8 mmol ) to the mixture and raise the temperature to 140 ° c . for reaction for about 4 hours , resulting in [ ru ( l )( l3 )( cl ) 2 ]. ( 3 ) finally , add excessive amount of kscn to the mixture and let react at about 140 ° c . for about 5 hours . after that , remove residual dmf in the reaction vessel using a distillation apparatus and residuals of kscn using water . after suction filtration , about 0 . 586 g of ruthenium complex photosensitizer dye 3 is obtained with the yield of about 82 . 3 %. fig1 shows the comparison of uv - visible spectra of ruthenium complex photosensitizer dyes 1 , 2 and 3 of this invention and conventional n719 dye . fig2 shows the comparison of iv curves of the ruthenium complex photosensitizer dyes 1 , 2 and 3 of this invention and conventional n719 dye . table 1 shows the comparison of photoelectric conversion efficiency of solar cell devices employing above - mentioned ruthenium complex photosensitizer dyes 1 , 2 and 3 and conventional n719 dye . as shown the efficiency of the ruthenium complex photosensitizer dyes 1 , 2 and 3 are better than that of the conventional n719 dye . the photoelectric conversion efficiency ( η ) is obtained by the equation below , η = p m p p i n = j m p * v m p p i n = j sc * v oc * ff p i n where p in is the input radiation power , and p mp is the maximum output power (= j mp × v mp ), and ff stands for the fill factor defined as ff = j m p * v m p j sc * v oc where l sc is the short circuit current , and v ∞ is the open circuit voltage . since the ruthenium complex photosensitizer dyes of this invention have smaller molecular structures than the conventional n719 photosensitizer dye , they can be adsorbed , in greater amount , on thin titanium dioxide photoanodes of solar cells , leading to larger photoelectric current . therefore , the layers of the titanium dioxide photoanodes can be reduced thus simplifying the processes and lowering the cost of manufacturing of the elements . since the dye - sensitized solar cells employing the ruthenium complex photosensitizer dyes of this invention have higher photocurrent density than those using conventional n719 photosensitizer dye , the former has superior overall solar elements efficiency than the latter . although some embodiments of this invention are described in details above , it is intended that the scope of this invention may not be limited by the descriptions above , but rather by the claims appended hereto . also , it is intended that the following appended claims be interpreted as that all possible alterations , pemiutations , and equivalents fall within the true spirit and scope of this invention .
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fig1 shows , in simplified block diagram form , details of an interactive system in which the invention may be advantageously employed . it should be noted that the arrangement shown in fig1 is but one example of an application of the invention . indeed , a plurality of different user interfaces and / or one more identical user interfaces may be employed as desired . specifically , shown in fig1 is sisl ( several interfaces , single logic ) service unit 101 ; home / office computer 102 used as a customer and / or provider interface , including automatic speech recognition having a natural language understanding , if desired , that is interfaced to sisl service unit 101 via an internet link 103 ; telephone 104 also used as a customer and / or provider interface that is interfaced to sisl service unit 101 via a telephone network 105 including , for example , touch - tone , i . e ., multi - frequency signaling ; computer 106 used as a customer and / or provider interface , which may also have automatic speech recognition including natural language understanding , that is interfaced to sisl service unit 101 via a local area network ( lan ); and atm ( automatic teller machine ) used as a customer interface and , typically , is interfaced to sisl service unit 101 via a direct connect 109 . a key advantage of sisl is that all user interfaces to a service share the same single service logic . sisl provides a clean separation between the service logic and the software for a variety of user interfaces including but not limited to java applets , html pages , speech - based natural language dialog , and telephone - based voice access . in this example , sisl is implemented using the java programming language . at the outset it is felt best to describe some of the principles employed in implementing the flexible interactive service including an embodiment of the invention . for simplicity and clarity of exposition , these principles will be presented in the context of a so - called any - time teller banking service employing the invention . the any - time teller is an interactive banking service . the service is login protected ; customers must authenticate themselves by entering an identifier ( login ) and pin , i . e ., personal identification number , ( password ) to access the functions . as customers may have many money accounts , most functions require the customer to select the account ( s ) involved . once authenticated , the customer may : make a withdrawal . the service makes sure the customer has enough money in the account , then withdraws the specified amount . transfer funds between accounts . the service prompts the customer to select a source and target account , and a transfer amount , and performs the transfer if ( 1 ) the customer has enough money in the source account , and ( 2 ) transfers are permitted between the two accounts . get the balance of an account . display the balance with respect to all posted transactions . the transfer capability of the any - time teller requires the collection of three events : the source account ( src ), target account ( tgt ), and dollar amount ( amt ). there are five constraints that those input events must meet before a transfer can take place : c 4 : amt must be less than or equal to the balance of src c 5 : the bank must allow transfers from src to tgt the service should check whether or not a constraint is violated as soon as possible ; hence , it must be prepared to react when only a subset of the three events is present . the service must then prompt for the remaining events . some basic principles are now considered related to the design and implementation of interactive services with multiple and varied user interfaces . these principles are especially important in the presence of multiple interfaces including those based on spoken natural language . the source account , target account , and dollar amount of the transfer capability should be independent events that can be collected in any order , where all three events are necessary to perform a transfer . by making explicit independent and dependent events , it in clear what events may be reordered without affecting the behavior of the service . this points the way to our first principle of the service specification : principle 1 : specify the service logic as a set of constraints on events and introduce a constraint between two events only when absolutely necessary for the correct functioning of a service . that is , the service logic should be able to accept independent input events in different orders . it is often desirable for a service to respond as soon as possible with error conditions about user input . since a constraint on the input events may refer to any arbitrary subset of those events , it is desirable that the service logic should be able to accept arbitrary subsets of events at any time . principle 2 : the service logic should accept an incomplete input , i . e ., subsets of the universe of possible events . unfortunately , humans often change their mind and / or make mistakes . whenever possible , services must accommodate these shortcomings of our species , providing a capability to correct information or back out of a transaction . this leads to our third principle : principle 3 : the service logic should allow the user to back up to correct or update previously submitted information at any time . principle 4 : the service logic should allow the user to back up to previous points in the service . services that obey the above principles generalize from linear user interactions to potentially allow multiple points of interaction to be enabled at a given instant . this information serves as an abstraction of the current control point of the service , and can be handled in a different manner by different user interfaces . for example , in automatic speech recognition interfaces , the information about currently enabled events is used by the user interface in two ways : to appropriately prompt the user for information , thus compensating for the lack of visual cues ; and a user interface need not respond to all currently enabled events of the service . thus , different user interfaces can formulate different queries to the user even though the control point in the underlying service logic , as revealed by the current set of enabled events , is the same . the decoupling that we are seeking between the user interface and the service logic , therefore points the way to our last principle of the service specification : principle 5 : at any point in the service , the service logic must automatically report to the user interfaces all currently enabled events , user prompts , help , and ways to revert back to previous points in the service . user interfaces have two main responsibilities with respect to the sisl architecture that reflect the two - way information flow between the user interface and service logic : based on the events received from the service logic , via the service monitor , prompt the user to provide the appropriate information and respond if the user requests help . collect the information from the user and transform the information into events to be sent to the service logic , via the service monitor . indeed , any user interface ( ui ) that performs these functions can be employed in conjunction with a sisl service logic . additionally , sisl provides a convenient framework for designing and implementing web - based , applet - based , automatic speech recognition - based and telephone voice - based interfaces . to implement such user interfaces , the ui designer need only specify two functions corresponding to the prompt and help mechanism . for automatic speech recognition interfaces , a set of speech grammars , i . e ., the input to a speech recognition engine that permits it to efficiently and effectively recognize spoken input , together with a third function that specifies which grammars to enable is also required . a prompt function that generates the string to be given as the prompt to the user . an example , in pseudo code form is shown in fig6 . the sisl infrastructure automatically causes automatic speech recognition - based interfaces to speak the prompt string . web - based interfaces automatically display the prompt string , as well as , radio buttons corresponding to the possible transaction choices . for the other prompt events , text fields are automatically displayed , while submit buttons are automatically displayed for enabled events that allow the user to return to earlier points in the service . screen snapshots are shown in fig7 and 8 . specifically , fig7 is a pictorial representation of a web page used in the web interface for a choice node , and fig8 is a pictorial representation of a web page used in the web interface for a constraint node . a help function that generates the string to be given as the prompt to the user . an example , in pseudo code form is also shown in fig6 . a grammar function that enables the correct set of grammar rules ; this function is only needed for automatic speech recognition - based interfaces . an example , in pseudo code form is shown in fig9 . as indicated , fig6 shows , in pseudo code form , portions of the prompt and help functions shared by an automatic speech recognition - based interface , web - based interface and telephone - based voice interface for the any - time teller banking service . portions of the grammar rules , against which the automatic speech recognition engine will parse spoken input from the user , are shown in fig9 . again , fig1 illustrates a portion of the associated grammar function shared by an automatic speech recognition - based interface and a telephone - based voice interface . from these functions and grammars , the sisl infrastructure automatically coordinates the collection and event transformation mechanisms , and integrates the user interface with the service logic and the service monitor . for automatic speech recognition - based interfaces , the sisl infrastructure automatically generates a desktop interface based on java speech api ( application programming interface ). to enable telephone - based voice access to the service , sisl automatically generates voxml pages , which specify the voice dialog to be carried out on a telephony platform . for web - based interfaces , the sisl infrastructure automatically generates html ( hypertext markup language ) pages . it is noted that sisl provides a mechanism for the ui designer to customize the look and feel of the interface . fig2 shows , in simplified block form , details of the sisl ( several interfaces , single logic ) architecture employed in the embodiment of fig1 . the sisl architecture together with the event communication protocol provides modularity between the service logic 201 and user interfaces 204 . in particular , two features of the event communication protocol allow service logic 201 to function completely without knowledge of the specifics of the individual user interfaces 204 . these features are : ( 1 ) events are multicast from service logic 201 via service monitor 202 to user interfaces 204 and , consequently , service logic 201 does not need to know the destinations of these events ; and ( 2 ) the source of the events from the user interfaces 204 is not recorded and , consequently , the service logic 201 does not know which one or more of user interfaces 204 sent the events . service monitor 202 is responsible for maintaining this communication protocol . this modularity allows service providers to provide interchangeable user interfaces 204 , or add new ones , to a single consistent source of service logic and data . specifically , shown in fig2 are service logic unit 201 , service monitor 202 and user interfaces 204 - 1 through 204 - n . the key principle underlying sisl is that all user interfaces 204 to a service share a single service logic 201 . all communications between the service logic 201 and its multiple user interfaces 204 are through events , via a service monitor 202 . events from the service logic 201 are broadcast to the user interfaces 204 via 203 to the service monitor 202 and , then , via 205 as a set of enabled events to the user interfaces 204 . at the outset of the service , for example the any - time teller banking service , each user interface 204 registers with the service monitor 202 to indicate which events it is interested in receiving . after collecting information from the user , the user interfaces 204 send events to the service monitor 202 via bi - directional links 205 ; the service monitor 202 does not record the source of these events . the service monitor 202 passes the events , one at a time , via 203 to the service logic 201 . details of a service monitor , which can be advantageously employed for service monitor 202 , are described in co - pending u . s . patent application ser . no . 09 / 386 , 093 ( t . j . ball et al .) filed concurrently herewith and assigned to the assignee of this application . event communication supports decoupling of the service logic 201 and the user interfaces 204 , and allows service providers to provide interchangeable user interfaces 204 , or add new ones , to a single consistent source of service logic 201 and data . in each round of interaction , the sisl infrastructure automatically sends out a set of events via 203 from the service logic 201 to the service monitor 202 , corresponding to the events that are currently enabled in the service logic 201 . there are three kinds of events : prompt events , up events , and notify events . prompt events indicate to the user interface what information to communicate to the user and what information the service is ready to accept . there are three kinds of prompt events : prompt_choice events are disjunctive choices currently enabled in the service logic 201 . for example , after the user has successfully logged into the any - time teller banking service , a choice among the different transaction types is enabled . the service logic 201 sends a prompt_choice_deposit , prompt_choice_withdrawal event , and a prompt_choice_transfer event , and so forth , via 203 to the service monitor 202 . prompt_req events are the events currently required by the service logic 201 . for example , suppose the user has chosen to perform a transfer transaction . the any - time teller requires that the user input a source account , a transfer account , and amount , and hence sends prompt_req_src , prompt_req_tgt , and prompt_req_amt events via 203 to the service monitor 202 . prompt_opt events are events enabled in the service logic 201 , for which the user may correct previously given information . for example , suppose the user is performing a transfer and has already provided his / her source and target accounts , but not the amount . the service logic 201 sends prompt_opt_src , prompt_opt_tgt , and prompt_req_amt events via 203 to the service monitor 202 . this indicates that the user may override the previously given source and target accounts with new information . up events correspond to prior points in the service logic 201 to which the user may go back . for example , the service logic 201 sends an up_mainmenu event via 203 to the service monitor 202 . this allows the user to abort any transaction and go back up to the main menu . notify events are simply notifications that the user interface 204 should give the user ; for example , that a transaction has completed successfully or that information provided by the user was incorrect or inconsistent . fig3 is a flowchart illustrating the steps in implementing the sisl architecture of fig2 . specifically , the implementation process is started via step 301 . then , step 302 causes the sisl logic to be written in sisl . step 303 causes the service monitor 202 to be written . thereafter , a plurality of user interfaces ui - 1 thorough ui - n are developed in steps 304 - 1 through 304 - n . fig4 is a flowchart illustrating the steps in the process of executing reactive constraint graphs . specifically , step 401 obtains a root node ( n ). then step 402 tests to determine if the obtained node is a data based choice node . if the test result in step 402 is no , step 403 tests to determine whether the obtained node is an event based choice node . if the tests result in step 403 is no , step 404 tests to determine if the obtained node is an action node . if the test result in step 404 is yes , step 405 causes the execution of the action , the execution of the notification associated with node “ n ” and sets “ n = child node ”, as determined from the current obtained node . if the test result in step 404 is no , step 406 causes the execution of the process of the constraint flowchart of fig5 as described below , until a new child node is determined and , then , assigns “ n ” to the determined new child node . returning to step 402 , if the test result is yes , the node is data based , and step 407 causes a unique arc “ a ” to be selected from node “ n ” whose precondition is true . then step 408 causes the execution of an action and notification associated with arc “ a ”. thereafter , step 408 sets “ n = child ” node of “ a ”. returning to step 403 , if the test result is yes , the node is event based , and step 409 causes a wait for any event “ e ” that is the label of some arc “ a ” from node “ n ” or is the uplabel of some ancestor node of node “ n ”. then , step 410 tests to determine if event “ e ” is the uplabel of some ancestor node of node “ n ”. if the test result in step 410 is yes , step 411 causes control to be transferred to the ancestor node . if the test result in step 410 is no , control is passed to step 408 , which is then effected as described above . reactive constraints are discussed further below . fig5 a and fig5 b when connected a — a , b — b , c — c , and d — d is a flowchart illustrating the steps in the process of executing constraint nodes . specifically , step 501 causes the entry action to be executed . then , step 502 causes initialization of a table to be one entry for each event occurring in an associated constraint ; value to false ; and data to empty . thereafter , step 503 causes a prompt_req to be sent to service monitor 202 for every event “ e ” whose value is set to false in the table , and a prompt_opt to be sent to service monitor 202 for every event “ e ” whose value is set to true in the table . step 504 waits for an event “ e ” that occurs in any associated constraint , or is the uplabel of an ancestor node . then , step 505 tests to determine whether event “ e ” is an uplabel of an ancestor node . if the test result instep 505 is yes , control is transferred to the ancestor node via step 506 . if the test result in step 505 is no , step 507 causes event “ e ” to be set true in the table , and assigns data to be “ e &# 39 ; s ” data . then , step 508 tests to determine if any constraints are enabled . if the test result in step 508 is yes , step 509 causes the next enabled constraint to be evaluated . then , step 510 tests to determine whether the evaluated constraint has been satisfied . if the test result in step 510 is no , the constraint is not satisfied and step 511 causes the execution to be effected of the violation action and the notification of violated constraint . step 512 causes the setting of event “ e ” to be false in the table and clears “ e &# 39 ; s ” data . thereafter , step 513 tests to determine if a child node is specified . if the test result instep 513 is yes , step 514 causes control to be transferred to the specified child node . returning to step 508 , if the test result is no , there are no remaining constraints that are enabled and step 515 causes the execution of the satisfaction action and the notification of all satisfied constraints . then , step 516 tests to determine whether all constraints have been satisfied . if the test result in step 516 is yes , step 517 causes the child node to be determined and , then , transfers control to it . if the test result in step 516 is no , control is returned to step 503 and appropriate ones of steps 503 through 517 are iterated until either step 506 is reached , or step 514 is reached , or step 517 is reached . returning to step 510 , if a yes result is obtained , control is returned to step 508 and steps 508 through 510 are iterated until either step 508 yields a no result or step 510 yields a no result . then , the processes , as described above regarding steps 508 or 510 yielding a no result are repeated . returning to step 513 , if the test result is no , the child node is not specified and control is returned to step 503 . thereafter , appropriate ones of steps 503 through 517 are iterated until either step 506 , or step 514 or step 517 is reached . fig6 . illustrates in pseudo code form a portion of an automatic speech recognition ( asr ) interface and a web user interface employed in the any - time teller example . the pseudo code of fig6 is self explanatory and is as follows : if ( transaction_type . equals (“ transfer ”)){ if ( req_events . contains ({“ src ”, “ tgt ”, “ amount ”})){ return (“ please specify the source account , target account , and the amount you would like to transfer .”) if ( req_events . contains_any_of (“ startdeposit ”, “ startwithdrawal ”, “ starttransfer ”, “ startbalance ”){ return (“ you may make a deposit , withdrawal or transfer . or you may quit the service ”); fig9 shows in pseudo code form a portion of the asr interface grammar used in the any - time teller example . the pseudo code of fig9 is self explanatory and is as follows : fig1 shows in pseudo code form a portion of an asr user interface employed in the any - time teller example . the pseudo code of fig1 is self explanatory and is as follows : fig1 is a flow diagram illustrating a reactive constraint graph for a portion of the any - time teller banking service example . in sisl , the service logic 201 ( fig2 ) of an application is specified as a reactive constraint graph , which is a directed acyclic graph with an enriched structure on the nodes . the traversal of reactive constraint graphs is driven by the reception of events from the environment ; these events have an associated label , i . e ., the event name , and may carry associated data . in response , the graph traverses its nodes and executes actions ; the reaction of the graph ends when it needs to wait for the next event to be sent by the environment . for example , fig1 shows a sisl reactive constraint graph that implements part of the functionality of the any - time teller . reactive constraint graphs can have three kinds of nodes , namely , choice nodes , constraint nodes and action nodes . these nodes represent a disjunction of information to be received from the user . every choice node has a specified set of events . there are two forms of choice nodes , namely , event - based and data - based . every event - based choice node has a specified set of events . for every event in this set , the sisl infrastructure automatically sends out a corresponding prompt_choice event from the service logic 201 to the user interface , via the service monitor 202 . the choice node waits for the user interface to send , via the service monitor 202 , any event in the specified set . when such an event arrives , the corresponding transition is taken , and control transfers to the descendent , i . e ., child , node . for example , if a starttransfer event arrives when control is at the choice node , the corresponding transition is taken and control is transferred to the target constraint node . to ensure determinism , all outgoing transitions of a choice node must be labeled with distinct event names . every data - based choice node has a specified set of preconditions on data . to ensure determinism , these preconditions must be specified so that exactly one of them is “ true ” in any state of the system . when control reaches a data - based choice node , the transition associated with the unique “ true ” precondition is taken , and control is transferred to the child node . the constraint nodes represent a conjunction of information to be received from the user . every constraint node has an associated set of constraints on events . constraints have the following components : the evaluation function is a boolean function on the events in the signature . the optional satisfaction tuple consists of an optional action , not involving user interaction , and an optional notify function that may return a notify event with an associated message . if the constraint evaluates to true , the action is executed , the notify function is executed and the returned notify event is sent to the user interface via the service monitor 202 . the optional violation tuple consists of an optional action , not involving user interaction , an optional notify function that may return a notify event with an associated message , an optional uplabel function that may return the uplabel of an ancestor node and an optional child node . if the constraint evaluates to “ false ”, the action is executed , the notify function is executed and the returned notify event is sent to the user interfaces 204 via the service monitor 202 . the uplabel function is also executed ; if it returns an ancestor &# 39 ; s uplabel , it is generated , and hence control reverts back to the ancestor node . if no ancestor node &# 39 ; s uplabel is returned and a child node is specified , control is transferred to the specified child node . for example , amt & lt ;= balance ( src ) of 1107 in fig1 is equivalent to ? amt & lt ;= balance (? src ) in fig1 a and 12b , and is the evaluation of constraint ( c 4 ) of fig1 a and 12b , as described below . the signature of this constraint is the set { amt , src }, and the satisfaction notify function and violation notify function , respectively , report to the user whether or not the source account has enough funds to cover the requested amount . the notification ? eventname refers to the data on the event with name eventname . an associated set of constraints . in the current semantics and implementation , this set is totally ordered , specifying the priority order in which the constraints are evaluated . an optional finished tuple , consisting of an optional exit action , not involving user action , an optional notify function , an optional uplabel function and an optional child node . a detailed description of constraint node execution is shown in fig1 a and 13b and summarized below . the sisl infrastructure automatically sends out a prompt_req event , from the service logic 201 ( fig2 ) to the user interfaces 204 via the service monitor 202 , for every event that is still needed in order to evaluate some constraint . additionally , the constraint node sends out a prompt_opt event for all other events mentioned in the constraints . these correspond to the information that can be corrected by the user . in every round of interaction , the constraint node waits for the user interface to send , via the service monitor 202 , any event that is mentioned in the signature of its associated constraints . each constraint associated with a constraint node is evaluated as soon as all of its events have arrived . if an event is resent by the user interfaces 204 , i . e ., information is corrected , all constraints with that event in their signature are re - evaluated . for every evaluated constraint , its optional satisfied / violated action is automatically executed , and a notify event is automatically sent to the user interfaces 204 , with the specified message . specifically , the constraints are evaluated in the specified priority order , currently the total ordered set . if any constraint is violated , the last received event is automatically erased from all constraints , since it caused an inconsistency . furthermore , the violation action is executed , the notify function is executed and the returned notify event is automatically sent to the user interfaces 204 via the service monitor 202 . the uplabel function is also executed ; if it returns an ancestor &# 39 ; s uplabel , it is generated and , hence control reverts back to that ancestor . for example , in fig1 , the constraint node 1103 for the transfer capability checks whether the source account is an active account of the given customer , i . e ., user , via constraint ( c 0 ) of fig1 . if not , it generates the uplabel “ loginmenu ”, and control is transferred back to the login node 1101 . then , the user must re - enter his / her login . if no ancestor node &# 39 ; s uplabel is returned and a child node is specified , control is transferred to that child node . for example , in fig1 , the login node 1101 checks whether the login is of a customer in good standing , via constraint good_customer of fig1 , which evaluates goodcustomer ( login ). if not , control is transferred to the quit node and the service is terminated . if no ancestor node &# 39 ; s uplabel is returned or child node specified for the violated constraint , the node reverts to waiting for events to arrive . if no constraints have been violated , the action of every satisfied constraint is executed , the associated notify functions are executed and the returned notify events are sent to the user interfaces 204 via the service monitor 202 . when all the constraints have been evaluated and are satisfied , the exit action and notify function associated with the constraint node are executed and the returned notify event is sent to the user interfaces 204 via the service monitor 202 . the uplabel function is also executed ; if it returns an ancestor node &# 39 ; s uplabel , it is generated , and hence control is returned back to the ancestor node . if no ancestor node &# 39 ; s uplabel is returned and a child node it specified , control is transferred to that child node . these nodes represent some action , not involving user interaction , to be taken . after the action is executed , control transfers to the child node . nodes can have an optional “ uplabel ”, which is used to transfer control from some child node back up to the node , allowing the user to revert back to previous points in the service . in each round of interaction , the sisl infrastructure automatically sends out an up event , from the service logic 201 to the user interfaces 204 via the service monitor 202 , corresponding to the uplabel of every ancestor of the current node . nodes can also have a self - looping arc , with a boolean precondition on data . this indicates that the subgraph from the node will be repeatedly executed until the precondition becomes false . by way of an example execution of the any - time teller banking service as shown in fig1 , the sisl based invention shall be illustrated using the web - based , automatic speech recognition - based and telephone voice - based user interfaces 204 partially set forth in pseudo code in fig6 and 10 , respectively . the service initially causes the statement “ welcome to any - time teller ” to be spoken . the control point is at the root node , which is a constraint node . for the constraint of the root node to be satisfied , the login and pin values must be identified , i . e ., login == pin , as shown in step 1101 of fig1 . the sisl infrastructure automatically sends out a prompt_req_login and a prompt_req_pin from the service logic 201 to the user interfaces 204 , via the service monitor 202 . the user interfaces 204 , via the prompt function , respond by saying “ please specify your login and personal identification number ”. for the web - based user interface , text fields for the login and pin are automatically generated , in known fashion ; for the speech recognition - based user interface , the grammars specified in the grammar function are automatically enabled . in this example , suppose that the user states “ my login is mary smith and my pin is mary smith ”, and hence a login event with the value “ mary smith ” and a pin event with the value “ mary smith ” are sent to the service logic 201 . since the login and pin are identical , the constraint is satisfied . the sisl infrastructure automatically sends out a notify event with the message “ hello mary smith ”. welcome to the sisl any - time teller ”. the user interface makes this statement to the user . control now proceeds to step 1102 and to the choice node . the sisl infrastructure automatically sends out : events from the service logic 201 ( fig2 ) to the user interfaces 204 , via the service monitor 202 , corresponding to the enabled choices . the user interfaces 204 ask the user “ what transaction would you like to do ?” fig7 shows a screen snapshot of the web - based user interface ; the possible choices are shown as radial buttons . for an automatic speech recognition - based user interface , if the user states “ i need help ”, the user interface states , via the help function shown in pseudo code form in fig6 “ you can make a withdrawal , deposit transfer or you can quit the service ”. consider that the user now chooses to perform a transfer , the starttransfer event is sent to the service logic 201 . control now proceeds to constraint node 1106 . the sisl infrastructure automatically sends out : events from the service logic 201 to the user interfaces 204 , via the service monitor 202 , together with a up_mainmenu event , since it is the uplabel of an ancestor node . assume that the user respond with “ i would like to transfer one thousand dollars ($ 1 , 000 . 00 ) from my checking account ”, or equivalently “ from checking , i would like to transfer one thousand dollars ($ 1 , 000 . 00 )”. either order of the transfer request information is allowed ; furthermore , this information in partial , since the target account is not specified . the user interface 204 sends a src event and an amt event , with the corresponding data , to the service monitor 202 , which sends them one at a time to the service logic 201 . assume that the src event is sent first , followed by the amt event . the constraints amt & gt ; o , isvalid ( src ) and amt & lt ;= balance ( src ) are automatically evaluated . assume that the checking account does not have a balance of at least $ 1 , 000 . 00 ; hence , there is a constraint violation and the supplied information is erased , since it was sent last . note that constraints are evaluated as soon as possible ; for example , the user is not required to specify a target account in order for the balance on the source account to be checked . the sisl infrastructure then automatically sends out a prompt_opt_src , prompt_req_tgt , prompt_req_amt and upmainmemu events from the service logic 201 to the user interfaces 204 , via the service monitor 202 , as well as , a notify event with the message “ your checking account does not have sufficient funds to cover the amount of $ 1 , 000 . 00 . please specify an amount and a target account .” the user interface 204 then notifies the user with this message and prompts the user for the information . assume now that the user states “ transfer five hundred dollars ($ 500 . 00 ) to savings ”. the amt and tgt events are sent to the service monitor 202 , and passed to the service logic 201 . the constraints are now all evaluated and satisfied , the service logic 201 automatically sends a notify event to the user interfaces 204 with the message “ your transfer of $ 500 . 00 from checking to savings was successful ”. control then is returned back up to the choice node 1102 ; the loop on the incoming arc to the choice node indicates that the corresponding subgraph is repeatedly executed until the condition on the arc becomes false . if the user wants to quit the service , the userquit event is sent to the service logic 201 , the hasquit variable is set to true , and the loop is terminated . while in step 1102 , a loop step 1104 is performed to test if the user has terminated , i . e ., quit , the session . if the user would like to abort at any time during a withdrawal , deposit or transfer transaction , he / she can state “ i would like to go back up to the main menu ”, which results in an up_mainmenu event to be sent to the service logic 201 . this causes control to be returned to the choice node 1102 , which has an associated upmainmenu label . if a user wishes to make a deposit control proceeds to the deposit constraint node 1106 . the sisl infrastructure automatically sends out events from the service logic 201 to the user interfaces 204 via service monitor 202 . if the target account is valid and the amount is greater than zero ( 0 ) the deposit is made and the associated notification is executed . if a user wishes to make a withdrawal control proceeds to the deposit constraint node 1107 . the sisl infrastructure automatically sends out : events from the service logic 201 to the user interfaces 204 via service monitor 202 . if the source account is valid and the amount is greater than zero ( 0 ), it is determined if amt & lt ;= balance ( src ) and , if so , the withdrawal is made and the associated notification is executed . fig1 a and fig1 b , when connected x — x , illustrate in pseudo code form the steps of a portion of the sisl service unit process used in the any - time teller banking service example . the pseudo code of fig1 a and 12b is self explanatory and is as follows : violation : notify (“ sorry , this account is not active . please log into the service again .”); violation : notify (“ sorry , your ”? src +“ account does not have sufficient funds to cover the amount of ”+? amt +“ dollars .”)); transfer = constraintnode ( constraints : { c 0 , c 1 , c 2 , c 3 , c 4 , c 5 }; fig1 a and fig1 b , when connected y — y , illustrate the steps performed in the execution of constraint nodes . the procedure of a constraint node is as follows : 1 . the node first executes its ( optional ) entry action . it then creates a table in which every event in the signature of a constraint associated with the node has a slot . each such event has a single slot in the table , even if it occurs in multiple constraints . each slot in the table contains three fields : the name of the event , the data associated with the event when it arrives , and a boolean variable that indicates whether the event arrived from the environment and did not cause a constraint violation . the data field of every slot is initially empty and the boolean variable in every slot is initially false . 2 . the node sends a prompt_req event to the user interfaces ( via the service monitor )— for every event “ e ” whose boolean variable is set to false in the table . 3 . the node sends a prompt_opt event to the user interfaces ( via the service monitor )— for every event “ e ” whose boolean variable is set to true in the table . 4 . the node then waits for any event that is in the signature of any constraint associated with the node , i . e ., has a slot in the table or is the uplabel of any ancestor node . 5 . upon arrival of any such event “ e ”, if “ e ” is the uplabel of some ancestor node , control is transferred to that ancestor . otherwise : ( a ) the boolean variable in the slot for “ e ” is set to true . the data associated with the event “ e ” is written in the table ; if previous data is present , it is first erased . ( b ) the enabled constraints “ c ” are those that satisfy the following conditions : all events in the signature of the constraint “ c ” have their boolean variables set to true in the table . ( c ) the enabled constraints “ c ” are evaluated in the specified priority order : its ( optional ) violation action and notify function are executed , and the returned notify event is sent to the user interfaces via the service monitor . the boolean variable in the slot for “ e ” is reset to false , and the data field is reinitialized to be empty . the uplabel function of constraint “ c ” is executed ( if it is specified ). if it returns the uplabel of an ancestor node , the uplabel is generated and control is transferred to the ancestor node . else the constraint node goes back to waiting for events , ( step 2 ). else the next enabled constraint is evaluated . if none remain to be evaluated , the constraint node goes to step5 ( d ). the ( optional ) satisfaction action and notify function of each satisfied constraint are executed , and the returned notify events are sent to the user interface via the service monitor . if all constraints associated with the node were enabled and satisfied . the ( optional ) exit action and notify function are executed and the returned notify event is sent to the user interfaces via the service monitor . the uplabel function of the constraint node is executed ( if it is specified ). if it returns the uplabel of an ancestor node , the uplabel is generated and control is transferred to the ancestor node . else the constraint node goes back to waiting for events , ( step 2 ). the above - described embodiment is , of course , merely illustrative of the principles of the invention . indeed , numerous other methods or apparatus may be devised by those skilled in the art without departing from the spirit and scope of the invention . for example , sisl may be advantageously implemented using an extensible markup language ( xml ). xml is a metalanguage for defining mark - up languages such as html . sisl can be implemented by defining an xlm document type declaration ( dtd ), corresponding to a grammar for reactive constraint graphs . sisl services are then specified in xml using dtd , and the sisl implementation of the service is automatically generated by the sisl infrastructure .
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according to embodiments of the invention , ram in devices separate from the main memory (“ separate ram ”) may be used for a stack and temporary storage during bios execution . the separate ram is typically dedicated , in its normal usage , to one or more functional logic blocks of a chipset . for example , ram in a local area network ( lan ) controller is available during bios execution . a lan controller includes thousands of bytes of ram that are normally used to transmit data packets . however , applications are not able to send data packets until the main memory is fully configured , which does not occur until bios has finished performing this task . accordingly , there is ram in the lan controller which is unused until bios execution has completed , and is therefore available to speed bios execution itself . similarly , a universal serial bus ( usb ) controller includes ram unused for its normal function during bios execution , and therefore available to bios . various other ( non - main memory ) rams are available in a typical chipset . according to embodiments of the invention , a selected range of available physical address space supported by the central processing unit ( cpu ), but not populated by physical main memory , may be mapped to separate ram . usually , there is substantially more physical address space supported than is needed to address the actual physical memory ( e . g ., simm ( single inline memory module ) or dimm ( dual inline memory module ) dram ( dynamic ram )) installed in a system . in accordance with embodiments of the invention , during boot - up , an operational mode may be entered in which space in separate ram is made available to the bios program for a stack and temporary storage . in an embodiment , this operational mode may be set by programming an enable bit in the chipset . the enable bit may be automatically turned on or may be set by the bios routine . the bios routine may then initialize the stack pointer of the cpu to point to an address in the selected range of addresses mapped to the separate ram . according to this embodiment , subsequent instructions of the bios program may now include operations on a stack , such as “ push ” or “ pop ” instructions for calling subroutines , to write to or read from the stack pointed to by the cpu &# 39 ; s stack pointer . when the address in the stack pointer is asserted on the cpu &# 39 ; s address bus due to , for example , a push or pop instruction , and the chipset is in the operational mode for using separate ram for bios processing , the address is recognized as being within the range mapped to the separate ram , and the appropriate data is accordingly written to or read from the selected range of addresses in the separate ram . an exemplary embodiment of the invention is shown in fig1 . fig1 illustrates components in an intel ® chipset architecture used in personal computers . the chipset includes a cpu 100 connected to a memory controller ( mch or memory control hub ) 101 . the mch is connected to main memory 102 , and performs reads and writes to main memory 102 under the control of an instruction sequence executed by the cpu 100 . the mch is further connected to an i / o controller ( ich or i / o control hub ) 103 comprising a usb controller 104 . the usb controller 104 includes a separate ram 106 . as indicated above , according to embodiments of the invention , a selected range of available physical address space supported by the cpu , but not populated by physical main memory , may be mapped to space in separate ram 106 . in an embodiment , the addresses in the selected range may be higher than the highest location in main memory addressable by the mch , or “ top of memory .” top of memory is the highest address in the physical address space supported by the cpu at which there is corresponding physically populated memory . by mapping the selected range above top of memory , it is ensured that the address range assigned to ram 106 will not conflict with a range assigned to main memory 102 when main memory is enabled . accordingly , in this embodiment , when during the execution of a stack operation called for by the bios program 109 , the cpu attempts to access an address above top of memory , the mch recognizes that it is unable to perform the access and passes the address to the ich 103 . direct memory access ( dma ) engine 105 as shown in fig1 represents already existing logic in the ich for moving data between the ram 106 and main memory 102 under the normal operating circumstances ( i . e ., post - boot - up ) of the usb controller . normally , the cpu is unable to directly access the ram 106 . rather , the ram 106 is only used locally by the dma engine 105 and is treated as a first - in - first - out ( fifo ) buffer , though the ram is physically implemented as a ram with two ports . address decoder 107 and multiplexer ( mux ) 108 , on the other hand , represent elements of the present invention according to the exemplary embodiment under discussion . in this embodiment , the address decoder 107 may be configured to decode the selected range of addresses mapped to the ram 106 , enabling the cpu to access the ram 106 when an address within the selected range is passed to the ich by the mch . the mux 108 may be configured to be responsive to the operational mode set during system boot - up . for example , the mux may be controlled by the enable bit to select access to the ram 106 by either address decoder 107 or dma engine 105 . referring to fig2 , an illustrative example of an embodiment of an application of the invention follows . as shown in block 200 , a selected range of addresses including , for example , address x ′ ffff6000 , may be mapped to space in the ram 106 . address x ′ ffff6000 is typically well above top of memory . due to a system power - on or reset , main memory is unconfigured and the mch has no information about the main memory . the cpu executes its first instruction cycle , in which it attempts an access to memory . since the mch has no information about main memory , it transfers the attempted memory access to the ich . the ich searches for attached memory , and finds the eprom ( erasable programmable read - only memory ) 109 storing the bios program . accordingly , the cpu begins to fetch the instructions of the bios program , as shown in block 201 then , an operational mode for accessing the ram 106 to use space therein as a stack may be entered , as shown in block 202 . in an embodiment , the operational mode may be controlled by an enable bit . the enable bit may be automatically turned on at system power - up or reset , or may be set by an instruction in the bios program . the enable bit may control the mux 108 to select the input from the address decoder 107 rather than the dma engine 105 . once the bios has substantially completed its work , the enable bit will be reset to indicate that the ram 106 is to be returned to its normal usage , and no longer used for a stack . as shown in block 203 , as one of its initial steps , the bios program may set the stack pointer of the cpu to the value x ′ ffff6000 . while in current systems the bios program does initialize the cpu &# 39 ; s stack pointer , this occurs much later in the bios process . moreover , the stack pointed to is in main memory and can only be used after main memory is configured . by contrast , according to the present invention , a stack is available in separate ram substantially from the outset of the bios process . once the cpu &# 39 ; s stack pointer is initialized , the bios program may execute stack operations which will access the ram 106 , including calling subroutines , as shown in block 204 . whenever the cpu 100 asserts an address within the range mapped to ram 106 and the enable bit is set , the mch 101 will pass the address to the ich 103 , since the address is not one that the mch can handle . the address will appear on an internal address bus of the ich and be decoded by address decoder 107 to access the stack in ram 106 . as discussed above , the bios code is typically very lengthy and would be greatly expedited if enabled to use a stack . availability of a stack enables the bios program to be coded more easily and compactly , since subroutines may be called . further , parallelism is possible due to multi - threading , and consequently the bios process is significantly speeded up . once the bios program has executed past a certain point , for example , once main memory is fully configured , the stack in separate ram is no longer needed and normal chipset operations are possible . accordingly , the cpu &# 39 ; s stack pointer may be re - programmed to point to main memory and the enable bit may be reset so that accesses to ram 106 are made only by dma engine 105 , as shown in block 205 . in an alternative embodiment of the invention , a separate ram may be shared for use in its normal or dedicated function , and also for providing stack space to the bios program . for example , bios processing may advance to a stage wherein normal operations by the usb controller are possible , but main memory is still not fully configured , and therefore a stack in separate ram is still needed or useful . to enable usb operations to proceed at the same time as bios processing continues , a portion of the ram 106 could be reserved for access by the dma 105 , while another portion could be set aside for a stack for the bios program . fig1 b illustrates such an alternative embodiment . in fig1 b , ram 106 is divided into a first portion 115 and a second portion 116 . the first and second portions need not be equal in size and can take on any desired relative proportions . the first portion 115 may be set aside for a stack and accessible as described in the foregoing . that is , an operational mode may control mux 108 to determine whether the first portion 116 is accessed by address decoder 107 or by dma engine 105 . second portion 116 , on the other hand , may be coupled to dma engine 105 and accessible independently of the operational mode controlling the mux . thus , second portion 116 may be available for operations by the usb as soon as bios processing has advanced to a stage wherein such operations are possible . while the efficiency of the usb operations might be somewhat reduced during a period of sharing the ram 106 , sharing would allow usb operations to proceed in parallel with bios processing , thereby reducing delay in available chipset functions . once bios processing was complete , the stack space could be returned to the usb controller , which would then operate with full efficiency . a bios program including computer - executable instructions according to embodiments of the present invention may be stored and transported on a computer - usable medium such as diskette , magnetic tape , disk or cd - rom . the instructions may be downloaded to a second storage medium such as eprom 109 , from which they may be fetched and executed by a processor such as cpu 100 to effect the advantageous features of the invention . several embodiments of the present invention are specifically illustrated and described herein . however , it will be appreciated that modifications and variations of the present invention are covered by the above teachings and within the purview of the appended claims without departing from the spirit and intended scope of the invention .
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hyperlipidemia relates to plasma cholesterol and triglyceride levels that exceed “ normal ”— arbitrarily defined as the 95 th percentile . but it is now clear that “ ideal ” or “ optimal ” levels are far below the normal levels of the population . a large proportion of united states adults have concentrations above the optimal range and should be considered to have hyperlipoproteinemia . j . hardman , supra , at 875 . in a preferred embodiment of the invention , a composition is administered that simultaneously affects several different mechanisms in the production of atherosclerosis , including the levels of ldl and hdl cholesterol , through inhibiting hmg - coa reductase , correcting any consequent depletion of coenzyme q 10 , and inhibiting the oxidation of ldl into lipid peroxidases . in another embodiment , chromium or inositol hexanicotinate , or both , is added for control of insulin and lipid metabolism and additional control or reduction of cholesterol levels . one theory is that both the presence of elevated plasma ldl and its oxidative modification within the artery wall is required to produce atherosclerosis . steinberg , supra . indeed , then the use of an appropriate antioxidant in vivo should decrease the rate at which ldl is taken up by macrophage foam cells and slow the development of the fatty streak lesion . this phenomena has been demonstrated in receptor deficient rabbits treated with probucol as an antioxidant . parthasarathy , supra . red yeast is a mixture of several species of monascus fungi ; the predominant one is monascus purpureus . monascus was first described in 1884 . van tieghem , 31 bull . soc &# 39 ; y botany france 226 ( 1884 ). monascus is has been used for centuries as in wine fermentation and as a food colorant and preservative . see http :// www . allok . com / ehistorie . htm . a traditional chinese product used to make rice wine and as a preservative is based on rice that has been fermented with monascus purpureus . heber , 69 am . j clinical nutrition 231 - 236 ( 1999 ), citing stuart , chinese materia medica — vegetable kingdom ( 1979 ). this product also has a tradition of being useful in “ improving the blood circulation .” d . bensky & amp ; r . barolet , chinese herbal medicine : materia medica ( revised ed . 1993 ). the medical applications of red yeast were described in the ancient chinese pharmacopoeia , pen ts &# 39 ; ao kang mu , published during the ming dynasty ( 1368 - 1644 ). it describes red yeast as useful for treating indigestion , diarrhea , and improving the health of the spleen , stomach , and circulation . in ancient china , monascus was called “ hongqu ” and was said to have the ability to cure stomach and spleen , to strengthen the blood , and the principle to preserve and endorse the common qi interdependent . ben cao gang mu von li shi - zen , book of medicinal herbs ( 1590 ). more recently , researchers discovered that a strain of monascus yeast used in the production of red yeast rice naturally produced a substance that inhibits cholesterol synthesis called monacolin k ( lovastatin ), along with a group of 8 monacolin - related substances that are hmg - coa reductase inhibitors . endo , supra . experiments in rabbits revealed that one extract , xuezhikang , lowered cholesterol levels by 44 % and 59 % at doses of 0 . 4 and 0 . 8 mg / kg , respectively . id ., see also li , 18 ( 1 ) nutrition research 71 - 81 ( 1998 ). these doses correspond to human doses of 24 mg and 48 mg ( for a 60 - kg person ). chinese red yeast rice costs only $ 20 - 30 per month at such doses , compared to the average cost of $ 187 / month for a cholesterol - lowering drug . id . the effects of monascus purpureus rice in 324 patients were compared with the effects of another chinese herbal medicine , jiaogulan ( gynostemma pentaphylla ) on serum cholesterol . wang , 58 ( 12 ) current therapeutic research 964 - 978 ( 1997 ). eligible patients were recruited if their serum total cholesterol ( tc ) was 240 mg / dl ( 5 . 95 mmol / l ) or higher , ldl - cholesterol was 130 mg / dl ( 3 . 41 mmol / l ), or triglycerides ( tg ) were 200 - 400 mg / dl ( 2 . 26 - 4 . 52 mmol / l ). in addition , hdl - cholesterol was 40 mg / dl ( 1 . 04 mmol / l ) or less for men or 45 mg / dl ( 1 . 16 mmol / l ) for women . after 8 weeks , total cholesterol decreased by 34 . 5 % ( p & lt ; 0 . 001 ) in treated patients while the positive controls had only an 8 . 3 % decrease . those patients with pretreatment cholesterol over 300 mg / dl had a greater reduction than did those whose cholesterol prior to treatment was below 240 mg / dl . and while the increase in hdl cholesterol was minor for those with pre - treatment levels & gt ; 45 mg / dl , significant increases were observed in those with pretreatment hdl of 35 - 45 mg / dl ( 16 %) and less than 35 mg / dl ( 25 . 1 %). coenzyme q 10 ( ubiquinone ) is a naturally occurring substance that plays a central role in oxidative respiration as a catalyst and has a separate direct membrane stabilizing effect . in man , vitamin e , beta - carotene , and coenzyme q 10 all appear to be endogenous antioxidants in ldl . epidemiologic data suggest a negative correlation between coronary disease and levels of vitamin e . witztum & amp ; steinberg , supra . it is also an antioxidant and free radical scavenger , and protects ischemic tissue from the damage that occurs when blood flow is restored ( reperfusion damage ). in studies of cardiac patients , deficiencies of the enzyme were found in 75 % of 132 biopsy specimens of heart tissues , and 20 % of 406 blood samples . studies performed by several different groups of researchers have shown that supplementation with coenzyme q 10 improves the signs and symptoms of cad at doses of 1 . 5 mg / kg per day ( 90 mg in a 60 kg person ), 150 mg / day and 600 mg / day . greenberg & amp ; frishman , 30 j . clinical pharmacology 596 - 608 ( 1990 ) at p . 599 . earlier clinical studies in japan used a dose of 5 mg , and later a dose range of 25 - 100 mg . folkers , et al , 2 j . molecular medicine 431 - 460 ( 1977 ). coenzyme q 10 and alpha - tocopherol in the ldl cholesterol are depleted faster on lovastatin therapy during peroxidative insult . the finding was associated with a shortened lag time of conjugated diene formation suggesting diminished resistance of ldl particles to the early phase of oxidative stress . a crossover study was conducted to investigate the effects of supplementation with 180 mg per day ubiquinone ( coenzyme q 10 ). there were no differences in the measurements for cholesterol , ldl , hdl , the ldl / hdl ratio , triglycerides , or apolipoprotein levels between treatment arms . but in the oxidative studies , the total depletion time of ldl coenzyme q 10 was 49 . 6 % longer on lovastatin but was comparable to pre - treatment levels with supplementation . the authors concluded that the improvement was scarce and its clinical relevance remained open . palomaki , 39 j . lipid research 1430 - 1437 ( 1998 ). in men with familial combined hyperlipidemia , ldl was more prone to oxidation and the coenzyme q 10 in the ldl was more predominantly in a reduced state , suggesting the coenzyme q 10 plays an important role in protecting ldl from in vivo oxidation . de rijke , 17 ( 11 ) arteriosclerosis , thrombosis , and vascular biology 127 - 133 ( 1997 ). this was studied by comparing patients treated with 20 - mg simvastatin per day with or without supplementation with coenzyme q 10 at 100 mg per day . in both groups , both total cholesterol and ldl cholesterol declined and results were highly statistically significant . but levels of coenzyme q 10 , which started out similar , decreased in the group treated with simvastatin alone , yet increased in the group that was supplemented . bargossi , 15 molecular aspects of medicine s187 - s193 ( supp . 1994 ). minimally oxidized ldl is believed to be involved in the early stages of atherosclerosis . in several studies of the hgm - coa reductase induced coenzyme q 10 deficiency , supplementation with coenzyme q 10 at 100 mg to 180 mg was shown to correct the depletion of the enzyme within the ldl particle . id . supplementation with coenzyme q 10 , 100 mg per day for 30 days resulted in increased coenzyme q 10 levels in all three ldl subfractions ( p & lt ; 0 . 01 ) in each of the 10 subjects studied . small increases in vitamin e were observed , as well as a significant decrease in hydroperoxide levels in the ldl 3 subfraction , which is commonly elevated in patients at high risk for coronary artery disease . alleva , 92 proc . nat &# 39 ; l acad . sci . 9388 - 9391 ( 1995 ). in an open label , eight - year study , 424 patients with various forms of cardiovascular disease added coenzyme q 10 , 75 mg to 600 mg / day , to their diets . improvements in myocardial function ( 58 %) and decreased dependency on drugs ( 43 %) were noted . langsjoen , 15 molecular aspects of medicine s165 - s175 ( supp . 1994 ). several prospective studies suggest an inverse association between dietary intake or plasma concentrations of antioxidants and cvd . in a cross - cultural study of 16 european populations , the strongest inverse correlation in this study was observed between ischemic heart disease and plasma concentration of vitamin e , a well - established anti - oxidant . meydani , 345 ( 8943 ) lancet 170 - 175 ( 1995 ). however , two earlier studies in finland and the netherlands reviewed by meydani in 1995 did not find an association between serum vitamin e and subsequent cvd mortality . in men , a borderline significant association was found for dietary intake of vitamin e alone , but it was much stronger for vitamin e supplement users consuming above 100 iu vitamin e daily for at least 2 years . id . in their review of published studies , jha et . al , reported , inter alia , the results of the u . s . nurses &# 39 ; health study . this study followed 87 , 000 female nurses for an average of 8 years . about 13 % of women regularly used vitamin e supplements . these women , after adjustment for age , smoking , alcohol use , menopausal status , hormone use , exercise , aspirin use , hypertension , cholesterol intake , diabetes , caloric intake , and vitamin c and beta - carotene intake , had a statistically significant reduction in relative risk of 31 % ( 95 % confidence limit , 3 %, to 51 %) for non - fatal myocardial infarction and death from cardiovascular disease in comparison with women who did not use the supplements . the absolute risk reduction was 3 . 4 women per 10 , 000 woman - years ( a woman - year is one woman followed for one year ) of follow - up ( 8 . 5 compared with 5 . 2 per 10 , 000 woman - years of follow - up ). jha , et al ., 123 ( 11 ) annals of internal medicine 860 - 872 ( 1995 ). vitamin e is a mixture of tocopherols . d - alpha - tocopherol has the highest biological activity and is the most widely available form of vitamin e in food . the other isomers ( beta , gamma , and delta ) are less biologically active than d - alpha - tocopherol . the commercially available synthetic forms of vitamin e comprise an approximately equal mixture of eight stereoisomeric forms of alpha - tocopherol . for practical purposes , 1 international unit ( iu ) of vitamin e is referred to as 1 mg of the synthetic form , racemic alpha - tocopheryl acetate , and the natural form of d - alpha - tocopherol has a biopotency of vitamin e equal to 1 . 49 iu . vegetables and seed oils including soybean , safflower and corn , sunflower seeds , nuts , whole grains , and wheat germ are the main sources of the tocopherols . meydani , supra . researches have observed a relation between deficient selenium ( an antioxidant ) and an excess risk of acute myocardial infarction as well as death from chd and cvd in eastern finland . low serum selenium levels and lipid peroxidation in vivo are associated with accelerated progression of carotid atherosclerosis in eastern finnish men . in a 1994 study , salonen reported that a subject &# 39 ; s hair mercury content correlated most strongly of all cardiovascular risk factors . mercury forms an insoluble complex with selenium ( mercury selenide ), thus binding selenium in an inactive form that cannot serve as a cofactor for glutathione peroxidase , an important scavenger of peroxides and lipid peroxides . salonen , 91 ( 3 ) circulation 645 - 655 ( 1995 ). but another study based on 251 subjects who had infarctions and an equal number of healthy controls matched by age , smoking status , and time from randomization , showed no statistical association between plasma selenium and myocardial infarction . salvini , 76 ( 17 ) am . j . cardiology 1218 - 1221 ( 1995 ). deficiency of chromium , a trace element , has been associated with lipid abnormalities and an increased risk of atherosclerotic disease . newman measured serum chromium levels in 32 subjects referred for selective coronary arteriography . patients with catheterization - proven coronary disease had significantly lower serum chromium levels and higher serum triglyceride ( tg ) than patients without coronary disease . newman ha , et . al . 24 ( 4 ) clinical chemistry 541 - 4 ( 1978 ). chromium is a cofactor in the maintenance of normal lipid and carbohydrate metabolism and its supplementation in normal volunteers has been shown to reduce the levels of total cholesterol , ldl , and apolipoprotein b , and raise levels of hdl . press , geller & amp ; evans , 152 ( 1 ) western j . medicine 41 - 5 ( 1990 ). chromium and two molecules of nicotinic acid form a biologically active complex referred to as “ glucose tolerance factor ,” which has been reported to enhance the action of insulin . jeejeebhoy confirmed the its importance in humans when he successfully treated an insulin - resistant diabetic patient with only chromium supplementation after she had become chromium deficient after 3 years of parenteral nutrition . see lee & amp ; reasner , 17 ( 12 ) diabetes care 1449 - 1452 ( 1994 ). an increase in hdl cholesterol levels was observed after chromium treatment in 23 healthy volunteers and in 72 hypertensive men on beta - blockers . id . other groups have shown chromium to improve the lipid profile , hyperglycemia , and body weight in persons with obesity or diabetes . type 2 diabetics were treated with 100 - mcg chromium bid or 500 mcg bid or placebo . the higher dose group showed lower blood sugar and cholesterol than the placebo group after 2 and 4 months . anderson , 46 ( 11 ) diabetes 1786 - 91 ( 1997 ). chromium supplementation is also useful for elevated triglycerides . in a prospective , double - blind , cross - over study of 14 men and 16 women supplementation with chromium picolinate for 2 months resulted in a statistically significant reduction in triglyceride levels of 17 . 4 % ( 133 vs . 161 mg / dl ; p & lt ; 0 . 05 ). lee & amp ; reasner , supra . inositol hexaphosphate is a form of nicotinic acid that does not produce a flush . nicotinic acid ( niacin , a water - soluble b vitamin ) has been shown to decrease triglyceride , increase hdl cholesterol , lower ldl cholesterol , and decrease lipoprotein ( a ); it also decreases fibrinogen . gotto jr ., 82 ( 9a ) am . j . cardiology 22q - 25q ( 1998 ). it was also shown to increase levels of hdl - cholesterol by 35 %, to 1 . 20 +/− 0 . 21 mmol / liter ( 46 . 5 +/− 8 . 1 mg / dl ) at a mean dose of 2 , 250 mg / day . zema , 35 ( 3 ) journal of the american college of cardiology 640 - 6 ( 2000 ). nicotinic acid was first reported to be hypolipidemic in 1955 . large doses ( 3 to 6 g / day ) rapidly decrease vldl and ldl and dramatically increase hdl even as much as 20 or 30 mg / dl . but it causes numerous side effects , most importantly an intense flushing and pruritis . abnormalities of hepatic function , including jaundice , are potentially serious and can occur with 2 - g day or delayed - release products . elevated fasting glucose and delayed glucose tolerance occur frequently and rare side effects include reversible optic maculopathy , toxic amblyopia , arrhythmias , and orthostatic hypotension . see j . hardman at pp . 889 - 90 . probucol , a potent antioxidant , was marketed for several years as a hypolipidemic but is now considered only a second or third line agent because of its erratic ldl response and persistent ability to lower hdl levels . it inhibits atherosclerosis in hypercholesterolemic rabbits and non - human primates independently of its hypolipidemic effects , supporting the hypothesis that oxidation is a key step in its development . j . hardman , supra , at pp . 891 - 2 . short - term adverse effects include gastrointestinal symptoms , headache , dizziness and increase in the qt interval i many patients . all of the ingredients used in the compositions of the present invention are obtainable commercially by suppliers well known to those skilled in the art of nutritional supplement formulation . red yeast rice , although also commercially available , may alternatively be prepared by traditional means . indeed , the solid state fermentation of rice by monascus has a long tradition in east asian countries ; its fermentation dates back at least to the first century ad . heber , supra . the fermentate is obtained as scarlet to purple red grains , which have the original rice grain structure well preserved . the commercial product is mostly a ground powder , which is know as “ ang kak ” or “ hong qu ” in chinese the japanese name for the product is “ koji ”. traditional or improved red yeast can be prepared by traditional fermentation procedures or their modification . in ancient china , monascus was called “ hongqu ” and was first described in the 16 th century . b . c . g . m . von li shizhen , book of medicinal herbs ( 1590 ). it was said to have the ability to cure stomach and spleen , to strengthen the blood , and the principle to preserve and endorse the common qi interdependent . id . the preparation of hongqu was described as follows : you take 1 dan and 5 dou jing mi [ the rice ]. clean this with water in a bowl and let it soak for one night . then you &# 39 ; ll cook it like normal food . further you separate [ the rice ] in 15 portions and add jin pilzmutter . roll and knead [ the mass ] to distribute all equally . form [ all ] together to one portion and cover it carefully with a silkcloth . first heat [ the whole ], then take off the silk and splay [ the rice pulp ]. if the rice pulp is warm , push it together to a heap . again cover it carefully [ with a silkcloth ]. next day at noon again make three heaps [ of the pulp ], let it rest for a while and form of each part five heaps . let it rest a short time . then form all together to a heap . then let it rest for w while . then form 15 pieces . heat a little and then form again a heap . repeat this 5 times . at the third day fill a big tun with fresh water . dip short time and process wet and form again a heap . handle again with this method . at the fourth day again dip it in fresh water if the fungus falls for half and swim for half at the surface , then again use the method from above : dip shortly . if the fungus completely is at the surface , it &# 39 ; s ready . take it out and dry it in the sun . if this rice responds , we call it shenghuang , a fresh yellow color . if you add hongqu to alcohol , fish sauces or hacked meat , it results a fresh and appealing red . if it doesn &# 39 ; t appeal to the heart his quality isn &# 39 ; t very well . if added to medicaments , take stored , old hongqu , that &# 39 ; s good . according to another early reported method ( sung , t &# 39 ; ien kung k &# 39 ; ai wu 291 - 294 ( 1637 , sun trans . 1966 )), red yeast can be prepared by the fermentation of washed and cooked non - glutinous rice using red wine mash , natural juice of polygons grass , and alum water . the rice is fermented in open air for 7 days on bamboo trays under very clean conditions . the rice changes its color from white to black , black to brown , and brown to red and then red to yellow , which is then harvested as red yeast . according to an alternative traditional method , non - glutinous rice can be fermented in a hole in the ground lined by bamboo mats , which is securely covered . fermentation is allowed to take place underground for one year or more , up to four years . wo 98 / 14177 ( 1998 ), at p . 9 . the traditional method has been improved with modern fermentation techniques and equipment to more precisely control temperature , ph , pressure and other fermentation parameters thus reducing the time required . one example is as follows : culture media containing kidney - bean juice 2 %, sugar 4 %, yeast 0 . 5 % are added to rice ( 40 - 80 ml per 100 g ) and sterilized by heat while the ph is maintained at ph3 to 8 . red yeast fungi monascus purpureus went strain m4184 is added and cultured at 15 - 35 ° c . for 9 days . at the end of the fermentation process , the fermentation broth is drained and discarded , while the solid residue is sterilized by heat , dried and crushed into powder . id . this powder can be used directly in the various compositions and formulations provided in the present invention . monascus purpureus is available commercially around the world , through distributors such as dr . win fried bear at friedrich - breuer - str . 86 - d - 53225 bonn , allok at lachenmeyrs tr . 18a , 81827 , munchen , germany and samlong chemical co ., ltd ., p . b . box 65 , changzhou , jiangsu , china . coenzyme q 10 , mixed tocopherols ( vitamin e ), selenium , chromium , and inositol hexaphosphate are available commercially , in bulk and wholesale , from suppliers well known to those with ordinary skill in the art . for instance , vitamin e may be obtained from ava health po box 730 , grove city , ohio 43123 - 0730 and wholesale vitamins usa , inc ., of brooklyn , n . y . offers over 8 , 000 vitamins at wholesale prices . any dosage form may be employed for providing the patient with an effective dosage of the composition . dosage forms include tablets , capsules , dispersions , suspensions , solutions , capsules , transdermal delivery systems , etc . . . tablets and capsules represent the most advantageous oral dosage unit form . any method known to those of ordinary skill in the art may be used to prepare capsules , tablets , or other dosage formulations . pharmaceutically acceptable carriers include binding agents such as pregelatinized maize starch , polyvinylpyrrolidone or hydroxypropyl methycellulose ; binders or fillers such as lactose , pentosan , microcrystalline cellulose or calcium hydrogen phosphate ; lubricants such as magnesium stearate , talc or silica ; disintegrants such as potato starch or sodium starch ; or wetting agents such as sodium lauryl sulfate . tablets or capsules can be coated by methods well known to those of ordinary skill in the art . according to one aspect of the invention a composition is provided comprising a pharmaceutically acceptable combination of the composition and at least one carrier . pharmaceutically acceptable carriers for inclusion into the present compositions include carriers most suitable for combination with lipid - based drugs such as diluents , excipients and the like which enhance its oral administration . suitable carriers include , but are not limited to , sugars , starches , cellulose and derivatives thereof , wetting agents , lubricants such as sodium lauryl sulfate , stabilizers , tabletting agents , anti - oxidants , preservatives , coloring agents and flavoring agents . reference may be made to remington &# 39 ; s pharmaceutical sciences , ( 17th ed . 1985 ) for other carriers that would be suitable for combination with the present compositions . as will be appreciated , the pharmaceutical carriers used to prepare compositions in accordance with the present invention will depend on the administrable form to be used . according to one embodiment of the invention , the novel composition of the present invention comprises red yeast fermented on rice , coenzyme q 10 , chromium , selenium and mixed tocopherols and inositol hexanicotinate , and is formulated for oral administration . oral dosage forms formulated in accordance with standard pharmaceutical practice may be employed . capsules are a particularly useful vehicle for administering the present composition . the administration of the composition is preferably in accordance with a predetermined regimen , which may be at least once daily and over an extended period of time as a chronic treatment , and could last for one year or more , including the life of the host . the dosage administered will depend upon administration frequency , the blood level desired , other concurrent therapeutic treatments , the condition &# 39 ; s severity , whether the treatment is for prophylaxis or therapy , the patient &# 39 ; s age , the severity of cholesterol elevation , and the like . in a preferred aspect of the invention , a composition of the present invention is administered to reduce or control blood cholesterol levels in persons having a total cholesterol of 240 mg / dl ( 5 . 95 mmol / l ) or higher . in another embodiment of the invention , the compositions are administered to reduce levels of ldl - cholesterol in persons with an ldl - cholesterol of 130 mg / dl ( 3 . 41 mmol / l ) or higher . in yet another embodiment of the invention , the compositions are administered to reduce triglycerides in persons having blood triglycerides of 200 mg / dl ( 2 . 26 mmol / l ) or higher . in another embodiment , a composition of the present invention is administered to raise levels of hdl to persons with an hdl - cholesterol of 35 mg / dl ( 1 . 04 mmol / l ) or lower to reduce the risk of atherosclerosis associated with low hdl levels . the compositions and methods of the present invention may also be utilized to improve or maintain vascular health in specific organ systems including the cardiovascular system , the cereberovascular system , the peripheral vascular system and the intestinal vascular system . according to an additional embodiment , the compositions of the present invention may be admixed by conventional methods and may be administered by an alternative route such as suppository , spray , liquid , powder , liposome , dermal patch , and inhalant . these methods are well known to those skilled in the art . for example , liposomes may be formulated according to methods such as those of u . s . pat . no . 5 , 853 , 755 , to foldvari , u . s . pat . no . 4 , 235 , 871 to papahadjopoulos , et al , or u . s . pat . no . 4 , 708 , 861 to popescu et al ( liposome - gel combination ). sublingual and transdermal methods are also well known to those skilled in the art , e . g ., u . s . pat . no . 5 , 922 , 342 to shah , et al describes a sublingual formulation and u . s . pat . no . 4 , 997 , 655 to nagy , et al describes a transdermal administration method . in a specific embodiment of the invention , the composition comprises between 50 mg and 3 . 6 gm red yeast rice , between 5 and 300 mg coenzyme q10 , between 10 mcg and 1 mg chromium , between 5 and 1 g inositol , between 10 mcg and 1 mg selenium , and between 5 iu and 800 iu mixed tocopherols . in yet another embodiment of the invention , the composition comprises between 100 mg and 2 . 4 gm red yeast rice , between 5 and 250 mg coenzyme q10 , between 10 mcg and 500 mcg chromium , between 10 and 800 mg inositol , between 10 mcg and 500 mcg selenium , and between 5 iu and 400 iu mixed tocopherols . in yet another embodiment of the invention , the composition comprises between 100 mg and 1 . 2 gm red yeast rice , between 5 and 150 mg coenzyme q 10 , between 10 mcg and 300 mcg chromium , between 20 and 500 mg inositol , between 10 mcg selenium , and between 5 iu and 200 iu mixed tocopherols . and in yet another embodiment of the invention , the composition may be administered in a daily dose of between 50 mg and 1 . 6 gm red yeast rice , between 10 and 600 mg coenzyme q10 and between 5 iu and 800 iu mixed tocopherols . in a preferred embodiment , the composition is administered in four tablets each comprising about 500 mg red yeast rice , about 15 mg coenzyme q 10 about 50 mcg chromium , about 13 mg inositol , about 50 mcg selenium , and about 20 iu mixed tocopherols to provide a total daily dose of about 2 gm red yeast rice , about 60 mg coenzyme q 10 , about 200 mcg chromium , about 52 mg inositol , about 200 mcg selenium and about 80 iu mixed tocopherols . the administration of the composition would be in accordance with a predetermined regimen , which would be at least once daily and over an extended period of time as a chronic treatment , and could last for one year or more , including the life of the host . the dosage administered will depend upon the frequency of the administration , the blood level desired , other concurrent therapeutic treatments , the severity of the condition , whether the treatment is for prophylaxis or therapy , the age of the patient , the levels of ldl - cholesterol and hdl - cholesterol in the patient , and the like . the invention will be further illustrated by the following non - limiting examples : a study of the effect of the red yeast rice , 200 mg qid , coenzyme q 10 10 mg qid , mixed tocopherols 10 iu qid , selenium 20 mcg qid , chromium 20 mcg qid , and inositol 20 mg qid on hdl - cholesterol , non hdl - cholesterol , and total cholesterol concentrations in the blood of men with elevated cholesterol levels is conducted over a 6 month period . a statistical analysis is performed to compare the resulting cholesterol levels of the test and a control ( placebo ) group to determine if a significant improvement in cholesterol levels results from administration of the test preparation . sixty men having total plasma cholesterol of between 240 and 300 mg / dl are selected for inclusion in the statistical study . two weeks prior to the start of the study each subject completes a two day dietary intake record and is interviewed by a registered dietitian to calculate each individual &# 39 ; s daily energy requirement for a basal low fat , low cholesterol national cholesterol education program step i diet . each subject is given a booklet published by the american heart association containing a long list of foods , along with a calculated “ fat gram prescription ” which complies with the criteria for the basal diet . all subjects follow the basal diet for a period of at least fourteen days . after this , baseline blood samples are drawn on two separate days , and the subjects are randomly assigned to one of two treatment groups , the test capsules or matching placebo capsules . both groups continue on their basal diet and incorporate four tablets of the test composition in the diet . the effects of the dietary supplementation on total cholesterol , hdl - cholesterol , and non - hdl cholesterol , as well as dietary intake , body mass index , and physical activity are evaluated using multiple linear regression analysis and a standard students t - test . in each analysis the baseline value of the outcome variable is included in the model as a covariant . treatment by covariant interaction effects is tested by the method outlined by weigel & amp ; narvaez , 12 controlled clinical trials 378 - 94 ( 1991 ). if there are no significant interaction effects , the interaction terms are removed from the model . the regression model assumptions of normality and homogeneity of variance of residuals are evaluated by inspection of the plots of residuals versus predicted values . detection of the temporal outset of effects is done sequentially by testing for the presence of significant treatment effects at 18 , 12 , and 6 weeks , proceeding to the earlier time in sequence only when significant effects have been identified at each later time period . in addition , differences between groups in nutrient intake , physical activity , and body mass index ( ht / wt . sup . 2 ) at each time point are compared using one - way analysis of variance . changes from the baseline within each group are evaluated using paired t - tests . in addition , analysis of variance is performed on all baseline measurements and measurable subject characteristics to assess homogeneity between groups . all statistical procedures are conducted using the statistical analysis system ( sas institute inc ., cary , n . c .). an alpha level of 0 . 05 is used in all statistical tests . a statistically significant increase in hdl - cholesterol and the decrease in non - hdl cholesterol including ldl - cholesterol are observed in the blood of the treated subjects upon completion of the study but not the controls . the differences between the levels of hdl - cholesterol and non - hdl cholesterol including ldl - cholesterol in the treated subjects and controls are statistically significant . a composition of the following formulation was prepared in table form by standard methods : 4 tablets per day is the recommended dosage for an average weight adult human ( 70 - kg ). the invention has been described in detail with particular reference to preferred embodiment thereof . however , it will be appreciated that those skilled in the art , upon consideration of this disclosure may make variations and modifications within the spirit and scope of the invention .
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fig1 represents the basic electrical circuit and drive parts of a magnetic tape drive arrangement without pressure rollers in accordance with the invention . the arrangement comprises a magnetic tape transport device with a take - up reel 2 driven by a take - up motor 6 and a feed reel 1 driven by a feed motor 7 ; of cpurse , the feed motor 7 is not always necessary and may be replaced by a braking device . this magnetic tape transport feeds the magnetic tape 3 along a capstan 4 , which is driven by a capstan drive motor 5 . for the stake of simplicity the recording and playback transducers co - operating with the magnetic tape 3 are not shown . these transducers may be stationary magnetic heads or rotary heads as frequently used in video tape recorders . the capstan drive motor 5 is energized by an energizing circuit 8 in order to drive the magnetic tape 3 with the desired speed . for this purpose the motor 5 may be coupled to a tachogenerator , whose output signal is compared with a reference signal . the arrangement further comprises a motor current detector 9 , which detects the current consumed by the capstan drive motor 5 , an acceleration detector 10 , which supplies a signal which is a measure of the acceleration of the capstan 4 , and a reference source 12 . the output signals of the detectors 9 and 10 and of the reference source 12 are supplied to a control signal generator 11 , which supplies a control signal for controlling the speed of the take - up motor 6 and , as the case may be , for a feed motor 7 . it is also possible to effect control by means of one feed motor only . if the capstan 4 exerts a driving torque t d on the magnetic tape 3 , then t d = t - t o - t v , where t is the total torque produced by the motor 5 , t o the zero - load torque representing the losses , and t v the accelerating torque . if the motor 5 is a d . c . motor , then ( t - t o )= k 1 ( i - i o ), where i is current consumed by the motor 5 and detected by the detector 9 , i o is the zero - load current in the motor 5 , which current is represented by the reference source 12 , and k 1 is a constant . the accelerating torque t v satisfies the equation t v = j ( d 2 φ )/( d t 2 ), where j is the moment of inertia of the rotor and capstan 4 and φ the capstan phase ; thus , t v = k 2 . a , where k 2 is a constant and a is the angular acceleration of the capstan 4 . the control signal generator 11 generates a signal proportional to k 1 ( i - i o )- k 2 a . by means of this signal the take - up motor is so controlled as to minimize this signal , so that the torque t d exerted on the tape 3 by the capstan 4 is minimal and the tape 3 can thus be driven by the capstan 4 without the use of a pressure roller and without the occurrence of slip . fig2 shows the relevant parts 9 , 10 and 11 of a first embodiment of an arrangement in accordance with the invention in more detail . in this embodiment a tachogenerator 13 -- which may also serve as speed reference for the energizing circuit 8 -- is employed , which is coupled to the capstan motor 5 . the acceleration detector 10 comprises this tachogenerator 13 and a differentiator 14 , which derives a signal proportional to the angular acceleration of the capstan from the tachosignal . the constant factor k 2 may be realized either in this differentiator , or in a further circuit ( for example a differential amplifier 17 ). the motor current detector 9 comprises a resistor 15 , which is included in the motor supply line and which generates a voltage ir , in which r is the value of the resistor 15 . the reference source 12 generates a voltage i o r . the signal generator 11 comprises a differential amplifier 16 , to which the voltages ir and i o r are applied , which differential amplifier may have a gain k 1 / r and then supplies a voltage equal to k 1 ( i - i o ) as output signal . if desired , the factor k . sub . 1 may be generated in a further amplifier . the output signal of amplifier 16 and the output signal of differentiator 14 are applied to a differential amplifier 17 , a voltage which is proportional to the desired signal k 1 ( i - i o )-- k 2 a appearing on the output 18 of said differential amplifier . fig3 shows the relevant parts 9 , 10 and 11 of a second embodiment of an arrangement in accordance with the invention in more detail . in this embodiment the back -- e . m . f . e of the d . c . motor 5 is employed for detecting the angular acceleration a of the capstan , which acceleration is proportional to the time derivative of e with a constant factor k 3 : a = k ( de / 3dt . a complication in this respect is the internal resistance r a of the motor 5 . except for the acceleration detector 10 this embodiment is further identical to that of fig2 . the acceleration detector 10 comprises an amplifier 19 , which measures the voltage across the motor 5 in series with the measuring resistor 15 and amplifies or attenuates this voltage by a factor r / r a . the output voltage of this amplifier 19 and the voltage across resistor 9 are applied to a differential amplifier 20 , so that the output signal of this amplifier is proportional to the e . m . f . e of the motor 5 . this voltage is differentiated with a differentiator 14 . if the amplifier 20 and / or differentiator 14 provide an amplification by a factor ( r a . k 2 )/( r . k 3 ), the output signal of amplifier 17 will be proportional to the desired signal k 1 ( i - i o )-- k 2 a . apart from the embodiments described in detail , numerous modifications are possible in order to realize the desired function k 1 ( i - i o )-- k 2 a with differentiators and amplifiers etc . it is for example possible to differentiate the total voltage across the motor 5 and the resistor 15 with a differentiator and to differentiate the difference between the voltage across the resistor 15 and the reference voltage from the source 12 with another differentiator , and to take the difference of the two differentials , allowance being made for the correct factors . in order to control the speed of the take - up motor 6 , the signal from output 18 may be applied to an energizing circuit for the motor 6 and , as the case may be , applied in phase opposition to an energizing circuit for the feed motor 7 . these signals , as the case may be with the inclusion of an additional control amplifier , should then be applied so that in the case of a positive signal on output 18 -- which corresponds to a positive torque td exerted on the magnetic tape 3 by the capstan 4 the take - up motor will produce a greater torque and in the case of a negative signal on output 18 the take - up motor 6 will produce a smaller torque . for a correct choice of the constants k 1 and k 2 the magnetic tape can then be driven by the capstan without pressure roller and without the occurrence of slip . in addition , the motor 6 , and as the case may be the motor 7 , may be connected to a separate control , known per se , for controlling the torque of said take - up motor 6 and any feed motor 7 , in conformity with the amounts of tape on the reels 1 and 2 .
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the term “ tissue ” is used in the general sense herein to mean any transplantable or implantable tissue , the survivability of which is improved by the methods described herein upon implantation . in particular , the overall durability and longevity of the implant are improved , and host - immune system mediated responses , are substantially eliminated . the terms “ transplant ” and “ implant ” are used interchangeably to refer to tissue , material or cells ( xenogeneic or allogeneic ) which may be introduced into the body of a patient . the terms “ autologous ” and “ autograft ” refer to tissue or cells which originate with or are derived from the recipient , whereas the terms “ allogeneic ” and “ allograft ” refer to cells and tissue which originate with or are derived from a donor of the same species as the recipient . the terms “ xenogeneic ” and “ xenograft ” refer to cells or tissue which originates with or are derived from a species other than that of the recipient . the present invention is directed towards a cartilage repair construct constructed of two separate pieces of allograft cancellous bone . both pieces of the two - piece allograft construct are to be derived from dense cancellous bone that may originate from proximal or distal femur , proximal or distal tibia , proximal humerus , talus , calceneus , patella , or iliium . cancellous tissue is first processed into blocks and then milled into the desired shapes . the top piece or cap member is substantially demineralized in dilute acid until the bone contains less than 0 . 2 % wt / wt residual calcium . subsequently , the resultant tissue form is predominantly type i collagen , which is sponge - like in nature with an elastic quality . following decalcification , the tissue is further cleaned and may also be treated so that the cancellous tissue is non - osteoinductive . this inactivation of inherent osteoinductivity may be accomplished via chemical or thermal treatment or by high energy irradiation . in a preferred embodiment , the cancellous cap member is treated with an oxidizing agent such as hydrogen peroxide in order to achieve a non - osteoinductive material . the bottom piece will be formed from mineralized cancellous bone or partially demineralized cancellous bone . the two piece allograft cancellous construct 20 has a base member 22 with a cap member 30 which is held fixed in place in the base member 22 by a pin . 40 . the base member 22 is preferably constructed of mineralized cancellous bone and is shaped in the form of a cylinder for easy insertion into bores cut into the patient to cut away cartilage defect areas . however , the base member 22 may be surface or partially demineralized or contain a region of cortical bone so that it is cortical / cancellous . the body of the base member 22 defines a blind bore 23 which holds a stem 36 of the cap member 30 , as further described below . the bottom surface 24 of the blind bore , as seen in fig5 - 7 , has a plurality of longitudinal through going bores 25 extending through the base member 22 and ending on the distal end surface 26 of the base member , which is preferably planar . the top surface 27 of the base member 22 is also preferably planar , forming a seat for the cap member 30 . a first lateral bore 28 extends generally transversely from an exterior wall of the base member 22 , above the bottom surface 24 of the blind bore 23 , and intersects the blind bore 23 . a second lateral bore 29 extends generally transversely from the exterior wall of the base member 22 , above the bottom surface 24 of the blind bore 23 , and intersects the blind bore 23 so as to be opposite the first lateral bore 28 ( see fig4 , 5 and 7 ) and in coaxial alignment therewith . a second plurality of longitudinal through going bores 31 are circumferentially positioned around the blind bore 23 parallel to the central axis of the base member 22 and extend from the top surface 27 to the bottom surface 26 . the longitudinal through going bores 25 and 31 have a smaller diameter than the blind bore 23 , with a diameter ranging from 0 . 5 to 2 . 0 mm . the cap member 30 has a cylindrical top section 32 which has a thickness of about 3 mm with a top planar surface 33 , an outer curved wall 34 and a bottom planar surface 35 which is seated adjacent the top surface 27 of the base member 22 when the components are mounted together . the top surface 33 while preferably planar may be milled to a degree of curvature that matches the physiological curvature of the articular cartilage being repaired , i . e ., a surface of a knee joint . larger constructs may have a cap member that has multiple stem sections and a base with an inverse “ female ” pattern which receives the stem sections . the cap member 30 includes an integral cylindrical stem 36 that depends from the bottom planar surface 35 of the top section 32 . the stem 36 has a length which is not longer than the depth of the blind bore 23 and has a diameter which is equal to or less than the diameter of the blind bore 23 . the stem 36 includes a transverse radial bore 37 which is aligned with the first and second lateral bores 28 , 29 of the base member 22 to receive a cylindrical pin 40 . more particularly , the pin 40 is inserted radially through the construct 20 to hold the cap member 30 in place within the base member 22 ( see fig3 ). the cap member 30 is preferably formed of demineralized cancellous allograft bone with a calcium content of less than 0 . 2 % calcium . alternatively , the cap member 30 has a substantially demineralized region , such as the top section 32 , with a calcium content of less than 0 . 2 % calcium . the cylindrical pin 40 is preferably constructed of cortical bone and has a length equal to or less than the diameter of the base member 22 . the pin 40 can also be constructed of a synthetic material . the cap member 30 can be secured to the base member 22 by a staple , suture , press fit or an adhesive compound such as fibrin based glue . the construct 20 is placed in a defect area bore which has been cut in the lesion area of the bone of a patient with the upper surface 26 of the cap member 30 being slightly proud , slightly below , or substantially flush with the surface of the original cartilage remaining at the area being treated . the construct 20 has a length which can be the same as the depth of the defect or more or less than the depth of the bore . if the construct 20 is the same as the depth of the bore 60 , the base of the implant is supported by the bottom surface of the bore and the top surface 33 of cap 30 is substantially level with the articular cartilage . if the construct 20 is of a lesser length , the base of the construct is not supported but support is provided by the wall of the defect area bore or respective cut out area as the plug is interference fit within the bore or cut out area with the cap being slightly proud , slightly below , or flush with the surrounding articular cartilage depending on the surgeon &# 39 ; s preference . with such load bearing support the graft surface is not damaged by weight or bearing loads which can cause micromotion interfering with the graft interface producing fibrous tissue interfaces and subchondral cysts . including the pluralities of longitudinal through going bores 25 and 31 in the construct 20 facilitates cell migration throughout the construct 20 . such cell migration promotes cartilage growth in the cartilage area and bone growth in the adjacent bone region . in operation , the lesion or defect is removed by cutting a . bore removing a lesion in the implant area . if desired , the open cancellous structure of the cap member 30 may be loaded with a cartilage paste or gel as noted below and / or one or more additives namely recombinant or native growth factors ( fgf - 2 , fgf - 5 , fgf - 7 , igf - 1 , tgf - β , bmp - 2 , bmp - 4 , bmp - 7 , pdgf , vegf ), human allogenic or autologous chondrocytes , human allogenic cells , human allogenic or autologous bone marrow cells , human allogenic or autologous stem cells , demineralized bone matrix , insulin , insulin - like growth factor - 1 , interleukin - 1 receptor antagonist , hepatocyte growth factor , platelet - derived growth factor , indian hedgehog parathyroid hormone - related peptide , viral vectors for growth factor or dna delivery , nanoparticles , or platelet - rich plasma . the construct 20 is then placed in the bore or cut away area in an interference fit with the surrounding walls . if the construct is moveable within the bore , suitable organic glue material can be used to keep the implant fixed in place in the implant area . suitable organic glue material can be found commercially , such as for example ; usseel ® or tissucol .® ( fibrin based adhesive ; immuno ag , austria ), adhesive protein ( sigma chemical , usa ), dow corning medical adhesive b ( dow corning , usa ), fibrinogen thrombin , elastin , collagen , casein , albumin , keratin and the like . the base of the blind bore 23 of the construct 20 can alternatively be provided with a matrix of minced cartilage putty or gel consisting of minced or milled allograft cartilage which has been lyophilized so that its water content ranges from 0 . 1 % to 8 . 0 % ranging from 25 % to 50 % by weight , mixed with a carrier of sodium hyaluronate solution ( ha ) ( molecular weight ranging from 7 . 0 × 10 5 to 1 . 2 × 10 6 ) or any other bioabsorbable carrier such as hyaluronic acid and its derivatives , gelatin , collagen , chitosan , alginate , buffered pbs , dextran , or polymers , the carrier ranging from ranging from 75 % to 50 % by weight . the cartilage is milled to a size ranging up to 1 mm . in the gel form , the minced cartilage has been lyophilized so that its water content ranges from 0 . 1 % to 8 . 0 %, ranging from 15 % to 30 % by weight and the carrier ranges from 85 % to 70 % by weight . the particle size of the cartilage when milled is less than or equal to 1 mm dry . the cartilage pieces can be processed to varying particle sizes and the ha or other carrier can have different viscosities depending on the desired consistency of the putty or gel . this cartilage matrix can be deposited into the demineralized cap member . the putty or gel enhances the tissue integration between the plug and host tissue . it is also envisioned that demineralized bone matrix and / or growth factors such as ( fgf - 5 , fgf - 7 , igf - 1 , tgf - β , bmp - 2 , bmp - 4 , bmp - 7 , pdgf , vegf ) or soluble factors such as insulin , interleukin - 1 receptor antagonist , hepatocyte growth factor , indian hedgehog and parathyroid hormone - related peptide , viral vectors for growth factor or dna delivery , nanoparticles may be adsorbed or combined with the construct or the cartilage pieces . in another embodiment , platelet - rich . plasma may be added to the construct . it is also envisioned that cells which have been grown outside the patient can be inserted by syringe into the cancellous cap member 30 before , during or after deposit of the construct 20 into the defect area . such cells include allogenic or autologous , bone marrow cells , stem cells and chondrocyte cells . the cellular density of the cells preferably ranges from 1 . 0 × 10 8 to 5 . 0 × 10 8 or from about 100 million to about 500 million cells per cc of putty or gel mixture . the cap member 30 can support the previously mentioned chondrogenic stimulating factors . the principles , preferred embodiments and modes of operation of the present invention have been described in the foregoing specification . however , the invention should not be construed as limited to the particular embodiments which have been described above . instead , the embodiments described here should be regarded as illustrative rather than restrictive . variations and changes may be made by others without departing from the scope of the present invention as defined by the following claims :
| 0 |
the present disclosure relates to systems and methods which can increase the recovery rate of fresh water from otherwise undesirable water , as well as provide additional uses for the by - products and / or wastewater of such systems and methods . one skilled in the art will appreciate that various aspects of the disclosure may be realized by any number or type of structures and systems , as well as various types of undesirable water . for example , much of the present disclosure finds utility in the desalinization of seawater . however , one skilled in the art will appreciate that other water which has varying contaminants may likewise be found to be treatable in accordance with the present disclosure , and as such , this disclosure should not be considered to be limited to desalination alone . moreover , while various membranes and filtration materials may be disclosed herein , those skilled in the art will appreciate that depending on the applications at hand , alternative materials , membranes , filters , and the like , as well as other structures , may likewise be suitable and fall within the scope of the present disclosure , even where not expressly recited . it should also be noted that the drawings herein are not all drawn to scale , but may be exaggerated to illustrate various aspects of the disclosure , and in that regard , the drawings should not be limiting . additionally , those items disclosed herein may be described herein in terms of functional block components , optional selections and various steps . it should be appreciated that such functional blocks may be realized by any number of components configured to perform the specified functions . the present disclosure provides various levels of increased fresh water recovery percentages above those presently attainable by current ro only technology . specifically , by integrating existing ro technology and systems with forward osmosis ( fo ) technology and nanofiltration ( nf ) technology , such recovery increases are attainable . in this regard , by combining the optimal performance properties of multiple technologies in a particular order , for example , ro , nf , and fo , such recovery increases may be obtained . in other words , by exploiting the best characteristics each of ro , nf , and fo , the inherent ceiling of ro can be improved , with recoveries well beyond ros thermodynamic limit of 1 . 8 cycles of concentration . such integration is referred to herein as “ integrated osmosis ” or “ io .” for example , a comparison of conventional two - pass swro to io is shown in table 1 below . as disclosed herein , io contemplates a process of providing additional freshwater recovery and a decreased volume of high total dissolved solids ( tds ) concentrate ( or wastewater ) from conventional freshwater extraction processes ( hereinafter , for simplicity , referenced as reverse osmosis or ro regardless of the type of freshwater extraction technology ). io affords these benefits by effecting a staged osmotic separation process , specifically , nf with specifically developed and selected morphology and zeta potential ( which may include one or more sw nf filtration structures or stages ) and , optionally and as described below , a very low energy nf stage , which prefaces a fo process upon the wastewater concentrate stream of a conventional ro system . the io process also provides a means to extract freshwater from other high tds concentrate feed waters which are otherwise intractable by the prior art . more specifically and as described in additional detail herein , with reference to fig1 , an io system may comprise a conventional two - pass sea water reverse osmosis ( swro ) stage 100 passing through a “ fence line ” 101 , a conditioning stage 110 where conditioning of swro concentrate ( e . g ., having a concentration of 58 , 000 ppm ) from the swro stage 100 occurs , for example , to reduce calcium , and an additive stage 115 where various additives may be added to the conditioned concentrate ( e . g ., surface tension lowering additives , etc .). after the additive stage 115 , as described below , a selective nf stage 120 processes the conditioned swro concentrate to remove certain ions , with about 72 % recovery rate of nf permeate , and about 23 % concentrate which can proceed to a byproducts harvesting stage 160 to harvest materials which may be used in other applications ( e . g ., concentrated brine solution which may be used in solvay process , soda ash , etc .). the sw nf permeate may then , as described in more detail below , optionally pass through a very low energy nf stage 170 ( vlenf or “ ultrafiltration ” or simply “ uf ”) and / or a weak base anion exchange ( wba ) stage 180 ( e . g ., bicarbonate hco 3 form ) to form a uf concentrate , or alternatively , may move directly to a fo stage 130 . the wba stage 180 acts as a carrier for a metallic bioenzyme toggle for h 2 co 3 and h 2 o and co 2 . in the event the sw nf permeate first goes through the vlenf 170 or wba 180 stage , the concentrate from these stages may be used in as draw solution osmolyte in the fo stage 130 . the fo stage 130 may see a recovery rate of about 80 %. after the fo stage 130 , a final separation osmolyte stage 140 may also be employed , providing about 95 % permeate recovery rate with an end use water output having less than about 150 tds . the remaining draw solution osmolyte from the final separation stage 140 may optionally be further processed in an additional purification stage 150 , if necessary . in accordance with another embodiment of an io system and with reference to fig6 , of note , the illustrated io system does not refer to swro elements , high pressure pumps , a compact skid , or energy recovery equipment . rather , the illustrated io system uses thermodynamics of mass and heat transfer , a catalytic performance of a metallic bioenzyme , and waste heat available at the source , or other economical means ( e . g ., thermal fluid , dmso and thermolytic nanoparticles ). the io system begins with seawater taken though a nf stage ( swnf ), with a pretreatment goal to reach a sdi value below 3 . 0 and turbidity below 0 . 2 ntu . at this point , the feed 690 and is processed through a sw nf stage 600 to selectively reject more than 70 % calcium , more than 80 % magnesium , and more than 90 % sulfate ions while passing as high a percent of monovalent ions as possible . a term defined as relative apparent molar enthalpy captures the value of an exotherm as a beneficial heat source as heat of dilution in kj / mol . multiply by total mols of dmso or libr to obtain the total heat . commercially available swnf membranes from ge water and dow ( filmtec ) are exemplary membranes which may be modified and used in accordance with the present disclosure . as illustrated in fig6 , using two stages of fo 610 a , 610 b , the mass transfer of water to the draw solute is maximized . additionally , the illustrated io system takes advantage of an almost eight - fold difference in osmotic pressures between osmolyte a 620 a , 620 b , as well as factors such as permeate suction , temperature , and the like . as those skilled in the art will appreciate , osmotic pressure is the pressure required to stop the process of osmosis . in other words , water moves down to its osmotic potential . moreover , the influential metallic enzyme lowers the pka of water from 15 . 7 to 7 . fo concentrate from nf stage 610 a is feed water to nf stage 610 b . the higher the fo retentate , the higher the recovery yields from ro 630 . by way of comparison , conventional two - pass swro gives a recovery of about 42 % and sec ( with erd ) is about 3 . 8 kwh / m3 . in contrast , the process illustrated by fig6 shows a recovery greater than 80 %. additionally , as described in further detail below , in accordance with the present disclosure and with reference back to fig1 , io employs nanofiltration of the high tds concentrate feedwater as a first stage , prior to any fo stages . in contrast to ro , wherein nearly all ions are removed from the feed water , the nanofiltration first stage of io selectively removes only a certain population of ions . for example , non - monovalent ( e . g ., divalent , trivalent , etc .) ions are preferentially removed with minimal effects upon monovalent ions to produce a lowered osmotic pressure solution . the removal of non - monovalent ions reduces scaling tendencies promoted by bonding with sulfates , carbonates , silicates and the like . an additional benefit is removal of fine and colloidal solids . the nf stage generates water that is essentially free of suspended solids and has a stable ph , offering a lowered osmotic pressure afforded by the reduced non - monovalent ion concentration . this water proceeds to the next stage process of io which incorporates one or more fo stages benefitting from the reduced osmotic pressure and a negative charge provided by the earlier stage of io . in accordance with various aspects of the present disclosure , by employing io with concentrate produced from ro , additional freshwater recovery can be achieved , a net benefit overall . benefits of io as contemplated herein include the ease of installation and “ retro - fitting ” to existing ro processes . in this regard , io processes can be readily added as a “ bolt - on ” type configuration , affording increased freshwater production using the combined processes . increased freshwater recovery from the combined existing ro and the nf and fo processes thus offer enhanced use of invested capital and infrastructure of the existing ro system &# 39 ; s intake , discharge and pretreatment associated processes . for example , in io retro - fit cases , where an existing ro process results in a 42 %/ 58 % freshwater / concentrate split , by increasing the daily freshwater product output by 50 percent of the feed ( 0 . 51 × 58 , 000 m3 / d =˜ 30 , 000 m3 / d ) using io , results in a about 70 % increase of freshwater recovery . this mass balance also allows a complete use of all the pretreatment ultrafiltration capacity and a modular design leaves space to accommodate adding more surface area for expansion . a io process can therefore complement the objective of adding more uf capacity ( with the hardware in place ) by inserting cassettes or modules with membrane area ( software ). additionally , there is a corresponding reduction in the volume and disposal cost of concentrate being discharged inland or in the ocean . in this regard , because io affords an increase of freshwater production and a concurrent decrease of waste concentrate volume , a further benefit is the reduction of waste concentrate and associated handling and disposal costs . this benefit also provides an additional object of io , namely , volumetric waste reduction lessens “ zero liquid discharge ” ( zld ) processing costs rendering zld environmental and / or regulatory goals more affordable ( see for example , fig6 ). moreover , if the waste concentrate tds level can be elevated to a high enough level ( e . g ., 230 , 000 ), there is no need to a crystallizing step or related apparatus , and rather , all that is needed is an evaporator , saving further capital cost . further still , licensing and permits for incremental expansion of existing ro systems may be straightforward and less cumbersome to obtain and implement , thereby bringing additional capacity on - line in less time . additionally , io generally does not require additional expensive , long lead time , high pressure swro pumps . moreover , io provides a higher and more efficient utilization of the treated feed water of an existing ro system , and higher salts content in the concentrate provide additional options for valuable by - product salt or mineral extraction , which may also be capable of reuse in the io process itself . examples of such by - products include concentrated , very high purity (& gt ; 99 %) brine which may be usable as feedstock for solvay processes . the same may also provide flexibility to convert various nanofiltration concentrates into sodium sulfate as a draw solution ( osmolyte ) for fo processes . additionally , in the united states for example , inland desalination would be a much needed and appreciated pathway for treating brackish water ( 3 , 000 ppm to 12 , 000 ppm tds ) were it not for the prohibitive concentrate disposal cost . depending on the mode of disposal , this cost can vary from about $ 3 . 5 mm per mgd to $ 12 mm per mgd . estimates put these high tds water / s in the state of texas alone at about 2 . 5 billion acre feet or about 830 trillion gallons . as such , an io process such as disclosed herein , offers the potential of affordability for use of this water as a source for potable and industrial needs . additionally as discussed in more detail herein , in regions or water bodies where the threat of habitual algae toxins ( hab ) puts the entire desalination system in a total shut down mode or operate with a risk of severe fouling of swro membranes , an io system such as disclosed herein , if installed with a disc filtration system like the integra ® system consisting of discs ranging in micron size from 200 microns to 2 microns with discs made of a blend of robust plastics along with the dissolved air filtration ( daf ) system from the original swro system can be programmed to work congruently to prepare the feed for the io system . thus , in times of hab , if the decision is made to operate the swro system due to need and no alternate resource of drinking water nearby , then the sw feed is taken past the intake screen infrastructure , then the daf system , then through the integra ® disc filtration system and then through the io system ( by - passing the two - pass swro system ). additionally , seawater nf has zwitterionic properties . therefore , lowering the ph to the iso - electric point and changing the zeta potential from minus ( 15 mv to 25 mv ) to neutral , along with addition of a food grade humectant bacteriostat , plus permeate suction , prevents buildup of a concentration polarization gradient adjacent to the nf membrane skin layer . in various embodiments , the fo membrane may have a contact angle below 60 degrees and the substrate osmolyte draw solution can be blended to keep the substrate continually moist , thus minimizing bacterial accumulation on the membrane skin layer . operating levers like osmotic backwash , permeate suction , and keeping the draw cross velocity higher than the feed velocity ( net cfv or cross flow velocity ) can also minimize biofouling or hab accumulation . those skilled in the art will appreciate that fo has many characteristics that are similar to ro , including fouling or plugging from suspended solids ( tss - total suspended solids ), osmotic pressure effects exerted by dissolved solids ( tds ), bacterial contamination and associated bio - fouling , contamination and fouling by natural organic materials ( nom ) as well as fouling from oil and grease . in contrast to ro , these characteristics and associated difficulties effect and interact with both the feed water and the draw solution sides of forward osmosis membranes burdening fo with additional and unique characteristics and difficulties . thus , until the present disclosure , fo was oft - ignored by those skilled in the art . in this regard , io is novel and counterintuitive in that it uses nf before uf and fo . by operating the nf process in a 2 × 1 array ( see fig2 for example ) with the first array consisting of a hydrophilic nf membrane operating at a ph of 3 . 0 to 3 . 5 , calcium removal can be maximized . the second array can operate at a ph above the iso - electric point to maximize rejection of sulfate ion and magnesium ion . additional nf membranes may be added to the io system as desired . for example , fig3 illustrates a three - stage nf process . by having a nf step before the fo step , the skin layer roughness and the cross linkage of the amide group relative to the linear pendant carboxylic acid groups can be maximized . this is beneficial in that increasing the amide linkage also increases hydrogen bonding sites and thus , osmotic permeability of water molecules through the fo membrane is accelerated , capitalizing on this feature of the fo membrane , namely , that it has the best mass transfer of water facilitated by the performance of the nf membrane rejecting divalent ions , suspended solids , nom and biofoulants . by focusing the nf step more exclusively on rejecting a large percentage of non - monovalent ions and sub - micron suspended solids , the nf membrane will pass monovalent ions , operate at moderate hydraulic pressure , and reduce the osmotic pressure on feed side of the fo process . thus , nf recovery can reach a range of about 75 % to about 80 %, and importantly , removal of calcium by nf allows raising the molar concentration or tds driven osmotic pressure of the draw solution in fo and allows fo to operate at high recovery rates , often greater than about 70 %, and approaching about 80 %. a result from fo is thus a maximizing of the mass transfer of water from the feed side to the draw side in a relatively more compact footprint . in various embodiments , the use of “ operating levers ” available can help facilitate , catalyze , humectize , reduce surface tension reduction , turbulence promoters , thermal enablers to accelerate transport phenomena and water transport . while this can increase operating expenses , because of the increases in recovery and other benefits noted above , including the reduction of footprint and capital expenditures of forward osmosis , the returns are significant . in accordance with various aspects of the present disclosure , both nf and fo elements can be manufactured in a “ full fit ” construction ( no fiber glass exterior and no brine seal ) for efficient osmosis . urethane glue can be applied in a “ w ” pattern in spiral wound fo elements thereby improving robustness and increasing available surface area . additionally , the layout of the fo elements may be placed in a parallel design ( longitudinally ) wherein each element is encased in its own cartridge housing providing increased cleanliness and economy , as well as the capability to maintain a substantially constant difference in pressure on feed and draw sides , allowing more uniform flux . in accordance with various embodiments , varying blends of different draw solutions / osmolytes may enable operating fo in either an active layer facing feed ( al fs ), solution diffusion first , convection second mode when the draw solution or osmolyte is mostly inorganic , or an acting layer facing draw ( al ds ), convection first , solution diffusion second mode when the osmolyte is mostly organic . as noted above , in accordance with various aspects of the present disclosure , io may use a metallic bioenzyme that provides a basis for deprotonation of water by lowering the pka of water from 15 . 7 to 7 . by virtue of this decrease , more water molecules are available to deprotonate at a lower ph to turn into hydroxyl ion , a better nucleophile . with reference briefly to fig7 , illustrating a flow diagram of a validation of a pilot demonstration using an integrated osmosis system as contemplated herein . the scalability of the pilot demonstration of 1440 gpd is about 500 : 1 — can go up to as 750 , 000 gpd . in accordance with various aspects of the present disclosure and with reference back to fig1 , a first step of io includes conditioning and pre - treatment 110 of the initial feed water ( e . g ., high salinity seawater concentrate ) from a conventional two - pass ro process 100 . a conventional two - pass swro has a feed salinity of about 33 , 000 ppm , a permeate tds of about 250 ppm and has a recovery rate of about 42 % with about 3 . 9 sec kwhr / m 3 . for io , the feed salinity is about 65 , 000 ppm , permeate tds is less than about 100 ppm and has a recovery rate of about 51 % with about 5 . 8 sec kwhr / m 3 . while the composition of tds in a swro concentrate is generally consistent throughout the year , frequent analysis of residuals in the concentrate like antiscalant degradation products , biocides , nom and recently reported leucothrix mucor and rugeria species is desirable . for example , analysis of a typical seawater concentrate sample is as follows : dependent upon the point of discharge of the concentrate and the re - entry as feed to an integrated osmosis process , there may be a presence of iron , bio - available manganese ( for example , as high as 230 ppb in the indian ocean ) to form ferromanganese blooms , dissolved organic matter , tep ( total exopolysaccharides ) and algae . as such , pre - treatment 110 may be important . as noted above , calcium is addressed first because of the potential difficulty of calcium complexing with nom and the potential of calcium sulphate precipitation dependent upon the state of calcium ( e . g ., dehydrate , hemihydrates and anhydrite ) and temperature . solubility of caso 4 @ 0 . 015 % molal is the highest at 30 ° c . thus , a chelating compound is used to bind calcium and trace levels ( e . g ., ppb ) of ferro - manganese bio foulants . exemplary chelating agents include , ethylenediaminetetraacetic acid ( edta ) and nitrilotriacetic acid ( nta ) though others may likewise be used . for example , alternate “ green compounds ” such as the tetra sodium salt of glutamic acid / n , n diacetic acid ( dissolvine gl 36 ) may be preferable . additionally , during “ red tide ” season ( or habs , as noted above ), suspended fine solids , red algae , algal cells ( 10μ to 15μ ), bacteria ( 1μ to 2μ ), aom ( algogenic organic matter ) and particulate matter (& lt ; 0 . 45μ ) can become ubiquitous . thus , an effective ( and often inexpensive ) adsorbent bed of hydrophilic polysulfone with chitosan and cloisite a 30 b media installed . this bed has a nominal pore size of about 3 microns . following this bed , an integra disc filter system ( high surface area and 26 , 000 linear feet depth per module ) alongside a smart sponge plus to provide adequate residence time or ebrt ( empty bed retention time ) to yield an effluent with sdi below 2 . 5 and turbidity below 0 . 2 ntu . additionally , these disc filters can be backwashed and are made of oleo phobic and hydrophilic engineered polymers . additionally ( or alternatively ), in various embodiments , to minimize calcium sulfate dehydrate scaling , a 1 : 1 ratio of a blend of two antiscalants , for example , polyacrylic acid and polyether polyaminophosphonic acid can provide about 80 % inhibition of calcium scaling . additional food safe additives , surfactants , and the like , may be added to the pretreated swro concentrate in stage 111 to lower surface tension and to end cap the unreacted monomers in order to minimize reverse salt flux or theft of ‘ a ’ value of a fo membrane from unreacted amine leaking through . by using a super spreader surfactant ( e . g ., siloxane polyalkyleneoxide such as silwet ® 77 or silwet ® 78 ) an improvement in the fo membrane &# 39 ; s hydrolytic stability vs . ph can be obtained . additionally , a lower amount of surfactant , namely about 0 . 15 wt . % instead of the more conventional 2 . 0 wt . %) required results in an even , homogeneous spread across the width of the membrane flat sheet in manufacturing . in accordance with various aspects of the present disclosure and with reference to fig1 , 3 and 6 , a second step of io includes nf 120 of high salinity seawater concentrate . nf covers the bandwidth between about 15 ° a to about 115 ° a and typically operates in a pressure range of about 40 psig to about 200 psig ( in sw sr applications ). in various embodiments , the non - monovalent ions are organic molecules with competitive osmotic pressure . in other embodiments , the non - monovalent ions are positively charged inorganic molecules . as mentioned above , in various embodiments , nf rejects non - monovalent ions such as sulfate , calcium and magnesium , and can also reject micron - sized suspended matter such that a very high percent of monovalent ions pass through to the fo process . removal of non - monovalent ions proceeds at a slower diffusion rate , resulting in a lower molar flux . however , the fo membrane is advantaged because the feed is homogeneous , accelerating the mass transfer of water . for example , rates of greater than about 95 % rejection of sulfate , greater than about 85 % rejection of calcium and magnesium can be obtained . single stage ( fig1 ), two stage ( fig2 ), three stage ( fig3 ) or more nf membranes may be used . an exemplary nf membrane is manufactured by ge water , and is known as swsr 400 ( 400 square feet area ). those skilled in the art will recognize that other nf membranes may also be used and still fall within the scope of the present disclosure . by using nf before fo , numerous benefits may be achieved . for example , the hydrated ionic radii of divalent ions diffuse slowly across the membrane skin layer interface resulting in a lower molar flux , proceeding at a rate to maintain electro neutrality . for example , hydrated ionic diameter of magnesium is 16 ° a while potassium is 6 ° a . additionally , a lower tds feed to fo means lower osmotic pressure . the nf rejection of any trace turbidity in the feed , gives flexibility in construction of the spiral wound fo element with respect to spacer thickness and permeate tricot fabric . moreover , permeate from nf has a negative zeta potential as it approaches the fo boundary layer . this will catalyze higher rejection of monovalent ions and lower reverse salt flux . further , the reject from nf can easily be converted to sodium sulfate ( na 2 so 4 ), giving a good osmolyte or draw solution at an economical and environmentally responsible cost . additionally , when the feed to the fo process is mostly monovalent ions and the draw solution is non - monovalent , the reverse salt diffusion is lower than the vice versa condition . because the osmotic pressure “ load ” in a nf membrane is primarily divalent and under 325 psi , a pathway is cleared to build the nf elements in a non - fiber reinforced polyester ( frp ) full fit construction without a brine seal . a further benefit is a lower pressure drop per element , a higher cross flow velocity , no biofilm growth and more room to pack more surface area . in various embodiments , permeate suction may be applied to keep the boundary layer destabilized and decrease concentration polarization , while at the same time increasing the mass transfer coefficient . the role of permeate suction in mass transfer through porous membranes is important as it enhances mass transfer from the bulk to the membrane surface . by applying suction at the end of the collector tube of the membrane module , an increased rate of pressure will be present . this ill destabilize the boundary layer at steady state conditions . permeate suction changes the solutions physical properties , such as viscosity , density and diffusivity — all functions of concentration . in accordance with various aspects of the present disclosure and with reference to fig1 , an optional third step of io may include uf stage 170 and / or wba 180 of the nf permeate . for example , permeate from nf as described herein may have more than 12 , 000 ppm of sodium and even more chloride . by installing a uf membrane with 0 . 5 nm pores and with sodium dodecyl benzene sulfonate adsorbed on the membrane , sodium complexed with chloride will show rejection up to about 50 % at a maximum loading of 0 . 05 mmols / gram while sodium complexed with sulfate shows a rejection of about 75 %. as noted above , a wba stage 180 acts as a carrier for a metallic bioenzyme toggle for h 2 co 3 and h 2 o and co 2 . in accordance with various aspects of the present disclosure and with continued reference to fig1 , and 6 , a fourth step of io includes a fo stage 130 / 140 / 615 a / 615 b . in the presently described example , swro concentrate going through the io system as a feed to the nf step has a tds of about 66 , 000 ppm . the swnf permeate has a tds of about 40 , 000 ppm as a feed to advanced uf step . the uf permeate has a tds of about 30 , 000 ppm and is fed to the fo step . at the fo stage 130 , with a feed of about 30 , 000 ppm , the osmotic pressure will be about 300 psi . briefly , with reference specifically to fig5 , the relationship between advection ( cross - flow velocity ), convection ( temperature ), and diffusion ( suction ) is shown . of note , the flux of a draw solution solute through a support layer in a fo membrane is equal to the sum of diffusive and convective components of flux . when the feed concentration is greater than about 0 . 5 m , more permeate suction may be applied to improve diffusivity . if temperature is raised , this may mitigate some effects of dilute internal concentration polarization gradient ( dicp ). with respect to fo membranes , the boundary layer thickness is inversely proportional to the square root of the peclet number . in an embodiment , an exemplary guideline for a balanced operation of a fo system with feed side concentration below 0 . 5 m ( about 29 , 000 ppm tds ) is as follows : 1 . feed and draw are countercurrent . 2 . in a thin film composite polyamide fo membrane , the cfv of draw is higher than the cfv of the feed . ( e . g . 25 cm / sec to 15 cm ) 3 . the draw solution concentration should be between 2 × to 3 × of the feed concentration . 4 . take advantage of heating the draw solution to 45 ° c . and also keep the feed at a constant temperature to avoid temporal variation and its impact on flux . 5 . situating the fo elements longitudinally in individual cartridges in a full fit design offers the ability to maintain a constant gap or gradient between the feed and the draw . in a conventional latitudinal arrangement of fo elements in a pv , the fo feed gets more concentrated while the ds moving in opposite direction is picking up more water , becoming more dilute and thereby decreasing the gap or gradient between the feed and the draw . when this happens , less water is drawn from the feed side , counter to the objective of fo . 6 . osmotic backwash and permeate suction help assure consistent performance of the fo system . 7 . high ionic strength ds may de - swell a cellulose triacetate fo membrane via charge neutralization which results in lower water permeability and higher salt passage and lower structural parameter . this trend may be exacerbated by the presence of divalent cations which tend to swell the polymer . though de - swelling is not as much of an issue in membranes made by interfacial polymerization , this is another reason to put sw nf before fo . 8 . de - swelling at high osmotic pressures leads to osmotic dehydration . 9 . in the al fs mode , the ds penetrates the porous support layer to the interior surface of the active layer before flux can occur . preferably , fo elements are shipped wet from the manufacturer in a preservative such as peg400 . in various embodiments , io the fo stage 130 may comprise a fo thin film composite membrane optimized for particular performance characteristics , such as maximizing the mass transfer of water from the polyamide skin layer to the substrate by allowing a two phase flow or simply bubbling high quality carbon dioxide gas through the feed solution . the fo membrane may be a carrier for a metallic bio - enzyme which is very fast and efficient in catalyzing formation of h 2 co 3 or carbonic acid and liberation of protons ( h 2 o + co 2 —←→ h + hco 3 ). by manipulating the zeta potential , the membrane is maintained as the transporter . the fo membrane may have a backing . for example , in an embodiment , the backing may be a tricot material , similar to what may be used to make a permeate channel tricot in spiral wound nf and ro membranes . alternately , a woven 2 . 7 mils thick , 70 microns in thickness may be used . the fo may also have a substrate . because cyclic dimer is an impurity and can makes a solution cloudy , low cyclic dimer ( lcd & lt ; 1 . 5 wt . %) grade of polysulfone may be included with a desiccant to assure no humidity or moisture enters the holding tank where polysulfone / solvent are kept before deposition on the casting line ( phase inversion process ). additionally , 5 micron and 1 micron cartridge filters may be provided to filter the polysulfone dope before deposition on the web . to obtain a narrower pore size distribution with high pore density and smaller interconnected pores , a hydrophobic surfactant may be added to the polysulfone dope before phase inversion and keep the coagulation tank temperature at 5 ° c . an effective fo membrane facilitates active mass transfer of water from the thin film composite layer to the uf substrate . this active role collaborates with the draw solution for an optimal mass transfer of water . this is achieved by maximizing the population of network pores ( 1 angstrom to 5 angstroms ) in the membrane skin layer and by using a super hydrophilic surfactant in the feed . residual acid chloride groups catalyze breakdown of amide functionality as h + ion availability is reduced . while it is common practice in interfacial polymerization process for brackish water ro membranes to use as much as 6 wt . % mpd ( amine ), the optimal amount for fo membrane is 2 wt . %. using analytical tools such as positive annihilation lifetime spectroscopy ( pals ) and quasi elastic neutron scattering ( qens ), it is known that the aggregate pores and network pores can have a variety of pore structures . the dynamics of movement of water in the polymeric membrane is best described as jump diffusion . in accordance with various embodiments , the functionality of io , and specifically the fo stages of io , is illustrated in table 2 below , comparing the functionality and the relative importance , and ranking the same : mass transfer of water through fo membranes is moderated by diffusion , particularly on the draw solution side of the fo membrane . osmolyte diffusion toward the reject layer of the membrane generates the osmotic pressure gradient necessary for mass transfer . diffusion may influenced by many factors or variables , temperature typically being the most significant and direct influencer . complementing this variable is the stability of thin film composite polyamide and to a degree , cellulose tri acetate membrane and element morphology . the increase in permeability and flux when temperature is increased is notable . for example , flux increases by almost 40 % when the temperature rises from 20 ° c . to 40 ° c . however , the cost of energy should be considered when analyzing the cost / benefit analysis of the thermal benefits . additionally , the advent and successful development of nanofluids as an enabling and increasing the efficiency of heat transfer medium may change the economic calculations of operating costs of fo . for example , nanofluids such as aluminum oxide and titanium dioxide are excellent choices as enablers for heat transfer , with titanium dioxide better than aluminum oxide . in accordance with various aspects of the present disclosure and with reference to fig1 and 6 , a fifth step of io includes separating a draw solution ( osmolyte ) in a final separation stage 160 . in the presently described embodiment , a dilute draw solution ( mixture of inorganic salt ) or osmolyte mixture is rejected by a high rugosity , high porosity , 0 . 5 nm pore size membrane , such as filmtec nf 90 . typical rejection is more than 99 . 5 %. additionally , to obtain additional rejection at low energy , a surfactant ( e . g . sodium dodecile benzene sulfonate ) charged uf ( about 3 nm pore size ) membrane at critical micelle concentration ( cmc ) may be used for rejecting sodium . io processes as contemplated herein provide incentives to various public interest groups and private sectors working towards the goal of achieving zero liquid discharge for a cleaner environment . in this regard , the applicability of io processes cover a wide bandwidth of waste waters with suspended and dissolved solids as well as other organic contaminants . for example , current practice globally is to re - inject the concentrate at twice the feed salinity back into the ocean . however , numerous studies done by various research groups show the adverse impact higher salinities have on marine life . as such , in accordance with various aspects of the present disclosure and with reference to fig8 , an example from a seawater desalination process using reverse osmosis membranes is illustrated , addressing some of these impacts . in sum , the io process accomplishes the following results : 1 . reduces the volume of water — by increasing the tds in swro concentrate to a tds range of 180 , 000 ppm to 230 , 000 ppm , the net volume to be handled by an evaporator and crystallizer stay small in size and affordable . 2 . little or no concentrate needs to go back in the ocean . 3 . significantly reduces the total cost of sea water disposal of the concentrate . 4 . reduces carbon footprint . 5 . if by - products do find their niche application ( like brine ) for most of the year , this further reduces waste . 6 . na 2 so 4 can also be made as a byproduct from the nf concentrate . last , the foregoing disclosure is illustrative of the present disclosure and is not to be construed as limiting the disclosure . although several embodiments of the disclosure have been described , persons of ordinary skill in the art will readily appreciate that numerous modifications could be made without departing from the scope and spirit of the disclosure . as such , it should be understood that all such modifications are intended to be included within the scope of this disclosure . the written description and drawings illustrate the present disclosure , and are not to be construed as limited to the specific embodiments disclosed .
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referring to fig1 , there is shown in perspective view a putter 1 with a scale 10 mounted to the putter shaft 2 . the shaft 2 includes a lower end 2 a that is connected to the putting head 4 , e . g . via a hosel . the upper end 2 b of the shaft 2 receives a grip 7 . referring to fig2 - 3 , the scale 10 indicates the degree of slope to a green by utilizing a pair of weighted ends 15 a , 15 b of a balance arm 14 configured to freely rotated about a shaft assembly 30 . the degree of movement of the arm 14 is appreciated by inspecting the deviation of the arm 14 relative to a fixed reference line 18 formed on the front surface of a backboard or reference surface 30 , the scale 10 may be enclosed in a glass or plastic case 11 . the case 11 may be formed as a diverging convex lens , which magnifies the relative positioning between the arm and reference line 18 for ease of viewing by the golfer . when the putter 1 is placed on the putting surface in the manner shown in fig2 , i . e ., with the reference line 18 extending parallel to the slope of the green and the rotation axis a ( see fig3 b ) orientated substantially perpendicular to the vertical , the arm 14 will rotate clockwise or counter clockwise if the slope of the putting surface is at an angle to the horizontal . the degree of slope may then be understood by the angle θ between the reference line 18 and the arm 14 . regardless of the tilt or slope of the putter , the arm 14 will extend parallel to the horizontal when the arm 14 is balanced about its support point 20 . thus , in fig2 the scale 10 indicates the degree of slope of the putting surface based on the difference between the horizontal ( arm 14 orientation ) and the slope of the green ( reference line 18 ). the difference in degree of slope being indicated by the angle θ between line 14 and line 18 . in some embodiments , this perturbation or rotation may be expressed visually to the golfer by simply inspecting the relative locations of the lines 14 , 18 , by using reference hash marks or reference lines displayed across the surface 30 or placed on the glass / plastic cover 11 , or by using distinguishing colors or patterns ( see fig6 a - 6b ). according to another aspect of the disclosure , the scale 10 includes a locking feature that enables a golfer to pick up the putter to inspect the slope depicted on the scale 10 . referring to fig4 a - 4b , which shows a cross - sectional view of the scale 10 as in fig3 b , the scale includes a shaft 20 about which the arm 14 pivots . the shaft includes a head 21 , a lower end having a knob 24 and a fitting 2 e that allows shaft to be pulled and pushed up or down , as indicated in fig4 a - 4b . when the knob 24 is pushed upwards as shown in fig4 a , the head 21 is separated from the surface 30 and does not obstruct the rotation of the arm 14 , so that the arm 14 can freely rotate about the shaft 20 . when the head 21 is brought down to abut the surface 30 , as indicated by reference 23 in fig4 b , the head 21 is pulled into abutment with the surface 30 and arm 14 , thereby retraining free rotation of the arm 14 . the knob 24 may be easily pressed towards the shaft opening 2 e , or pulled away from the shaft opening 2 e to selectively engage / disengage the head 21 from the arm 14 by known methods in the art , e . g ., by having a resilient , plastic ledge that engages with a ridge formed on the shaft 26 that selectively positions the head 21 in the locked ( fig4 b ) or unlocked position ( fig4 a ). this locking feature enables a golfer to pick up the putter to inspect the slope indicated on the scale 10 without disrupting the relative position between the arm 14 and reference line 18 . in use , the golfer would first place the putter 1 on the ground in the manner shown in fig2 ( so that the rotation axis a is about perpendicular to the vertical ) and allow the arm 14 to come to rest . next , the golfer would pull the knob 24 out ( fig4 b ) so as to fix the arm 14 in its balance position relative to the reference line 18 . the golfer may then pick up the putter to visually inspect the position of the arm 14 relative to the line 18 . this locking feature can obviate the need for a golfer to have to bend down to an uncomfortable position in order to inspect the scale 10 . referring to fig6 a - 6b , according to some embodiments , the scale 10 may include hash marks 40 that can be used to inspect the degree of slope , i . e ., the amount that the arm 14 has rotated relative to the reference line 18 . according to other embodiments , a scale 50 includes arms 14 which have a first color 52 and are shaped to cover a second color 54 when the putting surface is flat ( fig6 a ). when the putter 1 is placed on a sloped surface ( fig6 b ), the arm 14 having a first color 52 surface rotates to expose the second color 54 . the first color 52 may be , for example , green and the second color 54 red . while particular embodiments of the present invention have been shown and described , it will be obvious to those skilled in the art that changes and modifications can be made without departing from this invention in its broader aspects . therefore , the appended claims are to encompass within their scope all such changes and modifications as fall within the true spirit and scope of this invention .
| 0 |
in accord with the present invention , it has been unexpectedly found that the presence of an omega - 6 acid component , comprising either the free acid or a derivative thereof such as an ester or the like (“ omega - 6 acid component ”), will inhibit the isomerization of 17 - substituted hydrocortisones and other steroid materials . the present invention has particular utility in the stabilization of hydrocortisones having an ester moiety at the 17 position , and is particularly useful in stabilizing hc17 - b , and will be described with particular reference to the stabilization of hc17 - b . there are a variety of omega - 6 acids which function to stabilize the substituted hydrocortisones . “ omega - 6 ” signifies that the first double bond in the acid , counting from the end opposite the acid group , occurs in the sixth carbon - carbon bond . there is some confusion due to the fact that there are various nomenclature and numbering systems used for fatty acids . hence materials of the present invention have been referred to as “ omega - 3 ” acids , as well as by other names . in any event , within the context of this disclosure , the foregoing definition of omega - 6 acids is utilized . linoleic acid , also known as 9 , 12 - octadecadienoic acid , is one omega - 6 acid having utility in the present invention . linoleic acid is generally a very safe material , and is readily available . safflower oil is a triglyceride , comprising a fatty acid ester of glycerol , and it contains large amounts of linoleic acid in esterified form , and in particular embodiments of the present invention , safflower oil is used as a stabilizing agent for hc17 - b and similar materials . safflower oil is particularly advantageous for use in pharmaceutical compositions , since it is generally nontoxic , and has been approved for both topical and internal formulations . additionally , safflower oil , as well as other omega - 6 acid materials , have additional beneficial effects in topical formulations since they can enhance skin penetration and restore lipid content to the skin . other omega - 6 acids include arachidonic acid . yet other polyunsaturated omega - 6 acids are known in the art . such omega - 6 acids , as well as their esters and like compounds , may also be used in the present invention . in general , the omega - 6 acid component will be present in an amount which is at least equimolar with the steroid compound which is to be stabilized . in most practical formulations , the omega - 6 acid component is present in a relatively large excess , since it further functions as a skin conditioning agent . for example , it may be present in a weight percentage ten , twenty , thirty or even more times the weight percentage of the steroid compound . two experimental hydrocortisone 17 - butyrate formulations were prepared . one ( formulation r6546 ) contained a substantial weight percentage ( 3 . 0 % w / w ) of refined safflower oil . the other formulation ( r6539 ) was similar in composition to the first formulation , but lacked any safflower oil . in both formulations , the hc17 - b was present in a weight percentage of 0 . 1 . table 1 shows , respectively , the recipes for the two formulations , showing the various components respectively thereof as weight percentages . table 2 shows the analytic results of samples of the resultant respective compositions , showing the exact percentages of the hc 17 - b ( as well as propylparaben and butylparaben ) found in the two formulations expressed as weight percentages . from table 2 , it can be ascertained that the formulation containing the safflower oil had an average weight percentage of 0 . 101 hc17 - b , whereas the sample which did not contain the safflower oil had an average weight percentage of hc17 - b of 0 . 104 , a slightly greater weight percentage . the stability of the respective formulations was tested by analyzing the two formulations over a six - month period , at various intervals . the stability study was performed at a temperature of 40 ° centigrade , considerably greater than normal room temperature . as can be readily ascertained by comparing the six - month results for the two compositions , the composition containing the safflower oil ( r6546 ) did lose some hc17 - b . the weight percentage went from 0 . 101 at the start of the study ( from table 2 ) to 0 . 095 after six months . furthermore , the isomer hc21 - b began to make its appearance at the three - month interval , and was found at the six - month endpoint of the study in a concentration of 5 . 00 weight percent of the hc17 - b content . furthermore , there were various other impurities found at the six - month endpoint in a percentage of 0 . 56 weight percent . in contrast , the formulation which did not contain the safflower oil ( r6539 ), although starting out containing slightly more hc17 - b , it lost this component more rapidly and wound up with a considerably lower weight percentage of 0 . 86 at the six - month endpoint of the study . as would be expected , the formulation without the safflower oil and its constituent linoleic acid contained an even larger percentage of the isomer hc21 - b , namely , 6 . 36 %. furthermore , other impurities were found in this formulation after six months in a much larger percentage as well , namely , 2 . 81 weight percent as compared to only 0 . 56 weight percent . as can be seen from this data , adding the omega - 6 acid component in the form of the linoleic acid - containing safflower oil considerably increased the stability of the valuable hydrocortisone 17 - butyrate compound . in fact , the formulation which did not contain the safflower oil lost approximately 18 % of its original hc17 - b , whereas the formulation containing the safflower oil lost only approximately 6 %. in other words , the improvement in stability was practically threefold . furthermore , the level of the hc21 - b isomer and the other impurities was about 60 % less in the formulation containing the safflower oil than in the formulation where the safflower oil was absent . thus , adding an omega - 6 acid component in the form of safflower oil has been shown to be an effective way of stabilizing 17 - substituted hydrocortisone compounds . while the methods and compositions of the present invention have been described with reference to certain exemplifications and embodiments thereof , the invention is by no means limited to the specifically depicted examples and embodiments . for example , other 17 - substituted hydrocortisone compounds could also be stabilized through the use of the present invention . the omega - 6 acid component could be provided in other forms than as linoleic acid generally , or as safflower oil specifically . it is only necessary that the omega - 6 acid component be provided in a form which is pharmacologically compatible with topical hydrocortisone creams and lotions . doubtless , one of skill in the art could , after routine experimentation , employ other pharmacologically compatible omega - 6 components with similar efficacy without departing from the scope of the present invention . it is the claims appended hereto , rather than the exact exemplifications and embodiments , which define the scope of the present invention .
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with reference to fig1 , this invention has an ambiguity envelope ( ae ) security system 10 , which has a bounded random number generator function 16 , an ambiguity envelope function 12 and a jitter function 14 . the output of the bounded random number generator function 16 is called bounded random numbers or brns 17 . brns 17 are input to the ambiguity envelope function 12 : the ae function 12 using a shuffling and pairing sub - function 22 , and an envelope creating sub - function 24 creates an ambiguity envelope 13 . an envelope offset sub - function 26 uses envelope 13 and when inputted packet number 22 , outputs an envelope offset 27 , which is input to the jitter function 14 . the jitter function 14 using the input of the ambiguity envelope offset 27 and the prior art key 20 outputs random - variant - keys 18 . the ae implementation uses a small memory and processing throughput footprint that rides over the existing prior encryption schemes thus making the ae implementation relatively convenient in prior art encryption devices and prior art devices that embody embedded encryption mechanisms . integrated circuits , firmware and components that facilitate use of ae may be manufactured and sold to manufacturers of wireless devices such as cell phones , wireless access points , and other devices . with respect to upper part 60 of fig2 , the system 10 uses prior art encryption scheme using encryption algorithm 42 , seed value 44 , plain text 46 and encryption key 20 over a prior art wireless network 40 . as illustrated in lower part 62 of fig2 , in ae 10 , the prior art encryption key 20 is jittered or randomly modified to create random - variant - keys 18 for each packet # x . the random - variant - key 18 is then what is used for each packet instead of the prior art key 20 . the random - variant - key 18 is like the prior art key 20 in every respect including the key length . the difference between the random - variant - keys 18 and the encryption key 20 is that the random - variant - keys 18 are randomly created variants of the encryption key 20 . as shown , the random - variant key 18 is created by a jitter function 14 to which is input , the prior art encryption key 20 , and the ambiguity envelope offset 27 . the offset 27 is output by the ae function 12 , when the ae function 12 is input the packet sequence # x 21 . the envelope 13 , which is used to compute the offset 27 is based on the brns 17 and the ae parameters 48 as described later . in the ae function 12 , the packet sequence # x 21 is used to read an offset value 27 from the envelope 13 and is used by the jitter function 14 to create a random - variant - key for that packet number # x 21 . the ambiguity envelope 13 has x - axis as packet sequence number and y - axis has as the amplitude or offset of the envelope . this offset value is read from the envelope for a given packet number and is used by the jitter function 14 to create a random - variant - keys 18 for this packet . hence , the random - variant - keys are different for every packet and is created at the time of use for one time use in the temporary memory and then discarded . a time slice such as one second or some other time , in place of packet number 22 may also be used . the packet number is preferred as it is a recognized unique prior art mechanism to identify the order and sequence of transmission of packets between the two ends of transmission . however a time slice instead of packet may also be used provided the time system clocks at the ends of transmission are synchronized and can be relied upon . with reference to fig2 , the ae function 12 and jitter function 14 are present at both ends of the transmission path . for illustration purposes , the line 40 divides the transmitting end 40 a and the receiving end 40 b . the brns 17 and the ae parameters 48 enable the random variation of the prior art key 20 resulting in random - variant - keys 18 . the brns 17 are created at one end of the transmission path and then transferred to the other end by an out - of - band method depending upon the application as described later with reference to fig4 , 6 and 7 . with reference to fig1 and 2 , ae parameters 48 determine how the brns 17 are transformed into an ambiguity envelope 13 using shuffling and pairing function 22 and a envelope creation function 24 . the offset function 26 outputs an offset 27 of the envelope 13 when input a packet sequence 21 . these functions 22 , 24 and 26 are described in more detail later and add or provide multiple degrees of random separation from the brns to the envelope itself . thus knowledge of the brns 17 themselves does not provide knowledge or computation of the ambiguity envelope 13 . the ae parameters 48 may be unique and different for different classes of wireless devices that use encryption such as wireless access point &# 39 ; s network and cell phones . with reference to fig1 and 2 , in a system of encryption for communication security that uses an encryption algorithm 42 and a pre - placed encryption key 20 , this invention provides a security function 10 that generates a sequence of random - variant - keys 18 one at a time , on a per packet basis in temporary memory of an encryption device from the pre - placed key 20 at the time of encryption and not before and uses these random - variants - keys 18 for encryption instead of the pre - placed key 20 and immediately thereafter discards the random - variant - keys 18 . prior art random generators of any type may be used to generate a sequence or set of random numbers of specified number of digits . when the random number is limited to a specified number of digits it may be called a bounded random number or a brn . for example , if an up to 2 digit random number is derived from a larger random number generated from a prior art random number generator function it is a bounded random number . the random numbers may be bounded to any number of digits depending upon the application . for some applications they may be single digit bounded and for some other applications they may be bounded to such as 2 or many more digits . further , a sequence of such bounded random numbers is created . such a sequence may have a short sequence of 6 , or a medium sequence , or a long sequence that have many tens of bounded random numbers . a sequence that is even and of at least six numbers is preferred as is described later . these bounded random numbers are used for creating an indeterminate envelope as described later . the envelope is considered indeterminate having multiple stages or degrees of random separation from the brns themselves . this function has three sub - functions as described here . the input to the function 12 is the sequence of brns from the function 16 and the output is an ambiguity envelope offset 27 , which is input to the jitter function 14 . the three sub - functions are : this sub - function takes the brns 17 shuffles them , and then pairs them so that each pair may describe cycle time and amplitude parameters of a wave . as a simplified illustration , if there are six numbers , 12 , 45 , 56 , 23 , 67 , 98 generated in that order by the brn function 16 , then the shuffling function shuffles this sequence in one of many shuffles . an ae parameter 48 a may be used to define one of many shuffle approaches . the shuffled brns are then paired in three pairs . another ae parameter 48 b may be used to define the pairing . the pairs then may be further shuffled to define which of the number of a pair represent the cycle time of the wave and which represents the amplitude . the output of this sub - function is a number of pairs . as a simplified illustration , when the brns are six in number , output of this function , are three pairs of numbers , where each pair represents the cycle time and amplitude of a wave . the three wave pairs from the six brns after the operation of this function may be ( 56 , 98 ), ( 45 , 12 ), and ( 23 , 67 ) where the first number of the pair is cycle time and the second number is the amplitude . in this function , each pair of brns is then mapped to a wave type such as a sine wave , or a square wave or a triangle wave . again an ae parameter 48 c may define which one of many possible approaches to mapping may be used . the wave types are chosen to be a sinusoidal , a triangle and a square wave type . other wave types may also be used but these wave types are preferred as they are defined by a pair of numbers that map to two of the brns and are distinct in their properties of how their amplitude on y - axis varies along the x - axis . once the mapping to the wave types is done , this function then takes the three waves and additively combines them into one envelope . by adding these wave types of different types results is an ambiguity envelope 13 . optionally a phase value may be assigned to each of the waves before they are additively combined if one of the brns may be used to represent a phase value . in addition , a phase may be added to the entire envelope , where such a phase would be different for the sending and receiving ends of the transmission . how the brns 17 may be converted to an ambiguity envelope 13 has been described . many approaches in addition to the above may be used and are not ruled out . the shuffling , pairing and then shuffling within the pair that map to one of the wave types provide different types of random approaches to separate the envelope from the brn itself . mere knowledge of the brns themselves would make impossible the creation of the envelope . alternatively the brns may be straight forward used to create an envelope without the use of shuffling , pairing and shuffling with in pairs as defined by the ae parameters 48 . however , it is believed that these functions add different types of randomness for the creation of the envelope from the brns and thus provide additional level or layer of security . therefore , the compromise of the brns does not affect the security as provided by this invention in creating random - variant - keys 18 . furthermore , the ambiguity envelope 13 that results is indeterminate and could not have been duplicated by any means as it is a summation of different wave types , randomly selected , and used randomly assigned parameters from a random set of parameters . the ambiguity envelope does repeat but at a random cycle time . the cycle time of the envelope is based on the factorial of the cycle time of the three waves . for example , if the three cycle times are 56 , 45 and 23 , then the cycle time of the envelope would be a lowest number that is divisible by 56 , 45 and 23 . hence the ambiguity envelope is indeterminate having been derived from the brns by a series of operations as described herein . the amplitude of the envelope 13 would randomly vary between the positive and negative values of maximum of sum of individual wave amplitudes . hence the offset value 27 for a packer sequence number # x 21 may be positive or negative between these maximums or zero . given the same brns 17 at the two ends of the transmission and the same ae parameters 48 , the same ambiguity envelope can be created . there may be two envelopes at each end of the transmission , one for generating random - variant - keys for encrypting outgoing packets and one for generating random - variant keys for decrypting the incoming packets . these two different envelopes may use a different set of brns or use the same set of brns but add a different phase to the envelope , so that a different random - variant - key would result for the incoming packet and the outgoing packet , even if the packet sequence number is the same and even if the packet sequence number is different . in a real transmission the packet sequence numbers may be different as more packets may be transmitted in one direction than in the other direction . for example when the same brns are used at the two ends , the phase offset may be zero at one end and another number at the other end . for this offset , some of the numbers from the sequence of the brns themselves may be used . this function , when input a value for an x - axis , computes a y - axis value from the ambiguity envelope . the x - axes value is a packet sequence number in a session of communication . the y - axis is an envelope offset which is input to the jitter function 14 . this function is input the packet sequence number at the time of the packet creation and outputs an offset value . the offset value from the envelope for a given packet sequence number maybe an integer , maybe an integer plus a fraction , or maybe positive or negative or zero . this offset may be used in a variety of random ways to provide random - variant - keys 18 as described in the jitter function 14 . the jitter function 14 transforms the y - axis offset of the envelope into a series of numbers and this series of numbers is used to alter the pre - placed key 20 to arrive at a random - variant - key 18 , where each y - axis offset yields a new random - variant - key . the jitter function 14 may use one or a combination of techniques of , ( i ) the pre - placed key is altered by performing an operation such as bit reversal corresponding to the series of numbers , ( ii ) the pre - placed key is altered by performing an operation such as adding or subtracting the offset from the pre - placed key . any number of possible approaches from the envelope offset maybe used to create random - variant - keys in addition to the two described above . as a simplified illustration , using the first technique , if the offset is 329 . 7 , the series of numbers derived from this offset may be 3 , 2 , 9 , 32 , 29 , 39 , 5 , 11 , and 14 by a combination of the numbers 3 , 2 , and 9 . these bit numbers in the key may be flipped from a 0 to 1 or a 1 to a 0 . as a simplified illustration , using the 2 nd technique , the offset number 329 may be added to the prior art key at the 7 th bit position from one end of the key . other similar techniques that are derived from the offset value may be used . these techniques are embedded in the jitter function 14 that is present at both ends of the transmission . the technique that is used in a jitter function may be different for different classes of the devices that use the security function 10 . for example one technique may be used in cell phones and another technique may be used in the wireless access points of a network . a third technique may also be used for creating random - variant keys 18 . this third technique may create two random - variant - keys for each packet that may be used as layers of keys for double encryption . for example , technique 1 may be used to create a random - variant - key 1 18 and technique 2 may be used to create a random - variant - key 2 18 a as shown in fig3 b - 1 and 3b - 2 . then key 1 may be used to encrypt a data packet and key 2 may be used to further encrypt the same data packet . this technique provides an additional level of randomness in the generation of random - variant - keys and an additional layer of security . for a given packet even if brute force approach were attempted to break the random - variant - key for that packet alone , the plain text of the packet &# 39 ; s data contents would not result and would not verify the accuracy of the random - variant - key . fig3 a and 3b - 1 & amp ; 2 describes the operation of the security function 10 . as shown security function 10 of fig1 , has three steps , 82 , 84 and 86 . step 82 is a bounded random number ( brn ) function . the step 84 is an ambiguity envelope function . step 86 or 87 , is a jitter function . step 82 , as in fig3 a is a bounded random number ( brn ) generator function . it is used to create six two - digit numbers . since , such numbers are commonly used in a lottery , the output of step 82 , as such , may be named a lottery number . hence step 82 generates a lottery number made of six two - digit numbers . where manual methods maybe used to copy a brns from one device to another device , the concept of lottery number makes it easier to humanly read , receive and enter into a device . in this description , the terms ae coefficients , lottery number and brn mean the same thing and may be used interchangeably . these are a set of bounded randomly generated numbers by a random number generator function . when they are limited in size such as one digit , 2 digit , etc , they are referred to as bounded random numbers . when they are bounded to 2 digits and are six in number they are referred to as a lottery ticket , as customarily , a lottery ticket has six two - digit numbers . however , depending upon the application the brn may be longer numbers and may correspond to more than six numbers . step 82 is performed on one end of the two points of a wireless transmission path . which end of the transmission link it is performed , how often it is performed or the brns are refreshed and how the brns are carried or conveyed over to the other end of the transmission path is illustrated later with reference to fig4 , 6 and 7 for different applications . thus having the lottery number , ae coefficients or brns at both ends of the transmission now leads us to step 84 . as shown in fig3 a , step 84 has four sub - steps 1 to 4 . optionally an ae flag 33 may be used to turn the features of security function 10 on or off in a given application . in sub - step 1 , the ae function 12 takes the lottery number 17 and creates an ambiguity envelope 13 . a simplified representative envelope 13 is shown . the envelope 13 has an x - axis and y - axis . the x - axis is packet sequence number 21 and y - axis is amplitude or offset 27 for the packet sequence number 21 . three different ae parameters 48 may be used to quantify how the brns 17 may be transformed into an ambiguity envelope . the ae parameters may be , ( i ) wave pairs ( wp ), ( ii ) wave order ( wo ), and ( iii ) wave type ( wt ). as an illustration , if the brn is a set of six two digit numbers 24 , 64 , 23 , 89 , 72 44 , then for example , wp may be 1 , 6 , 2 , 4 , 3 , 5 . this means that 1st and 6th number form a pair , 2 nd and 4 th number form a pair and 3 rd and 5 th number form a pair , so that the pairs that define a wave are ( 24 , 44 ), ( 64 , 89 ), and ( 23 , 72 ). the wo defines in each pair , which number is cycle time and which number is amplitude . for example , wo may be , ( 23 is cycle time and 44 is amplitude ), ( 64 is amplitude and 89 is cycle time ) and ( 23 is amplitude and 72 is cycle time ). the wt defines the type of each of the waves , such as , first pair represents a triangle wave , second pair represents a square wave , and third pair represents a sine wave or even a cosine wave . these ae parameters take the original six randomly generated numbers and turn them into three waves , each with an amplitude and cycle time . thus the lottery number yields three waves of different amplitudes , cycle times and different shapes or types based on the lottery number set of six numbers . then these individual waves are additively combined to yield an ambiguity envelope 13 . these steps of starting from the random bounded random numbers 17 and arriving at the ambiguity envelope 13 provide different types of randomness and break the chain of mathematical causation between the brns 17 and the ambiguity envelope 13 . having a different set of ae parameters 48 enables ae function 12 to be different from application to application or even among applications by assigning a version number to the ae function . the ambiguity envelope would repeat after a number that is equal to factored number of multiplication of three cycle times . for example , if the cycle times of the three waves are 33 , 67 , 99 , and since 99 is divisible by 33 , then the envelope would repeat after 99 × 67 packets or seconds ( if time slice is used ), because at that interval , a whole number of each of the waves are present . the ae function 12 , performs the tasks of , given or initialized with a lottery number , creates the ambiguity envelope as described above , and when is inputted a packet sequence number or time sequence , looks up the corresponding offset for it . the amplitude or offset of the ambiguity envelope may be positive , zero or negative for different packet sequence numbers . it may be a whole number that may be rounded from a fraction or may be fraction . at sub - step 2 , the standard 128 - bit encryption key and the offset from the ambiguity envelope function 12 is input to the jitter function 14 . the jitter function 14 then yields a random - variant - key 18 for a given packet sequence number , as illustrated in step 86 . at sub - step 3 , a standard encryption function 42 is used with the random - variant - key 18 . at sub - step 4 , a function keeps track of the incoming and outgoing packet sequence numbers by incrementing these two variables . these variables are used in sub - step 1 and sub - step 3 as shown . the step 84 functions of ae function 12 and jitter function 14 , as outlined above , are duplicated in the software or firmware at both the ends of the wireless transmission . the separate incoming and outgoing packet sequence numbers synchronize the generation and use of the random - variant - keys 18 at both ends of transmission . generally for each transmission / communication , the packet sequence number is initialized . however , there may be reset or synch commands exchanged between the two ends of transmission that would reset or re - synch the packet counters to either zero or another fixed number . alternatively , instead of packet number a time such as in seconds referenced to the beginning of the session may be used . when time is used the ambiguity envelope on the x - axis will have time in seconds . a particular offset for a given time read on the x - axis may be used until the next time segment . the offset 2 is used to jitter or vary the prior art key 20 . for example , if the ae offset is 69 , this number may be used arbitrarily so that the random - variant - key for this packet may be where the 6 th , 9 th , 15 th and 69th bit are flipped in the 128 bit encryption key . if offset is zero , the packet data may be dummied up . if offset is negative , then a slightly different jitter approach may be used or the negative may be treated as a positive offset . if the offset is a whole number and a fraction such as 79 . 23 , then these numbers may be used to decide which of the bits will be altered or flipped . the random - variant - keys , as described above , have no mathematical relationship to the original static key 20 . thus the jitter function 14 creates a large number of random - variant - keys 18 from one original key 20 that permit a different random - variant - key to be used for each packet as long as the incoming and outgoing packet sequence numbers remain synchronized at the two ends of the wireless transmission path . in an alternative scheme different layers of random - variant - keys may be used . for example , what is described above with reference to fig3 b - 1 may become the first layer of random - variant - keys and what is described in step 87 , in fig3 b - 2 may become the second layer of random - variant - key . fig3 b - 2 illustrates that the offset number itself may be used to create another key , where the offset number is placed in some random variable location of the 128 bit key . as an illustration , if the offset is 329 . 72 , the second layer of random variant key may be the number 329 starting in the 72 nd bit location . similar other schemes may be used based on the offset . now with the help of fig4 to 7 , different applications where the security function 10 of fig1 and 2 may be used are described . fig4 describes a wireless network application , fig5 describes a cell phone application , fig6 describes a mobile ad hoc wireless network application , and fig7 describes the use of optical means for distribution of brns in some of the applications . with reference to fig4 a , this invention describes a system of security 100 in a nationwide wireless network that uses the security function 10 of this invention . the system 100 may use adapted wireless access points ( waps ) 140 connected to either a local area network , a wide area network of a business or to a global network 112 . the waps may be used by wireless devices such as laptops 132 , of users with cell phones 130 . the users may be employees of a business , or at large users who have subscribed to this service as described herein . in the system 100 , there is a call screening function 102 that receives cellular calls with caller id and geographic cell data and screens permitted calls based on a pre - stored list of caller id ; a call mapping function 104 that maps the call to a wap in the area identified by the cell ; and a call routing function 106 that routes the call to a telephone number assigned to a wap in the area . the service related to functions 102 , 104 , and 106 maybe provided by a service provider or the service maybe provided by a cellular telephone company 120 , which provides the telephone numbers . it is to be noted that the cell network provides a unique caller id mechanism that is tied to the sim card of the cell phone , along with a cell based geographic location identification of the caller &# 39 ; s physical location at the time the call was made . some of these functions , 102 , 104 and 106 may be provided by a cellular company and other functions provided by a service provider . for example , the cellular company may provide caller id and geographic location data for each call and the cellular company 120 may maintain a list of authorized account holder caller ids , who have subscribed to this service and screen calls against this list and forward such screened calls to a service provider . the service provider may a business entity that maintains the servers that facilitate the automatic operation of functions 102 , 104 and 106 . the service provider then may map the caller id and location data to a wap in that geographic area . the mapping may be based on both the geographic area as well as the caller id . this dual mapping would enable identifying and mapping the callers to those waps that are available for certain network as those belonging to a national business based on caller id identification . this would enable different wap and networks to be maintained for different national companies . the service provider then is able to route the calls from cell phones to a specific wap in the geographic area . in this system of security 100 , the prior art wap 108 is adapted with a telephone interface and a simplified ivr 110 that is able to voice deliver a sequence of numbers resembling a lottery ticket , such as two digit brns , to the caller . the wap 108 is further adapted with the functions of security function 10 , as was described earlier with reference to fig1 . these functions are bounded random number generator function 16 , ambiguity envelope function 12 , and jitter function 14 . these functions ( i ) generate brns , ( ii ) converts the brns numbers to an envelope , with x - axis packet and y - axis identifying envelope amplitude as an offset , and ( iii ) using the offset as a parameter provide random variants of the pre - placed encryption key and using the random - variant - key as the encryption key in place of the pre - placed key for encryption in the wap . the adaptation of wap 108 also includes a function to receive a call , create a data record anchored by the caller id of the call , and select a port number that may be assigned to this caller , use function 16 to generate brns 17 . the adapted wap 140 maintains data records with the information fields of , time stamp of the call , caller id of the call , port number assigned to this call and the brns that were generated for this call . similar records are maintained for each call that is received by the adapted wap 140 . the wap 140 may also have a feature to delete such a record at the end of session or 24 hours which ever occurs first the wireless card 134 present in the laptop computer 132 of the user is an adapted wireless network interface card . the wireless interface card 134 adapted with a function to display and be able to input a series of random numbers and a port number of a wap via a display screen 122 . the wireless card is further adapted with some of the function of security function 10 that is the ambiguity envelope function 12 and jitter function 14 . these functions ( i ) converts the brns numbers that are received via screen 122 , to an envelope , with x - ax - packet and y - axis identifying envelope amplitude as an offset , and ( ii ) a function that using the offset as a parameter provide randomly variants of the pre - placed encryption key and using the random - variant - key in place of the pre - placed key for encryption in the wireless card 134 . the wireless interface card 134 of the computer device 132 is adapted to work with the adapted wireless access point 140 . hence , the adapted wap 140 and the adapted wireless card 134 are able to use random - variant - keys for encryption and decryption of the wireless communication between the wireless card 134 and the wap 140 . fig4 b illustrates the operation of the nationwide wireless application of this invention . at step 1 , the laptop computer user equipped with an adapted wireless card , using his cell phone , calls a designated telephone number . at step 2 , the cell phone company 120 receives the call . at step 2a , the service provider performs a screen function , which screens the call as one who has subscribed to the service , based on caller id and then routes the call to a map function . at step 2b , the map function maps the call &# 39 ; s geographic cell location to available waps in that cell location . the mapping in addition to the physically proximity of the wap to the cell location may also use the caller id for mapping . the caller id mapping may be able to differentiate those waps that belong to a private business network belonging to a national business and are allowed to be used by pre - identified callers with pre - registered caller ids with this business . if the mapping function is unable to map such a refinement of location , due to multiple waps in the same location , the caller may be asked to select from a sorted list of locations in the specific cell by the map functions . at step 3 , the cellular company uses a route function , which routes the call via a public telephone network 121 to the specific wap approved for the caller &# 39 ; s use from the collection of waps in the database . at step 4 , thus the call , after being routed through the screen function , the map function and the route function , is answered by the specific wap adapted with a telephone modem interface with an ivr . the caller is unaware of these functions and the call is answered by the specific wap close to the caller &# 39 ; s physical location . at step 5a , the wap 140 creates a record with the time stamp and caller id , assigns a port number , generates and stores in the record the brns , and voice delivers brns to the caller along with the port number . at step 5b , the wap 140 monitors the sessions and deletes the record , if the wireless communication session is not established within a specified time threshold of the time of delivering the brns to the caller and deletes the record at the end of the session or up to a time limit such as 24 hours if the session is continuing . thus the wap does not maintain a long list of records anchored by the caller id and the port number and frees up the port for other users . at step 6a , the caller hears the seven numbers port number and the six brns and at step 6b enters them into the screen 122 that is provided by the adapted wireless card . the caller enters his caller id and clicks ok to complete step 6b . in this application , the caller id of the phone that is used to call the wap or some other number that is created by the caller may be used for authentication between the laptop and the wireless access point . if the caller id is used it is automatically recorded from the call by the wap , and is also entered by the user along with lottery numbers in screen 122 as shown in fig4 b . this number may be used in the body of the data packets to authenticate the laptop to the wap and vice versa . at step 7a , the adapted wireless card stores the brns and uses security function 10 to create random - variant - keys that are used in place of the standard key for encryption and decryption of the wireless communication . at step 7b , a similar function is performed in the wireless access point 140 . at step 8 , the packets that are exchanged between the laptop and the wap may provide the port number in the header of the packet in addition to the prior art information such as ssid . this enables the wap to identify the packets for one of the ports and be able to find the record that has the caller id and the brns and know which brns to use for this particular laptop transmission for this particular user . this enables the wap to apply the right envelope and the right random - variant - keys to decrypt the packet and find in the data the caller id , which is used to authenticate the laptop user as the one who made the call and was given this set of brns . cell phones and similar wireless devices are used by individuals , law enforcement groups , business entities , and other special groups who may wish to add extra security to their conversations and data transmittals than what is provided by the digital phones themselves as part of wireless security by the cellular telephone companies . such wireless devices are used for both voice and data communication . as part of the encryption already provided in digital cell phones , an encryption key that may be part of the sim of a cell phone encrypts the wireless communication from the cell phone to the cell company network , where the cell company decrypts the communication and may route it on a land line to the network of the recipient cell phone company , where the recipient phone company encrypts it with the encryption key of the recipient phone and routes it wirelessly to the recipient phone . thus this encryption security as provided by prior art devices protects the wireless part of the communication . many people are of the opinion that this encryption is not strong and may be broken by determined parties . the security provided by the security function 10 as described earlier with reference to fig1 may additionally be provided to such a wireless or cellular network . the security function 10 may be adapted in the cell phones to work at a layer below the mode of encryption security in prior art cell phones , thus leaving the prior art encryption intact . with reference to fig5 , a system of security 200 against eavesdropping between handheld wireless devices such as cell phone communication based on security function 10 is described . the system 200 has prior art cell towers 220 , prior art cell phones 202 , and prior art caller id 204 associated with each phone . in system 200 , each cell phone 202 is adapted to provide the security function 10 as has been described earlier with reference to fig1 . in this adaptation , each cell phone is further adapted with an ae cell phone function 206 , brn function key 208 and ae function key 210 . the ae cell phone function 206 provides interfaces to soft key 208 and soft key 210 and maintains a table 212 . the table 212 maintains a list of phones identified by caller id 204 and their corresponding brns 17 . when the brn function key 208 is activated , it launches the brn function 16 of the security function 10 and displays brns 17 on the screen of the phone 202 . these brns 17 are then manually transferred or copied to other cell phones . the brns may also be transferred via an optical interface , if the phones 202 are equipped with such an interface . the function 206 maintains a table 212 , which for each caller id 204 maintains the corresponding brn 17 . thus function 206 allows each phone to maintain a brn for itself and each phone it may choose to communicate with the use of security function 10 . soft key 210 enables each phone 202 to choose to activate the security function 10 for all calls or for some calls by turning the soft key on and off . when the soft key 210 is off , the phone works like a prior art phone without using the security function 10 . hence , in this system 200 , each phone may selectively enable and disable the security function 10 for each communication by setting a flag via soft key 210 that is under the control of the user . in fig5 , for the purpose of explanation , one of the cell phones 202 is identified as cell phone a 202 a and another is identified as cell phone b 202 b . when cell phone a communicates with the cell phone b , and when the soft key 210 is activated in the cell phone a , the cell phone a activates the function 206 . the ae cell phone function 206 searches for the brns in the table 212 , that are applicable to the caller id 310 332 4343 of cell phone a ( caller phone ), as 345679 and searches for the brns in the same table 212 , that are applicable to the caller id 626 332 4834 of cell phone b ( called phone ). the function 206 with the help of function 10 uses these brns to generate random - variant - keys and uses random - variant - keys for encrypting outgoing transmission that are from the brn associated with own caller id and uses the random - variant keys for decryption that are from the brn that is associated with the caller id of the other phone in the table 212 . a similar operation takes place in the called cell phone b . cell phone a and b each equipped with a security function 10 that generates brns for each phone or caller id , converts each brns at each end into an ambiguity envelope , with an x - axis and a y - axis and with a jitter function 14 that using the offset from the envelope creates a time and packet dependent sequence of random - variant - keys from the existing key and use such keys for encryption . hence in this application , it is possible , while leaving all the functions of existing cell phone intact , add or overlay ae encryption security between any two or more specific cell phones . each cell phone pair may have software functions that enable a layer of encryption using ae in addition to what ever is used in prior art . hence , the ae can be optionally be used between any two phones and not other phones and not all phones and it may be activated or deactivated to be used or not used for each call . when the call is received at a cell phone and if ae is on , then it checks the caller id against the list and if a brn is found , which will be the same as used by the caller , then ae encryption is used . the system of security 200 has an exchange mechanism where the cell phones may use manual , infrared , and radio frequency means of exchanging the brns . ae may also be used in many other wireless as well as wired applications that are not described here . some times ad hoc wireless networks may need to be set up in remote areas and or in a theatre of operation . fig6 shows the mobile ad hoc wireless network application 400 most likely to be used in a theatre of operation . assuming such an application 400 has a base station 402 and multiple forward base stations such as 404 and 406 , and each base station supports multiple hand held units 406 and 408 . these base stations 402 , forward stations 404 and 406 and handhelds 406 and 408 may be equipped with the security function 10 as has been described earlier with reference to fig1 . in such an application 400 , brns may be generated in the forward base station 404 and either may be manually keyed in each of the hand sets 406 for this forward base station . alternatively , as shown in fig7 , if the forward base station and the hand held units are equipped with infrared capability , then the brn may be transferred to all hand units at one time within a few seconds from the forward base station by placing them in close proximity to each other . as shown in fig7 , the base station # 2 406 is equipped with an optical transmitting means 410 and each of the handhelds 408 are equipped with an optical receiving means 412 . multiple handhelds 408 may be placed as a group in the optical transmitting path of optical interface 410 and thus would be able to simultaneously transfer the brns to the handhelds 408 . the brns may be changed for each mission or whenever desired for security reasons of the environment where the mobile ad hoc wireless network is put in place . hence , optical means such as use of infrared , if the devices are equipped with infrared sensors such as commonly used in televisions and like , may be used to quickly and efficiently transfer the brns to the other end of the transmission path . different brns may be used for different forward base stations . for example forward base station # 1 404 may use brn 1 that it generated for its hand held units 406 . forward base station # 2 406 may use brn 2 that is generated for its hand units 408 . forward base station # 1 to communicate with forward base station # 2 may generate brn 3 and that may be manually entered in forward base station # 2 or copied via other means . each of the forward base stations may use a different brn such as brn 4 and brn 5 when communicating with the base station 402 . these brns 4 and 5 may be generated by base station 402 and manually communicated and entered in by the people setting up the base units at the time of set up . this having different brns spread out over a theatre of operation of ad hoc mobile network provides additional transmission security . there are many other applications where the security function 10 may be used in addition to the three applications of wireless networks , cell phone networks and ad hoc wireless networks as described above . in an application , the wireless and wired part of a network may be combined to provide the security function 10 over an entire network from end to end . in this application the user of a laptop may directly contact the host computer and receive brns . while the user may still use a wireless network , the security function 10 may provide security over the entire network from the laptop to the host computer including the wireless and the wired part of the network to the host computer . the system of security 10 may also be used in the wireless device that may be bluetooth equipped device , where the communication is between the cell phone and a bluetooth extension of the device such as an earpiece . if the other end of the bluetooth device is an earpiece , which may use prior art means of switches and display window to manually transfer the brn . the cell phone owner reads the brns on the phone and one by one manually transfers them to the earpiece via the switches and the display . this manual operation is required to be done only once by the user or when ever he / she wants to reset the encryption , every few months or year or so . alternatively , if the bluetooth devices are so equipped , the brns may be transferred via bluetooth format or an optical format . another application may be satellite to ground communication , where the brns may be long and complex and are installed in the satellite at launch times or they may be updated at other times by other means . the security function 10 may be implemented in software , firmware and hardware integrated circuits depending upon the application . if implemented in an integrated circuit chip that embeds the security function 10 then it has , ( i ) an interface for inputting a series of bounded random numbers , ( ii ) a logic that converts the numbers to an envelope , with x - axis corresponding to a packet sequence and y - axis corresponding to an envelope amplitude offset for a packet sequence , and ( c ) a logic that uses the offset for a packet sequence number and a static encryption key as inputs and randomly variates the static encryption key outputting random - variant - keys , thereby enabling the use of the random - variant - keys for encryption and decryption of data packets in place of the static key . the use of security function 10 in these and other applications provides for a robust and in - depth transmission security , where the security of the communication is not dependent upon the security of prior art encryption keys and thus reduces the cost and effort of frequently updating the prior art encryption keys and maintaining a key management infrastructure for them . while the particular system and method as illustrated herein and disclosed in detail is fully capable of obtaining the objective and providing the advantages herein before stated , it is to be understood that it is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims .
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fig1 a , 2 and 2 a display one possible embodiment of the present invention . the figures display a template 11 manufactured , for example , using stereo lithography ( sla ) from a suitable material such as an extra clear resin . the template 11 has a body 13 that generally corresponds to the shape of the object targeted for gross error evaluation . the shape of the body 13 could be determined from a solid model computer file of the object targeted for gross error evaluation . the body 13 has an interior surface 15 that faces the object and an exterior surface 17 that faces away from the object . the interior surface 15 includes a plurality of protuberances 19 . the protuberances 19 contact the object , and keep the remainder of the body 13 offset from the surface of the object . the protuberances 19 preferably have a height that accommodates variation in object size without the remainder of the body 13 contacting the object . the location of the protuberances 19 could conform to a point system used during the manufacturing process . preferably , the body 13 has six protuberances 19 since the point system used during the manufacturing process identifies six points on the object . fig1 a is a detailed view of the exterior surface 17 of the body 13 . the exterior surface 17 preferably has one or more scribe lines 21 thereon . if formed during an sla process , the scribe lines 21 could be grooves that extend a distance into the exterior surface 17 of the body 13 . the present invention could utilize other suitable techniques to form the scribe lines 21 . for example , the scribe lines 21 could be printed indicia . in other words , the scribe lines are printed onto the exterior surface 17 of the body 13 . the scribe lines 21 allow the user to evaluate the object , specifically a feature of the object , for gross errors . accordingly , the scribes lines 21 are positioned on the exterior surface 17 so as to correspond to the location of such feature on the object . as shown in fig1 a , the template could have two scribe lines 21 per feature . one scribe line 21 could identify a minimum of a tolerance range for the location of the feature on the object . the other scribe line 21 could identify a maximum of a tolerance range for the location of the feature on the object . the template 11 could also include printed indicia 23 to identify the object targeted for gross error evaluation . for example , the printed indicia 23 could be the part number of the object targeted for gross error evaluation . other manners of identifying the object targeted for gross error evaluation , however , could be used . fig2 and 2 a display one possible application of the template 11 . the object targeted for gross error evaluation in the figure is a blade 50 of a gas turbine engine ( not shown ). the blade 50 includes a root section 51 for securing to a disc , an airfoil section 53 for converting the velocity of the fluid exiting the combustion section ( not shown ) of the engine into rotation of the disc , and a medial section 55 between the root section 51 and airfoil section 53 . the manufacturing process for the blade 50 identifies points 57 thereon . preferably , the manufacturing process identifies six points 57 on the blade 50 . due to the exposure of the airfoil section 53 to the high temperature fluid exiting the combustion section of the engine , the airfoil section 53 can have apertures 59 in communication with a hollow interior ( not shown ). cooling air ( not shown ) provided to the hollow interior exits the apertures 59 to provide film cooling to the blade 50 . the template 11 allows the user to ensure , after the manufacture of the blade 50 , that : ( 1 ) the apertures 59 exist on the suction side of the airfoil section 53 of the blade 50 ; and / or ( 2 ) the apertures 59 are properly located ( i . e . within the tolerance range of the location of the feature on the object ) on the suction side of the airfoil section 53 of the blade 50 . as seen in fig2 , the blade 50 receives the template 11 . the protuberances 19 engage the blade 50 at the points 57 identified during the manufacturing process . once associated with the blade 50 , the user can view through the template 11 to evaluate the blade 50 . fig2 a displays a view through the template 11 with a properly located cooling hole 59 ( the cooling hole 59 has been shown in phantom line to avoid confusion as the cooling hole 59 resides behind the clear template 11 ). as discussed above , the protuberances 19 keep the remainder of the body 13 of the template 11 away from the surface of the blade 50 . the distance between the body 13 and the blade 50 is kept to a minimum to avoid parallax error . fig3 displays another possible embodiment of the present invention . the figure displays a template 111 . the template 111 is preferably used to evaluate a different section of the object targeted for gross error evaluation . save for a change in the hundreds digit , the reference characters identifying features of template 111 correspond to the reference characters identifying the same features of template 111 . briefly , template 111 has a body 113 manufactured , for example , using stereo lithography ( sla ) from a suitable material such as an extra clear resin . the body 113 generally corresponds to the shape of the object targeted for gross error evaluation . the body 113 has an interior surface 115 that faces the object and an exterior surface 117 that faces away from the object . the interior surface 15 includes a plurality of protuberances 119 . the protuberances 119 contact the object , and keep the remainder of the body 113 offset from the surface of the object . the protuberances 119 conform to a point system used during the manufacturing process . preferably , the template 111 has six protuberances 119 . the exterior surface 117 of the body 113 preferably has one or more scribe lines 121 thereon . if formed during an sla process , the scribe lines 121 could be grooves that extend a distance into the exterior surface 117 of the body 113 . the present invention could utilize other suitable techniques to form the scribe lines 121 . for example , the scribe lines 121 could be printed indicia . in other words , the scribe lines are printed onto the exterior surface 117 of the body 113 . the scribe lines 121 allow the user to evaluate the object , specifically a feature of the object , for gross errors . accordingly , the scribe lines 121 are positioned on the exterior surface 117 so as to correspond to the location of such feature on the object . preferably , the template 111 has two scribe lines 121 per feature . one scribe line 121 could identify a minimum of a tolerance range for the location of the feature on the object . the other scribe line 121 could identify a maximum of a tolerance range for the location of the feature on the object . the template 111 could also include printed indicia 123 to identify the object targeted for gross error evaluation . for example , the printed indicia 123 could be the part number of the object targeted for gross error evaluation . other manners of identifying the object targeted for gross error evaluation , however , could be used . fig4 displays the template 111 mounted on the blade 50 . the template 111 allows the user to ensure , after the manufacture of the blade 50 , that : ( 1 ) the apertures 59 exist on the pressure side of the airfoil section 53 of the blade 50 ; and / or ( 2 ) the apertures 59 are properly located ( i . e . within the tolerance range of the location of the feature on the object ) on the pressure side of the airfoil section 53 of the blade 50 . the protuberances 119 engage the blade 50 at the points 57 identified during the manufacturing process . comparing fig2 and 4 ( note the figures show different sides of the blade ), it is clear that the protuberances 119 contact the same points on the blade 50 as the protuberances 19 when using the template 11 . fig5 - 7 display another possible embodiment of the present invention . the figures display a template 211 . the template 211 is preferably used to evaluate a different section of the object targeted for gross error evaluation than templates 11 , 111 . the template 211 has features corresponding to the features of templates 11 , 111 . these features used the same reference character , save a change in the hundreds digit . template 201 does have features different that those described with templates 11 , 111 . the features will have different reference characters . briefly , template 211 has a body 213 manufactured , for example , using stereo lithography ( sla ) from a suitable material such as an extra clear resin . the body 213 generally corresponds to the shape of the object targeted for gross error evaluation . the body 213 has an interior surface 215 that faces the object and an exterior surface 217 that faces away from the object . the interior surface 215 includes a plurality of protuberances 219 . the protuberances 219 conform to a point system used during the manufacturing process . the template 211 could also include printed indicia 223 to identify the object targeted for gross error evaluation . for example , the printed indicia 223 could be the part number of the object targeted for gross error evaluation . other manners of identifying the object targeted for gross error evaluation , however , could be used . due to the location of the feature on the object , the template 211 also includes a section 225 having a depressed area 227 . the depressed area 227 has scallops 229 therein . the scallops 229 allow the user to evaluate the object , specifically features of the object , for gross errors . accordingly , the scallops 229 are positioned on the depressed area 227 of the section 225 so as to correspond to the location of such features on the object . fig8 displays the template 211 mounted on the blade 50 . the template 211 allows the user to ensure , after the manufacture of the blade 50 , that : ( 1 ) the apertures 59 exist on the radial tip of the airfoil section 53 of the blade 50 ; and / or ( 2 ) the apertures 59 are properly located ( i . e . within the tolerance range of the location of the feature on the object ) on the radial tip of the airfoil section 53 of the blade 50 . fig8 a shows the protuberances 119 engage the blade 50 at the points 57 identified during the manufacturing process . comparing fig2 and 4 ( note the figures show different sides of the blade ), it is clear that the protuberances 119 contact the same points on the blade 50 as the protuberances 19 when using the template 11 . fig8 a displays a view through the template 211 with a properly located cooling hole 59 ( the cooling hole 59 has been shown in phantom line to avoid confusion as the cooling hole 59 resides behind the clear template 211 ). preferably , the template 211 has five protuberances 219 . the depressed area 227 serves as the sixth contact point with the blade 50 . in the embodiment shown in fig5 - 7 , the location where depressed area 227 contacts blade 50 does not correspond to the sixth point location used with templates 11 , 111 . nevertheless , the protuberances 219 and the depressed area 227 contact the object , and keep the remainder of the body 213 offset from the surface of the object . the present invention has been described in connection with the preferred embodiments of the various figures . it is to be understood that other similar embodiments may be used or modifications and additions may be made to the described embodiment for performing the same function of the present invention without deviating therefrom . therefore , the present invention should not be limited to any single embodiment , but rather construed in breadth and scope in accordance with the recitation of the appended claims .
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in fig1 two similar profiles 1 to be connected at an angle of 90 degrees in relation to each other are shown . these profiles are provided with a cut away 2 on the extremities facing each other which forms an angle of 45 degrees in relation to the longitudinal direction of the profile 1 . each profile according to the invention consists of a closed cavity 3 , on the one hand , and above this closed cavity 3 an open cavity 4 , on the other hand . the closed cavity 3 shows a lower wall 5 ; two side walls 6 , 7 and an upper wall 8 whereby this upper wall also forms lower wall of the open space 4 which is further completed by side walls , respectively 9 and 10 which as it were form an extension of the aforementioned walls 6 and 7 and flanges 11 and 12 which are provided with the walls 9 and 10 on the free extremities and which are directed towards each other and parallel with the aforementioned wall 8 . in the wall 5 , over the whole length , small holes 13 are provided . the wall 5 extends out on the sides of the walls 6 and 7 and there forms ribs 14 , 15 . furthermore the walls 6 - 9 and 7 - 10 are each provided on their outer side with a quantity of bitumen or similar 16 - 17 which is provided with a covering strip 18 - 19 , of which it is later the intention among others , after removing the strips 18 and 19 , to make a sealing contact with the sheets of glass not shown in the drawings . the connection of the profiles 1 according to the invention is obtained by means of a corner profile 20 that consists of arms , respectively 21 , 22 which in this case are placed at an angle of 90 degrees and that , have a sealing wall 23 in the corner where these arms 21 and 22 come together which is placed at an angle of 45 degrees in relation to the aforementioned arms . in this embodiment the arms 21 and 22 are produced conically in order to simplify their insertion into the profile 1 whereby these arms , at the position where they meet each other , show a thickness which is equal or almost equal to the corresponding measurement of the open cavity 4 of the profile 1 in which the arms 21 and 22 are installed . these thickened places are indicated by 24 , 25 in the drawings . the aforementioned sealing wall 23 in this case is so achieved that it shows two relatively thin parts , respectively 26 and 27 , on its terminal edges which will act as stop for the cut off extremities 2 of the profiles 1 , while the body 28 of the sealing wall 23 is produced thicker and , after installation of the profile 1 over the arms of the corner profile 20 , fits into the closed cavity 3 of the profiles 1 . in order to connect two such profiles to each other it is sufficient to place them to over the arms 21 and 22 of a corner profile 20 whereby these profiles 1 , when they lie with their walls 5 and 8 against the sealing wall 23 , more especially against the parts 26 and 27 of these , preferably fit tightly into the open cavities 4 at the location of the thickened places 24 and 25 of the corner profile 20 . through the open character of the cavity 4 it is achieved that during this insertion of the arms 21 and 22 the flanges 11 and 12 of the cavity 4 can yield somewhat if this should appear necessary . when the profiles 1 are thus secured in relation to each other , as shown in fig2 a distance a will obviously remain in existence between the cut off edges 2 of these profiles which is equal to the thickness of the parts 26 and 27 . since the width of the corner element 20 is equal to the internal distance between the walls 9 and 10 of the cavity 4 ; the thickened parts 24 and 25 of the corner profile 20 are equal to the internal distance between the wall 8 and the flanges 11 , 12 ; the parts 26 and 27 of the corner element 20 are placed between the adjacent walls 8 , on the one hand , and 5 , on the other hand , and finally the thickened part 28 of the sealing wall 23 is placed in the adjacent extremities of the closed cavity 3 of the profiles 1 , in this manner not only an efficient connection is obtained between two profiles 1 , but at the same time an efficient sealing of the extremities of these profiles 1 . when such joined together profiles 1 are subsequently warmed , at least at the location of the corner connection , the material 16 , 17 will melt somewhat and thus fill the space a between the profiles 1 through which an additional seal is obtained . notwithstanding a very good seal is already achieved in the manner described above such a seal can of course still be improved by at least providing the sealing wall 23 and possibly at least a part of the arms 21 and 22 of the corner profile 20 with a covering which can be formed by a soft metal , such as tin , lead or similar , a glue , a plastic , bitumen , or similar , through which not only an additional seal is obtained during the insertion of the arms 21 and 22 in the open cavities 4 of two profiles 1 , but whereby this seal becomes maximally efficient when at the same time at least at the location of the corner connection , heat is applied to allow the aforementioned covering to fill all possible remaining spaces . it is clear that in this case the drying agent that in the known manner is confined in the closed cavities 3 remains completely dry since , for one thing , a good seal is formed on the corners of the frame obtained , this of course on condition that the customary temporary strip 29 which is provided over the holes 13 has not yet been removed . it is clear that it is not necessary that the arms 21 and 22 of the corner profile 20 are produced conically . neither is it necessary that the sealing wall 23 shows a thickening 28 . indeed this sealing wall 23 , as is schematically shown in fig1 by means of dotted line 30 , could show the same thickness over the whole length . through the fact that the arms 21 and 22 of the corner profile 20 are not located in the closed cavities 3 of the profiles 1 it is clear that the frame that is produced in this manner can contain more drying agent than is the case when , as usual up until now , the arms of the corner profile are located in these cavities 3 . likewise it is achieved by placing the arms 21 , 22 of the corner profile 20 outside the cavities 3 and providing a sealing wall 23 , that the outer corner formed by the connection of the walls 8 with the part 26 of the sealing wall 23 as it were becomes an inner corner through which the seal is also improved . in order to make the mutual adjustment of the corner profile 20 even more adjustable in the open cavities 4 weakenings may possibly be provided in the inner corners 31 and 32 between the walls 9 - 10 and the flanges 11 - 12 through which these lips 11 and 12 become more transformable , respectively adjustable . a corner profile 20 according to the invention also further allows that it is easily transformable through which the arms of this can be placed at almost any angle when frames would have to be formed of which the angles are different from 90 degrees . through the design of the profile 1 it is also further obtained that the groove formed between the flanges 11 and 12 of it , which allows access to the open profile 4 can be applied to connect such frames with an additional construction , either by sliding in fixing elements in such cavity 4 beforehand , or by installing already known fixing elements which can block after rotation in such cavity 4 . in a particular application according to the invention implemented frames can be applied in glass walls and similar . finally the corner profile 20 , and / or the profiles 1 , can be implemented in metal , for example aluminum , or in a suitable plastic , whereby in this last case , in order to limit the permeability in the open cavity 4 , preferably an impermeable covering is provided against the wall 8 . it is clear that the present invention is in no way restricted to the embodiment described as example and shown in the drawings , but may be developed in all kinds of forms and dimensions .
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with reference now to the drawings , and in particular to fig1 through 5 thereof , a new miniature kick bag game and apparatus kit embodying the principles and concepts of the present invention and generally designated by the reference numeral 100 will be described . more specifically , it will be noted that the miniature kick bag game and apparatus kit 100 comprises a court boundary marker 10 displaying a rectangular playing court , portable reticulated nets 16 and 18 formed in an elongated rectangular shape positioned at the center of the rectangular court and aligned vertically thereby dividing the playing court into two team zones , and a foot bag 12 which is kicked by a player 14 with his side of foot 14 over the portable reticulated nets 16 and 18 . as best illustrated in fig1 through 4 , it can be shown that a first support pole 26 engages one end of one of the portable reticulated net supports 20 via an elbow 22 . the opposing end of the first support pole 26 engages a t - support 24 . t - support 24 is adapted to provide linear directional support and guidance to boundary marker 10 . also shown in fig2 , is portable reticulated net 16 suitable attached to net support 20 . it will be appreciated that portable reticulated net 16 may be any suitable material suitable for advertisement marking as shown in fig1 . also shown in fig1 , is second support pole 26 a engaging one end of one of the portable reticulated net supports 30 via an elbow 22 a . the opposing end of the first support pole 26 a engages a second t - support 24 a . second t - support 24 a is adapted to provide linear directional support and guidance to boundary marker 10 . also shown in fig1 , is portable reticulated net 18 suitable attached to net support 30 . it will be appreciated that portable reticulated net 18 may be any suitable netting material . it will be understood that in alternate embodiments net 16 , or net 18 , may be of sufficient length to reach from the first support pole 26 to the second support pole 26 a . referring also to fig3 there is shown is a perspective view of the portable reticulated nets supported by the third support structure . the third support pole 34 engages one end of net support 30 via third t - support 32 . the other third t - support 32 connects net support 20 to the third support pole 34 . the third support pole is also connected to a fourth t - support 36 to provide lateral stability . it will be understood and appreciated that the assembled height of net support 20 and net support 30 when assembled with the first support pole 26 , the second support pole 26 a and the third support pole 34 is approximately 2 feet high . referring also to fig4 there is shown a perspective view of a staked line boundary marker in accordance with the invention shown in fig1 . boundary marker 10 may be any suitable marker such as rope or line . boundary marker 10 may be a predetermined length to form a desired perimeter or measured according to the inventive features described herein . fig4 also shows stakes 10 a for staking boundary marker 10 and thereby defining a corner of the playing area . stakes 10 a may be any suitable stake such as , but not limited to , plastic camping type stakes . referring also to fig5 , there is shown an upper perspective view of the new miniature kick bag game and apparatus kit displaying the built in boundary measuring feature of the invention . net support 20 and net support 30 are predetermined lengths and correspond to the desired dimensions of the court boundaries as shown in fig5 . it will be appreciated that this feature is useful when marking the boundaries on a hard surface that does not permit the boundary marker 10 to be staked with stakes 10 a . it will be understood that any suitable combination of net support 20 and net support 30 may be used to measure and mark the desired dimensions of the court boundaries . for example the combined length of net support 20 and net support 30 could be , in one embodiment , ten feet . the corresponding court size measured by the combined lengths is on one side of the net a ten by ten foot area . the other side of the net is also a ten by ten foot area . basic rules of the game — to start the game you must volley for serve . it does not matter who starts the volley , which can be decided by a coin toss or the winner of the last game . during the volley the hackey sack must be kicked over the net three consecutive times . after the third consecutive times the first team who lets the hackey sack touch the ground loses the volley and looses the first serve , at the volley winner &# 39 ; s discretion . the hackey sack is served , i . e ., kicked over the net support 20 or net support 30 from outside boundary marker 10 . if the hackey sack is kicked out of bounds the serving side loses the serve to the opposing team or player . if the hackey sack is kicked within bounds the opposing team or player may return the serve , without letting the hackey sack touch the ground , with any part of the body except for using their hands . each side has up to three hits or kicks to return the hackey sack . in the case of team play , one person may use all three kicks or hits , or the hits or kicks , up to three , may be allocated amongst the team . points are awarded to the serving player or team when the opposing team lets the hackey sack touch the ground or fails to return the hackey sack within three kicks or hits , or kicks the hackey sack out - of - bounds . a game is won when a team reaches a score of twenty - one points first and is also at least two points over the opposing player or team score ; or , alternatively if a player or team reaches fifteen points before the opposing team or player scores any point . it will be appreciated that the game rules described herein may be suitably modified according to players abilities or preferences . it should be understood that the foregoing description is only illustrative of the invention . thus , various alternatives and modifications can be devised by those skilled in the art without departing from the invention . accordingly , the present invention is intended to embrace all such alternatives , modifications and variances that fall within the scope of the appended claims .
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referring now to fig1 a power supply 10 includes an input module 12 and an output module 14 . input module 12 contains rectifying , filtering and control circuitry and is connected to an ac source 16 . the input module rectifies the ac signal and generates an intermediate output . for example , input module 12 may generate an intermediate output of about 120 vdc . these functions are well known in the art and need not be described in any further detail . ( see for instance , u . s . pat . nos . 4 , 488 , 214 and 4 , 805 , 081 ). the output module 14 includes an inverter 16 , a transformer 18 and two half rectifier bridges 20 &# 39 ;, 20 &# 34 ;. transformer 18 has two secondary coils 18 &# 39 ;, 18 &# 34 ;, each feeding one of the half rectifier capacitor bridges 20 &# 39 ;, 20 &# 34 ;. the half bridges also include capacitors c1 and c2 respectively . half bridges 20 &# 39 ;, 20 &# 34 ; are composed of diodes d1 , d2 , d3 and d4 arranged as shown . the bipolar outputs ± vo , of the module 14 are delivered on lines 22 , 24 to a load l . the modules 12 and 14 may be constructed and sized to form , for example , a nominal 24 kw power supply to deliver for example to load l 70k volts dc at 200 ma . in order to provide a different power supply 10a having the same voltage but double the power rating , the input modules 12a , 12b and two modules 14a , 14b are provided . modules 12a , 12b are similar to module 12 . modules 14a and 14b are similar to the module 14 . more particularly , each has an inverter circuit 16a , 16b , a transformer 18a , 18b . importantly , the diodes of the half bridge rectifiers 20 &# 39 ;, 20 &# 34 ; are now rearranged as shown to form respectively two full wave rectifiers 20a and 20b . rectifier 20a is formed of diodes d1a - d4a , and capacitor c1a . rectifier 20b is formed of diodes d1b - d4b and capacitor c1b . diodes d1a - d4a , d1b - d4b are identical to diodes d1 - d4 respectively , except that the orientation of some of the diodes have been reversed as shown . capacitors c1a , c1b represent the parallel combinations of capacitors c1 , c2 . in this new arrangement , load l1 receives a voltage + vo from output module 14a and a voltage - vo ( with respect to ground ) from output module 14b . l1 may be , for example , a ct scanner . in this manner a nominal 48 kw power supply is formed to deliver a bipolar ± 70 kvolts dc at a maximum of 400 ma using the modules 12a , 12b , 14a , 14b . importantly the main modification between the configurations of fig1 and 2 is the orientation of the diodes as described . in addition , some of the control logic may have to be changed as well , if required . referring to fig3 power supply 10 may be constructed of two modules 40 and 42 , with module 40 containing the input section 12 and module 42 containing the output section 14 . in order to construct power supply 10a , a common case 40 may be used to house both input modules 12a , 12b . this arrangement is advantageous because the control circuitry may be shared for these input modules . thus , for a nominal bipolar ± 70 kv , 400 ma power supply , the case 40 could contain control circuitry and two 24 kw rectifieriltering subassemblies . the intermediate outputs therefrom , are fed to two cases 42 and 44 . cases 42 and 44 contain output sections 14a , 14b respectively , and generate outputs + 70 kv , and - 70 kv , as shown . although the invention has been described with reference to several particular embodiments , it is to be understood that these embodiments are merely illustrative of the application of the principles of the invention . accordingly , the embodiments described in particular should be considered exemplary , not limiting , with respect to the following claims .
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fig1 generally shows a pacemaker 10 implanted in a patient 12 . the pacemaker leads 14 and 15 electrically couple the pacemaker 10 to the patient &# 39 ; s heart 11 via a suitable vein 18 . the leads act to both sense polarizations in the heart , and to deliver pacing stimuli the heart . fig2 is a block circuit diagram illustrating a multi - programmable , implantable , dual - chamber , bradycardia pacemaker 10 capable of carrying out the present invention . although the present invention is described in conjunction with a microprocessor - based architecture , it will be understood by those skilled in the art that it could be implemented in other technology such as digital logic - based , custom integrated circuit ( ic ) architecture , if desired . it will also be understood that the present invention may be implemented in cardioverters , defibrillators and the like . lead 14 includes an intracardiac electrode 24 located near its distal end and positioned within the right ventricle 16 . electrode 24 is coupled by a lead conductor 14 through an input capacitor 26 to the node 28 , and to the input / output terminals of an input / output circuit 30 . similarly , the lead 15 has a distally located intracardiac electrode positioned within the right atrium 17 . electrode 22 is coupled by a lead conductor 15 through an input capacitor 75 to a node 76 , and to the input / output terminals of the input / output circuit 30 . input / output circuit 30 contains the operating input and output analog circuits for digital controlling and timing circuits necessary for the detection of electrical signals derived from the heart , such as the cardiac electrogram , output from sensors ( not shown ) connected to the leads 14 and 15 , as well as for the application of stimulating pulses to the heart to control its rate as a function thereof under the control of software - implemented algorithms in a microcomputer circuit 32 . microcomputer circuit 32 comprises an on - board circuit 34 and an off - board circuit 36 . on - board circuit 34 includes a microprocessor 38 , a system clock 40 , and on - board ram 42 and rom 44 . off - board circuit 36 includes an off - board ram / rom unit 46 . microcomputer circuit 32 is coupled by data communication bus 48 to a digital controller / timer circuit 50 . microcomputer circuit 32 may be fabricated of custom ic devices augmented by standard ram / rom components . it will be understood by those skilled in the art that the electrical components represented in fig2 are powered by an appropriate implantable - grade battery power source ( not shown ). an antenna 52 is connected to input / output circuit 30 for purposes of uplink / downlink telemetry through a radio frequency ( rf ) transmitter / receiver circuit ( rf tx / rx ) 54 . telemetering both analog and digital data between antenna 52 and an external device , such as an external programer ( not shown ), is accomplished in the preferred embodiment by means of all data first being digitally encoded and then pulse position modulated on a damped rf carrier , as substantially described in u . s . pat . no . 5 , 127 , 404 , issued on jul . 7 , 1992 , entitled &# 34 ; telemetry format for implantable medical device &# 34 ;, which is held by the same assignee as the present invention and which is incorporated herein by reference . a reed switch 51 is connected to input / output circuit 30 to enable patient follow - up via disabling the sense amplifier 146 and enabling telemetry and programming functions , as is known in the art . a crystal oscillator circuit 56 , typically a 32 , 768 hz crystal - controlled oscillator , provides main timing clock signals to digital controller / timer circuit 50 . a vref / bias circuit 58 generates a stable voltage reference and bias currents for the analog circuits of input / output circuit 30 . an adc / multiplexer circuit ( adc / mux ) 60 digitizes analog signals and voltages to provide telemetry and a replacement time - indicating or end - of - life function ( eol ). a power - on - reset circuit ( por ) 62 functions to initialize the pacemaker 10 with programmed values during power - up , and reset the program values to default states upon the detection of a low battery condition or transiently in the presence of certain undesirable conditions such as unacceptably high electromagnetic interference ( emi ), for example . the operating commands for controlling the timing of the pacemaker depicted in fig2 are coupled by bus 48 to digital controller / timer circuit 50 wherein digital timers set the overall escape interval of the pacemaker , as well as various refractory , blanking and other timing windows for controlling the operation of the peripheral components within input / output circuit 50 . digital controller / timer circuit 50 is coupled to sense amplifiers ( sense ) 64 and 67 , and to electrogram ( egm ) amplifiers 66 and 73 for receiving amplified and processed signals picked up from electrode 24 through lead 14 and capacitor 26 , and for receiving amplified and processed signals picked up from electrode 22 through lead 15 and capacitor 75 , representative of the electrical activity of the patient &# 39 ; s ventricle 16 and atrium 17 , respectively . similarly , sense amplifiers 64 and 67 produce sense event signals for re - setting the escape interval timer within circuit 50 . the electrogram signal developed by egm amplifier 66 is used in those occasions when the implanted device is being interrogated by the external programmer / transceiver ( not shown ) in order to transmit by uplink telemetry a representation of the analog electrogram of the patient &# 39 ; s electrical heart activity as described in u . s . pat . no . 4 , 556 , 063 , issued to thompson et al ., entitled &# 34 ; telemetry system for a medical device &# 34 ;, which is held by the same assignee as the present invention , and which is incorporated herein by reference . output pulse generators 68 and 71 provide the pacing stimuli to the patient &# 39 ; s heart 11 through output capacitors 74 and 77 and leads 14 and 15 in response to paced trigger signals developed by digital controller / timer circuit 50 each time the escape interval times out , or an externally transmitted pacing command has been received , or in response to other stored commands as is well known in the pacing art . in a preferred embodiment of the present invention , pacemaker 10 is capable of operating in various non - rate - responsive modes which include ddd , ddi , vvi , voo and vvt , as well as corresponding rate - responsive modes of dddr , ddir , vvir , voor and vvtr . further , pacemaker 10 can be programmably configured to operate such that it varies its rate only in response to one selected sensor output , or in response to both sensor outputs , if desired . details of the adir / vvir mode of the present invention follow below , with reference to fig3 through 9 . in those figures the following abbreviations are used to indicate the occurrence of cardiac events : as for atrial sense ; ap for atrial pace ; vs for ventricular sense ; and vp for ventricular pace . the pacemaker 10 operates as a combination of a separate aair pacemaker for the atrial channel , and a separate vvir pacemaker for the ventricular channel . atrial blanking follows both atrial and ventricular events , with the blanking period equal to approximately 180 ms when the ventricular event is either paced or premature , and approximately 120 ms at the start of an orthodromically conducted ventricular beat . the blanking periods may be different from the above numbers , according to the needs of the patient , etc . the lower rate of the ventricular pacemaker is lower than the lower rate of the atrial pacemaker so that ventricular pacing occurs only during episodes of av block . in addition to av block , the patient must also experience atrial arrhythmias ( i . e ., flutter , fibrillation ) in order for the ventricular pacemaker to be activated . thus , in cases of av block , but sinus rhythm , the pacemaker 10 switches to a fully automatic mode , which includes such modes as dddr , dddr with , ddir , vvir , etc . table 1 summarizes the operation of the pacemaker 10 under various conditions . table 1______________________________________summary of adir / vvir pacemaker operationcondition result______________________________________1 . av conduction aair activated ; vvir sensing only2 . sinus rhythm with av block pacemaker switches to dddr operation3 . atrial arrhythmia , vvi activated no av block4 . atrial arrythmia with vvir activated av block______________________________________ fig3 is a timing diagram illustrating condition 1 in table 1 , supra . during normal operation with av conduction , the atrial pacemaker is enabled while the ventricular pacemaker is disabled ( i . e ., the only function of the ventricular pacemaker in this case is to monitor ventricular sense events ). an atrial refractory period starts at the beginning of each atrial event . the pacemaker 10 uses atrial - to - atrial ( a - a ) timing to determine the escape interval . at the detection of a ventricular event ( sense in this case ) the atrial pacemaker begins an atrial blanking period ( 120 ms in the preferred embodiment ) followed by an atrial refractory period . fig4 illustrates the operation of the pacemaker 10 after the occurrence of a premature ventricular contraction ( pvc ), a ventricular sense event occurring without an intervening atrial event since the last ventricular event . at the occurrence of a pvc ( the third ventricular sense event shown ) the longer atrial blanking period starts ( 180 ms ), and the atrial pacemaker is reset to pace after the expiration of the current a - a interval minus the intrinsic conduction time of the patient as measured by the pacemaker . this reset delay period is hereby referred to as the &# 34 ; pseudo &# 34 ; v - a interval . fig5 illustrates an alternate approach to a pvc involving rate smoothing to minimize ventricular rate drops . in this approach the pseudo v - a interval used to reset the atrial pacemaker equals the current ventricular - to - ventricular ( v - v ) interval minus the intrinsic conduction time . fig6 illustrates the pacemaker &# 39 ; s adir / vvir operation during the presence of atrial arrhythmia and intermittent av block . as will be appreciated by those skilled in the art , numerous references discuss methods for detecting arrhythmias . one such reference is an article entitled &# 34 ; automatic tachycardia recognition &# 34 ; by robert arzbaecher et al ., pace 7 ( 1984 ) 541 - 547 , hereby incorporated by reference . another reference is u . s . pat . no . 4 , 880 , 005 issued to benjamin d . pless et al . on nov . 14 , 1989 for &# 34 ; pacemaker for detecting and terminating a tachycardia ,&# 34 ; which is also incorporated by reference . during the first two cardiac cycles shown , the atrial paces are conducted normally to the ventricles , thus inhibiting the ventricular pacemaker . in the third and fourth cardiac cycles , however , av block triggers the ventricular pacemaker , causing it to pace the ventricle at the expiration of the ventricular escape interval . recall that atrial blanking and atrial refractory periods follow each ventricular event ( when the ventricular event is paced the blanking period equals 180 ms in the preferred embodiment ). in the above example , a potential exists for retrograde conduction of ventricular pace events , which is undesirable . to eliminate this problem , the atrial pacemaker is reset following a ventricular pace ( at expiration of the ventricular escape interval ) as shown in fig7 . the pseudo v - a interval is chosen to be either the current a - a escape interval minus the intrinsic conduction time as described in conjunction with fig4 or the current ventricular rate minus the av interval as described in conjunction with fig5 . fig8 illustrates the response of the pacemaker 10 to a non - conducted premature atrial contraction ( pac ). after the third cardiac cycle in the illustration , an atrial sense event occurs during the atrial refractory period . in order to minimize the drop in ventricular rate after the occurrence of a non - conducted pac , the atrial escape interval is timed not from the pac , but from the previous atrial event . in order to determine that a pac has not conducted , the pacemaker must wait for the av interval plus a predefined interval unique to the delay in conduction from pacs . if the pac is conducted , the atrial escape interval is timed from the pac . otherwise , the atrial escape interval is timed from the previous atrial event . fig9 is a flowchart summarizing the procedure / program 900 used by the pacemaker 10 to implement the adir / vvir mode . steps 902 through 916 describe the operation of the atrial pacemaker , while steps 920 through 938 describe the operation of the ventricular pacemaker . atrial pace events ( step 904 ) trigger ventricular blanking at step 906 . both atrial sense events ( step 902 ) atrial pace events trigger the atrial blanking and atrial refractory periods at step 908 . at step 910 the atrial escape rate is set equal to the current sensor rate . the pacemaker 10 determines at step 912 whether a ventricular pace is scheduled within the programmed minimum ventricular pace ( vp )- to - atrial pace ( ap ) interval ( the minimum interval which must occur after a vp before an ap can occur ). if the vp is to occur in the minimum vp - ap interval , it is moved up in time to occur at the scheduled ap time minus the minimum vp - ap interval ( step 914 ). at step 916 the atrial refractory period is set to end 300 ms before the next scheduled atrial pace event . step 918 , the last step in the program 900 , places the pacemaker 10 in a monitoring mode to await re - triggering of the program by an atrial or ventricular event ( steps 902 , 904 , 920 or 922 ). a ventricular sense event ( step 920 ) advances the program 400 to step 924 , which determines whether the ventricular event is a pvc . if so , the program advances to step 930 , where a short atrial blanking period is started ( i . e ., about 120 ms , as described supra .). at step 926 , whenever a ventricular pace occurs ( step 922 ), or a pvc , a longer atrial blanking period is started ( i . e ., about 180 ms , as described supra .). following a ventricular pace or a pvc the next atrial pace is scheduled to occur after the atrial escape interval minus the av conduction time ( step 928 ). at step 932 the ventricular blanking and refractory periods are started , as well as the atrial refractory period ( the atrial period is set to end 300 ms before the next scheduled atrial pace , as in step 916 ). the pacemaker 10 determines at step 934 whether the next atrial pace is scheduled within the programmed minimum ventricular pace - to - atrial pace interval ( the minimum interval which must occur after a vp before an ap can occur ). if the ap is to occur in the minimum vp - ap interval , it is moved back in time to occur at the scheduled ap time plus the minimum vp - ap interval ( step 936 ). if the next atrial pace is not scheduled to occur within the minimum vp - ap interval , the next ventricular pace is then scheduled to occur at the current ventricular escape interval ( step 938 ). the program then advances to step 918 so that the pacemaker 10 resumes its monitoring mode , as described supra . variations and modifications to the present invention are possible given the above disclosure . however , such variations and modifications are intended to be within the scope of the invention claimed by this letters patent .
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a phage - inducible suicide system useful for fermentation methods requires an appropriate death gene , a phage - inducible promoter triggered only after phage infection ( i . e ., not constitutively active in the bacterial cell or activated by stimuli other than those presented by bacteriophage ), and a suitable vector that provides adequate copies of the suicide cassette in the bacterial host . numerous inducible phage promoters that are not expressed by the bacteria in the absence of a phage infection are available . many such promoter elements are responsible for temporal expression and have been described in well characterized bacteriophages attacking e . coli and bacillus subtilis ( lee and pero , ( 1981 ); dunn and studier , 1983 ; elliot and geiduschek , 1984 ; kassavetis et al ., 1986 ). however , only one inducible element has been characterized to date for a lytic lactococcal bacteriophage . a middle , phage - inducible promoter from the p335 species lactococcal bacteriophage φ31 was initially cloned on a 888 - bp fragment ( seq id no : 1 ) ( d . o &# 39 ; sullivan et al ., bio / technol . 14 : 82 - 87 ( 1996 )). molecular characterization and primer extension analysis of the promoter - containing region revealed four transcription sites , two of which were strictly inducible after infection of l . lactis with phage φ31 ( s . walker et al ., j . dairy sci . 78 , 108 ( 1995 )). as described below , a 239 - bp fragment was subcloned containing two tandem transcription starts that are expressed only after phage infection . the suicide system was assembled by placing the phage φ31 - specific , trigger promoter ( designated φ31p ) 5 &# 39 ; of the llair + cassette . additional sources of bacteriophage promoters useful for carrying out the present invention include phage φt3 ( morris et al ., gene 41 : 193 - 200 ( 1986 )), phage φsp6 ( butler and chamberlin , j . biol . chem . 257 : 5772 - 5778 ( 1982 )), phage φt4 ( geiduschek and kassavetis , in the bacteriophages pp . 93 - 115 ( r . calendar , ed . 1988 )), phage φsp ( talkington and pero , proc . natl . acad . sci . usa 76 : 5465 - 5469 ( 1978 )) and phage φ29 ( monsalve et al ., virology 207 : 23 - 31 ( 1995 )). as indicated above , the promoter employed should be a phage - inducible promoter . this is , the promoter should be normally silent , or should not be a constitutively active promoter ( i . e ., have insufficient constitutive activity to activate transcription of the dna encoding the product lethal to the bacterial cell to an extent sufficient to kill the cell in the absence of phage infection ). promoters that possess constitutive activity may be modified so that they are phage - inducible promoters , as described herein . any suitable vector may be used to carry out the present invention , including both plasmid vectors and cassettes inserted into the bacterial genome by recombinant techniques . copy number of the vector is not critical , and may be adjusted as necessary in light of the choice of the . particular dna encoding the lethal product , and the sensitivity of the particular bacterial cell thereto . heterologous dnas employed in carrying out the present invention encode a product which is lethal to bacterial cells . a wide variety of protein or peptide products that are lethal to bacterial cells can be used , including ( but not limited to ) enzymes capable of degrading nucleic acids ( dna , rna ) such as nucleases , restriction endonucleases , micrococcal nuclease , rnase a , rnase cl - 3 , rnase t1 , and barnase ; enzymes that attack proteins such as trypsin , pronase a , carboxypeptidase , endoproteinase asp - n , endoproteinase glu - c , cellulase with an export signal , and endoproteinase lys - c ; toxins from plant pathogenic bacteria such as phaseolotoxin , tabtoxin , and syringotoxin ; lipases such as produced from porcine pancrease and candida cyclindracea , membrane channel proteins such as glp f and connexins ( gap junction proteins , and antibodies that bind proteins in the cell so that the cell is thereby killed or debilitated . genes which produce antibodies to bacterial cell proteins can be produced as described in w . huse et al ., science 246 , 1275 - 1281 ( 1989 ). proteins to which such antibodies can be directed include , but are not limited to , rna polymerase , respiratory enzymes , cytochrome oxidase , krebs cycle enzymes , protein kinases , and aminocyclopropane - 1 - carboxylic acid synthase . additional products lethal to bacterial cells that may be used in carrying out the present invention are discussed below . particularly preferred is a structural gene encoding mature bacillus amyloliquefaciens rnase ( or barnase ). see , e . g ., c . mariani et al ., nature 347 , 737 - 741 ( 1990 ); c . paddon and r . hartley , gene 40 , 231 - 39 ( 1985 ). it is preferred , particularly where the bacteria is employed in the fermentation of a food product , that the bacteria - lethal product of the heterologous dna is non - toxic to animals , and particularly is non - toxic to mammals , including humans . the art of fermentation is well known and the instant method is useful in a wide variety of fermentation processes . in a preferred embodiment of the present invention , the instant method relates to bacteria capable of fermenting food substrates , and more particularly milk . bacteria capable of fermenting foods include those bacteria used in any type of food fermentation , including , but not limited to , the fermentation of milk , egg , meat , fruit , vegetables , and cereals . see generally food biotechnology , ( d . knorr ed . 1987 ) ( marcel dekker , inc . ); fermented foods ( a . rose ed . 1982 )( academic press ); c . pederson , microbiology of fermented foods , ( 2d ed . 1979 )( avi publishing co .). bacteria used for the fermentation of meat ( including beef , pork , and poultry ) include , but are not limited to , lactic acid bacteria , pediococcus cerevisiae , lactobacillus plantarum , lactobacillus brevis , micrococcus species , leuconostoc citrovorum , leuconostoc citrovorum , and mixtures thereof . see food biotechnology , 538 - 39 ( d . knorr ed . 1987 ); c . pederson , microbiology of fermented foods , 210 - 34 ( 2d ed . 1979 ); u . s . pat . no . 2 , 225 , 783 to jensen and paddock . bacteria used for the fermentation of vegetables ( e . g ., carrots , cucumbers , tomatoes , peppers , and cabbage ) include , but are not limited to , lactobacillus plantarum , lactobacillus brevis , leuconostoc mesenteroides , pediococcus pentosaceus , and mixtures thereof . see food biotechnology , 540 ( d . knorr ed . 1987 ); c . pederson , microbiology of fermented foods , 153 - 209 ( 2d ed . 1979 ); u . s . pat . no . 3 , 024 , 116 to engelland ; u . s . pat . no . 3 , 403 , 032 to etchells et al . ; u . s . pat . no . 3 , 932 , 674 to etchells et al . ; u . s . pat . no . 3 , 897 , 307 to porubcan et al . bacteria used in the fermentation of dough formed from cereals ( e . g ., wheat , rye , rice , oats , barley , and corn ) include yeasts such as saccharomyces cerevisiae and candida utilis ; and lactic acid bacteria of the genera lactobacillus , lactococcus , pediococcus and leuconostoc , including , but not limited to lactobacillus delbrueckii , lactobacillus debreuckii subsp . leichmanni , lactobacillus plantarum , lactobacillus casei , lactobacillus brevis , lactobacillus fermenti , lactobacillus pastorianus , lactobacillus buchneri , and leuconostoc mesenteroides . see generally food biotechnology , 235 - 70 ( d . knorr ed . 1987 ); u . s . pat . no . 3 , 734 , 743 to kline and sugihara ; u . s . pat . no . 3 , 681 , 083 to everson ; u . s . pat . no . 3 , 993 , 783 to khoudokormoff and langejan ; u . s . pat . no . 3 , 843 , 800 to langejan ; u . s . pat . no . 3 , 410 , 692 to wutzel . wine is produced by the fermentation of fruit juice , typically grape juice , with yeasts , such as saccharomyces cerevisiae and saccharomyces ellipsoideus , as well as with a broad variety of lactic acid bacteria including pediococcus pentosaceus , lactobacillus plantarum , leuconostoc mesenteroides , leuconostoc dextranicum , leuconostoc cremoris , lactobacillus brevis , and lactobacillus fermenti . beer is produced by the fermentation of malt with yeasts such as saccharomyces cerevisiae and saccharomyces carlsbergensis . see c . pederson , microbiology of fermented foods , 271 - 309 ( 2d ed . 1979 ). milk is fermented to produce products such as cheese , yoghurt , kefir , and acidophilus milk . cheese fermentation bacteria are discussed separately below . otherwise , bacteria used for the fermentation of milk include , but are not limited to , lactobacillus debreuckii subsp . bulgaricus , lactobacillus acidophilus , streptococcus salivarius subsp . thermophilus , and mixtures thereof . see food biotechnology , 530 ( d . knorr ed . 1987 ); c . pederson , microbiology of fermented foods , 105 - 35 ( 2d ed . 1979 ). bacteria used for the fermentation of milk to produce cheese include , but are not limited to , lactobacillus bulgaricus , lactobacillus helveticus , streptococcus salivarius subsp . thermophilus , lactococcus lactis subsp . lactis , lactococcus lactis subsp . cremoris , lactococcus lactis subsp . lactis biovar . diacetylactis , and mixtures thereof . see food biotechnology , 530 ( d . knorr ed . 1987 ); c . pederson , microbiology of fermented foods , 135 - 51 ( 2d ed . 1979 ). bacteria used for the fermentation of egg include pediococcus pentosaceus , lactobacillus plantarum , and mixtures thereof . see food biotechnology , 538 - 39 ( d . knorr ed . 1987 ). in a particularly preferred embodiment , the present invention is employed for the fermentation of milk with the lactococci ( previously classified as the group n streptococci ), such as lactococcus lactis subsp . lactis , lactococcus lactis subsp . cremoris , and lactococcus lactis subsp . lactis biovar . diacetylactis . while the present invention is , in one embodiment , directed to the fermentation of food , the invention may be practiced with any process involving fermentative bacteria susceptible to disruption by bacteriophage infection , including but not limited to processes for the production of antibiotics , amino acids , and solvents . products produced by fermentation which are known to have encountered bacteriophage infection , and the corresponding infected fermentation bacteria , include cheddar and cottage cheese ( lactococcus lactis , lactococcus cremoris ), yogurt ( lactobacillus bulgaricus , streptococcus thermophilus ), swiss cheese ( s . thermophilus , lactobacillus lactis , lactobacilluis helveticus ), blue cheese ( leuconostoc cremoris ), italian cheese ( l . bulgaricus , s . thermophilus ), viili ( lactococcus cremoris , lactococcus lactis subsp . diacetylactis , leuconostoc cremoris ), yakult ( lactobacillus casei ), casein ( lactococcus cremoris ), natto ( bacillus subtilis var . natto ), wine ( leuconostoc oenos ), sake ( leuconostoc inesenteroides ), polymyxin ( bacillus polymyxa ), colistin ( bacillus colistrium ), bacitracin ( bacillus licheniformis ), l - glutamic acid ( brevibacterium lactofermentum , microbacterium ammoniaphilum ), and acetone and butanol ( colstridium acetobutylicum , clostridiumsaccharoperbutylacetoni - cum ). see generally m . sanders , bacteriophages of industrial importance , in phage ecology , 211 - 44 ( s . goyal , c . berba and g . bitton eds . 1987 ). escherichia coli genetically engineered to produce materials such as chymosin , insulin , or factor viii by fermentation is susceptible to phage infection . thus , the present invention may , for example , be employed in a fermentation process for producing any of the foregoing products with the foregoing bacteria in the manner described herein . starter cultures employed in practicing the present invention may be in any physical form , including liquid cultures of the fermentation bacteria in a suitable growth medium , as well as lyophilized cultures and frozen cultures prepared therefrom . starter cultures employed in the present invention are preferably defined cultures , that is , cultures of known bacterial content . such defined cultures may be either single strain cultures , i . e ., pure cultures , or multiple strain cultures , i . e ., mixed cultures . all of the bacteria in the culture may contain the defense mechanism described herein , or some of the bacteria may contain the defense mechanism while others do not . the fermentation apparatus and conditions under which fermentation may be selected and determined by persons of skilled in the art to produce the desired product , in accordance with known fermentation techniques . bacteria of the present invention may be employed with or without rotation with other bacteria in a rotation strategy . when employed in a rotation strategy , the other , or second , bacteria employed may be nonisogenic or isogenic ( i . e ., have the same bacteriophage binding characteristics ) with the bacteria of the present invention . where isogenic bacteria are employed as the second bacteria in the rotation strategy , they may carry a different bacteriophage defense mechanism ( including , but not limited to , any of those defense mechanisms set forth below ) as will be appreciated by those skilled in the art , bacteria of the present invention may optionally include one or more additional bacteriophage defense mechanisms in addition to the phage - inducible suicide system described herein . the additional bacteriophage defense mechanism ( s ) may be directed against the same or different bacteriophage as the phage - inducible suicide system described herein . any additional bacteriophage defense mechanism may be employed , including , but not limited to , restriction / modification ( r / m ) systems and abortive infection ( abi ) systems including phage - encoded resistance ( per ) systems ( as described in u . s . pat . no . 5 , 538 , 864 to c . hill and t . klaenhammer ), and the particular plasmid - based defense mechanisms as described in u . s . pat . no . 4 , 883 , 756 , 4 , 931 , 396 ; 4 , 732 , 859 ; 4 , 918 , 014 ; and 4 , 874 , 616 ( applicant specifically intends that the disclosures of all u . s . patent references cited herein be incorporated herein by reference . abortive infection systems are particularly preferred . described herein is a novel bacteriophage protection strategy by genetic engineering of a mechanism that aborts the phage infection and intentionally kills the propagation host . as described below , the killing capacity of a three gene restriction cassette extracted from the llai r / m operon was exploited to develop a novel bacterial suicide system , triggered by a phage infection . the phage φ31 - inducible promoter used to drive expression of the llair + cassette did not exert detrimental effects on the host in the absence of a phage infection . however , when transcription of the restriction cassette was initiated by phage infection , the plaquing efficiencies of φ31 and related phages were limited to very low levels of 10 - 4 - 10 - 6 . moreover , phage progeny that escape restriction are not modified and will continue to suffer full restriction in subsequent attempts to infect host cells carrying φ31p / llair +. as a result , any phage development within liquid cultures is severely retarded since each new host infected is triggered to commit suicide and destroy the incoming phage genome . both components of this particular embodiment of a bacterial suicide system , the category of death gene and the inducible expression signal , are unique . first , the promoter and restriction cassette are of lactococcal origin and , therefore , could be considered within a generally recognized as safe ( gras ) category for food - grade applications . the gras status of this phage protection system allows deployment of the φ31p / llair + cassette in starter cultures used in dairy fermentations . second , to our knowledge , this is the first attempt to employ a restriction endonuclease component of an r / m system as a death gene in a conditional - suicide system . numerous types of conditional - suicide systems have been developed where potent killing genes are coupled to inducible expression signals ( reviewed by s . molin et al ., annu . rev . microbiol . 47 : 139 - 166 ( 1993 )). the combinations are designed not to interfere with normal growth and expression occurs under very specific conditions defined by the physical or chemical composition of the environment . environmental signals used to trigger expression of bacterial suicide systems have included iptg ( a . bej et al ., appl . environ . microbiol . 54 : 2472 - 2477 ( 1988 ); k . knudsen et al ., appl . environ . microbiol . 61 : 985 - 991 ( 1995 ); d . kloos et al ., j . bacteriol . 176 : 7352 - 7361 ( 1994 )), poor nutrient conditions ( k . tedin et al ., j . biotechnol . 39 : 2 137 - 148 ( 1995 )), limitation of phosphate ( t . schweder et al ., appl . microbiol . biotechnol . 42 : 718 - 723 ( 1995 )) or tryptophan ( s . molin et al ., bio / technol . 5 : 1315 - 1318 ( 1987 )), and availability of aromatic compounds in environment ( a . contreras et al ., appl . environ . microbiol . 57 : 1504 - 1508 ( 1991 )). conditional suicide systems in bacteria have been developed for a single purpose , to prevent release of recombinant strains outside a controlled environment . signals most successfully applied are those directing plasmid transfer ( gerdes et al ., new biologist 2 : 946 - 956 ( 1990 ); e . bahassi et al ., mol . microbiol . 15 ( 6 ): 1031 - 1037 ( 1995 ); r . roberts et al ., j . mol . biol . 237 : 35 - 51 ( 1994 ); s . tsuchimoto et al ., mol . gen . genet . 215 : 463 - 468 ( 1989 )). the death genes studied most extensively in these applications are two - component toxin / antidote e . coli suicide systems involved in postsegregational killing of plasmid - free cells . suicide systems of this kind include members of the gef gene family , such as hok / sok gene pair responsible for the maintenance of plasmid rl ( s . molin et al ., supra ( 1987 ); k . gerdes et al ., supra ( 1990 )) and hok / sok homologous chromosomal loci relf ( k . gerdes et al ., supra ( 1986 ); k . knudsen et al ., appl . environ . microbiol . 61 : 985 - 991 ( 1995 )) and gef ( l . poulsen et al ., mol . microbiol . 5 : 1639 - 1648 ( 1991 )), ccd loci of sex - factor f ( e . bahassi et al ., supra ( 1995 )), parde of rp4 plasmid ( r . roberts et al ., supra ( 1994 )), and pem of r100 ( s . tsuchimoto et al ., supra ( 1989 )). potent killing genes used to design several suicide systems have also included the following : gene e from φ174 ( d . kloos et al ., supra ( 1994 )), phage φt7 lysozyme gene ( t . schweder et al ., supra ( 1995 )), gene s from φλ ( k . tedin et al ., supra ( 1995 )), bacillus subtilis sacb gene ( g . recorbet et al ., appl . environ . microbiol . 59 : 1361 - 1366 ( 1993 )), barnase from bacillus amyloliquefaciens ( g . strittmatter et al ., bio / tech . 13 : 1085 - 1089 ( 1995 )), and endonucleases from serratia marcescens ( t . ball et al ., gene , 57 : 183 - 192 ( 1987 )) and staphylococcus aureus ( a . davis et al ., j . biol . chem . 18 : 6544 - 6553 ( 1977 )). in contrast to these suicide systems , the φ31p / llair + cassette is designed to provide protection against bacteriophage by creating a genetic trap that triggers after a phage infection and destroys both the phage genome and bacterial host . the efficiency of the φ31p / llair + system was improved by two approaches . presenting the suicide cassette on a high - copy - number replicon dramatically increased the level of phage restriction . this construction was largely responsible for development of a functionally effective defense system . noting this , efforts to stabilize the phage - inducible restriction cassette in the chromosome would likely require use of a stronger promoter , a promoter recognized earlier in the phage development cycle , and / or a more effective death gene . second , the presence of c . llai elevated restriction 10 - fold against phage φ31 . this regulatory protein appears to serve a bifunctional role in the native llai r / m operon by both repressing transcription and promoting restriction activity ( d . o &# 39 ; sullivan and t . klaenhammer , vol . 85 , p . 591 - 595 . in j . j . feretti , m . s . gilmore , t . r . klaenhammer , f . brown ( eds . ), genetics of the streptococci , enterococci , and lactococci . dev . biol . stand . basel , karger . 1995 )). in this latter role , the c · llai protein has been proposed to enhance rna stability and facilitate translation of the three gene restriction cassette . the existing φ31lp / llair + system could be improved by incorporating llaic within the cassette . the φ31p trigger promoter selected and used in the design of the suicide system presents two inherent limitations , timing and tight recognition specificity . φ31p is a middle phage promoter that is transcribed approximately 20 minutes following the phage infection ( s . walker et al ., j . dairy sci . 78 : 108 ( 1995 )). considering the dynamics of the phage life cycle , activation of the φ31p / llair + cassette at this later stage does allow some dna to escape restriction and progeny phage to survive in 15 % of the infected cells . the efficiency of the llai - based suicide system could be improved substantially if the restriction cassette is expressed from a phage - specific promoter triggered earlier during the phage infection . however , it is critical that the earlier trigger promoter is completely phage - specific and that it is not recognized by bacterial host in the absence of phage . such trigger promoter is being sought , but has not yet been defined . therefore , in the design of the phage - induced suicide system a fine balance must be accomplished between tight control of expression signals and the optimal stage of temporal phage development when those promoters are recognized . suicide genes expressed too late in the cycle may serve only to facilitate cell death and release of assembled phage progeny . second , because of the high specificity of phage expression signals , the φ31p / llair +- based suicide cassette can be triggered only by phage φ31 or related phages that contain similar promoter regions or encode transcriptional factors with similar promoter specificity . attempts to induce the φ31p promoter with other phages from the p335 species , as well as phages from other lactococcal species ( p936 and c2 ) were not successful ( data not shown ). due to this promoter specificity , the defense system would not be practically effective against the diverse combinations of phage strains and species that attack lactococci . in conclusion , disclosed is a novel bacteriophage defense strategy that programs cell death and intracellular destruction of phage dna post infection . the system is designed as a genetic trap to invite phage adsorption and dna injection . in bacterial populations where every cell harbors a phage - inducible suicide cassette , infected cells hydrolyze the phage genome and undergo programmed cell death in an altruistic fashion designed after naturally - occurring abortive infection mechanisms . various combinations of death genes and promoter elements can be envisioned to design similar systems for virtually any bacteria . when alone , or combined with other defense systems , phage - triggered . intracellular suicide / defense systems are capable of trapping and eliminating phages , and their genetic potential , from fermentation environments . the examples which follow are illustrative of specific embodiments of the invention , and various uses thereof . they are set forth for explanatory purposes only , and are not to be taken as limiting the invention . escherichia coli mc1061 ( n . casadaban and s . cohen , j . mol . biol . 138 : 179 - 210 ( 1980 )) was used as primary transformation host throughout the study . e . coli mc1061 derivatives harboring plasmids ptrk414l or ptrk414h were designated nck785 and nck781 , respectively . lactococcus lactis nck690 was the sensitive host for bacteriophage φ31 . this strain is a derivative of l . lactis nck203 ( c . hill et al ., appl . environ . microbiol . 55 : 2416 - 2419 ( 1989 )) spontaneously cured of all plasmids , except a 7 . 5 kb plasmid ( e . durmaz , unpublished data ). l . lactis nck690 harboring ptrk414l or ptrk414h were designated nck786 and nck782 , respectively . phage φ31 is a small isometric , p335 species , cohesive ended , lactococcal bacteriophage with a double - stranded dna genome of 31 . 9 kb . this phage is sensitive to both abia - mediated abortive resistance and llai restriction ( t . alatossava and t . klaenhammer , appl . environ . microbiol . 57 : 1346 - 1353 ( 1991 )). recombinant phages φ31 . 1 , 031 . 2 , φ31 . 7 , and φ31 . 8 are per31 - resistant derivatives of phage φ31 ( d . o &# 39 ; sullivan et al ., appl . environ . microbiol . 59 : 2449 - 2456 ( 1993 )), selected following a homologous recombination event between the phage genome and l . lactis nck203 chromosome ( d . o &# 39 ; sullivan and t . klaenhammer , in abstracts of the 7 th international symposium on the genetics of industrial microorganisms , montreal , canada , p . 186 ( 1994 ); e . durmaz et al ., j . dairy . sci . 78 : 109 ( 1995 )). plasmids used or constructed in this study are listed in table 1 . e . coli strains were grown at 37 ° c . in luria - bertani ( lb ) medium ( j . sambrook et al ., molecular cloning : a laboratory manual , 2nd ed . cold spring harbor laboratory , cold spring harbor , n . y . ( 1989 )) or brain heart infusion medium ( bhi , difco laboratories , detroit , mich .). erythromycin ( em ) 100 μg / ml was added for selective propagation of e . coli in broth where appropriate . agar plates ( 1 . 5 % granulated agar , bbl microbiology systems , cockeysville , md .) were prepared from bhi medium . erythromycin ( em r ) resistant e . coli transformants were selected on bhi agar with 200 μg / ml erythromycin . l . lactis was propagated at 30 ° c . in m17 broth ( difco ) containing 0 . 5 % glucose ( gm17 ). erythromycin 2 . 5 μg / ml or chloramphenicol 3 . 0 μg / ml were used for antibiotic selection in lactococci . bacteriophage plaque assays were conducted as described previously ( b . terzaghi and w . sandine , appl . microbiol . 29 : 807 - 813 ( 1975 )). center of infection ( coi ) assays , one - step growth curves , and burst size determinations were all performed at 30 ° c . in accordance with known techniques ( w . sing and t . klaenhammer , j . gen . microbiol . 136 : 1807 - 1815 ( 1990 )). table 1______________________________________plasmids used or constructed herein . plasmid relevant characteristics______________________________________pbluescript 2 . 96 kb , ap . sup . r ( stratagene ) ks ii + ptrkl2 6 . 4 kb , lacz , em . sup . rptrkh2 6 . 9 kb , lacz , em . sup . rptrk370 15 . 9 kb , encodes complete llai operon , em . sup . r , r . sup .+ / m . sup .+ ptrk394 6 . 6 kb , ap . sup . r , pbluescriptiiks + with 3 . 7 kb pvuii - clai dna fragment from ptrk370 that contains the promoterless llai . 1 , ll / ai . 2 , llai . 3 cassette . ptrk395 9 . 8 kb , em . sup . r , ptrk12 with 3 . 7 kb pvui - hindii dna fragment from ptrk394 that contains the promoterless llai . 1 , llai . 2 , llai . 3 cassette . ptrk397 10 . 3 kb , em . sup . r , ptrk12 with 3 . 7 kb pvui - xhoi dna fragment from ptrk394 that contains the promoterless llai . 1 , llai . 2 . llai . 3 cassette . ptrk414l 10 . 1 kb , em . sup . r , the 239 bp fspi - bamhi φ31 promoter fragment from ptrk391 . sup . 4 added to ptrk395ptrk414h 10 . 6 kb , em . sup . r , the 239 bp fspi - bamhi φ31 promoter fragment from ptrk391 . sup . 4 added to ptrk397ptrk400 7 . 9 kb , km . sup . r , cm . sup . r , pnz18 with 2 . 4 kb fragment from ptrk370 , encoding llaic with the native promoter from the llai operon______________________________________ . sup . 1 d . o &# 39 ; sullivan and t . klaenhammer , gene 137 : 227 - 231 ( 1993 ). . sup . 2 d . o &# 39 ; sullivan et al ., j . bacteriol . 177 : 134 - 143 ( 1995 ). . sup . 3 g . djordjevic and t . klaenhammer , plasmid 35 , 37 - 45 ( 1996 ). . sup . 4 d . o &# 39 ; sullivan et al ., bio / technology 14 : 82 - 87 ( 1996 ). rapid isolation of e . coli plasmid dna was accomplished by an alkaline lysis method of h . birnboim and j . doly , nucleic acids res . 7 : 1513 - 1519 ( 1979 ). large scale isolation of e . coli plasmid dna was accomplished using the qiagen plasmid kit ( qiagen , inc ., chatsworth , calif .) following the manufacturer &# 39 ; s instructions . isolation of plasmid dna from lactococci was performed by the alkaline lysis protocol described by b . bojovic et al ., appl . environ . microbiol . 57 : 385 - 388 ( 1991 ). phage dna was isolated using the large scale protocol described by r . raya et al ., appl . environ . microbiol . 55 : 2206 - 2213 ( 1989 ). standard techniques were used for endonuclease restriction , dephosphorylation and ligation of bacterial dna ( sambrook et al ., supra ( 1989 )). ligation of phage dna was performed as described by sambrook et al ., supra ( 1989 ) with the following modifications : phage dna fragments were heated at 65 ° c . for 15 minutes before adding vector dna ; the ligation mixture was heated at 65 ° c . for an additional 10 minutes , and then slowly cooled to 30 ° c . before adding ligation buffer and t4 dna ligase . all dna used in cloning reactions was first purified in seakem gtg agarose ( fmc bioproducts , rockland , maine ) and extracted using qiaex dna extraction kit ( qiagen , inc ., chatsworth , calif .) following the manufacturer &# 39 ; s instructions . electrocompetent e . coli cells were prepared as described by w . dower et al ., nucleic acids res . 16 : 6127 - 6145 ( 1988 ) and electroporated using the gene pulser ™ apparatus ( bio - rad laboratories , richmond , calif .). l . lactis cells were electrotransformed as described by g . djordjevic and t . klaenhammer , plasmid 35 : 37 - 45 ( 1996 ) the promoterless llai restriction cassette , composed of three genes llai . 1 , llai . 2 , and llai . 3 , designated llair +, was first cloned as a 3 . 7 - kb pvuii - clai fragment from the r / m plasmid ptrk370 into pbluescript ii ks + ( ptrk394 , table 1 ). the llair + cassette was then subcloned into the low and high - copy - number shuttle vectors ptrkl2 and ptrkh2 to generate ptrk395 and ptrk397 , respectively ( see table 1 ). to prevent transcription from lacz promoter , the restriction cassette was positioned in an orientation opposite to lacz in all three plasmids . the 239 bp fspi - bamhi dna subfragment encoding a phage - inducible promoter with tandem transcription starts was isolated from ptrk391 ( d . o &# 39 ; sullivan et al ., bio / technol . 14 : 82 - 87 ( 1996 )) and designated φ31p . the promoter element exhibits no detectable activity in the absence of a φ31 infection ( s . walker et al ., supra 1995 ). the φ31p fragment was cloned 5 &# 39 ; of the llair + cassette encoded on ptrk395 and ptrk397 , and ptrk414l ( low copy number ) and ptrk414h ( high copy number ) plasmids were recovered in e . coli mc1061 ( see table 1 , fig1 and fig2 .). the two plasmids were transformed subsequently into l . lactis nck690 by electroporation . no differences in transformation frequencies were observed when e . coli or l . lactis were transformed with ptrk414l and ptrk414h , compared to ptrk395 and ptrk397 encoding the promoterless llair + cassette . as llai ( r + / m - ) plasmids are lethal in l . lactis ( d . o &# 39 ; sullivan et al ., j . bacteriol . 177 : 134 - 143 ( 1995 )), it was evident that the φ31p promoter was not recognized in these l . lactis transformants in the absence of a phage infection . the plasmids were stable during repeated subculture under antibiotic selection . standard plaque assays were used to evaluate the efficiency at which phage φ31 infected l . lactis harboring the restriction cassettes ( table 2 ). when l . lactis nck690 contained either ptrk395 or ptrk397 , both encoding the promoterless restriction cassette , was infected with phage φ31 it plaqued at full efficiency . however , in the presence of ptrk414l that contains the φ31p / llair + cassette on a low - copy number replicon , the eop was reduced to 0 . 5 with no notable changes in plaque size or morphology . in the presence of ptrk414h that contains the φ31p / llair + on the high - copy number replicon ptrk414h , the eop for φ31 was reduced dramatically to 2 . 2 × 10 - 4 ( table 2 ) and the plaques were very small and aberrant in size . therefore , the φ31p / llair + cassette did restrict the plaquing efficiency of phage φ31 at levels that correlated with the high or low copy number of the replicon on which it was cloned . l . lactis nck690 and nck690 ( ptrk414h ) were also challenged with 10 5 , 10 6 , and 10 7 pfu / ml of phage φ31 in broth cultures ( fig3 ). the multiplicities of infection ( moi ) ranged from 0 . 001 to 0 . 1 . as expected , phage φ31 readily lysed l . lactis nck690 ( fig3 b ). in contrast , lactococcal cells harboring the suicide system on ptrk414h did not suffer phage - induced cell lysis at any level of infection and continued to grow normally ( fig3 c ). when the suicide system was presented on the low copy replicon , ptrk414l , phage φ31 was still able to lyse the culture when challenged with 10 5 - 10 7 pfu / ml . these results correlated with negligible effect of ptrk414l on the eop of phage φ31 in l . lactis nck690 ( table 2 ). table 2______________________________________efficiency of plaquing ( eop ) for phage φ31 on lactococcuslactis nck690 harboring phage - inducible llai restriction cassette . plasmidcontent relevant characteristics eop______________________________________none * propagation host for phage φ31 1 . 0ptrk395 promoterless llair + cassette encoded on 1 . 0 the low - copy plasmidptrk397 promoterless llair + cassette encoded on 1 . 0 the high - copy plasmidptrk414l the φ31p / llair + cassette encoded on the 0 . 5 low - copy plasmidptrk414h the φ31p / llair + cassette encoded on the 2 . 2 × 10 . sup .- 4 high - copy plasmidptrk400 the regulatory protein c . llai encoded on 1 . 0 a high - copy plasmidptrk414l + the φ31p / llair + cassette encoded on the 0 . 6ptrk400 low - copy plasmid in the presence of the regulatory protein c . llaiptrk414h + the φ31p / llair + cassette encoded on the 2 . 0 × 10 . sup .- 5ptrk400 high - copy plasmid in the presence of the regulatory protein c - llai______________________________________ * l . lactis nck690 is a derivative of l . lactis nck203 cured of all plasmids , but one ( e . durmaz , unpublished data ). one - step growth curves and center of infection ( coi ) assays for phage φ31 were conducted on l . lactis nck690 ( ptrk414h ) harboring the φ31p / llair + suicide cassette ( fig4 ). cells were propagated until the od 600 reached 0 . 4 and then infected with 10 8 pfu / ml of phage φ31 ( moi = 5 ). the number of infective centers ( pfu / ml ) formed initially on l . lactis nck690 ( ptrk414h ) was 5 . 4 × 10 4 , 85 % lower than on l . lactis nck690 ( 3 . 6 × 10 5 ; fig4 ). only 15 % of infected cells harboring ( ptrk414h ) released progeny phages and phage development was notably retarded over the course of the one - step growth experiment . phage burst sizes in l . lactis nck690 , with and without ptrk414h , were estimated at 41 and 161 , respectively . therefore , the φ31p / llair + suicide cassette encoded on ptrk414h reduced the burst size of phage φ31 four - fold and severely limited the efficiency at which infections were completed . phages present in plaques formed on lawns of the restrictive host l . lactis nck690 ( ptrk414h ) were evaluated for their sensitivity or resistance to restriction by the llai r / m system . several small plaques were recovered from l . lactis nck690 ( ptrk414h ) and suspended by vortexing in 2 ml gm17 . the samples were then plaqued on l . lactis nck690 ( r - / m - ), l . lactis nck690 ( ptrk370 ) ( r + / m + ), and on l . lactis nck690 ( ptrk414h ). approximately 10 7 pfu / ml were obtained on l . lactis nck690 . no plaques were detected on l . lactis nck690 bearing either ptrk370 or ptrk414h . therefore , progeny phages released from cells bearing ptrk414h remained fully sensitive to restriction by llai . these results are consistent with the appearance of small aberrant φ31 plaques on l . lactis nck690 ( ptrk414h ). phage φ31 is limited in burst size and progeny phage continue to be severely restricted during subsequent infections of surrounding cells in the lawn . the llaic gene product , encoded upstream of the methylase llaim gene in the llai r / m operon , enhances the restriction activity of the llai system ( d . o &# 39 ; sullivan and t . klaenhammer , supra ( 1995 ); g . djordjevic and t . klaenhammer , supra ( 1996 )). the effects of c - llai on the efficiency of the phage - inducible restriction cassette were evaluated . plasmid ptrk400 encoding llaic ( table 1 ) was introduced into l . lactis nck690 , l . lactis nck690 ( ptrk414l ), and l . lactis nck690 ( ptrk414h ). the ptrk400 transformants were challenged with 10 6 pfu / ml of phage 31 ( moi of 0 . 01 ). the results in table 2 show that the eop for φ31 on l . lactis nck690 ( ptrk414h + ptrk400 ) was 2 . 0 × 10 - 5 , ten - fold lower than the eop of 2 . 2 × 10 - 4 obtained for nck690 bearing ptrk414h alone . no enhancement was observed due to the presence of ilaic in lactococcal cells harboring ptrk414l ( table 2 ). this likely reflects the low baseline level of restriction activity encoded on the low copy number vector . at functional levels of restriction activity , the c · llai protein markedly enhanced the effectiveness of the φ31p / llair + cassette . the phage - inducible promoter φ31p is positioned near the right cos end of the phage φ31 genome ( d . o &# 39 ; sullivan et al ., supra ( 1996 )). this region has been recently identified in the genomes of a series of φ31 - derived , per31 resistant , recombinant phages ( e . durmaz et al ., supra ( 1995 )). therefore , we evaluated if the φ31p / llair + suicide cassette would also confer resistance to φ31 - derived recombinant phages ( table 3 ). in all cases , the recombinant phages were restricted by the presence of the φ31p / llair + suicide cassette at levels which were at least 10 - fold greater than phage φ31 ( table 3 ). plaques formed by the recombinant phages were substantially smaller in size and their appearance altered as compared to φ31 plaques . the lower eops observed for φ31 - derived recombinant phages suggest that they are more sensitive to the lethal activity of the φ31p / llair + cassette than phage φ31 . of the φ31 - derived recombinant phages , phage φ31 . 1 was the most sensitive to restriction by the φ31lp / llair + suicide cassette . table 3______________________________________efficiency of plaquing ( eop ) for phage φ31 and φ31 - derivedrecombinant phages on lactococcus lactis nck690 ( ptrk414h ) phage eop * ______________________________________ plaque size ** on l . lactis nck690φ31 1 . 0 2 . 1 plaque size on l . lactis nck690 ( ptrk414h ) φ31 2 . 14 × 10 . sup .- 4 0 . 5 - 1 . 3φ31 . 1 5 . 24 × 10 . sup .- 6 0 . 4φ31 . 2 1 . 86 × 10 . sup .- 5 0 . 5 - 0 . 7φ31 . 7 3 . 04 × 10 . sup .- 5 0 . 5 - 0 . 7φ31 . 8 3 . 67 × 10 . sup .- 5 0 . 5 - 1 . 2______________________________________ eops represent the average of 3 - 4 independent experiments . ** plaque size ( mm ) on sensitive host l . lactis nck690 ranged from 2 . 1 ( φ31 ), 1 . 9 ( φ31 . 8 ) 1 . 8 ( φ31 . 1 , φ31 . 2 ) to 1 . 7 ( φ31 . 7 ). l . lactis nck690 ( ptrk414h ) broth cultures were also challenged with φ31 - derived recombinant phages . four cultures at an od 600 of 0 . 15 - 0 . 2 were individually infected with 10 7 pfu / ml ( moi of 0 . 1 ) of the recombinant phages φ31 . 1 and φ31 . 8 and cell growth monitored over 320 min . ( fig5 ). those cultures harboring ptrk414h were unaffected by the phage challenge and continued to grow normally . evaluation of the φ31p / llair + cassette with abortive phage devenses per3l and abia in this example , the llaic gene and the φ31p / llair + cassette were combined on the same replicon ( ptrk414ht711aic ). the plasmid also contains the t7 terminator cloned 5 &# 39 ; to the restriction cassette . when l . lactis nck690 ( ptrk414ht711aic ) was challenged with page φ31 , the eop was 4 . 4 × 10 - 5 ( table 4 ), a five - fold lower compared to that on l . lactis nck690 ( ptrk414h ). the abortive phage defenses per31 ( d . o &# 39 ; sullivan et al ., bio / technology 14 : 82 - 87 ( 1996 )) are encoded on high - copy - number plasmids ptrk375 and ptrk406 , respectively . ptrk375 is a pnz - 18 - derivative ( de vos , ( 1987 )) with a 4 . 5 - kb fragment of φ encoding phage replication origin ( e . durmaz and t . klaenhammer , appl . environ . microbiol . 61 : 1266 - 1273 ( 1995 )). ptrk406 is also a pnz18 - derivative , with a 2 . 2 - kb fragment encoding the abia abortive infection gene ( dinsmore and klaenhammer , 1996 ). to evaluate the efficiency of the φ31p / llair + cassette in l . lactis in the presence of per31 or abia , plasmid ptrk414ht711aic was combined with ptrk375 and ptrk406 , respectively . when either per31 or abia were present in trans , the eop for phage φ31 was lowered to & lt ; 10 - 10 ( table 4 ). similarly , when l . lactis nck690 ( ptrk414ht711aic - ptrk375 ) and l . lactis nck690 ( ptrk414ht711aic + ptrk406 ) broth cultures were challenged with 10 6 pfu / ml ( moi = 0 . 01 ) of φ31 , phage was eliminated from the infected population which continued to grow normally . table 4______________________________________efficiency of plaquing ( eop ) of φ31pllair . sup .+ cassette incombination with abortive phage defenses per 31 and abia . plasmid content relevant characteristics eop______________________________________ptrk414ht7llaic the φ31p / llair . sup .+ cassette and 4 . 4 × 10 . sup .- 5 regulatory protein c . llai encoded on the same high - copy plasmidptrk414ht7llaic the φ31p / llair . sup .+ cassette and & lt ; 10 . sup .- 10 + per31 regulatory protein c . llai encoded on the same high - copy plasmid , in the presence of per31ptrk414ht7llaic the φ31p / llair . sup .+ cassette and & lt ; 10 . sup .- 10 + abia regulatory protein c . llai encoded on the same high - copy plasmid , in the presence of abia______________________________________ the foregoing examples are illustrative of the present invention , and are not to be construed as limiting thereof . the invention is defined by the following claims , with equivalents of the claims to be included therein . a1 __________________________________________________________________________sequence listing ( 1 ) general information :( iii ) number of sequences : 2 ( 2 ) information for seq id no : 1 :( i ) sequence characteristics :( a ) length : 888 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : dna ( genomic )( xi ) sequence description : seq id no : 1 : gatccgatgtttataaacaaaatccacttagcagagcatttgtaaggttggttggtattc60cagttacagacagagatattgaagaacattttacaaaatatgatgaatctaaagatgtat120taatgccagattaataacaaaaaaagcccactgcaatgggctttaaaaacagatttctta180actactattatatcataaatataaggagttgagacactatgagtagaagatataacctta240ctgacagcgacttgaaagctatagagaagaagctctttatgtgtcaacgaattgaccacg300ctattcaatatcgcaagtatgagttagaagttaaacaatcacatgataataatgtaggtg360gtggtaggtcaagtataatctcaaagccagtagaagatatggttatgaaatgggatgctg420acagtaaactccaaagtctatatgagtttaagaaccgaatcaatgagttacaagattggt480ttggagatgatgaagatatgcaattggtattccactaccgttggttatctggtaaacgtt540atacagtaccagagatagctgataagtgtcacataacagagcgccaatactttagaaaga600gaagagcaatacttgagaagtatgatgagatatgtgacggcttctggtaatttgtcacct660tttgggcgaaaactgacaagataaatgttgtattatagtatcatcaaataaaacaaataa720agccagcggatatattctgttggctttttgtgtggagaaagtgaggtgacctcccatagc780attacgtgctgaccgtactggtgcgcatcgtgtagcctttgataagaatagaaagattct840tttaaagacacagaacacttgtggaatatgtggcaagccaatcggatc888 ( 2 ) information for seq id no : 2 :( i ) sequence characteristics :( a ) length : 265 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : dna ( genomic )( xi ) sequence description : seq id no : 2 : ggatccgtgtcacataactgagcgccaatactttagaaagagaagagcaatacttgagaa60gtatgatgagatatgtgacggcttctggtaatttgtcaccttttgggcgaaaactgacaa120gataaatgttgtattatagtatcatcaaataaaacaaataaagccagcggatatattctg180ttggctttttgtgtggagaaagtgaggtgacctcccatagcattacgtgctgaccgtact240ggtgcgggctgcagaattcgatctg265__________________________________________________________________________
| 2 |
the invention will be explained below in more detail with reference to a few examples . immersion extraction of cocoa aroma with hot water , determination of the effect of the extraction temperature in a stirred 10 liter autoclave , 400 g of natural cocoa powder having a fat content of 10 . 5 % and denoted by the type code n - 11 - n were admixed with 4 liters of demineralized water . the autoclave was sealed and the whole set - up then heated to the desired extraction temperature while being stirred intensively with a speed of 1000 rpm , followed by extraction over a period of 1 hour . after the extraction , the aqueous extract was separated from the residue with the aid of an ultracentrifuge at a speed of 30 , 000 rpm . an entirely clear extract was thus obtained . the clear extract was then inspissated to a thick paste by means of freeze - drying . the paste was then pasteurized at 80 ° c . to make it suitable for the tasting panel . in this way , four extractions were carried out at 90 , 110 , 125 and 150 ° c ., respectively . the pastes were assessed in terms of smell and taste in a tasting panel consisting of six persons . to this end , 2 g of paste were mixed with 100 ml of warm water of about 50 ° c . for each panel member . as a reference , a 2 % strength suspension of the original cocoa powder was also assessed . the taste was assessed in terms of various top notes on a scale from 0 to 6 , no taste being observed at 0 and the aroma aspect in question being very prominent at 6 . the table below reproduces the results from the tasting panel . the results show that the best results were obtained at 110 ° c . at 125 ° c . and above an anomalous taste is produced which resembles burnt milk . at 90 ° c ., aroma and taste are less intense . compared with the reference , the aroma and taste intensity is less , with the exception of the “ bitter ” note , which is distinctly more prominent in the case of the aqueous extracts . notwithstanding advice to the contrary in the literature ( k . h . ney , gordian , 1986 ( 11 ), 204 - 205 ), a good extract is obtained with an extraction above 100 ° c . ( 100 - 125 ° c ., the preference being between 105 - 115 ° c .). at 125 ° c . and above , distinctive taste anomalies are obtained . immersion extraction of cocoa aroma with hot water determination of the effect of the extraction time the extraction was carried out in the same way , using 500 g of cocoa powder , as in example 1 , except that the extraction was carried out at 110 ° c . and the extraction time was extended to 3 hours . after 1 , 2 and 3 hours a sample was drawn which was worked up and assessed in the same way as in example 1 . the table shows that the taste strength , in particular , increases with time . after 3 hours , however , an anomalous taste begins to be observed in the aroma . extraction times of less than 1 hour give a lower yield . longer extraction times lead to anomalies in taste . immersion extraction of cocoa aroma with hot water , pilot plant - scale experiment , effect of repeating the extraction in this experiment , 6 kg of cocoa powder were extracted with 60 liters of demineralized water in a stirred 100 liter autoclave . the extraction was carried out at 110 ° c . over a period of 3 hours . after extraction , the extract was separated in a centrifuge at 2200 rpm . the residue from the centrifuge was re - extracted under identical conditions and was separated . the extract was then admixed with 0 . 1 % of potassium sorbate to prevent the growth of mould during storage . part of the extracts was inspissated by means of freeze - drying for the purpose of the taste being assessed in the tasting panel . in addition , a sample of the residue after the second extraction was drawn , which was treated in the same way as the reference . the table indicates that even on a pilot - plant scale it is possible to obtain good extraction , with a powerful cocoa aroma , under the stated conditions , with the exception of the “ bitter ” note , which again is more prominent than in the reference . as it was not possible to use an ultracentrifuge at this scale , the separation had to be carried out by means of an ordinary centrifuge , with the result that the extract was not entirely clear . the residue after the second extraction has a weak cocoa taste . this indicates that by means of the immersion extraction using hot water the aroma components are removed effectively . immersion extraction of cocoa aroma with hot water pilot plant - scale experiment effect of the technique of inspissating the extract portions of the extract of the pilot plant experiment in example 3 were inspissated in various ways : by means of freeze - drying , the extract having been clarified beforehand by means of microfiltration . by means of reverse osmosis , the extract having been clarified beforehand by means of microfiltration . the results indicate that freeze - drying does afford an aroma concentrate having a good odour and taste , except that the taste is considerably more bitter compared with the reference . moreover , the solution of the concentrate in water remains turbid , which is also less desirable . to counteract the turbidity , the aqueous extract was first clarified via a microfilter and then inspissated by means of freeze - drying . now the concentrate did produce a clear solution . however , as the table shows , the cocoa aroma has considerably decreased and the taste notes “ bitter ”, “ astringent ” and “ acidic ” have increased . all this indicates that the quality of the aroma considerably diminishes by this action . when the concentrate is inspissated by means of vacuum distillation , the aroma and the taste are largely lost . only the bitter , acidic and astringent components remain . this therefore is an unacceptable inspissation technique . in the case of inspissation by means of reverse osmosis , the aroma and the taste were well preserved , except that the “ bitter ” note became more prominent . in the course of inspissation , however , crystalline material formed in the concentrate , causing clogging of the membrane and thereby considerably hampering industrial implementation , as the membrane had to be cleaned each time with a solution of dilute hydrochloric acid . when analysed , these crystals were found largely to consist of theobromine . this is a component which occurs in amounts of about 2 to 3 % in cocoa and is co - extracted with hot water . for the purpose of inspissation by means of freeze - drying the solid particles must first be separated off . this can be done effectively only with the aid of ultracentrifuging ( examples 1 and 2 ). this is a very expensive technique . if an ordinary centrifuge is used ( example 3 ), a clear extract is not obtained . to achieve this , the extract must first be filtered via an ultrafilter . this produces a loss in aroma . another drawback of inspissation by means of freeze - drying is that the aroma is very bitter , since the bitter components are co - extracted . concentration by vacuum evaporation results in a large loss of aroma components even at a low temperature of 40 ° c . effectively , all that remains are the bitter and astringent components . many of the literature references relate to the use of vacuum evaporation . concentration by means of reverse osmosis presents major problems on an industrial scale , because of crystallization of the theobromine . furthermore , the aroma is again very bitter . moreover , a clear extract can again be obtained only by ultracentrifuging . in this experiment , various techniques of isolating the cocoa aroma from cocoa powder were compared with one another : 1 . immersion extraction as specified in example 2 using an extraction time of 3 hours 2 . extraction using steam over a filter bed comprising cocoa powder . 100 g of cocoa powder of type n - 11 - n were mixed with 200 g of calcined sea sand to keep the filter bed open during the extraction . the mixture was introduced into a double - layer press filter of type sietz supra 2600 , provided with paper filters s & amp ; s 589 - 2 . after the filter had been sealed , open steam of 100 ° c . was forced through the filter bed . this experiment had to be aborted , because the bed became entirely clogged owing to moisture being absorbed in the cocoa powder , despite the admixture of calcined sea sand . this extraction method was therefore not considered in the assessment . 25 g of cocoa powder of type n - 11 - n were placed on a fluted filter . then , four portions of 250 ml of demineralized water of 85 ° c . were poured onto the powder . the extracts were collected and inspissated by means of freeze - drying as specified hereinabove . the extraction sleeve was filled with 25 g of cocoa powder of type n - 11 - n , and the flask was charged with 100 ml of demineralized water , the powder subsequently being extracted for 4 hours under reflux . the extract was then inspissated by means of freeze - drying as specified earlier . after extraction , the ethanol was evaporated at room temperature in vacuo , and the residue was taken up in a small amount of water to produce a thick paste . in a batch set - up for supercritical extraction , 120 g of cocoa powder were extracted , at a pressure of 175 bar and a temperature of 50 ° c ., for 35 hours using 10 , 000 1 of atmospheric c 2 . the extract was collected in the decompression vessel at 60 - 80 bar . the extract obtained consisted of fat and was suspended in the warm water for the assessment . the trials show that by far the best and most powerful aroma is obtained by means of immersion extraction at 110 ° c . whilst percolation does in principle afford a good aroma , its extraction from the powder is highly incomplete . in the case of the soxhlet extraction , a significant fraction of the aroma is lost , both with water and with ethanol . in the case of supercritical extraction , the yield of the extraction was very unsatisfactory . assessment of aroma concentrates of various aroma producers compared with cocoa powder of type n - 11 - n in a chocolate coating samples of cocoa aroma were obtained from three producers . these samples were assessed in a liquid white chocolate coating . the composition of the coating was as follows : the aroma was admixed to the liquid coating in a percentage as stated in the table . they were tasted in comparison with reference 2 . a negative number means that the aroma in question was characteristically less intense than the reference . in the case of a positive score it was more intense . the aromas tested in exp . 1 to 5 inclusive are so - called nature - identical aromas from haarman & amp ; riemer . experiment no 6 is a natural cocoa aroma from prova sa . experiment no 7 is a natural aroma from nutritec . as stated by the panel , the cocoa sensation is much weaker compared with cocoa powder and many differences in taste are found . 50 kg of cocoa powder were added to 500 1 of water at room temperature . mixing produced a homogeneous mixture . the mixture was heated for 1 hour at 100 ° c . with continuous stirring , followed by cooling to 60 ° c . within 30 minutes . it is important that the extract be rapidly cooled after extraction , given the risk of thermal degradation of aromatic substances in the extract . the liquid extract was filtered with a 0 . 1 mm filter and then , at a temperature of 45 ° c ., passed through a hollow - fibre module at a flow rate of 2 m 3 / h . the hollow fibres were internally coated with a pdms layer having a thickness of 2 μm . the feed side was subject to atmospheric pressure , the permeate side to a pressure of 7 mbar . the permeate was condensed in two steps , a first condenser operating at a temperature of + 3 ° c ., with about 95 % of the permeated water being collected in said first condenser . the uncondensed permeate , viz . the remaining water , and the major fraction of the cocoa aromas were collected in a second condenser . this condenser operated at a temperature of − 196 ° c . the yield of condensate , i . e . the contents of the second condenser , was about 175 g after 1 . 5 hours pervaporation . on the basis of instrumental analyses it could be established that enrichments of relevant aroma compounds in the extract in the second condenser were at an order of magnitude of 200 - 400 compared with the feed . the extract was colourless and had an intense cocoa aroma . sensoric tests by an expert panel confirmed the enrichment found and the high quality of the product . the drawbacks mentioned in example 4 regarding the various inspissation methods do not apply to pervaporation . in the case of pervaporation a simple separation is carried out in which the bitter taste constituents remain in the retentate and may afterwards be added back to the cocoa aroma as desired , since the cocoa aroma requires the bitter components . furthermore , virtually no loss of aromatic substances occurs with the aid of this method , as can be demonstrated with the aid of dynamic - headspace gc ( dh - gc ) analyses ( wampler , see above ) and static - headspace gc ( sh - gc ) analyses . for dh - gc , aroma concentrate and cocoa ( d - ii - a , from adm cocoa bv , netherlands ) were obtained in accordance with the above and a dh - gc analysis was carried out as follows ( for details see wampler hereinabove ): chromatograms of samples of the undiluted pervaporation feed ( i . e . liquid cocoa extract ) of aroma concentrate diluted 30 × ( with water ) as collected in the first condenser and of a 400 × dilution ( with water ) as collected in the second condenser , as shown in fig1 a , b and c , respectively . this technique can be compared with the p & amp ; t gc technique used earlier . in the case of dgi - gc , a small amount of vapour from the thermostatted headspace of the sample is injected directly into the gc . this method is quicker than the p & amp ; t - gc method , but provides reliable results , particularly for the volatile components . about 2 grams of a cocoa sample were weighed into a 40 ml glass vial and sealed with an aluminium screw cap having a teflon ® septum in the centre . the samples were equilibrated for 30 minutes , before 0 . 5 ml of the headspace was injected into the gc ( 1 : 10 split ). an hs850 ce instruments autosampler was used , coupled to a fisons 8533 gc . a 50m × 0 . 32 mm internal diameter ( d f = 1 . 0 μm ) db - waxetr ( j & amp ; e scientific ) column was used for separating the samples , with a helium flow rate of 3 . 8 ml / min . the column temperature was kept isothermal during a run time of 15 minutes . the volatile components were detected by means of an fid detector at a temperature of 250 ° c . all measurements were carried out in duplicate or triplicate ; the results are shown in fig2 . fig2 a shows a chromatogram of undiluted pervaporation feed of cocoa powder n - 11 - n , and fig2 b is a chromatogram of permeate diluted by a factor of 5 , in which extracts of condenser 1 and 2 were combined . this clearly shows that the peak pattern after pervaporation ( fig1 b and 1c , and fig2 b ) substantially matches the pattern after extraction ( fig1 a and fig2 a , respectively ), which means that the concentration ratio of the aromatic substances in question in the condensate ( i . e . after pervaporation ) substantially matches the ratio in the extract .
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referring to fig1 lamp bulbs such as bulbs 11 and 12 are supplied to the accumulator on a flat belt conveyor 13 which receives the bulbs from a bulk storage facility , not shown . from flat belt conveyor 13 , the bulbs enter an infeed section 14 in which the bulbs are transferred in a manner well known to those of skill in the art from flat belt conveyor 13 to a pair of parallel round belts which enable the bulbs to be suspended by the bulbous portion thereof so that the cullet portion is pendent . infeed section 14 is well known per se to those of skill in the art and typically includes , for example , devices for orienting the randomly positioned bulbs transferring from flat belt conveyor 13 and a device to remove bulbs with no cullet . it is preferred that the round belts be driven faster than the flat belt so that any groups of bulbs on the flat belt are pulled apart upon transfer . infeed section 14 also removes broken glass from the system since it falls off flat belt conveyor 13 between the parallel round belts . from infeed section 14 , the bulbs pass to accumulator section 15 which comprises a cullet drag strip 16 positioned beneath the support level provided by round conveyor belts 17 so that the cullet of the bulb drags on the strip causing the cullet to be inclined away from the direction of travel . leading edge 18 of drag strip 16 ( as seen by the bulbs ) is preferably curved to aid in the transition from pendent to inclining . other transition aids may be used as well . positioned above the support level of the bulbs , at a distance sufficient to enable the bulbs to convey underneath without touching , is hold - down strip 19 which serves to prevent one bulb from climbing too high on the bulb in front of it during accumulation . it also prevents the bulb from becoming misoriented and thus jamming the accumulator . the mechanism by which the bulbs are accumulated and stacked slightly to relieve contact with round conveyor belts 17 may be more fully understood by considering fig2 which represents an enlarged portion of accumulation section 15 . in fig2 drag strip 16 comprises a metal base 21 having a plastic covering or coating 22 . covering 22 may comprise any suitable material upon which the cullets drag . it is only required that the material exhibit friction against glass , and , for practical reasons , it is also desired that the material be highly resistant to abrasion for long life . by way of example only , polyurethane has been found to fulfill these requirements . in particular , polyurethane 85 shore a as sold by newage industries , inc . is suitable . as known in the art , the 85 indicates hardness and &# 34 ; shore a &# 34 ; indicates the test procedure . the covering may be provided in any suitable fashion , e . g ., a strip fastened by adhesive . a preferred embodiment is the use of an inverted u - shaped strip which snaps in place around base 21 . round belts 17 may comprise a material similar to that of covering 22 , i . e ., they exhibit friction against glass . by way of example only , &# 34 ; super rounthane &# 34 ; 92 shore a has been found suitable . it is this frictional engagement of the bulbs with the round belts that limits round belt conveyors of the prior art to 12 to 20 bulbs . beyond 12 bulbs or so , the bulb - to - bulb pressure on the first becomes considerable , leading to breakage . by removing the bulbs from contact with the belts in accordance with the present invention , the bulb - to - bulb pressure is greatly reduced . hold - down strip 19 , on the other hand , comprises a material across which the bulbs may readily slide ; for example , flexible high density linear polyethylene . it is necessary that the bulbs be able to slide when in contact with hold - down strip 19 to prevent jamming . in general , the coefficient of friction between glass and the drag strip or round belts is higher than the coefficient of friction between glass and the hold - down . in operation , consider that bulb 24 is at rest and and is resting on the neck portion of the bulb in front of it . contact with round belt conveyor 17 is eliminated due to the lifting of bulb 24 away from belt 17 . a succeeding bulb , in contact with belts 17 , travels in the position indicated by dashed line 25 and , upon encountering the neck of bulb 24 , climbs slightly up and away from round belt conveyor 17 to assume position 26 in which it is similarly removed from contact with belt 17 . as bulbs are removed from accumulation section 15 , the mass of accumulated bulbs move forward with only momentary contact with the round belts . as can be seen from fig2 successive bulbs are supported by the bulb in front of it and by drag strip 16 . in this manner , the accumulation of the bulbs is made considerably more gentle and damage to the bulbs is reduced compared to accumulation systems of the prior art . it is to be noted that an additional advantage of the present invention is that the construction of the present invention is open such that if a bulb should break it can easily fall away from drag strip 16 without pieces thereof causing a jam - up in the accumulator . another advantage of the open construction is that , if a piece of broken glass should lodge on drag strip 16 , the cullets of the succeeding bulbs merely ride up and over the obstruction , thus not impeding the normal flow of bulbs . from accumulation section 15 , the bulbs are removed by escapement section 27 in fig1 and shown in a top view in fig3 . the bulbs are removed , without the use of a stop gate , by means of a pair of opposing cleated belts 28 , which gently grip the bulbs from opposing sides and move them forward continuously , at a slower rate than that of conveyor belt 17 . cleated belts 28 are parallel , and the portions facing each other move in the same direction and at the same speed , forming a moving defile for the bulbs . cleated belts 28 are supported and driven by pulleys 29 and 31 , one of which may comprise an idler pulley . it is essential that , to provide translation without rotation of the bulbs , one pulley for each belt is a driving pulley , driven synchronously with the other by any suitable means ( not shown ). this is most easily implemented , for example , by drive pulleys of equal diameter rotating at the same speed . while the cleated belts may stop and start , depending upon the needs of the sealing machine , which is downstream therefrom , the operation of the cleated belts is continuous in that , as opposed to prior art devices , a physical impediment is not inserted in the train of bulbs to stop the procession thereof . round belt conveyor 17 may operate continuously , and operates at a higher rate than belts 13 and 28 . as bulbs are removed from the accumulator , the remaining bulbs are momentarily lowered into contact with round belts 17 and moved forward where they again accumulate . the visual impression of the procession of bulbs is one of undulation or a waving motion . this undulation could be used as an indication for setting the proper spacing of drag strip 16 from belts 17 , although it is not preferred . if drag strip 16 is too far from belts 17 , the bulbs are too vertical , with the effect that the bulbs move almost simultaneously . this tends to eliminate the wave action , causing the entire accumulation of bulbs to contact the belt and then stop simultaneously , resulting in a greatly increased noise level and greater jarring of the bulbs . if drag strip 16 is too near belt 17 , the bulbs are inclined too much with the result that the bulbs may drop sufficiently so that the bulbous portion strikes the cullet rather than the neck of the bulb in front , which may crack or break a percentage of the bulbs . this will also reduce the potential amount of accumulated bulbs significantly . while optimum spacing depends upon the size and shape of the bulbs , a spacing producing a bulb inclination of 45 ° ± 15 ° has been found suitable for use in the present invention . while forming no part of the present invention , various control devices known in the art may be used in conjunction with the present invention . for example , as previously noted , the operation of output or escapement section 27 is typically controlled by the needs of the sealing machine into which output section 27 feeds the bulbs . similarly , means for sensing the fullness of the accumulation section , for stopping flat belt conveyor 13 , may also be incorporated with the present invention . there is thus provided by the present invention an in - line bulb accumulator that is more gentle than those of the prior art since the bulbs are removed from contact with the round conveyor belts and are therefore not continuously jammed into one another . recovery time is short since the drum - type accumulator is eliminated and the bulbs travel at a high speed over the empty portion of accumulation section 15 , i . e ., at the speed of the belt , and at a low speed after accumulation , as determined by the escapement . further , a smoother escapement is provided which does not cause further impacting of the bulbs . having thus described the invention , it will be apparent to those of skill in the art that various modifications can be made within the spirit and scope of the present invention . for example , while described in conjunction with lamp bulbs , it is apparent that the accumulator of the present invention can also be utilized to accumulate finished lamps . also , while illustrated in fig1 as inclined from the horizontal , the accumulator of the present invention can operate over a range of approximately a 30 ° angle from horizontal , either uphill or downhill ; i . e ., it is not critical that the accumulator be inclined downhill for proper operation . also , accumulation section 15 can be as long as desired , comprising a number of separate sections . while any suitable mechanism can be used to drive the belts , it is preferred that the round belt driving mechanism include a slip clutch and a spring - loaded take - up , known per se in the art , to accommodate variations in load or stretching of the round belts .
| 1 |
preferred embodiments of the present invention will now be described with reference to the attached drawings . in the drawings , like numerals are assigned to corresponding elements , and duplicate description are omitted . referring to fig1 - 5 , a transmission type reticle according to an embodiment of the present invention will be described . fig1 is a schematic view of an example wherein the present invention is applied to a reduction projection exposure apparatus . fig2 a and 2b illustrate reflection light inside a reticle . fig3 shows changes in the light intensity distribution upon a wafer surface , due to reflection light . fig4 shows reflectance characteristic of a monolayer anti - reflection film , and fig5 is a schematic view for explaining irradiation of a region outside a device region , with reflection light . in fig5 , denoted at 1 is an illumination optical system for projecting light from a light source , onto a reticle . denoted at 11 is that reticle having a circuit pattern 12 formed thereon . denoted at 2 is a projection optical system for projecting the circuit pattern 12 onto a wafer 3 , in a reduced scale . in this embodiment , illumination light 21 projected from the illumination system 1 is incident on the transmission type reticle 11 , such that the pattern 12 formed in a pattern region of the reticle is transferred to the wafer 3 through the projection optical system 2 and with exposure light 22 ( see fig1 ). in accordance with a step - and - repeat method or step - and - scan method , the pattern is transferred to different shots of the wafer successively . in accordance with this embodiment , an anti - reflection film 13 is provided at the back surface of the reticle 11 , that is , on the surface remote from the reticle 11 surface where the circuit pattern 12 is formed ( see fig2 b ). illumination light 12 a incident on the reticle passes through the light transmitting portion 12 a formed on the reticle pattern surface 12 , and it is projected on the wafer surface as exposure light 22 . on the other hand , illumination light 21 b incident on the reticle is intercepted by a light blocking portion 12 b . a portion of the illumination light 12 b is then reflected and it reaches the reticle back surface . since however there is an anti - reflection film 13 provided at the reticle back surface , almost no light of illumination light 21 b is reflected by the reticle back surface . thus , there is substantially no possibility that the illumination light 21 b passes the transmitting portion 12 a and impinges on the wafer 3 through the projection optical system 2 . namely , creation of stray light can be avoided . the effect of such anti - reflection film 13 will be explained in terms of gaussian intensity distribution ( fig3 ). the curve denoted in fig3 at 32 is an intensity distribution of exposure light to be defined on a wafer 3 when fine lines are to be produced on the wafer . in this case , if it is assumed that the finish linewidth after exposure and development is determined with a certain slice level ( which is determined by exposure amount or resist sensitivity ) and that the slice level is 50 % of the peak intensity , a finish linewidth of about 140 nm is obtainable . on the other hand , the curve denoted at 33 is an intensity distribution in a case where there is stray light of 5 % to light 22 . if the width of the curve at the slice level ( exposure amount ) 50 %, as determined by the region where flare is small , is the region to be patterned by the exposure , the exposure linewidth of the curve 32 becomes larger by about 7 . 5 % as compared with the curve 32 . namely , it is seen that , as compared with a case wherein the exposure amount is determined on the basis of a region having small stray light , the linewidth in the region having stray light grows by about 1 . 5 % per 1 % of stray light . this means that the linewidth becomes larger by 1 . 5 % from what has been aimed at . fig4 shows the reflectance characteristic as calculated when an anti - reflection film of monolayer type , for example , is provided on the back surface of the reticle . according to this reflectance characteristic , if exposure light having a wavelength 248 nm , for example , is used , the reflectance can be suppressed to 0 . 5 % or less . taking into account that the reflectance in a case where light is perpendicularly incident on a glass surface without an anti - reflection film is about 4 %, creation of stray light can be reduced to ⅛ or lower . thus , a distribution of exposure light near the idealistic intensity distribution 32 can be produced on the wafer , and a correct linewidth can be formed by exposure . the anti - reflection film is not limited to a monolayer film . a multilayered film , for example , may be used , and the reflectance can be lowered more in that occasion . the advantageous effects as described above can be extended . further , while the exposure wavelength is 248 nm in the above - described example , a different wavelength such as 157 nm or 134 nm may be used . this embodiment is effective also in regard to a case wherein reflection light at a light blocking portion provided at the outer periphery of a device region of a reticle , where a circuit pattern is formed , produces an adverse influence to a region outside the device region . this will be explained below , in conjunction with fig5 . usually , while taking into account the light shielding of an illumination region , a reticle is provided with a light blocking zone 14 at the outer periphery of the reticle pattern region . the width thereof is 1 . 5 mm , for example . where the na is small ( na = sin θc ), illumination light 21 c enters from the device region ( the region of the reticle at the left - hand side of the light blocking zone 14 as viewed in the drawing ). illumination light 22 c as reflected by the light blocking zone is again reflected by the reticle back surface and , again , it is blocked by the light blocking zone . thus , it does not go out to the wafer side , as stray light . the illumination light as reflected plural times between the light blocking zone 14 and the reticle back surface may advance toward the wafer side . in such case , however , it would be easily expected that the intensity is very low so that it does not have an influence to the exposure . if , on the other hand , the na is large ( na = sin θd ) and illumination light 21 d incident from the device region is reflected twice by the light blocking zone and the reticle bask surface , the light may goes beyond the width of the light blocking zone and it may leaks toward the outside of the device region , as shown at 22 d . namely , this means that an area not included in the exposure region is exposed thereby . since this applies an adversely influence to an adjacent shot region , reflection light from the reticle back surface as described above should be avoided . it may be possible to make the light blocking zone larger as the exposure na becomes large . however , usually , at an area on the reticle which is outside the device region , namely , outside the light blocking zone , there are marks provided for alignment operation . if the light blocking zone becomes larger , these alignment marks have to be placed outwardly . since the alignment marks should be projected onto a wafer through a projection optical system , this necessitates enlargement of the effective region of the projection optical system . however , because it requires extension of the performance assured region of the projection optical system , production difficulties are much raised on one hand and the size is enlarged on the other hand . in consideration of this , the light blocking region should be kept small . now , the relationship between the range of influence of reflection light due to enlargement of the na and the width of the light blocking zone , will be considered . if the refractive index of a medium before incidence of light upon the reticle is n 1 , the refractive index of the reticle is n 2 , the thickness of the reticle is t , the width of the light blocking zone is d , and the incidence angle of light is θ ( it is θc if na is low , and θd if na is high ), the condition for that the light goes beyond the width of the light blocking zone and leaks to the outside of the device region can be given by : if , for example , numerical condition that n 1 = 1 . 0 , n 2 = 1 . 5 , t = 6 . 35 mm , and d = 15 mm are applied as the conditions in an ordinary exposure apparatus , the na ( sin θ ) must be not less than about 0 . 175 upon the reticle , otherwise it couldn &# 39 ; t be set up . thus , the present invention can be effectively applied to a case where the na is not less than 0 . 175 . the conditions described above are a mere example , and the invention is not limited to them . furthermore , not only they can be used for calculation of the na but also they can be used for calculation of d or t for a certain na . if the projection magnification ( reduction ratio ) for transferring a pattern of a reticle onto a wafer is 4 ×, the numerical aperture 0 . 175 or more upon the reticle means that the numerical aperture on the wafer is 0 . 7 or more . of course , if the projection magnification is different , the na on the wafer becomes different . furthermore , this embodiment can provide a larger technical advantage with higher reflectance from the reticle pattern surface is . generally , a dual - layer coated reticle has a higher reflectance than a triple - layer coated reticle . an example is that , with respect to an exposure wavelength of 248 nm , the reflectance of a pattern surface of a triple - layer coated reticle may be about 5 %, whereas the reflectance of a pattern surface of a dual - layer coated reticle may be about 35 %. although the numerical values of the reflectance are not limited to this example , it is well known that there would be produced a large difference in reflectance . thus , it can be said that the present invention provides a larger advantageous effect with a dual - layer coated reticle . the semiconductor exposure process includes a variety of processes such as from a process for performing a fine exposure to a process for performing exposure of a relatively rough linewidth . thus , production of reticles may be carried out appropriately selectively . that is , the anti - reflection treatment may be carried out to those reticles to be used in such exposure process that should satisfy the conditions described above , whereas the anti - reflection treatment may be omitted for those reticles to be used in a process of relatively rough linewidth , that is , a process with relatively small na . in this manner , the production cost can be minimized , and yet a uniform and satisfactory fine - exposure operation is assured . next , referring to fig7 and 8 , an embodiment of a device manufacturing method which uses a projection exposure apparatus such as shown in fig1 , will be explained . fig7 is a flow chart for explaining the procedure of manufacturing various microdevices such as semiconductor chips ( e . g ., ics or lsis ), liquid crystal panels , ccds , thin film magnetic heads or micro - machines , for example . step 1 is a design process for designing a circuit of a semiconductor device . step 2 is a process for making a mask on the basis of the circuit pattern design . step 3 is a process for preparing a wafer by using a material such as silicon . step 4 is a wafer process which is called a pre - process wherein , by using the thus prepared mask and wafer , a circuit is formed on the wafer in practice , in accordance with lithography . step 5 subsequent to this is an assembling step which is called a post - process wherein the wafer having been processed at step 4 is formed into semiconductor chips . this step includes an assembling ( dicing and bonding ) process and a packaging ( chip sealing ) process . step 6 is an inspection step wherein an operation check , a durability check an so on , for the semiconductor devices produced by step 5 , are carried out . with these processes , semiconductor devices are produced , and they are shipped ( step 7 ). fig8 is a flow chart for explaining details of the wafer process . step 11 is an oxidation process for oxidizing the surface of a wafer . step 12 is a cvd process for forming an insulating film on the wafer surface . step 13 is an electrode forming process for forming electrodes upon the wafer by vapor deposition . step 14 is an ion implanting process for implanting ions to the wafer . step 15 is a resist process for applying a resist ( photosensitive material ) to the wafer . step 16 is an exposure process for printing , by exposure , the circuit pattern of the mask on the wafer through the exposure apparatus described above . step 17 is a developing process for developing the exposed wafer . step 18 is an etching process for removing portions other than the developed resist image . step 19 is a resist separation process for separating the resist material remaining on the wafer after being subjected to the etching process . by repeating these processes , circuit patterns are superposedly formed on the wafer . with the provision of an anti - reflection film at the back surface of a reticle , according to the present invention , the influence of reflection light can be reduced significantly . this effectively avoids creation of stray light from any other element , or prevents light reflected by the pattern surface from being reflected by a glass surface and from impinging on a wafer surface to cause a non - uniform linewidth in an adjacent region . furthermore , unwanted reflection , inside the reticle , of illumination light from a device region and resultant illumination of a non - exposure region with such light , can be avoided effectively . particularly , if a light blocking zone is provided outside the pattern region and alignment marks should be placed outside the light blocking zone , the arrangement of the present invention effectively assures uniform and fine exposure without enlargement of the size of the apparatus or an increase of the cost . while the invention has been described with reference to the structures disclosed herein , it is not confined to the details set forth and this application is intended to cover such modifications or changes as may come within the purposes of the improvements or the scope of the following claims . this application claims priority from japanese patent application no . 2003 - 194940 filed jul . 10 , 2003 , for which is hereby incorporated by reference .
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with reference to the drawing , fig1 illustrates the portable test set of the invention . a box like container 10 contains all elements of the testing system . the box may be provided with a hinged ( 12 ) cover 14 with conventional snap latches 16 and a handle for carrying 17 . fig2 shows the housing with the cover open . a chain 18 or other suitable means would be appropriate to restrain the cover from opening excessively and damaging the cover . attached to the inside of the cover is the power supply for the system shown as a battery 20 . the battery is secured to the cover by straps 22 which are attached at one end to the cover by screws 24 thereby making removal of the battery more convenient . the power supply is connected electrically to the test system via wires 26 . within the container are a pair of test plug adapters 28 , 30 shown with wire plugs 32 , in phantom for purposes of illustration . control display panel 36 contains three operational controls and five visual indicators . a power on - off switch 38 controls all power to the test system . start - reset switch 40 resets led digital indicators 42 and causes the system to begin its scan . led 44 indicates a short and led 46 indicates an open . led &# 39 ; s 48 and 50 indicate which wire of the pair is defective , tip or ring respectively . advance switch 52 causes the system to resume its scan once it has been stopped by a defect indication . fig3 shows in block diagram form , the system of the invention . the power supply 20 is connected through on - off switch 38 to start - reset switch 40 . activation of switch 40 resets the binary coded decimal ( bcd ) counter 54 and led display 56 , 58 and additionally activates free running clock 60 . the clock outputs approximately sixteen pulses per second and feeds the bcd counter which counts clock pulses and provides bcd information to the display section . block 56 utilizes a standard seven segment light emitting diodes cascaded for a two digit display . block 58 is an odd - even display and functions with block 56 to display the specific wire of the pair under test , e . g ., tip or ring . a manual advanced switch 52 provides a method of advancing the bcd and test counters to continue testing after clock 60 is stopped when a defect is found , as will be explained hereinafter . the output from clock 60 is also sent to binary counter 62 which sends a binary count of clock pulses to drive the decoder circuit 64 . the decoder circuit then takes binary information from binary counter 62 , and provides it to each of fifty - three outputs , thereby allowing each wire of a twenty - six paired cable to be tested as an individual basis . the additional output ( fifty - three ) provides a signal to stop the clock when the entire cable has been tested . the wire test circuit 66 provides the input to the wire being tested and provides for drivers to feed each wire . although fifty - two circuits are required to test the fifty - two wires in a twenty - six paired cable for purposes of illustration and convenience only one circuit will be shown since the circuits are identical . wire test circuit 68 is the output test circuit and compares the wire being tested for a known condition and in this circuit it is determined if the wire is good , open or shorted . two outputs are provided to show open or short conditions . the cable under test ( 70 ) is connected between input circuit 66 and output circuit 68 . wire 111 represents a plurality of wires , one wire for each wire in cable 70 detailed in fig4 b . open circuit information from wire test circuit 68 is fed to &# 34 ; and &# 34 ; gate combiner 72 . this circuit is effectually a fifty - two input and gate and collects information from all test circuits and combines it in order that information from each tested wire is combined into one output which will drive &# 34 ; or &# 34 ; gate 74 . output from combiner 72 also operates the led open display 76 . short circuit information from wire test circuit 68 is fed to the &# 34 ; or &# 34 ; gate combiner 78 where short information from the fifty - two tested wires is combined into one output which will also drive or gate 74 . output from combiner 78 operates the led short display 80 . or gate 74 is driven then by either the fifty third output from decoder 64 , a signal showing an open or a signal showing a short in the wires under test . if any of these conditions exist or gate 74 sends a signal to clock 60 which causes the clock to stop . the clock is restarted by either the manual advance switch 52 or start - reset switch 40 . fig4 a , 4b , 4c and 4d refer to the specific circuit of the invention . where applicable , boxes represent integrated circuits utilizing transistor - to - transistor logic and specific information and technical data describing the circuits may be found in the t . t . l . data book for design engineers , published by texas instruments corporation . concerning fig4 a , the components of fig3 are shown in dashed lines with their corresponding reference numerals . clock 60 consists of a standard ne 555 timer 82 that sends approximately sixteen pulses per second through nand gate 84 and inverter gate 86 to a 7476 microprocessor circuit 88 . manual advance switch 52 is also connected through nand gate 84 to the microprocessor . output from the processor is sent to display 58 where led &# 39 ; s identifying the tip 48 and ring 50 wires are located . connected to the processor is bcd counter 54 and binary counter 62 . the bcd consists of a pair of 74192 counters ( 90 , 92 ) for the units and tens display ( 56 ) and a pair of 7448 decoders 94 , 96 which convert the clock pulses to information useable by the seven segment led &# 39 ; s ( 56 ). binary counter 62 provides six outputs to decoder 64 containing four , 1 of 16 decoders 98 , 100 , 102 and 104 . this allows system to start with zero then progress to wire 1 , 2 , 3 etc . as counter 62 counts clock pulses . the pulses pass through wire under test as shown by example for one wire . this circuit is duplicated fifty - one more times for a twenty - six pair cable . using open collector logic , line 106 from decoder 64 passes a logical low pulse through the 7404 inverter gate 108 , to test for short circuits in the cable . line 110 represents only one of fifty - two wires 111 , hardwired between input test circuit 66 and output test circuit 68 . using reverse logic and comparing all wires in the cable to the wire under test ( in or gate combiner 78 ) a logical high output from nor gate 112 indicates a good circuit i . e ., no short defect . using conventional logic , the logical low passes through 7407 gate 114 through the wire under test 116 to nand gate 118 . an open circuit will cause an output from nand gate 118 which is processed in and gate combiner 72 and an indication of a defect . if the wire is fault free nand gate 118 will have no output indicating a closed circuit output . the fifty third output 120 is sent to the 7400 nand gate 122 fig3 d and stops clock 60 when the fifty two wires have been tested . output from nand gate 118 is sent to the and gate combiner 72 ( 745133 processor ) where the signals from all circuits are combined and reduced to a single output via nand gates 124 , 126 , 128 , 130 , inverter gates 132 , 134 , 136 , 138 and nand gate 140 . the output signal , if any , is sent via line 142 ( fig4 d ) to nor gate 74 where a pulse will be sent to clock 60 and the scanning stopped . output ( if any ) from nand gate 112 is sent to or gate combiner 78 where the signals from all the wires are reduced to a single output via a series of or gates sent through nand gate 122 to nor gate 74 and to clock 60 . the signal from or gate combiner follows line 144 to 7407 gate , 146 to the open led 76 . similarly , a signal from the and gate combiner follows line 142 to 148 through 7404 inverter gate 150 , 7407 gate 152 to short led 80 . although the invention has been described with reference to a particular embodiment , it will be understood to those skilled in the art that the invention is capable of a variety of alternative embodiments within the spirit and scope of the appended claims .
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reference will now be made in detail to potentially preferred embodiments of the invention , examples of which have been illustrated in the accompanying drawings . it is to be understood that it is in no way intended to limit the invention to such illustrated and described embodiments . on the contrary , it is intended to cover all alternatives , modifications and equivalents as maybe included within the true spirit and scope of the invention as defined by the appended claims and equivalents thereto . turning now to the drawings , wherein like elements are denoted by like reference numerals throughout the various views , in fig1 there is shown a fabric web 10 , wherein eight fabric panels to be cut 12 , 14 , 16 , 18 , 20 , 22 , 24 , and 26 have been outlined . also , specific fabrics pieces to be removed and slits 28 , 30 , 32 within the two largest fabric panels 12 , 14 are outlined as well . the fabric web 10 in this specific example comprised nylon 6 , 6 , 630 denier yarns , woven on a jacquard loom into a fabric comprising 41 picks by 41 ends per inch . in fig2 , two smaller preferred fabric panels 16 , 18 have been connected to one preferred large fabric panel 12 by substantially straight seams 34 , 36 , 38 , 40 . the composite fabric structure now has two small fabric portions 39 , 41 uncovered by the two smaller fabric panels 16 , 18 . the free space 30 remains and an imaginary straight line 42 denotes the future fold line within the fabric composite of the fabric panels 12 , 16 , 18 . in fig3 , tie - rods 31 , 44 have been placed over the small fabric portions 39 , 41 parallel to the seams 38 , 40 , and the fabric portions 39 , 41 have been folded back in a manner to form a right angle at the point of contact between the two portions 39 , 41 . in fig4 , the small fabric portions 39 , 41 have been folded over once again and seams 35 , 37 have been produced to connect the fabric portions 39 , 41 to themselves and to the smaller fabric panels 16 , 18 . the folded over fabric portions 39 , 41 provide reinforcement in order to withstand inflation pressures at the mouth opening of the cushion . in fig5 , the fabric panel 12 has been folded over imaginary line 42 ( in half ) leaving one smaller fabric panel 16 in view ( the other is not illustrated as it is now located on the bottom portion of fabric panel 12 directly beneath smaller fabric panel 18 ). a seam 46 connects fabric panel 12 to itself and also connects the smaller fabric panels 16 , 18 both to the larger panel 12 and to themselves . upon unfolding of the connected composite , the non - connected ends of the panel 12 will form the same shape as the front panel 24 of fig6 . fig7 then shows the seam 48 needed to sew the non - connected ends of the large panel 12 ( of fig5 ), and fig8 provides a side view of the finished cushion 50 after all the connections through seams 34 , 35 , 46 have been made . fig9 shows a fully deployed inflatable restraint cushion 60 in opposing relation to an occupant 52 located on the front seat 54 of a vehicle 56 such as an automobile , airplane , and the like . as shown , the cushion 50 may be outwardly deployed from the dash panel 57 by an inflation means 58 from a position directly opposite the occupant 52 . it is to be understood , however ) that the cushion 50 may likewise be deployed from any other desired location in the vehicle 56 including the steering wheel ( not illustrated ), the vehicle side panels ( not illustrated ), the floor ( not illustrated ), or the backrest of the front seat 54 for disposition in opposing relation to a rear passenger ( not illustrated ). in fig1 there is shown a fabric web 110 , wherein eight fabric panels to be cut 112 , 114 , 116 , 118 , 120 , 122 , 124 , and 126 have been outlined . also , specific slits 128 , 129 , 130 , 32 within the two largest fabric panels 112 , 114 are outlined as well . the fabric web 110 in this specific example comprised nylon 6 , 6 , 630 denier yarns , woven on a jacquard loom into a fabric 110 comprising 41 picks by 41 ends per inch . in fig1 , two smaller preferred fabric panels 116 , 118 have been connected to one preferred large fabric panel 112 by substantially straight seams 144 , 146 , 148 . the composite fabric structure now has two small fabric portions 131 , 150 , 152 uncovered by the two smaller fabric panels 116 , 118 . an imaginary straight line 142 denotes the future fold line within the fabric composite of the fabric panels 112 , 116 , 118 , which is noticeably off - center relative to the center of the mouth m , in order to ultimately allow for the bag to be deployed at an angle from a horizontally disposed dashboard ( not illustrated ). in fig1 , tie - rods 153 , 155 have been placed over the small fabric portions 150 , 152 which have been folded back over the tie - rods 153 , 155 as shown , folded again , as in fig1 , and connected to themselves by seams 154 , 156 . the folded over fabric portions 150 , 152 provide reinforcement in order to withstand inflation pressures at the mouth opening of the cushion . in fig1 , the fabric panel 112 has been folded over imaginary line 142 leaving one smaller fabric panel 116 in view ( the other is not illustrated as it is now located on the bottom portion of fabric panel 112 directly beneath smaller fabric panel 118 ). a seam 158 connects fabric panel 112 to itself and also connects the smaller fabric panels 116 , 118 both to the larger panel 112 and to themselves . upon unfolding of the connected composite , the non - connected ends of the panel 112 will form the same shape as the front panel 124 of fig1 . fig1 then shows the seam 159 needed to sew the non - connected ends of the large panel 112 ( of fig1 ), and fig1 provides a side view of the finished cushion 160 . fig1 shows a fully deployed inflatable restraint cushion 160 in opposing relation to an occupant 162 located on the front seat 164 of a vehicle 166 such as an automobile , airplane , and the like . as shown , the cushion 160 may be outwardly deployed from the dash panel 167 by an inflation means 168 from a position directly opposite the occupant 162 . it is to be understood , however , that the cushion 160 may likewise be deployed from any other desired location in the vehicle 166 including the steering wheel ( not illustrated ), the vehicle side panels ( not illustrated ), the floor ( not illustrated ), or the backrest of the front seat 164 for disposition in opposing relation to a rear passenger ( not illustrated ). in fig1 there is shown a fabric web 210 , wherein eight fabric panels to be cut 212 , 214 , 216 , 218 , 220 , 222 , 224 , and 226 have been outlined . also , specific fabrics pieces to be removed and slits 228 , 230 , 232 within the two largest fabric panels 212 , 214 are outlined as well . the fabric web 210 in this specific example comprised nylon 6 , 6 , 630 denier yarns , woven on a jacquard loom into a fabric 210 comprising 41 picks by 41 ends per inch . in fig2 , two smaller preferred fabric panels 216 , 218 have been connected to one preferred large fabric panel 212 by substantially straight seams 234 , 236 , 238 , 240 . an imaginary straight line 242 denotes the future fold line within the fabric composite of the fabric panels 212 , 216 , 218 . in fig2 , the fabric panel 212 has been folded over imaginary line 242 ( in half ) leaving one smaller fabric panel 216 in view ( the other is not illustrated as it is now located on the bottom portion of fabric panel 212 directly beneath smaller fabric panel 218 ). a seam 244 connects fabric panel 212 to itself and also connects the smaller fabric panels 216 , 218 both to the larger panel 212 and to themselves . upon unfolding of the connected composite , the non - connected ends of the panel 212 will form the same shape as the front panel 224 of fig2 . fig2 then shows the seam 252 needed to sew the non - connected ends of the large panel 212 ( of fig2 ), and fig2 provides a top view of a finished cushion 260 and showing a looped pocket 250 for an inflation means and fig2 provides a side view of a finished cushion 260 after all the connection through seams 234 , 244 , 248 have been made . fig2 shows a fully deployed inflatable restraint cushion 260 in opposing relation to an occupant 262 located on the front seat 264 of a vehicle 266 such as an automobile , airplane , and the like . as shown , the cushion 260 may be outwardly deployed from the dash panel 267 by an inflation means 268 from a position directly opposite the occupant 262 . it is to be understood , however , that the cushion 260 may likewise be deployed from any other desired location in the vehicle 266 including the steering wheel ( not illustrated ), the vehicle side panels ( not illustrated ), the floor ( not illustrated ), or the backrest of the front seat 264 for disposition in opposing relation to a rear passenger ( not illustrated ). these specific configurations and shapes provide the lowest overall fabric usage as compared to the available inflation airspace volume . specific measurements for each inventive cushion manufactured in this configuration ( but with different amounts of fabric utilized ) are further described in table 2 , below . each of the panels utilized in these preferred embodiments may be formed from a number of materials including by way of example only and not limitation woven fabrics , knitted fabrics , non - woven fabrics , films and combinations thereof . woven fabrics may be preferred with woven fabrics formed of tightly woven construction such as plain or panama weave constructions being particularly preferred . such woven fabrics may be formed from yarns of polyester , polyamides such as nylon 6 and nylon - 6 , 6 or other suitable material as may be known to those in the skill in the art . multifilament yarns having a relatively low denier per filament rating of not greater than about 1 - 4 denier per filament maybe desirable for bags requiring particular good foldability . in application , woven fabrics formed from synthetic yarns having linear densities of about 40 denier to about 1200 denier are believed to be useful in the formation of the airbag according to the present invention . fabrics formed from yarns having linear densities of about 315 to about 840 are believed to be particularly useful , and fabrics formed from yarns having linear densities in the range of about 400 to about 650 are believed to be most useful . while each of the panels maybe formed of the same material , the panels may also be formed from differing materials and or constructions such as , without limitation , coated or uncoated fabrics . such fabrics may provide high permeability fabric having an air permeability of about 5 cfm per square foot or higher , preferably less than about 3 cfm per square foot or less when measured at a differential pressure of 0 . 5 inches of water across the fabric . fabrics having permeabilities of about 1 - 3 cfm per square foot may be desirable as well . fabrics having permeabilities below 2 cfm and preferably below 1 cfm in the uncoated state may be preferred . such fabrics which have permeabilities below 2 cfm which permeability does not substantially increase by more than a factor of about 2 when the fabric is subjected to biaxial stresses in the range of up to about 100 pounds force may be particularly preferred . fabrics which exhibit such characteristics which are formed by means of fluid jet weaving may be most preferred , although , as noted previously , weaving on jacquard and / or dobby looms also permits seam production without the need for any further labor - intensive sewing or welding operations . in the event that a coating is utilized on one or more material panels , neoprene , silicone urethanes or disperse polyamides may be preferred . coatings such as dispersed polyamides having dry add on weights of about 0 . 6 ounces per square yard or less and more preferably about 0 . 4 ounces per square yard or less and most preferably about 0 . 3 per square yard or less may be particularly preferred so as to minimize fabric weight and enhance foldability . it is , of course , to be understood that aside from the use of coatings , different characteristics in various panels may also be achieved through the use of fabrics incorporating differing weave densities and / or finishing treatments such as calendaring as may be known to those in the skill of the art . while the airbag cushions according to the present invention have been illustrated and described herein , it is to be understood that such cushions may also include additional components such as shape defining tethers , gas vents , and the like as may be known to those in the skill of the art . with regard to comparable airbag cushions , the following table presents comparative seam usage factors for other well known and commercially available airbag cushions . the labels used are those used within standard & amp ; poor &# 39 ; s dri , a well known publication which denotes many different types of products offered for sale to the automotive industry . the 414t and cf bags listed above are tilted cushions for use in conjunction with relatively horizontal dashboards . the others are used in conjunction with substantially vertically configured dashboards . generally , an airbag module manufacturer or automobile manufacturer will specify what dimensions and performance characteristics are needed for a specific model and make of car . thus , airbag inflation airspace volume , front panel protection area ( particularly for passenger - side airbag cushions ), and sufficient overall protection for a passenger are such required specifications . in comparison with those commercially available airbag cushions listed above , the inventive airbag cushions which meet the same specifications ( and actually exceed the overall passenger protection characteristics versus the prior art cushions ) but require less fabric , less seam length for sewing operations , and thus cost appreciably less than those competitive cushions . the dimensions and seam usage factors for the inventive bags ( which compare with those in table 1 , above , directly , and as noted ) are presented below in tabular form : clearly , the inventive bags , which possess the same available inflation airspace volume and front fabric panel area as the comparative prior art commercially available cushions ( bags ), require much less in the way of total fabric utilization , which thus correlates into overall much lower effective fabric usage factors . furthermore , as noted above , in standard crash tests , these inventive bags ( cushions ) either performed as well as or outperformed their commercially available , more expensive , counterparts . while specific embodiments of the invention have been illustrated and described , it is to be understood that the invention is not limited thereto , since modifications may certainly be made and other embodiments of the principals of this invention will no doubt occur to those skilled in the art . therefore , it is contemplated by the appended claims to cover any such modifications and other embodiments as incorporate the features of this invention which in the true spirit and scope of the claims hereto .
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the craft in the unfolded position is shown in fig1 . the main deck 10 is flanked by left folding deck 11 and right folding deck 12 . hinges such as 13 serve to connect the folding decks 11 and 12 to the main deck . in the folded position , the folding decks 11 and 12 are upside down with their upper surfaces facing downward atop the main deck 10 . cables such as 14 are attached to each outboard edge of the folding decks 11 and 12 and are attached at their other end to winches such as 15 . the winches such as 15 are used for raising and lowering the folding deck sections 11 and 12 . the winches such as 15 are mounted upon a swivel so that they may be moved passed dead center when the folding decks 11 and 12 are passing the vertical position . when the decks are in the unfolded position as drawn in fig1 they are locked in place by locking pins such as 16 attached to the left deck lock bar 17 and the right deck lock bar 18 . the locking pins such as 16 fit into cylindrical chambers in the structural frame of main deck 10 . the deck lock bars 17 and 18 are provided with holes such as 19 to receive side rail supports such as 20 . the side rail supports such as 20 serve both to provide support for the side rails such as 21 and to lock the deck lock bars 17 and 18 into place . the side rail supports can be provided with a simple locking mechanism to prevent inadvertant raising of the rails . only the locking pins such as 16 actually transfer the load from main deck 10 to folding decks 11 and 12 . left pontoon 22 and right pontoon 23 are firmly attached to the underside of folding decks 11 and 12 respectively . the pontoons provide buoyancy for the entire craft . when in the folded position , the pontoons 22 and 23 are upside down atop the folded decks . a retractable wheel mechanism such as 24 at the front and rear of the pontoons is provided a means for lowering pontoon wheels ( left front wheel 25 shown ) during launching and landing , and for raising pontoon wheels out of the way into the pontoons during towing and during periods afloat . tow socket 26 is attached to tow structure 27 to permit towing behind a vehicle on land . the tow structure 27 has three positions . the towing position is drawn in fig1 . additionally , the tow structure is mounted on axles which carry rollers which run in tracks afixed beneath each edge of the main deck 10 . the &# 34 ; c &# 34 ; shaped track 28 is visible in fig1 in its furtherest forward projection beneath the right edge of the main deck 10 . the rear most extention of track 28 is visible extending over the stern of the craft and is labelled 28a . during towing , the tow structure 27 is locked in place relative to track 28 by means of pins or other locking device . when the tow vehicle is to mount the craft , the tow structure 27 is unlocked and moved along the tracks until it is sufficiently out of the way beneath main deck 10 . after the vehicle has mounted aboard the craft , the tow structure 27 is brought to the extreme forward position and pivoted upward on its support axle . this provides for tow structure 27 to be out of the water when the craft is launched and for protection of tow socket 26 from damage . water resistance is diminished since tow structure 27 would not be in the water . finally , in the upright position , tow structure 27 provides protection to those on the craft from accidentally falling off the craft forward . rear tower supports 29 and 30 serve as a continuation of the tracks to the rear of the craft and upward . the rear tower supports 29 and 30 also serve to support the truck winch 31 and the winches and swivels for the folding decks . the operations of the rear extentions of the tracks and the operation of the truck winch 31 will be described below . four hooks such as 32 are placed strategically at the left and right edges of main deck 10 . these hooks receive the cables and turnbuckles that serve to hold the vehicle fast to the deck . four cutouts such as 33 in the folding decks 11 and 12 provide the recess needed for hooks like 32 when the craft is folded in the towing position . the cutouts such as 33 may be provided with covers to prevent accidental injury . the front tower supports 34 and 35 support the winches and swivels for the folding decks . in addition , they may be provided with hooks to serve to tie down a canopy that extends from the front of the mounted vehicle . ramp slots 36 and 37 provide recessed storage for the ramps used to load and unload the vehicle . when pulled forward to their furtherest extention , the ramps are free to swivel downward to engage the ground . control panel 38 is unfolded from its storage position in folding deck 12 . it provides a place for craft and motor controls . seat 39 , seen here in the folded position pops up for use when control panel 38 is operational . fig2 shows the craft from below with the tow structure 27 removed to the lower right corner of the drawing for clarity . tow structure 27 is free to swivel about axle 40 of tow frame 41 . axle 42 and axle 40 carry roller wheels such as 43 that run in track 44 and 28 . this arrangement permits the three positions described above for tow structure 27 and the attached tow socket 26 . rear wheel 45 as well as all other pontoon wheels are visible in this view . the enlargement of a pontoon wheel is drawn in the upper left corner . internal division 46 is provided to maintain watertight integrity to the entire pontoon independent of the position of the wheel mechanism . piston 47 raises pontoon wheel mechanism 24 flush with pontoon 22 and serves to lower pontoon wheel mechanism 24 towards the ground . the wheel mechanism is provided with ski like framework to prevent the wheel from digging into underwater mud . the truck 48 carries the tow wheels such as 49 mounted on springs such as 50 . two additional axles 51 and 52 pass through the truck and are afixed to roller wheels such as 53 that ride in tracks 44 and 28 . the tow wheels such as 49 and the track wheels such as 53 are provided braking mechanisms , one for the tow wheels and one for the track wheels . the track wheels or their axles need not carry brakes if the tracks themselves are provided with a mean of locking the truck in place , such as by means of a pressure plate or locking pins . the brake controls may be run by cable to the upper side of the craft . axles 51 and 52 further carry hook mechanisms such as 54 that are free to rotate about the axles . the front hook 54 is attached by chain or cable around pulley 55 around pulley 56 and thence to truck winch 31 . rear hook mechanism 57 ( on fig3 ) is attached similarly via pulley 58 to winch 31 . the chain labelled 59 from front hook mechanism 54 around pulleys 55 and 56 to winch 31 may continue to pulley 58 to rear hook mechanism 57 . the action of the truck winch will either tend to pull the truck forward or rearward relative to the tracks 44 and 28 and hence relative to the entire craft . if the tow wheels such as 49 are locked and fixed relative to the ground , then the action of winch 31 will be to pull itself and hence the entire craft over the fixed ( relative to the ground ) truck 48 . it is this action which serves to launch and land the craft . fig3 shows the truck in an upright position . the rear hook mechanism 57 is now visible as are the four track wheels 53 , 60 , 61 , and 62 . the relative placement of tracks 44 and 28 are shown . fig4 is a cross - section through the craft with the left side unfolded and the right side folded . visible in this view is pontoon supports 63 which serve to attach the pontoons to the folding decks . the pontoon wheels such as 25 are shown extended on the left . normally they are not extended fully to assure that most weight remains on the tow wheels . the right pontoon shows the pontoon wheel mechanism 24 in the fully retracted position . only a portion of the wheel extends beyond the pontoon . this provides some protection to the bottom of the pontoon but minimizes the water resistance . ramp 64 is visible inside of ramp slot 36 . rollers 65 provide for ease of movement of the ramp in its slot . pivot pin 66 provides for pivoting the ramp to the ground when in the fully extended position . hinge 13 is visible as are deck lock bars 17 and 18 . locking pin 16 is set all the way into the receptacle 67 in the main deck 10 . deck lock bar 18 can be seen to be locked in place by side rail support 20 . pins 68 and 69 are provided in folding decks 12 and 11 to permit the raising and lowering of side rail supports . they also provide for the rail supports to pivot flat when in the folded position , yet without permitting their removal . slots 70 and 71 cut in support 20 allow this action . on the right , the same mechanisms are shown in the unlocked and folded position . fig5 shows the craft in various modes . in part a , the craft is folded and being towed by a recreational vehicle . upon reaching the launch area , track wheels are unlocked and the tow wheels are locked and the recreational vehicle is driven forward a short distance . this brings the craft forward over the stationary truck as shown in part b . the track wheels are locked in place and the tow wheels are unlocked and the recreational vehicle is backed up down the launching ramp to the water &# 39 ; s edge . the tow wheels are now locked again . if the slope of the ramp is shallow rather than steep as drawn , the craft may have to be backed up into the water , but not so far as to provide for buoyancy . the craft is unfolded as shown in part c . the front pontoon wheels are lowered lifting the tow socket off the recreational vehicle &# 39 ; s tow ball as shown in part d . the vehicle drives forward . the rear pontoon wheels are lowered , the tow structure is pushed along the tracks under the craft and the loading ramps are extended and pivoted until they reach the launching ramp as shown in part e . the recreational vehicle drives up the loading ramps onto the craft and held fast by means of turnbuckles . the tow structure is brought forward and pivoted upward as shown in part f . the track wheels are unlocked and the craft slides down the launching ramp over the truck . if the craft does not slide down by gravity , the truck winch may be used . a mid position is illustrated in part g . the process continues in parts h and i until the buoyancy of the pontoons lifts the craft off the bottom as shown in part j . finally the pontoon wheels are raised and the truck is winched out of the water and the craft is afloat as shown in part k . landing essentially reverses the steps .
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the present invention is predicated upon the provision of at least one intraocular lens ( iol ) and preferably two iols that have a coating for aiding in the prevention of opacification , particularly interlenticular lens opacification ( ilo ). the iol [ s ] typically form an intraocular lens system such as a dual optic or piggyback lens system . the coating is typically formed of a hydrophilic or super - hydrophobic material for aiding in the resistance or prevention of ilo . unless otherwise specifically stated , percentages of materials as used herein are weight percentages ( w / w ). fig1 illustrates an exemplary intraocular lens system 10 in accordance with an aspect of the present invention . the system 10 includes a first intraocular lens 12 and a second intraocular lens 14 . as used herein , the terms “ first ” and “ second ” as they are used to indicate a lens of the system are merely used to indicate one of the lenses as opposed to the other . these terms are not intended to suggest any order such as order of implantation , unless otherwise specifically stated . each of the lenses 12 , 14 includes a body 18 defining an outer surface 20 and a coating 24 disposed upon a region 28 of that outer surface 20 . the coatings 24 of the lenses 12 , 14 can aid in the prevention of ilo as is discussed further below . each of the lenses 12 , 14 also includes haptics 32 extending outwardly from the bodies 18 of the lenses 12 , 14 . each coating 24 of each of the lenses 12 , 14 faces and opposes the outer surface 20 of the other of the lenses 12 , 14 . this is particularly the case after both lenses have been implanted within an eye . the intraocular lenses 12 , 14 define an interlenticular space 36 therebetween and the coatings 24 of the lenses 12 , 14 are both located directly adjacent and at least partially define the interlenticular space 36 . in the embodiment shown in fig1 , each of the lenses 12 , 14 has its own coating 24 . however , it is contemplated that only one of the lenses may have a coating while the other lens may be uncoated . this configuration is shown in fig2 . this may be the case , for example , when the intraocular system includes a set of piggyback lenses for which a first uncoated lens has already been implanted and a second coated lens is implanted as an adjustment to the first lens . in the embodiment of fig1 , the coating 24 of each lens 12 , 14 is disposed upon a region 28 of the body 18 and more particularly is disposed only upon one of two opposing sides 40 , 42 of the body 18 . it is contemplated , however , that the coating may be disposed upon other regions of the body or the entirety of the body of the lens . the term “ region ” as used herein is intended to mean only a portion of the body . however , the suggestion that the coating covers or is disposed upon a region of the outer surface of the body is not intended to restrict the coating from being located on other portions of the body unless it is specifically stated that the coating is only disposed upon that region . in instances where the coating is selectively disposed upon only a region of the iol , it is generally preferred that the region be a substantial portion of the outer surface of the body of the iol . preferably , that substantial portion is at least 20 %, more preferably at least 40 % and even possibly at least 60 % of the outer surface of the body . the substantial portion is typically less than 90 % and more typically less than 80 % of the outer surface of the body . the aforementioned percentages are taken as percentages of total surface area of the body . the outer surface of the body is considered exclusive of any outer surface area of the haptics . of course , the haptics may also be coated , but are not considered part of the body . in one preferred embodiment , the coating is formed as a ring about only a peripheral region of the iol body as shown in fig3 . in such an embodiment , the peripheral region may be on only one side of the iol or on both sides . it is contemplated that a second iol in a system according to the present invention could have a ring shaped coating that is configured to oppose and face the ring shaped coating of fig3 or such second iol may have an alternative coating shape such as a coating covering one entire side of its body . the body , the haptics or both of any of the intraocular lenses according to the present invention are preferably formed of a hydrophobic material . such hydrophobic material will typically have a contact angle that is no greater than 90 degrees , more typically no greater than 85 degrees and even possibly no greater than 80 degrees . such material will also typically have a contact angle that is at least 50 degrees and more typically at least 60 degrees and even possibly at least 65 degrees . unless stated otherwise , contact angles for the materials of the present invention are determined in accordance with young &# 39 ; s equation as discussed in physical chemistry of surfaces ( sixth edition ), adamson , arthur w . et al ., chapter x , pgs . 352 - 354 . the material of the body , the haptics or both is preferably an acrylate based material . acrylate based materials are defined as having a substantial portion of acrylate monomers , which are preferably of formulation 1 below : y is nothing , o , s , or nr wherein r is h , ch 3 , c n h 2n + 1 ( n = 1 - 10 ), iso - oc 3 h 7 , c 6 h 5 , or ch 2 c 6 h 5 ; ar is any aromatic ring which can be unsubstituted or substituted with ch 3 , c 2 h 5 , n - c 3 h 7 , iso - c 3 h 7 , och 3 , c 6 h 11 , c 6 h 5 , or ch 2 c 6 h 5 ; suitable monomers of structure ( i ) include , but are not limited to : 2 - ethylphenoxy methacrylate ; 2 - ethylphenoxy acrylate ; 2 - ethylthiophenyl methacrylate ; 2 - ethylthiophenyl acrylate ; 2 - ethylaminophenyl methacrylate ; 2 - ethylaminophenyl acrylate ; phenyl methacrylate ; phenyl acrylate ; benzyl methacrylate ; benzyl acrylate ; 2 - phenylethyl methacrylate ; 2 - phenylethyl acrylate ; 3 - phenylpropyl methacrylate ; 3 - phenylpropyl acrylate ; 4 - phenylbutyl methacrylate ; 4 - phenylbutyl acrylate ; 4 - methylphenyl methacrylate ; 4 - methylphenyl acrylate ; 4 - methylbenzyl methacrylate ; 4 - methylbenzyl acrylate ; 2 - 2 - methylphenylethyl methacrylate ; 2 - 2 - methylphenylethyl acrylate ; 2 - 3 - methylphenylethyl methacrylate ; 2 - 3 - methylphenylethyl acrylate ; 24 - methylphenylethyl methacrylate ; 2 - 4 - methylphenylethyl acrylate ; 2 -( 4 - propylphenyl ) ethyl methacrylate ; 2 -( 4 - propylphenyl ) ethyl acrylate ; 2 -( 4 -( 1 - methylethyl ) phenyl ) ethyl methacrylate ; 2 -( 4 -( 1 - methylethyl ) phenyl ) ethyl acrylate ; 2 -( 4 - methoxyphenyl ) ethyl methacrylate ; 2 -( 4 - methoxyphenyl ) ethyl acrylate ; 2 -( 4 - cyclohexylphenyl ) ethyl methacrylate ; 2 -( 4 - cyclohexylphenyl ) ethyl acrylate ; 2 -( 2 - chlorophenyl ) ethyl methacrylate ; 2 -( 2 - chlorophenyl ) ethyl acrylate ; 2 -( 3 - chlorophenyl ) ethyl methacrylate ; 2 -( 3 - chlorophenyl ) ethyl acrylate ; 2 -( 4 - chlorophenyl ) ethyl methacrylate ; 2 -( 4 - chlorophenyl ) ethyl acrylate ; 2 -( 4 - bromophenyl ) ethyl methacrylate ; 2 -( 4 - bromophenyl ) ethyl acrylate ; 2 -( 3 - phenylphenyl ) ethyl methacrylate ; 2 -( 3 - phenylphenyl ) ethyl acrylate ; 2 -( 4 - phenylphenyl ) ethyl methacrylate ; 2 -( 4 - phenylphenyl ) ethyl acrylate ; 2 -( 4 - benzylphenyl ) ethyl methacrylate ; and 2 -( 4 - benzylphenyl ) ethyl acrylate , and the like . it is contemplated that the first and second iols of a system can be formed of substantially identical material , but may be formed of different materials . preferably , the material of both iols of the system are acrylate based , however , it is possible for one to be acrylate based while another may be formed of a different material ( e . g ., a silicone based material ). in such circumstances , the acrylate based iol will typically include a coating according to the present invention while the other iol of different material may or may not include a coating . the material of the body and / or haptics is typically formed from at least 30 %, more typically at least 70 % and even possibly at least 95 % acrylate monomers . the material of the body and / or haptics is typically formed from no greater than about 99 . 9 % acrylate monomers . these acrylate based materials are typically mixed with a curing agent and / or a polymerization initiator so that the materials may be cured to form the iols . as such , it will be understood that these monomers are linked to form polymers in the finished iols . examples of acrylate - based lenses are , without limitation , described in u . s . pat . nos . 5 , 922 , 821 ; 6 , 313 , 187 ; 6 , 353 , 069 ; and 6 , 703 , 466 , all of which are fully incorporated herein by reference for all purposes . the coating is preferably formed of a hydrophilic material or a super - hydrophobic material . a suitable hydrophilic material will typically have a contact angle that is no greater than 50 degrees , more typically no greater than 45 degrees and even possibly no greater than 35 degrees . such material will typically have a contact angle that is at least 5 degrees . a hydrophilic coating can also be formed of a hydrogel material . in such an embodiment , functionalized hydrogel precursors of hydrogel materials such as polyacrylic acid ( paa ), polyvinyl acetate ( pva ), polyvinyl pyrrolidone ( pvp ), polyethylene glycol ( peg ), polyether imide ( pei ), combinations thereof or the like may be coated upon the outer surface of the iol body . the precursors can then be cross - linked by ultraviolet and / or visible light , plasma , radiation , heat energy or the like to form the coating of hydrogel material . a suitable super - hydrophobic material for the coating will typically have a contact angle that is at least 90 degrees , more typically at least 100 degrees and even more possibly at least 130 degrees . such material will typically have a contact angle no greater than 177 degrees . when the coating is formed of a super - hydrophobic material , silicone based materials are typically quite desirable . silicone based materials are those materials that include a substantial portion of silicon or silicon monomers ( e . g ., silane or siloxane ). when silicone based , the material of the coating typically is formed from at least 30 %, more typically at least 60 % and even possibly at least 80 % silicone monomers . in such embodiment , the material of the coating is typically formed from no greater than about 99 . 9 % silicone monomers . examples of silicone materials are , without limitation , described in u . s . pat . nos . 5 , 420 , 213 ; 5 , 494 , 946 ; 7 , 033 , 391 ; and 7 , 071 , 244 , all of which are fully incorporated herein by reference for all purposes . silicone based coatings can be formed upon the body of the iol using various techniques . in one embodiment , silicon monomers ( e . g ., silane or siloxane monomers ) can be coated on the outer surface of the body by plasma deposition or polymerization onto the surface of the body . in another embodiment , plasma treatment ( e . g ., oxygen or water plasma treatment ) can be employed to introduce hydroxyl groups onto the outer surface of the iol body followed by a silanization treatment . in yet another embodiment , a surface modifying agent containing silicone block copolymer can be blended with the acrylate material prior to casting and curing of the iol . as an alternative to silicone , super - hydrophobic materials with even greater hydrophobicity ( e . g ., contact angles of at least 130 degrees ) may be used . these super - hydrophobic coatings can be formed using continuous or , more preferably , modulated plasma deposition / polymerization treatment of perfluorocarbons monomers , which can then be cross - linked to form a polytetrafluoroehtylene ( ptfe ) coating . as an alternative , benzene moieties can be attached to the iol body outer surface by direct fluorination to form a super - hydrophobic coating . as another alternative , plasma treatment ( e . g ., oxygen or water plasma treatment ) can be used to introduce hydroxyl groups onto the outer surface of the iol body followed by a fluorinated silanization treatment . as an alternative or addition to a hydrophilic or super - hydrophobic coating , it is contemplated that a coating may be formed of bioactive agents . as one example , natural or synthetic molecules that modulate or inhibit protein adsorption and / or cell adhesion can be attached to the outer surface of the body to form a modified surface coating ( e . g ., a modified surface that preferentially adsorb serum albumin ). as another example , pharmacological agents such as immunosuppressants , mtor inhibitors or the like can be attached or otherwise coated on the outer surface of the iol body to form a coating that prohibits or inhibits lens epithelial cell ( lec ) growth . it is also contemplated that a coating may only cover a peripheral region ( e . g ., a peripheral edge ) of the lens body and , for example , may form a ring about the lens body and / or may extend radially outwardly from the peripheral region . still further , it is contemplated that the coating may be formed as a separate solid film ( e . g ., an annular disc shape film ) that is then disposed over the surface of the lens body and preferably attached ( e . g ., adhered ) thereto . lens systems of the present invention can be implanted in the eye according various protocols . typically a first lens is implanted followed by a second lens . it is contemplated , however , that two lenses may be implanted at least partially simultaneously . both lenses may be implanted in the capsular bag or one may be located in the capsular bag while the other is outside of the capsular bag . in one preferred embodiment , a first lens is implanted in the capsular bag and then , upon discovery that the first lens is not providing the desired visual performance , a second lens is implanted in the sulces of the eye . such lenses are typically referred to as piggy - back lenses . as example of such lenses are shown in fig4 . as can be seen , a first lens 50 is disposed in the capsular bag and is without a coating . however , a second lens 52 , which has been implanted later in the sulces does include a coating 54 in accordance with the present invention . generally , for piggy - back lens systems , the lens implanted in the sulces or the second lens implanted will be the only lens to include a coating since the lens in the capsular bag will have been implanted without the knowledge that a second lens would necessarily be implanted . of course , it would be possible for the first implanted lens 50 ( i . e ., the lens in the capsular bag ) to also include a coating , particularly if there is a likelihood that a second piggyback lens will be implanted later . in the embodiment shown , the coating 54 is in opposing facing relation to an outer side surface 56 of the first lens 50 and directly adjacent an interlenticular space 58 between the lenses . in another preferred embodiment , a first lens is implanted in the capsular bag and then a second lens is implanted in the capsular bag and connected to the first lens to form a dual optic intraocular lens system ( e . g ., an accommodative system ). as can be seen in fig5 , a first lens 60 having positive power is implanted and a second lens 62 having negative power is implanted . they are then attached to each other with attachment members 64 ( e . g ., interlocking haptics or other members ) to form a dual optic accommodative intraocular lens system . as can also be seen , both of the lenses 60 and 62 having coatings 66 , 68 on only one side of the lenses 60 , 62 and those coatings 66 , 68 are in opposing facing relation to each other and adjacent an intralenticular space 70 . the entire contents of all cited references in this disclosure are specifically incorporated herein by reference . further , when an amount , concentration , or other value or parameter is given as either a range , preferred range , or a list of upper preferable values and lower preferable values , this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or preferred value and any lower range limit or preferred value , regardless of whether ranges are separately disclosed . where a range of numerical values is recited herein , unless otherwise stated , the range is intended to include the endpoints thereof , and all integers and fractions within the range . it is not intended that the scope of the invention be limited to the specific values recited when defining a range . other embodiments of the present invention will be apparent to those skilled in the art from consideration of the present specification and practice of the present invention disclosed herein . it is intended that the present specification and examples be considered as exemplary only with a true scope and spirit of the invention being indicated by the following claims and equivalents thereof .
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the invention is based at least in part on cells that have been modified with an ltbeta receptor agonist . in particular , cells have ltbeta receptor agonist attached , conjugated or coupled to the membrane of a cell . such cells are useful for treating undesirable or aberrant cell proliferation , hyperproliferation ( e . g ., hyperproliferative disorders ), tumors , cancer , metastasis and neoplasia , as well as pathogen - infected cells . in accordance with the invention , there are provided cells that have been modified with an ltbeta receptor agonist , including cells in which ltbeta receptor agonist has been attached , conjugated or coupled to the membrane of the cell . ltbeta receptor agonists include , for example , light ( p30 polypeptide ), light ( p30 polypeptide ) variants and polymorphic forms , light ( p30 polypeptide ) chimeras , ltalpha1 beta2 , ltalpha2 beta1 , ltbeta and an ltbeta receptor antibody . cells modified with an ltbeta receptor agonist include undesirable cells or hyperproliferating cells , tumor cells , cancer cells , neoplastic cells , metastatic cells and pathogen infected cells . cells modified with an ltbeta receptor agonist include eukaryotic cells , such as mammalian ( e . g ., primate or human ) cells , which may be alive , non - viable or dead . the invention is also based in part on light ( p30 polypeptide ) variants and polymorphic forms that exhibit altered affinity and / or avidity for a receptor . such light ( p30 polypeptide ) variants and polymorphic forms have altered affinity and / or avidity for receptors , such as ltbeta receptor , hvem , or dcr3 ( decoy receptor 3 ), as compared to native wild type light ( p30 polypeptide ), set forth as seq id no : 1 , for example . in accordance with the invention , there are provided light ( p30 polypeptide ) variants that exhibit altered affinity and / or avidity for a receptor , such as ltbeta receptor , hvem , or dcr3 ( decoy receptor 3 ). in one embodiment , a light ( p30 polypeptide ) variant exhibits reduced or less affinity and / or avidity for dcr3 ( decoy receptor 3 ) as compared to native wild type light ( p30 polypeptide ) set forth as seq id no : 1 . in another embodiment , a light ( p30 polypeptide ) variant exhibits increased or greater affinity and / or avidity for ltbeta receptor or hvem as compared to native wild type light ( p30 polypeptide ) set forth as seq id no : 1 . light ( p30 polypeptide ) variants include polymorphic forms that have been isolated or purified from the naturally occurring environment , and have a sequence distinct from seq id no : 1 . as used herein , the terms “ attached , conjugated or coupled ” to the membrane of the cell and grammatical variations thereof , when used in reference to an ltbeta receptor agonist , means that the agonist binds to or is physically attached to the membrane of a cell or a molecule ( e . g ., a polypeptide , carbohydrate , etc .) present on the membrane of a cell . thus , for example , an ltbeta receptor agonist attached to or present on the membrane of a cell is not on the cell surface due to expression of an ltbeta receptor agonist from a nucleic acid in the cell that encodes the ltbeta receptor agonist . an ltbeta receptor agonist can be attached , conjugated or coupled to any molecule present on the membrane of the cell , such as a hyperproliferative cell , a tumor cell , cancer cell , neoplastic cell , metastatic cell , or a pathogen infected cell . ltbeta receptor agonist binding to the molecule on the cell membrane can be mediated by a covalent ( e . g ., cross - linking ) or non - covalent ( e . g ., ligand - receptor , antibody - antigen ) bond . cells upon which ltbeta receptor agonist is bound can be or express an antigen selected from a tumor cell or a cancer cell antigen , a neoplastic cell or a metastatic cell antigen , a viral antigen , a bacterial antigen , a fungal antigen , or a parasite antigen . ltbeta receptor agonists can be “ attached , conjugated or coupled ” to the membrane of the cell or an molecule present on the membrane of a cell by non - covalent or covalent bonds . non - covalent bonds include hydrogen bonding , ionic interactions , van der waals interactions , and hydrophobic interactions . non - limiting examples of non - covalent bonds are receptor - ligand , antibody - antigen and enzyme - substrate . covalent bonds typically involve sharing of electrons and are also referred to as chemical bonds . non - limiting examples of covalent bonds are amide bonds , non - natural and non - amide chemical bonds , other chemical bonds or coupling means including , for example , a carbon chain , such as carboxylic acids , multi - carbon chains ( e . g ., dicarboxylic acids , such as glutaric acid , succinic acid and adipic acid ), glutaraldehyde , n - hydroxysuccinimide esters , bifunctional maleimides , n , n ′- dicyclohexylcarbodiimide ( dcc ) or n , n ′- diisopropylcarbodiimide ( dic ). groups alternative to amide bonds include , for example , ketomethylene ( e . g ., — c (═ o )— ch 2 — for — c (═ o )— nh —), aminomethylene ( ch 2 — nh ), ethylene , olefin ( ch ═ ch ), ether ( ch 2 — o ), thioether ( ch 2 — s ), tetrazole ( cn 4 —), thiazole , retroamide , thioamide , or ester ( see , e . g ., spatola ( 1983 ) in chemistry and biochemistry of amino acids , peptides and proteins , vol . 7 , pp 267 - 357 , “ peptide and backbone modifications ,” marcel decker , n . y .). an ltbeta receptor agonist can be attached , conjugated or coupled to the membrane of the cell or an molecule present on the membrane of a cell via a distinct molecular entity , or an intermediary molecule . an intermediary molecule can be itself covalently or non - covalently bound to the membrane of the cell or an molecule present on the cell membrane . in one embodiment , an intermediary molecule includes two or more components such as a first moiety and a second moiety . in particular aspects , a first and second moiety binds to or physically interacts with each other , for example , a first moiety includes biotin or a biotin derivative , and a second moiety includes avidin , neutravidin or streptavidin , or a derivative or amino acid variant thereof . ltbeta receptor agonist binding to cell membrane or an molecule present on the membrane of a cell therefore includes binding to avidin , neutravidin or streptavidin , or a derivative or amino acid variant thereof that binds to an molecule present on the cell membrane . the ltbeta receptor agonist or the molecule to which the agonist is attached , conjugated or coupled , can each be bound via covalent or non - covalent binding to biotin or a biotin derivative , or avidin , neutravidin or streptavidin . ltbeta receptor agonists include mammalian forms , such as primate and human ltbeta receptor agonists . such agonists include “ amino acid ” “ protein ,” “ polypeptide ” and “ peptide ” sequences . the terms “ amino acid ,” “ protein ,” “ polypeptide ” and “ peptide ” are used interchangeably herein to refer to two or more amino acids , or “ residues ,” covalently linked by an amide bond or equivalent . amino acid sequences can be linked by non - natural and non - amide chemical bonds including , for example , those formed with glutaraldehyde , n - hydroxysuccinimide esters , bifunctional maleimides , or n , n ′- dicyclohexylcarbodiimide ( dcc ). non - amide bonds include , for example , ketomethylene , aminomethylene , olefin , ether , thioether and the like ( see , e . g ., spatola in chemistry and biochemistry of amino acids , peptides and proteins , vol . 7 , pp 267 - 357 ( 1983 ), “ peptide and backbone modifications ,” marcel decker , n . y .). ltbeta receptor agonists , chimeras and light ( p30 polypeptide ) include full length native wild type , variant and polymorphic forms of ltbeta receptor agonists , such as light ( p30 polypeptide ), hvem and light ( p30 polypeptide ) chimeras that retain at least partial ltbeta receptor agonist or binding activity . exemplary ltbeta receptor agonist variant and polymorphic forms include light ( p30 polypeptide ) with reduced or less affinity for dcr3 ( decoy receptor 3 ) as compared to native wild type light ( p30 polypeptide ), e . g ., seq id no : 1 , light ( p30 polypeptide ) with increased or greater affinity or avidity for ltβr or hvem as compared to native wild type light ( p30 polypeptide ), e . g ., seq id no : 1 , as well as light ( p30 polypeptide ) with increased or greater affinity or avidity for ltβr or hvem and with reduced or less affinity for dcr3 ( decoy receptor 3 ), as compared to native wild type light ( p30 polypeptide ), e . g ., seq id no : 1 . particular non - limiting variant and polymorphic forms of light ( p30 polypeptide ) include an amino acid sequence selected from any one of seq id nos : 3 to 10 . full length human light ( amino acid sequence ) ( seq id no : 1 ) meesvvrpsvfvvdgqtdipftrlgrshrrqscsvar qlhwrlgemvtrlpdgpagsweqliqerrshevnpa ahltganssltgsggpllwetqlglaflrglsyhdgalvvtkagyyyiys kvqlggvgcplglastithglykrtprypeelellvsqqspcgratsssr vwwdssflggvvhleageevvvrvlderlvrlrdgtrsyfgafmv the amino acid residues of the transmembrane domain are shaded . the amino acid residues of the extracellular domain of light are underlined . soluble form of light ( aka : lightt66 , amino acid sequence ) ( seq id no : 2 ) gemvtrlpdgpagsweqliqerrshevnpaahltganssltgsggpllwe tqlglaflrglsyhdgalvvtkagyyyiyskvqlggvgcplglastithg lykrtprypeelellvsqqspcgratsssrvwwdssflggvvhleageev vvrvlderlvrlrdgtrsyfgafmv human light e214k ( amino acid sequence ) ( seq id no : 3 ) meesvvrpsvfvvdgqtdipftrlgrshrrqscsvarvglglllllmgag lavqgwfllqlhwrlgemvtrlpdgpagsweqliqerrshevnpaahltg anssltgsggpllwetqlglaflrglsyhdgalvvtkagyyyiyskvqlg gvgcplglastithglykrtprypeelellvsqqspcgratsssrvwwds sflggvvhleage vvvrvlderlvrlrdgtrsyfgafmv the amino acid residue at position 214 of seq id no : 3 is highlighted . human light s32l ( amino acid sequence ) ( seq id no : 4 ) meesvvrpsvfvvdgqtdipftrlgrshrrq csvarvglglllllmgag lavqgwfllqlhwrlgemvtrlpdgpagsweqliqerrshevnpaahltg anssltgsggpllwetqlglaflrglsyhdgalvvtkagyyyiyskvqlg gvgcplglastithglykrtprypeelellvsqqspcgratsssrvwwds sflggvvhleageevvvrvlderlvrlrdgtrsyfgafmv the amino acid residue at position 32 of seq id no : 4 is highlighted . human light s9a ( mutation from s to a at amino acid position 9 , amino acid sequence ) ( seq id no : 5 ) meesvvrp vfvvdgqtdipftrlgrshrrqscsvarvglglllllmgag lavqgwfllqlhwrlgemvtrlpdgpagsweqliqerrshevnpaahltg anssltgsggpllwetqlglaflrglsyhdgalvvtkagyyyiyskvqlg gvgcplglastithglykrtprypeelellvsqqspcgratsssrvwwds sflggvvhleageevvvrvlderlvrlrdgtrsyfgafmv the amino acid residue at position 9 of seq id no : 5 is highlighted . human light s27a ( mutation from s to a at amino acid position 27 , amino acid sequence ) ( seq id no : 6 ) meesvvrpsvfvvdgqtdipftrlgr hrrqscsvarvglglllllmgag lavqgwfllqlhwrlgemvtrlpdgpagsweqliqerrshevnpaahltg anssltgsggpllwetqlglaflrglsyhdgalvvtkagyyyiyskvqlg gvgcplglastithglykrtprypeelellvsqqspcgratsssrvwwds sflggvvhleageevvvrvlderlvrlrdgtrsyfgafmv the amino acid residue at position 9 of seq id no : 6 is highlighted . human light s9a & amp ; s27a ( mutation from s to a at amino acid positions 9 and 27 , amino acid sequence ) ( seq id no : 7 ) meesvvrp vfvvdgqtdipftrlgr hrrqscsvarvglglllllm gaglavqgwfllqlhwrlgemvtrlpdgpagsweqliqerrshevnpaah ltganssltgsggpllwetqlglaflrglsyhdgalvvtkagyyyiyskv qlggvgcplglastithglykrtprypeelellvsqqspcgratsssrvw wdssflggvvhleageevvvrvlderlvrlrdgtrsyfgafmv the amino acid residue at positions 9 and 27 of seq id no : 7 are highlighted . human light s9a & amp ; s32l ( mutation from s to a at amino acid position 9 and s to l at position 32 , amino acid sequence ) ( seq id no : 8 ) meesvvrp vfvvdgqtdipftrlgrshrrq csvarvglglllllm gaglavqgwfllqlhwrlgemvtrlpdgpagsweqliqerrshevnpaah ltganssltgsggpllwetqlglaflrglsyhdgalvvtkagyyyiyskv qlggvgcplglastithglykrtprypeelellvsqqspcgratsssrvw wdssflggvvhleageevvvrvlderlvrlrdgtrsyfgafmv the amino acid residue at positions 9 and 32 of seq id no : 8 is highlighted . human light s27a & amp ; s32l ( mutation from s to a at amino acid position 27 and s to l at position 32 , amino acid sequence ) ( seq id no : 9 ) meesvvrpsvfvvdgqtdipftrlgr hrrq csvarvglglllllm gaglavqgwfllqlhwrlgemvtrlpdgpagsweqliqerrshevnpaah ltganssltgsggpllwetqlglaflrglsyhdgalvvtkagyyyiyskv qlggvgcplglastithglykrtprypeelellvsqqspcgratsssrvw wdssflggvvhleageevvvrvlderlvrlrdgtrsyfgafmv the amino acid residue at positions 27 and 32 of seq id no : 9 are highlighted . human light s9a & amp ; s27a & amp ; s32l ( mutation from s to a at amino acid positions 9 and 27 , and s to l at position 32 , amino acid sequence ) ( seq id no : 10 ) meesvvrp vfvvdgqtdipftrlgr hrrq csvarvglglllllm gaglavqgwfllqlhwrlgemvtrlpdgpagsweqliqerrshevnpaah ltganssltgsggpllwetqlglaflrglsyhdgalvvtkagyyytyskv qlggvgcplglastithglykrtprypeelellvsqqspcgpatsssrvw wdssflggvvhleageevvvrvlderlvrlrdgtrsyfgafmv the amino acid residue at positions 9 , 27 , and 32 of seq id no : 10 are highlighted . ltbeta receptor agonists also include subsequences of full length native wild type , variant and polymorphic forms of ltbeta receptor agonists , light ( p30 polypeptide ), hvem and light ( p30 polypeptide ) chimeras . exemplary lengths of ltbeta receptor agonists , chimeras and light ( p30 polypeptide ) include full length native wild type , variant and polymorphic forms of ltbeta receptor agonists , light ( p30 polypeptide ) chimeras , light ( p30 polypeptide ) and hvem , as well as subsequences of ltbeta receptor agonists , light ( p30 polypeptide ) chimeras , light ( p30 polypeptide ) and hvem that retain at least partial ltbeta receptor agonist or binding activity . exemplary ltbeta receptor agonist subsequences include from about 5 to 15 , 20 to 25 , 25 to 50 , 50 to 100 , 100 to 150 , 150 to 200 , or 200 to 300 amino acid residues in length . in particular embodiments , ltbeta receptor agonists , light ( p30 polypeptide ) chimeras and light ( p30 polypeptide ) and hvem include or consist of an amino acid sequence of about 1 to 10 , 10 to 20 , 15 to 20 , 20 to 30 , 30 to 40 , 40 to 50 , 60 to 70 , 70 to 80 , 80 to 90 , 90 to 100 or more residues . specific non - limiting examples include soluble forms of ltbeta receptor agonist , for example , agonists that lack a transmembrane domain , e . g ., an extracellular amino acid sequence of light ( p30 polypeptide ), set forth in any of seq id nos : 1 - 10 , or a soluble form of light ( p30 polypeptide ) set forth in seq id no : 2 ( lightt66 ), that bind to and retain at least partial ltbeta receptor activity . additional specific non - limiting examples include soluble forms of light ( p30 polypeptide ) variants and polymorphisms set forth in any of seq id nos : 3 - 10 , that bind to ltbeta receptor or hvem , exhibit ltbeta receptor agonist activity , or exhibit reduced or less binding to dcr3 , as compared to seq id no : 1 . ltbeta receptor agonists , such as light ( p30 polypeptide ), light ( p30 polypeptide ) chimeras , light ( p30 polypeptide ) variants and polymorphic forms , and hvem therefore include sequences with one or more ( 2 , 3 , 4 , 5 , etc .) conservative and non - conservative substitutions . a “ conservative substitution ” is a replacement of one amino acid by a biologically , chemically or structurally similar residue . biologically similar means that the substitution is compatible with a biological activity , e . g ., agonist activity . structurally similar means that the amino acids have side chains with similar length , such as alanine , glycine and serine , or having similar size , or the structure of a first , second or additional domain is maintained . chemical similarity means that the residues have the same charge or are both hydrophilic or hydrophobic . particular examples include the substitution of one hydrophobic residue , such as isoleucine , valine , leucine or methionine for another , or the substitution of one polar residue for another , such as the substitution of arginine for lysine , glutamic for aspartic acids , or glutamine for asparagine , serine for threonine , etc . routine assays can be used to determine whether a variant or polymorphic form has activity , e . g ., agonist activity or binding activity . specific examples include a substitution or deletion of one or more amino acid ( e . g ., 1 - 3 , 3 - 5 , 5 - 10 , 10 - 20 , or more ) residues of an ltbeta receptor agonist , such as light ( p30 polypeptide ) variants and polymorphic forms . a variant or polymorphic sequence typically has 85 %, 90 %, 95 %, 96 %, 97 %, 98 %, or more identity to a reference sequence . the term “ identity ” and “ homology ” and grammatical variations thereof mean that two or more referenced entities are the same . thus , where two amino acid sequences are identical , they have the same amino acid sequence . “ areas , regions or domains of identity ” mean that a portion of two or more referenced entities are the same . thus , where two amino acid sequences are identical or homologous over one or more sequence regions , they share identity in these regions . due to variation in the amount of sequence conservation between structurally and functionally related proteins , the amount of sequence identity required to retain a function or activity depends upon the protein , the region and the function or activity of that region . the term “ complementary ,” when used in reference to a nucleic acid sequence means the reference regions are 100 % complementary , i . e ., exhibit 100 % base pairing with no mismatches . the extent of identity between two sequences can be ascertained using a computer program and mathematical algorithm known in the art . such algorithms that calculate percent sequence identity ( homology ) generally account for sequence gaps and mismatches over the comparison region . for example , a blast ( e . g ., blast 2 . 0 ) search algorithm ( see , e . g ., altschul et al ., j . mol . biol . 215 : 403 ( 1990 ), publicly available through ncbi ) has exemplary search parameters as follows : mismatch - 2 ; gap open 5 ; gap extension 2 . for polypeptide sequence comparisons , a blastp algorithm is typically used in combination with a scoring matrix , such as pam100 , pam 250 , blosum 62 or blosum 50 . fasta ( e . g ., fasta2 and fasta3 ) and ssearch sequence comparison programs are also used to quantitate the extent of identity ( pearson et al ., proc . natl . acad . sci . usa 85 : 2444 ( 1988 ); pearson , methods mol . biol . 132 : 185 ( 2000 ); and smith et al ., j . mol . biol . 147 : 195 ( 1981 )). programs for quantitating protein structural similarity using delaunay - based topological mapping have also been developed ( bostick et al ., biochem biophys res commun . 304 : 320 ( 2003 )). ltbeta receptor agonists , such as light ( p30 polypeptide ), light ( p30 polypeptide ) chimeras , light ( p30 polypeptide ) variants and polymorphic forms , and hvem sequences can be entirely composed of natural amino acids or synthetic , non - natural amino acids or amino acid analogues , or derivatized forms . non - naturally occurring amino acid sequences include l - amino acid sequences , d - amino acid sequences and amino acid sequences with mixtures of l - amino acids and d - amino acids . in various embodiments , a ltbeta receptor agonist includes one or more d - amino acids substituted for l - amino acids , mixtures of d - amino acids and l - amino acids , or a sequence composed entirely of d - amino acid residues . amino acid sequences can be a linear or a cyclic structure , attached , conjugated or coupled to a distinct moiety ( e . g ., an intermediary ), form intra or intermolecular disulfide bonds , be modified to include , for example , sugar or carbohydrate residues , phosphate groups , fatty acids , lipids , and also form higher order multimers or oligomers with the same or different amino acid sequence , e . g ., different ltbeta receptor agonists , such as wild type and variants or polymorphisms of light ( p30 polypeptide ) in a multimer combination . additional examples of ltbeta receptor agonists include antibodies and antibody fragments . an “ antibody ” refers to any monoclonal or polyclonal immunoglobulin molecule , such as igm , igg , iga , ige , igd , and any subclass thereof . exemplary subclasses for igg are igg 1 , igg 2 , igg 3 and igg 4 . specific examples of ltbeta receptor agonist antibodies include 3c8 and 4h8 ( rat anti - mouse ), goat polyclonal antibodies and mouse anti - human bda8 antibody . additional specific examples of ltbeta receptor agonist antibodies include fully human antibodies . ltbeta receptor agonists include chimeric proteins in which a portion that is distinct from ltbeta receptor agonist . in other words , a chimeric ltbeta receptor agonist can include a portion that is distinct from a native wild type ltbeta receptor . specific examples include an antigen , ligand , receptor or an antibody that binds to an antibody , receptor , ligand or antigen present on a cell membrane . additional specific examples include protein a domains that bind immunoglobulin . peptides and peptidomimetics can be produced and isolated using methods known in the art . peptides can be synthesized , whole or in part , using chemical methods known in the art ( see , e . g ., caruthers ( 1980 ). nucleic acids res . symp . ser . 215 ; horn ( 1980 ); and banga , a . k ., therapeutic peptides and proteins , formulation , processing and delivery systems ( 1995 ) technomic publishing co ., lancaster , pa .). peptide synthesis can be performed using various solid - phase techniques ( see , e . g ., roberge science 269 : 202 ( 1995 ); merrifield , methods enzymol . 289 : 3 ( 1997 )) and automated synthesis may be achieved , e . g ., using the abi 431a peptide synthesizer ( perkin elmer ) in accordance with the manufacturer &# 39 ; s instructions . peptides and peptide mimetics can also be synthesized using combinatorial methodologies . synthetic residues and polypeptides incorporating mimetics can be synthesized using a variety of procedures and methodologies known in the art ( see , e . g ., organic syntheses collective volumes , gilman , et al . ( eds ) john wiley & amp ; sons , inc ., ny ). modified peptides can be produced by chemical modification methods ( see , for example , belousov , nucleic acids res . 25 : 3440 ( 1997 ); frenkel , free radic . biol . med . 19 : 373 ( 1995 ); and blommers , biochemistry 33 : 7886 ( 1994 ). the invention further provides nucleic acids encoding light ( p30 polypeptide ) variants and polymorphisms and subsequences thereof that are distinct from native naturally occurring light ( p30 polypeptide ) ( e . g ., seq id no : 1 ). nucleic acids also provided encode variants , polymorphic forms and subsequences of light ( p30 polypeptide ) that have reduced or exhibit no detectable binding to dcr3 , as compared to native naturally occurring light ( p30 polypeptide ) ( e . g ., seq id no : 1 ), but retain at least partial binding to one or more of lt beta receptor or hvem . nucleic acids further provided encode variants , polymorphic forms and subsequences of light ( p30 polypeptide ) that have increased or greater binding to one or more of ltbeta receptor and hvem , as compared to native naturally occurring light ( p30 polypeptide ) ( e . g ., seq id no : 1 ). in particular embodiments , a nucleic acid encodes any of seq id nos : 3 - 10 , or a subsequence thereof . in further embodiments , a nucleic acid is complementary to a nucleic acid sequence encoding any of seq id nos : 3 - 10 , or a subsequence thereof . nucleic acid , which can also be referred to herein as a gene , polynucleotide , nucleotide sequence , primer , oligonucleotide or probe refers to natural or modified purine - and pyrimidine - containing polymers of any length , either polyribonucleotides or polydeoxyribonucleotides or mixed polyribo - polydeoxyribo nucleotides and α - anomeric forms thereof . the two or more purine - and pyrimidine - containing polymers are typically linked by a phosphoester bond or analog thereof . the terms can be used interchangeably to refer to all forms of nucleic acid , including deoxyribonucleic acid ( dna ) and ribonucleic acid ( rna ). the nucleic acids can be single strand , double , or triplex , linear or circular . nucleic acids include genomic dna , cdna , and antisense . rna nucleic acid can be spliced or unspliced mrna , rrna , trna or antisense . nucleic acids include naturally occurring , synthetic , as well as nucleotide analogues and derivatives . as a result of the degeneracy of the genetic code , nucleic acids include sequences degenerate with respect to sequences encoding light ( p30 polypeptide ) variants and polymorphic forms of the invention . thus , degenerate nucleic acid sequences encoding light ( p30 polypeptide ) variants and polymorphisms and subsequences thereof that are distinct from native naturally occurring light ( p30 polypeptide ), for example , seq id no : 1 , are provided . nucleic acid can be produced using any of a variety of known standard cloning and chemical synthesis methods , and can be altered intentionally by site - directed mutagenesis or other recombinant techniques known to one skilled in the art . purity of polynucleotides can be determined through sequencing , gel electrophoresis , uv spectrometry . nucleic acids of the invention may be inserted into a nucleic acid construct in which expression of the nucleic acid is influenced or regulated by an “ expression control element ,” referred to herein as an “ expression cassette .” the term “ expression control element ” refers to one or more nucleic acid sequence elements that regulate or influence expression of a nucleic acid sequence to which it is operatively linked . an expression control element can include , as appropriate , promoters , enhancers , transcription terminators , gene silencers , a start codon ( e . g ., atg ) in front of a protein - encoding gene , etc . an expression control element operatively linked to a nucleic acid sequence controls transcription and , as appropriate , translation of the nucleic acid sequence . the term “ operatively linked ” refers to a juxtaposition wherein the referenced components are in a relationship permitting them to function in their intended manner . typically expression control elements are juxtaposed at the 5 ′ or the 3 ′ ends of the genes but can also be intronic . expression control elements include elements that activate transcription constitutively , that are inducible ( i . e ., require an external signal for activation ), or derepressible ( i . e ., require a signal to turn transcription off ; when the signal is no longer present , transcription is activated or “ derepressed ”). also included in the expression cassettes of the invention are control elements sufficient to render gene expression controllable for specific cell - types or tissues ( i . e ., tissue - specific control elements ). typically , such elements are located upstream or downstream ( i . e ., 5 ′ and 3 ′) of the coding sequence . promoters are generally positioned 5 ′ of the coding sequence . promoters , produced by recombinant dna or synthetic techniques , can be used to provide for transcription of the polynucleotides of the invention . a “ promoter ” is meant a minimal sequence element sufficient to direct transcription . nucleic acids may be inserted into a plasmid for propagation into a host cell and for subsequent genetic manipulation if desired . a plasmid is a nucleic acid that can be stably propagated in a host cell ; plasmids may optionally contain expression control elements in order to drive expression of the nucleic acid . a vector is used herein synonymously with a plasmid and may also include an expression control element for expression in a host cell . plasmids and vectors generally contain at least an origin of replication for propagation in a cell and a promoter . plasmids and vectors are therefore useful for genetic manipulation of peptide and antibody encoding nucleic acids , producing peptides and antibodies or antisense , and expressing the peptides and antibodies in host cells or organisms , for example . bacterial system promoters include t7 and inducible promoters such as pl of bacteriophage λ , plac , ptrp , ptac ( ptrp - lac hybrid promoter ) and tetracycline responsive promoters . insect cell system promoters include constitutive or inducible promoters ( e . g ., ecdysone ). mammalian cell constitutive promoters include sv40 , rsv , bovine papilloma virus ( bpv ) and other virus promoters , or inducible promoters derived from the genome of mammalian cells ( e . g ., metallothionein iia promoter ; heat shock promoter ) or from mammalian viruses ( e . g ., the adenovirus late promoter ; the inducible mouse mammary tumor virus long terminal repeat ). alternatively , a retroviral genome can be genetically modified for introducing and directing expression of a protein or antibody in appropriate host cells . expression systems further include vectors designed for in vivo use . particular non - limiting examples include adenoviral vectors ( u . s . pat . nos . 5 , 700 , 470 and 5 , 731 , 172 ), adeno - associated vectors ( u . s . pat . no . 5 , 604 , 090 ), herpes simplex virus vectors ( u . s . pat . no . 5 , 501 , 979 ), retroviral vectors ( u . s . pat . nos . 5 , 624 , 820 , 5 , 693 , 508 and 5 , 674 , 703 ), bpv vectors ( u . s . pat . no . 5 , 719 , 054 ) and cmv vectors ( u . s . pat . no . 5 , 561 , 063 ). yeast vectors include constitutive and inducible promoters ( see , e . g ., ausubel et al ., in : current protocols in molecular biology , vol . 2 , ch . 13 , ed ., greene publish . assoc . & amp ; wiley interscience , 1988 ; grant et al . methods in enzymology , 153 : 516 ( 1987 ), eds . wu & amp ; grossman ; bitter methods in enzymology , 152 : 673 ( 1987 ), eds . berger & amp ; kimmel , acad . press , n . y . ; and , strathern et al ., the molecular biology of the yeast saccharomyces ( 1982 ) eds . cold spring harbor press , vols . i and ii ). a constitutive yeast promoter such as adh or leu2 or an inducible promoter such as gal may be used ( r . rothstein in : dna cloning , a practical approach , vol . 11 , ch . 3 , ed . d . m . glover , irl press , wash ., d . c ., 1986 ). vectors that facilitate integration of foreign nucleic acid sequences into a yeast chromosome , via homologous recombination for example , are known in the art . yeast artificial chromosomes ( yac ) are typically used when the inserted polynucleotides are too large for more conventional vectors ( e . g ., greater than about 12 kb ). expression vectors also can contain a selectable marker conferring resistance to a selective pressure or identifiable marker ( e . g ., beta - galactosidase ), thereby allowing cells having the vector to be selected for , grown and expanded . alternatively , a selectable marker can be on a second vector that is cotransfected into a host cell with a first vector containing an invention polynucleotide . selection systems include but are not limited to herpes simplex virus thymidine kinase gene ( wigler et al ., cell 11 : 223 ( 1977 )), hypoxanthine - guanine phosphoribosyltransferase gene ( szybalska et al ., proc . natl . acad . sci . usa 48 : 2026 ( 1962 )), and adenine phosphoribosyltransferase ( lowy et al ., cell 22 : 817 ( 1980 )) genes which can be employed in tk −, hgprt − or aprt − cells , respectively . additionally , antimetabolite resistance can be used as the basis of selection for dhfr , which confers resistance to methotrexate ( o &# 39 ; hare et al ., proc . natl . acad . sci . usa 78 : 1527 ( 1981 )); the gpt gene , which confers resistance to mycophenolic acid ( mulligan et al ., proc . natl . acad . sci . usa 78 : 2072 ( 1981 )); neomycin gene , which confers resistance to aminoglycoside g - 418 ( colberre - garapin et al ., j . mol . biol . 150 : 1 ( 1981 )); puromycin ; and hygromycin gene , which confers resistance to hygromycin ( santerre et al ., gene 30 : 147 ( 1984 )). additional selectable genes include trpb , which allows cells to utilize indole in place of tryptophan ; hisd , which allows cells to utilize histinol in place of histidine ( hartman et al ., proc . natl . acad . sci . usa 85 : 8047 ( 1988 )); and odc ( ornithine decarboxylase ), which confers resistance to the ornithine decarboxylase inhibitor , 2 -( difluoromethyl )- dl - ornithine , dfmo ( mcconlogue ( 1987 ) in : current communications in molecular biology , cold spring harbor laboratory ). host cells that express a light ( p30 polypeptide ) variant or polymorphic amino acid sequence are also provided . such cells which have a nucleic acid encoding light ( p30 polypeptide ) variant or polymorphic amino acid sequence introduced into the cell are referred to as a transformed cell . host and transformed cells include cells that do not express light ( p30 polypeptide ) variant or polymorphic amino acid sequence , but are used to propagate nucleic acid or vector which includes a nucleic acid encoding a light ( p30 polypeptide ) variant or polymorphic amino acid sequence , or subsequence thereof . exemplary host and transformed cells express an amino acid sequence selected from any one of seq id nos : 3 to 10 . in one embodiment , a host or transformed cell is a prokaryotic cell . in another embodiment , a host or transformed cell is a eukaryotic cell . in various aspects , the eukaryotic cell is a yeast or mammalian ( e . g ., primate , human , etc .) cell . host and transformed cells include but are not limited to microorganisms such as bacteria and yeast ; and plant , insect and mammalian cells . for example , bacteria transformed with recombinant bacteriophage nucleic acid , plasmid nucleic acid or cosmid nucleic acid expression vectors ; yeast transformed with recombinant yeast expression vectors ; plant cell systems infected with recombinant virus expression vectors ( e . g ., cauliflower mosaic virus , camv ; tobacco mosaic virus , tmv ) or transformed with recombinant plasmid expression vectors ( e . g ., ti plasmid ); insect cell systems infected with recombinant virus expression vectors ( e . g ., baculovirus ); and animal cell systems infected with recombinant virus expression vectors ( e . g ., retroviruses , adenovirus , vaccinia virus ), or transformed animal cell systems engineered for transient or stable propagation or expression , are provided . cells in which an ltbeta receptor agonist has been attached , conjugated or coupled to the membrane of the cell or to an molecule present on the cell , such as light ( p30 polypeptide ), light ( p30 polypeptide ) chimeras , ltalpha1 beta2 , ltalpha2 beta1 , ltbeta or an ltbeta receptor antibody , light ( p30 polypeptide ) variants and polymorphisms and subsequences thereof , as well as nucleic acids encoding light ( p30 polypeptide ) variants and polymorphisms and subsequences thereof include isolated or purified forms . the term “ isolated ,” when used as a modifier of a composition , means that the composition is made by the hand of man or is separated , substantially completely or at least in part , from the naturally occurring in vivo environment . generally , an isolated composition is substantially free of one or more materials with which it normally associates with in nature , for example , one or more protein , nucleic acid , lipid , carbohydrate , cell membrane . the term “ isolated ” does not exclude alternative physical forms of the composition , such as multimers / oligomers , variants , modifications or derivatized forms , or forms expressed in host cells produced by the hand of man . the term “ isolated ” also does not exclude forms ( e . g ., pharmaceutical formulations and combination compositions ) in which there are combinations therein , any one of which is produced by the hand of man . an “ isolated ” composition can also be “ purified ” when free of some , a substantial number of , most or all of the materials with which it typically associates with in nature . thus , a light ( p30 polypeptide ) variant or polymorphism that also is substantially pure does not include polypeptides or polynucleotides present among millions of other sequences , such as proteins of a protein library or nucleic acids in a genomic or cdna library , for example . a “ purified ” composition can be combined with one or more other molecules . in accordance with the invention , there are provided mixtures or combination compositions . in one embodiment , a mixture includes two or more cells in which an ltbeta receptor agonist has been attached , conjugated or coupled , each of which cells optionally have a different ltbeta receptor agonist attached thereto . in another embodiment , a mixture includes two or more light ( p30 polypeptide ) sequences , such as a variant or polymorphism and a wild type light ( p30 polypeptide ), or a first light ( p30 polypeptide ) variant or polymorphism and a second light ( p30 polypeptide ) variant or polymorphism different from the first light ( p30 polypeptide ) variant or polymorphism . in a further embodiment , a mixture includes a pharmaceutically acceptable carrier or excipient , i . e ., a pharmaceutical composition or pharmaceutical formulation . compositions such as cells modified with an ltbeta receptor agonist and light ( p30 polypeptide ) variants and polymorphic amino acid sequences can be used to target undesirable , aberrant or abnormal cells , hyperproliferative cells such as tumor , cancer , neoplastic and metastatic cells , and pathogen infected cells for lysis , cell death or apoptosis . disorders treatable in accordance with the invention therefore include undesirable , aberrant or abnormal cell proliferation and hyperproliferative cells and disorders , for example , a subject having or at risk of undesirable , aberrant cell or abnormal hyperproliferative cells , tumor cells , cancer cells , neoplastic cells , metastatic cells , or pathogen infected cells . cells modified with an ltbeta receptor agonist include cells that express one or more antigens of the target undesirable , aberrant or abnormal cells or hyperproliferating cells , tumor cells , cancer cells , neoplastic cells , metastatic cells and pathogen infected cells are applicable in various methods . thus , to target undesirable , aberrant or abnormal cells , hyperproliferative cells , tumor , cancer , neoplastic and metastatic cells , these cells can be modified to have an ltbeta receptor agonist attached , conjugated or coupled to the cell membrane , and the modified cells are then in turn used to target the undesirable , aberrant or abnormal cells , hyperproliferative cells , tumor , cancer , neoplastic , metastatic or pathogen infected cells for lysis , cell death or apoptosis . in this way , cells so modified can be used to target the undesirable , aberrant or abnormal cells , hyperproliferative cells , tumor , cancer , neoplastic and metastatic cells , and pathogen infected cells . in accordance with the invention , there are provided methods of promoting , stimulating , inducing or increasing immunity against a hyperproliferative cell , tumor cell , cancer cell , neoplastic cell or metastatic cell , or pathogen infected cell . in one embodiment , a method includes administering to a subject or contacting a subject with an amount of a cell having ltbeta receptor agonist attached , conjugated or coupled to the cell membrane sufficient to promote , stimulate , induce or increase the subject &# 39 ; s immunity against the hyperproliferative cell , tumor cell , cancer cell , neoplastic cell metastatic cell or pathogen infected cell . in accordance with the invention , there are also provided methods of treating a subject for undesirable or abnormal hyperproliferative cells , tumor cells , cancer cells , neoplastic cells , metastatic cells , or pathogen infected cells . in one embodiment , a method includes administering to the subject or contacting a subject with an amount of a cell having ltbeta receptor agonist attached , conjugated or coupled to the cell membrane effective to treat the subject for undesirable or abnormal hyperproliferative cells , tumor cells , cancer cells , neoplastic cells , metastatic cells , or pathogen infected cells . in various aspects , the ltbeta receptor agonist includes light ( p30 polypeptide ), ltalpha1 beta2 , ltalpha2 beta1 , ltbeta or an ltbeta receptor antibody . in a particular aspect , an ltbeta receptor agonist includes light ( p30 polypeptide ) variant or polymorphic sequence , e . g ., light ( p30 polypeptide ) with increased or greater binding affinity for ltbeta receptor or hvem , or reduced or less binding affinity or avidity for dcr3 , such as any of seq id nos : 1 , 2 - 10 alone , or in combination . in an additional particular aspect , an antibody is an agonist that stimulates or increases activity of ltbeta receptor . the term “ hyperproliferative disorder ” refers to any undesirable , aberrant or abnormal cell survival ( e . g ., failure to undergo programmed cell death or apoptosis ), growth or proliferation . such disorders include benign hyperplasias , non - metastatic tumors and metastatic ( neoplastic ) tumors and cancers . undesirable , aberrant or abnormal cell proliferation and hyperproliferative disorders can affect any cell , tissue , organ , region or system in a subject . a tumor can arise from a multitude of tissues and organs , including but not limited to breast , lung , nasopharynx , thyroid , head and neck , brain , lymphoid , gastrointestinal ( mouth , esophagus , stomach , small intestine , colon , rectum ), genito - urinary tract ( uterus , ovary , cervix , bladder , vagina , testicle , penis , prostate ), kidney , pancreas , liver , bone , muscle , skin , which may or may not metastasize to other secondary sites . undesirable or aberrant cell proliferation and hyperproliferative disorders can affect any cell or tissue type , e . g ., carcinoma , sarcoma , melanoma , neural , and reticuloendothelial or hematopoietic neoplastic cells and disorders ( e . g ., myeloma , lymphoma or leukemia ). undesirable or aberrant cell proliferation and hyperproliferative disorders can be present in a subject locally , regionally or systemically . the terms “ tumor ,” “ cancer ” and “ neoplasia ” are used interchangeably and refer to a cell or population of cells whose growth , proliferation or survival is greater than growth , proliferation or survival of a normal counterpart cell , e . g . a cell proliferative or differentiative disorder . typically , the growth is uncontrolled . the term “ malignancy ” refers to invasion of nearby tissue . the term “ metastasis ” refers to spread or dissemination of a tumor , cancer or neoplasia to more distal tissues or sites within the subject . the term “ pathogen infected cell ” refers to cells such as a autologous human blood cell infected with a virus , or is induced ( transformed ) to express a viral , bacterial or parasite ( pathogen ) gene or genes that may stimulate immunity when that cell also has attached , conjugated or coupled thereto an ltbeta receptor agonist . administering such pathogen infected cells that have attached , conjugated or coupled thereto an ltbeta receptor agonist allows the expressed pathogen antigens to induce an immune response ( e . g ., protective immunity ) against the antigen . the term “ contacting ” means direct or indirect binding or interaction between two or more entities ( e . g ., between ltbeta receptor and an agonist , a cell in which ltbeta receptor agonist has been attached , conjugated or coupled to the membrane and a subject , etc .). contacting as used herein includes in solution , in solid phase , in vitro , ex vivo , in a cell and in vivo . contacting in vivo can be referred to as administering , or administration . cells comprising a tumor may be aggregated in a cell mass or be dispersed . a “ solid tumor ” refers to neoplasia or metastasis that typically aggregates together and forms a mass . specific non - limiting examples include visceral tumors such as melanomas , breast , pancreatic , uterine and ovarian cancers , testicular cancer , including seminomas , gastric or colon cancer , hepatomas , adrenal , renal and bladder carcinomas , lung , head and neck cancers and brain tumors / cancers . carcinomas , which refer to malignancies of epithelial or endocrine tissue , include respiratory system carcinomas , gastrointestinal system carcinomas , genitourinary system carcinomas , testicular carcinomas , breast carcinomas , prostatic carcinomas , endocrine system carcinomas , and melanomas . exemplary carcinomas include those forming from the uterus , cervix , lung , prostate , breast , head and neck , colon , pancreas , testes , adrenal , kidney , esophagus , stomach , liver and ovary . the term also includes carcinosarcomas , e . g ., which include malignant tumors composed of carcinomatous and sarcomatous tissues . adenocarcinoma includes a carcinoma of a glandular tissue , or in which the tumor forms a gland like structure . sarcomas refer to malignant tumors of mesenchymal cell origin . exemplary sarcomas include for example , lymphosarcoma , liposarcoma , osteosarcoma , chondrosarcoma , leiomyosarcoma , rhabdomyosarcoma and fibrosarcoma . a “ liquid tumor ,” which refers to neoplasia that is diffuse in nature , as they do not typically form a solid mass . particular examples include neoplasia of the reticuloendothelial or hematopoetic system , such as lymphomas , myelomas and leukemias . non - limiting examples of leukemias include acute and chronic lymphoblastic , myeolblastic and multiple myeloma . typically , such diseases arise from poorly differentiated acute leukemias , e . g ., erythroblastic leukemia and acute megakaryoblastic leukemia . specific myeloid disorders include , but are not limited to , acute promyeloid leukemia ( apml ), acute myelogenous leukemia ( aml ) and chronic myelogenous leukemia ( cml ). lymphoid malignancies include , but are not limited to , acute lymphoblastic leukemia ( all ), which includes b - lineage all and t - lineage all , chronic lymphocytic leukemia ( cll ), prolymphocytic leukemia ( pll ), hairy cell leukemia ( hll ) and waldenstrom &# 39 ; s macroglobulinemia ( wm ). specific malignant lymphomas include , non - hodgkin lymphoma and variants , peripheral t cell lymphomas , adult t cell leukemia / lymphoma ( atl ), cutaneous t - cell lymphoma ( ctcl ), large granular lymphocytic leukemia ( lgf ), hodgkin &# 39 ; s disease and reed - sternberg disease . the tumor , cancer , malignancy or neoplasia , may be in any stage , e . g ., early or advanced , such as a stage i , ii , iii , iv or v tumor . the tumor may have been subject to a prior treatment or be stabilized ( non - progressing ) or in remission . cells in which ltbeta receptor agonist has been attached , conjugated or coupled to the membrane , light ( p30 polypeptide ) variants and polymorphic forms , and methods of the invention include anti - proliferative , anti - tumor , anti - cancer , anti - neoplastic treatments , protocols and therapies , which include any other composition , treatment , protocol or therapeutic regimen that inhibits , decreases , retards , slows , reduces or prevents a hyperproliferative disorder , such as tumor , cancer , malignant or neoplastic growth , progression , metastasis , proliferation or survival , or worsening in vitro or in vivo . particular non - limiting examples of an anti - proliferative ( e . g ., tumor or cancer ) therapy include chemotherapy , immunotherapy , radiotherapy ( ionizing or chemical ), local thermal ( hyperthermia ) therapy and surgical resection . any composition , treatment , protocol , therapy or regimen having an anti - cell proliferative activity or effect can be used in combination with a cell in which ltbeta receptor agonist has been attached , light ( p30 polypeptide ) variants and polymorphic forms , in a method of the invention . anti - proliferative or anti - tumor compositions , therapies , protocols or treatments include those that prevent , disrupt , interrupt , inhibit or delay cell cycle progression or cell proliferation ; stimulate or enhance apoptosis or cell death , inhibit nucleic acid or protein synthesis or metabolism , inhibit cell division , or decrease , reduce or inhibit cell survival , or production or utilization of a necessary cell survival factor , growth factor or signaling pathway ( extracellular or intracellular ). non - limiting examples of chemical agent classes having anti - cell proliferative and anti - tumor activities include alkylating agents , anti - metabolites , plant extracts , plant alkaloids , nitrosoureas , hormones , nucleoside and nucleotide analogues . specific examples of drugs having anti - cell proliferative and anti - tumor activities include cyclophosphamide , azathioprine , cyclosporin a , prednisolone , melphalan , chlorambucil , mechlorethamine , busulphan , methotrexate , 6 - mercaptopurine , thioguanine , 5 - fluorouracil , cytosine arabinoside , azt , 5 - azacytidine ( 5 - azc ) and 5 - azacytidine related compounds such as decitabine ( 5 - aza - 2 ′ deoxycytidine ), cytarabine , 1 - beta - d - arabinofuranosyl - 5 - azacytosine and dihydro - 5 - azacytidine , bleomycin , actinomycin d , mithramycin , mitomycin c , carmustine , lomustine , semustine , streptozotocin , hydroxyurea , cisplatin , mitotane , procarbazine , dacarbazine , taxol , vinblastine , vincristine , doxorubicin and dibromomannitol . additional agents that are applicable with the compositions and methods can be employed . for example , monoclonal antibodies that bind tumor cells or oncogene products , such as rituxan ® and herceptin ( trastuzumab )( anti - her - 2 neu antibody ), bevacizumab ( avastin ), zevalin , bexxar , oncolym , 17 - 1a ( edrecolomab ), 3f8 ( anti - neuroblastoma antibody ), mdx - ctla4 , campath ®, mylotarg , imc - c225 ( cetuximab ), aurinstatin conjugates of cbr96 and cac10 ( doronina et al . nat . biotechnol . 21 : 778 ( 2003 )) can be used in combination with , inter alia , a modified cell or light ( p30 polypeptide ) variant or polymorphic form in accordance with the invention . methods of treating a tumor , cancer , neoplasia malignancy , or pathogen infected cells , methods of treating a subject in need of due to having or at risk of having a tumor , cancer , neoplasia , malignancy , or pathogen infected cells and methods of increasing effectiveness or improving an anti - tumor , anti - cancer , anti - neoplasia , anti - malignancy , or anti - pathogen infected cell therapy are provided . in respective embodiments , a method includes administering to a subject with or at risk of a tumor , cancer , neoplasia , malignancy , or pathogen infected cells an amount of cell in which ltbeta receptor agonist has been attached , conjugated or coupled to the membrane of the cell , or an amount of a variant and polymorphic form of light ( p30 polypeptide ), sufficient to treat the tumor , cancer , neoplasia , malignancy or pathogen infected cells ; administering to the subject an amount of a cell in which ltbeta receptor agonist has been attached , conjugated or coupled to the membrane of the cell , or a light ( p30 polypeptide ) variant or polymorphic form , sufficient to treat the subject ; and administering to a subject that is undergoing or has undergone tumor , cancer , neoplasia , malignancy therapy or therapy for pathogen infected cells , an amount of a cell in which ltbeta receptor agonist has been attached , conjugated or coupled to the membrane of the cell , or variant or polymorphic form of light ( p30 polypeptide ), sufficient to increase effectiveness of the anti - tumor , anti - cancer , anti - neoplasia , anti - malignancy or anti - pathogen infected cell therapy . methods of the invention may be practiced prior to ( i . e . prophylaxis ), concurrently with or after evidence of the presence of undesirable , aberrant or abnormal cell proliferation or a hyperproliferative disorder , or pathogen infected cells e . g ., one or more symptoms . administering cells in which ltbeta receptor agonist has been attached , conjugated or coupled to the membrane , or a light ( p30 polypeptide ) variant or polymorphic form , prior to , concurrently with or immediately following development of a symptom of undesirable , aberrant or abnormal cell proliferation , a hyperproliferative disorder or pathogen infected cells may decrease the occurrence , frequency , severity , progression , or duration of one or more symptoms in the subject . in addition , administering cells in which ltbeta receptor agonist has been attached , conjugated or coupled to the membrane , or a light ( p30 polypeptide ) variant or polymorphic form , prior to , concurrently with or immediately following development of one or more symptoms may decrease or prevent the spread of hyperproliferating cells ( e . g ., tumor or cancer metastasis ) or pathogen infected cells to other regions , tissues or organs in a subject . cells having ltbeta receptor attached , conjugated or coupled to the membrane , light ( p30 polypeptide ) variants and polymorphic forms , and the methods of the invention , such as treatment methods , can provide a detectable or measurable therapeutic benefit or improvement to a subject . a therapeutic benefit or improvement is any measurable or detectable , objective or subjective , transient , temporary , or longer - term benefit to the subject or improvement in the condition , disorder or disease , an adverse symptom , consequence or underlying cause , of any degree , in a tissue , organ , cell or cell population of the subject . therapeutic benefits and improvements include , but are not limited to , reducing or decreasing occurrence , frequency , severity , progression , or duration of one or more symptoms or complications associated with a disorder , disease or condition , or an underlying cause or consequential effect of the disorder , disease or condition . cells having ltbeta receptor attached , conjugated or coupled to the membrane , light ( p30 polypeptide ) variants and polymorphic forms , and methods of the invention therefore include providing a therapeutic benefit or improvement to a subject . in a method of the invention in which a therapeutic benefit or improvement is a desired outcome , cells in which ltbeta receptor agonist has been attached , conjugated or coupled to the membrane , or light ( p30 polypeptide ) variants and polymorphic forms , can be administered in a sufficient or effective amount to a subject in need thereof . an “ amount sufficient ” or “ amount effective ” refers to an amount that provides , in single or multiple doses , alone or in combination , with one or more other compositions ( therapeutic agents such as a chemotherapeutic or immune stimulating drug ), treatments , protocols , or therapeutic regimens agents , a detectable response of any duration of time ( long or short term ), a desired outcome in or a benefit to a subject of any measurable or detectable degree or for any duration of time ( e . g ., for hours , days , months , years , or cured ). the doses or “ sufficient amount ” or “ effective amount ” for treatment ( e . g ., to provide a therapeutic benefit or improvement ) typically are effective to ameliorate a disorder , disease or condition , or one , multiple or all adverse symptoms , consequences or complications of the disorder , disease or condition , to a measurable extent , although reducing or inhibiting a progression or worsening of the disorder , disease or condition or a symptom , is considered a satisfactory outcome . the term “ ameliorate ” means a detectable objective or subjective improvement in a subject &# 39 ; s condition . a detectable improvement includes a subjective or objective reduction in the occurrence , frequency , severity , progression , or duration of a symptom caused by or associated with a disorder , disease or condition , an improvement in an underlying cause or a consequence of the disorder , disease or condition , or a reversal of the disorder , disease or condition . treatment can therefore result in inhibiting , reducing or preventing a disorder , disease or condition , or an associated symptom or consequence , or underlying cause ; inhibiting , reducing or preventing a progression or worsening of a disorder , disease , condition , symptom or consequence , or underlying cause ; or further deterioration or occurrence of one or more additional symptoms of the disorder , disease condition , or symptom . thus , a successful treatment outcome leads to a “ therapeutic effect ,” or “ benefit ” or inhibiting , reducing or preventing the occurrence , frequency , severity , progression , or duration of one or more symptoms or underlying causes or consequences of a condition , disorder , disease or symptom in the subject . treatment methods affecting one or more underlying causes of the condition , disorder , disease or symptom are therefore considered to be beneficial . stabilizing or inhibiting progression or worsening of a disorder or condition is also a successful treatment outcome . a therapeutic benefit or improvement therefore need not be complete ablation of any one , most or all symptoms , complications , consequences or underlying causes associated with the condition , disorder or disease . thus , a satisfactory endpoint is achieved when there is an incremental improvement in a subject &# 39 ; s condition , or a partial reduction in the occurrence , frequency , severity , progression , or duration , or inhibition or reversal , of one or more associated adverse symptoms or complications or consequences or underlying causes , worsening or progression ( e . g ., stabilizing one or more symptoms or complications of the condition , disorder or disease ), of one or more of the physiological , biochemical or cellular manifestations or characteristics of the disorder or disease , over a short or long duration of time ( hours , days , weeks , months , etc .). an amount sufficient or an amount effective can but need not be provided in a single administration and , can but need not be , administered alone or in combination with another composition ( e . g ., chemotherapeutic or immune stimulating agent ), treatment , protocol or therapeutic regimen . for example , the amount may be proportionally increased as indicated by the need of the subject , status of the disorder , disease or condition treated or the side effects of treatment . in addition , an amount sufficient or an amount effective need not be sufficient or effective if given in single or multiple doses without a second composition ( e . g ., chemotherapeutic or immune stimulating agent ), treatment , protocol or therapeutic regimen , since additional doses , amounts or duration above and beyond such doses , or additional compositions ( e . g ., chemotherapeutic or immune stimulating agents ), treatments , protocols or therapeutic regimens may be included in order to be considered effective or sufficient in a given subject . amounts considered sufficient also include amounts that result in a reduction of the use of another treatment , therapeutic regimen or protocol . an amount sufficient or an amount effective need not be effective in each and every subject treated , prophylactically or therapeutically , nor a majority of treated subjects in a given group or population . as is typical for treatment or therapeutic methods , some subjects will exhibit greater or less response to a given treatment , therapeutic regimen or protocol . an amount sufficient or an amount effective refers to sufficiency or effectiveness in a particular subject , not a group or the general population . such amounts will depend in part upon the condition treated , such as the type or stage of undesirable , aberrant or abnormal cell proliferation or hyperproliferative disorder ( e . g ., a cancer , tumor , neoplasia or malignancy ), or pathogen infected cell , the therapeutic effect desired , as well as the individual subject ( e . g ., the bioavailability within the subject , responsiveness of the subject , gender , age , etc .). particular non - limiting examples of therapeutic benefit or improvement for undesirable , aberrant or abnormal cell proliferation , such as a hyperproliferative disorder ( e . g ., a cancer , tumor , neoplasia or malignancy ) or pathogen infected cells , include a reduction in size , mass or volume , inhibiting or preventing an increase in size , mass or volume , or increased numbers or metastasis of hyperproliferative cells ( e . g ., tumor cells , cancer cells , neoplastic cells , metastatic cells ), or pathogen infected cells , a slowing or inhibition of worsening or progression , stimulating cell lysis or apoptosis , decreasing , reducing or inhibiting proliferation or numbers of the hyperproliferative cells , tumor cells , cancer cells , neoplastic cells , metastatic cells , or pathogen infected cells , or decreasing , reducing or inhibiting tumor or cancer metastasis , or stabilizing numbers of hyperproliferative cells ( e . g ., tumor cells , cancer cells , neoplastic cells , metastatic cells ), or pathogen infected cells , reducing mortality , and prolonging lifespan of a subject . thus , inhibiting or delaying an increase in size , mass , volume or metastasis ( stabilization ) can increase lifespan ( reduce mortality ) even if only for a few days , weeks or months , even though complete ablation of the cancer , tumor , neoplasia , malignancy or pathogen infected cells has not occurred . a reduction in the occurrence , frequency , severity , progression , or duration of a symptom of undesirable , aberrant or abnormal cell proliferation , such as a hyperproliferative disorder ( e . g ., a cancer , tumor , neoplasia or malignancy ), or pathogen infected cells , such as an improvement in subjective feeling ( e . g ., increased energy , appetite , reduced nausea , improved mobility or psychological well being , etc . ), are all examples of therapeutic benefit or improvement . adverse symptoms and complications associated with a hyperproliferative disorder ( e . g ., a cancer , tumor , neoplasia or malignancy ) that can be reduced or decreased include , for example , pain , nausea , lack of appetite , lethargy and weakness . for example , a sufficient or effective amount of cells in which ltbeta receptor agonist has been attached , conjugated or coupled to the membrane , or a light ( p30 polypeptide ) variant or polymorphic form , is considered as having a therapeutic effect if administration results in less chemotherapeutic drug , radiation , immunotherapy or pathogen therapy being required for treatment of undesirable , aberrant or abnormal cell proliferation , such as a hyperproliferative disorder ( e . g ., a cancer , tumor , neoplasia or malignancy ) or pathogen infected cells . the term “ subject ” refers to animals , typically mammalian animals , such as humans , non human primates ( apes , gibbons , chimpanzees , orangutans , macaques ), domestic animals ( dogs and cats ), farm animals ( horses , cows , goats , sheep , pigs ) and experimental animal ( mouse , rat , rabbit , guinea pig ). subjects include animal disease models , for example , animal models of undesirable or aberrant cell proliferation , such as a hyperproliferative disorder ( e . g ., a cancer , tumor , neoplasia or malignancy ) or pathogen infected cells for analysis or study in vivo . subjects appropriate for treatment include those having or at risk of having undesirable , aberrant or abnormal cells , such as tumor , cancer , neoplastic , malignant or metastatic cells , or pathogen infected cells , those undergoing as well as those who are undergoing or have undergone anti - tumor , anti - cancer , anti - neoplastic , anti - malignant or anti - metastatic cells , or anti - pathogen infected cells therapy , including subjects in remission . the invention is therefore applicable to treating a subject who is at risk of undesirable , aberrant or abnormal cells , a tumor , cancer , neoplastic , malignancy or metastasis , or pathogen infected cells or an associated complication , for example , due to reappearance or regrowth following a period of quiescence or remission . “ at risk ” subjects typically have risk factors associated with undesirable or aberrant immune response , immune disorder or immune disease , development of hyperplasia ( e . g ., a cancer or tumor ), or exposure to or contact with a pathogen . risk factors include gender , lifestyle ( diet , smoking ), occupation ( medical and clinical personnel , agricultural and livestock workers ), environmental factors ( carcinogen exposure ), family history ( autoimmune disorders , diabetes , etc . ), genetic predisposition , exposure , etc . for example , subjects at risk for developing melanoma include excess sun exposure ( ultraviolet radiation ), fair skin , high numbers of naevi ( dysplastic nevus ), patient phenotype , family history , or a history of a previous melanoma . subjects at risk for developing cancer can therefore be identified by lifestyle , occupation , environmental factors , family history , and genetic screens for tumor associated genes , gene deletions or gene mutations . subjects at risk for developing breast cancer lack brca1 , for example . subjects at risk for developing colon cancer have early age or high frequency polyp formation , or deleted or mutated tumor suppressor genes , such as adenomatous polyposis coli ( apc ), for example . subjects at risk for immunodeficiency with hyper - igm ( him ) have a defect in the gene tnfsf5 , found on chromosome x at q26 , for example . susceptibility to autoimmune disease is frequently associated with mhc genotype . for example , in diabetes there is an association with hla - dr3 and hla - dr4 . compositions , including cells in which ltbeta receptor agonist has been attached , conjugated or coupled to the membrane of the cell , light ( p30 polypeptide ) variants and polymorphic forms , can be administered to provide the intended effect as a single or multiple , for example , in an effective or sufficient amount . exemplary dosages are administered on consecutive days , or alternating days or intermittently . single or multiple doses can be administered on the same or consecutive days , alternating days or intermittently . compositions can be administered and methods may be practiced via systemic , regional or local administration , by any route . for example , cells in which ltbeta receptor agonist has been attached , or light ( p30 polypeptide ) variants and polymorphic forms , may be administered systemically , regionally or locally , intravenously , orally ( e . g ., ingestion or inhalation ), intramuscularly , intraperitoneally , intradermally , subcutaneously , intracavity , intracranially , transdermally ( topical ), parenterally , e . g . transmucosally or rectally . compositions and methods of the invention including pharmaceutical formulations can be administered via a ( micro ) encapsulated delivery system or packaged into an implant for administration . the invention further provides cells in which ltbeta receptor agonist has been attached , conjugated or coupled to the membrane , light ( p30 polypeptide ) variants and polymorphic forms , and light ( p30 polypeptide ) chimeras , included in pharmaceutical compositions and formulations . a pharmaceutical composition refers to “ pharmaceutically acceptable ” and “ physiologically acceptable ” carriers , diluents or excipients . as used herein , the term “ pharmaceutically acceptable ” and “ physiologically acceptable ,” when referring to carriers , diluents or excipients includes solvents ( aqueous or non - aqueous ), detergents , solutions , emulsions , dispersion media , coatings , isotonic and absorption promoting or delaying agents , compatible with pharmaceutical administration and with the other components of the formulation . such formulations can be contained in a tablet ( coated or uncoated ), capsule ( hard or soft ), microbead , emulsion , powder , granule , crystal , suspension , syrup or elixir . pharmaceutical compositions can be formulated to be compatible with a particular route of administration . compositions for parenteral , intradermal , or subcutaneous administration can include a sterile diluent , such as water , saline solution , fixed oils , polyethylene glycols , glycerine , propylene glycol or other synthetic solvents . the preparation may contain one or more preservatives to prevent microorganism growth ( e . g ., antibacterial agents such as benzyl alcohol or methyl parabens ; antioxidants such as ascorbic acid or sodium bisulfate ; chelating agents such as ethylenediaminetetraacetic acid ; buffers such as acetates , citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose ). pharmaceutical compositions for injection include sterile aqueous solutions ( where water soluble ) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion . for intravenous administration , suitable carriers include physiological saline , bacteriostatic water , cremophor el ™ ( basf , parsippany , n . j .) or phosphate buffered saline ( pbs ). the carrier can be a solvent or dispersion medium containing , for example , water , ethanol , polyol ( e . g ., glycerol , propylene glycol , and polyetheylene glycol ), and suitable mixtures thereof . fluidity can be maintained , for example , by the use of a coating such as lecithin , or by the use of surfactants . antibacterial and antifungal agents include , for example , parabens , chlorobutanol , phenol , ascorbic acid and thimerosal . including an agent that delays absorption , for example , aluminum monostearate and gelatin can prolonged absorption of injectable compositions . for transmucosal or transdermal administration , penetrants appropriate to the barrier to be permeated are used in the formulation . such penetrants are known in the art , and include , for example , for transmucosal administration , detergents , bile salts , and fusidic acid derivatives ; for transdermal administration , ointments , salves , gels , or creams . additional pharmaceutical formulations and delivery systems are known in the art and are applicable in the methods of the invention ( see , e . g ., remington &# 39 ; s pharmaceutical sciences ( 1990 ) 18th ed ., mack publishing co ., easton , pa . ; the merck index ( 1996 ) 12th ed ., merck publishing group , whitehouse , n . j . ; pharmaceutical principles of solid dosage forms , technonic publishing co ., inc ., lancaster , pa ., ( 1993 ); and poznansky , et al ., drug delivery systems , r . l . juliano , ed ., oxford , n . y . ( 1980 ), pp . 253 - 315 ). in accordance with the invention , there are provided , methods of producing a cell having an ltbeta receptor agonist attached , conjugated or coupled to the membrane of the cell ( e . g ., to a molecule present on the cell membrane , such as a polypeptide , or carbohydrate ). in one embodiment , a method includes contacting a cell with ltbeta receptor agonist under conditions allowing binding between said cell and said ltbeta receptor agonist ( e . g ., via an intermediary molecule ), thereby producing a cell having ltbeta receptor agonist attached , conjugated or coupled to the membrane of the cell . in a particular aspect , the ltbeta receptor agonist is not expressed from a nucleic acid in the cell that encodes the ltbeta receptor agonist , but rather is attached , conjugated or coupled to the membrane via a covalent or non - covalent bond . in another embodiment , a method includes contacting a cell with a light ( p30 polypeptide ) variant or polymorphic form under conditions allowing binding between the light ( p30 polypeptide ) variant or polymorphic form , thereby producing a cell having light ( p30 polypeptide ) variant or polymorphic form attached , conjugated or coupled to the membrane of the cell . in a particular aspect of this embodiment , the light ( p30 polypeptide ) variant or polymorphic form is expressed from a nucleic acid in the cell that encodes the light ( p30 polypeptide ) variant or polymorphic form . in particular aspects , an ltbeta receptor agonist includes one or more of light ( p30 polypeptide ), ltalpha1 beta2 , ltalpha2 beta1 , ltbeta or an ltbeta receptor antibody , or a chimeric protein which comprises a binding portion , such as a ligand , receptor or antibody or antibody subsequence that binds to a molecule present on the cell membrane . in more particular aspects , light ( p30 polypeptide ) includes a full length amino acid sequence , an extracellular amino acid sequence of light ( e . g ., as set forth in seq id no : 1 ), or a soluble form of light ( e . g ., lightt66 , or as set forth in seq id no : 2 ). in additional particular aspects , light ( p30 polypeptide ) includes light ( p30 polypeptide ) amino acid sequence with reduced affinity for dcr3 ( decoy receptor 3 ) as compared to native wild type light ( p30 polypeptide ), a light ( p30 polypeptide ) amino acid sequence with greater affinity for ltβr or hvem as compared to native wild type light ( p30 polypeptide ), or a light ( p30 polypeptide ) amino acid sequence with greater affinity for ltβr or hvem and with reduced affinity for dcr3 ( decoy receptor 3 ) as compared to native wild type light ( p30 polypeptide ), for example , a light ( p30 polypeptide ) amino acid sequence selected from any one of seq id nos : 3 to 10 . in further particular aspects , the cell is a hyperproliferative cell , a tumor cell , cancer cell , neoplastic cell , a metastatic cell or a pathogen infected cell , or the cells expresses a molecule selected from a tumor cell or a cancer cell antigen , a neoplastic cell or a metastatic cell antigen , a viral antigen , a bacterial antigen , a fungal antigen , or a parasite antigen . cells may be eukaryotic , mammalian ( e . g ., human ) cells , that may be dead or alive . in additional particular aspects , the cell is contacted with a first moiety ( e . g ., biotin or a biotin derivative ) followed by contact with a second moiety ( e . g ., avidin , neutravidin or streptavidin , or a derivative or amino acid variant thereof ) thereby producing a molecule comprising a first moiety bound to the cell , and a second moiety bound to the first moiety , said moieties comprising an intermediary molecule . in still further particular aspects , the ltbeta receptor agonist binding to the cell membrane occurs via binding to an antibody present on the cell membrane , the ltbeta receptor agonist binds to the cell membrane via cross - linking the ltbeta receptor agonist to a molecule ( e . g ., protein or carbohydrate ) on the cell membrane . the invention provides kits including a cell having an ltbeta receptor agonist attached , conjugated or coupled to the membrane , light ( p30 polypeptide ) variants or polymorphic forms , combination compositions and pharmaceutical formulations thereof , packaged into suitable packaging material . a kit optionally includes a label or packaging insert including a description of the components or instructions for use in vitro , in vivo , or ex vivo , of the components therein . exemplary instructions include instructions for reducing or inhibiting proliferation of a cell , reducing or inhibiting proliferation of a hyperproliferating cell , reducing or inhibiting proliferation of a neoplastic , tumor or cancer cell , malignancy or metastasis , or pathogen infected cell , treating a subject having a hyperproliferative disorder , treating a subject having a metastatic or non - metastatic neoplasia , tumor , cancer , or malignancy , or pathogen infected cells . the term “ packaging material ” refers to a physical structure housing the components of the kit . the packaging material can maintain the components sterilely , and can be made of material commonly used for such purposes ( e . g ., paper , corrugated fiber , glass , plastic , foil , ampules , vials , tubes , etc .). kits of the invention can include labels or inserts . labels or inserts include “ printed matter ,” e . g ., paper or cardboard , or separate or affixed to a component , a kit or packing material ( e . g ., a box ), or attached to an ampule , tube or vial containing a kit component . labels or inserts can additionally include a computer readable medium , such as a disk ( e . g ., floppy diskette , hard disk , zip disk ), optical disk such as cd - or dvd - rom / ram , dvd , mp3 , magnetic tape , or an electrical storage media such as ram and rom or hybrids of these such as magnetic / optical storage media , flash media or memory type cards . labels or inserts can include identifying information of one or more components therein , dose amounts , clinical pharmacology of the active ingredient ( s ) including mechanism of action , pharmacokinetics and pharmacodynamics . labels or inserts can include information identifying manufacturer information , lot numbers , manufacturer location and date . labels or inserts can include information on a condition , disorder , disease or symptom for which a kit component may be used . labels or inserts can include instructions for the clinician or for a subject for using one or more of the kit components in a method , treatment protocol or therapeutic regimen . instructions can include dosage amounts , frequency or duration , and instructions for practicing any of the methods , treatment protocols or therapeutic regimes set forth herein . exemplary instructions include instructions for treating undesirable , aberrant or abnormal cells , a hyperproliferative disorder or pathogen infected cells . kits of the invention therefore can additionally include labels or instructions for practicing any of the methods of the invention described herein including treatment , detection , monitoring or diagnostic methods . labels or inserts can include information on any benefit that a component may provide , such as a prophylactic or therapeutic benefit . labels or inserts can include information on potential adverse side effects , such as warnings to the subject or clinician regarding situations where it would not be appropriate to use a particular composition . adverse side effects could also occur when the subject has , will be or is currently taking one or more other medications that may be incompatible with the composition , or the subject has , will be or is currently undergoing another treatment protocol or therapeutic regimen which would be incompatible with the composition and , therefore , instructions could include information regarding such incompatibilities . invention kits can additionally include other components . each component of the kit can be enclosed within an individual container and all of the various containers can be within a single package . invention kits can be designed for cold storage . invention kits can further be designed to contain host cells expressing peptides or antibodies of the invention , or that contain encoding nucleic acids . the cells in the kit can be maintained under appropriate storage conditions until the cells are ready to be used . for example , a kit including one or more cells can contain appropriate cell storage medium so that the cells can be thawed and grown . unless otherwise defined , all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs . although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention , suitable methods and materials are described herein . all applications , publications , patents and other references , genbank citations and atcc citations cited herein are incorporated by reference in their entirety . in case of conflict , the specification , including definitions , will control . as used herein , the singular forms “ a ”, “ and ,” and “ the ” include plural referents unless the context clearly indicates otherwise . thus , for example , reference to “ a cell in which ltbeta receptor agonist has been attached , conjugated or coupled to the membrane ” or a “ light ( p30 polypeptide ) variant or polymorphic form ” includes a plurality of such cells , variants or polymorphic forms , and so forth . as used herein , all numerical values or numerical ranges include integers within such ranges and fractions of the values or the integers within ranges unless the context clearly indicates otherwise . thus , for example , reference to a range of 90 - 100 %, includes 91 %, 92 %, 93 %, 94 %, 95 %, 95 %, 97 %, etc ., as well as 91 . 1 %, 91 . 2 %, 91 . 3 %, 91 . 4 %, 91 . 5 %, etc ., 92 . 1 %, 92 . 2 %, 92 . 3 %, 92 . 4 %, 92 . 5 %, etc ., and so forth . the invention is generally disclosed herein using affirmative language to describe the numerous embodiments . the invention also specifically includes embodiments in which particular subject matter is excluded , in full or in part , such as substances or materials , method steps and conditions , protocols , procedures , assays or analysis . thus , even though the invention is generally not expressed herein in terms of what the invention does not include , aspects that are not expressly included in the invention are nevertheless disclosed herein . a number of embodiments of the invention have been described . nevertheless , it will be understood that various modifications may be made without departing from the spirit and scope of the invention . accordingly , the following examples are intended to illustrate but not limit the scope of invention described in the claims . biotin based immobilization of light on tumor cells : a schematic illustration for the assembling of a light decorated cancer cells ( fig1 ) shows the procedure involves three successive steps : ( i ) biotinylation of cancer cells , ( ii ) biotinylation of soluble light , and ( iii ) immobilization of soluble light on the biotinylated cancer cells . aseptic techniques are required throughout the procedures . biotinylation of cancer cells : the source of cancer cells can be purified from wide variety of malignant tissues after tumor resection ( greiner , et al ., j lab clin med 109 : 244 ( 1987 ); and o &# 39 ; brien , et al ., cytometry 28 : 81 ( 1997 ). in this preparation , we used el4 cells . 50 × 10 6 of el4 cells were washed 3 times with ice - cold dulbecco &# 39 ; s phosphate buffer saline ( pbs ) ph 8 . 0 ( invitrogen corporation , usa ; cat . # 14190 - 144 ) to remove any contaminating proteins from the tissue culture media . the cells were equally divided into 2 tubes ( 25 × 10 6 cells / tube ), and were resuspended in 1 ml pbs ( ph 8 . 0 ). a commercially available biotinylation reagent , nhs - peo4 - biotin ( pierce , ill ., usa ; cat . # 21329 ), was used in this labeling reaction . immediately before use , 200 μl of ultrapure distilled water ( invitrogen corporation , cat . # 10977 - 015 ) was added to 2 mg of nhs - peo4 - biotin , and 50 μl of the nhs - peo4 - biotin solution was added to each tube containing 25 × 10 6 el4 cells . the samples were incubated at room temperature for 30 minutes with intermittent mixing in every 5 minutes . the cells were then washed 3 times with 1 ml cold pbs ( ph 8 . 0 ) to remove non - reacted biotinylation reagent . the prepared el4 cells were fixed in 1 % formalin ( protocol ™, usa ; cat . # 245 - 684 ) on ice for 30 minutes , washed for 4 times with 1 . 2 ml ice - cold pbs ( ph 7 . 4 ), and stored at 4 ° c . biotinylation of soluble light : purified soluble human light ( lightt66 , concentration = 0 . 262 mg / ml in pbs , ph 8 . 0 ) was used in the biotin labeling reaction ( rooney , et al . j . biol . chem . 275 : 14307 ( 2000 )). immediately before use , 200 μl of ultrapure distilled water ( invitrogen ) was added to 2 mg of nhs - peo4 - biotin , and 3 . 7 ml of the nhs - peo4 - biotin solution was added to lightt66 . the sample was incubated on ice for 2 hours . afterwards , 42 μl of 1 m tris ( ph 8 . 0 ) ( fisher scientific , usa ; cat . # bp154 - 1 ) was added to stop the reaction . the sample was dialyzed against 1 liter of pbs with buffer exchanged three times . the biotinylated lightt66 was sterilized by filtering through a 0 . 22 mm millex - gv filter ( millipore , ireland , cat . # slgv004sl ), subdivided into small aliquots , and stored in − 80 ° c . immobilization of soluble light on the biotinylated cancer cells : biotinylated and formalin fixed el4 cells ( 30 × 10 6 ) were used in this preparation . the cells were resuspended in 1 ml pbs ( ph 7 . 4 ) and were incubated with 10 μg / ml of neutravidin ™ ( pierce ; cat . # 31000 ) for 30 minutes . the cells were washed 4 times with 1 ml ice - cold pbs ( ph 7 . 4 ) to remove the free neutravidin ™. the cells were then incubated with biotinylated lightt66 ( 1 μg / ml ) for 45 minutes and washed 3 times with 1 ml ice - cold pbs ( ph 7 . 4 ) to remove the unincorporated light . the prepared cells were resuspended in sterile pbs ( 40 × 10 6 cells / ml ) and stored in 4 ° c . for in vivo anti - tumor studies . this example shows data demonstrating suppression of tumor growth by expressing light on the surface of tumor cells . to analyze the efficacy of light mediating tumor rejection , the el4 tumor model was used . el4 is a mouse thymoma cancer cell line derived from c57 / bl6 ( b6 ) mouse . when el4 cells were injected subcutaneously into syngeneic b6 mouse , a solid tumor develops in 5 to 7 days and progresses to a lethal tumor typically by 15 - 20 days . human light as a potential immunotherapeutic was used . an el4 cell line stably expressing light was made using recombinant retrovirus . human light expressing el4 cells ( el4 - light ) were injected subcutaneously into syngeneic b6 mice , and the growth of the tumor was monitored . the average tumor size achieved between the control ( 7 . 5 cm 3 ) and the test group over a 15 - 20 day time frame was significantly different ( p & lt ; 0 . 05 ) ( fig1 a ). a massive tumor grew in mice injected with el4 cells that were transduced with control empty vector ( el4 - v ). in contrast , in mice injected with el4 - light cells tumors did not grow and thus were rejected . this result demonstrates that human light induced anti - tumor responses when expressed in mouse tumor cells . to determine if unmodified el4 cells would grow in the presence of light - expressing el4 cells , equal numbers of el4 - v and el4 - light cells were separately injected in the same mouse . el4 - v cells were used as a control ( fig1 b ). in mice injected with el4 - v cells , the tumor grew rapidly . for the co - injection group , the presence of light - expressing el4 cells triggered the rejection of the non - light expressing el4 tumor at the distal location , showing a systemic effect of tumor rejection . this result is important for two reasons . first , it shows that the tumor rejection was not due to the present of a human protein because the el4 - v cells , which did not have light , were also rejected . second , the results demonstrated that light expressing el4 cells were capable of mediating a systemic response against the el4 tumor . this example shows the effect of the light isoform in stimulating anti - tumor responses . in human and mouse , there exist at least three major isoforms of light ( membrane light , soluble light and lightδtm )( granger , et al ., j immunol 167 : 5122 ( 2001 ). membrane light represents the full - length form of light with a transmembrane anchor . membrane light can be shed ( proteolytically cleaved on the outside of the cell ), into a soluble form , and the third isoform of light is formed by alternate splicing , generating a deletion of the transmembrane domain ( lightδtm ). lightδtm lacks the transmembrane domain and is located to the cytosol . to determine if these other isoforms of light induce anti - tumor responses , el4 cell lines that stably express a soluble form of light ( el4 - lightt66 ) and lightδtm ( el4 - lightδtm ) were made using recombinant retroviruses . these cell lines were injected into two groups of mice and the growth of tumor monitored . the results ( fig2 a ) establish that cells expressing either soluble light or lightδtm were unable to induce an anti - tumor response . to determine if soluble light impairs tumor rejection mediated by el4 - light , a mixture of el4 - light and el4 - lightt66 were injected into b6 mice and the tumor growth was monitored ( fig2 b ). mice injected with el4 - light cells showed a complete loss of tumor growth . in contrast , in mice injected with both el4 - light and el4 - soluble light tumors grew rapidly . thus , soluble light impaired light - dependent anti - tumor responses . these results indicate that membrane bound light is essential for light - mediated anti - tumor activity . viral and bacterial based vector delivery systems in humans have inherent safety issues . to circumvent these inherent issues with vector - based delivery systems , a biochemical - based approach , independent of vectors , was developed to attach functional light to the surface of tumor cells . the procedure is an immobilization system to display soluble proteins on virtually any cell surface in a stable format using a chemical ( biotin ) linkage . this method ( illustrated in fig3 a and b ) used purified recombinantly expressed soluble light ( lightt66 ) ( rooney , et al ., j . biol . chem . 275 : 14307 ( 2000 )) and el4 tumor cells for enhanced immunity . first , the cell surface proteins on el4 cells were biotinylated . second , soluble light ( lightt66 ) was also biotinylated . biotinylated soluble light was immobilized to the biotinylated el4 cell membrane proteins through addition of tetrameric neutriavidin . since the binding between biotin and neutriavidin is very strong , this biotin - neutriavidin - biotin complex is extremely stable in vivo . to determine the efficiency of immobilization , lightt66 was detected by flow cytometry and el4 - light cells were used for comparison . immobilized soluble light on the surface of em cells was detected by antibody staining or with hvem - fc ( fig3 c , e ). surrogate receptors for light , ltβr - fc and hvem - fc were prepared as described ( rooney , et al ., methods enzymol 322 : 345 ( 2000 )). the fluorescence intensity of the light - decorated el4 cells ( el4 - na - lightt66 ) was 27 % of the level expressed by retrovirus transduced el4 cells ( el4 - light ) ( fig3 d ) indicating that the method can deliver light to cell membrane comparable to retrovirus transduction . the results demonstrate that this biotin - based immobilization system is an effective way to attach purified light to the surface of cells , such as tumor cells . thus , this biotin - based immobilization system serves as an example that biologically active ltbeta receptor agonists such as light can be attached or coupled to tumor cell surface . this biotin - based cell membrane immobilization system is a viable non - vector based alternative for modifying tumor cells with ltbeta receptor agonists such as light in order to enhance immune responses against tumor cells when cells are administered to animals . this example includes data demonstrating suppression of tumor growth by el4 cells having light attached , coupled or conjugated to the cell membrane . to ascertain the ability of light decorated cells to function as a cancer vaccine , a protocol was designed to evaluate efficacy of light conjugated el4 cells as cancer vaccine ( fig4 a ). two groups of mice were injected with formalin fixed el4 cells either conjugated to lightt66 ( el4 - na - lightt66 ) or conjugated to neutravidin ( el4 - na ). mice were injected with el4 - na - lightt66 or el4 - na cells 14 days prior to injection with viable el4 tumor cells in order to generate an immune response , as in a typical vaccine strategy . to examine the induction of humoral immunity by light - decorated el4 cells , pre - and post - immune sera were collected from each group of mice and tested for anti - el4 antibody activity by flow cytometry using unmodified el4 cells ( fig4 b ). mice vaccinated with el4 - na cells did not generate detectable anti - el4 activity . in contrast , anti - el4 antibody activity was detected in sera of 3 of 5 mice that were injected with el4 - na - light , demonstrating that immunization with light - decorated el4 cells elicited antibody responses to el4 antigens . to determine efficacy of light decorated el4 cells as an immune enhancing vaccine , el4 cells were injected in each group and tumor growth was monitored . the mice immunized with lightt66 - decorated el4 cells showed a significant reduction in tumor growth rate ( fig4 c ). these data demonstrate immunization with light - decorated el4 cells generates an immune response against the el4 tumor that inhibits tumor progression . this example includes data demonstrating suppression of primary tumor growth with el4 cells having light attached , coupled or conjugated to the cell membrane . to evaluate the ability of light - decorated el4 cells to inhibit growth of a primary tumor , el4 cells were injected into mice subcutaneously and the cells were allowed to proliferate so a pre - established tumor was formed . then , formalin fixed el4 - na - light cells were injected into tumor area , and tumor growth was monitored for an additional 16 days ( fig5 a ). formalin fixed el4 - na was used as control . mice injected with el4 - na - light cells showed a reduction of tumor growth compared to the el4 - na control . these results demonstrate the efficacy of light - decorated el4 cells to suppress growth of an established tumor . tumor cells having attached , conjugated or coupled ltbeta receptor agonists such as light are therefore also useful as treatments of established tumors ( fig5 b ). this example includes data demonstrating receptor requirement for light - mediated anti - tumor responses . to gain molecular insight into light - mediated anti - tumor response , receptor requirement for light - mediated anti - tumor activity was evaluated . light can interact with 2 signaling receptors , hvem and ltβr . to determine which of these two receptors were required for light - mediated anti - tumor responses , analysis of tumor rejection in ltβr and hvem knockout ( ko ) mice was performed . in hvem ko mice , el4 - light cells were rejected ( fig6 a ), suggesting that hvem was not essential for light - mediated anti - tumor responses . when these mice were later challenged with parental el4 cells , no tumor developed . in contrast , in ltβr ko mice , el4 tumors were not rejected , indicating that light signaling through ltβr participates in light - mediated anti - tumor activity ( fig6 b ). this example includes data demonstrating that light stimulates ccl21 production in tumor environment . eta - light cells when injected into recombinase activating gene - 2 ( rag2 −/− ) mice , which lack t and b cells , through the intravenous route , were detected in spleen , liver and lung . to examine the ability of light to stimulate chemokines in tumor environment , eta - light cells were injected into rag2 −/− mice and spleens were collected for the detection of ccl21 using real time rtpcr ( fig7 a ). mice injected with eta - light exhibited a 2 . 5 fold increase in ccl21 expression compared to mice injected with eta cells as control ( fig7 b ). this result demonstrates that light in the tumor environment increases ccl21 production in the absence of t and b cells . this example includes a discussion of data indicating a mechanism of light - mediated anti - tumor activity . ltβr interacts with light , ltβ , and ltα1β2 . to examine the contribution of endogenous light , ltβ and ltα to light - meditated anti - tumor activity , el4 - light cells were injected subcutaneously into mice genetically deficient in one or more of the cellular ligands of the ltβr ( light −/− ltβ −/− , light −/− , ltβ −/− , and ltα −/− ). in mice deficient in both light −/− and ltβ −/− , eta - light tumors were not rejected , suggesting that endogenous light and / or ltβ participate in light - mediated anti - tumor activity ( fig8 a ). however , when eta - light cells were injected into light −/− mice , the tumor was rejected , indicating that endogenous light was not required for tumor control . when these mice were later challenged with parental eta cells , the tumor was still rejected ( fig8 b ). to determine if lymphotoxin participates in tumor rejection , el4 - light cells were injected into ltβ −/− or ltα −/− mice ( fig8 c and d ). mice deficient in ltβ were not able to reject the eta - light tumor , indicating that ltβ participates in light - mediated tumor control . in contrast , the eta - light tumor was rejected in the ltα −/− mice , although it required a longer time for the process of rejection , suggesting that ltα may contribute to but was not essential for light - mediated tumor control . el4 - light cells were capable of inducing anti - tumor responses in the absence of secondary lymphoid organs which are missing in the ltα −/− mice . furthermore , ltα −/− mice served as a phenotypic control for the other mutant mice lacking secondary lymphoid organs such as ltβr −/− ( fig6 b ) and ltβ −/− ( fig8 c ). mice deficient in light −/− or ltα −/− , which rejected el4 - light tumors , when subsequently challenged with unmodified el4 cell , showed no tumor formation ( fig8 b and d ) and these mice remained tumor free of tumors for & gt ; 5 months , indicating a sustained memory response to the el4 tumor was induced by the treatment . this example includes data indicating that expression of ltβ in t and b lymphocytes contributes to light - mediated anti - tumor activity . to further investigate the cellular requirement for ltβ expression for light - mediated tumor rejection , conditional knock out mice with ltβ specifically deleted in either t cells ( t - ltβ −/− ) or b cells ( b - ltβ −/− ) were used as a host to examine the immunostimulating effect of el4 - light . el4 - light cells were injected subcutaneously into t - ltβ −/− and b - ltβ −/− mice , and tumor growth was monitored for 22 days . mice deficient in ltβ in either t or b cells were unable to reject the el4 - light tumor . this data indicates that both t or b cell expression of ltβ participates in light - mediated tumor rejection ( fig9 ). this example includes a description of variant forms of light that can enhance immunotherapy . the efficacy of light in cancer - immunotherapy in humans is potentially adversely affected by dcr3 expressed by tumors in humans . certain combinations of the variant forms of human light alter its binding affinity to human ltβr and human dcr3 . a combination of light subunits ( 32l - 214e and 32s - 214k ) enables light to attain a high affinity binding to human ltβr , but a reduced affinity for human dcr3 relative to the predominant form of human light ( fig1 and table 1 ). furthermore , the interaction between this heterotrimeric form of light 32l - 214e / 32s - 214k and ltβr in the presence of dcr3 was evaluated . competition binding assays demonstrated that the inhibition concentration at 50 % binding ( ic50 ) of dcr3 - fc to the binding of ltβr to a combination of light - e214k ( mutation from e to k at amino acid position 214 ) and light - s32l ( mutation from s to l at amino acid position 32 ) is approximately 2 . 5 times higher than the predominant form of light ( light 32s and 214e , fig1 , seq id no : 1 ). in particular , 2 . 5 times higher concentration of dcr3 - fc was needed to inhibit binding of ltβr - fc to the combination of light - e214k and light - s32l compared to the predominant form of light ( seq id no : 1 ). thus , light - e214k and light - s32l could be a potent reagent for activating ltβr signaling system . light variant 32l - 214e / 32s - 214k molecule is therefore likely to be a more effective form for enhancing immune responses , particularly but not limited to cancer cells . enhanced efficacy is due to high binding avidity to ltβr and low binding avidity to dcr3 . as dcr3 has been found to be highly expressed in a wide variety of cancer cells , light variant 32l - 214e / 325 - 214k will minimize the inhibitory effect of dcr3 towards the interaction between light and its receptors hvem and ltβr . in addition , the high binding avidity of light 32l - 214e / 32s - 214k to ltβr can also enhance anti - tumor activity mediated by light as the data above demonstrate that ltβr contributes to light - mediated anti - tumor responses .
| 2 |
in the motion compensation encoding system according to the present invention , the motion prediction error can be decreased by enlarging the range of detection and by detecting pixels with high accuracy . on the other hand , increased accuracy of the motion detection causes an increase in variations of motion vectors , increasing the amount of information generated by the motion vector . such a relationship between the amount of information of the motion vector and the amount of information of the prediction error , in one macro block , is given by the following equation ( 2 ). b mb = vlc ( dmv x )+ vlc ( dmv y )+ f ( sad , q ) ( 2 ) in the above , vlc ( dmv x ) and vlc ( dmv y ) are code length of vlc ( variable length code ) of difference motion vectors in the x and y directions , respectively , and the function f ( sad , q ) is the number of bits which are produced when the sum of absolute differences sad between the motion vectors mv x and mv y is quantized using a step size q . since the number of bits assigned to each macro block is constant irrespective of the motion vector value , the quantization of the macro block with the highest degree of accuracy requires the detection of a motion vector which minimizes the step size q in eq . ( 2 ). to find the property of the function f , the relationships between the sum of absolute differences , sad , of prediction errors calculated over the entire range of motion detection for each macro block and the number of bits generated by quantizing the value sad with the step size q were derived from real images ; these relationships are shown in fig6 and 7 . it is evident from fig6 and 7 that there is a meaningfull correlation between the value sad and the number of bits generated , but the latter varies greatly with respect to the value sad in the image domain . on the other hand , these figures demonstrate that the number of bits generated does not greatly vary with respect to the value sad calculated in the dct domain , and hence it can be predicted with high accuracy . this is considered to be attributable to the fact that the quantization of the motion compensation error is carried out after dct . based on the above , the function f in eq . ( 2 ) can be approximated by the following equation ( 3 ) using α and β as constants . f ( sad , q ) = α q sad dct + β ( 3 ) accordingly , a motion detection evaluation function , which is used to provide the minimum step size for each macro block , is such as given by the following equation ( 4 ) based on eqs . ( 2 ) and ( 3 ), and the motion vector which provides the maximum evaluation value e is the optimum point . e = b mb - { vlc ( dmv x ) + vlc ( dmv y ) } - β sad dct ( 4 ) since this evaluation function e is b mb −[ vlc ( dmv x )+ vlc ( dmv y )} ≈ b mb at high bit rates where the proportion of vector is small , the motion vector which provides the maximum evaluation value e is one minimizes sad dct , that is , sad . [ 0038 ] fig1 illustrates in block form an embodiemnt of the present invention , in which the input terminal 1 , the current frame memory 2 , the previous frame ( reference frame ) memory 3 , the motion vector generator 4 , the motion compensation circuit 5 and the substractor 6 are the same as those used in the prior art example depicted in fig1 . an orthogonal transformation circuit 7 is used as required , from which is provided an orthogonal transformation output produced by subjecting the motion prediction error information from the subtrator 6 to orthogonal transformation such as dct , hadamard transformation or fourier transformation . the orthogonal transformation output ( sad dct , for instance ) is fed to a generated information - quantity prediction circuit 8 , which generates an output indicative of the aforementioned function f ( sad , q ) corresponding to a generated information - quantity prediction value . such an orthogonal transformation as shown in fig2 a may be replaced with a transformation which obtains an absolute value - sum by an absolute - sum circuit 7 a as shown in fig2 b or a square sum by a square sum circuit 7 b as depicted in fig2 c . a difference vector , which corresponds to a difference between the motion vector from the motion vector generator 4 and the motion vector from the motion vector memory 9 , is provided from the subtractor 10 . this difference vector is used to make a step size prediction in a step - size predictor 11 , then the resulting prediction value is used to choose a difference vector by a minimum value detector 12 so that the predicted step size is minimized , and the difference vector is fed to and encoded by an encoder 16 . the motion vector read out of the motion vector memory 9 is added by an adder 13 to the output from the minimum value detector 12 , and the added output is delayed by a delay circuit 14 for a predetermined period of time and is then stored as an updated motion vector in the motion vector memory 9 . [ 0043 ] fig3 illustrates an example of the generated information - quantity prediction circuit 8 ; the output from the substractor 6 or the orthogonal transformation circuit 7 is applied to a switch 8 - 1 . the switch 8 - 1 is turned on by a timing pulse which is generated upon each readout of the block from the aforementioned memory 2 or 3 . reference numeral 8 - 2 denotes an absolute value circuit or a square circuit , 8 - 3 an adder and 8 - 4 a memory ; the circuits 8 - 2 , 8 - 3 and 8 - 4 constitute a sum circuit 8 - 0 . in case of using the square sum circuit 7 a or the absolute value - sum circuit 7 b in place of the orthogonal transformation circuit 7 as described previously with reference to fig2 the sum circuit 8 - 0 is omitted . the output sad dct from the sum circuit 8 - 0 is provided to a logical operation circuit 8 - 5 , wherein an operation [ α / q ( sad dct + β )] is performed using the step size q from the step - size predictor 11 and from which an output corresponding to the function f ( sad , q ) is taken out and applied to the step - size predictor 11 . [ 0044 ] fig4 shows an example of the step - size predictor 11 , in which the difference motion vector ( dmv x , dmv y ) from the adder 10 is coded by a vlc coder 11 - 1 into a vlc code , which is then coded by a bit - length calculator 11 - 2 into a bit - length signal vlc ( dmv x )+ vlc ( dmv y ). this bit - length signal is applied to a step - size calculator 11 - 3 , wherein a signal representative of the function f ( sad , q ) from the generated information - quantity prediction circuit 8 is used to calculate the step size q , which is fed to the generated information - quantity prediction circuit 8 . the step size q is converted by a step - size evaluation function calculator 11 - 4 into the step size evaluation function e , which is provided to the minimum value detector 12 . [ 0045 ] fig5 illustrates an example of the minimum value detector 12 , wherein the maximum value of the step size evaluation function e is detected by a maximum value detector 12 - 1 , and a switch 12 - 2 is held - on by the detected output for an extremely short time but returns again to the off state . while the switch 12 - 2 is the on - state , the difference motion vector ( dmv x , dmv y ) from the substractor 10 is fed as the minimum value of the difference motion vector to the encoder 16 and the adder 13 . for performance evaluations of the scheme according to the present invention , simulations were done by h . 263tmn5 . the frame rate was fixed at 5 fbp and the coding bit rate was set at 10 kbps , 20 kbps , 50 kbps , 100 kbps and 200 kbps . in fig8 there are shown the simulation results obtained on a qcif image “ carphone ” at 20 kbps . in fig9 the relationships between the proportion of the motion vector obtained by the conventional motion detection intended to minimize the prediction error and improvements in snr values obtained by the present invention are depicted in respect of a total of 15 values obtained by encoding three test images ( carphone , susie , kdd original ) at the abovementioned five bit rates . the proportion of the motion vector and the improved snr value are mean values throughout the sequence . according to fig8 the snr by the present invention are better than those by the conventional system over the entire area of the scene , and reaches a maximum of 0 . 5 db . the proportion of the motion vector present in this image is 20 . 4 % per scene in the conventional system but 12 . 3 % in the present invention . the conventional motion detection system is employed with a view to minimizing the prediction error ; hence , at ultra - low bit rates below 20 kbps , the situation may sometimes arise where the number of bits of the motion vector increases relative to the number of bits assigned to the quantization of the prediction error and makes the latter unaptly small . on the other hand , the use of the present invention permits an 8 . 1 % reduction of the proportion of the motion vector . by assigning this surplus proportion to the quantization of the prediction error , the snr could be improved . according to fig9 the higher the proportion of the vector bits , the more the snr is improved by the present invention . further , the snr improving effect greatly differs , depending on whether the proportion of the vector is above or below 5 %. this confirms that the present invention is effective in improving the picture quality at ultra - low bit rates above 5 % and that the present invention covers the conventional system at high bit rates where the proportion of the motion vector decreases . as described above in detail , it has been confirmed that the motion detection scheme according to the present invention , which minimizes the quantization step size for the prediction error based on the estimation of the number of quantization bits and the motion - vector bit length , is effective at ultra - low bit rates where the proportion of the motion vector increases . moreover , it has been clarified that the influence of the motion vector length on the quantization depends on whether the proportion of the vector is above or below 5 %. from such points of view , the present invention is highly effective and of great utility when employed in the image information transmission field .
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the present invention , stalk and root eliminator 10 , is illustrated in fig1 . stalk and root eliminator 10 generally includes chassis 12 which may be attached behind a tractor by 3 - point linkage 14 . one or more front wheels 24 and rear wheels 36 are attached to chassis 12 . the height of chassis 12 may be adjusted relative to front wheels 24 and rear wheels 36 to set a maximum plow depth . front wheel 24 is attached to chassis 12 by post 26 which is height - adjustably mounted within post receiver 80 . similarly , rear wheel 36 is attached to chassis by post 38 which is also situated within a height - adjustable receiver . cutting manifold 16 is attached beneath chassis 12 . cutting manifold 16 houses a cutting device for cutting vegetation such as cotton stalks . the cutting device may be driven by the power take - off of the tractor via drive shaft 18 or by a separate motor . a series of plows 28 are attached to chassis 12 rearward of cutting manifold 16 . each plow 28 is attached to beam 30 which extends beneath chassis 12 . rotary picker 32 is attached rearward of plow 28 on chassis 12 by extender arm 34 . as shown more clearly in the rear view of stalk and root eliminator 10 in fig4 , each plow 28 has a corresponding rotary picker 32 . the purpose of this linear arrangement of the cutting device , plows , and rotary pickers will be described in greater detail subsequently . a front view of stalk and root eliminator 10 is illustrated in fig2 . flaps 60 cover the front of cutting manifold 16 and prevent cut vegetation and other objects from being kicked - back toward the operator of the tractor . flaps 60 are made of a flexible material , however , to permit vegetation to pass between and under flaps 60 to be cut . opening 20 is provided in the middle of cutting manifold 16 for receiving drive shaft 18 ( see fig1 ). referring back to fig2 , drive shaft 18 engages transmission 56 which transfers the torque from drive shaft 18 to shafts 52 and 54 . shafts 52 and 54 transmit power to blade shaft 58 via gearboxes 22 and 42 . this powertrain is illustrated more clearly in fig3 . the reader will note that a series of cutting blades 40 are attached to blade shaft 58 . each cutting blade 40 rotates with blade shaft 58 along a horizontal axis of rotation which is substantially perpendicular to the direction of travel of the tractor . fig5 is a detail view of rotary picker 32 . each rotary picker 32 is attached to chassis 12 by extender arm 34 . rotary picker 32 is attached below extender arm 34 by swivel shaft 62 and includes a plurality of pick fingers 64 which freely rotate about shaft 66 . rotary picker 32 separates stalks and roots from the soil after plow 28 passes through the soil ahead of rotary picker 32 . pick fingers 64 roll and “ comb ” through the plowed soil and separate the vegetation from the soil . although not shown in fig5 , extender arm 34 may be removably attached to chassis 12 , so that rotary pickers 32 may be removed from chassis 12 when desired . fig6 and fig7 illustrate cutting blade 40 which may be used with stalk and root eliminator 10 . four l - shaped blades 68 are attached to mounting plate 74 by bolts 70 . fig7 shows the opposite side of cutting blade 40 . each l - shaped blade 68 has flange 76 that wraps around mounting plate 74 . bolts 70 pass through mounting plate 74 and flange 76 and the assembly is secured together with nuts 78 . if one of l - shaped blades 68 is bent or otherwise damaged during cutting , it is only necessary to replace the part that is bent — which can be easily unbolted from mounting plate 74 . fig8 illustrates the operation of stalk and root eliminator 10 . stalk and root eliminator 10 is pulled behind a tractor across uncut vegetation 50 . the top portion of the vegetation passes into cutting manifold 16 where it is chopped off by cutting blades 40 leaving cut vegetation 44 . plow 28 passes through the soil behind cutting manifold 16 and loosens the roots of cut vegetation 44 leaving behind an area of plowed vegetation 46 . rotary pickers 32 then comb through plowed vegetations 46 and lift the vegetation to the surface of the soil , leaving behind an area of separated vegetation 48 . fig9 illustrates how a harrow may be substituted for the rotary picker . harrow 82 is attached to chassis 12 like — rotary picker 32 — via extender arm 34 and swivel shaft 62 . harrow disks 84 rotate about shaft 66 when harrow 82 is allowed to roll on the ground . those that are skilled in the art will appreciate that harrow disks 84 will break up clods and lumps of soil created by the plows , thus providing a finer soil finish that is more suitable for seeding and planting operations . fig1 illustrates yet another cutting blade that may be employed on stalk and root eliminator 10 . cutting blade 90 includes plate 86 having collar 88 for receiving the blade drive shaft . keyway 92 is provided to allow cutting blade 90 to be locked in place on the blade drive shaft . blades 94 are attached to flanges 102 with bolts 96 or other fasteners . blades 94 extend from plate 86 parallel to the blade drive shaft . as such , blades 94 extend in both the positive and negative z direction when plate 86 lies in the x - y plane . each blade 94 includes both two cutting edges — leading edge 98 and trailing edge 100 . when oriented as shown in fig9 , only leading edge 98 cuts the vegetation . cutting blade 90 may be reversed on the blade drive shaft from time to time such that trailing edge 100 may be used to cut the vegetation . thus , if collar 88 normally extends in the positive z direction relative to plate 86 , cutting blade 90 may be turned such that collar 88 extends in the negative z direction . this may be useful when leading edge 98 begins to dull after extended use . when leading edge 98 and trailing edge 100 are both dull , the user can replace blade 94 or sharpen the cutting edges . with the present invention now more thoroughly described , the reader may now appreciate the various features of the present invention which allows stalk and root eliminator 10 to transform a field of rooted vegetation into a field of “ separated ” vegetation in a single pass . referring back to fig5 , the reader will now appreciate that swivel shaft 62 allows rotary picker 32 to turn with the tractor ( such as when executing a u - turn ) so as not to stress pick fingers 64 . pick fingers 64 are curved to induce angular rotation of rotary picker 32 when rolled through the plowed soil . the direction of angular rotation is preferably the same direction as the rotation of the wheels of the tractor . the curvature also helps lift the vegetation as each pick finger 64 rotates out of the soil . the preceding description contains significant detail regarding the novel aspects of the present invention . it should not be construed , however , as limiting the scope of the invention but rather as providing illustrations of the preferred embodiments of the invention . thus , the scope of the invention should be fixed by the following claims , rather than by the examples given .
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fig1 is a block diagram of a microprocessor based system utilizing a dynamically selected operating system 100 . battery backup 102 or a / c power source 104 can be automatically switched at switch 118 to deliver power depending up on power availability . when alternating - current for power supply 104 is disconnected or otherwise interrupted , power delivery is automatically switched from power supply 104 to battery backup 102 . microprocessor based systems , such as illustrated in fig1 , are generally built around a central processing unit , such as microprocessor 112 . supporting devices such as peripherals 110 , memory 114 , data storage devices 106 , and cache 108 are power consuming devices commonly found in microprocessor based systems . a plurality of different operating systems are stored in a data storage device 106 that is connected to microprocessor 112 . data storage devices 106 exist on the data bus and can reside internally to the system in such forms as a hard drive , a solid state drive , flash memory drive or other similar form of data storage . data storage devices 106 may also exist on the data bus while residing externally to the system in such forms as universal serial bus drives , network attached devices , external hard drives or other similar form of data storage . the plurality of operating systems 109 can be accessed by microprocessor 112 so that microprocessor 112 can load any of the operating systems 109 that is the most desirable for the operating environment of the microprocessor based system 100 . operating systems 109 vary depending upon the operating environment of the system and the functions the system performs . operating systems can be written , for instance , to maximize system speed and minimize power efficiency , or maximize power efficiency at the expense of system speed . an operating system written to increase power efficiency may often sacrifice system performance and system features in order to reduce power consumption . some operating systems may go so far as not enabling certain devices to minimize power consumption . such a strategy may be important when limited power resources may be available to protect critical data . as shown in fig1 , operating power for the microprocessor 112 , and other parts of the system is typically obtained from an alternating current power supply 104 . in the event of loss of power emanating from the alternating current power supply 104 , a battery backup 102 system can supply power to the system as illustrated in fig1 via the switch 118 . the microprocessor 112 checks the status and consistency of the power delivery and stores the status in a bit register . the bit register will send an instruction signal to the microprocessor depending upon value found in the boot option matrix ( explained in fig3 ), the microprocessor 112 will load the appropriate operating system 109 in accordance with the current status of the power delivery system . the microprocessor 112 also registers the status of the peripherals 110 , the configured memory 114 , input - output controller 116 and any cache 108 in use and stores them in the bit register 406 as explained in fig4 . in the event that the microprocessor based system 100 boots into an operating system with a restricted instruction set , the operating system will load only critical devices necessary for retrieving important data and securely storing that data to the data storage device 106 . loading only critical devices is needed for placing a limited load on the battery backup 102 to allow the system to shutdown , reboot , load a limited operating system , save critical data and shutdown again before running out of backup power . fig2 is a chart illustrating flow diagram of a boot - up sequence 200 utilized in accordance with an embodiment of the present invention showing multiple boot options based upon current hardware states and operating system selections . as shown in fig2 , at step 202 the process is initiated . at step 204 , microprocessor 112 scans the data bus to determine the current status of the power source , either battery backup power source 102 or alternating current power source 104 . a common data bus used in microprocessor based systems is the peripheral component interconnect or pci bus , but a boot up sequence will work on most data bus systems . at step 208 , the bit register 406 reads the current device status including the power source status . the microprocessor then reads the bit register to check the power source status at step 212 . at step 214 , if alternating - current power is not available and the battery is engaged , the system described in fig1 will send an instruction signal from the bit register to proceed to step 216 and select secondary operating system ( 2 ). however , if a / c power is available and the battery is not engaged , the system 100 will continue to step 218 and select primary operating system ( 1 ). the microprocessor 112 continues to monitor the bit register 406 for current power source state at step 222 . if the power source changes as in step 206 , the system shuts down and reboots and then re - reads bit register 406 for a / c power availability and loads the appropriate operating system for the microprocessor based system . at step 224 the system is available for normal use . at step 226 the boot sequence is complete . fig3 illustrates an embodiment showing a boot option table 300 of a dynamically selected operating system 100 that can be accessed by microprocessor 112 , as shown in fig1 . fig3 demonstrates various options available to the microprocessor based system 100 , which the processor can use to select an operating system without user intervention , based upon the bits that are set in a register that stores a data bit indicating the power status , such as illustrated in fig3 . for example , when the battery enabled bit is read as 0 , and a / c available bit is read as 0 , the microprocessor shuts down due to non - availability of power . when the battery enabled bit is read as 0 , and a / c available bit is read as 1 , the microprocessor dynamically selects boot operating system ( 1 ). however , when battery enabled bit is read as 1 , and a / c available bit is read as 0 , the microprocessor dynamically selects boot operating system ( 2 ). in the final example when battery enabled bit is read as 1 , and a / c available bit is read as 1 , the microprocessor will dynamically select boot operating system ( 1 ). this list is not exhaustive and could continue on with multiple bit selection options as well as multiple boot operating system options . fig4 is a block diagram of one embodiment of a microprocessor 400 that can be used in the microprocessor based system 100 shown in fig1 . most microprocessors 400 have internal cache 402 , which stores recently or frequently used data . a data bus 404 connects the cache 402 , bit register 406 , processing unit 408 and boot loader 410 , and delivers data from peripherals 110 . a bit register 406 stores data bits containing system and data information ( such as the data stored in boot option table 300 of fig3 ). the processing unit 408 processes system instructions from bit register 406 send via the instruction signal including the selection of an operating system from the boot option table 414 from data contained in table 300 of fig3 . when microprocessor 400 is first powered up , boot loader 410 loads the operating system selected by processing unit 408 utilizing the logic from table 300 to select the operating system for the conditions as determined by the data in the bit register 406 . the boot loader 410 is a small program which may be stored in read - only memory along with data needed to access nonvolatile devices from which operating system programs and data are loaded into random access memory . the boot loader program functions to load other data and programs which are then executed from random access memory . hence , the microprocessor 400 does not utilize an operating system in read - only memory or random access memory , but rather , is able to select from various operating systems stored on a data storage device 412 and delivered on the data bus 404 . the foregoing description of the invention has been presented for purposes of illustration and description . it is not intended to be exhaustive or to limit the invention to the precise form disclosed , and other modifications and variations may be possible in light of the above teachings . the embodiment was chosen and described in order to best explain the principles of the invention and its practical application to thereby enable others skilled in the art to best utilize the invention in various embodiments and various modifications as are suited to the particular use contemplated . it is intended that the appended claims be construed to include other alternative embodiments of the invention except insofar as limited by the prior art .
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the following reaction schemes illustrate the preparation of the compounds of the present invention . unless otherwise indicated r 1 , r 2 , r 3 , r 4 , n and ar in the reaction schemes and the discussion that follow are defined as above . ## str6 ## in reaction 1 or scheme 1 , the amino acid compound of formula vii , wherein r 16 is ( c 1 - c 6 ) alkyl , benzyl , allyl or tert - butyl , is converted to the corresponding compound of formula vi by reacting vii with a reactive functional derivative of an arylsulfonic acid compounds , such as an arylsulfonyl chloride , in the presence of a base , such as triethylamine , and a polar solvent , such as tetrahydrofuran , dioxane , water or acetonitrile , preferably a mixture of dioxane and water . the reaction mixture is stirred , at room temperature , for a time period between about 10 minutes to about 24 hours , preferably about 60 minutes . in reaction 2 or scheme 1 , the arylsulfonyl amino compound of formula vi , wherein r 16 is ( c 1 - c 6 ) alkyl , benzyl , allyl or tert - butyl , is converted to the corresponding compound of formula v , wherein n is 1 , 3 , 4 , 5 or 6 , by reacting vi with a reactive derivative of an alcohol of the formula ## str7 ## such as the chloride , bromide or iodide derivative , preferably the bromide derivative , wherein the r 17 protecting group is ( c 1 - c 6 ) alkyl , benzyl , allyl or tert - butyl , in the presence of a base such as potassium carbonate or sodium hydride , preferably sodium hydride , and a polar solvent , such as dimethylformamide . the reaction mixture is stirred , at room temperature , for a time period between about 60 minutes to about 48 hours , preferably about 18 hours . the r 17 protecting group is chosen such that it may be selectively removed in the presence of and without loss of the r 16 protecting group , therefore , r 17 cannot be the same as r 16 . removal of the r 17 protecting group from the compound of formula v to give the corresponding carboxylic acid of formula iv , in reaction 3 or scheme 1 , is carried out under conditions appropriate for that particular r 17 protecting group in use which will not affect the r 16 protecting group . such conditions include ; ( a ) saponification where r 17 is ( c 1 - c 6 ) alkyl and r 16 is tert - butyl , ( b ) hydrogenolysis where r 17 is benzyl and r 18 is tert - butyl or ( c 1 - c 6 ) alkyl , ( c ) treatment with a strong acid such as trifluoroacetic acid or hydrochloric acid where r 17 is tert - butyl and r 16 is ( c 1 - c 6 ) alkyl , benzyl or allyl , or ( d ) treatment with tributyltinhydride and acetic acid in the presence of catalytic bis ( triphenylphosphine ) palladium ( ii ) chloride where r 17 is allyl and r 16 is ( c 1 - c 6 ) alkyl , benzyl or tert - butyl . in reaction 4 of scheme 1 , the carboxylic acid of formula iv is condensed with an amine , r 1 r 2 nh , or the salt thereof , to give the corresponding amide compound of formula iii . the formation of amides from primary or secondary amines or ammonia and carboxylic acids is achieved by conversion of the carboxylic acid to an activated functional derivative which subsequently undergoes reaction with a primary or secondary amine or ammonia to form the amide . the activated functional derivative may be isolated prior to reaction with the primary or secondary amine or ammonia . alternatively , the carboxylic acid may be treated with oxalyl chloride or thionyl chloride , neat or in an inert solvent , such as chloroform , at a temperature between about 25 ° c . to about 80 ° c ., preferably about 50 ° c ., to give the corresponding acid chloride functional derivative . the inert solvent and any remaining oxalyl chloride or thionyl chloride is then removed by evaporation under vacuum . the remaining acid chloride functional derivative is then reacted with the primary or secondary amine or ammonia in an inert solvent , such as methylene chloride , to form the amide . the preferred method for the condenation of the carboxylic acid of formula iv with an amine to provide the corresponding amide compound of formula iii is the treatment of iv with ( benzotriazol - 1 - yloxy ) tris ( dimethylamino ) phosphonium hexafluorophosphate in the presence of a base , such as triethylamine , to provide the benzotriazol - 1 - oxy ester in situ which , in turn , reacts with the amine , r 1 r 2 n , in an inert solvent , such as methylene chloride , at room temperature to give the amide compound of formula iii . removal of the r 16 protecting group from the compound of formula iii to give the corresponding carboxylic acid of formula ii , in reaction 5 of scheme 1 , is carried out under conditions appropriate for the particular r 16 protecting group in use . such conditions include ; ( a ) saponification where r 16 is lower alkyl , ( b ) hydrogenolysis where r 16 is benzyl , ( c ) treatment with a strong acid , such as trifluoroacetic acid or hydrochloric acid , where r 16 is tert - butyl , or ( d ) treatment with tributyltinhydride and acetic acid in the presence of catalytic bis ( triphenylphosphine ) palladium ( ii ) chloride where r 16 is allyl . in reaction 6 of scheme 1 , the carboxylic acid compound of formula ii is converted to the hydroxamic acid compound of formula i by treating ii with 1 -( 3 - dimethylaminopropyl )- 3 - ethylcarbodiimide and 1 - hydroxybenztriazole in a polar solvent , such as dimethylformamide , followed by the addition of hydroxylamine to the reaction mixture after a time period between about 15 minutes to about 1 hour , preferably about 30 minutes . the hydroxylamine is preferably generated in situ from a salt form , such as hydroxylamine hydrochloride , in the presence of a base , such as n - methylmorpholine . alternatively , a protected derivative of hydroxylamine or its salt form , where the hydroxyl group is protected as a tert - butyl , benzyl or allyl ether , may be used in the presence of ( benzotriazol - 1 - yloxy ) tris ( dimethylamino ) phosphonium hexafluorphosphate and a base , such as n - methylmorpholine . removal of the hydroxylamine protecting group is carried out by hydrogenolysis for a benzyl protecting group or treatment with a strong acid , such as trifluoroacetic acid , for a tert - butyl protecting group . the allyl protecting group may be removed by treatment with tributyltinhydride and acetic acid in the presence of catalytic bis ( triphenylphosphine ) palladium ( ii ) chloride . n , o - bis ( 4 - methoxybenzyl ) hydroxylamine may also be used as the protected hydroxylamine derivative where deprotection is achieved using a mixture of methanesulfonic acid and trifluoroacetic acid . in reaction 1 of scheme 2 , the arylsulfonylamino compound of formula vi , wherein r 16 ( c 1 - c 6 ) alkyl , benzyl or tert - butyl , is converted to the corresponding compound of formula viii , wherein r 18 is 2 - propenyl or 3 - butenyl , by reacting ix with a reactive functional derivative , such as the halide , preferably the iodide derivative , of 2 - propen - 1 - ol when r 18 is 2 - propenyl or 3 - buten - 1 - ol when r 18 is 3 - butenyl , in the presence of a base , such as potassium carbonate , cesium carbonate or sodium hydride , preferably sodium hydride when r 18 is 2 - propenyl or cesium carbonate when r 18 is 3 - butenyl . the reaction is stirred in a polar solvent , such as dimethylformamide , at room temperature , for a time period between about 2 hours to about 48 hours , preferably about 18 hours . in reaction 2 of scheme 2 , the compound of formula viii is converted to the carboxylic acid compound of formula iv , wherein n is 2 . the compound of formula viii , wherein r 18 is 2 - propenyl , is converted to the compound of formula iv , wherein n is 2 , by reacting viii with borane - dimethylsulfide complex , followed by immediate oxidation using chromium trioxide in aqueous acetic acid . the oxidative cleavage of terminal olefins to carboxylic acids can be achieved by several methods known in the art . the preferred method for the oxidative cleavage of the compound of formula viii , wherein r 18 is 3 - butenyl , to obtain the carboxylic acid compound of formula iv is to react viii with sodium periodate in the presence of a catalytic amount of ruthenium ( iii ) chloride in a mixture of carbon tetrachloride , acetonitrile and water . the compound of formula iv , wherein n is 2 , is further reacted to provide the hydroxamic acid compound of formula i , wherein n is 2 , according to the procedure described above in reactions 4 , 5 and 6 of scheme 1 . an alternative method for the synthesis of the hydroxamic acid compound of formula i , wherein n is 1 and r 3 and r 4 are both hydrogen , is shown in reaction 1 of scheme 3 , beginning with reacting iminoacetic acid or a metal or ammonium salt of iminoacetic acid of formula x with a functional derivative or an arylsulfonic acid compound , such as an arylsulfonyl chloride , at room temperature , in the presence of a suitable base , such as triethylamine , and a polar solvent such as tetrahydrofuran , dioxane , water or acetonitrile , preferably a mixture of dioxane and water , to give the corresponding dicarboxylic acid compound of formula xi . in reaction 2 of scheme 3 , the dicarboxylic acid compound of formula xi is dehydrated to give a cyclic anhydride compound of formula xii . the formation of cyclic anhydrides by dehydration of dicarboxylic acids may be achieved by a variety of means . the preferred method for the dehydration of the dicarboxylic acid compound of formula xi to give a cyclic anhydride compound of formula xii is to treat xi with an excess of acetic anhydride at a temperature between about 25 ° c . to about 80 ° c ., preferably about 60 ° c . excess acetic anhydride and acetic acid , a by - product of the reaction , are removed by evaporation under reduced pressure leaving the cyclic anhydride compound of formula xii . in reaction 3 of scheme 3 , the cyclic anhydride compound of formula xii is reacted , at room temperature , with an amine , nr 1 r 2 , or a salt of the amine , such as the hydrochloride , in the presence of a base , such as triethylamine , to give the carboxylic acid of formula ii , wherein n is 1 and r 3 and r 4 are both hydrogen . suitable solvents for the reaction are those that will not react with the starting materials , which include chloroform , methylene chloride and dimethylformamide , preferably methylene chloride . the compound of formula ii is further reacted to give the hydroxamic acid compound of formula i , wherein n is 1 and r 3 and r 4 are both hydrogen , according to the procedure described above in reaction 6 of scheme 1 . in reaction 1 of scheme 4 , the carboxylic acid compound of formula iv , wherein n is 2 , is converted to the corresponding compound of formula v , wherein r 19 is ( c 1 - c 6 ) alkyl or tert - butyl , by reacting iv with a compound of the formula wherein r 19 is ( c 1 - c 6 ) alkyl or tert - butyl , in an inert solvent , such as toluene , at a temperature between about 60 ° c . to about 100 ° c ., preferably about 100 ° c ., for a time period between about 1 hour to about 3 hours , preferably 2 hours . in reaction 2 of scheme 4 , the arylsulfonyl amino compound of formula vi wherein n is 1 , 3 , 4 , 5 or 6 and r 16 is ( c 1 - c 6 ) alkyl , benzyl , allyl or tert - butyl , is converted to the corresponding compound of formula xiii , wherein r 19 is ( c 1 - c 6 ) alkyl or tert - butyl , by reacting vi with a reactive derivative of an alcohol of the formula ## str8 ## such as the chloride , bromide or iodide derivative , preferably the bromide derivative , wherein r 19 is ( c 1 - c 6 ) alkyl or tert - butyl , in the presence of base such as potassium carbonate or sodium hydride , preferably sodium hydride , and a polar solvent , such as dimethylformamide . the reaction is stirred , at room temperature , for a time period between about 60 minutes to about 48 hours , preferably about 18 hours . the r 16 protecting group , of the compounds of formulas iv and vi , is chosen such that it may be selectively removed in the presence of and without loss of the r 19 ( c 1 - c 6 ) alkyl or tert - butyl group , therefore , r 16 cannot be the same as r 19 . removal of the r 16 protecting group from the compound of formula xiii to give the corresponding carboxylic acid of formula xiv , wherein n is 1 to 6 , in reaction 3 of scheme 4 , is carried out under conditions appropriate for that particular r 16 protecting group in use which will not affect the r 19 ( c 1 - c 6 ) alkyl or tert - butyl group . such conditions include ; ( a ) saponification where r 16 is ( c 1 - c 6 ) alkyl and r 19 is tert - butyl , ( b ) hydrogenolysis where r 16 is benzyl and r 19 is tert - butyl or ( c 1 - c 6 ) alkyl , ( c ) treatment with a strong acid such as trifluoroacetic acid or hydrochloric acid where r 16 is tert - butyl and r 19 is ( c 1 - c 6 ) alkyl , or ( d ) treatment with tributyltinhydride and acetic acid in the presence of catalytic bis ( triphenylphosphine ) palladium ( ii ) chloride where r 16 is allyl and r 19 is ( c 1 - c 6 ) alkyl or tert - butyl . in reaction 4 of scheme 4 , the carboxylic acid of formula xiv is converted to the to the hydroxamic acid compound of formula xv , wherein n is 1 to 6 , by treating xiv with 1 -( 3 - dimethylaminopropyl )- 3 - ethylcarbodiimide and 1 - hydroxybenztriazole in a polar solvent , such as dimethylformamide , followed by the addition of hydroxylamine to the reaction mixture after a time period between about 15 minutes to about 1 hour , preferably about 30 minutes . the hydroxylamine is preferably generated in situ from a salt form , such as hydroxylamine hydrochloride , in the presence of a base , such as n - methylmorpholine . alternatively , a protected derivative of hydroxylamine or its salt form , where the hydroxyl group is protected as a tert - butyl , benzyl or allyl ether , may be used in the presence of ( benzotriazol - 1 - yloxy ) tris ( dimethylamino ) phosphonium hexafluorophosphate and a base , such as n - methylmorpholine . removal of the hydroxylamine protecting groups is carried out by hydrogenolysis for a benzyl protecting group or treatment with a strong acid , such as trifluoroacetic acid , for a tert - butyl protecting group . the allyl protecting group may be removed by treatment with tributyltinhydride and acetic acid in the presence of catalytic bis ( triphenylphosphine ) palladium ( ii ) chloride . n , o - bis ( 4 - methoxybenzyl ) hydroxylamine may also be used , when r 19 is ( c 1 - c 6 ) alkyl , as the protected hydroxylamine derivative where deprotection is achieved using a mixture of methanesulfonic acid and trifluoroacetic acid . in reaction 5 of scheme 4 , the amide formula of formula xv is , if desired , converted to the corresponding carboxylic acid compound of formula xvi by ( a ) saponification where r 19 is lower alkyl or ( b ) treatment with a strong acid , such as trifluoroacetic acid or hydrochloric acid , where r 19 is tert - butyl . pharmaceutically acceptable salts of the acidic compounds of the invention are salts formed with bases , namely cationic salts such as alkali and alkaline earth metal salts , such as sodium , lithium , potassium , calcium , magnesium , as well as ammonium salts , such as ammonium , trimethyl - ammonium , diethylammonium , and tris -( hydroxymethyl )- methylammonium slats . similarly acid addition salts , such as of mineral acids , organic carboxylic and organic sulfonic acids e . g . hydrochloric acid , methanesulfonic acid , maleic acid , are also possible provided a basic group , such as pyridyl , constitutes part of the structure . the ability of the compounds of formula i or their pharmaceutically acceptable salts ( hereinafter also referred to as the compounds of the present invention ) to inhibit matrix metalloproteinases or the production of tumor necrosis factor ( tnf ) and , consequently , demonstrate their effectiveness for treating diseases characterized by matrix metalloproteinase or the production of tumor necrosis factor is shown by the following in vitro assay tests . human recombinant collagenase is activated with trypsin using the following ratio : 10 μg trypsin per 100 μg of collagenase . the trypsin and collagenase are incubated at room temperature for 10 minutes then a five fold excess ( 50 μg / 10 μg trypsin ) of soybean trypsin inhibitor is added . 10 mm stock solutions of inhibitors are made up in dimethyl sulfoxide and then diluted using the following scheme : twenty - five microliters of each concentration is then added in triplicate to appropriate wells of a 96 well microfluor plate . the final concentration of inhibitor will be a 1 : 4 dilution after addition of enzyme and substrate . positive controls ( enzyme , no inhibitor ) are set up in wells d1 - d6 and blanks ( no enzyme , no inhibitors ) are set in wells d7 - d12 . collagenase is diluted to 400 ng / ml and 25 μl is then added to appropriate wells of the microfluor plate . final concentration of collagenase in the assay is 100 ng / ml . substrate ( dnp - pro - cha - gly - cys ( me )- his - ala - lys ( nma )-- nh 2 ) is made as a 5 mm stock in dimethyl sulfoxide and then diluted to 20 μm in assay buffer . the assay is initiated by the addition of 50 μl substrate per well of the microfluor plate to give a final concentration of 10 μm . fluorescence readings ( 360 nm excitation , 460 nm emission ) were taken at time 0 and then at 20 minute intervals . the assay is conducted at room temperature with a typical assay time of 3 hours . fluorescence vs time is then plotted for both the blank and collagenase containing samples ( data from triplicate determinations is averaged ). a time point that provides a good signal ( the blank ) and that is on a linear part of the curve ( usually around 120 minutes ) is chosen to determine ic 50 values . the zero time is used as a blank for each compound at each concentration and these values are subtracted from the 120 minute data . data is plotted as inhibitor concentration vs % control ( inhibitor fluorescence divided by fluorescence of collagenase alone × 100 ). ic 50 &# 39 ; s are determined from the concentration of inhibitor that gives a signal that is 50 % of the control . if ic 50 &# 39 ; s are reported to be & lt ; 0 . 03 μm then the inhibitors are assayed at concentrations of 0 . 3 μm , 0 . 03 μm , 0 . 03 μm and 0 . 003 μm . inhibition of gelatinase activity is assayed using the dnp - pro - cha - gly - cys ( me )- his - ala - lys ( nma )- nh 2 substrate ( 10 μm ) under the same conditions as inhibition of human collagenase ( mmp - 1 ). 72 kd gelatinase is activated with 1 mm apma ( p - aminophenyl mercuric acetate ) for 15 hours at 4 ° c . and is diluted to give a final concentration in the assay of 100 mg / ml . inhibitors are diluted as for inhibition of human collagenase ( mmp - 1 ) to give final concentrations in the assay of 30 μm , 3 μm , 0 . 3 μm and 0 . 03 μm . each concentration is done in triplicate . fluorescence readings ( 360 nm excitation , 460 emission ) are taken at time zero and then at 20 minutes intervals for 4 hours . ic 50 &# 39 ; s are determined as per inhibition of human collagenase ( mmp - 1 ). if ic 50 &# 39 ; s are reported to be less than 0 . 03 μm , then the inhibitors are assayed at final concentrations of 0 . 3 μm , 0 . 03 μm , 0 . 003 μm and 0 . 003 μm . inhibition of stromelysin activity is based on a modified spectrophotometric assay described by weingarten and feder ( weingarten , h . and feder , j ., spectrophotometric assay for vertebrate collagenase , anal . biochem . 146 , 437 - 440 ( 1985 )). hydrolysis of the thio peptolide substrate [ ac - pro - leu - gly - sch [ ch 2 ch ( ch 3 ) 2 ] co - leu - gly - oc 2 h 5 ] yields a mercaptan fragment that can be monitored in the presence of ellman &# 39 ; s reagent . human recombinant prostromelysin is activated with trypsin using a ratio of 1 μl of a 10 mg / ml trypsin stock per 26 μg of stromelysin . the trypsin and stromelysin are incubated at 37 ° c . for 15 minutes followed by 10 μl of 10 mg / ml soybean trypsin inhibitor for 10 minutes at 37 ° c . for 10 minutes at 37 ° c . to quench trypsin activity . assays are conducted in a total volume of 250 μl of assay buffer ( 200 mm sodium chloride , 50 mm mes , and 10 mm calcium chloride , ph 6 . 0 ) in 96 - well microliter plates . activated stromelysin is diluted in assay buffer to 25 μg / ml . ellman &# 39 ; s reagent ( 3 - carboxy - 4 - nitrophenyl disulfide ) is made as a 1m stock in dimethyl formamide and diluted to 5 mm in assay buffer with 50 μl per well yielding at 1 mm final concentration . 10 mm stock solutions of inhibitors are made in dimethyl sulfoxide and diluted serially in assay buffer such that addition of 50 μl to the appropriate wells yields final concentrations of 3 μm , 0 . 3 μm , 0 . 003 μm , and 0 . 0003 μm . all conditions are completed in triplicate . a 300 mm dimethyl sulfoxide stock solution of the peptide substrate is diluted to 15 mm in assay buffer and the assay is initiated by addition of 50 μl to each well to give a final concentration of 3 mm substrate . blanks consist of the peptide substrate and ellman &# 39 ; s reagent without the enzyme . product formation was monitored at 405 nm with a molecular devices uvmax plate reader . ic 50 values were determined in the same manner as for collagenase . human recombinant mmp - 13 is activated with 2 mm apma ( p - aminophenyl mercuric acetate ) for 1 . 5 hours , at 37 ° c . and is diluted to 400 mg / ml in assay buffer ( 50 mm tris , ph 7 . 5 , 200 mm sodium chloride , 5 mm calcium chloride , 20 μm zinc chloride , 0 . 02 % brij ). twenty - five microliters of diluted enzyme is added per well of a 96 well microfluor plate . the enzyme is then diluted in a 1 : 4 ratio in the assay by the addition of inhibitor and substrate to give a final concentration in the assay of 100 mg / ml . 10 mm stock solutions of inhibitors are made up in dimethyl sulfoxide and then diluted in assay buffer as per the inhibitor dilution scheme for inhibition of human collagenase ( mmp - 1 ): twenty - five microliters of each concentration is added in triplicate to the microfluor plate . the final concentration in the assay are 30 μm , 3 μm , 0 . 3 μm , and 0 . 03 μm . substrate ( dnp - pro - cha - gly - cys ( me )- his - ala - lys ( nma )- nh 2 ) is prepared as for inhibition of human collagenase ( mmp - 1 ) and 50 μl is added to each well to give a final assay concentration of 10 μm . fluorescence readings ( 360 nm excitation ; 450 emission ) are taken at time 0 and every 5 minutes for 1 hour . positive controls consist of enzyme and substrate with no inhibitor and blanks consist of substrate only . ic 50 &# 39 ; s are determined as per inhibition of human collagenase ( mmp - 1 ). if ic 50 &# 39 ; s are reported to be less than 0 . 03 μm , inhibitors are then assayed at final concentrations of 0 . 3 μm , 0 . 03 μm , 0 . 003 μm and 0 . 0003 μm . the ability of the compounds or the pharmaceutically acceptable salts thereof to inhibit the production of tnf and , consequently , demonstrate their effectiveness for treating diseases involving the production of tnf is shown by the following in vitro assay : human mononuclear cells were isolated from anti - coagulated human blood using a one - step ficoll - hypaque separation technique . ( 2 ) the mononuclear cells were washed three times in hanks balanced salt solution ( hbss ) with divalent cations and resuspended to a density of 2 × 10 6 / ml in hbss containing 1 % bsa . differential counts determined using the abbott cell dyn 3500 analyzer indicated that monocytes ranged from 17 to 24 % of the total cells in these preparations . 180μ of the cell suspension was aliquoted into flate bottom 96 well plates ( costar ). additions of compounds and lps ( 100 ng / ml final concentration ) gave a final volume of 200 μl . all conditions were performed in triplicate . after a four hour incubation at 37 ° c . in an humidified co 2 incubator , plates were removed and centrifuged ( 10 minutes at approximately 250 × g ) and the supernatants removed and assayed for tnfα using the r & amp ; d elisa kit . for administration to humans for the inhibition of matrix metalloproteinases or the production of tumor necrosis factor ( tnf ), a variety of conventional routes may be used including orally , parenterally and topically . in general , the active compound will be administered orally or parenterally at dosages between about 0 . 1 and 25 mg / kg body weight of the subject to be treated per day , preferably from about 0 . 3 to 5 mg / kg . however , some variation in dosage will necessarily occur depending on the condition of the subject being treated . the person responsible for administration will , in any event , determine the appropriate dose for the individual subject . the compounds of the present invention can be administered in a wide variety of different dosage forms , in general , the therapeutically effective compounds of this invention are present in such dosage forms at concentration levels ranging from about 5 . 0 % to about 70 % by weight . for oral administration , tablets containing various excipients such as microcrystalline cellulose , sodium citrate , calcium carbonate , dicalcium phosphate and glycine may be employed along with various disintegrants such as starch ( and preferably corn , potato or tapioca starch ), alginic acid and certain complex silicates , together with granulation binders like polyvinylpyrrolidone , sucrose , gelation of acacia . additionally , lubricating agents such as magnesium stearate , sodium lauryl sulfate and talc are often very useful for tabletting purposes . solid compositions of a similar type may also be employed as fillers in gelatin capsules ; preferred materials in this connection also include lactose or milk sugar as well as high molecular weight polyethylene glycols . when aqueous suspensions and / or elixirs are desired for oral administration , the active ingredient may be combined with various sweetening or flavoring agents , coloring matter or dyes , and , if so desired , emulsifying and / or suspending agents as well , together with such diluents as water , ethanol , propylene glycol , glycerin and various like combinations thereof . for parenteral administration ( intramuscular , intraperitoneal , subcutaneous and intravenous use ) a sterile injectable solution of the active ingredient is usually prepared . solutions of a therapeutic compound of the present invention in either sesame or peanut oil or in aqueous propylene glycol may be employed . the aqueous solutions should be suitably adjusted and buffered , preferably at a ph of greater than 8 , if necessary and the liquid diluent first rendered isotonic . these aqueous solutions are suitable intravenous injection purposes . the oily solutions are suitable for intraarticular , intramuscular and subcutaneous injection purposes . the preparation of all these solutions under sterile conditions is readily accomplished by standard pharmaceutical techniques well know to those skilled in the art . the present invention is illustrated by the following examples , but it is not limited to the details thereof . to a solution of d - valine benzyl ester hydrochloride ( 2 . 4 grams , 10 mmol ) and triethylamine ( 2 . 5 grams , 3 . 5 ml , 25 mmol ) in water 50 ml ) and 1 , 4 - dioxane ( 50 ml ) is added 4 - methoxybenzenesylfonyl chloride ( 2 . 3 grams , 11 mmol ). the mixture was stirred at room temperature for 1 hour and then most of the solvent was removed by evaporation under vacuum . the mixture was diluted with ethyl acetate and was washed successively with dilute hydrochloric acid solution , water and brine . the organic solution was dried over magnesium sulfate and concentrated to leave n -( 4 - methoxybenzenesulfonyl )- d - valine benzyl ester as a white solid , 3 . 6 grams ( 97 %); m . p . 92 - 94 ° c . n -( 4 - methoxybenzenesulfonyl )- d - valine benzyl ester ( 1 . 50 grams , 4 . 0 mmol ) was added to a suspension of sodium hydride ( 0 . 1 grams , 4 . 2 mmol ) in dry dimethylformamide ( 20 ml ) and , after 30 minutes , tert - butyl bromoacetate ( 0 . 8 ml , 4 . 2 mmol ) was added . the resulting mixture was stirred overnight at room temperature and was then quenched by addition of saturated ammonium chloride solution ( 3 ml ). the dimethylformamide was removed by evaporation under vacuum . the residue was taken up in ethyl acetate and washed with water and brine . after drying over magnesium sulfate , ethyl acetate was evaporated to leave an oil from which 2 -( r )- 2 -[ tert - butoxycarbonylmethyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester , a clear oil ( 1 . 92 grams , 98 %), was isolated using flash chromatography on silica gel eluting with 15 % ethyl acetate in hexane . to a cold ( 0 ° c .) solution of 2 -( r )- 2 -[ tert - butoxycarbonylmethyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester ( 1 . 92 grams , 3 . 9 mmol ) in methylene chloride ( 28 ml ) was added trifluoroacetic acid ( 7 ml ). the resulting solution was allowed to warm to room temperature and was stirred overnight . the methylene chloride and trifluoroacetic acid were evaporated under vacuum leaving 2 -( r )- 2 -[ carboxylmethyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester as a clear oil , 1 . 70 grams ( 100 %). to a solution of 2 -( r )- 2 -[ carboxylmethyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester ( 573 mg , 1 . 32 mmol ) in methylene chloride ( 12 ml ) were added sequentially triethylamine ( 0 . 46 ml , 3 . 28 mmol ), morpholine ( 0 . 127 ml , 1 . 46 mmol ) and benzotriazol - 1 - yloxy ) tris ( dimethylamino ) phosphonium hexafluorophosphate ( 646 mg , 1 . 46 mmol ). the mixture was stirred at room temperature overnight and then diluted with ethyl acetate . the solution was washed with 0 . 5 n hydrochloric acid solution and brine , dried over magnesium sulfate and concentrated under vacuum . the residue was chromatographed on silica gel using 40 % ethyl acetate in hexane affording 2 -( r )- 2 -[( 4 - methoxybenzenesulfonyl )( 2 - morpholin - 4 - yl - oxoethyl ) amino ]- 3 - methylbutyric acid benzyl ester as a clear oil , 590 mg ( 89 %). to a solution of 2 -( r )- 2 -[( 4 - methoxybenzenesulfonyl )( 2 - morpholin - 4 - yl - oxoethyl ) amino ]- 3 - methylbutyric acid benzyl ester ( 590 mg , 1 . 17 mmol ) in ethanol ( 50 ml ) was added 10 % palladium on activated carbon ( 200 mg ). the mixture was agitated under 3 atmospheres hydrogen in a parr shaker for 2 hours . the catalyst was removed by filtration through nylon ( pore size 0 . 45 μm ) and the solvent was evaporated leaving 2 -( r )- 2 -[( 4 - methoxybenzenesulfonyl )( 2 - morpholin - 4 - yl - oxoethyl ) amino ]- 3 - methylbutyric acid as a white foam , 485 mg ( 100 %). to a solution of 2 -( r )- 2 -[( 4 - methoxybenzenesulfonyl )( 2 - morpholin - 4 - yl - oxoethyl ) amino ]- 3 - methylbutyric acid ( 485 mg , 1 . 17 mmol ) in methylene chloride ( 12 ml ) were added sequentially triethylamine ( 0 . 52 ml , 3 . 71 mmol ), o - benzylhydroxylamine hydrochloride ( 205 mg , 1 . 28 mmol ) and ( benzotriazol - 1 - yloxy ) tris ( dimethylamino ) phosphonium hexafluorophosphate ( 570 mg , 1 . 29 mmol ). the mixture was stirred at room temperature overnight and then diluted with ethyl acetate . the solution was washed sequentially with 0 . 5 n hydrochloric acid solution , water , saturated sodium hydrogen carbonate solution and brine , dried over magnesium sulfate and concentrated under vacuum . the residue was chromatographed on silica gel using 20 % hexane in ethyl acetate to afford 2 -( r )- n - benzyloxy - 2 -[( 4 - methoxybenzenesulfonyl )( 2 - morpholin - 4 - yl - oxoethyl ) amino ]- 3 - methylbutyramide as a white foam , 510 mg ( 84 %). to a solution of 2 -( r )- n - benzyloxy - 2 -[( 4 - methoxybenzenesulfonyl )( 2 - morpholin - 4 - yl - oxoethyl ) amino ]- 3 - methylbutyric ( 510 mg , 0 . 98 mmol ) in methanol ( 50 ml ) was added 5 % palladium on activated carbon ( 120 mg ). the mixture was agitated under 2 atmospheres hydrogen in a parr shaker for 2 hours . the catalyst was removed by filtration through nylon ( pore size 0 . 45 μm ) and the solvent was evaporated leaving 2 -( r )- n - hydroxy - 2 -[( 4 - methoxybenzenesulfonyl )( 2 - morpholin - 4 - yl - oxoethyl ) amino ]- 3 - methylbutyramide as a white solid , 418 mg ( 99 %); 1 h nmr ( cdcl 3 ): δ10 . 3 ( br s , 1h ), 7 . 90 ( br s , 1 h , overlapped ), 7 . 86 ( d , j = 8 . 8 hz , 2h , overlapped ), 6 . 94 ( d , j = 8 . 8 hz , 2h ), 4 . 39 ( d , j = 17 . 1 hz , 1h ), 4 . 09 ( d , j = 17 . 1 , 1h ), 3 . 84 ( s , 3h ), 3 . 80 - 3 . 48 ( m , 9h ), 2 . 20 - 1 . 95 ( m , 1h ), 0 . 82 ( d , j = 6 . 5 hz , 3h ), 0 . 45 ( d , j = 6 . 5 hz , 3h ); ms ( lsims ): m / z 430 ( m + h ). to a solution of n -( 4 - methoxybenzenesulfonyl )- d - valine benzyl ester ( 2 . 2 grams , 5 . 83 mmol ) in dry dimethylformamide ( 40 ml ) were added cesium carbonate ( 2 . 3 grams , 7 . 1 mmol ) and 1 - iodo - 3 - butene ( 1 . 3 grams , 7 . 1 mmol ). the mixture was stirred at room temperature overnight and was then poured into water . the mixture was extracted twice with ether and the combined ether extracts were washed with brine , dried over magnesium sulfate and concentrated under reduced pressure . the residue was taken up in 20 % ethyl acetate / hexane ; starting material n -( 4 - methoxybenzenesulfonyl )- d - valine benzyl ester ( 1 . 5 g ) crystallized from the mixture and was recovered by filtration . the filtrate was concentrated under vacuum and the residue was chromatographed on silica gel using 20 % ethyl acetate / hexane as eluant to provide 2 -( r )- 2 -[ but - 3 - enyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester as a clear oil , 404 mg ( 16 %). to a mixture of 2 -( r )- 2 -[ but - 3 - enyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester ( 780 mg , 1 . 81 mmol ) and ruthenium ( iii ) chloride hydrate ( 10 mg , 0 . 048 mmol ) in acetonitrile ( 6 ml ), carbon tetrachloride ( 6 ml ) and water ( 8 ml ) was added sodium periodate ( 1 . 7 grams , 7 . 9 mmol ). after stirring at room temperature for 2 hours , the mixture was diluted with methylene chloride and filtered through diatomaceous earth . the organic layer was separated , washed with dilute hydrochloric acid solution and brine , dried over magnesium sulfate and concentrated to leave 2 -( r )- 2 -[ 2 - carboxyethyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester as a clear oil , 710 mg ( 87 %). alternatively , the intermediate 2 -( r )- 2 -[ 2 - carboxyethyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester was prepared by the following higher yielding procedure : n -( 4 - methoxybenzenesulfonyl )- d - valine benzyl ester ( 18 . 8 grams , 49 . 8 mmol ) was added to a suspension of sodium hydride ( 1 . 3 grams , 54 mmol ) in dry dimethylformamide ( 200 ml ) and , after 1 . 5 hours , a solution of allyl bromide ( 4 . 7 ml , 54 mmol ) was added . the resulting mixture was stirred overnight at room temperature and was then quenched by addition of saturated ammonium chloride solution . the dimethylformamide was removed by evaporation under vacuum . the residue was taken up in ether and washed with water and brine . after drying over magnesium sulfate , ether was evaporated to leave an oil from which 2 -( r )- 2 -[( 4 - methoxybenzenesulfonyl ) prop - 2 - enylamino ]- 3 - methylbutyric acid benzyl ester , a clear oil ( 18 . 1 grams , 87 %), was isolated using flash chromatography on silica gel eluting with 10 % ethyl acetate in hexane and then 20 % ethyl acetate in hexane . to a 1 m solution of borane / disulfide complex in methylene chloride ( 1 . 45 ml , 2 . 9 mmol ) was added a solution of 2 -( r )- 2 -[ 2 -( r )- 2 -[( 4 - methoxybenzenesulfonyl ) prop - 2 - enylamino ]- 3 - methylbutyric acid benzyl ester ( 3 . 6 grams , 8 . 6 mmol ) in methylene chloride ( 8 ml ). the solution was stirred at room temperature for 4 hours at which time more 1 m solution of borane / disulfide complex in methylene chloride ( 2 . 0 ml , 4 . 0 mmol ) was added . the mixture was stirred at room temperature overnight and was then added dropwise to a mechanically stirred solution of chromium trioxide ( 5 . 1 grams , 51 . 6 mole ) in acetic acid ( 31 ml ) and water ( 3 . 5 ml ) while keeping the internal temperature between - 5 ° c . and 10 ° c . after stirring at room temperature overnight , the mixture was diluted with water and extracted with methylene chloride . the extract was washed with brine , dried ( magnesium sulfate ) and concentrated . the residue was chromatographed on silica gel eluting successively with chloroform and 2 % methanol in chloroform to afford 2 -( r )- 2 -[ 2 - carboxyethyl2 -( r )- 2 -[( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl as an oil ( 2 . 42 grams , 63 %). to a solution of 2 -( r )- 2 -[ 2 - carboxyethyl2 -( r )- 2 -[( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester ( 710 mg , 1 . 58 mmol ) in methylene chloride ( 15 ml ) were added sequentially triethylamine ( 0 . 47 ml , 3 . 35 mmol ), morpholine ( 0 . 15 ml , 1 . 72 mmol ) and ( benzotriazol - 1 - yloxy ) tris ( dimethylamino ) phosphoniumhexafluorophosphate ( 769 mg , 1 . 74 mmol ). the mixture was stirred at room temperature overnight and then diluted with methylene chloride . the solution was washed with 0 . 5 n hydrochloric acid solution and brine , dried over magnesium sulfate and concentrated under vacuum . the solid residue was chromatographed on silica gel using 20 % hexane in ethyl acetate affording 2 -( r )- 2 -[( 4 - methoxybenzenesulfonyl )( 3 - morpholin - 4 - yl - 3 - oxopropyl ) amino ]- 3 - methylbutyric acid benzyl ester as a clear oil , 725 mg ( 88 %). to a solution of 2 -( r )- 2 -[( 4 - methoxybenzenesulfonyl )( 3 - morpholin - 4 - yl - 3 - oxopropyl ) amino ]- 3 - methylbutyric acid benzyl ester ( 725 mg , 1 . 40 mmol ) in ethanol ( 35 ml ) was added 10 % palladium on activated carbon ( 50 mg ). the mixture was agitated under 3 atmospheres hydrogen in a parr shaker for 3 hours . the catalyst was removed by filtration through nylon ( pore size 0 . 45 μm ) and the solvent was evaporated leaving 2 -( r )- 2 -[( 4 - methoxybenzenesulfonyl )( 3 - morpholin - 4 - yl - 3 - oxopropyl ) amino ]- 3 - methylbutyric acid as a white solid , 540 mg ( 90 %). to a solution 2 -( r )- 2 -[( 4 - methoxybenzenesulfonyl )( 3 - morpholin - 4 - yl - 3 - oxopropyl ) amino ]- 3 - methylbutyric acid ( 540 mg , 1 . 26 mmol ) and 1 - hydroxybenztriazole hydrate ( 205 mg , 1 . 33 mmol ) in dry dimethylformamide ( 12 ml ) was added 1 -( 3 - dimethylaminopropyl )- 3 - ethylcarbodimide hydrochloride ( 289 mg , 1 . 51 mmol ). after stirring for 30 minutes , hydroxylamine hydrochloride ( 350 mg , 5 . 04 mmol ) and then triethylamine ( 1 . 0 ml , 7 . 17 mmol ) were added . the mixture was stirred at room temperature overnight and then diluted with ethyl acetate . the solution was washed sequentially with water , 0 . 5 n hydrochloric acid solution and brine . the solution was then dried over magnesium sulfate and concentrated under vacuum to leave a white foam . the material was dissolved in toluene , filtered and concentrated . the residue was triturated with ether to afford 2 -( r )- n - hydroxy - 2 -[( 4 - methoxybenzenesulfonyl )( 3 - morpholin - 4 - yl - 3 - oxoethyl ) amino ]- 3 - methylbutyramide as a solid , 200 mg ( 36 %); 1 h nmr ( cdcl 3 ): δ9 . 35 ( br s , 1h ), 7 . 73 ( d , j = 8 . 9 hz , 2h ), 6 . 95 ( d , j = 8 . 9 hz , 2h ), 3 . 86 ( s , 3h ), 3 . 83 - 3 . 73 ( m , 1h ), 3 . 70 - 3 . 52 ( m , 7h ), 3 . 46 - 3 . 43 ( m , 2h ), 3 . 41 - 3 . 29 ( m , 1h ), 2 . 92 - 2 . 69 ( m , 2h ), 2 . 30 - 2 . 17 ( m , 1h ), 0 . 84 ( d , j = 6 . 5 hz , 3h ), 0 . 41 ( d , j = 6 . 5 hz , 3h ); ms ( particle beam ): m / z 444 ( m + h ), 428 , 383 , 329 ; hrms calculated for c 19 h 30 n 3 o 7 s ( m + h ): 444 . 1804 , found : 464 . 1818 . the title compounds of examples 3 - 6 were prepared by a method analogous to that described in example 2 using 2 -( r )- 2 -[ 2 - carboxyethyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester as the starting material which is coupled with the amine indicated . coupled with benzylamine ; 1 h nmr ( dmso - d 6 ): δ10 . 72 ( s , 1h ), 8 . 89 ( s , 1h ), 8 . 39 ( m , 1h ), 7 . 74 ( d , j = 9 . 0 hz , 2h ), 7 . 32 - 7 . 21 ( m , 5h ), 7 . 05 ( d , j = 9 . 0 hz , 2h ), 4 . 21 ( d , j = 5 . 9 hz , 2h ), 4 . 02 - 3 . 87 ( m , 1h ), 3 . 82 ( s , 3h ), 3 . 63 ( d , j = 10 . 8 hz , 1h ), 3 . 29 - 3 . 17 ( m , 1h ), 2 . 71 - 2 . 57 ( m , 1h ), 2 . 52 - 2 . 40 ( m , 1h ), 2 . 06 - 1 . 94 ( m , 1h ), 0 . 77 ( d , j = 6 . 6 hz , 3h ), 0 . 74 ( d , j = 6 . 5 hz , 3h ); ms ( lsims ): m / z 464 ( m + h ); hrms calculated for c 22 h 30 n 3 o 6 s ( m + h ): 464 . 1855 . found : 464 . 1832 . coupled with 3 - pyridylmethylamine : 1 h nmr ( dmso - d 6 ): δ10 . 72 ( s , 1h ), 8 . 89 ( s , 1h ), 8 . 49 - 8 . 42 ( m , 3h ), 7 . 73 ( d , j = 8 . 9 hz , 2h ), 7 . 63 - 7 . 60 ( m , 1h ), 7 . 32 ( dd , j = 4 . 8 , 7 . 8 hz , 1h ), 7 . 05 ( d , j = 8 . 9 hz , 2h ), 4 . 23 ( d , j = 5 . 8 hz , 2h ), 4 . 00 - 3 . 88 ( m , 1h ), 3 . 81 ( s , 3h ), 3 . 62 ( d , j = 10 . 8 hz , 1h ), 3 . 27 - 3 . 17 ( m , 1h ), 2 . 69 - 2 . 58 ( m , 1h ), 2 . 52 - 2 . 41 ( m , 1h ), 2 . 07 - 1 . 94 ( m , 1h ), 0 . 76 ( d , j = 6 . 5 hz , 3h ), 0 . 72 ( d , j = 6 . 4 hz , 3h ); ms ( lsims ): m / z 465 ( m + h ). coupled with 3 -( n - methylaminomethyl ) pyridine : 1 h nmr ( dmso - d 6 ): δ10 . 75 ( br , s , 1h ), 8 . 92 ( s , 1h ), 8 . 52 - 8 . 29 ( m , 2h ), 7 . 75 ( d , j = 8 . 8 hz , 1 . 4 h ), 7 . 67 ( d , j = 8 . 8 hz , 0 . 6 h ), 7 . 62 - 7 . 58 ( m , 1h ), 7 . 42 - 7 . 32 ( m , 1h ), 7 . 06 ( d , j = 8 . 8 hz , 1 . 4 h ), 7 . 01 ( d , j = 8 . 8 hz , 0 . 6h ), 4 . 55 - 4 . 41 ( m , 2h ), 3 . 94 - 3 . 82 ( m , 1h ), 3 . 81 ( s , 2 . 1 h ), 3 . 80 ( s , 0 . 9 h ), 3 . 68 - 3 . 60 ( m , 1h ), 3 . 33 - 3 . 19 ( m , 1h ), 2 . 90 - 2 . 50 ( m , 2h ), 2 . 88 ( s , 2 . 1 h overlapped ), 2 . 79 ( s , 0 . 9 h ), 2 . 05 - 1 . 80 ( m , 1h ), 0 . 79 - 0 . 63 ( m , 6h ): ms ( thermospray ): m / z 479 ( m + h ), 364 . coupled with tert - butyl - 1 - piperazinecarboxylate : 1 h nmr ( dmso - d 6 ): δ10 . 77 ( br , s , 1h ), 8 . 93 ( s , 1h ), 7 . 74 ( d , j = 8 . 9 hz , 2h ), 7 . 06 ( d , j = 8 . 9 hz , 2h ), 3 . 90 - 3 . 80 ( m , 1h ), 3 . 82 ( s , 3h , overlapped ), 3 . 64 ( d , j = 10 . 8 hz , 1h ), 3 . 60 - 3 . 16 ( m , 9h ), 2 . 80 - 2 . 71 ( m , 1h ), 2 . 59 - 2 . 47 ( m , 1h ) 2 . 03 - 1 . 91 ( m , 1h ), 1 . 39 ( s , 9h ), 0 . 77 ( d , j = 6 . 5 hz , 3h ), 0 . 71 ( d , j = 6 . 5 , 3h ); ms ( thermospray ): m / z 543 ( m + h ), 443 , 382 , 328 . a solution of 4 -( 3 -[( 1 -( r )- 1 - hydroxycarbamoyl - 2 - methylpropyl )( 4 - methoxybenzenesulfonyl ) amino ] propionyl ) piperazine - 1 - carboxylic acid , tert - butyl ester [ example 6 ] ( 430 mg , 0 . 79 mmol ) in methylene chloride ( 11 ml ) was cooled to 0 ° c . hydrogen chloride gas was then bubbled through the solution for about 0 . 5 minute . the solution was allowed to warm to room temperature with stirring over 1 hour . volatiles were removed by evaporation and the residue was filtered , washing with methylene chloride to collect solid 2 -( r )- n - hydroxy - 2 -[( 4 - methoxybenzenesulfonyl )( 3 - oxo - 3 - piperazin - 1 - ylpropyl ) amino ]- 3 - methylbutyramide hydrochloride , 375 mg ( 99 %). 1 h nmr ( dmso - d 6 ): δ10 . 78 ( br s , 1h ), 9 . 16 ( br , s 1h ), 7 . 74 ( d , j = 8 . 8 hz , 2h ), 7 . 07 ( d , j = 8 . 9 hz , 2h ), 3 . 82 ( s , 3h ), 3 . 62 ( br , s 4h ), 3 . 38 - 3 . 18 ( m , 1h ), 3 . 16 - 3 . 07 ( br s , 2h ), 3 . 07 - 2 . 98 ( br s , 2h ), 2 . 83 - 2 . 73 ( m , 1h ), 2 . 65 - 2 . 53 ( m , 1h ), 2 . 06 - 1 . 90 ( m , 1h ), 0 . 76 ( d , j = 6 . 5 hz , 3h ), 0 . 72 ( d , j = 6 . 5 hz , 3h ). a broad water peak between δ4 . 0 and 3 . 5 obscured some signals from this compound ; ms ( thermospray ): m / z 443 m + h ), 382 , 328 . to a solution of 2 -( r )- 2 -[ carboxymethyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester ( example 1 ) ( 905 mg , 2 . 08 mmol ) in methylene chloride ( 18 ml ) were added sequentially triethylamine ( 0 . 72 ml , 5 . 14 mmol ), benzylamine ( 0 . 25 ml , 2 . 29 mmol ) and benzotriazol - 1 - yloxy ) tris ( dimethylamino ) phosphonium hexafluorophosphate ( 1 . 01 grams , 2 . 28 mmol ). the mixture was stirred at room temperature overnight and then diluted with ethyl acetate . the solution was washed with 0 . 5 n hydrochloric acid solution and brine , dried over magnesium sulfate and concentrated under vacuum . the residue was chromatographed on silica gel using a 2 : 5 : 16 ratio of methylene chloride / ethyl acetate / hexane affording 2 -( r )- 2 -[( benzylcarbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester as a clear oil , 933 mg ( 86 %). to a solution of 2 -( r )- 2 -[( 2 - benzylcarbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester ( 933 mg , 1 . 17 mmol ) in ethanol ( 50 ml ) was added 10 % palladium on activated carbon ( 85 mg ). the mixture was agitated under 3 atmospheres hydrogen in a parr shaker for 4 hours . the catalyst was removed by filtration through nylon ( pore size 0 . 45 μm ) and the solvent was evaporated leaving 2 -( r )- 2 -[( 2 - benzylcarbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid as a white foam , 755 mg ( 98 %). to a solution of 2 -( r )- 2 -[( 2 - benzylcarbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid ( 655 mg , 1 . 51 mmol ) and 1 - hydroxybenztriazole hydrate ( 224 mg , 1 . 46 mmol ) in dry dimethylformamide ( 15 ml ) was added 1 -( 3 - dimethylaminopropyl )- 3 - ethylcarbodiimide hydrochloride ( 316 mg , 1 . 65 mmol ). after stirring for 30 minutes , hydroxylamine hydrochloride ( 416 mg , 6 . 0 mmol ) and then n - methylmorpholine ( 0 . 99 ml , 9 . 0 mmol ) were added . the mixture was stirred at room temperature overnight and then diluted with ethyl acetate . the solution was washed sequentially with water , 0 . 5 n hydrochloric acid solution and brine . the solution was then dried over magnesium sulfate and concentrated under vacuum to leave a white foam which was chromatographed on silica gel eluting with ethyl acetate to afford 2 -( r )- 2 -[( 2 - benzylcarbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyramide as a white foam , 570 mg ( 84 %); 1 h nmr ( dmso - d 6 ): δ10 . 75 ( br s , 1h ), 8 . 90 ( s , 1h ), 8 . 47 ( m , 1h ), 7 . 85 ( d , j = 8 . 9 hz , 2h ), 7 . 83 - 7 . 19 ( m , 5h ), 7 . 04 ( d , j = 8 . 9 hz , 2h ), 4 . 37 ( d , j = 11 . 4 hz , 1h ), 4 . 28 ( d , j = 5 . 9 hz , 2h ), 3 . 89 ( d , j = 11 . 4 hz , 1h ), 3 . 82 ( s , 3h ), 3 . 45 ( d , j = 10 . 3 hz , 1h ), 1 . 90 - 1 . 79 ( m , 1h ), 0 . 73 ( d , j = 6 . 3 hz , 6h ); ms ( lsims ): m / z 450 ( m + h ). to a solution of 2 -( r )- 2 -[ carboxymethyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester ( example 1 ) ( 1 . 05 grams , 2 . 41 mmol ) in methylene chloride ( 20 ml ) were added sequentially triethylamine ( 0 . 84 ml , 6 . 0 mmol ), n - benzylmethylamine ( 0 . 34 ml , 2 . 63 mmol ) and benzotriazol - 1 - yloxy ) tris ( dimethylamino ) phosphonium hexafluorophosphate ( 1 . 17 grams , 2 . 69 mmol ). the mixture was stirred at room temperature overnight and then diluted with ethyl acetate . the solution was washed with 0 . 5 n hydrochloric acid solution and brine , dried over magnesium sulfate and concentrated under vacuum . the residue was chromatographed on silica gel using 35 % ethyl acetate in hexane ( plus a small amount of methylene chloride to load the sample on the column ) affording 2 -( r )- 2 -[( benzylcarbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyramide benzyl ester as a clear oil , 1 . 14 grams ( 88 %). to a solution of 2 -( r )- 2 -[( benzylcarbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester ( 1 . 14 grams , 2 . 12 mmol ) in ethanol ( 100 ml ) was added 10 % palladium on activated carbon ( 400 mg ). the mixture was agitated under 3 atmospheres hydrogen in a parr shaker for 3 hours . the catalyst was removed by filtration through nylon ( pore size 0 . 45 μm ) and the solvent was evaporated leaving 2 -( r )- 2 -[( 2 - benzylcarbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid as a white foam , 902 mg ( 95 %). to a solution of 2 -( r )- 2 -[( 2 - benzylcarbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid ( 902 mg , 2 . 01 mmol ) in methylene chloride ( 20 ml ) were added sequentially triethylamine ( 0 . 90 ml , 6 . 42 mmol ), o - allylhydroxylamine hydrochloride ( 242 mg , 2 . 21 mmol ) and ( benzotriazol - 1 - yloxy )- tris ( dimethylamino ) phosphonium hexafluorophosphate ( 978 mg , 2 . 21 mmol ). the mixture was stirred at room temperature overnight and then diluted with ethyl acetate . the solution was washed with 0 . 5 n hydrochloric acid solution and brine , dried over magnesium sulfate and concentrated under vacuum . the residue was chromatographed on silica gel using 40 % hexane in ethyl acetate to afford 2 -( r )- n - allyloxy - 2 -[( benzylmethylcarbamoylmethyl )( 4 - methoxy - benzenesulfonyl ) amino ]- 3 - methylbutyramide as an oil , 1 . 008 grams ( 100 %). to a solution of 2 -( r )- n - allyloxy - 2 -[( benzylmethylcarbamoylmethyl )( 4 - methoxy - benzenesulfonyl ) amino ]- 3 - methylbutyramide ( 500 mg , 0 . 99 mmol ) in methylene chloride ( 40 ml ) was added bis ( triphenylphosphine ) palladium ( ii ) chloride ( 280 mg , 0 . 4 mmol ) and then , dropwise , tributyltinhydride ( 0 . 43 ml , 2 . 2 mmol ). the solution was stirred at room temperature for 1 hour , diluted with methylene chloride , washed with 1n hydrochloric acid solution , dried over magnesium sulfate and concentrated . the residue was taken up in ethyl acetate and filtered to remove a solid . after concentration , the filtrate was chromatographed on silica gel eluting with chloroform and then 2 % methanol in chloroform to afford 2 -( r )- 2 -[( 2 - benzylcarbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyramide as a white solid ( 340 mg , 74 %). 1 h nmr ( dmso - d 6 ): δ10 . 66 ( br s , 1h ), 8 . 87 ( br s , 0 . 6h ), 8 . 84 ( s , 0 . 4 h ), 7 . 91 ( d , j = 8 . 9 hz , 1 . 2 h ), 7 . 78 ( d , j = 8 . 9 hz , 0 . 8 h ), 7 . 43 - 7 . 21 ( m , 5h ), 7 . 05 ( d , j = 8 . 9 hz , 1 . 2 h ), 7 . 00 ( d , j = 8 . 9 hz , 0 . 8 h ) 4 . 72 ( d , j = 17 . 7 hz , 0 . 4h ), 4 . 70 ( d , j = 17 . 7 hz , 0 . 6h ), 4 . 59 - 4 . 25 ( d , j = 17 . 8 hz , 0 . 6h ), 4 . 07 ( d , j = 17 . 7 hz , 0 . 4h ), 3 . 82 ( s , 3h ), 3 . 46 - 3 . 40 ( m , 1h ), 2 . 91 ( s , 1 . 8h ), 2 . 83 ( s , 1 . 2 h ), 1 . 92 - 1 . 70 ( m , 1h ), 0 . 75 - 0 . 69 ( m , 6h ); ms ( thermospray ): m / z 464 ( m + h ), 307 , 239 . the title compounds of examples 10 - 11 were prepared by a method analogous to that described in example 9 using 2 -( r )- 2 -[ carboxymethyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester ( example 1 ) as the starting material which is coupled with the amine indicated . coupled with 4 -( 2 - aminoethyl ) morpholine : 1 h nmr ( dmso - d 6 ): δ10 . 74 ( br s , 1h ), 8 . 90 ( br s , 1h ), 7 . 84 ( br s , 1h , overlapped ), 7 . 84 ( d , j = 8 . 8 hz , 2h ), 7 . 06 ( d , j = 8 . 8 hz , 2h ), 4 . 33 ( d , j = 17 . 5 hz , 1h ), 3 . 83 ( s , 3h ), 3 . 78 ( d , j = 17 . 5 hz , 1h ), 3 . 57 - 3 . 54 ( m , 4h ), 3 . 49 ( d , j = 10 . 2 hz , 1h ), 3 . 28 - 3 . 06 ( m , 2h ), 2 . 34 - 2 . 30 ( m , 6h ), 1 . 93 - 1 . 77 ( m , 1h ), 0 . 77 - 0 . 74 ( m , 6h ). coupled with pyrrolidine : 1 h nmr ( cd 3 od ): δ7 . 90 ( d , j = 8 . 9 hz , 2h ), 7 . 04 ( d , j = 8 . 9 hz , 2h ), 4 . 50 ( d , j = 17 . 6 hz , 1h ), 4 . 15 ( d , j = 17 . 6 hz , 1h ), 3 . 87 ( s , 3h ), 3 . 56 - 3 . 39 ( m , 5h ), 2 . 07 - 1 . 82 ( m , 5h ), 0 . 3 ( d , j = 6 . 6 hz , 3h ), 0 . 73 ( d , j = 6 . 6 hz , 3h ); ms ( thermospray ): m / z 414 ( m + 1 ); hrms calculated for c 18 h 28 n 3 o 6 s ( m + h ): 414 . 1699 . found 414 . 1703 . a solution of 2 -( r )- 2 -[ carboxymethyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester ( example 1 ) ( 1 . 89 grams , 4 . 34 mmol ) in thionyl chloride ( 25 ml ) was heated at reflux for 1 hour . after cooling , the excess thionyl chloride was evaporated . the residue was taken up in methylene chloride ( 50 ml ) and the solution was cooled in an ice bath . dimethylamine gas was slowly bubbled through the solution for 1 hour . after evaporation of the solvent , the residue was taken up in ethyl acetate , washed with 1 n hydrochloric acid solution , water and brine , dried over magnesium sulfate and concentrated to leave dimethylcarbamoylmethyl ( 4 - methoxybenzensulfonyl ) amino - 3 - methylbutyric acid benzyl ester as an oil , 1 . 77 grams ( 88 %). to a solution of dimethylcarbamoylmethyl ( 4 - methoxybenzenesulfonyl ) amino - 3 - methylbutymic acid benzyl ester ( 1 . 77 grams , 3 . 83 mmol ) in ethanol ( 100 ml ) was added 10 % palladium on activated carbon ( 644 mg ). the mixture was agitated under 3 atmospheres hydrogen in a parr shaker for 1 . 5 hours . the catalyst was removed by filtration through nylon ( pore size 0 . 45 μm ) and the solvent was evaporated leaving dimethylcarbamoylmethyl ( 4 - methoxybenzensulfonyl ) amino - 3 - methylbutyric acid as a white foam , 1 . 42 grams ( 100 %). to a solution of dimethylcarbamoylmethyl ( 4 - methoxybenzensulfonyl ) amino - 3 - methylbutyric acid ( 1 . 42 grams , 3 . 81 mmol ) and 1 - hydroxybenztriazole hydrate ( 687 mg , 4 . 48 mmol ) in dry dimethylformamide ( 7 ml ) was added 1 -( 3 - dimethylaminopropyl )- 3 - ethylcarbodiimide hydrochloride ( 974 mg , 5 . 08 mmol ). after stirring for 30 minutes , hydroxylamine hydrochloride ( 1 . 17 grams , 16 . 8 mmol ) and then n - methylmorpholine ( 2 . 8 ml , 25 . 5 mmol ) were added . the mixture was stirred at room temperature overnight and then concentrated under vacuum . the residue was taken up in ethyl acetate and the resulting solution was washed sequentially with water , 0 . 5 n hydrochloric acid solution and brine . the solution was then dried over magnesium sulfate and concentrated under vacuum to leave an oil which was chromatographed on silica gel eluting successively with ethyl acetate , 5 % methanol in chloroform and 10 % methanol in chloroform to afford 2 -[ dimethyl - carbamoylmethyl ( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyramide as a white solid , 390 mg ( 26 %). 1 h nmr ( dmso - d 6 ): δ10 . 70 ( br s , 1h ), 8 . 89 ( s , 1h ), 7 . 80 ( d , j = hz , 2h ), 7 . 10 ( d , j = 8 . 9 hz , 2h ), 4 . 62 ( d , j = 17 . 7 hz , 1h ), 4 . 14 ( d , j = 17 . 7 hz , 1h ), 3 . 84 ( s , 3h ), 3 . 40 ( d , j = 10 . 4 hz , 1h ), 2 . 97 ( s , 3h ), 2 . 82 ( s , 3h ), 1 . 88 - 1 . 72 ( m , 1h ), 0 . 72 ( d , j = 6 . 5 hz , 6h ); ms ( thermospray ): m / z 388 ( m + 1 ); hrms calculated for c 18 h 28 n 3 o 6 s ( m + h ): 388 . 1542 . found : 388 . 1592 . 2 -( r )- n - hydroxy - 2 -(( 4 - methoxybenzenesulfonyl )([( pyridin - 3 - ylmethyl )- carbamoyl ] methyl ) amino - 3 - methylbutyramide was prepared by a procedure similar to that of example 12 starting with 2 -( r )- 2 -[ carboxymethyl ( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester ( example 1 ) and coupling this to 3 - pyridylmethylamine via the acid chloride . 1 h nmr ( cd 3 od ): δ8 . 55 - 8 . 53 ( m , 1h ), 8 . 43 - 8 . 40 ( m , 1h ), 7 . 90 - 7 . 82 ( m , 1h , overlapped ), 7 . 86 ( d , j = 8 . 9 hz , 2h ), 7 . 40 ( dd , j = 4 . 8 , 7 . 8 hz , 1h ), 7 . 04 ( d , j = 8 . 9 hz , 2h ), 4 . 50 ( d , j = 17 . 5 hz , 1h ), 4 . 39 ( d , j = 17 . 5 hz , 1h ), 4 . 32 ( d , j = 17 . 7 hz , 1h ), 4 . 02 ( d , j = 17 . 7 hz , 1h ), 3 . 87 ( s , 3h ), 3 . 60 ( d , j = 10 . 3 hz , 1h ), 2 . 08 - 1 . 93 ( m , 1h ), 0 . 85 ( d , j = 6 . 5 hz , 3h , 0 . 70 ( d , j = 6 . 5 hz , 3h ); ms ( thermospray ): m / z 451 ( m + h ), 336 , 320 . to a solution of iminoacetic acid disodium salt monohydrate ( 5 . 0 grams , 25 . 6 mmol ) in dioxane ( 50 ml ) and water ( 50 ml ) was added triethylamine ( 5 . 3 ml , 38 mmol ) followed by 4 - methoxybenzenesulfonyl chloride ( 5 . 8 grams , 28 . 0 mmol ). the mixture was stirred overnight at room temperature and diluted with methylene chloride . the solution was washed with 1 n hydrochloric acid solution , water and brine , dried over magnesium sulfate and concentrated under vacuum leaving [ carboxymethyl ( 4 - methoxybenzenesulfonyl ) amino ] acetic acid as a white solid , 3 . 83 grams ( 49 %). [ carboxymethyl ( 4 - methoxybenzenesulfonyl ) amino ] acetic acid ( 0 . 5 grams , 1 . 65 mmol ) in acetic anhydride ( 15 ml ) was dissolved in acetic anhydride by gentle warming . the resulting solution was stirred at room temperature overnight . the acetic anhydride was removed by evaporation under vacuum ; the residue was dissolved in methylene chloride and morpholine ( 0 . 16 ml , 1 . 82 mmol ) was added . the mixture was stirred overnight at room temperature and then concentrated under vacuum . the residue was dissolved in ethyl acetate , washed with 1n hydrochloric acid solution , water and brine , dried over magnesium sulfate and concentrated to afford [( 4 - methoxybenzenesulfonyl )( 2 - morpholin - 4 - yl - 2 - oxoethyl ) amino ] acetic acid as an oil , 0 . 33 grams ( 54 %). to a solution of [( 4 - methoxybenzenesulfonyl )( 2 - morpholin - 4 - yl - 2 - oxoethyl ) amino ] acetic acid ( 0 . 33 grams , 0 . 89 mmol ) in methylene chloride ( 10 ml ) were added sequentially triethylamine ( 0 . 43 ml , 3 . 1 mmol ), o - benzylhydroxylamine hydrochloride ( 0 . 15 grams , 0 . 94 mmol ) and ( benzotriazol - 1 - yloxy ) tris ( dimethylamino ) phosphonium hexafluorophosphate ( 0 . 43 grams , 0 . 97 mmol ). the mixture wsa stirred at room temperature overnight and then diluted with ethyl acetate . the solution wsa washed sequentially with 0 . 5 n hydrochloric acid solution , water and brine , dried over magnesium sulfate and concentrated under vacuum . the residue was chromatorgraphed on silica gel using ethyl acetate to afford n - benzyloxy -[( 4 - methoxybenzenesulfonyl )( 2 - morpholin - 4 - yl - 2 - oxoethyl ) amino ] acetamide as a white solid , 0 . 33 grams ( 78 %). to a solution of n - benzyloxy -[( 4 - methoxybenzenesulfonyl )( 2 - morpholin - 4 - yl - 2 - oxoethyl ) amino ] acetamide ( 0 . 33 grams , 0 . 69 mmol ) in methanol ( 35 ml ) was added 5 % palladium on activated carbon ( 85 mg ). the mixture was agitated under 2 atmospheres hydrogen in a parr shaker for 1 . 5 hours . the catalyst was removed by filtration through nylon ( pore size 0 . 45 μm ) and the solvent was evaporated . the residue was chromatorgraphed on silica gel with 5 % methanol in methylene chloride to afford n - methoxy -[( 4 - methoxybenzenesulfonyl )( 2 - morpholin - 4 - yl - 2 - oxoethyl ) amino ] acetamide as a white solid , 65 mg ( 24 %); 1 h nmr ( cd 3 od ): δ7 . 82 ( d , j = 9 . 0 hz , 2h ), 7 . 08 ( d , j = 9 . 0 hz , 2h ), 4 . 24 ( s , 2h ), 3 . 88 ( s , 3h ), 3 . 84 ( s , 2h ), 3 . 68 - 3 . 64 ( m , 4h ), 3 . 58 - 3 . 50 ( m , 4h ); ms ( thermospray ): m / z 388 ( m + 1 ), 387 ( m ); hrms calculated for c 16 h 22 n 3 o 7 s ( m + h ): 388 . 1178 , found 338 . 1180 . the title compounds of examples 15 - 16 were prepared by a method analogous to that described in example 14 using [ carboxymethyl ( 4 - methoxybenzenesulfonyl ) amino ] acetic acid as the starting material which , after treatment with acetic anhydride , is coupled with the amine indicated . coupled with pyrrolidine : 1 h nmr ( dmso - d 6 ): δ11 . 26 ( br s , 1h ), 8 . 89 ( s , 1h ), 7 . 81 ( d , j = 8 . 9 hz , 2h ), 7 . 10 ( d , j = 8 . 9 hz , 2h ), 4 . 09 ( s , 2h ), 3 . 85 ( s , 3h ), 3 . 74 ( s , 2h ), 3 . 45 - 3 . 25 ( m , 4h ), 1 . 93 - 1 . 72 ( m , 4h ); ms ( thermospray ): m / z 372 ( m + 1 ): analysis calculated for c 15 h 21 n 3 o 6 s : c , 48 . 51 ; h , 5 . 70 ; n , 11 . 31 . found c , 48 . 51 ; h , 5 . 82 ; n , 11 . 24 . coupled with dimethylamine : mp : 170 ° c . ( dec . ); 1 h nmr ( dmso - d 6 ): δ10 . 69 ( br s , 1h ), 8 . 88 ( s , 1h ), 7 . 91 ( d , j = 8 . 9 hz , 2h ), 7 . 06 ( d , j = 8 . 9 hz , 2h ), 4 . 19 ( s , 2h ), 3 . 85 ( s , 3h ), 3 . 73 ( s , 2h ), 2 . 94 ( s , 3h ), 2 . 84 ( s , 3h ); ms ( thermospray ): m / z 346 ( m + 1 ); analysis calculated for c 13 h 19 n 3 o 6 s : c , 45 . 21 ; h , 5 . 55 n , 12 . 17 . found : c , 44 . 93 , h , 5 . 61 ; n , 12 . 03 . to a solution of 2 -( r )- 2 -[( 2 - carbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester ( example 2 ) ( 900 mg ., 2 . 0 mmol ) in methylene chloride ( 10 ml ) was added thionyl chloride ( 0 . 16 ml , 2 . 2 mmol ). the reaction mixture was stirred for 1 . 5 hours at room temperature and then concentrated in vacuo . after dissolving the residue in methylene chloride ( 10 ml ), ammonia gas was bubbled through the solution for 0 . 5 minutes . the solution was stirred at room temperature overnight and was concentrated under vacuum . flash chromatography of the residue on silica gel eluting with 2 % methanol in chloroform provided 2 -( r )- 2 -[( 2 - carbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyric acid benzyl ester as a clear oil ( 275 mg , 31 %). to a solution of 2 -( r )- 2 -[( 2 - carbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyric acid benzyl ester ( 275 mg , 0 . 61 mmol ) in ethanol ( 15 ml ) was added 10 % palladium on activated carbon ( 30 mg ). the mixture was agitated under 3 atmosphers hydrogen in a parr shaker for 5 hours . the catalyst was removed by filtration through diatomaceous earth and the solvent was evaporated leaving 2 -( r )- 2 -[( 2 - carbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyric acid as a white foam , 211 mg ( 96 %). to a solution of 2 -( r )- 2 -[( 2 - carbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyric acid ( 205 mg , 0 . 57 mmol ) and 1 - hydroxybenztriazole hydrate ( 85 mg , 0 . 55 mmol ) in dry dimethylformamide ( 5 ml ) was added 1 -( 3 - dimethylaminopropyl )- 3 - ethylcarbodiimide hydrochloride ( 120 mg , 0 . 63 mmol ). after stirring for 30 minutes , hydroxylamine hydrochloride ( 158 mg , 2 . 3 mmol ) and then n - methylmorpholine ( 0 . 37 ml , 3 . 4 mmol ) were added . the mixture was stirred at room temperature overnight and then diluted with ethyl acetate . the solution was washed with water and brine . the solution was then dried over magnesium sulfate and concentrated under vacuum to leave an oil which was chromatographed on silica gel eluting with 2 % methanol in chloroform to afford 2 -( r )- 2 -[( 2 - carbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyramide as a white solid , 45 mg ( 21 %); 1 h nmr ( dmso - d 6 ): δ10 . 74 ( br s , 1h ), 8 . 91 ( br s , 1h ), 7 . 74 ( d , j = 8 . 8 hz , 2h ), 7 . 33 ( br s , 1h ), 7 . 07 ( d , j = 8 . 8 hz , 2h ), 6 . 79 ( br s , 1h ), 3 . 93 - 3 . 82 ( m , 1h , overlapped ), 3 . 83 ( s , 3h ), 3 . 64 ( d , j = 10 . 7 hz , 1h ), 3 . 25 - 3 . 12 ( m , 1h ), 2 . 62 - 2 . 48 ( m , 1h ), 2 . 42 - 2 . 30 ( m , 1h ), 2 . 06 - 1 . 94 ( m , 1h ), 0 . 79 ( d , j = 6 . 6 hz , 3h ), 0 . 76 ( d , j = 6 . 6 hz , 3h ); ms ( thermospray ): m / z 374 ( m + h ). a solution of n , n - dimethylformamide di - tert - butyl acetal ( 1 . 9 ml , 7 . 9 mmol ) in toluene ( 15 ml ) was added dropwise to a solution of 2 -( r )- 2 -[( 2 - carbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- 3 - methylbutyric acid benzyl ester ( example 2 ) 900 mg , 2 . 0 mmol ) in toluene at 80 ° c . after heating for 2 hours at 80 ° c ., the mixture was cooled and concentrated to leave an amber oil which was chromatographed on silica gel eluting with chloroform to afford 2 -( r )- 2 -[( 2 - tert - butoxycarbonylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyric acid benzyl ester as an oil , 3 . 75 mg ( 37 %). to a solution of 2 -( r )- 2 -[( 2 - tert - butoxycarbonylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyric acid benzyl ester ( 370 mg , 0 . 73 mmol ) in ethanol ( 20 ml ) was added 10 % palladium on activated carbon ( 40 mg ). the mixture was agitated under 3 atmospheres hydrogen in a parr shaker for 5 hours . the catalyst was removed by filtration through diatomaceous earth and the solvent was evaporated leaving 2 -( r )- 2 -[( 2 - tert - butoxycarbonylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyric acid as a white foam , 30 mg ( 100 %). to a solution of 2 -( r )- 2 -[( 2 - tert - butoxycarbonylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyric acid ( 303 mg , 0 . 73 mmol ) and 1 - hydroxybenztriazole hydrate ( 108 mg , 0 . 70 mmol ) in dry dimethylformamide ( 10 ml ) was added 1 -( 3 - dimethylaminopropyl )- 3 - ethylcarbodiimide hydrochloride ( 153 mg , 0 . 80 mmol ). after stirring for 45 minutes , hydroxylamine hydrochloride ( 203 mg , 2 . 9 mmol ) and then n - methylmorpholine ( 0 . 48 ml , 4 . 4 mmol ) were added . the mixture was stirred at room temperature overnight and then concentrated under vacuum . the residue was chromatographed on silica gel cluting with 2 % methanol in chloroform and again with 10 % ethyl acetate in hexane to afford 2 -( r )- 2 -[( 2 - tert - butoxycarbonylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyramide as a white foam , 135 mg ( 43 %); 1 h nmr ( dmso - d 6 ): δ10 . 77 ( br s , 1h ), 7 . 74 ( d , j = 8 . 9 hz , 2h ), 7 . 08 ( d , j = 8 . 9 hz , 2h ), 3 . 93 - 3 . 82 ( m , 1h , overlapped ), 3 . 83 ( s , 3h ), 3 . 64 ( d , j = 10 . 8 hz , 1h ), 3 . 26 - 3 . 14 ( m , 1h ), 2 . 70 - 2 . 60 ( m , 1h ), 2 . 50 - 2 . 38 ( m , 1h ), 2 . 04 - 1 . 91 ( m , 1h ), 1 . 38 ( s , 9h ), 0 . 78 ( d , j = 6 . 5 hz , 3h ), 0 . 72 ( d , j = 6 . 5 hz , 3h ); ms ( thermospray ): m / z 431 ( m + h ), 375 , 314 . to a solution of 2 -( r )- 2 -[( 2 - tert - butoxycarbonylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyramide ( example 18 ) ( 100 mg , 0 . 23 mmol ) in methylene chloride ( 1 ml ) at 0 ° c . was added trifluoroacetic acid ( 1 ml ). the mixture was allowed to warm to room temperature while stirring overnight . after evaporation of the trifluoroacetic acid and methylene chloride , the residue was chromatographed on silica gel eluting with 5 % methanol in chloroform . concentration of the appropriate fractions afforded 2 -( r )- 2 -[( 2 - carbamoylethyl )( 4 - methoxybenzenesulfonyl ) amino ]- n - hydroxy - 3 - methylbutyramide as a white solid , 35 mg ( 41 %). 1 h nmr ( dmso - d 6 ): δ10 . 79 ( br s , 1h ), 8 . 97 ( br s , 1h ), 7 . 76 ( d , j = 8 . 9 hz , 2h ), 7 . 09 ( d , j = 8 . 9 hz , 2h ), 3 . 95 - 3 . 82 ( m , 1h , overlapped ), 3 . 84 ( s , 3h ), 3 . 66 ( d , j = 10 . 8 hz , 1h ), 3 . 30 - 3 . 20 ( m , 1h ), 2 . 73 - 2 . 62 ( m , 1h ), 2 . 50 - 2 . 40 ( m , 1h ), 2 . 07 - 1 . 94 ( m , 1h ), 0 . 80 ( d , j = 6 . 5 hz , 3h ), 0 . 74 ( d , j = 6 . 5 hz , 3h ): ms ( thermospray ): m / z 375 ( m + h ), 314 .
| 2 |
it is noted that like parts are designated by like reference numerals . fig5 shows a storage container for a magnetic recording tape cartridge , suitable for storing a so - called philips type magnetic recording tape cartridge &# 34 ; compact cassette &# 34 ;, as a preferred embodiment of the present invention , wherein the receptacle container body 1 and the lid 2 are constituted in the same manner as in the conventional storage container of this kind . a pair of hub locking members 11 for preventing rotation of tape hubs 6 of the magnetic tape cartridge 3 are provided on the bottom surface 1a of the body 1 at the positions corresponding to the driving shaft insertion holes 10 of the magnetic tape cartridge 3 as shown in fig6 . the locking members are parallel and protrude upwardly from the container bottom surface 1a . the hub locking members 11 are each constituted by a columnar boss 12 and the two engaging keys 13 and 14 projected radially outwardly from said boss 12 . fig7 and 8 illustrate an example of the hub locking member 11 for preventing the rotation of the hub applied to the storage container . in this embodiment , a columnar boss 12 having the diameter of about 6 . 7 mm is vertically erected at a height of about 12 mm from the bottom wall 1a of the body 1 , with its top portion tapered to form a cone 15 of the vertical or apex angle α of about 135 °. from each boss 12 the first engaging key 13 protrudes toward the front wall 1b of the body 1 and the second engaging key 14 protrudes toward the right rear portion , respectively in radial directions at the length l of about 1 . 2 mm , with the angle β between the engaging keys 13 and 14 being set at about 150 °. the angle β between the engaging keys 13 and 14 is so determined that , when one hub toothing 9a is positioned opposite to the first engaging key 13 , the second engaging key 14 is positioned in the intermediate space defined by other hub toothings 9c and 9d as shown in fig1 a . the upper ends of the engaging keys 13 and 14 are positioned on the level lower than the bottom end of the cone 15 of said boss 12 , and are inclined downward from said boss 12 with an angle of inclination of about 20 ° to the bottom surface 1a . the upper ends of the engaging keys 13 and 14 are pointed in trigonal pyramid forms . the width α and a &# 39 ; of the engaging keys 13 and 14 are of about 2 . 0 mm . in general , the width α of one key 13 is set to be smaller than the distance c between the tub toothings adjacent each other ( about 2 . 8 mm ) and larger than the difference obtained by deducting the total of the width a &# 39 ; of the other key 14 and the diameter b of the section of the hub toothings ( about 1 . 5 mm ) from the distance c between the two hub - toothings , namely a & lt ; c and a & gt ; c -( a &# 39 ;+ b ). also , the total length of the diameter d3 of the boss 12 ( 6 . 7 mm ) and the length l of the engaging keys 13 or 14 ( 1 . 2 mm ), d3 + l = 6 . 7 + 1 . 2 = 7 . 9 mm , is smaller by about 0 . 1 mm than the diameter d0 ( 8 . 0 mm ) of the above inscribed circle 16 along each end face of the hub toothings 9 ( see fig1 b or 11 ). by setting the respective dimensions of the hub locking member 11 as described above , it is understood from fig1 , that since either of the engaging keys 13 or 14 is out of the inscribed circle 16 or 16 &# 39 ;, when any one of the hub - toothings 9 opposes to one of the engaging key 13 ( or 14 ), another engaging key 14 ( or 13 ) is located in the space between two hub - toothings 9c and 9d ( or 9a and 9b ). on the other hand , generally , the hub 6 is placed with a play t of about 0 . 7 mm between the hub supporting wall 17 of the magnetic tape cartridge 3 and the shoulder 18 of the hub 6 . accordingly , the hub 6 can be moved idly within the play t ( see fig9 ). therefore , when the width of the hub - toothing 9 is smaller than predetermined value , the hub 6 is unexpectedly brought into rotation as hereinafter described . this mechanism is explained with reference to fig1 a through 10d and 11 as follows : fig1 b and 10c show critical states for the engaging key 14 to be in contact with either hub - toothings 9c or 9d . between the both states shown in fig1 b and 10c , the hub - toothing 9c can be offset relative to the engaging key 14 by the difference ( c - a &# 39 ;) obtained by deducing the width a &# 39 ; of the engaging key 14 from the distance c between the hub - toothings 9c and 9d . in this case , the end face 13a of the other engaging key 13 must be located within the range of the hub - toothing 9a . the maximum length over which the engaging key 13 can move within the range of the hub toothings 9a is ( c - a &# 39 ;). accordingly , if this length of ( c - a &# 39 ;) were larger than the value of ( a + b ). the engaging key 13 which had been in contact with or closely opposed to the hub - toothing 9a would be disengaged from the hub - toothing 9a . when the hub - toothing 9a is disengaged from the engaging key 13 under such state as shown in fig1 b or 10c , the hub 6 may be allowed to rotate by way of planetary movement . accordingly , the relation of ( c - a &# 39 ;)& lt ;( a + b ) is to be maintained . the above relation between the first and the second engaging keys must be satisfied even when their positions are reversed . in view of the above relations , when the columnar boss 12 is inserted into the openings of the drive shaft insertion hole of the hub 6 and the drive shaft insertion hole 10 of the magnetic tape cartridge 3 when the lid 2 is closed , if the hub 6 in the magnetic tape cartridge 3 is offset from the regular position , the hub 6 is moved toward the predetermined position by the action wherein the cone 15 of the boss 12 pushes the hub - toothings contacting the cone 15 , thereby resulting in engaging of the engaging keys 13 , 14 with the hub - toothings 9 . even if the hub 6 in the magnetic recording tape cartridge 3 is inserted into the boss 12 in such way that a hub - toothing is opposed to the engaging key 14 , the hub 6 can be inserted by being guided to a correct position ( as shown in fig1 a ) by the aid of the cone 15 of the boss 12 and the inclined surface on the upper end of the engaging keys 13 and 14 . in this case , the hub 6 may be allowed to move slightly around the axis of the boss 12 , but the second engaging key 14 can be engaged with the hub - toothings 9d or 9c to prevent rotation of the hub 6 . such action and effect of the second engaging key 14 is obtained by substantially protruding the first and the second engaging keys 13 and 14 from the boss 12 in such manner that , when the first engaging key 13 is protruded from the boss 12 with a length that the total length ( d3 + l ) i . e ., the length of the first engaging key 13 plus the diameter of the boss 12 does not exceed the diameter d0 of the inclined circle along the hub - toothings 9 and when the end face 13a of said first engaging key 13 may be brought into contacting with an end face g &# 39 ; of one of the hub - toothings , e . g . 9a , while the second engaging key 14 is located within the space between the hub - toothings 9c and 9d . and yet the diameter d4 of the circumscribed circle of hub locking member 11 is set to be larger than the diameter d0 of the inserted circle 16 along said hub - toothings 9 . in the above embodiment , the boss 12 of the hub locking member 11 for preventing the rotation of the hub 9 is made of a columnar shape with conical top portion . however , the hub locking member 11 need not be of a columnar boss with a conical top portion , but , as shown in fig1 and 13 , be of a post of polygonal cross - section such as ellipse or hexagon boss 20 with polygonal pyramid top portion 21 . but , when the hub locking member is formed into a conical topped columnar shape as shown in fig5 in the above embodiment , the hub 6 may slide readily along the conical tapered top portion of the boss , causing the hub to be placed in a correct position where the hub entirely engages with the hub locking member , and , in case of displacing the hub 6 by means of the upper face of the first and / or second engaging keys 13 and / or 14 , the hub - toothing comes into contact with the outer periphery of the boss to permit smooth displacement of the hub 6 . when the top cone portion 15 of the boss 12 is formed into a tapered configuration with the vertical angle smaller than 160 °, displacement of the hub 6 is effectively performed . another embodiment of the hub locking member is shown in fig1 and 15 , wherein two engaging keys 23 and 24 are protruded from the columnar boss 12 having the conical top portion 15 . the engaging keys 23 and 24 extend up to the conical top portion 15 . a further embodiment of the hub locking member is shown in fig1 and 17 . in this embodiment , the boss 12 is constituted in combination of two half columnar parts 12a and 12b with different radii r 1 and r 2 . the ridgeline 14a of the engaging key 14 is offset from the center of the engaging key 14 . a still further embodiment of the hub locking member is shown in fig1 , wherein two engaging keys 13 and 14 are located with the angle of about 90 °. in any of the embodiments described above , in order to prevent the rotation of the hub 6 when the end of the first engaging key 13 is directly contacted or opposed with the end of a hub - toothing , for example 9a , the second engaging key 14 may be in a position to receive the hub idly in the space which comes either the first space 9ab or the second space 9bc ( see fig1 a ). but , when the second engaging key 14 is so positioned as to receive the hub 6 idly in the third space 9cd , the allowance of the length of projection of the engaging key 14 becomes the largest , by which the projection can prevent the rotation of the hub easily and securely . the first engaging key 13 and the second engaging key 14 are not required to have the same length of projection from the boss 12 . their lengths of projection may be selected according to necessity . also , it is possible to provide each engaging key with a ridge at its top , so that the ridgeline can help to guide the hub - toothing . further , the hub locking members for preventing the rotation of the tape hub adopted in the present invention may be provided on either the receptacle container body 1 or the lid 2 which constitutes the storage container . it is not essential for the hub locking members to be provided by the number corresponding to the number of the hubs of the magnetic recording tape cartridge to be contained in the storage container . however , in order to store a magnetic tape cartridge in which two hubs , engaging a magnetic tape at the starting end and the terminal end thereof respectively , are mounted in freely movable state as in the so - called &# 34 ; compact casette &# 34 ; of philips type , it is preferred to provide two hub locking members for preventing the rotation of the hubs at the positions corresponding to the hubs respectively , because , by so providing , charging of the magnetic tape cartridge in the storage container at a fixed position is assured and the rotation of the hub is effectively prevented . in a storage container having a receptacle container body and a lid , being operable to close the receptacle container body , with a magnetic recording tape loaded within the pocket as shown in fig1 or fig5 when the hub locking members according to the present invention are provided on the bottom wall of the receptacle container body , desirable results can be expected because of a successful prevention of wedging of the engaging keys of the hub locking members into the hub - toothings . in case of forming the hub locking members by molding with a plastic material in one body with the body 1 or with the lid 2 of the storage container , it is preferred to form the hub locking members with hollow space therein in which case deformation of boss that may result from shrinkage in molding can be prevented . according to the present invention , when the lid 2 in which the magnetic tape cartridge 3 is loaded is closed to enclose the cartridge 3 in the body 1 under such condition that some of the hub - toothings 9 lie on the boss 12 , said hub - toothings 9 come to contact the cone 15 of the boss 12 causing the hub 6 to move in both transverse direction and downward direction along said cone 15 . as a result , the hub 6 may be brought in the engaged position as shown in fig1 d where the rotation of the hub 6 is prevented . however , when two of the hub - toothings 9 contact onto the two engaging keys 13 and 14 at the time of enclosing into the body , the hub 6 may not be successfully engaged with the hub locking member 11 . in order to avoid such state , according to the present invention , the radius of the boss 12 should be selected within the predetermined range as explained hereinafter . before the description proceeds , it is noted that such state that the ridgelines of any two hub toothings contact the ridgelines of both of the engaging keys 13 and 14 is designated as critical state . various critical states are shown in fig2 through 22 . this critical state may cause collision of the hub - toothings and engaging keys which prevents the cartridge from being contained in the storage container correctly . an advantage of the present invention is to readily avoid the critical state as hereinafter explained . in order to avoid the occurrence of the critical state , the boss 12 must push the hub to move it in the directions of either x or - x shown in fig2 to 22 when the cartridge 3 is enclosed in the container . for this purpose , as understood from fig2 , for example , the radius r of the boss 12 must be larger than the radius r ac of the critical circle 30 . assuming that z is such point that the ridgeline of the hub - toothing 9a contacts the ridgeline of the engaging key 13 , while z &# 39 ; is such point that the ridgeline of the hub - toothing 9c contacts the ridgeline of the engaging key 14 ( such point is designated as critical point ), and the angle θ represents & lt ; z p z &# 39 ; ( critical angle ): wherein p is the center of the boss 12 . ( i ) where both engaging keys 13 and 14 engage with two hub - toothings 9a and 9c as shown in fig2 ; where the boss 12 pushes the hub - toothing 9b , as shown in fig2 , to move the hub 6 toward x direction , the angle θ falls within the range of 120 °& lt ; θ & lt ; 240 °. wherein r is the radius of the inscribed circle along the inner face of the hub - toothings ; thus , ## equ2 ## where the boss 12 pushes the hub - toothings 9e to move the hub 6 toward - x direction , the angle θ falls within the range of 60 °& lt ; θ & lt ; 120 °; ( ii ) in the case where the critical points z , z &# 39 ; occur on both hub - toothings 9a and 9b as shown in fig2 ; where the boss 12 pushes the hub - toothings 9b and 9c to move the hub 6 toward x direction , the angle θ falls within the range of 90 °& lt ; θ180 °. by adopting the rectangular co - ordinate with the origin coinciding the center p0 of the hub , the position of the center p of the boss is ( x , 0 ) while the critical points z is ( 0 , r ). since & lt ; z p p0 is θ / 2 , then ## equ5 ## on the other hand , the position of w where the boss contacts the hub - toothing 9b is nearly equaled to ## equ6 ## thus , ## equ7 ## is established . where the boss 12 pushes the hub - toothings 9e and 9f to move the hub 6 toward - x direction , the angle θ falls within the range of 180 °& lt ; θ & lt ; 270 °, then ## equ8 ## is also established ; wherein ## equ9 ## ( iii ) where the critical points z and z &# 39 ; occur on the hub - toothings 9a and 9b as shown in fig2 ; where the boss 12 pushes the hub - toothings 9a and 9b to move the hub 6 toward the x direction , the angular θ falls within the range of 60 °& lt ; θ & lt ; 180 °. the position of w where the boss contacts the hub - toothing 9a is nearly equal to ## equ10 ## thus , ## equ11 ## is established ; wherein ## equ12 ## in the case where the boss 12 pushes the hub - toothings 9d and 9e to move the hub 6 toward - x direction , the angle θ falls within the range about 32 °& lt ; θ & lt ; 60 °. the position of the center p of the boss 12 is represented by (- x , 0 ). thus , the value x appearing in the equation ( 6 ) is replaced by ## equ13 ## fig1 shows various curvatures plotted by the equations ( 1 &# 39 ;), ( 2 &# 39 ;), ( 4 ), ( 5 ) and ( 6 ) wherein vertical axis shows the values of the radii r ac , r ab and r ad while the horizontal axis shows the angle θ . it is sufficient to choose the radius of the boss 12 according to the present invention in the range higher than any curvatures as shown by the shadowed portions in fig1 . an example of the application of the equations mentioned above and graph shown in fig1 is explained below , taking the angle ω shown in fig1 as 142 °, the ( 2π - ω ) becomes 218 °. assuming that radius r is 4 mm ( which is the radius of the inscribed circle of the hub - toothings of &# 34 ; compact cassette &# 34 ;). by putting the values ω and r into any of the equations defined as above depending on the angle ω or ( 2π - ω ), two sets of radii are calculated as follows : ## equ14 ## thus , both radii r 1 and r 2 of the boss 12 shown in fig1 may be sufficient in case where ## equ15 ## such radii are depicted by r 1 &# 39 ; and r 2 &# 39 ; in fig1 . in the embodiment shown in fig1 , the radius r 1 is set at 3 . 27 mm and the radius r 2 is set at 2 . 92 mm so that the boss 12 always prevents the occurrence of the critical state defined as above .
| 6 |
it should be understood at the outset that although an exemplary implementation of the present invention is illustrated below , the present invention may be implemented using any number of techniques , whether currently known or in existence . the present invention should in no way be limited to the exemplary implementations , drawings , and techniques illustrated below , including the exemplary design and implementation illustrated and described herein . one aspect of the invention generally involves the conversion of any container , van , or trailer ( hereinafter referred to as “ storage container 50 ”) into a drying container 100 . in this aspect of the invention , a crop , such as peanuts , can be deposited through an opening 124 ( fig3 ) into a bin 200 ( fig3 ) within the drying container 100 . the crop , upon being inserted into the drying container 100 , rests upon a floor 150 ( fig3 ), which is made of a screen 152 ( fig8 ), having a plurality of holes therein . the holes are preferably small enough to prevent the crop from passing therethrough . the floor 150 ( fig3 ) is elevated above an interior bottom 148 ( fig3 ) of the drying container 100 to create a plenum 300 ( fig3 ), which may be referred to as a lower volume 300 . the elevation of the floor 150 ( fig3 ) above the interior bottom 148 ( fig3 ) is facilitated via a support system 160 ( fig4 - 6 ). the plenum 300 ( fig3 ) is in communication with at least one plenum opening 310 ( fig2 a , 12 , and 16 ), which couples with a blower to pressurize the plenum 300 ( fig3 ) with warm air flow . the pressurization of the plenum 300 with warm air flow forces air up into the bin 200 ( fig3 ), which may be referred to as an upper volume , through the screen 152 to facilitate a drying of the crop . after drying of the crop , the drying container 100 can be unloaded in a variety of manners . for example , the entire drying container 100 can be hydraulically lifted to a vertical position , doors 105 ( fig2 b ) can be opened , and the contents of the bin 200 can be dumped out . while these general aspects of the invention have been described above , other aspects of the invention will become apparent with reference to the description below and figures , corresponding thereto . another aspect of the invention generally includes utilization of a drying container 100 , having wheels 500 , which allows movement of the drying container 100 — e . g ., in a crop field or on the road towards a storage facility . fig1 , 2 a , and 2 b show a general “ before and after ” view of a storage container 50 / drying container 100 , according to an aspect of the invention . fig1 is a view of a storage container 50 ( the before ) while fig2 a and 2b are a view of a drying container 100 ( the after ). as referenced above , the storage container 50 can be any commercially - available storage container including , but not limited to , rail vans , cargo boxes , trailers , and the like . the general description of the storage containers 50 , described herein , is intended as being only illustrative of some of the many storage containers 50 that can be converted into a drying container 100 . other storage containers 50 should become apparent to one of ordinary skill in the art . additionally , while a general description of a conversion of a storage container is given herein it should be expressly understood that in other aspects of the invention the drying container 100 can be made directly rather than being converted from a storage container 50 . with reference to fig2 a and 2b , the conversion of the storage container 50 into the drying container 100 includes incorporation of several features , namely a plenum opening 310 and a ladder 106 at a front end 102 , which may also be referred to as a front wall , of the drying container 100 and a tarp 180 on the top of the drying container 100 . such features , along with other features described below , allow the drying container 100 to facilitate the drying of crops — e . g ., peanuts . fig2 b generally shows a back end 104 of the drying container 100 , which may also be referred to as a back wall . the back end 104 can include standard component parts generally available in a storage container 50 — e . g ., doors 105 . while the plenum opening 310 is generally shown on a front end 102 of the drying container 100 in the aspect of fig2 a , it should be expressly understood that the plenum opening 310 can be positioned in other locations as will be described below with reference to fig1 . in the general design of the drying container 100 , care must be taken to ensure that the drying container 100 can withstand the loads that will be placed thereon . therefore , for example , in aspects of the invention involving a conversion of a storage container 50 into a drying container 100 , consideration can be given to certain structural features of the storage container 50 , which have been designed to support a load . in several aspects of the invention , structural features of the storage container 50 can be utilized in support of the load being placed on the drying container 100 . more details of this aspect of the invention will be described below . fig3 shows a perspective view of an interior of the drying container 100 , according to an aspect of the invention . this view is taken from a back end 104 of the drying container with doors 105 opened . the plenum opening 310 is partially seen on an opposite end of the drying container 100 . in this aspect of the invention , the drying container 100 generally includes an interior side wall 140 which may include a first side wall and a second side wall , an interior bottom 148 , cross members 120 , ridge straps 170 , a floor 150 , and a support system 160 . while such features will generally be described below , it is to be expressly understood that in other aspects of the invention , other component parts may be utilized and the component parts described herein may additionally be modified . the ultimate design of the drying container 100 will , to a certain degree , depend on the dynamics of the particular use in which the drying container 100 will be used . the interior sidewalls 140 and interior bottom 148 help define the interior space of the drying container 100 . the insertion of a floor 150 above the interior bottom 148 divides the interior space of the drying container 100 into a bin 200 and a plenum 300 . generally , a crop , such as peanuts , can be placed inside the bin 200 — the bin 200 being elevated above the interior bottom 148 . warm air or the like can then be injected into the plenum 300 ( area between the interior bottom 148 and floor 150 ) and allowed to seep up through the floor 150 to dry the crop . the details of the floor 150 will be described in more detail below with reference to fig4 , 6 , 6 a , and 6 b . the crop can be placed into the storage bin 200 utilizing any techniques , now known or later developed . such techniques include , but are not limited to , depositions into the bin via an auger or conveyer belt . to facilitate the deposition of a crop , such as peanuts , into the bin 200 , this aspect of the drying container 100 includes an opening 124 . in aspects of the invention involving the conversion of a storage container 50 that has a roof ( e . g ., if the storage container 50 is a rail van ), the roof can be cut off or stripped from the storage container 50 . roof bows or cross members 120 can serve to provide structural integrity similar to that provided by a roof — e . g ., a brace for the interior sidewalls 140 . the cross member 120 can be mounted to top rails 122 atop the interior sidewalls 140 of the drying container 100 . such cross members 120 can be made of virtually any material suitable for their intended purposes including , but not limited to , tube steel . a tarp 180 can be incorporated adjacent the cross members 120 to allow selective covering of the opening 124 of the drying container 100 to prevent environmental elements , such as rain , from entering the interior of the drying container 100 . the use of a tarp 180 — e . g ., that is rolled over the cross members 120 — should become apparent to one of ordinary skill in the art . the cross members 120 in this aspect of the invention have a peaked center portion , which allows the environmental elements to roll off the tarp 180 . to prevent environmental elements , such as water , from standing in areas upon the tarp 180 between the cross members 120 , ridge straps 170 can be used . in this aspect of the invention , two independent ridge straps 170 are positioned on top of the cross members 120 down the length of the drying container 100 . the ridge straps 170 elevate the tarp 180 ( when placed over the cross members ) to decrease the surface area of the tarp 180 between the cross members 120 — helping to prevent sinking of the tarp 180 between the cross members 120 . the ridge straps 170 can be adjusted ( e . g ., tightened down onto the cross members 120 ), utilizing ridge strap winches 172 . the interior sidewalls 140 in this aspect of the invention include sidewall members 142 — one on each interior sidewall 140 . the sidewall members 142 can be coupled to posts ( not seen ), which may extend inside the interior sidewalls 140 . chains 190 are stretched between the sidewall members 142 to provide additional structural support to the interior sidewalls 140 . when a large crop load is placed within the bin 200 , the chains 190 prevent the sidewall members 142 and sidewalls 140 from extending outwardly . the deposition of a large crop load in the bin 200 creates a large force on the floor 150 . the support system 160 works to support the floor 150 , resisting the load while facilitating air flow through the plenum 300 . in one aspect of the invention , gates ( not shown ) can be placed over an end area generally defined by the plenum 300 . in this aspect , the gates would not allow any particles that fell into the plenum 300 to escape , e . g ., during dumping of the drying container 100 as described above ( e . g ., hydraulically lifting the drying container 100 into a vertical position and opening the doors 105 ). such an aspect can be beneficial in circumstances in which sand , gravel , or the like fell into the plenum 300 . the gates that are placed over an end area generally defined by the plenum 300 would not allow the sand , gravel , or the like to escape the drying container 100 during dumping of the contents of the bin 200 . after dumping of the bin 200 , the sand , gravel , or the like can easily be cleaned out of the plenum 300 by opening the gates that are placed over an end area generally defined by the plenum 300 and the doors 105 and injecting air into the plenum opening 310 ( shown in fig2 a ). fig4 , 5 , 6 a , and 6 b show several views of a support system 160 which can be used to support the floor 150 , according to an aspect of the invention . as referenced above , the plenum 300 allows the circulation of airflow under the floor 150 to allow seeping through the floor 150 . to support the floor 150 , the support system 160 in this aspect of the invention includes a series of trussed support members 162 and angle members 164 . these may be referred to as “ engineered joists ” and are designed to support the crop , such as a load of peanuts , above the ventilated floor or screen 152 . with reference to fig6 a , a schematic of an orientation of the support member 162 , angle members 164 , interior bottom 148 , and floor 150 is shown . a pair of lower angle members 164 b are in contact with the interior bottom 148 and a pair of upper angle members 164 a are in contact with the floor 150 ( such as ventilated floor 150 ). the support member 162 is disposed between each pair of angle members between the floor 150 and the interior bottom 148 . with reference to fig6 b , a schematic of a side view of the support system 160 is shown in isolation , according to an aspect of the invention . the support members 162 are shown in a trussed configuration between the upper angle members 164 a and lower angle members 164 b . trussing the support members 162 provides structural advantages , which should become apparent to one of ordinary skill in the art — e . g ., a structural rigidity . while such a specific trussing configuration is shown in this aspect of the invention , it should be understood that in other aspects of the invention , other trussing configurations can additionally be used . with reference to fig4 , 6 a and 6 b , the trussed support members 162 ( along with angle members 164 ) can generally be seen in rows . with reference to fig1 , four rows of trussed support members 162 are shown through the plenum opening 310 . the trussed support members 162 are preferably primed or processed to prevent rust and / or deterioration . such priming and / or processing can include any technique , now known or later developed . additionally , in one aspect of the invention , the rows of trussed support members 162 can be coupled to the interior bottom 148 at two locations : near the front end 102 and the back end 104 of the drying container 100 , e . g , via welding . such a coupling prevents the rows of trussed support members 162 from rising up from the interior bottom 148 . in other aspects of the invention , the rows of trussed support members 162 can be coupled in other areas . as the air flows through the plenum 300 , the trussed support members 162 will create some disturbance of the air flow . in some aspects of the invention , additional disturbance may be necessary . as such , in those aspects of the invention , baffles ( not shown ) can be positioned in various locations of the plenum 300 . with the configuration shown in this aspect of the invention ( four rows of trussed support members 162 ), the support system 160 can support 125 , 000 pounds of pressure — allowing heavy crop loads to be placed upon the floor 150 . such a support loading is intended as only illustrative of a load that can be supported as other loads can be supported in other aspects of the invention — e . g ., heavier loads or lighter loads . fig7 shows a bottom perspective view of the floor 150 , looking up . the floor 150 in this aspect of the invention is shown as a screen 152 , which will be described in more detail below with reference to fig8 . the support members 162 are providing support to the upper angle members 164 a . the screen 152 could be placed directly on the upper angle members 164 a ; however , in this aspect of the invention , a flat bar or support piece 166 is mounted on the upper angle members 164 a between the rows of trussed support members 162 and angle members 164 . the mounting of the support piece 166 to the upper angle members 164 a can include a variety of coupling techniques known by one of ordinary skill in the art , including , but not limited to , soldering . the support piece 166 provides additional support to the screen 152 as should be recognized by one of ordinary skill in the art — e . g , a reduced support area that prevents sinking of the screen 152 between the rows of double trussed members and double paired angle members . the screen 152 is coupled to the support piece 166 via coupling members 154 , which in this aspect of the invention is shown as rivets . the use of rivets for the coupling members 154 allows an ease of removability of the coupling members 154 . for example , rivets can be drilled out and easily replaced if the coupling member 154 or a portion of the screen 152 becomes damaged . fig8 shows a top perspective view of the floor 150 looking down . the floor 150 , as referenced above , can be a screen 152 . the screen 152 in this aspect of the invention is shown having a plurality of holes disposed therein . preferably , the screen 152 has a 40 % opening ; however , other percentages of opening can additionally be used as will become apparent to one of ordinary skill in the art . additionally , the screen 152 preferably has a fourteen gauge thickness ; and the material for the screen 152 is preferably a cold rolled metal that is processed with a brush and a rust prevention oil . cold rolling is a metal processing technique , which should become apparent to one of ordinary skill in the art . the use of cold rolled metal that has been brushed and processed with rust prevention oil extends the life of the floor 150 . fig9 shows a bottom perspective view of the floor 150 and its coupling to the interior sidewall 140 . in addition to the use of support members 162 ( described with reference to fig4 - 6a and 6 b ), the support system 160 can utilize portions of interior sidewall 140 . in such an aspect of the invention , the interior sidewall 140 can include posts or side supports ( not seen in fig9 , but generally referenced in fig1 ) that are typically available in the interior sidewalls 140 of a storage container 50 . a mounting member 146 can be coupled to the posts utilizing a mounting piece 149 ( e . g ., bolts and screws ). in some aspects of the invention ( e . g ., a conversion of a storage container 50 into a drying container 100 ), the sidewalls 140 may already have a mounting member 146 . in other aspects of the invention , the mounting member 146 may need to be coupled to the post of the interior sidewall 140 . in yet other aspects of the invention , the floor 150 may not utilize portions of the interior sidewall 140 . the screen 152 is shown coupled to the mounting member 146 via a coupling member 154 in the same manner in which the screen 152 is coupled to the support piece 166 via the coupling member 154 . fig1 shows another bottom perspective view of the floor 150 and its coupling to the interior sidewall 140 . the mounting member 146 is shown generally secured to the interior sidewall 140 . a support piece 166 is mounted on top of the mounting member 146 . in this aspect of the invention , the support piece 166 is shown as soldered onto the mounting member 146 . the screen 152 is shown positioned on top of the support piece 166 and the screen 152 is shown coupled to the mounting member 146 via the coupling member 154 . the mounting member 146 is additionally shown in this aspect of the invention as being coupled to a corner post 144 — for example , via soldering . fig1 shows a close - up view of a front of a standard storage container 50 similar to fig1 . in the standard storage container 50 , a variety of component parts exist , including items such as hookups 52 ( e . g ., an air break access point ) and document boxes 54 . fig1 shows a close - up view of a front of a drying container 100 — e . g ., converted from the storage container 50 of fig1 — with a new location for various component parts . the hookups 52 of fig1 have been elevated to the location of hookup 52 a of fig1 . additionally , the document box 54 in fig1 has been moved to the new location of document box 54 a of fig1 . the new location of these component parts allows the positioning of a plenum opening 310 in the front of the drying container 100 . the front of the drying container 100 in this aspect of the invention includes blower couplings 188 , which facilitate the connection of any blower , now known or later developed . the blower injects air pressure into the plenum opening 310 and into the plenum 300 to seep up through the floor 150 and dry the crop that is placed within the bin 200 . additionally shown is the ladder 106 , which allows an individual to view the opening 124 ( fig3 ). fig1 and 14 show close - up views of component parts that can be utilized to tighten down a tarp 180 . fig1 generally shows tarp straps 184 . the tarp straps 184 , as should be recognized by one of ordinary skill in the art , facilitate the bracing of the tarp 180 to the top of the drying container 100 . with reference to fig1 and 14 , winches 182 can be used to tighten down the tarp straps 184 . additionally shown in fig1 are sidewall support members 141 , which correspond to side supports that are within the walls of the drying container 100 . as indicated above with reference to fig9 , such side supports can be contained within a variety of different storage containers 50 ( ultimately transformed into drying containers 100 ). the sidewall member 142 ( fig3 ) and mounting member 146 ( fig9 ) can be coupled to the side supports of drying containers 100 containing such side supports . fig1 shows a close - up view of a tarp stop 186 , which can be used with the tarp 180 . the particular tarp stop 186 shown in fig1 is an easy off tarp stop 186 , which allows for easy removal of the tarp 180 without using any tools , as would be recognized by one of ordinary skill in the art . fig1 shows a view of a back of a drying container 100 with a conversion at the back end 104 a of the drying container 100 . the back end 104 a can be a custom made end to replace doors 105 ( see fig2 b ) to include the plenum opening 310 at this location in addition to or instead of being located at the front end 102 or elsewhere on the drying container 100 . additionally , the back end 104 a can be made to hingeably position to the remaining portion of the drying container 100 , for example , to empty the bin 200 in a manner similar to that described above ( the entire drying container 100 can be hydraulically lifted to a vertical position , the dump gate can be opened , and the contents of the bin 200 can be dumped out ). such a conversion of the back end 104 a illustrates that the plenum opening 310 can be in a variety of locations . for example , in some aspects of the invention , the plenum opening 310 could be positioned on a side of the drying container 100 or underneath the drying container 100 . in yet other aspects of the invention , more than one plenum opening 310 can be utilized — e . g , one in the front and one in the back with blowers or other equipment being capable of connecting to both plenum openings 310 . in still further aspects of the invention , multiple plenum openings 310 can be provided , but only one plenum opening 310 utilized — e . g ., giving an operator a choice of which plenum opening 310 to utilize in particular situations . in such an aspect of the invention , the plenum openings 310 can be outfitted with sealable doors such that the plenum that is not utilized can be sealed to maintain the pressure buildup inside the plenum 300 . fig1 shows a view of another type of storage container 50 , which can be converted into a drying container 100 . the illustration of the storage container 50 in fig1 is intended as expounding upon the concept briefly described above — that any storage container 50 can be utilized . the storage container 50 of fig1 is a 28 - foot pup trailer . such a storage container 50 allows for smaller drying containers 100 . as described above , features of storage container 50 can be utilized in facilitating structural support of the drying container 100 . in fig1 , the corner posts 144 can be utilized in a manner similar to that described above with reference to fig1 . additionally , an end 104 a — e . g ., a custom made end — can be used on the back of the drying container 100 to replace , e . g ., a roll - up door that may exist on the storage container 50 . fig1 a , 18 b , 18 c , 18 d , 18 e , and 18 f are a series of drawings that illustrate the conversion of the support legs of a mobile drying container 600 to a skid support system with moveable connections or couplings to allow the mobile drying container 600 to be supported on uneven ground . the mobile drying container 600 is shown with an opening 602 in a front wall ( or end wall ) leading to the lower volume of the mobile drying container 600 so that a dryer , such as a peanut dryer , may be connected to the mobile drying container 600 to allow hot or warmed air to flow into the lower volume , up through the ventilated floor , and through the crop , such as peanuts , previously loaded into the upper volume of the mobile drying container 600 . in other embodiments , the opening 602 may be provided on the opposite back wall or , in some embodiments , on the long side wall . it should be understood that the present invention is not limited to the number or the placement of the opening ( s ) 602 . wheels are shown to illustrate that the mobile drying container 600 may be easily and conveniently moved . the moveable connections , described more fully in connection with fig1 e and 18f , reduce the likelihood that the skid support system will bind when the skid support system is being raised and lowered . a traditional support leg system is shown in fig1 a . this support leg system includes a first extendable support leg and second extendable support leg connected through a horizontal member 652 . the first extendable leg includes an upper portion 614 , a retractable end 606 , and a footing 608 . the second extendable leg includes an upper portion 612 , a retractable end 604 , and a footing 608 . a crank 610 is shown for raising and lowering ( or extending and retracting ) the skid support system . in fig1 b , the footings 608 are shown removed from the retractable end of each extendable leg . in fig1 c , a first plate 622 is shown coupled or attached to the end of the retractable end 606 , and a second plate 620 is shown attached to the end of the retractable end 604 . this may be achieved , in certain embodiments , by welding the plates to the end of the retractable ends of the extendable legs . fig1 d illustrates a tray or skid 624 shown positioned under the first plate 622 and the second plate 620 , and extending between the two extendable and retractable legs . in one embodiment , a rigid member 626 is provided between the two legs and on the skid 624 to provide additional stability or rigidity to prevent the skid 624 from bending or buckling when the mobile drying container is positioned on an uneven surface or ground . the depth of the skid 624 is illustrated by the distance 630 . this distance is greater than the thickness of the first plate 622 and the second plate 620 . because , in one embodiment , the first plate 622 and the second plate 620 are not directly welded or coupled to the skid 624 , the difference in the thickness or distance 630 and the thickness of the plates 622 and 620 allow for some movement , as will be discussed more fully below . fig1 e illustrates the installation of an end cap 640 and 642 to both ends of the skid 624 . the end caps 640 and 642 prevent the skid from being removed from the first plate 622 and the second plate 620 , but allow for a “ moveable connection ” because the distance 630 is greater than the thickness of the first plate 622 and the second plate 620 . this provides the significant advantage of reducing the frequency and tendency for the extendable legs to “ freeze ” or “ bind ” up when being raised and lowered using the crank 610 . this allows the skid 624 of the mobile drying container 600 to be conveniently raised and lowered , even when positioned on uneven ground while still being able to raise and lower the legs . fig1 f illustrates the mobile drying container 600 with a chain 650 attached between the horizontal member 652 and the skid 624 ( or the rigid member 626 ). this provides additional safety assurances to prevent the skid 624 from falling or breaking loose while the mobile drying container 600 is in transit . fig1 , 20 , 21 and 22 illustrate an opening 602 , such as a plenum opening , at a front wall leading to a lower volume of the mobile drying container 600 , and the installation of a front opening cover . fig2 illustrates a close - up view illustrating one mechanism to hold an opening cover in position as desired when the opening is not being used . a rod 702 may extend above the opening and include tabs that rotate up and down when a lever 704 is moved . the tabs can grip the opening plate or cover . fig2 and 22 shows this installation of the opening cover 730 with the tabs at the top holding the upper edge of the cover 730 and the slots 700 holding the bottom edge of the opening cover 730 to securely hold the opening cover 730 . fig2 illustrates a hinged gate 802 of the back wall of a mobile drying container . the hinges 800 are shown at the top of the hinged gate 802 so that the crop , such as a load of peanuts , may be safely dumped from the top or upper volume of the mobile drying container . a lever 750 is shown connected to a member or rod 760 such that the lever 750 may be pulled , while standing at the side of the container to rotate the rod 760 allowing for one or more tabs on the rod 760 to be moved away from the bottom edge of the hinged gate 802 . this allow for the crop to push open the bottom edge of the hinged gate 802 so that the crop can be dumped . fig2 , 25 , and 26 illustrate an opening at a back wall leading to a lower volume within the mobile drying container , and included as part of the hinged gate , such as that illustrated in fig2 . a bar 720 is shown with various tabs 706 , 708 and 710 shown with a lever 704 to operate as described above in connection with fig2 - 22 to hold and secure an opening cover . a lever 750 is shown coupled to a rod 760 with various tabs 752 , 754 and 756 to secure the bottom edge of the hinged gate 802 . a hinge 800 is shown in fig2 . when the rod 760 is turned the tabs release the bottom edge of the hinged gate so that the upper volume of crop , such as peanuts may be dumped . although the preferred embodiment has been described , it should be understood that various changes , substitutions , and alterations can be made herein without departing from the scope of the present invention , even if all , one , or some of the advantages identified above are not present . these are only a few of the examples of other arrangements or configurations of the system that is contemplated and covered by the present invention . the various components , configurations , and materials described and illustrated in the preferred embodiment as discrete or separate may be combined or integrated with other components , configurations , and materials of other embodiments without departing from the scope of the present invention . other examples of changes , substitutions , and alterations are readily ascertainable by one skilled in the art and could be made without departing from the spirit and scope of the present invention .
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fig1 and 2 show a monolithic flexure hinge suspension system suitable for gyroscopes and accelerometers in accordance with the present invention . in the immediately following discussion , assistance may be had by viewing fig9 a perspective view showing the completed invention in elevation , as well as the cross - section views of fig1 and 2 . a common numbering scheme will be used throughout for aid in understanding the invention . a monolithic flexure hinge suspension 10 is shown having three distinguishable portions . a gimbal portion 12 is substantially cylindrical in shape , and spaced from a shaft connection portion 14 , also cylindrical in shape . portion 14 is spaced from portion 12 , and aligned along a common axis 16 . while the portions are described herein as cylindrical or like a ring , it should be understood that substantially ring - like , or closed annular shapes may , in fact , prove useful . a rotor connecting portion 18 is also substantially cylindrical in shape . rotor connecting portion 18 is aligned along axis 16 and spaced from portion 12 . portion 18 is separated from portion 12 by an irregular cut 20 passing completely through the suspension 10 . portion 12 is similarly separated from portion 14 by an irregular cut 22 , also passing completely through the suspension 10 . portion 18 is integrally connected with portion 12 by flexures 26 and 28 disposed diametrically opposite each other . flexure 26 comprises a first bridge 30 and a second bridge 32 . both bridges 30 , 32 consist of a thin , blade - shaped portion of material integrally connecting portion 12 and portion 18 . bridge 30 is positioned in skew relation with bridge 32 within the cylindrical opening through the cylindrical walls of the portions 12 and 18 which the bridges 30 , 32 are positioned . bridges 34 and 36 are positioned within the same geometric cylinder encompassing the bridges 30 , 32 but on the opposite side of the axis 16 . the bridges 34 and 36 are integral with the connected portions 12 and 18 and are skew in relation to each other . it should be noted that there is a discrete gap between the proximate bridges 34 and 36 , as well as between the proximate bridges 30 and 32 . similarly , a pair of flexures 40 and 42 integrally connect portion 12 with shaft - connecting portion 14 . flexures 40 and 42 are encompassed by a common cylinder , and are positioned in diametrically opposite sides of the substantially cylindrical portions 12 and 14 . flexure 40 comprises two skew bridges 44 and 46 integral with the connected portions 12 and 14 . flexure 42 comprises two skew bridges 48 and 50 similarly integral with the connected portions 12 and 14 . these bridges , as well as the bridges in the afore - mentioned flexures , are considered skew in that they do not touch each other . each has a distinct gap between it and the adjacent bridge within its respective opening through the cylindrical walls of the portions . since the principles of rotational pivoting about the intersection of crossed straps are well known in the specific art of gyroscope engineering and design , these principles need not be described here for conveying an understanding of the invention , and no further detailed description nor illustration is believed necessary . u . s . pat . no . 3 , 832 , 906 to the inventor of the present invention , which discloses , for example in fig7 crossed blade x - flexures , and of u . s . pat . no . 3 , 413 , 858 to samet , as well as other patents cited in the background of the present specification show flexure pivots and hinge assemblies utilizing the criss - crossed blade pivoting concept . as will be appreciated by those skilled in the art from the foregoing description , portion 14 is now able to rotate about axis 52 relative to the gimbal portion 12 . similarly , rotor connecting portion 18 can rotate about axis 38 relative to the gimbal portion 12 . in fig3 , 5 , 6 , 7 , 8 , 8a , 9 , 10 , 10a and 11 , a method for manufacturing the unique monolithic flexure hinge suspension of fig1 and 2 is illustrated . in the manufacture or formation of the flexure hinge suspension , a workpiece 60 is mounted to a rotatable mandrel 62 , which in turn is mounted to a movable block 64 . the workpiece 60 , shown in cross - section in fig3 may have a central portion 66 vacated , bored or otherwise formed prior to mounting on the mandrel 62 . if desired , however , boring or other machining of the cylindrical interior 66 may be performed as the first step . the workpiece 60 is substantially , therefore , cylindrical in form having an annular flare or flange 68 at one end . the cylindrical workpiece 60 has an outside surface 61 and an interior surface 67 . a movable cutting tool 70 is mounted on a vertically movable machine element 72 . the cutter 70 is held to the element 72 by a holder 74 which is capable of , along with the cutter 70 , being inserted within the cylindrical interior 66 , the operation therein being described in greater detail below . the cutter 70 is brought vertically into contact with the outside of the cylindrical wall of workpiece 60 . the cutter 70 comprises an electro - discharge machining cutter having the spaced semi - cylindrical tips form detailed in fig5 . thus , by the development of a voltage potential at the two tips 73a and 73b , two semi - cylindrical depressions or holes are formed from the exterior or outside surface of the cylindrical workpiece 60 , as shown in perspective in fig4 . edm tip 73a forms the hole 76 , and edm tip 73b forms hole 78 . both holes 76 and 78 are spaced apart from each other to fit within a common cylinder , and to leave a bridge 30 diametrically thereacross . other shapes for the edm spaced tips may be used . for example , a pair of spaced triangularly shaped , complemental tips may be used with satisfactory results . other edm tips will provide the resulting desired bridge . the holes 76 , 78 are formed or cut to a depth slightly more than one - half the thickness of the cylindrical wall of workpiece 60 . the cutter 70 is then vertically removed from the so - formed holes or depresssions , and the mandrel 62 is rotated precisely one - quarter of a turn three times in succession . after each quarter turn , the cutter 70 forms similar holes or depressions partially through the cylindrical wall from the outside surface of the workpiece 60 . the method encompassed by the present description is directed to the formation of a three portion hinge gimbal having two degrees of freedom . it should be readily appreciated from this description that a two portion gimbal having only one degree of freedom may be formed using the same method , but omitting the formation of half of the described depressions and flexures , and by omitting half of the separation cuts that will be described below . for example , to form two flexures oppositely disposed relative to the cylinder axis , the workpiece may be rotated only twice , a half - turn each time . at the end of this hole - forming step , the workpiece 60 will have the general appearance as seen in fig4 . the workpiece 60 , it may be appreciated , may remain connected to the mandrel 62 for the next step illustrated in fig6 and 7 . the movable machine element 72 is manuevered so as to insert the cutter holder 74 within the cylindrical interior 66 , as seen in elevation in fig6 . the cutter 70 is then vertically brought into contact with the workpiece 60 at its interior surface 67 . the cutter 70 then , again preferably by electro - discharge machine techniques , forms two semi - cylindrical holes or depressions 82 and 84 , seen in fig7 . the holes 82 and 84 are formed within the coincidental cylinder encompassing holes 76 and 78 formed from the outside surface 61 as described above . the cutter forms the depressions slightly more than half - way through the thickness of the cylindrical wall of the workpiece 60 . thus , in forming the holes from the interior surface 67 , the cutter removes part of the bridge 30 left remaining after the formation of the holes 76 and 78 . the formation of the holes 82 and 84 leave the bridge 32 diametriclly across the encompassing cylinder . the bridge 32 , it is noted , criss - crosses bridge 30 and is skew relative thereto . this relationship of the bridge 30 to bridge 32 is formed without manuevering or adjusting the orientation of cutter 70 . the gap 73 in the cutting end of cutter 70 has an alignment which is substantially at variance with the longitudinal diameter of the workpiece 60 . the cutter holder 70 is then elevated in a vertical direction to remove the cutter 70 from the newly formed holes 82 , 84 . the workpiece 60 is then rotated 90 degrees three times to form additional holes 82 , 84 coaxially with , and totally encompassed by the encompassing cylinders encompassing the diametrically opposite flexure hinges 28 , 40 and 42 . the cutter 70 and cutter holder 74 are then removed from the interior 66 . there remains openings 86 , 88 and 90 , as well as a fourth opening not seen in fig7 of the drawings , each of which openings penetrates all the way through the cylindrical wall of workpiece 60 . each of the openings 82 , 88 , 90 are bifurcated two separate ways by the corresponding bridges 30 , 32 , in opening 84 , bridges 44 , 46 in opening 88 , bridges 34 and 36 in opening 90 , and bridges 48 and 50 and the opening not seen in fig7 . the cutter 70 , in the preferred method of production , is now discarded . it may be appreciated that in forming the openings 86 , 88 , 90 , etc ., it is important that the formations be identical with the others , in order to insure symmetry of the hinge arrangement . thus , in order that the rotations of the portions relative to each other be sufficiently symmetrical about the spin axis and the pivot axes , it is desirable that the bridges 34 and 36 in flexure 28 be identical with and symmetrical to corresponding bridges 30 and 32 in the diametrically opposite flexure 26 . if all of the holes or depressions , therefore , are formed by the same identical cutter 70 , the depressions as well as the remaining bridges more likely will be identical on the same workpiece . fig8 a and 9 illustrate the steps of separating the workpiece into the three coaxially aligned and spaced portions 12 , 14 and 18 . while this step is described next in the sequence , it may be understood that the order of performing this step in relation to the formation of the holes and of steps which follow may be interchanged in accordance with manufacturing techniques and skill . the workpiece 60 , having the openings 86 , 88 , 90 , etc ., formed therein if desired , remains on the mandrel 62 . the cutter 70 and cutter holder 74 are removed from the movable machine element 72 . in their place is inserted a second cutter holder 94 holding an electro - discharge machine cutter 96 , shown in cross - sectional detail in fig8 a . edm cutter 96 has the general appearance of three sides of a rectangle , having flared ends 100 . the cutter 96 has a gap 98 between two halves thereof . the gap 98 is positioned over the workpiece to coincide with the cylinder encompassing the openings 86 , 88 , 90 , etc . the cutter 96 is then brought into engagement with the workpiece 60 , and cuts gap 22 from the uppermost portion of the outside surface 61 , through the cylindrical wall , through the opposite portion of the same cylindrical wall from the interior surface and on through the entire workpiece , as indicated by the broken lines in fig8 . in such a manner , portion 14 is completely separated from gimbal portion 12 , except for the criss - crossed bridge connections 44 , 46 of flexure 40 , and bridge connections 48 and 50 of flexure 42 . the cutter is then repositioned 180 degrees from the position as shown in fig8 . the flanges 100 are aligned with the annular flange 68 , so that upon descent they will pass in contact with the annular step 68 &# 39 ;. the workpiece , prior to this second separating step , is rotated 90 degrees so that the gap 98 coincides with the second encompassing cylinder encompassing the openings 90 and 86 . the edm cutter 96 is then moved to cut gap 20 completely through the workpiece 60 . in such a step , the gimbal portion 12 is completely separated from the rotor engaging portion 18 except for the integral bridge connections 30 and 36 in flexure 28 , and bridges 30 and 32 in flexure 26 . the annular flange 68 , along with a substantially rectangular t - shaped legs comprises one portion 18 of the flexure hinge arrangement . when the flange 68 is fixed to the rotor , it may be appreciated that there is a cylindrical gap between the workpiece flexure hing assembly &# 39 ; s outside surface 67 and the attached rotor , so that the rotor may exercise its degrees of freedom relative to the gimballed portion 14 . the edm cutter 96 is then removed from the workpiece 60 . if the aligning of the edm cutter 96 is precise , the gaps 20 and 22 will have substantially equal volumes . further , by precisely positioning the cutter 96 relative to the workpiece 60 , the weight and distribution of workpiece material will be symmetrical about a plane encompassing the mutually orthogonal axes 38 and 52 . as indicated in fig1 , 10a and 11 , the process of forming the flexure hinge thus far described leaves a tether 104 connecting the two skew bridges in each opening . opening 90 is shown representatively in fig1 having the bridges 34 and 36 connecting portions 12 and 18 across gap 20 . the tether 104 integrally connects bridge 34 with bridge 36 . in order for the flexure 28 to pivot , however , it will be necessary for the adjacent bridges within each opening to criss - cross each other across the opening in an unconnected , skew relationship . an l - shaped edm cutter 106 can be inserted through the opening 90 and manuevered into contact with the tether 104 as illustrated in fig1 a . the tether 104 then is removed to free bridge 34 from bridge 36 . a similar process of tether removal can be used to remove the corresponding tethers remaining in the remaining openings 86 , 88 , 90 , etc ., to result in the cross bridge flexure 28 illustrated in the cutaway , enlarged detail perspective of fig1 . it may be noted that the flexure hinge suspension system of fig1 and 2 , if used in a gyroscope , will have the portion 14 connected to the spinning shaft , while the portion 18 is connected to the inertially sensitive element such as a rotor . if the portion 14 suffers an axial force , the bridges 30 , 32 , 34 and 36 , providing a degree of freedom about axis 38 , as well as the bridges 44 , 46 , 48 and 50 providing rotational freedom about axis 52 are all placed under a tensive stress relative to the portion 18 . it has been discovered that the thin metal strips comprising these bridges have far greater tensile strength than compressive strength . if the portion 14 is compressed toward portion 18 , the failure of the thin metal strips under such a compression will occur at a pressure much less than a failure of the same thin metal strips under a tensive stress . that is to say , the thin metal strips of flexure pivot - type hinges have a far greater tensile strength than an ability to sustain compressive stresses . it can be seen , therefore , that the unique methods employed herein produce a novel , monolithic flexure hinge gyro gimbal arrangement . there are many applications where extreme stresses will be placed on the flexure pivot connection strips or blades . it is not inconceivable that such stresses might approach hundreds of times the force of gravity in some applications , a force which the thin metal strips comprising a flexure pivot hinge will simply not take in compression without failure . the structure of the present flexure hinge suspension system invention is to be compared with the more common flexure hinges of the prior art , a representative example of which is illustrated in exploded form in fig1 for convenient reference . in the prior art , a completely separate inner hinge unit 110 and outer hinge unit 140 are provided . in the inner hinge unit 110 , circumferentially extending slots 114 , 116 are formed through the cylindrical unit . a bore having a diameter exceeding the width of the slots forms openings 118a and 118b as well as similar openings , not shown , on the opposite portion of the cylindrical side of the hinge unit 110 . the bores 118a and 118b form what has been called a &# 34 ; necked - down &# 34 ; thin metal flexure portion 120 therebetween . an additional pair of circumferential slots 124 and 126 are formed through the inner hinge member 110 axially spaced from the slots 114 , 116 . like slots 114 and 116 , slots 124 and 126 are generally u - shaped but inverted with respect to the slots 114 , 116 . at the end of these slots , bores 128a and 128b as well as corresponding bores generally on the opposite portion of the cylindrical wall of hinge 110 are formed to leave a thin , metal flexure strip 130 having a thickness comparable to the so - called &# 34 ; necked - down &# 34 ; flexure portion 120 . the inner hinge unit 110 then comprises gimbal portions 132 , 134 and 136 connected to each other only by the flexure strips 120 , 130 , etc . in a similar manner , the outer hinge unit 140 is formed . a pair of slots 144 and 146 are circumferentially formed through the wall of unit 140 at an axial location precisely identical with the slots 114 and 116 formed in the inner unit 110 . the somewhat u - shaped slots 144 , 146 terminate in bores 148a and 148b which are oriented quite differently than the bores 118 , 128 of the inner unit 110 . additional slots 154 and 156 are circumferentially formed in a somewhat u - shape pattern to precisely coincide with corresponding slots 124 and 126 of the inner unit 110 . the slots 154 and 156 also terminate in bores 158a and 158b having an orientation similar to , but 90 degrees rotatably spaced from the bores 148a and 148b . the bores 148a and 148b have corresponding , diametrically opposite bores , not shown in fig1 . similarly , bores 158a and 158b have diametrically opposite bores not shown . the bores 148a and 148b are formed to leave a thin metal , flexure strip 150 therebetween . similarly , the bores 158a and 158b are formed in proximity to each other to result in a thin flexure strip 160 . the slots and bores of the outer hinge unit 140 separate the outer hinge unit into gimbal portions 162 , 164 and 166 connected to adjacent gimbal portions only by corresponding flexure strips 150 or 160 . the inner hinge unit is then telescopically inserted within the outer hinge unit so that the slot 114 coincides substantially with slot 146 , slot 116 coincides substantially with slot 144 , slot 124 coincides substantially with slot 154 and slot 126 coincides substantially with slot 156 . inner hinge unit gimbal portion 136 is fixed to outer gimbal hinge unit 166 . the gimbal portions 134 and 164 probably will be substantially independent of each other , and the flexure strip 120 will criss - cross flexure strip 150 . similarly , flexure strip 130 will criss - cross flexure strip 160 . other flexure strip criss - crossings occur on the opposite sides of the assembled inner and outer hinge units 110 , 140 . it will be noted that each flexure has only a single blade that will accept the compressive ( or tensive stress ) and such stress is not shared by a pair of blades as in the present invention , thus providing approximately half as much strength as the suspension system of the present invention . axial force in the opposite , downward direction as seen in the view of fig1 will place simple bending or flexion load stresses on the flexure strips 150 and 160 . such a structure inherently and severely limits the applications of such a gyro flexure hinge . further , the ferocious precision with which the slots and bores must be made in separate , independent elements also may be appreciated . moreover , in the prior art the use of cement or other bonding means to interconnect the many separable elements of the suspension system causes severe problems of both short and long term mechanical and thermal instability , especially because of lack of free thermal flow between parts . the presently described method of making a flexure hinge assembly , and the flexure hinge assembly produced thereby , obviates substantial portions of problems herein observed in the prior art . the present method of forming a monolithic flexure hinge assembly may be utilized to form a flexure hinge suspension system connected to the spinning shaft and the inertially sensitive rotor at approximately the same axial position . fig1 , for example , shows such a formed , monolithic flexure hinge suspension system in an alternative embodiment . a workpiece , similar to workpiece 60 , but not having a cylindrical bore formed completely along the longitudinal length therethrough , is placed on the mandrel 62 . a cylindrical hole is removed from a portion of the axial length of the workpiece , to form substantially a cylindrical workpiece having one end closed . flexures substantially identical to flexures 26 , 28 , 40 and 42 are formed through the cylindrical portion of the workpiece to form flexures 170 and 180 at 90 degree intervals as shown . it is to be understood , of course , that diametrically opposite flexures are formed on that portion of the cylindrical flexure hinge suspension system of fig1 not shown . separation cuts 182 and 184 can then be made to separate the closed end of the workpiece from the cylindrical portion . in a separate step , or simultaneously with the step of forming the separation cuts 182 and 184 , cuts 186 and 188 can be formed . the gimbal portion 190 is then completely separated from the remaining portion of the workpiece , except by the integral bridges of the flexures 170 , 180 , etc . a second separation cut can then be made concentrically with the axis to form cuts 192 and 194 on opposite sides of a diametrical cross piece 196 . additionally , separation cuts 198 and a corresponding cut in the cutaway portion diametrically opposite thereof can be axially made to completely separate gimbal portions 200 and 202 . an axial opening 204 can be formed to allow attachment to the gyroscope spinning shaft . similar to the preferred embodiment , a flange on the workpiece can result in a gimbal portion 200 having a radius greater than the radius of gimbal portion 190 , for attachment to a concentrically positioned rotor . it can be seen that the embodiment of fig1 provides for attachment of the rotor and the shaft to the intermediate gimbal at a substantially coincidental position along the spin axis . axial forces on the shaft will therefore be communicated to the rotor through the flexures 170 , 180 wherein the integral , skew bridges will sustain simultaneously compressive and tensive stresses . perfect symmetry about the spin and pivot axes , however , can be achieved in the monolithic structure as described . in fig1 , we turn to yet another alternative embodiment of the invention comprising a gyroscope assembly 230 . the gyroscope 230 comprises a housing having a cover 232 and a base 234 . the lip of the cover 232 is fitted over a groove 236 of the base 234 , and on top of an annular seal ring 238 . the seal ring 238 may be welded to create a vacuum - tight seal . alternatively , a strip of metal 240 may be welded or otherwise secured to cover the seal ring 238 and the joinder of the cover 232 in the groove 236 . a flexible tube 244 pneumatically communicates with the interior of the single compartment of the gyroscope assembly 230 and its housing . air can be evacuated through the tube 244 , and a substitute medium may be inserted into the interior compartment . typically , a one - half atmosphere of hydrogen is inserted into the interior . the pressure within the single interior compartment is thus reduced , reducing the windage affects of the rotating rotor . thermal gradients caused by differential thermal expansion characteristics of the various materials can be controlled better . the tube 244 can be pinch - sealed at its tip 246 , which can be then tucked into a short groove formed along a portion of the circumference of the base 234 . prior to the sealing of the cover 232 to the base 234 , the gyroscope is assembled . particularly , an annular hysteresis motor 250 is mounted to a mounting plate 252 . the mounting plate forms a central recessed cylinder to receive shaft bearings 254 appropriately spaced by annular spacer 256 . annularly disposed torquers 257 and are mounted to the mounting plate 252 by threaded fasteners 259 . fig1 and 15 illustrate the assembly of a portion of the gyroscope unit . an annular rotor 270 , having a somewhat inverted u - shape in cross section , is assembled to the shaft 260 through the flexure hinge arrangement as described above with regard to fig1 and 2 . shaft connecting portion 14 can be bonded or cemented beneath upper flange 262 of the upper shaft portion 264 by bond 265 . either cumulatively or alternatively , the upper flange 262 can be secured to the shaft engaging portion 14 by a threaded fastener 266 . a balancing wheel 267 can be assembled onto the upper flange 262 . the balancing wheel 267 may be supplied with balancing lugs 268 for balancing the spin of the shaft about the spin axis 269 . the rotor engaging portion 18 can be bonded as by epoxy bond 265 to the rotor 270 . rotor 270 can be formed to cooperate with balancing lugs 272 , 274 . the balancing lugs 272 , 274 have external threads on a shank adapted to be received by internal threads 276 . internal threads 276 are formed wholly within the rotor 270 itself , thus minimizing any unbalancing effects sometimes caused by special nut arrangements for balancing lugs . permanent magnets 278 are mounted on the interior of the rotor u - shape design so that when the rotor 270 is aligned with the spin axis 269 , the permanent magnets 278 are arranged in a concentric path with , and in flux influencing proximity to the torquers 257 and 258 . the permanent magnets 278 and the torquers 257 , 258 are shielded from the effects of the hysteresis motor 250 by the mounting plate 252 in the ultimate assembly . it can be seen at this point that the rotor 270 is gimballed to shaft upper portion 264 by the flexure hinge arrangement 10 through the gimbal portion 12 . the flexure bridges of flexures 40 and 42 , and flexure 28 in phantom can be seen in fig1 , while the flexures 26 and 40 can be seen in fig1 . the thus assembled upper shaft portion 264 can be connected to lower shaft portion 260 through threaded fastener 282 through the axial opening 284 in the upper shaft portion 264 . a drive flange 288 on one side of the mounting plate 252 , can be joined with the shaft 260 by nut 290 . by tightening nut 290 , the shaft 260 can be preloaded into the bearing assembly by virtue of upper flange 292 . the driving flange 288 has an annular wheel concentric with the driving means such as motor 250 , the wheel having permanent magnet 294 attached to inductively receive power from the motor 250 . inductive sensors 296 and 298 are positioned on the mounting plate 252 to receive differential , inductively generated signals from the rotor 270 , to produce a signal corresponding to displacement of the shaft 260 relative to the rotor 270 . the thus assembled gyroscope can be fit into an annular seat 300 in the interior of base 234 . threaded fasteners 302 can be used to secure the mounting plate , and thus the single unit assembled gyroscope to the base 234 . the cover 232 can then be mounted on the groove 236 and a vacuum - tight seal arranged as explained above . as can be seen by the foregoing description , a gyroscope can be completely assembled independent of a housing in which later it might be deployed . the gyroscope , as a single unit , can be very easily and efficiently mounted in a single interior compartment of a housing which can be made vacuum - tight by securing a single seal . the housing can be substantially evacuated and a controlled medium for controlling the atmosphere within the housing supplied . the unitary housing compartment shown in fig1 illustrates an alternative method of gyro construction which provides for greater accuracy of shaft and bearings . the motor 250 , bearings 254 , shaft 260 and drive plate 288 can be mounted to the mounting plate 252 and , as a unit , positioned on seat 300 and secured by threaded fastener 302 . the shaft 260 then can be rotated at operational speeds to pre - test the shaft stability and bearing balance precision prior to the seating of the rotor assembly constructed on shaft upper portion 264 . indeed , the shaft and bearing balance can be pre - tested in the actual housing base 234 prior to rotor assembly mating . for further manufacturing and assembly convenience , the shaft 260 , bearings 254 , drive plate 288 and race 256 may be pre - assembled on the mounting plate 252 to form a bearing cartridge . the cartridge , if desired , may include also the motor 250 . power can be supplied to the drive means 250 from leads 308 . the leads 308 supply power through electrical connector 310 penetrating through the base 234 in sealed cap 312 . signals from pickups 296 , 298 can be similarly conveyed through the vacuum - tight interior compartment to electrical circuitry 314 mounted on a circuit board 316 , which may be of the conventional printed circuit board or printed wire board types well known in the art . fig1 and 16 illustrate alternative embodiments of uses of the discoveries encompassed by the present invention . it may be noted that one advantageous embodiment of the monolithic flexure hinge arrangement is that the hinge portion 14 connected to the shaft 264 is axially spaced a distance relative to the spin axis 269 , from the hinge portion 18 connected to the rotor 270 . as may be seen in fig1 , if the shaft 264 is positioned vertically having portion 14 higher than portion 18 , the bridges in each and every flexure are in tension . the rotor 270 &# 34 ; hangs &# 34 ; through the gimbal portion 12 from the rotatably mounted shaft 264 . of course , if the rotor , shaft and gimbal assembly of fig1 were inverted along a vertical spin axis 269 , each and every bridge in the flexure hinge system would suffer compressive stress . it has been found , however , that thin blades used for flexure hinges buckle and fail far more readily , by a factor of five or more , under compressive stress loads than under tensive stresses . it is now desired to have a tensile strength in the flexure bridges equal to many times gravity without failure . the present embodiment is believed to provide such capability , when the assembly is aligned vertically to establish tensive stress loading in the flexure bridges . it will be appreciated that in the present structure , in each flexure hinge g - loads are shared by both bridges of the flexure hinge . in fig1 , the spin axis is aligned orthogonally to the vertical so that the spin axis is substantially orthogonal to the field forces of gravity . the rotor 270 is connected by gimbal 2 to the horizontal shaft 264 . the stresses in the bridge 30 will be different from the stresses in bridge 32 . in many applications , the embodiment of fig1 is desired . it is believed that the tension stress of one such paired bridge cancels any imbalance effect caused by the compressive stress of the other bridge in the pair . in any event , a slight but crucial structural change is made in the resonant spin frequency of the embodiment of fig1 , from that of the embodiment of fig1 . in field activities , especially where large inventories of replacement gyros are maintained it is desirable to have complete interchangeability and uniformity for replacement and routine servicing . this uniformity , however , can result in serious , practical problems in gyro operation in certain applications . for example , in two gyro systems , such as the strapped - down platform system shown in fig1 , the spin axis 330 on one gyro 332 is oriented orthogonally to the spin axis 336 in the second gyro 338 . if the axis 330 is considered oriented in the z direction , and the axis 336 is considered to be oriented in the y direction the x axis in the cartesian coordinate system will be seen to lie in a plane parallel to the base 340 . the gyroscope 332 will then sense movements about its x axis and the y axis . the second gyroscope 338 will sense movements about its x axis and its z axis . movement about all 3 of the cartesian coordinate axes will be sensed by either one or the other of the two gyros 332 , 338 with a redundant reading about the x axes by both gyros . power is supplied from motor power supply 342 through leads 344 , 346 to , respectively , gyroscopes 332 and 338 . it is well known that if two dynamically tuned gyros are mounted on the same base 340 and are operated at the same spin speeds , the slight vibrations set up by one gyro 332 degrades the performance of the other gyro 338 . this effect is referred to as &# 34 ; cross - talk &# 34 ; and is described in greater detail in craig &# 34 ; theory of errors of a multigimbal , elastically supported , tuned gyroscope &# 34 ;, i . e . e . e . transactions on aerospace and electronic systems , vol . aes - 8 , no . 3 , may 1972 and &# 34 ; dynamically tuned gyros in strapdown systems &# 34 ;, conference proceedings no . 116 , agard , nato . in order to eliminate this degradation of accuracy , it is a common practice to operate the two gyros at different speeds . thus , a frequency f 1 is delivered to gyroscope 332 , while a different frequency f 2 is transmitted to the motor of gyroscope 338 . such practice , however , inherently leaves problems unresolved . where two gyros have the same tune independent of their orientation with respect to gravity , one such practice known is to drive the gyros with two different frequencies , each of which is slightly off the tuned frequency . both instruments are thereby detuned , in effect . the operation at different spin speeds thus produces detuning errors . if the gyros are tuned to different speeds , on the other hand , the normal requirement for interchangeability is not satisfied . the present invention , as embodied by the use simultaneously of the embodiments of fig1 and 16 in the gyro system , eliminates the necessity for such de - tuning . identical gyros can be used , and the inherent tuned spin frequency shift caused by the differential loading of the differently oriented flexure bridges will result in sufficiently different spin frequency to prevent gyro coupling or interference . that is to say , if f 1 = f 2 in fig1 , the stress in all of the bridges being tensive or being compressive establishes as in the embodiment of fig1 , a peculiar tuned frequency resonance . this tuned frequency resonance will be distinct from and observably different from a tuned frequency resonance established by the identical structure having its spin axis oriented in a substantially horizontal plane as illustrated in fig1 . the different tuned frequency resonance is caused by the fact that the bridges in each pair constituting a flexure will have opposed or opposite types of stress . fig1 shows yet another alternative embodiment to which the present invention is well suited . in fig1 , a three gimbal configuration 350 is shown in cross - sectional elevation . the upper shaft portion or hub 354 spins about the spin axis 352 . the inertially sensitive element is the rotor 356 . unlike the suspension system of fig1 and 2 , the three gimbal configuration 350 of fig1 contains three interrelated monolithic gimbal suspension systems 360 , 370 and 380 . gimbal suspension system 360 has a structure , and is made in a manner , similar to the gimbal suspension system 10 . suspension system 360 has a shaft attaching portion 362 , a rotor attaching portion 364 , and a gimbal portion 366 . the rotor attaching portion 364 has two degrees of freedom relative to the shaft attaching portion 362 by virtue of the monolithic flexures 368 , shown schematically in fig1 . the second monolithic suspension system 370 is constructed similarly to suspension system 360 , but having a greater diameter so that it can fit concentrically about suspension system 360 . suspension system 370 is comprised of a shaft attaching portion 372 , a gimbal portion 376 , and rotor attaching portion 374 . shaft attaching portion 372 is fixed to suspension system shaft attaching portion 362 by a bonding , such as weld 378 . similarly , rotor attaching portion 374 is fixed to rotor attaching portion 364 of monolithic suspension system 360 by a bonding such as weld 379 . in like manner , monolithic suspension system 380 is constructed similarly to the hinge suspension 10 , having a greater diameter than monolithic suspension system 370 . suspension system 380 fits concentrically about suspension system 370 , having a shaft attaching portion 382 , a rotor attaching portion 384 , and a gimbal portion 386 . rotor attaching portion 384 has two degrees of freedom about orthogonal pivot axes relative to shaft attaching portion 382 , even as rotor attaching portion 374 of suspension system 370 has two degrees of freedom relative to its shaft attaching portion 372 , by virtue of mutually orthogonal pivot axes in the gimbal portion 376 . shaft engaging portion 372 is fixed to shaft engaging portion 382 by a bonding such as weld 388 . similarly , rotor engaging portion 374 is fixed to rotor engaging portion 384 . the mutually orthogonal axes of suspension system 370 are rotatably or angularly spaced from the mutually orthogonal axes of suspension system 360 by 60 degrees . further , the mutually orthogonal axes of suspension system 380 are rotatably spaced from the mutually orthogonal axes of suspension system 360 by 120 degrees . the shaft attaching portions 362 , 372 and 382 are fixed to the shaft upper portion or hub 354 . since the rotor attaching portions 364 , 374 and 384 are fixed to the rotor 356 , it can be seen that only the gimbal portions 366 , 376 and 386 are free relative to each other . the rotor 356 will have the desired two degrees freedom about the hub 354 , even as in the flexure hinge suspension system 10 of fig1 and 2 , but will have such two degrees of freedom about three separate sets of mutually orthogonal axes , each set of mutually orthogonal axes rotatably displaced 60 ° from the other of the two mutually orthogonal axes . the principal moments of inertia of the three gimbal configuration 350 can be selected to completely cancel errors of twice spin frequency rectification effects by merely adjusting the inertias of the gimbals 366 , 376 and 386 . the concept of a dynamically tuned , three rotor gyro having three concentric gimbals is described in greater detail in u . s . pat . no . 3 , 832 , 906 to the inventor of the present invention . some advantage in a multi gimbal arrangement can be achieved by having two concentrically positioned , attached gimbal suspension systems , such as suspension systems 360 and 370 in fig1 . the suspension system 380 is eliminated , so that the rotor 356 can be connected directly to the rotor connecting portion 374 of suspension system 370 . in such a two gimbal arrangement , the degree of freedom pivot axes of the individual gimbals are rotatably displaced from each other by 90 °. for further detailed description , of the advantages and operation of such a multigimbal configuration , attention is directed to fig1 of the aforementioned u . s . pat . no . 3 , 832 , 906 . the foregoing detailed description is illustrative of several embodiments of the invention . it is to be understood , however , that additional embodiments will be perceived by those skilled in the art . the embodiments described herein together with those additional embodiments are considered to be within the scope of the present invention .
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referring to fig1 a principal embodiment of the present invention may be represented by a data acquisition block 10 , a data sampling block 12 , an output determination block 14 , and a reset block 16 . the data acquisition block 10 includes light shielding means subsequently described which defines an airspace 18 through which ambient light 20 passes for incidence upon light sensor means internal to the data acquisition block via a narrow window or slit disposed orthogonally to the direction of anticipated object movement . a detection signal 22 , produced by data acquisition block 10 , is responsive to a change or blockage in ambient light 20 , this blockage being caused by the presence of an object in airspace 18 . while no object is present in the airspace , detection signal 22 remains at a quiescent level . as an object passes through airspace 18 , detection signal 22 rises above its quiescent level in response to the size and shape of the object . the term &# 34 ; ambient light &# 34 ; as used in this specification and claims is meant to comprehend existing light conditions not associated with the activation circuit . that is to say , the presently described activation circuit is not dependent on a particular light source . the term &# 34 ; optical airspace &# 34 ; as used herein refers to a space through which ambient light passes and impinges upon light sensitive elements such as photoconductors . the presence of an object in the airspace results in a decrease in ambient light incident upon light sensitive elements . the signal sampling block 12 monitors the detection signal 22 and captures a peak value occurring therein to provide a scaled peak signal 24 , e . g ., a fixed percentage of the captured peak value . the output determination block 14 detects the occurrence of the peak in the detection signal 22 by comparison of the scaled peak signal 24 with the detection signal 22 ; when the detection signal 22 falls below the scaled peak signal 24 , a peak in the detection signal 22 is implied . when a peak has been found in the detection signal 22 , the output determination block 14 generates an activation signal 26 . the reset block 16 supplies a reset signal 28 in response , for example , to the activation signal 26 , or in response to manual push buttons or the like to initiate a reset condition in blocks 10 and 12 . the data acquisition block 10 compensates for naturally occurring changes in ambient light unrelated to the passage of objects through window 18 . during reset , the data sampling block 12 abandons the currently held peak value in preparation for the next peak in the detection signal 22 whereby the circuit is then ready for detection of the next object passing through airspace 18 . referring to fig2 describing portions of the circuit of fig1 in greater detail , an operational amplifier 30 , having its non - inverting input grounded and its inverting input coupled to a voltage v1 through a photoconductor array 32 , produces at its output the detection signal 22 representative of the blockage of ambient light 20 incident upon photoconductor array 32 from airspace 18 . a photoconductive feedback resistor 31 is connected between the output and the inverting input of amplifier 30 . the photoconductor array 32 and feedback resistor 31 cooperate to provide automatic gain control for amplifier 30 . without a photoconductive resistor in the feedback , the gain of amplifier 30 would vary as the ambient light conditions vary , the gain of amplifier 30 being a function of the relative resistance of the array 32 and resistor 31 . by utilizing a photo sensitive resistor , i . e ., a resistor 31 similar to those in the array 32 , the relative resistance of the array 32 and the feedback resistance is stabilized despite changes in ambient light , and , accordingly , the gain of operational amplifier 30 is more nearly constant . data acquisition block 12 suitably includes an input amplifier 34 , an output amplifier 36 , a diode 38 , and a holding capacitor 40 . the amplifier 34 receives the detection signal at its non - inverting input , while its output is coupled by way of diode 38 to the non - inverting input of the amplifier 36 . the output of the amplifier 36 is fed back to the non - inverting input of amplifier 34 . holding capacitor 40 is interposed between the non - inverting input of the amplifier 36 and ground , while the output of amplifier 36 is returned to a voltage source - v through serially connected resistors r1 and r2 , the resistors r1 and r2 being interconnected at a node 44 for scaling the output of the amplifier 36 to a predetermined percentage value . the signal present at the node 44 suitably provides the scaled peak signal 24 . prior to &# 34 ; arming &# 34 ; of the circuit , a switch 42 is momentarily set to a reset position to discharge any voltage across the holding capacitor 40 , and is then returned to an arm position . when an object enters airspace 18 ( fig1 ), a portion of the ambient light 20 otherwise incident upon photoconductor array 32 is blocked . as a result , detection signal 22 rises and the output of amplifier 34 rises to charge holding capacitor 40 , while the output of amplifier 36 , taking its input as the voltage across the holding capacitor 40 terminals , also begins to rise . when a peak in the detection signal 22 has occurred , detection signal 22 begins to fall , causing the output of amplifier 34 to fall , thereby discontinuing the charging of the holding capacitor 40 . the voltage then present across the terminals of the holding capacitor 40 is stabilized and the output of the operational amplifier 36 is representative of the peak in detection signal 22 . the scaled peak signal 24 present at the node 44 comprises a predetermined percentage of the detection signal 22 , the predetermined percentage being a function of the resistances of the resistors r1 and r2 . the output determination block 14 includes a comparator 46 , receiving the scaled peak signal 24 at its positive input and the detection signal 22 at its negative input . comparator 46 asserts at its output the activation signal 26 when the scaled peak signal 24 is greater than the detection signal 22 . it is desirable to ignore peak values in the detection signal which are below a given threshold . to this end , fet 46 having its drain coupled to node 44 and its source coupled to voltage source - v is utilized to maintain the scaled peak signal 24 normally at or near the voltage of source - v . a potentiometer p1 is connected between a voltage v2 and ground and includes a movable tap 48 . the output of a comparator 50 is coupled to the gate of fet 46 , while its positive input is coupled to tap 48 . the negative input of comparator 50 receives detection signal 22 . potentiometer p1 is adjusted for providing a threshold voltage such that when the detection signal 22 is below the threshold , the output of the comparator 50 turns the fet 46 on and drives the voltage at the node 44 close to the potential of source - v , inhibiting production of an activation signal 26 . when the detection signal 22 rises above the threshold , fet 46 is turned off and the voltage at the node 44 is representative of the predetermined percentage of the detection signal . referring to fig3 an aircraft 100 is illustrated as passing through airspace 18 in the direction of arrow 102 while the corresponding detection signal 22 is seen immediately therebelow . as the aircraft 100 passes airspace 18 , the ambient light 20 blocked by the aircraft 100 varies . a shaded portion 104 of an optical window or slit 18 &# 39 ; represents the blockage of ambient light due to the presence of aircraft 100 in the corresponding airspace , and , at the instant depicted in fig3 represents the amount of blockage due to a body section 106 . the waveform presented by the detection signal 22 is generally proportional to the size of shaded portion 104 and is therefore generally a function of the size and shape of the passing aircraft 100 . the various portions of the illustrated waveform of the detection signal depict its amplitude when parts of the aircraft immediately thereabove are aligned with window 18 &# 39 ;. as the aircraft 100 first enters airspace 18 , the body section 106 causes the detection signal 22 to rise as indicated by reference numeral 114 . when a wing section 108 of aircraft 100 passes through the window 18 &# 39 ;, the size of the shaded portion 104 will increase to a maximum as noted by reference numeral 116 . as the last of the winged section 108 passes , the shaded portion 104 suddenly becomes smaller as a body section 110 then enters airspace 18 . the passage of wing section 108 thus causes a peak 118 in detection signal 22 , while a second peak 120 in detection signal 22 is the result of passage of a tail section 122 . the output of amplifier 36 ( fig2 ), a signal 123 , follows the detection signal 22 through regions 114 and 116 until the occurrence of the peak 118 and thereafter maintains a value substantially equal to the peak 118 value . the scaled peak value 24 follows the signal 123 as a fixed percentage thereof . when the detection signal 22 then becomes less than the scaled peak signal 24 , at a point indicated by reference numeral 124 , the activation signal 26 increases from a non - activation state to an activation state , i . e ., at a time tφ . at a later time , not shown in fig3 the signal 123 , the scaled peak signal 24 , the detection signal 22 , and the activation signal 26 will be returned to their respective initial values in preparation for the detection of another aircraft passing through the same airspace . in fig4 and 5 , with fig5 being taken along lines 5 -- 5 of fig4 a first light sensitive activator 150 and a second light sensitive activator 152 , each similar to the one depicted in fig1 - 3 , are positioned along the flight path of an aircraft 154 having a direction of travel indicated by arrow 156 . the light sensitive activators 150 and 152 include light shields 151 and 153 which define , respectively , airspace 158 and airspace 160 intersecting the path of aircraft 154 . a first activation signal 162 , generated by light sensitive activator 150 in response to the passage of aircraft 154 through window 158 , is employed to start a counting operation by counter element 164 . a second activation signal 166 , generated in response to the passage of aircraft 154 through window 160 , is used to terminate the counting operation . the value remaining in the counter element 164 after termination of the counting operation is representative of the ground speed of aircraft 154 between airspace 158 and airspace 160 . the light sensitive activator 150 is further illustrated in fig6 and 7 wherein the photoconductive array 32 and photoconductive feedback resistor 31 are illustrated as mounted on a slidable circuit board 170 and coupled to operational amplifier 30 as well as voltage source v1 . each of the photoconductive resistors of the array 2 and resistor 31 include a rectangular photoconductive area of approximately 0 . 25 inches by 0 . 050 inches , the photoconductive areas being aligned on the board 170 to form an overall photoconductive area 171 of approximately 1 . 25 inches by 0 . 050 inches . a slot 172 having dimensions of 1 . 25 inches by 0 . 040 inches is formed in a section of tape 174 disposed immediately above the photoconductive array 32 and photoconductive resistor 31 . a second slot 176 , substantially proportional to the slot 172 and having dimensions 4 inches by 0 . 2 inches , is formed in an upper portion 178 of activator 150 at a location directly above the photoconductive array 32 at the base of the light shield 153 . the board 170 is moved vertically to adjust the spacing between the photoconductive array 32 and the slot 176 as a means changing the dimensions of airspace 18 . as the board 170 is moved toward the slot 176 , airspace 18 increases in dimension , while moving the board 170 down and away from the slot 176 reduces the dimensions of airspace 18 . to compensate for the loss of contrast at higher altitudes due to dust and moisture in the air , and to adjust for the amount of light received , the voltage v1 is varied in accordance with the vertical position of the board 170 . the voltage v1 is increased as the board 170 is moved away from slot 176 and decreased as it is moved toward slot 176 . the voltage v1 ( fig2 and 7 ) may be derived from a potentiometer , such as indicated at reference numeral 60 of fig8 operated by movement of the board 170 or alternatively may be taken from a terminal on the board 170 contacting a portion of a stationary resistor ladder ( not shown ) adjacent the board 170 . thus , for a higher altitude aircraft the voltage v1 is increased to improve the sensitivity of the photoconductors and provide a relatively consistent detection signal 22 for any given airplane as the board 170 is moved to provide an airspace corresponding to the altitude of the given airplane . fig8 is a more detailed schematic diagram illustrating a further and preferred embodiment of the circuit of fig1 . in fig8 reset block 16 includes a flip - flop 54 controlled by an arm switch and a reset switch . the flip - flop 54 suitably comprises pnp transistors q1 and q2 having their emitters returned to positive voltage source v3 and their collectors connected to negative voltage source v4 via resistors r3 and r4 . the base of transistor q1 is coupled to the collector of transistor q2 through a resistor r5 , to positive voltage source v3 by way of resistor r6 , and to negative voltage source v4 through resistor r7 and the arm switch in series . in similar fashion , the base of transistor q2 is coupled to the voltage source v3 by resistor r8 , to the collector of transistor q1 by resistor r9 , and to the voltage source v4 through resistor r10 and the reset switch . a reset signal on lead 28 is taken from the collector of transistor q2 whereby when the reset switch is engaged , the voltage at the base of transistor q2 is reduced causing transistor q2 to conduct current through resistor r4 and raise the voltage on lead 28 . by virtue of the connection including resistor r5 , the potential at the base of transistor q1 also rises such that transistor q1 ceases conducting current through resistor r3 , and transistor q2 is then maintained in a conductive state even after the reset switch is disengaged . when the arm switch is engaged the potential at the base of q1 is reduced whereby transistor q1 conducts current through resistor r3 . as a result the potential at the base of transistor q2 increases cutting off the flow of current in resistor r4 and lowering the reset signal 28 voltage . thus , the reset signal 28 can be asserted and remains asserted until the arm switch is pressed at which time the reset line returns to a relatively low voltage . photoconductor array 32 , comprising a plurality of separate photoconductive resistors pcr connected in parallel , is interposed between variable voltage source 60 and the inverting input of operational amplifier 30 . amplifier 30 is connected in substantially the manner described in reference to fig2 . variable current source 74 couples voltage v3 to the emitters of pnp transistors q8 and q9 , the collectors of which are connected to negative voltage v4 via resistors r13 and r14 respectively . the base of transistor q9 is connected to ground through resistor r15 . the base of transistor q8 is returned to ground through diode d2 while also being coupled to detection signal path 22 at the output of amplifier 30 via resistor r16 . a negative voltage , between ground and negative v4 , is provided at a node 75 from a transistor circuit configured as a voltage source 76 wherein node 75 is connected to the inverting input of operational amplifier 30 by way of resistor r17 and fet 77 in series . the gate of fet 77 is returned selectively to voltage v4 through one of the capacitors c4 , c5 , and c6 . resistor r18 connects the collector of transistor q8 to the base of fet 77 , with resistor r18 being disposed in parallel with the combination of resistor r19 and diode d3 in series . it is desirable to be able to adjust the output of operational amplifier 30 , i . e ., the detection signal on lead 22 , to a quiescent state near ground in preparation for detecting changes in the detection signal . operational amplifier 30 comprises an inverting summing amplifier wherein a first input is provided through the photoconductor array 32 , and a negative compensating input is supplied from the negative voltage at the node 75 through resistor r17 and fet 77 . the negative compensating input is used to bring the detection signal path 22 up to ground level . when the circuit is armed , voltage source potentiometer 60 together with array 32 presents a positive signal to operational amplifier 30 and correspondingly a negative signal occurs at the output of amplifier 30 . transistor q8 then conducts current from current source 74 raising its collector voltage to charge a selected one of capacitors c4 , c5 , and c6 , increasing the gate voltage of fet 77 . a resulting reduction in the resistance of fet 77 has the effect of raising the path 22 level towards ground . as signal path 22 approaches ground potential , transistor q8 tends toward turn off causing a drop in potential at the collector of transistor q8 . current source 74 is adjusted to maintain the quiescent state of the detection signal path 22 substantially at ground potential . a relatively short term increase in the detection signal above ground potential then indicates a blockage of ambient light otherwise incident upon the photo conductor array 32 . the selected one of the capacitors c4 , c5 , and c6 establishes a sensitivity level whereby relatively slow moving objects such as clouds do not produce significant changes in the detection signal , while faster moving objects such as airplanes are able to produce detection signal peaks . in conjunction with the aforementioned operation of photoresistor 31 , the circuit compensates for changes in ambient light not associated with the passage of airplanes . it will be seen the selected capacitance ( c4 , c5 or c6 ) establishes a time constant for voltage change at the gate of fet 77 wherein a large capacitance would allow only relatively slow voltage changes at the gate of fet 77 and a smaller capacitance would permit relatively faster voltage changes at the gate of fet 77 . if the voltage at the gate of fet 77 is held to change relatively slowly , then the activation circuit is more sensitive in that the negative compensation voltage provided by the fet 77 will be less effective in maintaining the detection signal 22 near ground potential . the signal sampling block 12 receives the detection signal 22 at the non - inverting input of operational amplifier 34 , the latter having its output fed back to its inverting input by way of resistor r22 , and its output returned to ground through diode 38 , resistor r23 , and holding capacitor 40 in series . amplifier 36 takes as its non - inverting input the voltage present across holding capacitor 40 while its output is fed back to its inverting input via resistor r24 and to the inverting input of amplifier 34 through resistor r25 . serially connected resistors r1 and r2 return the output of operational amplifier 36 to ground for providing scaled peak signal 24 at node 44 . fet 80 , with its drain coupled to the non - inverting input of amplifier 36 through resistor r26 , its source returned to ground , and its gate coupled to reset signal 28 through drive circuitry 82 , is employed to discharge the holding capacitor 40 when the reset signal on lead 28 is asserted . after arming , and as the detection signal on lead 22 rises above its quiescent level due to the blockage of ambient light otherwise incident upon the photo conductor array 32 , the output of amplifier 34 charges the holding capacitor 40 until the detection signal on lead 22 reaches a peak and begins to fall . the voltage present across the terminals of the holding capacitor 40 becomes stabilized for representing the peak value detection signal , since diode 38 prevents discharge of the holding capacitor . the output of amplifier 36 , i . e ., on lead 240 , is then representative of the peak in the detection signal whereby the voltage present at the node 44 provides the scaled peak signal on lead 24 as a fixed percentage of the peak in the detection signal . the last mentioned percentage is a function of the relative resistances of resistors r1 and r2 . output determination block 14 compares the detection signal on lead 22 with the scaled peak signal on lead 24 and , when the detection signal has peaked , solenoid 90 is activated to cause a camera 92 to take a picture of an object in airspace 18 ( fig1 ). the peak in the detection signal is implied when the detection signal falls below the scaled peak signal . a comparator 94 for detecting this condition comprises transistors q3 and q4 having their collectors returned to positive voltage source v3 through resistors r28 and r29 , their emitters connected together and coupled to negative voltage source v4 via the collector - emitter path of current source transistor q5 , and their bases coupled to detection signal lead 22 and scaled peak signal lead 24 respectively . the base of transistor q5 connects to node 75 of voltage source 76 for maintaining a constant current flow through transistor pair q3 , q4 . pnp transistor q6 , having its base attached to the collector of transistor q3 , its emitter returned to voltage source v3 , and its collector coupled to voltage source v4 via resistor r30 and capacitor c3 in series , is controlled by the voltage present at the collector of transistor q3 for charging capacitor c3 . similarly , pnp transistor q7 is controlled by the voltage present at the collector of transistor q4 , wherein the base of transistor q7 is connected to the collector of transistor q4 , its emitter is connected to the voltage source v3 , and its collector is coupled to the voltage source v4 through resistor r31 , capacitor c7 , and resistor r32 in series . a first lead of solenoid 90 connects to the junction between capacitor c3 and resistor r30 while a second terminal of the solenoid is returned to voltage source v4 via silicon controlled rectifier 96 whereby when the silicon controlled rectifier conducts current , the voltage across capacitor c3 is discharged through solenoid 90 , e . g ., for activating camera 92 , or a counter ( not shown ). the gate of silicon control rectifier 96 is coupled to the midpoint between capacitor c7 and resistor r32 so that when the resistor conducts a predetermined current , the rectifier 96 gate voltage rises and the rectifier 96 fires . as long as the detection signal on lead 22 is more than the scaled peak signal on lead 24 , transistor q3 conducts and transistor q4 does not . the voltage at the collector of transistor q3 is low enough to turn on transistor q6 while the voltage at the collector of transistor q4 is high enough to turn off the transistor q7 . it will be seen the flow of current through transistor q6 results in charging of the capacitor c3 . subsequently , when the detection signal on lead 22 first becomes less than scaled peak signal 24 , transistor q3 ceases conduction and transistor q4 turns on which turns off transistor q6 as transistor q7 conducts . the current through transistor q7 passes through resistor r32 dropping a voltage thereacross and bringing about conduction in silicon controlled rectifier 96 whereby capacitor c3 is discharged through solenoid 90 to activate camera 92 . potentiometer 93 can be used to determine the minimum turn - on level for transistor q4 . hence the minimum peak in the fig3 waveform is detected . during reset , the output determination block 14 is inhibited from activating the camera 92 . pnp transistor q10 , having its base coupled to lead 28 through drive circuitry 98 , its emitter returned to voltage source v3 , and its collector connected to the collector of transistor q4 , is responsive to an asserted reset signal on lead 28 for maintaining the voltage at the collector of transistor q4 and the base of transistor q7 high enough to ensure the transistor q7 remains off . thus , silicon controlled rectifier 96 is held in a non - conductive state whereby solenoid 90 is inoperative . as previously noted it is desirable to inhibit the activation circuit for peaks in the detection signal 22 below a given threshold . as an alternative to manually adjusting a threshold voltage , e . g ., with a potentiometer p1 of fig2 or potentiometer 93 in fig8 an automatic threshold circuit as illustrated in fig9 may be employed for storing a voltage level corresponding to a forward portion of a plane body to establish a reliable threshold voltage above which the wing section is known to drive the detection signal . the established threshold voltage is used to inhibit the activation circuit until the detection signal is found to be above the threshold . referring to fig9 a flip - flip circuit 200 , having a first input terminal 201 coupled to the reset signal 28 line of the activation circuit in fig8 and a second input terminal 202 connected to a timed pulse circuit 203 , is used to operate fets 204 and 206 . fet 204 receives at its source terminal a version of the increasing detection signal ( stored on capacitor 40 ) from lead 240 via resistor r40 , while its drain terminal is returned to ground through a capacitor c10 as well as being coupled to the non - inverting input of an operational amplifier 208 . the gate of fet 204 is connected to a first output lead 210 of the circuit 200 through resistor r42 . fet 206 is coupled at its gate to another output lead 212 of circuit 200 via resistor r44 and to ground through a diode 214 . the source terminal of fet 206 is returned to ground . the drain terminal of the same fet is connected to the positive input of the operational amplifier 208 by way of resistor r46 . a timed pulse circuit 203 is controlled by the output of a comparator 218 such that when the output of comparator 218 is driven negative , circuit 203 presents a positive pulse of predetermined duration at input terminal 202 of circuit 200 . the duration of the pulse is less than the time required for the forward portion of a body section of a plane , not including the wing section , to pass through an optical window . the non - inverting input of comparator 218 is taken from a voltage divider 220 set to provide a voltage level comparable to the signal produced pursuant to detecting the nose section of an airplane . the inverting input of the comparator 218 receives the stored detection signal from lead 240 for comparison with the last mentioned voltage level such that its output is driven negative when the detection signal from lead 240 rises above the voltage level . a positive pulse is consequently presented at the terminal 202 when a nose section of an airplane is detected . at the inverting input of the operational amplifier 208 , a - 50 mv signal is applied through a resistor r48 , and the output of operational amplifier 208 is fed back to its inverting input through resistor r50 having twice the resistance of resistor r48 so as to provide amplifier 208 with a gain of two . the output of operational amplifier 208 is connected to an auto contact of a switch 222 . a manual contact of the switch 222 is connected to a movable terminal 224 of potentiometer p3 coupled between a positive and a negative voltage . the signal on lead 240 is applied to the inverting input of operational amplifier 230 while the non - inverting input of amplifier 230 is connected to the movable contact of switch 222 for providing selective coupling between the operational amplifier 230 and either potentiometer p3 or the output of the operational amplifier 208 . the output of operational amplifier 230 is connected via resistor r52 to the gate of fet 232 having its source terminal coupled to a - 1 . 2 voltage supply 234 and its drain connected to terminal 44 of the activation circuit of fig8 . by means of coupling the terminal 44 ( fig8 ) to the negative voltage supply 234 ( fig9 ), the activation circuit is disabled because the scaled peak signal on lead 24 ( fig8 ) will be held below the detection signal . thus , when the output of operational amplifier 230 is driven high , the activation circuit is disabled , and when its output is negative the activation circuit is enabled . the circuit may be operated in one of two modes , i . e ., manual setting of the threshold level and automatic setting of the threshold level . manual adjustment of the threshold level can be most effective when the sun is near the horizon . when the switch 222 is set to couple the movable terminal 224 to the non - inverting input of operational amplifier 230 , the potentiometer is manually adjusted to provide a suitable threshold voltage . when the switch 222 couples the output of operational amplifier 208 to the non - inverting input of operational amplifier 230 , the threshold circuit will detect the presence of a nose section in the window 18 ( fig1 ) and establish a suitable threshold voltage . when the activation circuit is reset via lead 28 , circuit 200 presents a high voltage at its output 212 and a low voltage at its output 210 thereby turning fet 204 off and fet 206 on . at this time , the detection signal on lead 240 will be substantially at ground potential and the output of operational amplifier 208 is approximately + 0 . 1 volts , such that the output of operational amplifier 230 is positive , turning on fet 232 and disabling the activation circuit . when the activation circuit is then armed , i . e ., the signal on lead 28 drops , circuit 200 changes state whereby fet 204 is turned on and fet 206 is turned off . in this condition it will be seen the voltage across capacitor c10 follows the detection signal on lead 240 . as the nose of an airplane passes through the optical window and the detection signal on lead 240 exceeds the voltage level taken from voltage divider 220 , the output of operational amplifier 218 becomes negative and causes the timed pulse circuit 203 to present a positive pulse at terminal 202 of circuit 200 . during this positive pulse , the voltage across the capacitor c10 increases to a point corresponding to the width of the forward body section of the airplane ; this voltage is doubled by operational amplifier 208 and presented as a suitable threshold voltage to the non - inverting input of the operational amplifier 230 , assuming switch 222 is in the auto position . on the falling edge of the positive pulse presented to terminal 202 , circuit 200 changes state to turn fet 204 off and thereby decouple the operational amplifier 208 from the detection signal on lead 240 , the output of operational amplifier 208 then being a function of a stored voltage on the capacitor c10 . in this manner a suitable threshold voltage is stored and provided to operational amplifier 230 . subsequently when the system is reset , transistor 206 is again turned on for discharging capacitor c10 . the automatic threshold circuit may be used in an alternative manner wherein it is incorporated into an activation circuit used to generate and store a threshold voltage on a first fly by for use during a subsequent fly by . while plural embodiments of the present invention have been shown and described , it will be apparent to those skilled in the art that many changes and modifications may be made without departing from the invention in its broader aspects . the appended claims are therefore intended to cover all such changes and modifications as fall within the true spirit and scope of the invention .
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referring to fig1 - 2 , a heat dissipation device in accordance with the preferred embodiment of the present invention comprises a heat sink 10 , a pair of heat pipes 20 , a fan 30 and a fan holder 40 . the heat sink 10 comprises a base 12 for intimately contacting with a cool - waiting component ( not shown ) by a contact face , and having a flatly main face disposed opposing to the contact face and a plurality of side faces surrounding the contact face . the heat sink 10 further comprises a plurality of fins 16 spanning on the base 12 . each fin 16 forms a perpendicularly bent flange facing the base 12 . the fins 16 are parallel to each other , and are arranged at substantially uniform intervals via the flanges formed therebetween . all of the perpendicularly bent flanges of the fins 16 define a continuous surface exposed to the base 12 . the base 12 defines two parallel grooves 122 on the main face facing the fins 16 . two separate through holes 162 extend across the fins 16 . the through holes 162 are parallel to the grooves 122 . the through holes 162 are closer to the fan 30 than to the base 10 . each heat pipe 20 comprises an evaporating section 22 and a condensating section 26 parallel to the evaporating section 22 . the evaporating sections 22 of the heat pipes 20 are accommodated in the grooves 122 of the base 12 , for transferring heat accumulated on the base 12 to the condensating section 26 . the condensating sections 26 of the heat pipes 20 are engagingly inserted in the through hoes 162 of the fins 16 , for releasing heat accumulated thereon to the fins 16 distant from the base 12 . the fan holder 40 covers the fins 16 and is disposed at an opposite side of the fins 16 relative to the base 12 . the fan holder 40 comprises a support plate 42 and locating ears 46 . the locating ears 46 extend perpendicularly from a pair of opposite edges of the support plate 42 . the support plate 42 defines a central opening 422 . the opening 422 communicates with an outlet ( not labeled ) of the fan 30 and an inlet ( not labeled ) of the heat sink 10 . the support plate 42 further defines locking holes 426 . the locking holes 426 are aligned with the positioning holes 32 of the fan 30 . screws or pins ( not shown ) pass through the positioning holes 32 of the fan 30 , and further engage within the locking holes 426 of the fan holder 40 , to thereby secure the fan 30 to the fan holder 40 . the locating ears 46 are parallel to the fins 16 . the locating ears 46 attach outmost fins 16 and sandwich all of the fins 16 therebetween . an engaging hole 462 is defined in each locating ear 46 for receiving a corresponding condensating section 26 of the heat pipes 20 . a cutout 466 is defined at a free end of each locating ear 46 , communicating with the engaging hole 462 . the width of the cutouts 466 are smaller than the diameter of the engaging holes 462 , and provide a guide way for having the condensating sections 26 to enter the engaging holes 462 . in assembly of the heat dissipation device , the heat pipes 20 are first secured into the through holes 162 of the heat sink 10 . the fan holder 40 is then placed onto the heat sink 10 and is pressed . the condensating sections 26 of the heat pipes 20 enter the engaging holes 462 via the cutouts 466 . eventually , the locating ears 46 of the fan holder 40 grip the condensating sections 26 of the heat pipes 20 at the engaging holes 462 . thus , the fan holder 40 is mounted onto the heat sink 10 by means of the heat pipes 20 . it is practicable that the locating ears 46 merely define the engaging holes 462 without the cutouts 466 . under this circumstance , the fan holder 40 is first placed onto the heat sink 10 . the condensating sections 26 of the heat pipes 20 respectively extend through the engaging holes 462 at one side of the heat sink 10 , the through holes 162 of the fins 16 , and the engaging holes 462 at an opposite side of the heat sink 10 . as a result , the ears 46 grip opposite ends of the condensating sections 26 of the heat pipes 20 , and thus the fan holder 40 is secured to the heat sink 10 . it is understood that the invention may be embodied in other forms without departing from the spirit thereof . thus , the present examples and embodiments are to be considered in all respects as illustrative and not restrictive , and the invention is not to be limited to the details given herein .
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now , the present invention will be described in detail hereunder with reference to the accompanying drawings which illustrate a preferred embodiment thereof . referring first to fig1 and 2 , a crankcase 1 for an engine e mounted on a body frame f of a scooter type motorcycle is connected with a rearwardly extending transmission case 2 on one side of the crankcase 1 and an axle 3 spline - connected to a hub of a rear wheel wr is rotatably supported at the rear end of the transmission case 2 via a pair of left and right ball bearings 4 and 4 &# 39 ;. in addition , a belt type continuously variable transmission t operatively connected to a crankshaft ( not shown ) of the engine e and a gear type deceleration unit r adapted to rotate the axle 3 at a reduced speed via an output shaft 5 of the transmission t are accommodated in the transmission case 2 . in order to assure that the transmission case 2 freely rocks along with the rear wheel wr in the vertical direction , the fore part of the crankcase 1 is supported on the body frame f via a link 6 and the rear end part of the transmission case 2 is connected to the body frame f via a damper 7 . a caliper 9 adapted to impart a braking force to the rear wheel wr in cooperation with a rotor 8 secured to the hub of the rear wheel wr and an antilock controlling device a for controlling a braking hydraulic pressure to be applied to the caliper 9 are arranged in association with the transmission case 2 . particularly , the antilock controlling device a is located rearwardly of the transmission t so as not to be adversely affected by collision with any foreign matter coming from the foreward side as viewed from the motorcycle and moreover it is located at a possibly high position so as not to be adversely affected by foreign matters scattered upwardly from the road surface . the rotor 8 and the caliper 9 as mentioned above constitute a known disc brake b . additionally , a master cylinder m to be operated by a brake pedal 10 and an oil reservoir 11 located upwardly of the master cylinder m are fitted to the body frame f . the oil reservoir 11 is communicated with the master cylinder m via a first oil supply passage l 1 , the master cylinder m is communicated with the antilock controlling device a via an upstream - side braking oil passage l 3 , the antilock controlling device a is communicated with the caliper 9 for the disc brake b via a downstream - side braking oil passage l 4 and moreover the antilock controlling device a is communicated with the oil reservoir 11 via a second oil supply passage l 2 . owing to the communication established in this way , a working oil stored in the oil reservoir 11 is supplied to the master cylinder m and the antilock controlling device a and an output hydraulic pressure from the master cylinder m is applied to the caliper 9 of the disc brake b via the antilock controlling device a . the antilock controlling device a includes a casing 12 which is comprised of a case body 12a having a locating boss 13 fitted into the outer wall of the transmission case 2 and secured thereto by means of bolts 14 and a cap - shaped cover 12b fitted onto the open end of the case body 12a . an extension portion 12c extending rearwardly of the rear surface of the case body 12a is made integral with the latter . a driving shaft 15 , a hydraulic pump 16 , a modulator 17 , a discharge valve 20 and a wheel deceleration sensor 21 are arranged in the casing 12 . the driving shaft 15 is supported by the casing 12 via bearings 19 and 19 &# 39 ;. one end of the driving shaft 15 is protruded into the interior of the transmission case 2 and is spline - fitted thereat with a pinion 23 which meshes with a final gear 22 having the largest diameter among a group of gears of the deceleration unit r . the hydraulic pump 16 comprises an eccentric cam 26 formed on the driving shaft 15 in a region located between both the bearings 19 and 19 &# 39 ;, a push rod 27 of which inner end is located opposite to the eccentric cam 26 , a pump piston 28 placed in abutment against the outer end of the push rod 27 , a working piston 29 placed in abutment against the outer end of the pump piston 28 and a return spring 30 for biasing the push rod 27 in a direction of moving away from the eccentric cam 26 . the push rod 27 and the pump piston 28 are slidably inserted in a first cylinder bore 33 in such a manner as to define an inlet chamber 31 and outlet chamber 32 around their outer peripheral surfaces . in addition , a plug 34 is threadably engaged with the outer end of the first cylinder bore 33 to define a pump chamber 35 between the pump piston 28 and the plug 34 , and the working piston 29 is slidably inserted into the plug 34 to define a hydraulic chamber 36 . the inlet chamber 31 is communicated with the oil reservoir 11 via the second oil supply passage l 2 and is moreover communicated with the pump chamber 35 which in turn is communicated with the outlet chamber 32 via a one way seal member 39 adapted to function as a delivery valve . additionally , the hydraulic chamber 36 is hydraulically connected to the upstream - side braking oil passage l 3 in such a manner that it is normally communicated with the output port of the brake master cylinder m . the modulator 17 comprises a pressure reducing piston 46 , a stationary piston 47 adapted to receive one end of the pressure reducing piston 46 to define a limit of backward movement thereof and a return spring 48 for biasing the pressure reducing piston 46 in a direction of coming in contact with the stationary piston 47 . both the pistons 46 and 47 are slidably inserted in a second cylinder bore 52 which is formed adjacent to the first cylinder bore 33 in the extension portion 12c . the pressure reducing piston 46 defines a controlling hydraulic chamber 18 between it and the inner wall surface of the second cylinder bore 52 and moreover defines an output hydraulic chamber 55 between it and the stationary piston 47 , while the stationary piston 47 defines an input hydraulic chamber 54 around the outer peripheral surface thereof . the input hydraulic chamber 54 is communicated with the hydraulic chamber 36 of the hydraulic pump 16 via a hydraulic passage 56 and the output hydraulic chamber 55 is hydraulically connected to the downstream - side braking oil passage l 4 so as to be normally communicated with the input port of the caliper 9 . further , the controlling hydraulic chamber 18 is communicated with the outlet chamber 32 of the hydraulic pump 16 via a hydraulic passage 57 . the stationary piston 47 is formed with a valve chamber 58 which is normally communicated with the input hydraulic chamber 54 and a valve bore 59 for allowing the valve chamber 58 to be communicated with the output hydraulic chamber 55 therethrough . a valve body 60 for opening and closing the valve bore 59 and a valve spring 61 for biasing the valve body 60 in a direction of closing the valve bore 59 are accommodated in the valve chamber 58 . to open the valve body 60 , a valve stem 62 is provided so as to extend through the valve bore 59 . when the pressure reducing piston 46 assumes its position at a limit of its backward movement , the valve stem 62 thrusts the valve body 60 whereby the latter is brought in an opened state . the outer opening of the second cylinder bore 52 is closed with a plug 63 which is threadably engaged with the extension portion 12c , and the stationary piston 47 is normally held at a position where it comes in contact with the plug 63 , under the effect of resilient force of the return spring 48 or hydraulic pressure introduced into the input hydraulic chamber 54 and the output hydraulic chamber 55 . referring to fig3 and 4 , the pressure discharge valve 20 comprises a valve casing 65 fitted into a fitting recess 64 formed on the inner wall of the casing body 12a , a valve body 67 accommodated in the valve casing 65 to open or close a valve bore 66 and a valve spring 68 for resiliently biasing the valve body 67 in a direction of closing the valve bore 66 . the outer end of the valve bore 66 is communicated with the controlling hydraulic chamber 18 of the modulator 17 via a through hole 70 and the interior of the valve casing 65 leading to the inner end of the valve bore 66 is communicated with the inlet chamber 31 of the hydraulic pump 16 via a hydraulic passage 71 . after all , it follows that the interior of the valve casing 65 is communicated with the oil reservoir 11 . referring to fig3 to 7 , the wheel deceleration sensor 21 includes a cam mechanism 73 adapted to be driven by the driving shaft 15 via a clutch plate 75 , a flywheel 72 adapted to be driven by the cam mechanism 73 via a resilient driving member 76 and an output lever mechanism 74 for actuating the pressure discharge valve 20 in response to actuation of the cam mechanism 73 due to overrunning of the flywheel 72 . all the above - mentioned components are accommodated in the casing 12 . the cam mechanism 73 comprises a driving cam plate 82 for rotatably but axially immovably supporting a boss 82a on the driving shaft 15 via ball bearings 78 , a driven cam plate 83 located closer to the eccentric cam 26 from the driving plate 82 and located opposite to the plate 82 and a plurality of thrust balls 84 annularly arranged between both the cam plates 82 and 83 . the clutch plate 75 spline - fitted onto the driving shaft 15 is brought in pressure contact with one end face of the boss 82a of the driving cam plate 82 under the effect of resilient force of a clutch spring 79 . a plurality of cam recesses 85 and 86 allowing the thrust balls 84 to be engaged therewith are provided on opposite surfaces of both the cam plates 82 and 83 . specifically , each of the cam recesses 85 on the driving cam plate 82 is inclined in such a manner that its bottom surface becomes shallower in a rotational direction a of the driving shaft 15 , while each of the cam recesses 86 on the driven cam plate 83 is inclined in such a manner that its bottom surface becomes deeper in the rotational direction a . accordingly , in a normal case where the driving cam plate 82 assumes a driving side with respect to the driven cam plate 83 , the thrust balls 84 are brought in engagement with both the recesses 85 and 86 at their deepest positions so that the driving cam plate 82 transmits rotational torque received from the driving shaft 15 to the driven cam plate 83 , causing no relative rotation to occur between both the cam plates 82 and 83 . however , in a contrary case where the driven cam plate 83 overruns with respect to the driving cam plate 82 , the result is that relative rotation occurs between both the cam plates 82 and 83 and thereby the thrust balls 84 roll and climb the inclined bottom surfaces of the cam recesses 85 and 86 . this causes a certain intensity of thrust force to be imparted to both the cam plates 82 and 83 whereby the driven cam plate 83 is axially displaced away from the driving cam plate 82 . the flywheel 72 is supported on the boss 82a of the driving cam plate 82 on the opposite side to the driven cam plate 83 so as to be rotatable relative to the boss 82a via a ball bearing 87 but against movement in the axial direction . additionally , the flywheel 72 is connected to the driven cam 83 via the driving member 76 . the driving member 76 is made of elastic material such as spring steel plate , synthetic resin or the like material and comprises an annular plate 76a and a plurality of driving pawls 76b projecting radially inwardly of the inner periphery of the annular plate 76a . each of the driving pawls 76b has such a flexibility that it can flex only in the axial direction of the flywheel 72 . when the flywheel 72 is connected to the driven cam plate 83 , the annular plate 76a is secured to the side surface of the flywheel 72 by using bolts 77 and the driving pawls 76b are engaged with radially extending grooves 89 on the outer side surface of the driven cam plate 83 . to prevent the driving pawls 76b from being disengaged from the grooves 89 , an inner race of a ball bearing 92 to be described later is fitted onto the boss 83a of the driven cam plate 83 . the output lever mechanism 74 includes a support column 90 projecting from the inner end surface of the case body 12a at an intermediate position between the driving shaft 15 and the pressure discharge valve 20 and a lever 91 supported by a semispherical fulcrum portion formed at the foremost end of the support shaft 90 so as to be swingable in the axial direction of the driving shaft 15 . the lever 91 comprises a first arm 91a extending from the support column 90 while bypassing the driving shaft 15 and a second arm 91b extending from the support column 90 toward the pressure discharge valve 20 . additionally , a semispherical abutment portions 93 formed at an intermediate portion of the first arm 91a are brought in engagement with the driven cam plate 83 via the ball bearing 92 . a set spring 94 for resiliently biasing the first arm 91a toward the ball bearing 92 side is provided between the foremost end of the first arm 91a and the case body 12a , and the foremost end of the second arm 91b is jointed to the valve disc body of the pressure discharge valve 20 with a predetermined amount of play kept therefore . a resilient force imparted to the lever 91 by the set spring 94 permits the abutment portions 93 on the first arm 91a to abut against the outer race of the ball bearing 92 . this allows the lever 91 to be normally parted away from the valve body 67 of the pressure discharge valve 20 whereby the latter is maintained in a closed state . the biasing force imparted to the ball bearing 92 by the set spring 94 functions to urge the driven cam plate 83 toward the driving cam plate 82 . while a vehicle travels , the final gear 22 in the deceleration unit r directly rotates the axle 3 of the rear wheel wr and moreover rotates the pinion 23 on the driving shaft 15 at an increased speed . the rotational torque generated by the pinion 23 is transmitted to the flywheel 72 via the driving shaft 15 , the clutch plate 75 , the driving cam plate 82 , the thrust balls 84 , the driven cam plate 83 and the driving member 76 to rotate the flywheel 72 at a speed higher than that of the rear wheel wr . this leads to a result that the flywheel 72 has a large rotational inertia force . now , when the master cylinder m is actuated to brake the rear wheel wr by depressing the brake pedal 10 , an output hydraulic pressure from the master cylinder m is transmitted to the disc brake b via the upstream - side braking oil passage l 3 , the hydraulic chamber 36 in the hydraulic pump 16 , the input hydraulic chamber 54 in the modulator 17 , the valve chamber 58 , the valve bore 59 , the output hydraulic chamber 55 and the downstream - side braking oil passage l 4 so that a braking force can be imparted to the rear wheel wr . on the other hand , since the output hydraulic pressure from the master cylinder m is introduced into the hydraulic chamber 36 in the hydraulic pump 16 , a reciprocal movement is imparted to the pump piston 28 by a biasing function given to the working piston 29 under the effect of the hydraulic pressure as well as a lifting function of the eccentric cam 26 given to the push rod 27 . during a suction stroke in which the pump piston 28 moves to the push rod 27 side , the suction valve 38 is caused to open so that an oil in the oil reservoir 11 is introduced into the pump chamber 35 via the second oil supply passage l 2 and the inlet chamber 31 . during a delivery stroke in which the pump piston 28 is displaced toward the working piston 29 side , the one - way seal member 39 is opened so that an oil in the pump chamber 35 is pumped to the output chamber 32 and then to the controlling hydraulic chamber 18 in the modulator 17 via the hydraulic passage 57 . when a pressure in the outlet chamber 32 and the controlling hydraulic chamber 18 is increased to a predetermined value , the pump piston 28 is held along with the working piston 29 at an abutment position against the plug 34 , under the effect of hydraulic pressure in the outlet chamber 32 . here , since communication between the controlling hydraulic chamber 18 in the modulator 17 and the oil reservoir 11 is initially interrupted due to closing of the pressure discharge valve 20 , a hydraulic pressure fed to the controlling hydraulic chamber 18 from the hydraulic pump 16 acts directly on the pressure reducing piston 46 to forcibly displace the latter to its rearward position and thereby the valve body 60 is maintained in an opened state by means of the valve stem 62 . this permits an output hydraulic pressure from the master cylinder m to pass through the valve bore 59 . accordingly , in a normal braking state , a braking force to be applied to the disc brake b is in proportion to an output hydraulic pressure from the master cylinder m . when an angular deceleration ( namely , a negative angular acceleration ) is produced on the rear wheel wr during such braking operation , the flywheel 72 which has sensed that condition tends to perform overrunning rotation along with the driven cam plate 83 with respect to the driving shaft 15 under the effect of its rotational inertia force . namely , a relative rotation tends to occur between both the cam plates 82 and 83 . however , at a stage where there is no possibility that the rear wheel wr is locked , the rear wheel wr has a low angular deceleration and thereby the relative rotation between both the cam plates 82 and 83 is suppressed under the influence of a set load of the set spring 94 . when the rear wheel wr is liable to be locked due to an excessively increased braking force or a reduced frictional coefficient of the road surface , this causes an angular deceleration of the rear wheel wr to exceed a predetermined value , resulting in a relative rotation being produced between both the cam plates 82 and 83 by a rotational inertia force of the flywheel 72 . thus , a thrusting force caused by rolling of the thrust balls 84 exceeds the set load of the set spring 94 whereby the driven cam plate 83 is axially displaced toward the lever 91 side . at this moment , the driving pawls 76b are caused to flex in response to the driven cam plate 83 being displaced in the axial direction . thus , there is no need of allowing the flywheel 72 having a high magnitude of inertia mass to be displaced in the axial direction . accordingly , the driven cam plate 83 can reliably respond to a thrusting force greater than a specified level which has been produced between both the cam plates 82 and 83 , while preventing a delay in actuation of the cam mechanism 73 . additionally , the output lever mechanism 74 can be actuated quickly . in response to the axial displacement of the driven cam plate 83 , the lever 91 is caused to turn about the support column 90 serving as a fulcrum in such a manner as to compress the set spring 94 whereby the valve body 67 of the pressure discharge valve 20 is moved leftward against a resilient force of the valve spring 68 . consequently , the pressure discharge valve 20 assumes an opened state . after an axial displacement of the driven cam plate 83 , if the rotational torque caused by the inertia of the flywheel 72 is in excess of the transmission torque specified for the clutch plate 75 , a slippage occurs between the driving cam plate 82 and the clutch plate 75 and the flywheel 72 continues overrunning rotation with respect to the driving shaft 15 along with the cam mechanism 73 . this assures that transmission of any excessive load to the cam mechanism 73 or the like can be interrupted . when the pressure discharge valve 20 is opened , the hydraulic pressure in the controlling hydraulic chamber 18 is released to the oil reservoir 11 via the through hole 70 , the valve bore 66 , the interior of the valve casing 65 , the oil passage 71 , the inlet chamber 31 of the hydraulic pump 16 and the second oil supply passage l 2 whereby the pressure reducing piston 46 is displaced toward the control hydraulic chamber 18 side against the resilient force of the return spring 48 . this permits the valve body 60 to be closed by retraction of the valve stem 62 so that communication between the input hydraulic chamber 54 and the output hydraulic chamber 55 is interrupted and the volume of the output hydraulic chamber 55 is increased . as a result , the braking hydraulic pressure applied to the disc brake b is reduced , followed by a decrease in braking force for the rear wheel wr so that an occurrence of locking phenomenon at the rear wheel wr can be avoided . then , as the rear wheel wr restores its rotating state , the thrusting force imparted to the lever 91 via the cam mechanism 73 is released and thereby the lever 91 returns to its original position under the effect of resilient force of the set spring 94 , resulting in the pressure discharge valve 20 being kept in a closed state . once the pressure discharge valve 20 is closed , a hydraulic oil delivered from the hydraulic pump 16 is promptly enclosed in the controlling hydraulic chamber 18 , causing the pressure reducing piston 46 to be displaced rearwardly toward the output hydraulic chamber 55 side to increase a hydraulic pressure in the output hydraulic chamber 55 . otherwise , the pressure reducing piston 46 thrusts the valve body 60 upwardly to open the latter so that an output hydraulic pressure from the master cylinder m is transmitted to the output hydraulic chamber 55 and thereby a braking force is restored . since the aforementioned operations are repeated at a high speed , the rear wheel wr can be braked at a high efficiency .
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for the following description of preferred , but purely exemplary embodiments , it should first be noted that essentially the same components or those with equivalent properties are represented in the drawings with the same reference signs . fig1 to 3 represent a simplified view of a first embodiment according to the invention of a flat cable connector in different successive assembling stages , embodying a pressurization device , i . e . a device for applying pressure , with which two sealing elements are moved pincer like in direction of the upper and lower side of the flat cable arrangement into a position essentially closing a flat cable insertion opening and are subjected to pressure . in detail there is a representation of a flat cable connector , generally marked with 100 with a connector housing generally marked with 101 . the connector 100 is engineered as a connector socket and as in fig1 has a rear receptacle opening 102 for the reception of a complementarily designed counter - connector , but which is not shown . on the opposite side of the receptacle opening 102 as in fig1 the flat cable connector 100 comprises a flat cable insertion opening to insert a flat cable arrangement 200 of a familiar variety . an exemplary representation of a flat cable arrangement 200 as in fig1 in the preferred form is designed as essentially being a flex foil , in particular comprising a flexible flat cable ( ffc ) or a flexible printed circuit ( fpc ). however , a flat cable capable of use according to the invention can comprise another flat ribbon cable , an extruded ( flat ) cable or a laminated ( flat ) cable . hence fundamentally in the following description and in the claims the general term of a flat cable or a flat cable arrangement is used . the flat cable arrangement 200 represented comprises in addition connecting leads or terminals 201 specific to the application , which are connected to the conductors of the flat cable e . g . by pressure , crimping , welding or also by ( laser -) soldering technologies . the flat cable arrangement 200 as a whole is normally provided by a cable harness manufacturer prior to insertion in the connector in order to effect the electrical connection of the flat cable arrangement . the housing 101 of the connector 100 is on principle sealed at transition or interface faces and depending on the application has at the connecting points or areas in the interior corresponding terminal contacts and / or terminal position assurance means ( tpa ), as it is known in general . the flat cable insertion opening 103 has a larger and essentially rectangular cross - section , which is limited laterally as well as to the top and bottom , in relation to the flat cable arrangement 200 which must be inserted . the lateral limitation is achieved by plate - formed frame elements 104 and 105 , which are connected to the housing 101 . guiding grooves 106 are formed on the frame elements 104 and 105 , e . g . by means of cutting or by the use of corresponding pre - formed parts during manufacture , each running in the insertion direction of the flat cable arrangement diagonally from the upper or lower area of the frame elements 104 , 105 to the middle section of the frame elements 104 , 105 . two pillow or cushion - like sealing elements 107 and 108 made out of a compressed gel are installed movably across and between the frame elements 104 and 105 and limit the flat cable insertion opening 103 at the top and bottom . assigned to the sealing elements 107 and 108 are guiding projections 109 extending in direction of the frame plates 104 and 105 up to the guiding grooves 106 . hence the sealing elements 107 and 108 can be moved along the guiding grooves 106 between a position opening the flat cable insertion opening 103 and a position closing the flat cable insertion opening 103 , that is in the insertion direction e of the flat cable arrangement from the upper or lower area of the frame elements 104 , 105 to the middle area of the frame elements 104 , 105 and vice versa . furthermore assigned to the sealing element 107 are snapping , catching or locking means 107 a and 107 b working in combination with complementary catching or locking means 108 a and 108 b assigned to the sealing element 108 to achieve catching or locking , when the sealing elements 107 and 108 are in the position closing the flat cable insertion opening 103 . the guiding projections 109 and the catching means 107 a , 107 b , 108 a and 108 b can be directly connected to the sealing elements 107 and 108 . however , the guiding projections 109 and the catching or locking devices 107 a , 107 b , 108 a and 108 b are constructed in a preferred manner at respective cassette - shaped support devices 110 , as in fig1 to 3 , in which the sealing elements 107 and 108 being insertable in such a way that the opposing surfaces of the sealing elements 107 and 108 project out of the support device 110 . as can be seen in fig2 , in the position of the sealing elements 107 and 108 unblocking the flat cable insertion opening 103 , the flat cable arrangement 200 is inserted with the end providing the terminals 201 into the flat cable insertion opening 103 until the terminals are aligned at a predefined , not represented position within the flex foil connector , in accordance with the example described , at the terminal contacts or terminal position assurance means . since the sealing elements 107 and 108 are here far apart , an unimpeded insertion of the flat cable arrangement 200 and in particular of the terminals 201 is ensured . the terminals 201 must in particular not penetrate through the sealing gel during insertion . hence there is no danger that the compressed sealing gel has an effect on the flat cable arrangement prematurely or unintentionally or that particles of the sealing elements 107 and 108 , for example as a result of friction , penetrate into terminals 201 . since in addition no or very little force is required for the insertion , the flat cable arrangement as a whole is not subjected to any damaging strain during insertion . following the insertion of the flat cable arrangement 200 there follows , as can be seen in fig3 , its sealing by moving the sealing elements 107 and 108 into the position closing the flat cable insertion opening 103 . due to the guidance means 106 and 109 , especially the arrangement of the guiding grooves 106 , only minimal force need be applied here , an undesired canting or displacement of the sealing elements is prevented and a pressurization of the gel - based sealing elements 107 and 108 to achieve sealing both in the normal ( n ) and axial ( a ) direction in relation to the flat cable arrangement 200 is guaranteed . to support the sequence of movements , housing walls 111 arranged behind the support constructions 110 have essentially the same angle of inclination as the guiding grooves 106 . once the sealing elements 107 and 108 have reached their final position , they are fixed in this by the interlocking of the locking means 107 a and 108 a or 107 b and 108 b and maintained by pressure in a functional manner . depending on the application it is particularly advantageous if the gel - based sealing elements are pre - selected , sized and arranged in the housing 101 with such a viscosity that the gel used for sealing in the sealing elements 107 and 108 during pressurization reaches from the terminals 201 at least as far as to the conductors of the flat cable 200 as well as to the predefined areas in the connector housing 101 . in addition different gels can be used depending on the application area , e . g . silicon gels , which are particularly media - resistant , but other gel - based elastomers as well . sealing with gel has in particular the advantage that depending on the degree of firmness of the gel used it reaches virtually every cranny , creates no sharp edges and closes the open edges of a meniscus that may have been caused . in addition the gel sealant in accordance with the invention provides protection against vibration , anti - kink protection and soft kink edges as well as , if so selected , a certain strain relief . depending on the gel selected , the flat cable connector is sealed against water splashes and pressurized water , both at excess and negative pressure , other fluids , including aggressive kinds , e . g . petrol , and / or air and correspondingly protected . since the gel sealant is also a dielectric , based a suitable choice and the dimensions of the compressed gel used an adjustment depending on the application is attainable with regard to a desired protection against disruptive discharges , a desired impedance , especially in hf ( high frequency )- applications and / or a reflector attenuation . if the connector housing has a hole opening leading outwards in the area of at least one of the gel sealing cushions , of such a kind that when the pressurized gel gets into the hole opening or an indicator agent is pressed outwards this can be seen from the outside , then this will in addition provide an indicator in relation to the spreading process of the gel produced by the pressurization and hence on the sealing achieved by the gel . fig4 to 8 show a further preferred embodiment of the invention as an example , which includes a pressurization device with guidance and catching means dedicated to it to guide the pressurization device , first in a normal direction in relation to the flat cable arrangement at the connecting point and then in an axial direction in relation to the flat cable arrangement at the connecting point . the flat cable connector 100 as in fig4 to 8 in addition to the design as in fig1 to 3 features a gasket sleeve 150 which can be inserted into the housing 101 , as is particularly evident in fig4 and 5 a , from the side of the receptacle opening 102 for receiving a complementarily shaped , but not represented counter plug connector . this gasket sleeve 150 is kept in housing 101 by the attachment clip 151 in the area of the terminal contacts in the housing for additional sealing . in turn , the flat cable insertion opening 103 according to the embodiment of fig4 to 8 has a larger and essentially rectangular cross - section in relation to the flex foil that has to be inserted . furthermore two plate - like frame elements 104 and 105 attached to the housing 101 and having guiding grooves or ribs 106 ′ arranged therewith provide lateral limitation of the flat cable insertion opening 103 . but in amendment to the first embodiment described , these guiding grooves or ribs 106 ′ essentially run vertically to the insertion direction e ( fig5 a ) of a flat cable arrangement 200 . one of the two remaining sides of the flat cable insertion opening 103 , in fig4 the left or upper side , is limited by a further plate - like frame element 125 connected to the housing 101 and / or to the plate - like frame elements 101 and 105 . on the side opposite of the frame element 125 a cover 130 is inserted and guided , as hereafter described in more detail , to achieve sealing pressurization as well as to close the insertion opening 103 in assembled condition with the flat cable arrangement 200 . for this purpose the cover 130 has two frame elements 131 and 132 , essentially arranged to each other at a right angle , whose longitudinal extension essentially corresponds to the inner distance of the frame elements 104 and 105 . the frame element 132 , for the purpose of the insertion of the cover 130 , being aligned diagonally or at an angle to the insertion direction of the flat cable arrangement 200 and the frame element 131 essentially being aligned parallel to the insertion direction of the flexible foil 200 ( fig5 a , b ). the open side areas formed by the angled arrangement of the frame elements 131 and 132 are closed by two frame elements 133 which are connected essentially vertically at their long side ends with the frame elements 131 and 132 . hence the frame elements 133 limit the frame elements 131 and 132 in their longitudinal extent and are aligned parallel to the frame elements 104 and 105 and inserted between these to achieve the attachment of the cover 130 . on the outer sides of the frame elements 131 and 132 guidance strips or ribs 109 ′ and 136 are formed , which work in combination with the guidance tracks 106 ′ during the insertion of the cover 130 . thus the cover 130 , as can be seen in fig4 to 8 , is essentially inserted at first across the insertion direction of the flat cable arrangement in the housing 101 between the frame elements 104 and 105 , that is , in a kind of upside down installed drawer without a back wall , and is guided in direction to the frame element 125 . also in this embodiment two sealing elements 107 ′ and 108 ′ are used to seal a flat cable arrangement 200 connected with a flat cable connector 100 . the sealing element 107 ′, as can be seen in particular in fig4 and 5 b , is inserted into the insertion opening 103 between the frame element 125 and the terminal contacts or terminal position assurance means 140 arranged within connector 100 for the terminals 201 attached to the conductors of the flat cable and essentially completely fills this intermediate area . the sealing element 108 ′ is inserted in the cover 130 , as shown by the arrow x in fig4 , and thus routed together with the cover 130 in direction to the frame element 125 , so that in the end there is a sealing element arranged on each side of the inserted flat cable arrangement at the connecting area . in this embodiment both sealing elements 107 ′ and 108 ′ are again preferably compressed gel cushions , though in this design it is in principle sufficient to provide only the sealing element 108 ′ in gel form , since as will be - hereafter described , no or very little pressure is exercised on sealing element 107 ′, so that in order to reduce costs resort could also be had to another sealant material . cover 130 in addition has catching or locking devices 134 on the frame elements 133 formed with guidance devices 109 ′. the catching or locking devices 134 interact with complementarily formed catching or locking devices 135 a and 135 b on the frame elements 104 and 105 to lock the cover in a first or second snap - in or locking position , as is described in detail below . to install the flat cable connector 100 as in fig4 to 8 with the flat cable arrangement 200 the two sealing elements 107 ′ and 108 ′ are first inserted in the insertion opening 103 or the cover 130 . then the cover is installed in a functional manner as in fig5 a and 5 b between the frame elements 104 and 105 and guided into the first snap - in or locking position . then the flat cable arrangement 200 is inserted into the insertion opening 103 with its attached terminals 201 to the terminal contacts or terminal position assurance means 140 in the connector 100 ( fig6 a , 6 b ). hence in this embodiment an unimpeded insertion of the flat cable arrangement 200 and especially the terminals 201 in relation to the sealing elements 107 ′ and 108 ′ is also provided for . hereafter the cover 130 , as shown in fig7 , is guided further in direction to the frame element 125 up to the second snap - in or locking position , whereby in the embodiment shown the flat cable arrangement 200 is led via the sealing element 107 ′ to the frame element 125 and thus in its final position projects outwards directly between the frame element 125 and the cover - frame element 132 . this achieves a strain relief of the flat cable arrangement and through the cover 130 a pressurization on the gel - based sealing element 108 ′ in relation to the flat cable arrangement in the normal direction n . after this the cover , as can be seen in fig8 , is guided into by light pressurization in the insertion direction of the flat cable arrangement into its final position , thereby completing the sealing of at least the connection area through axial pressurization a of the sealing element 108 ′, and is preferably locked by further complementarily designed catching or locking means . for this purpose the ribs 136 arranged on the frame element 133 can in addition snatch behind one of the ribs 106 ′ arranged on the inside of the frame elements 104 and 105 in order to fix the cover 130 closing the insertion opening . it is worth pointing out that in modification to the embodiment shown in fig4 to 8 , depending on the application the cover and the sealing elements to be inserted can also be so designed , that the flat cable arrangement does not project straight out of the connector between the frame element 125 and the cover 130 , but instead on the side , in particular essentially turned by 90 °, that is , in relation to fig5 b for example , it projects below the frame element 131 . here it is preferable that the flat cable arrangement is inserted first and then the cover is installed on the connector housing in the first position . in this case depending on the application , an arrangement of the guidance and catching devices can also be provided for that first a displacement of the cover in an axial direction in relation to the insertion direction is carried out and then a displacement in the normal direction . given a correspondingly mirrored design of the cover and the frame elements 104 , 105 and 125 the extension of the flex foil 200 to the opposite side , that is with reference to fig8 for example essentially in an angle of 90 ° to the left , also can be guaranteed . the fundamental design of a cover that is positioned off - set to the insertion opening on the connector housing , which can then be successively moved in the insertion opening in a normal or axial direction , or vice versa , to achieve the corresponding pressurization of the sealing elements , thus enables a “ straight ” and an angled flat cable connector in combination with the sealing elements suitable inserted in the housing and cover . the fig9 to 12 show an example of another embodiment of a flat cable connector according to the invention , which has been realized with sealing elements and a pressurization device , which can inserted following the insertion of the flat cable arrangement in the insertion opening . as can be seen in the first essential modifications with regard to the first embodiment as afore - described based on fig1 to 3 , result from the fact that the gel - based sealing elements 107 ″ and 108 ″, designed in the form of pillows or cushions , are only arranged after a pre - assembly of the flat cable connector 100 as in fig9 to 12 with the flat cable arrangement 200 inside the flat cable connector 100 and / or the housing 101 . in addition , to achieve a pressurization of the sealing elements 107 ″ and 108 ″ following their arrangement in the flat cable insertion opening 103 , a cover 120 for pressurization is provided , which is connectable in the insertion direction e of the flat cable 200 with the wall of the flat cable insertion opening 103 . for this purpose the exterior dimensions of the opening cover 120 designed for pressurization are so sized that it can be inserted in direction of the insertion direction of the flat cable arrangement 200 at least partly into the flat cable insertion opening 103 and preferably here undergoes a sliding — or press fit with the flat cable insertion opening 103 . complementary catching or snapping devices 121 and 122 are constructed on the opening cover 120 and the wall of the flat cable insertion opening 103 to achieve the final fixation . in addition the opening cover 120 has a slot 123 essentially corresponding to the cross - section of the flat cable arrangement 200 , through which the flat cable arrangement 200 is led . a preferred assembly of the flat cable connector 100 with the flat cable arrangement 200 according to fig9 to 12 is described below . first the flat cable arrangement 200 is guided through the slot 123 of the opening cover 120 and then the terminal 201 are linked by crimping or soldering to the conductors of the flat cable arrangement 200 . the flat cable arrangement 200 with the end possessing the terminals 201 is then inserted into the flat cable insertion opening 103 , as shown in fig1 . if the other end of the flat cable arrangement is freely available and not equipped with terminals , the opening cover 123 can also subsequently be pushed on to the flat cable arrangement in its insertion direction . it is worth pointing out that for the purposes of the subsequent attachment of the opening cover 120 at the flat cable arrangement 200 the opening cover 120 can also e . g . be in one piece with two halves that can be brought together or in two parts , depending on the application . thus in this embodiment too essentially the same advantages accrue during the insertion of the flat cable arrangement 200 as in the first embodiment . following the insertion of the flat cable arrangement 200 with the terminals 201 in the desired position the two sealing elements 107 ″ and 108 ″ are inserted above and below the flat cable arrangement in the insertion opening 103 , as can be seen in fig1 . the sealing elements 107 ″ and 108 ″ are preferably so sized that in this assembled state the outer overall dimension of both sealing elements 107 ″ and 108 ″ combined essentially corresponds to the inner cross - section of the insertion opening 103 and as a result remain in position as a matter of principle . in a next step , represented in fig1 , the opening cover 120 is inserted for pressurization purposes in the insertion opening 103 from behind , that is in the insertion direction e of the flat cable arrangement 200 , until the complementary catching or snapping devices 121 and 122 engage with each other and fix the opening cover 120 on the flat cable connector 100 , preferably by applying pressure , so that in this final position permanent pressure is exercised on the sealing gel by the opening cover 120 . in this embodiment too the insertion opening 103 can be reopened by releasing the interacting catching devices .
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the origin of pain are the biochemical mediators of inflammation and the inflammatory response . to treat pain , we must block these mediators and block the signals they send up through the nerve cells . we can now measure many of these inflammatory mediators in the blood and spinal fluid . however , our current technology does not allow us to image these mediators . hopefully sometime in the future we will be able to do so . inflammation occurs when there is infection or tissue injury . tissue injury may arise from a physical , chemical or biological trauma or irritation . degeneration of tissue subsequent to aging or previous injury can also lead to inflammation . injured tissues can be muscle , ligament , disks , joints or nerves . a variety of mediators are generated by tissue injury and inflammation . these include substances produced by damaged tissue , substances of vascular origin as well as substances released by nerve fibers themselves , sympathetic fibers and various immune cells 24 . there are three phases of an inflammatory response : initiation , maintenance and termination . upon tissue injury or painful stimulation , specialized blood cells in the area such as basophils , mast cells and platelets release inflammatory mediators serotonin , histamine and nitric oxide . subsequent to the binding of serotonin to its receptor , there is inflammation of the adjacent nerves and the nerve endings release short - lived inflammatory peptide proteins such as substance p , calcitonin gene - related peptide ( cgrp ). in addition , clotting factors in the blood produce and activate potent inflammatory mediator peptide proteins called neurokinin a , bradykinin , kallidin and t - kinin . all of these proteins increase blood flow to the area of injury , stimulate arachidonic acid metabolism to generate inflammatory mediators prostaglandins and attract specialized immune cells to the area . the first immune cells to the area are tissue macrophages , which provide the front line defense against bacterial infection . macrophages release powerful enzymes to digest any bacteria that are present and produce potent inflammatory chemical mediators ( called cytokines ) to attract and activate other cells of the immune system . shortly thereafter the area of bacterial invasion or tissue injury is invaded by the other immune cells , which include white blood cells such as t helper cells , lymphocytes , neutrophils , eosinophils , and other cells such as fibroblasts and endothelial cells . these immune cells respond to the chemical mediators , release destructive enzymes to kill any invading organism and release more chemical mediators to attract more immune cells . a consequence of this immune response is tissue damage , pain and spasm . in a sense the initial immune reaction ignites a cascade of immune reactions and generates an inflammatory soup of chemical mediators . these chemical mediators produced by the immune cells include prostaglandin , nitric oxide , tumor necrosis factor alpha , interleukin 1 - alpha , interleukin 1 - beta , interleukin - 4 , interleukin - 6 and interleukin - 8 , histamine , serotonin , in the area of injury and subsequently in the spinal cord , enzymes such as cyclooxygenase increase the production of these inflammatory mediators . these chemical mediators attract tissue macrophages and white blood cells to localize in an area to engulf ( phagocytize ) and destroy foreign substances . the chemical mediators released during the inflammatory response give rise to the typical findings associated with inflammation . the primary physical effect of the inflammatory response is for blood circulation to increase around the affected area . blood vessels around the site of inflammation dilate , allowing increased blood flow to the area . gaps appear in the cell walls surrounding the area , allowing the larger cells of the blood , i . e . the immune cells , to pass through . as a result of the increased blood flow , the immune presence is increased . all of the different types of cells that constitute the immune system congregate at the site of inflammation , along with a large supply of chemical mediators , which fuel the immune response . there is an increase in local or body heat . the main symptoms of the inflammatory response are as follows . 1 . the tissues in the area are red and warm , as a result of the large amount of blood reaching the site . 2 . the tissues in the area are swollen , again due to the increased amount of blood and proteins that are present . 3 . the tissues in the area are painful , due to the presence of the inflammatory mediators and due to the expansion of tissues , causing mechanical pressure on nerve cells . the inflammatory mediators activate local pain receptors and nerve terminals and produce hypersensitivity in the area of injury . activity of the mediators results in excitation of pain receptors in the skin , ligaments , muscle , nerves and joints . excitation of these pain receptors stimulate the specialized nerves e . g . c fibers and a - delta fibers that carry pain impulses to the spinal cord and brain . subsequent to tissue injury , the expression of sodium channels in nerve fibers is altered significantly thus leading to abnormal excitability in the sensory neurons . nerve impulses arriving in the spinal cord stimulate the release of inflammatory protein substance p . the presence of substance p and other inflammatory proteins such as calcitonin gene - related peptide ( cgrp ) neurokinin a and vasoactive intestinal peptide removes magnesium induced inhibition and enables excitatory inflammatory proteins such as glutamate and aspartate to activate specialized spinal cord nmda receptors . this results in magnification of all nerve traffic and pain stimuli that arrive in the spinal cord from the periphery . activation of motor nerves that travel from the spinal cord to the muscles results in excessive muscle tension . more inflammatory mediators are released which then excite additional pain receptors in muscles , tendons and joints generating more nerve traffic and increased muscle spasm . persistent abnormal spinal reflex transmission due to local injury or even inappropriate postural habits may then result in a vicious circle between muscle hypertension and pain 25 . separately , constant c - fiber nerve stimulation to transmission pathways in the spinal cord resulting in even more release of inflammatory mediators but this time within the spinal cord . inflammation causes increased production of the enzyme cyclooxygenase - 2 ( cox - 2 ), leading to the release of chemical mediators both in the area of injury and in the spinal cord . widespread induction of cox - 2 expression in spinal cord neurons and in other regions of the central nervous system elevates inflammatory mediator prostaglandin e 2 ( pge 2 ) levels in the cerebrospinal fluid . the major inducer of central cox - 2 upregulation is inflammatory mediator interleukin - 1 β in the cns 26 . basal levels of the enzyme phospholipase a 2 activity in the cns do not change with peripheral inflammation . abnormal development of sensory - sympathetic connections follow nerve injury , and contribute to the hyperalgesia ( abnormally severe pain ) and allodynia ( pain due to normally innocuous stimuli ). these abnormal connections between sympathetic and sensory neurons arise in part due to sprouting of sympathetic axons . studies have shown that sympathetic axons invade spinal cord dorsal root ganglia ( drg ) following nerve injury , and activity in the resulting pericellular axonal ‘ baskets ’ may underlie painful sympathetic - sensory coupling 27 . sympathetic sprouting into the drg may be stimulated by neurotrophins such as nerve growth factor ( ngf ), brain derived neurotrophic factor ( bdnf ), neurotrophin - 3 ( nt - 3 ) and neurotrophin 4 / 5 ( nt - 4 / 5 ). the central nervous system response to pain can keep increasing even though the painful stimulus from the injured tissue remains steady . this “ wind - up ” phenomenon in deep dorsal neurons can dramatically increase the injured person &# 39 ; s sensitivity to the pain . local tissue inflammation can also result in pain hypersensitivity in neighboring uninjured tissue ( secondary hyperalgesia ) by spread and diffusion of the excess inflammatory mediators that have been produced as well as by an increase in nerve excitability in the spinal cord ( central sensitization ). this can result in a syndrome comprising diffuse muscle pain and spasm , joint pain , fever , lethargy and anorexia . the inflammatory mediators interact in a complex way to induce , enhance and propagate persistent pain . there are also natural anti - inflammatory mediators produced by the body to cool down inflammation and the inflammatory response . interleukin - 1 beta is a potent pain - generating mediator . two pain producing pathways have been identified : inflammatory stimuli or injury to soft tissue induces the production of mediator bradykinin , which stimulates the release of mediator tumor necrosis factor alpha . the tnf - alpha induces production of ( i ) interleukin - 6 and interleukin - 1 - beta which stimulate the production of cyclooxygenase enzyme products , and ( ii ) inflammatory mediator interleukin - 8 , which stimulates production of sympathomimetics ( sympathetic hyperalgesia ) 28 . effects of interleukin - 1 beta include : interleukin - 1 beta stimulates inflammatory mediators prostaglandin e 2 ( pge 2 ), cyclooxygenase - 2 ( cox - 2 ) and matrix metalloproteases ( mmps ) production 29 , 30 interleukin - 1 beta is a significant catalyst in cartilage damage . it induces the loss of proteoglycans , prevents the formation of the cartilage matrix 31 and prevents the proper maintenance of cartilage . interleukin - 1 beta is a significant catalyst in bone resorption it stimulates osteoclasts cells involved in the resorption and removal of bone 323334 this is another potent pain - generating inflammatory mediator . a significant amount of interleukin - 6 is produced in the rat spinal cord following peripheral nerve injury that results in pain behaviors suggestive of neuropathic pain . these spinal il - 6 levels correlated directly with the mechanical allodynia intensity following nerve injury 35 . this is a pain - generating inflammatory mediator . in one study of patients with post herpetic neuralgia , the patients who received methylprednisolone , had interleukin - 8 concentrations decrease by 50 percent , and this decrease correlated with the duration of neuralgia and with the extent of global pain relief 36 ( p & lt ; 0 . 001 for both comparisons ). this is one of the natural anti - inflammatory cytokines , which also include interleuken - 1 receptor antagonist ( il - 1ra ), interleukin - 4 , interleukin - 13 and transforming growth factor - betal ( tgf - betal ). interleukin - 10 ( il - 10 ) is made by immune cells called macrophages during the shut - off stage of the immune response . interleukin - 10 is a potent anti - inflammatory agent , which acts partly by decreasing the production of inflammatory cytokines interleukin - 1 beta ( interleukin - 1 beta ), tumor necrosis factor - alpha ( tnf - alpha ) and inducible nitric oxide synthetase ( inos ), by injured nerves and activated white blood cells , thus decreasing the amount of spinal cord and peripheral nerve damage 3738 . in rats with spinal cord injury ( sci ), a single injection of il - 10 within half an hour resulted in 49 % less spinal cord tissue loss than in untreated rats . the researchers observed nerve fibers traveling straight through the spared tissue regions , across the zone of injury . they also reported a decrease in the inflammatory mediator tnf - alpha , which rises significantly after sci . prostaglandins are inflammatory mediators that are released during allergic and inflammatory processes . phospholipase a2 enzyme , which is present in cell membranes , is stimulated or activated by tissue injury or microbial products . activation of phospholipase a2 causes the release of arachidonic acid from the cell membrane phospholipid . from here there are two reaction pathways that are catalyzed by the enzymes cyclooxygenase ( cox ) and lipoxygenase ( lox ). these two enzyme pathways compete with one another . the cyclooxygenase enzyme pathway results in the formation of inflammatory mediator prostaglandins and thromboxane . the lipoxygenase enzyme pathway results in the formation of inflammatory mediator leukotriene . because they are lipid soluble these mediators can easily pass out through cell membranes . in the cyclooxygenase pathway , the prostaglandins d , e and f plus thromboxane and prostacyclin are made . thromboxanes are made in platelets and cause constriction of vascular smooth muscle and platelet aggregation . prostacyclins , produced by blood vessel walls , are antagonistic to thromboxanes as they inhibit platelet aggregation . prostaglandins have diverse actions dependent on cell type but are known to generally cause smooth muscle contraction . they are very potent but are inactivated rapidly in the systemic circulation . leukotrienes are made in leukocytes and macrophages via the lipoxygenase pathway . they are potent constrictors of the bronchial airways . they are also important in inflammation and hypersensitivity reactions as they increase vascular permeability and attract leukocytes . tumor necrosis factor alpha — this inflammatory mediator is released by macrophages as well as nerve cells . very importantly , tnf - alpha is released from injured or herniated disks . during an inflammatory response , nerve cells communicate with each other by releasing neuro - transmitter glutamate . this process follows activation of a nerve cell receptor called cxcr4 by the inflammatory mediator stromal cell - derived factor 1 ( sdf - 1 ). an extraordinary feature of the nerve cell communication is the rapid release of inflammatory mediator tumor necrosis factor - alpha ( tnf alpha ). subsequent to release of tnf - alpha , there is an increase in the formation of inflammatory mediator prostaglandin . excessive prostaglandin release results in an increased production of neurotransmitter glutamate and an increase in nerve cell communication resulting in a vicious cycle of inflammation there is excitation of pain receptors and stimulation of the specialized nerves e . g . c fibers and a - delta fibers that carry pain impulses to the spinal cord and brain . studies have established that herniated disk tissue ( nucleus pulposus ) produces a profound inflammatory reaction with release of inflammatory chemical mediators . disk tissue applied to nerves may induce a characteristic nerve sheath injury 394041 increased blood vessel permeability , and blood coagulation . the primary inflammatory mediator implicated in this nerve injury is tumor necrosis factor - alpha but other mediators including interleukin 1 - beta may also participate in the inflammatory reaction . recent studies have also shown that that local application of nucleus pulposus may induce pain - related behavior in rats , particularly hypersensitivity to heat and other features of a neuropathic pain syndrome . nitric oxide — this inflammatory mediator is released by macrophages . other mediators of inflammation such as reactive oxygen products and cytokines , considerably contribute to inflammation and inflammatory pain by causing an increased local production of cyclooxygenase enzyme . the cyclooxygenase enzyme pathway results in the formation of inflammatory mediator prostaglandins and thromboxane . concurrently to the increased production of the cyclooxygenase - 2 ( cox - 2 ) gene , there is increased production of the gene for the enzyme inducible nitric oxide synthetase ( inos ), leading to increased levels of nitric oxide ( no ) in inflamed tissues . in these tissues , no has been shown to contribute to swelling , hyperalgesia ( heightened reaction to pain ) and pain . no localized in high amounts in inflamed tissues has been shown to induce pain locally and enhances central as well as peripheral stimuli . inflammatory no is thought to be synthesized by the inducible isoform of nitric oxide synthetase ( inos ). substance p ( sp )— an important early event in the induction of neuropathic pain states is the release of substance p from injured nerves which then increases local tumor necrosis factor alpha ( tnf - alpha ) production . substance p and tnf - alpha then attract and activate immune monocytes and macrophages , and can activate macrophages directly . substance p effects are selective and substance p does not stimulate production of interleukin - 1 , interleukin - 3 , or interleukin - 6 . substance p and the associated increased production of tnf - alpha has been shown to be critically involved in the pathogenesis of neuropathic pain states . tnf protein and message are then further increased by activated immune macrophages recruited to the injury site several days after the primary injury . tnf - alpha can evoke spontaneous electrical activity in sensory c and a - delta nerve fibers that results in low - grade pain signal input contributing to central sensitization . inhibition of macrophage recruitment to the nerve injury site , or pharmacologic interference with tnf - alpha production has been shown to reduce both the neuropathologic and behavioral manifestations of neuropathic pain states 42 gelatinase b or matrix metallo - proteinase 9 ( mmp - 9 )— this enzyme is one of a group of metalloproteinases ( which includes collagenase and stromelysin ) that are involved in connective tissue breakdown . normal cells produce mmp - 9 in an inactive , or latent form . the enzyme is activated by inflammatory mediators such as tnf - alpha and interleukin - 1 that are released by cells of the immune system ( mainly neutrophils but also macrophages and lymphocytes ) and transformed cells 4344 . mmp - 9 helps these cells migrate through the blood vessels to inflammatory sites or to metastatic sites . activated , mmp - 9 can also degrade collagen in the extra cellular matrix of articular bone and cartilage and is associated with joint inflammation and bony erosions 45 . consequently , mmp - 9 plays a major role in acute and chronic inflammation , in cardiovascular and skin pathologies as well as in cancer metastasis . mmp - 9 can also degrade a protein called beta amyloid . normal cells produce mmp - 9 in an inactive , or latent form , converting it to active enzyme when it is needed . but when normal brain cells producing mmp - 9 fail to activate the enzyme , insoluble amyloid - b could accumulate in brain tissue . previous research has shown that the undegraded form of amyloid - beta accumulates in the brain as senile “ plaques ” that signal the presence of alzheimer &# 39 ; s disease 46 . immune cells produce anti - inflammatory cytokine mediators that help to suppress the inflammatory response and suppress the production of pro - inflammatory cytokines . the natural anti - inflammatory cytokines are interleuken - 1 receptor antagonist ( il - 1ra ), interleukin - 10 , interleukin - 4 , interleukin - 13 and transforming growth factor - betal ( tgf - betal ). research has shown that administration of these anti - inflammatory cytokines prevents the development of painful nerve pain that is produced by a naturally occurring irritant protein called dynorphin a 47 under normal circumstances ,, the inflammatory response should only last for as long as the infection or the tissue injury exists . once the threat of infection has passed or the injury has healed , the area should return to normal existence . one of the ways that the inflammatory response ends is by a phenomenon known as “ apoptosis ”. most of the time , cells of the body die by being irreparably damaged or by being deprived of nutrients . this is known as necrotic death . however , cells can also be killed in another way , i . e . by “ committing suicide ”. on receipt of a certain chemical signal , most cells of the body can destroy themselves . this is known as apoptotic death . there are two main ways in which cells can commit apoptosis . 1 . by receiving an apoptosis signal . when a chemical signal is received that indicates that the cell should kill itself , it does so . 2 . by not receiving a “ stay - alive ” signal . certain cells , once they reach an activated state , are primed to kill themselves automatically within a certain period of time , i . e . to commit apoptosis , unless instructed otherwise . however , there may be other cells that supply them with a “ stay - alive ” signal , which delays the apoptosis of the cell . it is only when the primed cell stops receiving this “ stay - alive ” signal that it kills itself . the immune system employs method two above . the immune cells involved in the inflammatory response , once they become activated , are primed to commit apoptosis . helper t cells emit the stay - alive signal , and keep emitting the signal for as long as they recognize foreign antigens or a state of injury in the body , thus prolonging the inflammatory response . it is only when the infection or injury has been eradicated , and there is no more foreign antigen that the helper t cells stop emitting the stay - alive signal , thus allowing the cells involved in the inflammatory response to die off . if foreign antigen is not eradicated from the body or the injury has not healed , or the helper t cells do not recognize that fact , or if the immune cells receive the stay - alive signal from another source , then chronic inflammation may develop . the final pathway for the natural suppression of the inflammatory response is in the spinal cord where there is a complex network of inhibitory neurons (‘ gate control ’) that is driven by descending projections from brain stem sites . these inhibitory neurons act to dampen and counteract the spinal cord hyper excitability produced by tissue or nerve injury . thus , peripherally evoked pain impulses pass through a filtering process involving inhibitory transmitters gamma - aminobutyric acid ( gaba ), glycine and enkephalins . the activity of these substances in the spinal cord usually attenuates and limits the duration of pain . in the case of persistent pain , there is evidence of pathological reduction of the supraspinal inhibitory actions in combination with ectopic afferent input in damaged nerves 48 . arthritis means inflammation of the joints . people of all ages including children and young adults can develop arthritis . the symptoms are intermittent pain , swelling , redness and stiffness in the joints . there are many different types of arthritis , some of which are rheumatoid arthritis , osteoarthritis , infectious arthritis and spondylitis . in rheumatoid arthritis , and other autoimmune diseases like systemic lupus erythematosus ( sle ), the joints are destroyed by the immune system . in osteoarthritis , the biggest risk factor is a previous injury to the joint , ligament or cartilage . injuries that seem to heal perfectly well appear to set up a process of deterioration that can produce severe pain and disability decades later . the injury need not be sustained in one episode . long term or repeated trauma can have the same effect . tnf - alpha and interleukin 1 - beta play an important role in rheumatoid arthritis by mediating cytokines that cause inflammation and joint destruction . tnf - alpha , interleukin 1 - beta and substance p are elevated in the joint fluids in patients with rheumatoid arthritis 49 . these inflammatory mediators are also elevated in the joint fluid in patients with osteoarthritis albeit to a far less extent . along with mechanical factors , growth factors and cytokines such as tgf beta 1 , il - 1 alpha , il - 1 beta and tnf - alpha may be involved in the formation and growth of osteophytes , since these molecules can induce growth and differentiation of mesenchymal cells . the incidence and size of osteophytes may be decreased by inhibition of direct or indirect effects of these cytokines and growth factors on osteoid deposition in treated animals 5051 . inhibition of interleukin - 1 receptor also decreases the production of metalloproteinase enzymes collagenase - 1and stomelysin - 1 in the synovial membrane and cartilage . these enzymes are involved in connective tissue breakdown 52 . back and neck pain most commonly results from injury to the muscle , disk , nerve , ligament or facet joints with subsequent inflammation and spasm . degeneration of the disks or joints produces the same symptoms and occurs subsequent to aging , previous injury or excessive mechanical stresses that this region is subjected to because of its proximity to the sacrum in the lower back . herniated disk tissue ( nucleus pulposus ) produces a profound inflammatory reaction with release of inflammatory chemical mediators most especially tumor necrosis factor alpha . subsequent to release of tnf - alpha , there is an increase in the formation of inflammatory mediator prostaglandin and nitric oxide . it is now known that tumor necrosis factor alpha is released by herniated disk tissue ( nucleus pulposus ), and is primarily responsible for the nerve injury and behavioral manifestations of experimental sciatica associated with herniated lumbar discs 53 . this has been confirmed by numerous animal studies and research wherein application of disk tissue ( nucleus pulposus ) to a nerve results in nerve fiber injury , with reduction of nerve conduction velocity , intracapillary thrombus formation , and the intraneural edema formation 5455 . one study demonstrated that disk tissue ( nucleus pulposus ) increases inducible nitric oxide synthetase activity in spinal nerve roots and that nitric oxide synthetase inhibition reduces nucleus pulposus - induced swelling and prevents reduction of nerve - conduction velocity . according to the authors , the results suggest that nitric oxide is involved in the pathophysiological effects of disk tissue ( nucleus pulposus ) in disc herniation 56 . tumor necrosis factor alpha and other inflammatory mediators induce phospholipase a2 activation . high levels of phospholipase a2 previously have been demonstrated in a small number of patients undergoing lumbar disc surgery . phospholipase a2 is the enzyme responsible for the liberation of arachidonic acid from cell membranes at the site of inflammation and is considered to be the limiting agent in the production of inflammatory mediator prostaglandins and leukotrienes 57 . subsequent to the release of inflammatory mediators , activation of motor nerves that travel from the spinal cord to the muscles results in excessive muscle tension , spasm and pain . the vast majority of herniated disk pain is inflammatory in origin , can be treated medically and does not require surgery . surgery is only indicated when there is compression of the nerve roots producing significant muscle weakness and or urinary or bowel incontinence . fibromyalgia is a chronic , painful musculoskeletal disorder characterized by widespread pain , pressure hyperalgesia , morning stiffness , sleep disturbances including restless leg syndrome , mood disturbances , and fatigue . other syndromes commonly associated with fibromyalgia include irritable bowel syndrome , interstitial cystitis , migraine headaches , temporomandibular joint dysfunction , dysequilibrium including nerve mediated hypotension , sicca syndrome , and growth hormone deficiency . fibromyalgia is accompanied by activation of the inflammatory response system , without immune activation 58 . in fact , there is some evidence that fibromyalgia is accompanied by some signs of immunosuppression 59 . several studies have shown that there are increased levels of the inflammatory transmitter substance p ( sp ) and calcitonin gene related peptide ( cgrp ) in the spinal fluid of patients with fibromyalgia syndrome ( fms ) 606162 . the levels of platelet serotonin are also abnormal 63 . furthermore , in patients with fibromyalgia , the level of pain intensity is related to the spinal fluid level of arginine , which is a precursor to the inflammatory mediator nitric oxide ( no ) 64 . another study found increases over time in blood levels of cytokines interleukin - 6 , interleukin - 8 and interleukin - 1r antibody ( il - 1ra ) whose release is stimulated by substance p . the study authors concluded that because interleukin - 8 promotes sympathetic pain and interleukin - 6 induces hypersensitivity to pain , fatigue and depression , both cytokines play a role in producing fm symptoms 65 . interstitial cystitis is a severe debilitating bladder disease characterized by unrelenting pelvic pain and urinary frequency . this sterile painful bladder disorder is associated with a defective glycosaminoglycan bladder mucosal layer and an increased number of activated mast cells . mast cells are ubiquitous cells derived from the bone marrow and are responsible for allergic reactions as they release numerous vasodilatory , nociceptive and pro - inflammatory mediators in response to immunoglobulin e ( ige ) and specific antigen . mast cell secretion is also triggered by a number of peptides , such as bradykinin and substance p , and may also be involved in the development of inflammatory responses 66 . sp - containing nerve fibres are increased in the submucosa of the urinary bladder of interstitial cystitis ( ic ) patients and are frequently seen in juxtaposition to mast cells 6768 . there is enhanced sympathetic innervation of the bladder in the submucosa and detrusor muscle . in interstitial cystitis the number of neurons positive for inflammatory mediator vasoactive intestinal polypeptide and neuropeptide y is higher 69 . substance p ( sp ) and bradykinin ( bk ) influence the excitatory motor innervation of the urinary bladder . these peptides potentiate the responses to the purinergic component of the neurogenic stimulation ( that part of the contractile response that remains after treatment with atropine ) and potentiate the responses to exogenously applied adenosine triphosphate ( atp ) 70 . significant elevations in interleuken - 2 , interleukin - 6 , and interleukin - 8 have also been found in the urine of subjects with active interstitial cystitis compared with subjects with interstitial cystitis in remission and control subjects 71 migraine headache is caused by activation of trigeminal sensory fibers by known and unknown migraine triggers . there is subsequent release of inflammatory mediators from the trigeminal nerve . this leads to distention of the large meningeal blood vessels in the skull and brain and the development of a central sensitization within the trigeminal nucleus caudalis ( tnc ). genetic abnormalities may be responsible for altering the response threshold to migraine specific trigger factors in the brain of a migraineur compared to a normal individual 72 . the painful neurogenic vasodilation of meningeal blood vessels is a key component of the inflammatory process during migraine headache . the cerebral circulation is supplied with two vasodilator systems : the parasympathetic system storing vasoactive intestinal peptide , peptide histidine isoleucine , acetylcholine and in a subpopulation of nerves neuropeptide y , and the sensory system , mainly originating in the trigeminal ganglion , storing inflammatory mediator substance p , neurokinin a and calcitonin gene - related peptide ( cgrp ) 73 . a clear association between migraine and the release of inflammatory mediator calcitonin gene - related peptide ( cgrp ) and substance p ( sp ) has been demonstrated . jugular plasma levels of the potent vasodilator , calcitonin gene - related peptide ( cgrp ) have been shown to be elevated in migraine headache . cgrp - mediated neurogenic dural vasodilation is blocked by anti - migraine drug dihydroergotamine , triptans , and opioids 74 . in cluster headache and in chronic paroxysmal hemicrania , there is additional release of inflammatory mediator vasoactive intestinal peptide ( vip ) in association with facial symptoms ( nasal congestion , runny nose ) 75 . immunocytochemical studies have revealed that cerebral blood vessels are invested with nerve fibers containing inflammatory mediator neuropeptide y ( npy ), vasoactive intestinal peptide ( vip ), peptide histidine isoleucine ( phi ), substance p ( sp ), neurokinin a ( nka ), and calcitonin gene - related peptide ( cgrp ). in addition , there are studies reporting the occurrence of putative neurotransmitters such as cholecystokinin , dynorphin b , galanin , gastrin releasing peptide , vasopressin , neurotensin , and somatostatin . the nerves occur as a longitudinally oriented network around large cerebral arteries . there is often a richer supply of nerve fibers around arteries than veins . the origin of these nerve fibers has been studied by retrograde tracing and denervation experiments . these techniques , in combination with immunocytochemistry , have revealed a rather extensive innervation pattern . several ganglia , such as the superior cervical ganglion , the sphenopalatine ganglion , the otic ganglion , and small local ganglia at the base of the skull , contribute to the innervation . sensory fibers seem to derive from the trigeminal ganglion , the jugular - nodose ganglionic complex , and from dorsal root ganglia at the cervical spine level c2 . the noradrenergic and most of the npy fibers derive from the superior cervical ganglion . a minor population of the npy - containing fibers contains vasoactive intestinal peptide ( vip ), instead of na and emanates from the sphenopalatine ganglion . the cholinergic and the vasoactive intestinal peptide ( vip )- containing fibers derive from the sphenopalatine ganglion , the otic ganglion , and from small local ganglia at the base of the skull . most of the substance p ( sp -), neurokinin a ( nka ), and calcitonin gene - related peptide ( cgrp )- containing fibers derive from the trigeminal ganglion . minor contributions may emanate from the jugular - nodose ganglionic complex and from the spinal dorsal root ganglia . neuropeptide y ( npy ), is a potent vasoconstrictor in vitro and in situ . vasoactive intestinal peptide ( vip ), peptide histidine isoleucine ( phi ), substance p ( sp ), neurokinin a ( nka ), and calcitonin gene - related peptide ( cgrp ) act via different mechanisms to induce cerebrovascular dilatation 76 . meningeal blood vessels are involved in the generation of migraine pain and other headaches . classical experiments have shown that blood vessels of the cranial dura mater are the most pain - sensitive intracranial structures . dural blood vessels are supplied by trigeminal nerve fibers , and dilate in response to activation of the trigeminal nerves and release of neuropeptide cytokines such as substance p ( sp ) and calcitonin gene - related peptide ( cgrp ) 77 . cgrp can be released experimentally from dural nerve fibers , and there is evidence that this occurs also during migraine attacks . stimulation of dural nerve fibers causes vasodilatation and an increase in dural arterial flow , which depends on the release of cgrp but not sp . sp , on the other hand , is known to mediate plasma leakage ( extravasation ) from small veins in the dura mater . the dural arterial flow depends also on the formation of cell wall nitric oxide . the introduction of serotonin ( 5 - ht 1 ) receptor agonists such as sumatriptan changed the treatment strategies for migraine . sumatriptan and other triptans may inhibit the release of inflammatory mediators from the trigeminal nerve . sumatriptan has been shown to block the release of vasoactive cytokines from trigeminal nerves that surround the blood vessels in the dura mater during migraine . sumatriptan blocks nerve fiber induced plasma extravasation but has only minor effects on nerve fiber mediated vasodilatation and dural arterial flow . foods like cheese , beer , and wine can also induce migraine in some people because they contain the mediator histamine and / or mediator - like compounds that cause blood vessels to expand . women tend to react to histamine - containing foods more frequently than men do , on account of a deficiency in an enzyme ( diamine oxidase ) that breaks histamine down . taking supplemental b 6 has been shown to be helpful in migraine , as it can increase diamine oxidase activity . nerve ( neuropathic ) pain syndromes ( e . g . carpal tunnel syndrome , trigeminal neuralgia , post herpetic neuralgia , phantom limb pain ) nociceptive pain is mediated by receptors on a - delta and c nerve fibers , which are located in skin , bone , connective tissue , muscle and viscera . these receptors serve a biologically useful role at localizing noxious chemical , thermal and mechanical stimuli . nociceptive pain can be somatic or visceral in nature . somatic pain tends to be well - localized , constant pain that is described as sharp , aching , throbbing , or gnawing . visceral pain , on the other hand , tends to be vague in distribution , spasmodic in nature and is usually described as deep , aching , squeezing and colicky in nature . examples of nociceptive pain include : post - operative pain , pain associated with trauma , and the chronic pain of arthritis . neuropathic pain , in contrast to nociceptive pain , is described as “ burning ”, “ electric ”, “ tingling ”, and “ shooting ” in nature . it can be continuous or paroxysmal in presentation . whereas nociceptive pain is caused by the stimulation of peripheral a - delta and c - polymodal pain receptors , by inflammatory mediators , ( e . g . histamine bradykinin , substance p , etc .) neuropathic pain is produced by injury or damage to peripheral nerves or the central nervous system the hallmarks of neuropathic pain are chronic allodynia and hyperalgesia . allodynia is defined as pain resulting from a stimulus that ordinarily does not elicit a painful response ( e . g . light touch ). hyperalgesia is defined as an increased sensitivity to normally painful stimuli . examples of neuropathic pain include carpal tunnel syndrome , trigeminal neuralgia , post herpetic neuralgia , phantom limb pain , complex regional pain syndromes and the various peripheral neuropathies . subsequent to nerve injury , there is increase in nerve traffic . expression of sodium channels is altered significantly in response to injury thus leading to abnormal excitability in the sensory neurons . nerve impulses arriving in the spinal cord stimulate the release of inflammatory protein substance p . the presence of substance p and other inflammatory proteins such as calcitonin gene - related peptide ( cgrp ) neurokinin a , vasoactive intestinal peptide removes magnesium induced inhibition and enables excitatory inflammatory proteins such as glutamate and aspartate to activate specialized spinal cord nmda receptors . this results in magnification of all nerve traffic and pain stimuli that arrive in the spinal cord from the periphery . in one study , monocytes / macrophages ( ed - 1 ), natural killer cells , t lymphocytes , and the pro - inflammatory cytokines tumor necrosis factor - alpha ( tnf - alpha ) and interleukin - 6 ( il - 6 ), were significantly produced in nerve - injured rats . interestingly , ed - 1 -, tnf - alpha - and interleukin - 6 - positive cells increased more markedly in allodynic rats than in non - allodynic ones . the magnitude of the inflammatory response was not related to the extent of damage to the nerve fibers because rats with complete transection of the nerves displayed much lower production of inflammatory cytokines than rats with partial transection of the nerve 78 . this is a finding commonly observed in patients where a minor injury results in severe pain that is out of proportion to the injury . getting back to the study , the authors determined that the considerable increase in monocytes / macrophages induced by a nerve injury results in a very high release of interleukin - 6 and tnf - alpha . this may relate to the generation of touch allodynia / hyperalgesia , since there was a clear correlation between the number of ed - 1 and interleukin - 6 - positive cells and the degree of allodynia . abnormal development of sensory - sympathetic connections follow nerve injury , and contribute to the hyperalgesia ( abnormally severe pain ) and allodynia ( pain due to normally innocuous stimuli ). these abnormal connections between sympathetic and sensory neurons arise in part due to sprouting of sympathetic axons . studies have shown that sympathetic axons invade spinal cord dorsal root ganglia ( drg ) following nerve injury , and activity in the resulting pericellular axonal ‘ baskets ’ may underlie painful sympathetic - sensory coupling 79 . sympathetic sprouting into the drg may be stimulated by neurotrophins such as nerve growth factor ( ngf ), brain derived neurotrophic factor ( bdnf ), neurotrophin - 3 ( nt - 3 ) and neurotrophin 4 / 5 ( nt - 4 / 5 ). in another study , animals exhibiting heat hyperalgesia as a sign of neuropathic pain seven days after loose ligation of the sciatic nerve exhibited a significant increase in the concentration of brain derived neurotrophic factor ( bdnf ) in their lumbar spinal dorsal horn . 80 administration of nerve growth factor to rodents has resulted in the rapid onset of hyperalgesia . in clinical trials with nerve growth factor for the treatment of alzheimer disease and peripheral neuropathy , induction of pain has been the major adverse event 81 . in one study , the use of trka - igg , an inhibitor of nerve growth factor ( ngf ) reduced neuroma formation and neuropathic pain in rats with peripheral nerve injury 82 in another study , the systemic administration of anti - nerve growth factor ( ngf ) antibodies significantly reduced the severity of autotomy ( self mutilating behavior induced by nerve damage ) and prevented the spread of collateral sprouting from the saphenous nerve into the sciatic innervation territory 83 . activity in sympathetic fibers is associated with excessive sweating , temperature instability of the extremities and can induce further activity in sensitized pain receptors and , therefore , enhance pain and allodynia ( sympathetically maintained pain ). this pathologic interaction acts via noradrenaline released from sympathetic terminals and newly expressed receptors on the afferent neuron membrane 84 . activation of motor nerves that travel from the spinal cord to the muscles results in excessive muscle tension . more inflammatory mediators are released which then excite additional pain receptors in muscles , tendons and joints generating more nerve traffic and increased muscle spasm . persistent abnormal spinal reflex transmission due to local injury or even inappropriate postural habits may then result in a vicious circle between muscle hypertension and pain 85 . separately , constant c - fiber nerve stimulation to transmission pathways in the spinal cord results in even more release of inflammatory mediators but this time within the spinal cord . the transcription factor , nuclear factor - kappa b ( nf - kappab ), plays a pivotal role in regulating the production of inflammatory cytokines 86 . inflammation causes increased production of the enzyme cyclooxygenase - 2 ( cox - 2 ), leading to the release of chemical mediators both in the area of injury and in the spinal cord . widespread induction of cox - 2 expression in spinal cord neurons and in other regions of the central nervous system elevates inflammatory mediator prostaglandin e 2 ( pge 2 ) levels in the cerebrospinal fluid . the major inducer of central cox - 2 upregulation is inflammatory mediator interleukin - 1 β din the cns 87 . basal levels of the enzyme phospholipase a 2 activity in the cns do not change with peripheral inflammation . the central nervous system response to pain can keep increasing even though the painful stimulus from the injured tissue remains steady . this “ wind - up ” phenomenon in deep dorsal neurons can dramatically increase the injured person &# 39 ; s sensitivity to the pain . the neurotrophins are a family of growth promoting proteins that are essential for the generation and survival of nerve cells during development , neurotrophins promote growth of small sensory neurons and stimulate the regeneration of damaged nerve fibers they consist of four members , nerve growth factor ( ngf ), brain derived neurotrophic factor ( bdnf ), neurotrophin - 3 ( nt - 3 ) and neurotrophin 4 / 5 ( nt - 4 / 5 ). nerve growth factor and brain - derived neurotrophic factor modulate the activity of a sodium channel ( nan ) that is preferentially expressed in pain signaling neurons that innervate the body ( spinal cord dorsal root ganglion neurons ) and face ( trigeminal neurons ). transection of a nerve fiber ( axotomy ) results in an increased production of inflammatory cytokines and induces marked changes in the expression of sodium channels within the sensory neurons 88 . following axotomy the density of slow ( tetrodotoxin - resistant ) sodium currents decrease and a rapidly repriming sodium current appears . the altered expression of sodium channels leads to abnormal excitability in the sensory neurons 89 . studies have shown that these changes in sodium channel expression following axotomy may be attributed at least in part to the loss of retrogradely transported nerve growth factor 90 . in addition to effects on sodium channels , there is a large reduction in potassium current subtypes following nerve transection and neuroma formation . studies have shown that direct application of nerve growth factor to the injured nerve can prevent these changes 91 . reflex sympathetic dystrophy ( rsd ) syndrome also called chronic regional pain syndrome ( crps ) has been recognized clinically for many years . it is most often initiated by trauma to a nerve , neural plexus , or soft tissue . diagnostic criteria are the presence of regional pain and other sensory changes following a painful injury . the pain is associated with changes in skin color , skin temperature , abnormal sweating , tissue swelling . with time , tissue atrophy may occur as well as involuntary movements , muscle spasms , or pseudoparalysis 92 . like other organs with a blood supply , the bones also react to the disturbances in permeability caused by various inflammatory mediators . there is fluid accumulation in the bones and loss of bone density ( osteoporosis ) 93 . in addition , the inflammatory mediators accelerate the rate at which bone is broken down . the bone loss is further aggravated by decreased use of the affected body part due to pain . complex regional pain syndrome , type i ( reflex sympathetic dystrophy ; crps - i / rsd ) can spread from the initial site of presentation . in one study of 27 crps - i / rsd patients who experienced a significant spread of pain , three patterns of spread were identified . ‘ contiguous spread ( cs )’ was noted in all 27 cases and was characterized by a gradual and significant enlargement of the area affected initially . ‘ independent spread ( is )’ was noted in 19 patients ( 70 %) and was characterized by the appearance of crps - i in a location that was distant and non - contiguous with the initial site ( e . g . crps - i / rsd appearing first in a foot , then in a hand ). ‘ mirror - image spread ( ms )’ was noted in four patients ( 15 %) and was characterized by the appearance of symptoms on the opposite side in an area that closely matched in size and location the site of initial presentation . only five patients ( 19 %) suffered from cs alone ; 70 % also had is , 11 % also had ms , and one patient had all three kinds of spread 94 . in 1942 paul sudeck suggested that the signs and symptoms of rsd / crps including sympathetic hyperactivity might be provoked by an exaggerated inflammatory response to injury or operation of an extremity . his theory found no followers , as most doctors incorrectly believe that rsd / crps is solely initiated by a hyperactive sympathetic system . recent research and studies including various clinical and experimental investigations now provide support to the theory of paul sudeck 95 . as we now understand , soft tissue or nerve injury causes excitation of sensory nerve fibers . reverse ( antidromic ) firing of these sensory nerves causes release of the inflammatory neuropeptides at the peripheral endings of these fibers . these neuropeptides may induce vasodilation , increase vascular permeability , attract other immune cells such as t helper cells and excite surrounding sensory nerve fibers — a phenomenon referred to as neurogenic inflammation . at the level of the central nervous system , the increased input from peripheral pain receptors alters the central processing mechanisms . sympathetic dysfunction , which often has been purported to play a pivotal role in rsd / crps , has been suggested to consist of an increased rate of outgoing ( efferent ) sympathetic nerve impulses towards the involved extremity induced by increased firing of the sensory nerves . however , the results of several experimental studies suggest that sympathetic dysfunction also consists of super sensitivity to catecholamines induced by nerve injury ( autonomic denervation ) 96 . part of this occurs due to injured sensory nerves and immune cells developing receptors for the chemical transmitter norepinephrine and epinephrine ( catecholamines ), which are normally released by sympathetic nerves and also circulate in the blood . stimulation of these receptors by locally released or circulating catecholamines produces sympathetic effects such as sweating , excessive hair growth and narrowing of blood vessels 97 . in addition and under certain conditions , catecholamines may boost regional immune responses , through increased release of interleukin - 1 , tumor necrosis factor - alpha , and interleukin - 8 production . in several studies , patients with rsd / crps showed a markedly increased level of the inflammatory peptide bradykinin as well as calcitonin gene - related peptide 98 . the levels of bradykinin were four times as high as the controls . a few showed increased levels of the other inflammatory chemical mediators 99 . two pain producing pathways have been identified : inflammatory stimuli induce the production of bradykinin , which stimulates the release of tnf - alpha . the tnf - alpha induces production of ( i ) interleukin - 6 and interleukin - 1b , which stimulate the production of cyclooxygenase products , and ( ii ) interleuken - 8 , which stimulates production of sympathomimetics ( sympathetic hyperalgesia ) 100 . abnormal development of sensory - sympathetic connections follow nerve injury , and contribute to the hyperalgesia ( abnormally severe pain ) and allodynia ( pain due to normally innocuous stimuli ). these abnormal connections between sympathetic and sensory neurons arise in part due to sprouting of sympathetic axons . this can be induced by neurotrophins such as nerve growth factor ( ngf ), brain derived neurotrophic factor ( bdnf ), neurotrophin - 3 ( nt - 3 ) and neurotrophin 4 / 5 ( nt - 4 / 5 ). inflammation of the bursa is known as bursitis . a bursa is a small sac containing fluid that lies between bone and other moving structures such as muscles , skin or tendons . the bursa allows smooth gliding between these structures . a bursa allows a tendon or muscle to move smoothly over a bone by acting as an anti - friction device and shielding the structures from rubbing against bones . bursae are found in the knee , elbow , shoulder and wrist . if the tendons become thickened and bumpy from excessive use , the bursa is subjected to increased friction and may become inflamed . tendonitis is inflammation or irritation of a tendon . tendons are the thick fibrous cords that attach muscles to bone . they function to transmit the power generated by a muscle contraction to move a bone . since both tendons and bursae are located near joints , inflammation in these soft tissues will often be perceived by patients as joint pain and mistaken for arthritis . symptoms of bursitis and tendonitis are similar : pain and stiffness aggravated by movement . pain may be prominent at night . almost any tendon or bursa in the body can be affected , but those located around a joint are affected most often . the most common cause of tendonitis and bursitis is injury or overuse during work or play , particularly if the patient is poorly conditioned , has bad posture , or uses the affected limb in an awkward position . occasionally an infection within the bursa or tendon sheath will be responsible for the inflammation . tendonitis or bursitis may be associated with diseases such as rheumatoid arthritis , gout , psoriatic arthritis , thyroid disease and diabetes . in one study of thirty - nine patients with rotator cuff diseases , the levels of the cytokine interleukin - 1 beta was significantly correlated with the degree of pain . the combined results of immunohistochemistry indicated that both synovial lining and sublining cells produce il - 1beta , while synovial lining cells predominantly produce the anti - inflammatory intracellular interleukin - 1 receptor antagonist ( icil - 1ra ) and sublining cells secrete secreted interleukin - 1 receptor antagonist ( sil - 1ra ) 101 . in another study , the levels of interleukin - 1 beta were significantly higher in the shoulder joints in patients with anterior instability and chronic inflammation of the joint 102 . in another study , immunohistological staining demonstrated the expression of interleukin - 1 beta ( interleukin - 1 beta ), tumor necrosis factor alpha ( tnf - alpha ), transforming growth factor beta ( tgf - beta ), and basic fibroblast growth factor ( bfgf ) in subacromial bursa derived from the patients suffering from rotator cuff tear 103 . vulvar vestibulitis syndrome is a major subtype of vulvodynia . it is a constellation of symptoms and findings involving and limited to the vulvar vestibule that consists of : ( 1 ) severe pain on vestibular touch to attempted vaginal entry , ( 2 ) tenderness to pressure localized within the vulvar vestibule , and ( 3 ) physical findings confined to vulvar erythema of various degrees . the syndrome has been seen in association with subclinical human papillomavirus , chronic recurrent candidiasis , chronic recurrent bacterial vaginosis , chronic alteration of vaginal ph , and the use of chemical and destructive therapeutic agents 104 . in a study of vvs cases and asymptomatic controls , median tissue levels of inflammatory cytokines : il - 1 b and tnf - a , from selected regions of the vulva ,, vestibule , and vagina were 2 . 3 - fold and 1 . 8 - fold elevated , respectively , in women with vvs compared to pain - free women . analysis revealed a significant 2 . 2 - fold higher median level of tnf alpha at the vulvar site compared to the vestibule . cytokine elevations correlated poorly with inflammatory cell infiltrate and suggested cytokine production from another cell source . the study authors concluded that inflammatory cytokine elevation may contribute to the pathophysiology of mucocutaneous hyperalgesia 105
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attention is first directed to fig1 of the drawings illustrating a gaming machine in accordance with an example of the present invention generally designated 10 . the gaming machine comprises a floor mounted main cabinet 12 fitted with a base unit 16 in the form of a lower door , and a main door 18 on the front of the machine , both being pivotally secured by hinges ( not seen ) to the main cabinet 12 and are openable to provide access to the interior of the machine . a pair of video display monitors 26 and 28 are provided ( mounted on a separate pivotable door extending behind the main door 18 ) and a card slot 30 ( e . g . a credit card reader ). fitted on the side wall 14 there are a key activated door lock 34 and key activated switches for administration purposes 36 , as well as a vent grate 38 for exhaustion of hot air from the machine &# 39 ; s interior . fitted on the main door 18 comprises a coin / slot scepter 40 and a coin / slot tray 42 as well as a pair of speakers 44 . further mounted on the base unit 16 an operating panel generally designated 50 and comprises a plurality of push button 52 for use at user &# 39 ; s choice . there is further provided an elongated wrist panel 46 to allow an individual to support his wrist and rest thereupon . as can further be seen in more detail in the remaining fig2 to 4 , the base unit 16 is provided with a wrist support and hand grip collectively designated 50 positioned so as to interact with two main push buttons namely 52 and 54 . the wrist support and hand grip 50 comprise a wrist support in the form of a wrist support 60 extending at the edge of a depression 62 with a cavity 64 formed under the wrist support 60 to facilitate gripping thereof as illustrated in fig3 a to 3c ( in the so - called second position ). wrist support 60 may be made of hard material e . g . a molded plastic martial , metal , etc . or it may be cushioned and comprise at least a layer of soft material . a hand grip 70 extends in alignment with the wrist support 60 , said hand grip 70 being in the form of a bent bar having a first portion 72 extending substantially horizontally and substantially parallel to the video displays ( fig1 ), with a second bar portion 76 extending from the first bar portion 72 in the direction away from the wrist support 60 , suitable for serving as a sun rest . the hand grip 70 is used in accordance with the so - called first position ( as illustrated in fig4 a to 4c ). as can be seen in fig3 a to 3c , the second position is used in conjunction with push button 52 easily engageable by the individual &# 39 ; s thumb 59 whilst fingers grip the wrist support pad 60 . however , in the so - called first position ( fig4 a - 4c ), push button 54 is easily engageable by individual &# 39 ; s thumb whilst gripping on a first bar portion 72 with the individual having the choice of resting his wrist over the cushioned wrist support 60 . while at the first position , the individual may opt to position his arm such that his wrist rests over the wrist support 60 . with further reference to fig5 a to 5c there is illustrated a third operating position , wherein three fingers of the individual , namely the little finger , ring finger and middle finger grip the bar section 72 whilst the index finger 88 manipulates push button 54 and the thumb 59 manipulates push button 52 and the open palm portion rests over wrist support 60 . as can be seen in fig2 c , the wrist support 60 is detachably attachable to the base unit 16 , at user &# 39 ; s / operator &# 39 ; s choice . likewise , as illustrated in fig2 d , the hand grip 70 is detachably attachable as well . those skilled in the art to which this invention pertains will readily appreciate that numerous changes , variations , and modifications can be made without departing from the scope of the invention . mutatis mutandis .
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various embodiments of the present invention will now be described in detail with reference to the accompanying drawings . fig1 is a sectional view of electrophotographic photoreceptors , according to one embodiment of the present invention . in the electrophotographic photoreceptor shown in fig1 barrier layer 2 is formed on conductive substrate 1 , photoconductive layer 3 consisting of charge - retaining layer 5 and charge - generating layer 6 formed on barrier layer 2 , and surface layer 4 is formed on photoconductive layer 3 . charge retaining layer 5 and charge - generating layer 6 have a superlattice structure . fig2 to 4 are sectional views of electrophotographic photoreceptors , according to the other embodiments of the present invention . in the electrophotographic photoreceptor shown in fig2 a part of charge - generating layer 6 has a superlattice structure . in the electrophotographic photoreceptor shown in fig3 a part of charge - retaining layer 5 has a superlattice structure . and , in the electrophotographic photoreceptor shown in fig4 parts of charge - retaining layer 5 and charge - generating layer 6 have a superlattice structure . the details of the parts in the embodiment shown in fig1 and 2 are as follows . barrier layer 2 may be formed using μc - si , a - si : h , or a - bn : h ( nitrogen - or hydrogen - doped amorphous boron ). barrier layer 2 may be made of an insulating film . for example , at least one element selected from the group consisting of carbon ( c ), nitrogen ( n ), and oxygen ( o ) is contained in μc - si : h or a - si : h to form an insulating barrier layer having a high resistance . the thickness of barrier layer 2 is preferably 100 a to 10 μm . barrier layer 2 restricts a flow of a charge between conductive substrate 1 and photoconductive layer 3 ( or charge - generating layer 6 ) to improve a charge - retaining capacity on the surface of the photoconductive layer and to improve a charging capacity of the photoconductive layer . therefore , when a carlson photoreceptor is manufactured using a semiconductor layer as a barrier layer , barrier layer 2 must have a p or n conductivity type so as not to degrade the charge - retaining capacity of the surface . more specifically , in order to positively charge the surface of the photoreceptor , p - type barrier layer 2 is formed to prevent an injection of electrons into the photoconductive layer for neutralizing the surface charge . however , in order to negatively charge the surface , n - type barrier layer 2 is formed to prevent an injection of holes for neutralizing the surface charge into the photoconductive layer . carriers injected from barrier layer 2 serve as noise for carriers generated in photoconductive layers 3 and 6 upon the radiation of light . by preventing the carrier injections described above , the sensitivity of the photoconductive layers can be improved . in order to obtain p - type μc - si : h or p - type a - si : h , elements belonging to group iii of the periodic table , such as boron ( b ), aluminum ( al ), gallium ( ga ), indium ( in ), and thallium ( tl ) are preferably doped in c - si : h or a - si : h . in order to obtain n - type c - si : h or n - type a - si : h , elements belonging to group v of the periodic table , such as nitrogen ( n ), phosphorus ( p ), arsenic ( as ), antimony ( sb ), and bismuth ( bi ) are preferably doped in c - si : h or a - si : h . in the electrophotographic photoreceptor shown in fig1 charge - generating layer 6 generates carriers upon the reception of incident light . the carriers having one polarity are neutralized with the charge on the surface of the photoreceptor , and the carriers having the other polarity are moved through charge - retaining layer 5 up to conductive substrate 1 . in the embodiment shown in fig1 charge retaining layer 5 and charge - generating layer 6 each have a superlattice structure obtained by alternately stacking thin layers 11 and 12 , as shown in fig5 . at least one element selected from the group , consisting of carbon , oxygen , and nitrogen , is contained in thin layers 11 and 12 constituting charge - generating layer 6 and in thin layer 11 or 12 constituting charge - retaining layer 5 . the concentrations of impurities in the thin layers 11 and 12 constituting charge - generating layer 6 are different from each other . the thickness of thin layers 11 and 12 falls within the range of 30 to 500 å . fig6 is a graph showing an energy band of the superlattice structure . the direction of thickness is plotted along the ordinate , and the optical band gap is plotted along the abscissa . surface layer 4 is formed on charge - generating layer 6 . the refractive index of μc - si : h or a - si : h , constituting charge - generating layer 6 , is as relatively large as 3 to 3 . 4 , and reflection tends to occur on the surface of the layer . when such reflection occurs , the amount of light to be absorbed in the charge - generating layer is decreased , and optical loss typically occurs . for this reason , surface layer 4 is preferably formed to prevent light reflection . in addition , surface layer 4 prevents charge - generating layer 6 from being damaged . furthermore , the formation of the surface layer allows for the improvement of the charging capacity , and the surface can be satisfactorily charged . a material of the surface layer is an inorganic compound ( e . g ., a - sin : h , a - sio : h , or a - sic : h ) or an organic material ( e . g ., polyvinyl chloride or polyamide ). when the surface of the electrophotographic photoreceptor is negatively charged by corona discharge with a voltage of about 500 v , a potential barrier shown in fig7 is formed . when light ( hν ) is incident on the photoconductive layer , carriers , i . e ., electrons and holes , are generated in the superlattice structure of charge - generating layer 6 . the electrons in the conduction band are accelerated toward surface layer 4 by an electric field in the photoreceptor , while the holes are accelerated toward conductive substrate 1 . in this case , the number of carriers generated at an interface between the adjacent thin layers having different optical band gaps is larger than that generated in the bulk . for this reason , in this superlattice structure , high light sensitivity can be obtained . in the potential well layer , due to the quantum effect , the carrier lifetime is 5 to 10 times that of a single layer which is not a superlattice structure . in addition , in the superlattice structure , discontinuity of the band gaps forms periodic barrier layers . however , the carriers can easily pass through the bias layer by the tunnel effect , so that the effective mobility of the carriers is substantially the same as that in the bulk , thus achieving high - speed carrier movement . also in the potential well layer of charge - retaining layer 5 , due to the quantum effect , the carrier lifetime is 5 to 10 times that of a single layer which is not a superlattice structure . in addition , in the superlattice structure , discontinuity of the band gaps forms periodic barrier layers . however , the carriers can easily pass through the bias layer by the tunnel effect , so that the effective mobility of the carriers is substantially the same as that in the bulk , thus achieving high - speed carrier movement . as described above , according to the electrophotographic photoreceptor having the charge - generating layer and charge - retaining layer of the superlattice structure wherein thin layers having different optical band gaps are stacked , a good photoconductive property can be obtained , and therefore a clearer image can be obtained as compared with a conventional photoreceptor . fig8 shows an apparatus for manufacturing an electrophotographic photoreceptor according to the present invention , utilizing the glow discharge method . gas cylinders 41 , 42 , 43 , and 44 store source gases such as sih 4 , b 2 h 6 , h 2 , and ch 4 . gases in cylinders 41 , 42 , 43 , and 44 can be supplied to mixer 48 , through flow control valves 46 and pipes 47 respectively . each cylinder has pressure gauge 45 . the operator controls each valve 46 while monitoring corresponding pressure gauge 45 , thereby controlling the flow rate of each gas and their mixing ratio . the gas mixture is supplied from mixer 48 to reaction chamber 49 . rotating shaft 10 vertically extends from bottom 11 of reaction chamber 49 , and can be rotated about the vertical axis . disk - like support table 52 is fixed on the upper end of shaft 50 such that the surface of table 52 is perpendicular to shaft 50 . cylindrical electrode 53 is arranged inside chamber 49 such a that the axis of electrode 53 is aligned with the axis of shaft 50 . drum - like substrate 54 for a photoreceptor is placed on table 52 such that the axis of the former is aligned with the axis of shaft 50 . drum - like substrate heater 55 is arranged inside substrate 54 . rf power source 56 is connected between electrode 53 and substrate 54 , and supplies an rf current therebetween . rotating shaft 50 is driven by motor 58 . the internal pressure of reaction chamber 49 is monitored by pressure gauge 57 , and chamber 49 is connected to a proper evacuating means , such as a vacuum pump , through gate valve 59 . in order to manufacture a photoreceptor in the 5 apparatus having the construction described above , drum - like substrate 14 is placed in reaction chamber 49 , and gate valve 59 is opened to evacuate chamber 49 to a vacuum of about 0 . 1 torr or less . the predetermined gases from cylinders 41 , 42 , 43 , and 44 are supplied to chamber 49 , at a predetermined mixing ratio . in this case , the flow rates of the gases supplied to chamber 49 are determined such that the internal pressure of chamber 49 is set to be 0 . 1 to 1 torr . motor 58 is operated to rotate substrate 54 . substrate 54 is heated to a predetermined temperature by heater 55 , and an rf current is supplied between electrode 53 and substrate 14 , thereby generating a glow discharge therebetween . an a - si : h layer is deposited on substrate 54 . n 2 o , nh 3 , no 2 , n 2 , ch 4 , c 2 h 4 , and o 2 gases and the like may be added to the feed gas to add the element n , c , or o in the a - si : h layer . as is apparent from the above description , the electrophotographic photoreceptor according to the present invention can be manufactured in a closed - system manufacturing apparatus , thus guaranteeing the safety of the operators . since the electrophotographic photoreceptor has high resistance to heat , to humidity , and to wear , repeated use thereof does not result in degradation ; thus , a long service life is assured . electrophotographic photoreceptors according to the present invention were formed , and their electrophotographic characteristics were tested in the following manner . an aluminum drum substrate having a diameter of 80 mm and a length of 350 mm and subjected to acid , alkali , and sandblast treatments as needed to prevent interference , was mounted in a reaction chamber , and the interior of the reaction chamber was exhausted by a diffusion pump ( not shown ) to obtain a vacuum pressure of about 10 - 5 torr . thereafter , the drum substrate was heated to a temperature of 250 ° c . and rotated at 10 rpm , and an sih 4 gas with a flow rate of 500 sccm , a b 2 h 6 gas with a ratio of flow rate of 10 - 5 with respect to the sih 4 gas , and a ch 4 gas with a flow rate of 100 sccm were supplied into the reaction chamber , so that the interior of the reaction chamber was adjusted to be 1 torr . then , a high - frequency electric power of 13 . 56 mhz was applied to an electrode to generate plasma of sih 4 , b 2 h 6 , and ch 4 between the electrode and the substrate , thereby forming a barrier layer consisting of p - type a - sic : h . high - frequency discharge was temporarily interrupted , an nh 3 gas was supplied at a flow rate of 120 sccm , a reaction pressure was controlled to 1 . 2 torr , and a 500 - w high - frequency power was applied to the chamber , thereby forming a 100 - å thick a - sin : h thin layer . the flow rate of the sih 4 gas was then controlled to 500 sccm , and b 2 h 6 was supplied at a flow rate ratio of 10 - 7 with respect to the sih 4 gas . a 500 - w high - frequency power was applied to the reaction chamber to form a 100 - å thick a - si : h thin layer . the above operations were repeated to alternately form 600 a - sin : h thin layers and 600 a - si : h thin layers to obtain a 1 . 2 μm thick charge - retaining layer having a heterojunction superlattice structure . thereafter , discharge was temporarily stopped , and the sih 4 , ch 4 , and h 2 gases , respectively with flow rates of 50 , 7 , and 450 sccm were supplied into the reaction chamber to adjust the reaction pressure to be 1 . 2 torr . then , the high - frequency electric power of 800 w was applied to form a 100 - å thin μc - sic : h layer ( carbon content : 0 . 5 atomic %). the flow rate of the ch 4 gas was increased to 9 sccm , and a 100 - å thick μ - sic : h thin layer ( carbon concentration : 8 atomic %) was formed . this operation was repeated to alternately form 250 μc - sic : h thin layers and 250 μc - sic : h thin layers having different carbon concentrations in the adjacent thin layers , thereby forming a 5 - μm thick charge - generating layer having a heterojunction superlattice structure . a 0 . 5 - μm thick a - sic : h layer was formed as a surface layer . when the photoreceptor surface thus formed was negatively charged at about 500 v and exposed to white light , the light was absorbed in the charge - generating layer , and photocarriers of electron - hole pairs were generated . in this test example , a large number of photocarriers were generated , and a long lifetime and high propagating property of photocarriers were obtained . as a result , a clear image of high quality was obtained . in addition , when the photoreceptor manufactured in this test example was repeatedly charged , a transferred image was proved to have very good reproducibility and stability and superior durabilities such as high resistance to corona , humidity , and wear . furthermore , the photoreceptor thus manufactured has a high sensitivity to light having a long wavelength of 780 to 790 nm which is an oscillation wavelength of a semiconductor laser . when the photoreceptor was mounted in a semiconductor laser printer to form an image by the carlson process , a clear image was obtained with high resolution even when an exposure amount of the photoreceptor was 25 erg / cm 2 . an electrographic photoreceptor was manufactured following the same procedures as in example 1 except that a 100 - å thick a - sic : h thin layer was used in place of the 100 - å thick a - sin : h layer constituting one thin layer of the charge - retaining layer . the a - sic : h layer was formed by setting the flow rate of the ch 4 gas at 75 sccm and the pressure of the reaction chamber at 1 . 2 torr , and applying 500 - w high - frequency power . the resultant photoreceptor was tested following the same procedures as in example 1 , and similar test results were obtained . note that in the above examples , a thickness of the charge - generating layer was 5 μm , but it is not limited to this value . for example , when the thickness is set to be , e . g ., 1 or 3 μm , the photoreceptor can be similarly put to practical use . furthermore , the number of types of the thin films is not limited to two as in the above examples , but three or more types of thin layers may be stacked . more specifically , a boundary need only be formed between thin layers having optical band gaps which are different from each other .
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with reference now to fig1 wherein like numerals designate like components throughout all of the several figures , the shut - down heat removal system of the invention is shown installed within a pool - type liquid metal reactor facility 1 , although it may be used within a loop - type liquid metal reactor as well . such pool - type reactor facilities 1 include a generally cylindrical reactor vessel 3 that is surrounded by a guard vessel 5 . fig1 illustrates the reactor vessel 3 as being of the bottom - supported type ; however , the invention is compatible with suspended - type reactor vessel designs as well . between the reactor vessel 3 and the guard vessel 5 is an annular gas space 7 that helps to insulate the walls of the reactor vessel 3 from the rest of the facility 1 . this annular gas space 7 is typically filled with an inert gas , such as nitrogen , that will not react with the liquid sodium in the unlikely event that the vessel 3 should develop a leak . both the reactor vessel 3 and the guard vessel 5 are in turn further surrounded by a concrete , reactor cavity structure 9 that is again generally cylindrical in shape . the guard vessel 5 is concentrically disposed within the reactor cavity structure 9 so as to create a second insulating annular gas space 11 therebetween . unlike the first annular gas space 7 , this space 11 may be filled with air or nitrogen . in order to provide both support and thermal insulation for the bottom of the reactor vessel 3 , an insulating bed 13 of sand - like magnesium oxide about twenty inches deep is placed over the base mat 15 of the reactor cavity structure 9 . this insulating bed 13 is circumscribed by an annular support ring 16 . the ring 16 includes a plurality of inwardly , radially extending members ( not shown ) that allow for radial thermal expansion of the vessel 3 , but which prevent lateral motions of the vessel 3 which may occur as a result of seismic disturbances . the reactor vessel 3 further includes a slightly tapered , circular bottom end wall 21 , as shown . this bottom end wall 21 overlies the insulating bed 13 of magnesium oxide . the edge of the circular , bottom end wall 21 is connected to the upper edge of the annular support ring 16 for support . the insulating bed 13 of magnesium oxide also provides support for the bottom end wall 21 of the reactor vessel 3 . centrally disposed over the bottom end wall 21 is a column 23 that helps to support a nuclear core 30 . on its upper end , the column 23 is surrounded by a conical wall 29 that defines an inlet plenum for the reactor core 30 . the reactor core 30 is centrally disposed within the reactor vessel 3 , as shown . although not specifically shown in fig1 the reactor core 30 includes an array of fuel rod assemblies that impart a substantial amount of heat to the liquid sodium that circulates through the core 30 . disposed between the column 23 and the nuclear core 30 is a circular support plate 39 . this plate 39 co - acts with column 23 to support the core 30 and also divides the liquid sodium within the reactor vessel 3 into a cold pool plenum 40 located at the bottom of the vessel 3 , and a hot pool plenum 41 located at the middle and upper portions of the vessel 3 . the support plate 39 also forms a pressure boundary between the liquid sodium in the cold pool plenum 40 , and the relatively hotter liquid sodium in the hot pool plenum 41 . underneath the circular support plate 39 are a plurality of radially oriented trusses 43 . these trusses 43 assist the plate 39 in supporting both the primary pump 44 ( located on the left side of the core 30 ) and the intermediate heat exchanger 45 ( located on the right side of the core 30 ). the primary pump 44 is generally formed from a vertically oriented standpipe 47 that is laterally supported by a lateral baffle 48 . the inlet port 49 of the pump 44 is located at the bottom edge of the pump standpipe 47 , in order that it may communicate through a port in the support plate 39 with the liquid sodium in the cold pool plenum 40 . the outlet of the pump 44 is connected to an outlet conduit 51 that communicates with an opening ( not shown ) in the inlet plenum defined by conical wall 29 . in operation , the primary pump 44 sucks the relatively cooler liquid sodium from the cold pool plenum 40 and forcefully circulates it through the outlet conduit 51 to the plenum within the conical wall 29 which in turn uniformly distributes the sodium to the fuel rod assemblies located within the core 30 in order to heat it up . under normal operating circumstances , the primary pump 44 creates approximately a 100 psi pressure differential between the liquid sodium in the cold pool plenum 40 , and the liquid sodium disposed in the inlet plenum defined by the conical wall 29 . this pressure is dissipated as the sodium passes through the core 30 , and flows into the hot pool plenum 41 , but remains large enough after reaching the hot pool plenum to create a substantial pressure differential between the hot and cold pools . like the primary pump 44 , the intermediate heat exchanger 45 includes a vertically oriented standpipe 54 that is prevented from lateral movement by the lateral baffle 48 . although not specifically illustrated in fig1 the intermediate heat exchanger 45 includes a secondary system conduit for circulating sodium through the hot pool to a secondary heat exchange system that ultimately generates nonradioactive steam that is used to turn the turbines of electric generators . the relatively cooler liquid sodium that circulates past the heat extraction tubes of the secondary heat exchange system is ultimately discharged through the outlet 58 at the bottom of the intermediate heat exchanger 45 and into the cold pool plenum 40 , as shown . such discharge , of course , is created as a result of the suction pressure differential that the primary pump 44 creates between the cold pool plenum 40 and the hot pool plenum 41 . located on top of the reactor vessel 3 is a closure deck 60 formed from steel plates , steel ribs , and iron oxide shielding materials . the purpose of the closure deck 60 is to provide a thermal barrier between the reactor vessel 3 and the ambient atmosphere , as well as a radiological barrier for blocking the radiation emitted by the nuclear core 30 . between the lower edge of the closure deck 60 and the upper edge of the reactor vessel 3 is a metallic bellows 62 . this metallic bellows 62 is a relatively flexible structure that will accommodate dimensional changes between the closure deck 60 and the walls of the reactor vessel 3 that are generated as a result of thermal differential expansion . also included around the upper edges of the reactor vessel 3 are a series of top guide assemblies 64 . these top guide assemblies 64 make sure that the vessel closure deck 60 moves in phase with the top edge of the reactor vessel 3 in case of a seismic disturbance . other features of the bottom supported reactor facility illustrated in fig1 are specifically described in u . s . patent application ser . no . 795 , 592 , filed nov . 6 , 1985 , by j . e . sharbaugh , and assigned to the westinghouse electric corporation , the entire specification of which is specifically incorporated herein by reference . although not shown in fig1 the primary pump drive motor includes an auxiliary ( or &# 34 ; pony &# 34 ;) motor capable of creating a circulation flow that amounts to at least one - tenth of the normal circulation flow between the cold pool plenum 40 and the hot pool plenum 41 . with reference now both to fig1 a and 2b , the first preferred embodiment of the shut - down heat removal system 70 includes a heat exchanger 72 whose inner end generally circumscribes the upper portion of the reactor vessel 3 , as well as a redan 76 or wall that likewise circumscribes the upper portion of the reactor 3 . as is best seen in fig2 b , the inner end of the heat exchanger 72 is formed from four banks 73a , 73b , 73c and 73d ( of which only banks 73a and 73b are shown ) of hairpin - shaped pipes 74 . each of the hairpin - shaped pipes 74 is bent in the shape of a quadrant so that it may conform to the circular shape between the upper part of the redan 76 , and the upper wall of the reactor vessel 3 . one end of each of the hairpin - shaped pipes in banks 73a , 73b ( as well as 73c , 73d , not shown ) converges into a header 75 which is essentially a manifold . both of the headers 75 ( only one of which is shown for simplicity ) are connected to inlet and outlet pipes 77 which terminate in coils 78 that are in turn situated in natural - draft flues 79 ( illustrated in schematic ). these flues 79 are constantly kept open so that the coils 78 may be continuously cooled by a draft of ambient air . because the invention 70 obviates the need for louvers across the draft entrances 79 . 1 of the flues 79 , there is considerably less flow resistance for the drafts entering the entrances 79 . 1 . this reduction in flow resistance allows the stacks 79 . 2 used in such flues to be advantageously shortened , thereby reducing the overall cost of constructing such flues 79 . in the preferred embodiment , each of the banks 73a - 73d shown in fig2 b includes between thirteen and fifteen hairpin - shaped pipes 74 stacked in the configuration indicated in fig1 . additionally , each of the pipes 74 is preferably formed from 21 / 2 inch , schedule 40 stainless steel piping . the use of headers 75 in lieu of individual connections between the hairpin - shaped pipes 74 and the inlet and outlet pipes 77 advantageously minimizes the amounts of pipe penetrations required in the closure deck 60 . while it would be possible to replace the banks 73a - 73d with a single coil structure with 360 ° coils that wound completely around the reactor vessel 3 , the pressure drop associated with such a design would lessen the efficiency of the heat exchanger 72 . accordingly , the use of four separate banks 73a - 73d of hairpin - shaped pipes 74 is preferred . finally , while liquid sodium would be operative as a coolant in each of the hairpin - shaped pipes 74 , a mixture of liquid sodium and liquid potassium ( or &# 34 ; nak &# 34 ;) is preferred since such a mixture will remain in a liquid phase at a lower temperature than pure liquid sodium would . this is an important consideration , because the response time of the system 70 could be impaired if the coolant within the coils 78 ever dropped to a temperature which allowed it to solidify , either partially or completely . turning now to fig1 and 2a and a more specific description of the redan 76 , this structure is formed from a first cylindrical wall 80 having an upper section 82 , a mid - section 84 that is offset from the upper section 82 , and a lower section 86 that is offset from the mid - section 84 . the bottom edge of the lower section 86 includes flow ports 88 for a purpose that will be described presently , while the top edge of the upper section 82 includes a plurality of spillover ports 89 . the provision of such ports 89 ensures that any spillover of liquid sodium from the hot pool plenum 41 will occur uniformly around the circumference of the cylindrical wall 80 . the mid - section 84 and the lower section 86 of the wall 80 are joined by a lower conical shell 90 , and the mid - section 84 and upper section 82 are further joined by an upper conical shell 92 . these shells 90 and 92 have the effect of spacing the midsection 84 and upper section 82 farther away from the inner wall of the reactor vessel 3 in a stepped fashion . as a result of this spacing , an annular space 93 is formed between the first cylindrical wall 80 and the reactor vessel 3 that radially increases in size from the lower section 86 to the upper section 82 of the first cylindrical wall 80 . the flow ports 88 located at the bottom of the lower section 86 of the wall 80 bring this annular space 93 into communication with the liquid sodium in the cold pool plenum 40 . the heat removal system 70 further includes a second cylindrical wall 94 that extends away from the inside surface of the reactor vessel 3 by means of a conical shell 96 that parallels the previously described conical shell 92 . the purpose of the second cylindrical wall 94 is to create an insulating gas space 98 between the upper portion of the reactor vessel 3 , and the hot liquid sodium in the hot pool plenum 41 . finally , the system 70 of the first preferred embodiment includes a syphon mechanism 100 , best seen in fig2 a . this syphon mechanism 100 straddles the edge 101 of the upper section 82 of the wall 80 with one leg 102 projecting into the liquid sodium in the hot pool plenum 41 , and another leg 104 projecting down over the heat exchanger 72 located between the walls 80 and 94 . a priming conduit 106 fluidly connects the syphon mechanism 100 to a suction pump 108 . this conduit 106 has a valve mechanism 109 that is preferably remotely operable for a purpose that will be described hereinafter . in operation , the flow ports 88 in the lower section 86 of the wall 80 allow the liquid sodium level 112 in the annular space 93 to fall to a level that barely immerses the lowest pipes 74 . if there were no pressure differential between the liquid sodium in the hot pool plenum 41 and the cold pool plenum 40 , then the sodium level 112 and the level of the sodium in the hot pool plenum 41 would be equal to the sodium level 110 . however , due to the suction pressure differential generated by the primary pump 44 , the level 112 of the sodium in the annular space 93 defined by the wall 80 of the redan 76 drops to the level that barely immerses the first or second pipes 74 of the heat exchanger 72 . while it would be possible to design the redan 76 so that the level 112 of the liquid sodium within the annular space 93 made no contact whatever with the lower pipes 74 of the heat exchanger 72 , some minimal contact is preferred in order to keep the liquid metal within the pipes 74 liquid at all times so that there is always at least some circulation of coolant moving through the heat exchanger 72 . such minimal contact is not enough to significantly affect the efficiency of the reactor facility 1 as a whole , but yet will insure that the system 70 will respond rapidly to a shut - down condition , since the coolant will never have a chance to solidify in the pipes 74 . as is evident from the foregoing description , if the primary pump 44 should ever fail to create the pressure differential between the sodium in the hot and cold plenums 41 and 40 , the level 112 of the liquid sodium in the annular space 93 will rise to a point where it substantially ( if not completely ) immerses all of the pipes 74 forming the heat exchanger 72 . such immersion will immediately heat the coils 78 that the hairpin - shaped pipes 74 are all ultimately connected to , which in turn will increase the draw of air through the flue 79 . the end result is that the heat exchanger 72 would immediately begin to conduct a substantial amount of heat out of the reactor system 1 and through the stack 79 . 2 of the flue 79 . moreover , as the temperature in the sodium in the hot pool plenum 41 began to rise as a result of the decay heat from the core 30 , the level 110 of the liquid sodium in the hot pool plenum 41 would rise to a level 114 ( shown in phantom ) level with the flow holes 89 in the upper section 82 of the wall 80 , thereby causing an overflow of liquid sodium over the redan 76 . such an overflow would in turn cause the hottest liquid sodium in the hot pool plenum 41 ( which has risen over the dashed line drawn across the plenum 41 to the top of the pool ) to flow down through the annular space 93 into the relatively cooler sodium in the cold pool plenum 40 , thereby circulating the sodium within the vessel 3 by natural convection . if the condition which caused the failure of the primary pump 44 does not render the syphon pump 108 inoperative , this pump 108 may be actuated ( after valve 109 is opened ) in order to induce such a natural circulation before the sodium in the hot pool plenum 41 thermally expands to a level 114 which causes it to overflow onto the heat exchanger 72 . if circumstances permit , this is the preferred manner of operation of the first embodiment of the invention , since it results in a lower peak temperature for the sodium in the hot pool plenum 41 . fig3 a and 3b illustrate an alternative embodiment of the shut - down heat removal system 70 of the invention . in this embodiment , a heat exchanger 120 is formed from a plurality of nesting coils 122 , each of which is formed in the shape of a conical helix . while the heat exchanger 120 preferably includes a multiplicity of such coils , only two are shown in fig3 in order to simplify the drawing . a liquid metal coolant such as nak is conducted to and from these nesting coils 122 by means of inlet and outlet manifolds 124a , 124b . the entire set of nesting coils 122 is contained in a cylindrical housing 125 as shown . inlet and outlet conduits 126a , 126b connected to the manifolds 124a , 124b in turn circulate the liquid metal coolant from the nesting coils 122 to coils ( not shown ) situated in natural air draft flues constructed like the previously described flue 79 . it should be noted that the cylindrical housing 125 includes a plurality of inlet ports 127 in order that liquid sodium from the hot pool plenum 41 may freely flow over these coils 122 in the event of a shut - down condition . in lieu of the wall - type redan 76 utilized in the first embodiment of the invention , the second embodiment houses the heat exchanger 120 in the upper portion of a vertically oriented , outer standpipe 128 . this standpipe 128 is secured against lateral motion by a lateral baffle 48 . the bottom edge 130 of the outer standpipe 128 is mechanically mounted and sealingly engaged onto the support plate 39 that forms the pressure boundary between the hot and cold sodium plena 41 and 40 . the top of the outer standpipe 128 is spaced a short distance away from the bottom surface of the closure deck 60 , and includes a set of upper inlet ports 134 , and a set of lower inlet ports 136 . a skirt - like annular wall 138 circumscribes the inner surface of the upper portion of the outer standpipe 128 . this annular wall 138 has an upper edge 140 that is sealingly engaged to the inner wall of the outer standpipe 128 just above the lower inlet ports 136 so that any liquid sodium that enters these ports 136 must flow through the space between the annular wall 138 and the inner surface of the outer standpipe 128 before reaching the heat exchanger 120 . the bottom edge of the annular wall 138 terminates in a ring - like lower edge 142 as shown . the second embodiment of the shut - down heat removal system further includes an inner standpipe 145 that is contained within the outer standpipe 128 . the bottom edge 147 of the inner standpipe 145 is also mounted onto and sealingly engaged with the support plate 39 . further , as is not the case with the outer standpipe 128 , the interior of the inner standpipe 145 communicates with the cold sodium plenum 40 through an aperture ( not shown ). the top edge 149 of the inner standpipe 145 extends to a point adjacent to the bottom of the cylindrical housing 125 of the heat exchanger 120 . in the preferred embodiment , the inner standpipe 145 is concentrically disposed with respect to the outer standpipe 128 , so that an elongated , annular space 150 is defined between the outer surface of the inner standpipe 145 , and the inner surface of the outer standpipe 128 . this elongated , annular space 150 communicates with the discharge outlet of the primary pump 44 through a laterally disposed port 152 that is connected to a discharge conduit 154 that leads to the outlet ( not shown ) of the primary pump 44 . hence , the elongated , annular space 150 is normally filled with liquid sodium that is pressurized relative to the liquid sodium in the cold pool plenum 40 . a ring - shaped piston member 158 is slidably disposed within the elongated , annular space 150 between the inner and outer standpipes 145 , 128 . this piston member 158 includes a plurality of outer seals 160 that engage the inner wall of the outer standpipe 128 , as well as a plurality of inner seals 162 that slidingly engage the outer surface of the inner standpipe 145 . finally , the inner standpipe 145 is circumscribed by an annular ledge 164 . as will be seen hereinafter , the ledge 164 defines the lowest position that the piston member 158 can attain , while the ring - like lower edge 142 of the annular wall 138 defines the highest position that the piston member 158 can attain . in operation , pressurized sodium from the primary pump 44 flows through the conduit 154 , port 152 , and pushes the ring - shaped piston member 158 upwardly so that its top surface sealingly engages the ring - shaped ledge 164 that defines the lower edge of the annular wall 138 . when the piston member 158 is so positioned , liquid sodium entering the lower inlet ports 136 of the outer standpipe 128 can flow no further than the annular space defined between the annular wall 138 , and the inside surface of the outer standpipe 128 . while liquid sodium from the cold plenum 40 can exist in the inner standpipe 145 , the level it attains will be no higher than the lowermost coils 122 of the heat exchanger 120 . it will not attain the same level as the liquid sodium in the hot pool plenum 41 due to the pump suction pressure differential developed between the cold and hot plenums 40 and 41 when the pumps 44 are operating . however , if the primary pump 44 should ever cease to create the suction pressure differential between the cold and hot plenums , the weight of the piston member 158 will cause it to fall down toward the annular ledge 164 that circumscribes the upper portion of the inner standpipe 145 , so that the piston member assumes the position illustrated in fig3 a . when this occurs , liquid sodium is free to flow through the lower inlet ports 136 , around the ledge 142 that forms the lower edge of the annular wall 138 , and up into the inlet port 127 of the cylindrical housing 125 of the heat exchanger 120 . from there , the liquid sodium will spill through the plurality of helical coils 122 that form the heat exchanger 120 , and ultimately spill downwardly to the liquid sodium in the cold plenum 40 ( which has risen to approximately the same level as the liquid sodium in the hot plenum 41 due to the lack of any pressure differential therebetween ). hence , not only are the coils 122 that form the heat exchanger completely immersed in liquid sodium , but the circulation path between the hot pool plenum 41 and the cold pool plenum 40 is also immediately established . as is evident from the foregoing , the second embodiment of the invention has the advantage of immediately establishing such a circulation path without depending upon decay heat from the nuclear core 30 to thermally expand the sodium in the hot pool plenum 41 to a spillover point over the redan .
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fig1 and 2 are schematic views of a winding machine 1 . the winding machine 1 comprises a rotary plate or a turret 2 . the turret 2 is rotated by an appropriate driving unit relative to a supporting structure 3 of the winding machine 1 about a rotational axis which has an orientation perpendicular to the plane of projection according to fig1 . the turret 2 supports spindles 4 , 5 . the rotational and longitudinal axes 18 , 19 of the spindles 4 , 5 also have an orientation perpendicular to the plane of projection according to fig1 . the rotational and longitudinal axes 18 , 19 are located on diametrically opposed sides of the rotational axis of the turret 2 . the axes 18 , 19 have the same distance from the rotational axis of the turret 2 . a completely wound package ( preferably with a sleeve 7 ) is located on the spindle 4 . the completely wound package 6 has a diameter d . on the spindle 5 , there is a partially wound package 8 ( preferably with a sleeve 9 ). the wound package 8 has a diameter d increasing to d during the winding process . the winding material 10 is fed to the wound package 8 by a traversing device 11 . like known from prior art , the distance between the traversing 11 and the longitudinal and rotational axis of the spindle 5 might vary during the build - up of the package with increasing diameter d . for this purpose the traversing device 11 or the spindle 5 might be provided with an appropriate degree of freedom in the projection plane of fig1 for a relative displacement . according to fig1 , the wound package 6 is located in a resting position 12 . in the resting position 12 , the wound package 6 has to be removed from the spindle 4 by an operator or in an at least partially automated manner . further , a new sleeve 7 might be put onto the spindle 4 in the resting position 12 . different from the wound package 6 , the wound package 8 is located in a working position 13 . in the working position 13 , the winding material 10 is caught by the spindle 5 or a sleeve 9 . it is possible that a fixation winding and / or a transfer winding or a spare winding is wound . the winding with increasing diameter d is performed . when the winding of the wound package 8 is completed , i . e . when the diameter d of the wound package 8 is equal to the diameter d , the turret 2 is rotated by 180 degrees about its rotational axis . by the rotation of the turret 2 , the spindle 5 is transferred into the resting position 12 . the spindle 4 ( from which the wound package 6 has already been removed ) is transferred into the working position 13 such that it is possible to wind a new package on spindle 4 . in fig1 , it is shown that a distance 21 between the outer surfaces of the wound packages 6 , 8 decreases with increasing diameter d . if no action is taken , at a certain time of the package build - up , the outer surface of the wound package 8 will finally collide with the outer surface of the wound package 6 . this would cause an interruption or a stop of the winding process . to prevent such a stop or interruption , the wound package 6 has to be removed from the spindle 4 before the diameter d has increased such that the distance 21 is equal to zero . fig2 shows that each of the wound packages 6 , 8 comprises an axial extension 14 , 15 . the axial extensions 14 , 15 are defined by the fanning width of the winding material and the traversing path of the traversing device 11 . further , fig2 shows that the sleeves 7 , 9 project beyond front surfaces of the wound packages 6 , 8 , i . e . the sleeves 7 , 9 have a length which is larger than the axial extensions 14 , 15 . the front surfaces 16 , 17 of the wound packages 6 , 8 are located without any offset in the same plane perpendicular to the rotational axis 18 , 19 of the wound packages 6 , 8 . consequently , the wound packages 6 , 8 have an overlap 20 , wherein the overlap 20 of the prior art is equal to the axial extensions 14 , 15 . the spacing 21 of the wound packages 6 , 8 is given in a plane comprising the longitudinal axes of the spindles 4 , 5 . in particular , the axial overlap 20 can be determined by projecting the axial extensions 14 , onto a longitudinal or rotational axis 18 , 19 of the wound packages 6 , 8 . the front view of a winding machine according to the invention might look like the front view shown in fig1 . fig3 shows a schematic top view of an inventive winding machine , wherein the completely wound package 6 is in the resting position 12 and wherein the wound package 8 is in the working position 13 for build - up of the package . initially , the wound packages 6 , 8 have an overlap 20 , because both wound packages 6 , 8 are in a winding position 22 , i . e . both wound packages 6 , 8 are located in the same vertical plane . the winding position 22 corresponds to a relative arrangement of the wound packages 6 , 8 with regard to the corresponding spindles 4 , 5 or with regard to the supporting structure 3 or the turret 2 . in the resting position 12 as well as in the winding position 22 of the wound package 6 according to fig3 , the completely wound package 6 is not yet removed . instead , before the spacing 21 of the outer surfaces of the wound packages 6 , 8 has reduced to zero due to the increasing diameter d , the completely wound package 6 is transferred by actuation of a shifting device 23 from the winding position 22 into the removal position 24 shown in fig4 . by actuation of the shifting device 23 the wound package 6 with sleeve 7 is axially shifted relative to the spindle 4 over a shifting path 25 from the winding position 22 into the removal position 24 . the shifting path 25 is chosen such that the axial extensions 14 , 15 of the wound packages 6 , 8 do not have any overlap 20 . instead , they are arranged at a distance 26 in a projection of the axial extensions 14 , 15 onto a longitudinal or rotational axis 18 , 19 . the shifting path 25 of the shifting device 23 is larger than the axial extensions 14 , 15 of the wound packages 6 , 8 . as shown in fig4 , a collision of the wound packages 6 , 8 is avoided independent from the diameter d of the wound package 8 . it is possible to shift the wound package 6 along the shifting path 25 at any time . for example , the wound package 6 might be shifted at the beginning of the winding process of the wound package 8 or during the package build - up of the wound package 8 . it is also possible that the wound package 6 normally is not shifted by the shifting device 23 but normally removed by an operator when being in the winding position 22 according to fig3 . for this embodiment also covered by the invention an actuation of the shifting device 23 is only performed in case of an emergency , i . e . in case of an automatic detection that the wound package 6 has not yet been removed from the spindle 4 although the diameter d of the wound package 8 has reached or passed a critical diameter d limit . in case of this emergency , the removal position 22 according to fig4 builds a kind of “ safety position ”. the shifting device 23 shown in fig3 and 4 comprises a movable push rod 27 controlled by an actuator . for moving the push rod 27 , a pneumatic piston / cylinder unit might be used . it is possible that the pneumatic piston / cylinder unit is pneumatically biased against a spring such that with an exhaustion of the pneumatic piston / cylinder unit the push rod 27 is returned by the spring . furthermore it is possible that , when the piston / cylinder unit is exhausted , the push rod 27 is returned , when a new sleeve 7 is put onto the spindle 4 . according to the embodiment shown in fig4 , the front surface of the push rod 27 contacts a front surface of the sleeve 7 , e . g . by a contact plate 37 , for shifting the wound package 6 along the shifting path 25 . it is also possible that a front surface of a respective push rod 27 directly engages the wound package 6 , in particular in case the wound package 6 is build without sleeve 7 . further , the wound package 6 or the sleeve 7 might be axially and / or radially fixed on the spindle 4 in the working position 13 as well as during the transfer from the working position 13 to the resting position 12 . in the latter case , the axial and / or radial fixation has to be released before an actuation of the shifting device 23 . a comparison of fig2 and 3 shows that the spindles 4 , 5 according to the invention are longer than those according to the prior art : as shown in fig3 , in the winding position 22 the spindles 4 , 5 project beyond the wound packages 6 , 8 ( here the sleeves 7 , 9 ) by a length 28 . this length 28 is individually chosen . preferably , the length 28 is about 50 percent to 100 percent of the axial extensions 14 , 15 of the wound packages 6 , 8 . for a minimal length 28 of 50 percent of the axial extensions 14 , 15 , the wound packages 6 , 8 are held in the removal position 24 without tilting . for a small length 28 , the path along which the wound package 6 has to be moved along the rotational axis 18 for removal by an operator or in an automatic manner is reduced . the length 28 might be about 60 percent , 70 percent , 80 percent , 90 percent or 100 percent of the axial extension 14 , 15 . the length 28 might also be longer than the above mentioned lengths . preferably , the distance 36 of the rotational axis 18 , 19 , i . e . the longitudinal axes of the spindles 4 , 5 , which is shown in fig3 and 5 in a projection , is smaller than the diameter d . the distance 36 of the rotational axis 18 , 19 might be about 60 percent , 70 percent , 80 percent , 90 percent or 100 percent of the diameter d . however , the distance of the rotational axes 18 , 19 might also be larger than the diameter d . all in all , according to the invention , the available space and the time for handling the completely wound package is increased , and the shifting device 23 might provide a partial execution of the removal . in step 29 , the complete winding of the wound package 6 is performed on the spindle 4 located in the working position 13 . with regard to the spindle 4 , the wound package 6 is in a winding position 22 . in a subsequent step 30 , the turret 2 is rotated by an angle of 180 degrees , and the spindle 4 is transferred into a resting position 12 as shown in fig3 . preferably , the wound package 6 remains in the winding position 22 with regard to the spindle 4 during the rotation of the turret 2 . in step 31 ( which might be executed concurrently with or after step 30 ), the winding material 10 is fed to the spindle 5 being located in the working position 13 or to the sleeve 9 located on spindle 5 . in the working position 13 , the winding material 10 might be caught by an appropriate catching device . further , for a preparation of the winding process , a fixation winding and / or transfer winding or spare winding might be wound . finally , in step 31 the winding material 10 is cut . in a subsequent step 32 , the winding material 10 is wound onto the wound package 8 located in the working position , wherein the wound package 8 is located in the winding position 22 with regard to the spindle 5 . the wound package 6 on the spindle 4 might be slowed down concurrently with the winding of the wound package 8 . steps 29 to 32 are equal to the steps during a changing or transfer process in a winding machine 1 known from the prior art . according to the invention , an additional step 33 is performed . in step 33 , the wound package 6 in the resting position 12 is shifted by the shifting device 23 from the winding position 22 into the removal position 24 . in the removal position 24 the axial extensions 14 , 15 have no overlap 20 . step 33 might include step 34 , wherein in step 34 , the shifting device 23 is automatically actuated under the control of a control unit of the winding machine 1 . in step 35 , the wound package 6 is removed from the spindle 4 . here , it is also possible that the wound package 6 has already been partially removed during step 35 with the actuation of the shifting device 23 by movement along the aforementioned length 28 . in fig5 , different dashed lines indicate that there are various options with regard to the sequence of the steps . in particular , the steps 33 , 34 might start at certain times or continue during at least one of the steps 30 to 32 . the upper dashed line indicates for example that the actuation of the shifting device 23 in step 34 is performed ( at least partially ) during the rotation of the turret 2 in step 30 . the dashed line in the middle indicates that the actuation of the shifting device 23 might be performed together with a preparation of the winding of the wound package 8 , i . e . together with the transfer of the winding material , the winding of the fixation winding , the transfer winding or the spare winding and / or the cutting of the winding material . furthermore , the partial actuation of the shifting device 23 in step 34 and / or the removal in step 35 might be performed during the winding of the wound package 8 . for each spindle 4 , 5 a respective shifting device 23 might be provided . these two shifting devices 23 might be supported by the turret 2 , and they might be rotated together with the turret 2 . a simplification in construction might be achieved by using a single shifting device 23 for both spindles 4 , 5 . for example , the shifting device 23 provided for both spindles 4 , 5 might be supported by a supporting structure 3 at a position to which the spindles 4 , 5 are moved by rotation of the turret 2 for removal of the wound packages . in case that the shifting device is built with a pneumatically actuated cylinder , the cylinder might be a double acting cylinder for enabling a pneumatic return or reset of the shifting device 23 . the wound packages or sleeves might be fixed on the spindles in a friction locked manner by radially expanding springs surrounding the spindles . the radial expansion of the springs effects that the springs are pressed at the inside at the sleeves so that both a rotary as well as an axial fixation is effected . the springs might be located in v - shaped grooves of the spindles , wherein the v - shaped outline of the grooves builds a wedge like bevel . by spiral springs these springs are pushed along the bevels to the outside , so that the radial expansion is effected . the fixation is pneumatically released by an actor counteracting the force of the spiral springs . here , the actor might be located immediately below the shifting device 23 . preferably , the ratio of the diameter d to the distance 36 is about 0 . 7 to 0 . 9 and even more preferred about 0 . 75 to 0 . 85 . for example , the ratio might be 0 . 80 . in terms of the volume that might be wound and thus in terms of the duration before a collision might occur , this ratio means that a collision would occur at about 1 / 5 of the total package build - up in case that the completely wound package is not removed . for a non - limiting example the ratio of the distance of the front surface of the spindle 4 from the front surface 16 of the wound package 6 and the axial extension 14 of the completely wound package 6 might be about 0 . 7 to 0 . 8 , e . g . 0 . 73 . the ratio of the length 28 and the axial extension 14 of the completely wound package 6 might be about 0 . 6 to 0 . 7 , in particular 0 . 66 . however , other ratios are also possible within the scope of the invention . preferably , the shifting device 23 is actuated not until the completely wound package 6 has been completely slowed down by an appropriate braking device . however , it is also possible that the shifting device 23 is actuated at a pint in time wherein the completely wound package 6 is still rotating . in the latter case , it might be advantageously if the shifting device 23 is integrated in the spindle ( i . e . if the rotating spindle or a part thereof is axially moved ). many variations and modifications may be made to the preferred embodiments of the invention without departing substantially from the spirit and principles of the invention . all such modifications and variations are intended to be included herein within the scope of the present invention , as defined by the following claims .
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the carrier shown in fig1 to 5 in a perspective view includes a base body 3 and a holding body 4 firmly connected with the base body , which contains two holding jaws 41 connected with each other via a connection tab 43 , between which a window pane 2 is clamped and firmly connected with the holding body 4 by means of a locking device 44 . the base body 3 is mounted on a guide rail 1 shown in fig1 in broken lines and is movable in longitudinal direction of the guide rail 1 for lifting and lowering the window pane 2 , wherein the adjustment of the carrier on the guide rail 1 is effected via a non - illustrated bowden cable which is provided with a nipple which is inserted into a nipple chamber 30 in the base body 3 and thus is connected with the carrier . by means of a likewise non - illustrated drive means , the carrier is shifted translatorily along the guide rail 1 . the window lift containing the guide rail 1 and the carrier 3 , 4 is mounted in a motor vehicle door and in particular in a frameless motor vehicle door for lifting and lowering the window pane 2 . the window pane 2 defines a window plane along which the window pane 2 extends in a state in which it is connected to the holding body 4 constituting a window pane holder for connecting the window pane 2 to the carrier . to ensure that in a frameless motor vehicle door the window pane bears on the sealing contour of the motor vehicle body in a tightly sealing manner , the window pane 2 is pretensioned in the direction of the sealing contour , so that with closed window pane 2 and closed motor vehicle door a sufficient contact pressure of the window pane 2 against the sealing contour also is ensured at higher speeds and hence at a corresponding excess pressure in the vehicle interior . the tightly sealing bearing of the window pane 2 on the sealing contour of the motor vehicle body is achieved both by a corresponding alignment of the pull - off line of the window pane 2 with respect to the sealing contour of the motor vehicle body and also by a corresponding inclination of the window pane 2 towards the sealing contour . as shown in fig1 , the guide rail 1 illustrated in broken lines includes a section which is embraced and engaged behind by two guiding claws 5 , 6 arranged on the base body 3 at a distance from each other and thus ensures a safe guidance of the carrier 3 , 4 and hence of the window pane 2 on the guide rail 1 of the window lift . while the one guiding claw 6 — the upper one in the embodiment — is firmly formed on the base body 3 of the carrier , the guiding claw 5 — the lower one in the embodiment — is adjustable with a component of adjustment vertical to the longitudinal extension of the guide rail 1 , i . e . in y - direction of the motor vehicle with a window lift mounted in a motor vehicle door . for this purpose , the adjustable guiding claw 5 as shown in fig2 to 5 includes a connecting link guide 52 , 53 extending at an angle with respect to the guide rail 1 , which consists of connecting link guide grooves 52 in guide legs 56 , 57 of a guiding claw holder 50 formed as part of the base body 3 of the carrier and of connecting link guide webs 53 slidingly engaging in the connecting link guide grooves 52 in an adjusting body of a movable guiding claw member 51 of the adjustably guiding claw 5 . due to this configuration of the connecting link guide 52 , 53 the adjustable guiding claw 5 is adjusted in z - direction , i . e . in direction of the vertical axis of the motor vehicle and hence with a corresponding alignment of the guide rail 1 in direction of the longitudinal extension of the guide rail 1 with a superposition in y - direction of the motor vehicle , i . e . vertical to the longitudinal extension of the guide rail 1 . for adjusting the adjustable guiding claw 5 an adjustment gear 7 is used , which consists of an adjusting screw 71 with an external thread 73 , an adjusting tab 72 with an internal thread 74 , which is firmly and integrally connected with the base body 3 of the carrier , a coupling ring 75 formed on the adjusting screw 71 and a coupling groove 77 in a coupling claw 76 , which is formed on the adjusting body 58 of the movable guiding claw member 51 of the adjustable guiding claw 5 . in the space surrounding the rail , which is formed by the adjustable guiding claw 5 and the fixed guiding claw 6 , a sliding insert 9 is inserted to improve the sliding properties of the guiding claws 5 , 6 on the guide rail 1 . the end of the adjusting screw 71 opposite the coupling ring 75 includes a tool holder 70 , which includes an internal polygon , in particular a torx holder , into which a turning tool 8 , in particular in the form of a torx tool , can be inserted . by rotating the turning tool 8 in the one or other direction of rotation , the adjusting screw 71 of the adjusting gear 7 is rotated in the corresponding direction , so that by engagement of the external thread 73 of the adjusting screw 71 into the internal thread 74 of the adjusting tab 72 firmly connected with the base body 3 , the adjusting screw 71 is lifted or lowered in the direction of the double arrow shown in fig1 . in the process , the coupling ring 75 likewise is lifted or lowered . as a result of the engagement of the coupling ring 75 into the coupling groove 77 of the coupling claw 76 , the coupling claw 76 is lifted or lowered together with the movable guiding claw member 51 , wherein as a result of the connecting link guide 52 , 53 with the connecting link guide grooves 52 and the connecting link guide webs 53 the adjustable guiding claw 5 is adjusted in z - direction of the motor vehicle with a superimposed adjusting movement in y - direction of the motor vehicle and the carrier thereby is swiveled about the fixed upper guiding claw 6 . by means of the elongated coupling claw 76 it is ensured that the coupling ring 75 remains in engagement with the coupling groove 77 during the y - z adjusting movement . by aligning the tool holder 70 in direction of the longitudinal extension of the guide rail 1 it is achieved that the turning tool 8 can be introduced for example through the upper slot of the door shaft and thereby the adjustment of the position and orientation of the window pane 2 in the completely mounted condition of the window lift can be effected with firmly mounted interior lining of the motor vehicle door . alternatively , an adjustment through the bottom of the door shaft is possible , when a correspondingly closeable opening is provided at the door bottom . the adjustment of the lower , adjustable guiding claw 5 is illustrated with reference to the longitudinal sections through the carrier as shown in fig6 and 7 . fig6 shows the carrier in a starting position in which the lower , adjustable guiding claw 5 is at a distance x from the holding body 4 connected with the base body 3 . in this setting , the movable guiding claw member 51 is in a lower position with respect to the guiding claw holder 50 . by actuating the turning tool 8 , the adjusting screw 71 is lifted with respect to the adjusting tab 72 , i . e . the coupling ring 75 is moved towards the adjusting tab 72 and hence the coupling claw 76 together with the movable guiding claw member 51 is lifted along the connecting link guides 52 , 53 in z - and y - direction of the motor vehicle , until the position shown in fig7 is reached , in which the movable guiding claw member 51 with the sliding element 9 inserted therein , which embraces the guide rail , has a distance x + a from the holding body 4 of the carrier . the dash - dotted line illustrates that a swivel angle is obtained with respect to the pull - off line of the window pane 2 defined by the extension of the guide rail 1 , as due to the adjustment of the adjustable guiding claw 5 and the fixed guiding claw 6 a corresponding swivel movement of the base body 3 of the carrier occurs around the fixed guiding claw 6 . instead of the connecting link guides 52 , 53 a combined connecting link and wedge - shaped guide can be provided for adjustment of an adjustable guiding claw 5 ′ in z - direction with a superposition of the adjusting movement in y - direction corresponding to the embodiment described below with reference to fig8 to 13 . the embodiment shown in fig8 to 13 corresponds with the embodiment described above with reference to fig1 to 7 with the exception of the formation of the adjusting means of the movable guiding claw 5 ′, so that with respect to the corresponding components reference is made to the above description , wherein in fig8 to 13 identical components are designated with reference numerals which correspond with the reference numerals of the components shown in fig1 to 7 . the embodiment shown in fig8 to 13 is characterized by improved guiding and sliding properties , since the guiding claw holder 50 ′ connected with the carrier 3 , 4 and the movable , adjustable guiding claw member 51 ′ have larger guiding and sliding surfaces . in an isometric representation with exploded representation of the movable guiding claw 5 ′, fig8 shows the guiding claw holder 50 ′ integrally connected with the base body 3 of the carrier 3 , 4 , which consists of two guide legs 56 ′, 57 ′ arranged parallel to and spaced from each other and of a guide tongue 54 ′ arranged between the guide legs 56 ′, 57 ′, which is arranged centrally between the guide legs 56 ′, 57 ′ and spaced from the same . in the guide legs 56 ′, 57 ′ a box - shaped guide channel 52 ′ is formed , which is aligned to extend at an angle with respect to the extension of the guide rail 1 , i . e . at an angle with respect to the pull - off direction of the carrier 3 , 4 and hence of the window pane 2 connected with the carrier 3 , 4 . the movable guiding claw member 51 ′ insertable in the guiding claw holder 50 ′ consists of an adjusting body 58 ′, in which an angled recess is arranged for holding the sliding and guiding member 9 and which includes laterally protruding guide webs 53 ′ directed away from each other , which slidingly engage in the guide channels 52 ′ of the guide webs 56 ′, 57 ′. from the adjusting body 58 ′, the coupling claws 76 protrude substantially vertically , which cooperate with the adjusting gear 71 , 72 , 75 . in addition , the movable guiding claw member 51 ′ on the adjusting body 58 ′ includes an opposing guide surface 55 , which corresponds with the guide surface of the guide tongue 54 ′ of the guiding claw holder 50 ′. due to the box - shaped guide channels 52 ′ and the large - surface guide surface 55 ′ in conjunction with the guide tongue 54 ′ a large sliding and guiding surface is provided , which increases the sliding and guiding properties of the adjustable guiding claw 5 ′ of the second embodiment as compared to the first embodiment . the embodiments described above with reference to fig1 to 13 permit numerous variants , some of which will briefly be outlined below . instead of a connecting link guide 52 , 53 a wedge - shaped guide can be provided for adjusting the adjustable guiding claw 5 in z - direction with a superposition in y - direction . by varying the angle included by the slotted guide 52 , 53 with the pull - off line of the window lift , the degree of adjustment of the movable guiding claw 5 in y - direction , which is superimposed on the adjustment in z - direction , can be varied . with the same path of adjustment in z - direction , the amount of the adjusting angle by which the base body 3 is swiveled with respect to the guide rail 1 about the fixed guiding claw 6 can be increased or decreased and the fineness of the adjusting movement can be increased or reduced , respectively . instead of an adjusting movement of the adjustable guiding claw 5 in z - direction with superimposed adjustment in y - direction , a purely translatory adjustment in y - direction can be provided . this purely translatory y - adjustment can be realized by means of an adjusting gear 7 , in which for example the rotary movement of the turning tool 8 is converted into a shifting movement of the movable guiding claw member 51 , 51 ′ in y - direction . an embodiment suitable for this purpose would be the arrangement of a pinion connected with the tool holder 70 , whose teeth engage in teeth of the coupling claw 76 formed in the manner of a rack - and - pinion gear , which is integrally or in some other way connected with the movable guiding claw member 51 , 51 ′. instead of an adjusting gear 7 formed in the manner of a rack - and - pinion gear , the adjusting gear 7 can consist of an eccentric gear in which the tool holder 70 is connected with an eccentric which is arranged in a bore of a coupling member which is connected with the movable guiding claw member 51 , so that by rotating the eccentric an adjusting movement of the movable guiding claw is effected in y - direction of the motor vehicle . if an adjustable guiding claw likewise is provided instead of an upper guiding claw 5 firmly connected with the base body 3 , the kind of adjustment of the carrier 3 , 4 with respect to the guide rail 1 is varied further and , if necessary , the swivel angle with which the carrier 3 , 4 can be swivelled with respect to the guide rail 1 can be increased . if both adjustable guiding claws 5 , 5 ′, 6 are connected with a separate adjusting device , an adjustment with large swivel angle can be performed beside a purely translatory adjustment of the carrier in y - direction of the motor vehicle , in that the adjustable guiding claws 5 , 5 ′, 6 are shifted with respect to each other in opposite directions . in addition , an adjustment of each of the two movable guiding claws 5 , 5 ′, 6 in z - direction with superposition in y - direction and a purely translatory adjustment in y - direction is possible as described above . with a common adjusting device for both movable guiding claws 5 , 5 ′, 6 both a common adjustment in z - direction with superposition of an adjustment in y - direction and a purely translatory adjustment in y - direction of the carrier can be performed with respect to the guide rail .
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turning to fig1 , a system 20 for rotating a work implement with respect to a track undercarriage , or , in other words , a slue positioning system 20 is disclosed . the positioning system 20 may include a swing motor assembly 21 disposed on top of a swing sensor housing 22 . the swing sensor housing 22 , in turn , may be disposed on top of a swing drive 23 . the swing drive 23 is illustrated in fig2 with the swing sensor housing 22 and swing motor assembly 21 removed . specifically , the swing drive 23 may include a casing 24 and a swing drive cover plate 25 . the swing drive cover plate 25 in combination with the swing casing 24 may house a series of gears , one of which is a sun gear 26 and a plurality of planetary gears , two of which are shown in partial view at 27 in fig2 . a series of studs 28 may be used to secure the swing sensor housing 22 to the swing drive cover plate 25 . turning to fig1 , an oil dip stick tube 31 and dip stick 32 are employed to check the oil levels in the swing drive 23 . a speed sensor 33 may be used to measure the speed of the angular motion transmitted from the swing motor assembly 21 to the swing drive 23 . as an alternative or for purposes of redundancy , a rotary position sensor 40 may be mounted to the swing sensor housing 22 . one or both of the sensors 33 , 40 may be used to determine the slue position and will be described in greater detail below in connection with fig1 - 13 . turning to fig3 , the swing sensor housing 22 may include a breather assembly 34 , a coupling opening 35 , which is used to accommodate and support a coupling end 36 of the target shaft 38 shown in fig4 . an additional opening 29 is provided for supporting the speed sensor 33 ( fig1 ), which may be used with the target shaft 38 and rotary position sensor 40 or instead of the target shaft 38 and rotary position sensor 40 . the studs 28 extend through the swing sensor housing 22 and may be used to secure the swing sensor housing 22 to the swing motor assembly 21 ( fig1 ) or , in other words , to sandwich the swing sensor housing 22 between the swing motor assembly 21 and the swing drive 23 . a series of fasteners 37 may be used to secure the swing drive cover plate 25 to the swing casing 24 . the target shaft 38 , the function of which will be described in greater detail in below , is illustrated in fig4 and may be used with a rotary position sensor 40 . again , as an alternative or as a back - up , a speed sensor 33 may be employed . the target shaft 38 may include a coupling end 36 and a sensor end 39 . bushings 41 may be used to support the target shaft for rotational movement within the swing sensor housing 22 as discussed below . the target shaft 38 may include a shaft portion 42 that may pass through a driven gear 43 . the shaft portion 42 may extend to the coupling end 36 or , as illustrated in fig4 , may pass through a separate sleeve 44 . the position and support of the target shaft 38 within the swing sensor housing 22 is illustrated in fig5 . the swing sensor housing 22 is illustrated in phantom for this purpose . the coupling end 36 of the target shaft 38 may be supported within a coupling opening 35 and the sensor end 39 of the target shaft 38 may be supported within a sensor opening 45 . the sensor housing 22 may include an upper opening 46 through which a splined drive shaft 47 ( fig6 - 7 ) may pass as well as through opening 59 through which the studs 28 may pass . turning to fig6 - 7 , the splined drive shaft 47 , target gear 48 , helical gear 49 and the coupling between the driven gear 43 and the target shaft 38 are illustrated . the splined drive shaft 47 may include a motor end 51 with a female splined opening 50 that may be coupled to the swing motor assembly 21 . the splined drive shaft 47 may pass through the target gear 48 as well as the helical gear 49 . as shown in fig7 , the splined drive shaft 47 may also include a swing drive end 60 , which may be splined , and which may be received in the sun gear 26 ( see fig2 and 5 ). the splined drive shaft 47 may pass through the helical gear 49 or the helical gear 49 may be an integral part of the splined drive shaft 47 . the target gear 48 may be held in place on the splined drive shaft 47 by one or more snap rings shown at 53 . a snap ring 54 can also be used to retain the coupling end 36 of the target shaft 38 in the coupling opening 35 ( fig3 ). an additional fastener such as a nut 55 may also be used to secure the bushings 41 in place against the sleeve 44 . the snap ring 56 ( fig7 ) may be used to secure the swing drive end 60 of the splined drive shaft 47 in the sun gear 26 ( fig9 ). turning to fig8 - 10 , and first to fig8 , the target gear 48 and motor end 51 of the splined drive shaft 47 are accommodated within the swing sensor housing 22 . as shown in fig9 , the coupling opening 35 may be enclosed by a cover 57 in suitable sealant or sealing members such as silicone or an o - ring . the distal end or swing drive end 60 of the splined drive shaft 47 may be received in the sun gear 26 and secured in place by the snap ring 56 . the sun gear 26 may be enmeshed with a plurality of planetary gears 58 as illustrated in fig9 . fig1 is a top view of the swing sensor housing 22 , particularly illustrating the opening 61 that receives the target gear 48 and splined drive shaft 47 . fig1 also illustrates the relative position of the target shaft 38 , which is shown in phantom and the rotary position sensor 40 . fig1 - 12 are sectional views of fig1 . in fig1 and 11 , it can be seen that the target shaft 38 may pass in close proximity to the speed sensor 33 . fig1 also illustrates the coupling or enmeshment between the helical gear 49 and the driven gear 43 of the target shaft 38 . fig1 also illustrates the female splined opening 50 for coupling the splined drive shaft 47 to the swing motor assembly 21 . fig1 illustrates the relative position between the target shaft 38 and the splined drive shaft 47 . the target shaft 38 may be supported in the sensor opening 45 and the coupling opening 35 by the bushings 41 . the driven gear 43 may be enmeshed with the helical gear 49 which rotates the target shaft 38 and the magnet or magnetized sensor end 39 of the target shaft 38 . rotation of the sensor end 39 in close proximity to rotary position sensor 40 provides a signal that reflects the number of rotations of the helical gear 49 and therefore the splined drive shaft 47 . this , in turn , can be directly converted to a slue position angle . thus , the slue positioning system 20 illustrated in fig1 - 12 may employ one speed sensor 33 , two speed sensors 33 , a rotary position sensor 40 / target shaft 38 or a combination of a speed sensor 33 and rotary position sensor 40 / target shaft 38 . fig1 illustrates the use of a speed sensor 33 in combination with a rotary position sensor 40 . fig1 illustrates the use of two speed sensors 33 . fig1 - 17 illustrate an embodiment applicable to equipment that does not include a target gear 48 . as shown in fig1 - 15 , and a lower frame 70 ( or undercarriage ) is rotatably coupled to an upper frame 71 by a ring gear 72 that is enmeshed with the swing gear 73 . the swing gear 73 is accommodated within a bearing 74 that is connected to the upper frame 71 . the lower frame 70 is connected to the ring gear 72 by one or more shafts or posts 75 . rotation of the upper frame 71 with respect to the lower frame 70 is detected and measured by the rotary position sensor assembly 80 , which is illustrated in greater detail in fig1 - 17 . turning to fig1 - 16 , rotary position sensor 40 is mounted to a cover 81 which encloses a slip ring assembly 82 ( see fig1 ). the cover 81 or the slip ring assembly 82 may be mounted to a swivel 83 . the swivel 83 may be a hydraulic swivel with a central passageway 84 and various ports shown at 85 in fig1 - 16 for the purpose of communicating hydraulic fluid between the upper and lower frames 70 , 71 . the swivel 83 includes an upper end 86 that is coupled to the upper frame 71 and a lower end 87 that is coupled to the lower frame 70 as best seen in fig1 . turning to fig1 , the upper end 86 of the swivel 83 includes a tab or fork 88 which is coupled to the upper frame 71 to maintain an alignment between the sensor 40 , cover 81 and the upper frame 71 . similarly , the lower end 87 of the swivel 83 also includes a tab 89 which is received in the fork 91 that is connected to the lower frame 70 to maintain an alignment between the magnet 92 , slip ring assembly 82 and lower frame 70 ( as well as lower end 87 of the swivel 83 ). as shown in fig1 , the rotary position sensor 40 is mounted on top of the cover 81 which encloses the slip ring assembly 82 . the slip ring assembly 82 is coupled to the upper end 86 of the swivel 83 . in operation , as the upper frame 71 rotates with respect to the lower frame 70 , the sensed element or magnet 92 rotates with respect to the rotary position sensor 40 , which has a fixed positional relationship with the upper frame 71 . the rotary position sensor 40 may be coupled to an electronic control module ( ecm ) 63 as shown . if the rotary position sensor assembly 80 of fig1 - 17 is not employed , a speed sensor 33 may be positioned above the swing gear 73 as illustrated in fig1 . regardless , the speed sensor 33 could be employed for the sake of redundancy . thus , a system for sensing or detecting the slue position of a machine , such as an excavator , crane , foundation drill , material handler , etc . is shown and described . one disclosed system may include a swing sensor housing sandwiched between a swing motor or swing motor assembly and a swing drive . the swing motor may be coupled to the swing drive assembly through the swing sensor housing . a rotary position sensor or a speed sensor may be used to measure the rotation of the target gear . as described above , the rotary position sensor or the speed sensor may be a mems based device . another disclosed slue position sensing system may be employed for upper and lower frames that rotate with respect to each other , such as an upper frame and an undercarriage of a wheel excavator that are rotatably coupled together by a ring gear and a swing gear . the upper frame is coupled to at least one of a rotary position sensor or speed sensor . when a rotary position sensor is employed , the rotary position sensor is part of an assembly that includes a slip ring assembly and a magnetized element disposed between the slip ring assembly and the rotary position sensor . the slip ring assembly is mounted to a swivel , one end of which is coupled to the upper frame and the other end of which is coupled to the lower frame . when a speed sensor is employed , the speed sensor is mounted to the upper frame in close proximity to the swing gear so the speed sensor can detect rotation of the swing gear . methods for retrofitting a swing motor and a swing drive assembly with a slue position sensing system are also disclosed . one disclosed method may include disassembling the swing motor from the swing drive and mounting a swing sensor housing between the swing motor and swing drive . a target gear may be installed in the swing sensor housing and may be coupled to a splined drive shaft that may be coupled to the swing motor through the swing sensor housing to the swing drive . a speed sensor or a rotary position sensor may be used to measure the rotation of the target gear for determining slue position . another method for retrofitting a swing drive assembly with a slue position sensing system includes providing an upper frame and a lower frame . the lower frame is coupled to a ring gear and the upper frame is coupled to a swing gear . the swing gear and ring gear are enmeshed so the upper frame may rotate about the ring gear . the method includes coupling at least one of a rotary position sensor or a speed sensor to the upper frame .
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an exemplary embodiment of the present invention will hereinafter be described in detail with reference to the accompanying drawings . it is understood that the term “ vehicle ” or “ vehicular ” or other similar term as used herein is inclusive of motor vehicles in general such as passenger automobiles including sports utility vehicles ( suv ), buses , trucks , various commercial vehicles , watercraft including a variety of boats and ships , aircraft , and the like , and includes hybrid vehicles , electric vehicles , plug - in hybrid electric vehicles , hydrogen - powered vehicles , fuel cell vehicles and other alternative fuel vehicles ( e . g . fuels derived from resources other than petroleum ). as referred to herein , a hybrid vehicle is a vehicle that has two or more sources of power , for example both gasoline - powered and electric - powered vehicles . additionally , it is understood that the below methods are executed by at least one controller . the term controller refers to a hardware device that includes a memory and a processor configured to execute one or more steps that should be interpreted as its algorithmic structure . the memory is configured to store algorithmic steps and the processor is specifically configured to execute said algorithmic steps to perform one or more processes which are described further below . furthermore , the control logic of the present invention may be embodied as non - transitory computer readable media on a computer readable medium containing executable program instructions executed by a processor , controller or the like . examples of the computer readable mediums include , but are not limited to , rom , ram , compact disc ( cd )- roms , magnetic tapes , flash drives , smart cards and optical data storage devices . the computer readable recording medium can also be distributed in network coupled computer systems so that the computer readable media is stored and executed in a distributed fashion , e . g ., by a telematics server or a controller area network ( can ). fig1 is an overall configuration diagram of a fuel cell system . referring to fig1 , the fuel cell system may include a stack 210 including a cooling channel , a fuel electrode , and an air electrode . the fuel cell system may include a filter 130 , a silencer 140 , a compressor 150 , an intercooler 160 , a humidifier 170 , and a discharge valve 180 as components that circulates air to the air electrode of the stack 210 . the fuel cell system may also include a coolant reservoir 105 , a radiator 120 , and a water pump 110 as components that circulate coolant to the cooling channel , and an ejector 100 , a humidifier 220 , a reservoir 202 , a purge valve 190 , and a drain valve 200 as components that supply hydrogen which is fuel to the fuel electrode . in the exemplary embodiment of the present invention , the related art is referred to for a detailed description of structures and functions of respective components of the fuel cell system and a detailed description thereof will be omitted . water is generated from the air electrode in a proton exchange membrane fuel cell ( pemfc ) of the stack 210 and conductivity of an electrode membrane is improved by moisture being supplied from the outside . that is , forming appropriate moisture to an mea is essential for proper operation . as illustrated , a humidifier is included in a line that is circulated to the air electrode and the humidifier is installed at a hydrogen supply side to achieve proper operation . however , a separate installation space is required to install a separate humidifier and piping may be complicated . moreover , the moisture ( h 2 o ) generated from the air electrode in the stack 210 is present in a liquid or vapor form depending on temperature and is transferred to the fuel electrode through a membrane of the air electrode due to a pressure difference . the amounts of water and vapor of the fuel electrode are changed depending on driving conditions and the water and vapor are discharged to the outside by a condensed water reservoir or drain valve through an appropriate method by reducing a hydrogen reaction . that is , an unbalanced driving pattern is provided in which the moisture is replenished from the outside in the air electrode and the moisture is discharged to the outside in the fuel electrode . fig2 is an overall configuration diagram of a fuel cell system having an ejector according to an exemplary embodiment of the present invention . fig3 is a partial detailed cross - sectional view of a fuel cell system having an ejector according to a first exemplary embodiment of the present invention . referring to fig2 and 3 , a part of the fuel cell system may include the stack 210 , the condensed water reservoir 202 , the ejector 100 , a fuel injection nozzle 255 , a mixture pipe 280 , a water injection nozzle 267 , a water supply line 265 , a heater 260 , a pressure sensor 280 , and a humidity sensor 282 . an intake chamber 275 is disposed inside the ejector 100 and the fuel injection nozzle 255 is disposed in the intake chamber 275 . a fuel injection aperture 270 is formed at the end of the fuel injection nozzle 255 the water injection nozzle 267 may be disposed inside the fuel injection nozzle 255 , and a water injection aperture 300 of the water injection nozzle 267 may be disposed at a center of the fuel injection aperture 270 of the fuel injection nozzle 255 . a fuel control valve 250 may be disposed in the system in order to control the flow of hydrogen which is the fuel supplied to the fuel injection nozzle 255 and a control unit 10 may be configured to control the fuel control valve 250 according to a driving condition including a load / pressure / humidity of the stack 210 . furthermore , a water supply line 265 may be provided in order to supply water to the water injection nozzle 267 . this water supply line 265 may extend downward into the condensed water reservoir 202 . when the fuel control valve 250 is opened by the control unit 10 , the hydrogen may be injected from the fuel injection aperture 270 of the fuel injection nozzle 255 . at this point , a vacuum is formed by the injected hydrogen . as a result , water is pulled through the water supply line 265 , and is injected from the water injection aperture 300 of the water injection nozzle 267 in to the fuel injection nozzle 255 . in the exemplary embodiment of the present invention , the amount of moisture discharged from the stack 210 of the fuel cell varies due to various factors including driving temperature , pressure , and the like . as such , the hydrogen injected by the fuel injection nozzle 255 has a sonic velocity ( mach = 1 , approximately 1200 m / s ) and the water is pulled into the fuel injection nozzle via vacuum pressure which is caused by the velocity . the water injected by the water injection nozzle 267 is atomized by the flow of the hydrogen to be mixed with the fuel . moreover , supply / mixture performance of the fuel and the water may be improved by intermittently opening the fuel control valve 250 . in the exemplary embodiment of the present invention , when a driving load is increased , an operating temperature of the stack is increased , an inlet of the fuel electrode becomes dry , and the amount of discharge water is increased . as described above , the discharged water is recirculated to the fuel electrode again to reduce a size of an external humidifier or omit the external humidifier altogether . fig4 is a partial detailed cross - sectional view of a fuel cell system having an ejector according to a second exemplary embodiment of the present invention . a description of similar parts will be skipped in fig4 as compared with fig1 to 3 and only a distinct difference will be described . referring to fig4 , a notch 400 is formed at the fuel injection aperture 270 of the fuel injection nozzle 255 . the notch 400 is formed inside the fuel injection aperture 300 ( fig3 ) in an a or v shape and turbulence intensity of the hydrogen injected from the fuel injection nozzle 255 is increased to minimize and unify a particle size and strengthen a mixture of the hydrogen and the recirculated gas . in the exemplary embodiment of the present invention , water injection may be suppressed under a low - load condition and the water injection may be performed under a set load or more . moreover , an inner diameter of the water supply line 265 may be controlled , an aperture ( not illustrated ) may be formed on the water supply line , or the height of the water supply line 265 may be controlled . in addition , a separate control valve ( not illustrated ) may be mounted on the water supply line 265 to actively control injection of water . further , a heater 260 ( fig2 ) may be applied to the mixture pipe 280 of the ejector 100 or the fuel recirculation line , and as a result , low - temperature operation efficiency may be improved by managing increasing the temperature of the water an internal circulation line . fig5 is a schematic configuration diagram of a fuel cell system having an ejector according to a third exemplary embodiment of the present invention . a description of similar parts will be skipped in fig5 as compared with fig1 to 4 and only a distinct difference will be described . referring to fig5 , the fuel cell system includes the stack 210 , the condensed water reservoir 202 , the ejector 100 , the mixture pipe 280 , and the control unit 10 . a main fuel injection nozzle 255 a is disposed at the center of the intake chamber 275 formed in the ejector 100 , and the control unit 10 controls a main hydrogen control valve 250 a to control the amount of hydrogen injected from the main fuel injection nozzle 255 a . a fuel injection nozzle 255 b may be disposed in the condensed water reservoir 202 and a water injection nozzle 267 may be disposed inside the fuel injection nozzle 255 b . the water supply line 265 may extend to supply water contained in the condensed water reservoir 202 to the water injection nozzle 267 . moreover , the control unit 10 may be configured to control a hydrogen control valve 250 b that regulates the amount of hydrogen supplied to the fuel injection nozzle 255 b . in addition , the amount of the water injected from the water injection nozzle 267 may also controlled according to the amount of hydrogen injected from the fuel injection nozzle 255 b . additionally , the fuel injection nozzle 255 b may be inclined to easily supply the fuel and the moisture to the ejector 100 from the condensed water reservoir 202 . fig6 is a schematic configuration diagram of a fuel cell system having an ejector according to a fourth exemplary embodiment of the present invention . a description of similar parts will be skipped in fig6 as compared with fig1 to 5 and only a distinct difference will be described . referring to fig6 , the main fuel injection nozzle 255 a is disposed at a center of the intake chamber 275 formed in the ejector 100 , and the control unit 10 may be configured to control the main hydrogen control valve 250 a to regulate the amount of hydrogen injected from the main fuel injection nozzle 255 a . in addition , a manifold 600 may be formed adjacent to the stack 210 and the hydrogen which is the fuel may be supplied to the stack 210 through the manifold 600 . the fuel injection nozzle 255 b may be disposed in the manifold 600 and the water injection nozzle 267 may be disposed inside the fuel injection nozzle 255 b . the water supply line 265 may extend into the condensed water reservoir 202 to supply the water contained in the condensed water reservoir 202 to the water injection nozzle 267 . moreover , the control unit 10 may be configured to control the hydrogen control valve 250 b to regulate the amount of hydrogen supplied to the fuel injection nozzle 255 b . in addition , the amount of water injected from the water injection nozzle 267 may also be controlled according to the amount of hydrogen injected from the fuel injection nozzle 255 b . fig7 is a schematic configuration diagram of a fuel cell system having an ejector according to a fifth exemplary embodiment of the present invention . fig7 is to compared with fig2 and a distinct difference will be described and a description of similar parts will be skipped . referring to fig7 , the fuel cell system may include an air condensed water reservoir 710 , a level sensor 720 , and a water supply control valve 730 . the air condensed water reservoir 710 may be a space that is disposed on an air circulation line that is circulated in the air electrode to condense and collect moisture included in air . the water supply line 265 may supply water gathered in a lower portion of the condensed water reservoir 202 and water gathered in a lower portion of the air condensed water reservoir 710 to the water injection nozzle 267 . in addition , the water supply control valve 730 may regulate the supply of the water contained in the air condensed water reservoir 710 . a level sensor 720 that senses stored water may be disposed in the air condensed water reservoir 710 , and the control unit 10 may be configured to determine a level of water through the level sensor 720 and control the water supply control valve 730 according to sensed level . that is , when it is determined that the level of the water contained in the air condensed water reservoir 710 is below a given value , the control unit 10 may close the water supply control valve 730 and when it is determined that the level of the water is equal to or higher than a set value , the control unit 10 may open the water supply control valve 730 . accordingly , air may be prevented from flowing into a line where the fuel of the fuel cell is circulated . fig8 a , 8b , and 8c are schematic configuration diagrams illustrating a method for heating hydrogen in the fuel cell system having an ejector according to the exemplary embodiment of the present invention . referring to fig8 a , the heater 260 may be installed within a hydrogen line supplied to the ejector 100 to heat hydrogen . referring to fig8 b , a heat exchanger may be installed within the hydrogen line supplied to the ejector 100 and coolant and hydrogen pass through the heat exchanger 800 and the hydrogen is heated by the coolant . referring to fig8 c , a heat exchanger 800 may be disposed within the hydrogen line supplied to the ejector 100 , condensed water may be discharged from the humidifier 170 through the discharge valve 180 and the discharged condensed water may pass through the heat exchanger 800 . the hydrogen may then be heated by the condensed water . fig9 is a schematic configuration diagram illustrating a position of a heat exchanger that heats hydrogen in the fuel cell system having an ejector according to the exemplary embodiment of the present invention . referring to fig9 , the stack 210 is installed at a front - wheel side of a vehicle and a hydrogen tank 900 is installed at a rear - wheel side . hydrogen is supplied from the hydrogen tank 900 to the stack 210 and the heat exchanger 800 is installed within a supply line . air discharged from the stack 210 to the outside may pass through the heat exchanger 800 and the discharged air heats the hydrogen . further , the discharged air can pass through the ejector housing 290 to heat the hydrogen passing the ejector housing 290 . fig1 a and 10b are a plan view and a side view illustrating a method for installing the ejector in the fuel cell system having an ejector according to the exemplary embodiment of the present invention . referring to fig1 a and 10b , the ejector 100 may be installed at an inlet side of a fuel supply manifold 101 , hydrogen may be injected from the ejector 100 and a to direction in which the hydrogen is injected and a longitudinal direction of the fuel supply manifold 101 may coincide with each other . moreover , recirculated combustion gas discharged from a fuel discharge manifold 102 may be supplied to the ejector 100 and new hydrogen gas may also be supplied to the ejector 100 . while this invention has been described in connection with what is presently considered to be practical exemplary embodiments , it is to be understood that the invention is not limited to the disclosed embodiments , but , on the contrary , is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims .
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the embodiments herein and the various features and advantageous details thereof are explained more fully with reference to the non - limiting embodiments that are illustrated in the accompanying drawings and detailed in the following description . descriptions of well - known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein . the examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein . accordingly , the examples should not be construed as limiting the scope of the embodiments herein . the embodiments herein provide devices and processes of fabricating ring - shaped devices ; i . e ., circular devices with a concentric hole . for example , the embodiments herein use nano - pillars as templates and a process that deposits some material to cover the sidewalls of the nano - pillars . embodiments herein benefit from the structure and processes described below , for example , by protecting the devices from shorting between layers of the device . referring now to the drawings , and more particularly to fig1 a through 7 , where similar reference characters denote corresponding features consistently throughout the figures , there are shown preferred embodiments . as described above , there is considerable interest in magnetic storage devices that include giant magnetic resistance devices and magnetic tunnel junctions especially in the form of rings . conventional systems , however , have been unable to reliably fabricate planar devices in the form of nano - rings . for example , conventionally fabricated planar devices ( e . g ., planar nano - rings ), which may include ferromagnetic layers , have a risk of creating short circuits between the different ferromagnetic layers that comprise the planar device . the embodiments described herein offer several improvements over conventional devices — for example , the embodiments herein minimize the risk of creating shorts between ferromagnetic layers and does not fabricate the individual devices in a serial fashion thus reducing the fabrication time . fig1 a and 113 illustrate schematic diagrams of planar device 1 in a closed ring geometry . while not shown , planar device 1 has active ferromagnetic films ( or layers , as described below ) and forms a closed ring . the geometry shown in fig1 a and 1b can have advantages over conventional devices in that planar device 1 may offer a small geometry ( as described below ) and thereby occupies less valuable area and does not have the domain walls ( e . g ., separating magnetic domains ) experienced by larger geometries . further , less energy is required to change the magnetization because there is no shape anisotropy . as shown in fig1 a and 1b , planar device 1 has two possible magnetization geometries ( e . g ., clockwise geometry 5 and counterclockwise geometry 10 ). the embodiments shown in fig2 a through 6 illustrate various steps used to fabricate planar device 1 . fig2 a , with reference to fig1 , illustrates a substrate 20 and a plurality of nano - pillars 25 affixed thereto . nano - pillars 25 further include a diameter 30 and each nano - pillar 25 is separated by spacing 35 . while not shown in the embodiment of fig2 a , each nano - pillar 25 has roughly the same diameter 30 to create a uniform array of nano - pillars 25 of spacing 35 . for example , in one embodiment herein , each nano - pillar 25 has a diameter 30 approximately equal to 30 nanometers and spacing 35 ( i . e ., the space between individual nano - pillars 25 ) is approximately equal to 50 nanometers . in addition , the embodiment shown in fig2 a also includes nano - pillars 25 with nearly vertical sidewalls 27 . while not shown , nano - pillars 25 of the embodiment shown in fig2 a are insulating pillars ( e . g ., oxide nano - pillars ). in addition , while not shown in the embodiment of fig2 a , spacer pillars may also be deposited on the edge of substrate 20 ( e . g ., on the edge of a wafer , where the wafer includes substrate 20 ). in such embodiment , these spacer pillars prevent subsequent masks from touching nano - pillars 25 . furthermore , although not shown , the embodiment of fig2 a uses photolithographic techniques to mask , standard deposition techniques to deposit material , and etching and lift off techniques to remove excess material from substrate 20 . an alternative embodiment is shown in fig2 b where each of the nano - pillars 25 may also include a cap 26 . in the embodiment shown , caps 26 are used to minimize the possibility of shorting between the ferromagnetic layers ( as described in further detail below ). the following is an example how the structure in fig2 b can be fabricated . a layer of silicon dioxide , which becomes the nano - pillars 25 followed by a layer of silicon , which becomes the cap 26 , is deposited or grown on substrate 20 . electron beam lithography can be used define the diameter of the nano - pillars 25 and silicon caps 26 . reactive ion etching can be used to remove the unwanted silicon and leave the silicon caps 26 . suitable etching with hydrofluoric ( hf ) acid can be used to remove the unwanted silicon dioxide and create the pillars . controlling the conditions of the hf step allows undercutting the silicon caps 26 as shown in fig2 b . fig3 a through 7b , with reference to fig2 a and 2b , illustrate various embodiments herein . according to fig3 a through 3d , a first embodiment is illustrated . in the first embodiment , a lithography plus vertical deposition process is provided . here , the process is shown to continue after the configuration of fig2 a . a sequential layering is applied to substrate 20 and nano - pillars 25 including a conducting , metallic layer that constitutes a first electrode 40 , followed by an anti - ferromagnetic pinning layer 45 , and then a first ferromagnetic layer 50 . next , as shown in fig3 b , a tunnel barrier layer 55 , and a second ferromagnetic layer 60 are deposited . the tunnel barrier layer 55 may be deposited using either atomic layer deposition ( to cover all exposed surfaces ) or the tunnel barrier layer 55 may be deposited at an angle while rotating substrate 20 ( e . g ., rotating a wafer that includes substrate 20 ). possible tunnel barrier materials include crystalline magnesium oxide ( mgo ). in so doing , in the embodiment of fig3 b , the tunnel barrier layer 55 covers the sidewalls 27 of nano - pillars 25 . those of ordinary skill in the art will recognize that other embodiments may include alternative and / or additional materials in tunnel barrier layer 55 and may include alternative and / or additional deposition techniques to cover sidewalls 27 of nano - pillars 25 . the thickness of the tunnel barrier layer 55 is controlled and kept sufficiently thin ( i . e ., approximately 1 nanometer ) to optimize the electron tunneling . while not explicitly , shown , the deposition in the embodiments of fig3 a and 3b is made with the atoms of the corresponding deposited material ( e . g ., layers 40 , 45 , 50 , 60 ) coming down normal to the surface of the substrate 20 thereby minimizing the deposition of material on sidewalls 27 of nano - pillars 25 . the tunnel barrier layer 55 deposition should be made so the sidewalls 27 of the nano - pillars 25 are covered . consequently , the embodiments of fig3 a and 33 minimize deposited metallic material on sidewalls 27 . next , as shown in fig3 c , a planarization step occurs down to the second ferromagnetic layer 60 on the portion of the stacked layers on top of substrate 20 with the nano - pillars 25 being planarized as well so that the top of layer 60 is co - planar with the top of nano - pillars 25 . thereafter , a conducting , metallic layer that constitutes a second electrode 65 is deposited . finally , as shown in fig3 d , the nano - ring structures 75 , having diameter d o , are formed by performing a photolithographic technique and etching to remove the excess material down to the first electrode 40 . according to fig4 a through 4c , a second embodiment is illustrated . in the second embodiment , a lithography plus cap process is provided . here , the process is shown to continue after the alternative configuration of fig2 b . a sequential layering is applied to substrate 20 and caps 26 including the first electrode 40 , followed by the anti - ferromagnetic pinning layer 45 , and then the first ferromagnetic layer 50 . in this embodiment , the first electrode 40 , anti - ferromagnetic pinning layer 45 , and first ferromagnetic layer 50 are deposited with the atoms coming down vertically to minimize the number of the atoms being deposited under the cap 26 near the sidewalls 27 of the nano - pillars 25 . then , the caps 26 and overlying material are removed by etching . next , the tunnel barrier layer 55 is deposited . the material of the tunnel barrier layer 55 fills the space between the three - layer stack of the first electrode 40 , anti - ferromagnetic pinning layer 45 , and first ferromagnetic layer 50 and the sidewalls 27 of the nano - pillars 25 . thereafter , the second ferromagnetic layer 60 is deposited on the tunnel barrier layer 55 . these steps minimize the likelihood of shorting between the two ferromagnetic layers 50 , 60 . after a planarization step that removes the nano - pillar 25 down to the level of the top of the second ferromagnetic layer 60 , the second electrode 65 is deposited with the resulting structure shown in fig4 b . finally , as shown in fig4 c , the nano - ring structures 75 , having diameter d o , are formed by performing a photolithographic technique and etching to remove the excess material down to the first electrode 40 . according to fig5 a through 5e , a third embodiment is illustrated . in the third embodiment , a sidewall spacer plus vertical deposition process is provided . here , the process is shown to continue after the configuration of fig2 a . a sequential layering is applied to substrate 20 and nano - pillars 25 including a first electrode 40 , followed by an anti - ferromagnetic pinning layer 45 , a first ferromagnetic layer 50 , a tunnel barrier layer 55 , and a second ferromagnetic layer 60 as illustrated in fig5 a . the metallic layers are deposited vertically to minimize covering the sidewalls 27 of the nano - pillars 25 and minimize creating shorting . one can then cover the sidewalls 27 of the nano - pillars 25 with a sidewall spacer 63 and then perform an etching process as shown in fig5 b that removes material down to the top of the first electrode 40 . now the space that has been etched is filled with sio 2 80 as shown in fig5 c . upon completion of this step , the surface is planarized by mechanical polishing down to the top of the second ferromagnetic layer 60 . at this point lithography is performed and the second electrode 65 is deposited as shown in fig5 d . the nano - ring structures 75 , having diameter d o , are defined by the thickness of the sidewall spacer 63 . the last step shown in fig5 e is to remove the sio 2 80 by etching down to the first electrode 40 . according to fig6 a through 6d , a fourth embodiment is illustrated . in the fourth embodiment , a sidewall spacer plus cap process is provided . here , the process is shown to continue after the configuration of fig4 a with a sequential layering having been applied to substrate 20 and caps 26 including the first electrode 40 , followed by the anti - ferromagnetic pinning layer 45 , and then the first ferromagnetic layer 50 . then , the caps 26 and overlying material are removed . next , the tunnel barrier layer 55 is deposited along the sidewalls 27 of the nano - pillars 25 all the way down to the substrate 20 . thereafter , the second ferromagnetic layer 60 is deposited on the tunnel barrier layer 55 . these steps minimize the likelihood of shorting between the two ferromagnetic layers 50 , 60 . the resulting structure is shown in fig6 a . after this , as illustrated in fig6 b , sidewall spacer material 63 is deposited to define the thickness of the ensuing nano - rings . next , the stack of films 40 , 45 , 50 , 55 , and 60 are etched . then , the space is again filled with silicon dioxide 80 . after a planarization step in which the planarization is performed to the top of the second ferromagnetic layer 60 , the second electrode 65 is deposited with the resulting structure shown in fig6 c with the nano - ring structures 75 having diameter d o . the last step shown in fig6 d is to remove the sio 2 80 by etching down to the first electrode 40 . a fifth embodiment , not specifically shown , is to start with the configuration shown in fig3 a . next , one can etch the sidewalls 27 of the nano - pillars 25 after depositing the first ferromagnetic layer 50 to create a space that will be filled when the tunnel barrier layer 55 is deposited . this prevents shorting . from the above , one can easily see other variations of this embodiment . fig7 , with reference to fig1 a through 6d , illustrates cross - sectional top view of the substrate 20 with nano - ring structure 75 , nano - pillar 25 , first electrode 40 , and second electrode 65 . it is noted that , in an alternative embodiment , the first electrode 40 may be deposited and structurally defined prior to the creation of nano - pillars 25 . the foregoing description of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can , by applying current knowledge , readily modify and / or adapt for various applications such specific embodiments without departing from the generic concept , and , therefore , such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments . it is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation . therefore , while the embodiments herein have been described in terms of preferred embodiments , those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the appended claims .
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fig1 is software flowchart view of a software application process in sequence from the moment a user is logged in successfully . it consists of an authoring module 10 , which allows the author to assort data ( text , audio , images ) appropriate for event , and to predetermine the tasks for the quizzes ( questions and answers , words and their correct spelling convention etc . ), along with the order in which the tasks will be presented . the authoring module 10 is supplying information to the quiz database 12 . they are the prerequisites for the quiz . the quiz database 12 is storing and managing the data created in the authoring module 10 , and sending it to the user interface upon demand . it may contain text , audio , images or similar information . the transmitting module sends the information to the quiz interface 14 in predefined order . a optional timer 16 may be used for limiting the total time available for each task . it monitors the time allowed for each task based on settings predetermined by the system administrator . it also provides visible feedback regarding time restrictions . the session terminator 18 will be terminating the session when a task is completed incorrectly or not completed in time . the final score registration 20 is computing and finalizing the user &# 39 ; s test score and submitting it to the user database 44 for storage . the user database 44 is maintaining and storing the session data of users . if used for fundraising purposes , this component may offer the option to “ buy a second chance ,” so that the session can be reactivated for another trial . the task trigger 42 is then triggering the quiz database 12 to display the next task to the user . the competition ends at the predetermined day and time . no further activity by the user is accepted and the final ranking table 28 starts processing the user scores . the final ranking table 28 sorts the scores of various users from highest to lowest score and other pre - defined criteria and ranks the users accordingly . it then sends the data on to the report generator 30 . the report generator 30 generates reports based on the information provided by final ranking table 28 and user database 44 that summarize the quiz session . it generates virtual reports and graphics or documents suitable for printout . the format chosen along with which user data is displayed or hidden is based on system administrator &# 39 ; s directives . the optional certificate mailer 32 generates documents or certificates that communicate the results of the quiz to the user , transmitted online , via email , mail or other suitable means . fig2 is software flowchart view of a procedure to verify that parameters for a user to log in are correct before the quiz session starts . the initial user registration 34 module allows the user to register with the program and to create a computer id that associates the user &# 39 ; s performance with the right user account . this user registration 34 then sends the identifying information to the user database 44 and creates a new account . the log - in module 36 is used to provide a means of verification of the true identity of the participating user , as well as of payment or other pre - qualifying requirements . it may also allow the user to choose which quiz to participate in , if more than one is offered . the identity verification engine 38 compares the data entered in the log - in module 36 with the associated user entry in the user database 44 and creates a record for the new quiz in the user database . the optional payment processor 40 secures payment if an entry fee is part of the quiz before allowing the user to proceed . the optional supervision verification 46 is an additional feature to ensure fair completion of the quiz in compliance with the competition standards , and without the use of non - allowed aids . this optional supervision verification 46 functionality can be provided by requesting that the quiz be taken in a certain environment and under supervision of a registered supervisor — a teacher , librarian , test administrator , for example . activating a web cam or automatically detecting the use of disallowed aids such as online dictionaries etc . maybe additional features utilized here . after successful completion of the prior steps , the task trigger 42 starts the quiz . since other modifications and changes varied to fit particular operating requirements and environments will be apparent to those skilled in the art , the invention is not considered limited to the example chosen for purposes of disclosure , and covers all changes and modifications which do not constitute departures from the true spirit and scope of this invention . having thus described the invention , what is desired to be protected by letters patent is presented in the subsequently appended claims .
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considering the drawings , wherein like reference numerals denote like parts throughout the various drawing figures , reference numeral 10 is directed to a impulse monitoring system : apparatus and method for determining impulse events of assets in the form of , for example , rotating and / or reciprocating machines . in its essence , and referring to the drawings , an embodiment of the invention provides a system 10 : apparatus and method for receiving , digitizing , transforming , compressing , storing , transmitting , and displaying transducer measurement data correlative to machine status in which the measurement data is continuously sensed by at least one transducer 20 , and digitized , transformed , compressed , and displayed by monitor 30 and computerized monitoring system 100 for determining impulse events of machines by , for example , comparing relative magnitudes to other known magnitudes or other measurements of the machine and / or relative to its own history ( e . g ., is it getting stronger or weaker ) and identifying emerging problems , correlating them to machine operation to determine probable cause , and formulating some proactive action to alleviate the problem . the system 10 also determines an event timing to be able to accomplish event correlation to other machine events ( such as suction and discharge valve operation , rod reversal , et cetera ), and determines relative magnitudes of the events so they can be compared historically to previous records . more specifically , and referring to fig1 , one embodiment of the system 10 is comprised of a monitor 30 including a sampling / digitizing device or analog to digital converter ( a / d ) device 40 , a processing device 50 , and an associated memory 60 . the analog to digital converter 40 is operatively coupled to at least the one transducer 20 via connection 22 and also to the processing device 50 via connection 42 . in turn , the processing device 50 is operatively coupled to the associated memory 60 as discussed below and includes a maximum and minimum ( max / min ) transform means 70 and a filter means 72 . each transducers 20 , 24 can take the form of a seismic or inertial transducer which is operatively coupled to an asset such as machine m for making , for example , bearing housing , casing , or structural vibration measurements from the machine and each outputting analog transducer measurements or an analog electrical signal indicative machine status . seismic transducers are well known in the art and a wide variety of seismic transducers such as velocity transducers and acceleration transducers are manufactured by bently nevada , llc , 1631 bently parkway south , minden ; nev ., usa 89423 . at least one transducer 20 is operatively coupled , via connection 22 , to the analog to digital converter device 40 for receiving , sampling and digitizing the analog signal from at least the one transducer 20 indicative of asset or machine status and transmitting the digitized signal to processing device 50 via connection 42 . the processing device 50 can provide a control signal to the analog to digital converter device 40 for sampling the analog signal at , for example , a known sampling rate . additionally , the processing device 50 can be comprised of one or more processors each having an associated memory such as one or more digital signal processors ( dsp ) 50 and associated memory 60 . the processing device 50 receives the digitized signal outputted from the analog to digital converter device 40 via connection 42 and , in turn , preferably employs filter 72 for filtering the sampled waveform with , for example , a low pass such as a butterworth filter and then , the processing means employs the max / min transform means 70 for determining a plurality of maximum and minimum sample or digital packets each comprising a maximum and a minimum value from a plurality of samples of the filtered digitized signal taken during predefined degrees of rotation of a rotating element of the asset for defining a location and a maximum and minimum value to each of the plurality of digital packets wherein each digital packet location is defined by each predefined degree of rotation of the rotating element thereby transforming the analog signal outputted by at least the one transducer 20 into the plurality of maximum and minimum sample or digital packets each having a unique identified location . the system 10 then further compresses the analog signal outputted by the transducer 20 by only storing in memory 60 , preferably consecutively , each maximum and minimum value in each digital packet including its associated location , for example , first a maximum and then a minimum per each predefined degree of rotation for defining a waveform of maximum and minimum values associated with a unique location or predefined degree of rotation . monitor 30 may be used to compare the maximum and minimum values and locations to previously known values for determining impulse events based on the comparison step such as , for example , having at a particular location a maximum and / or minimum meeting or exceeding a predefined criteria based on the previously known values . furthermore , and in one embodiment of the invention , fig1 shows that the monitor 30 can also include a controller or microcontroller 80 operatively coupled to the processing device 50 such that the processing device 50 and associated memory 60 are connected , via connections 82 ( data bus ), 84 ( address bus ), and 86 ( control lines ), to each other and to the controller 80 . the monitoring system 30 and thus , the processor 50 including the max / min transform 70 and filter 72 , may be programmed via the microcontroller 80 or other external computer . additionally , and in one embodiment of the invention , the system 10 is further comprised of a computerized condition monitor 100 operatively coupled to the monitoring system 30 via connection 102 . the computerized condition monitor 100 can be a laptop , notebook , desktop , networked , and / or a distributed computer or the like . computerized condition monitor 100 is generally comprised of software running on a processing and storage means or device 104 comprised of a processor , memory , and storage medium . the processing and storage device 104 is operatively coupled to at least one entry device such as a selection or mouse device 106 , and / or a keyboard 108 and also , to a graphical user interface 110 including a display 112 . communication between a user , the processing and storage device 104 , and the monitor 30 is done through the graphical user interface 110 such that the computerized condition monitor 100 can be employed for displaying , for comparison , the defined maximum and minimum value waveform with a known waveform and / or criteria for determining any impulse events based on the comparison step which can be done visually or computationally via the computerized condition monitor 100 . the computerized condition monitor 100 and monitor 30 can be programmed to provide bi - directional communication via connection 102 and thus , provide the means for communicating , among other things , the digitized analog electrical signals engendered from the transducer 20 and transformed by the monitor 30 and transmitted to the computerized condition monitor 100 for displaying , for comparison purposes , the defined maximum and minimum waveform with a known waveform and for determining any impulse events based on the comparison step such as by having the maximum and / or minimum at a location meeting or exceeding a predefined criterion for a same location on the known waveform . hence , impulse events can be determined visually or computationally via the system 10 . the monitor 30 can further include a digital to analog converter 90 operatively coupled to the controller 80 via connection 91 , to the processing device 50 via connection 92 , and / or to the computerized condition monitor 100 via connection 102 for providing , for example , means for receiving and conveying information , via connection 93 , to physical output devices 94 such as relay outputs , current output such as 4 - 20 ma outputs , and communication links between processors or monitors and other external platforms for , among other things , generating alarms 96 based on determined impulse events and using the alarms to automatically shut down the machine m being monitored by at least the one transducer 20 and / or automatically annunciate machinery problems to operators and other plant personnel . one or more power supplies 98 are operatively coupled to provide any required power to transducers 20 , 24 , monitor 30 , physical output devices 94 , and / or computerized condition monitor 100 . referring to fig2 , in combination with fig1 , and in light of the above description , one method embodiment of the invention for determining impulse events of a machine correlative to machine status includes the steps of : 1 ) monitoring a machine with at least one transducer outputting an electrical signal correlative to machine status ; 2 ) sampling the electrical signal into a digitized signal ; 3 ) transforming the digitized signal into a plurality of digital packets by determining for each of the plurality of digital packets a maximum and a minimum value of the digitized signal taken over a sampling range correlated to a predefined degree of rotation of a rotating element of the machine and each of the plurality of digital packets having a location defined by the correlated predefined degree of rotation of the rotating element over which it was sampled for transforming and compressing analog transducer measurements into the plurality of digital packets each having a unique location ; 4 ) comparing the values of the plurality of digital packets to known values ; and 5 ) determining impulse events based on the comparison step for providing machine protection . the above steps in the above method can be further comprised of any one or more of the following : step 1 can further include the step of monitoring vibration of a reciprocating or rotating machine with at least one transducer outputting an electrical signal correlative to machine status ; step 2 can further include the step of sampling and digitizing the electrical signal into a digitized vibration signal at a known sampling rate ; step 3 can further include the step of employing a digital signal processor and associated memory for transforming the digitized vibration signal into a plurality of digital packets by filtering the digitized vibration signal and then determining , for each of the plurality of digital packets , a maximum and a minimum value of the filtered digitized vibration signal taken over the sampling range correlated to a predefined degree of rotation of a rotating element of the machine and each of the plurality of digital packets having a location defined by the correlated predefined degree of rotation of the rotating element over which it was sampled for transforming and compressing analog transducer measurements or outputs into the plurality of digital packets each having a unique location for use in identifying impulse events based on the comparison step ; step 3 can further include the step of consecutively storing each of the plurality of digital packets and its associated location , for example , first a maximum and then a minimum per each predefined degree of rotation for defining a waveform of max / min values for each unique predefined degree of rotation ; step 4 can further include the step of displaying for comparison the defined waveform with a known waveform for determining any impulse events based on the comparison step such as by having the maximum and minimum meeting or exceeding a predefined criterion based on the known waveform for visually or computationally determining impulse events ; step 5 can further include the step of generating alarms based on impulse events determined based on the comparison step of comparing the maximum and minimum values at particular locations to previously known values and using the alarms to automatically shut down the machine being monitored by the transducer and / or automatically annunciate machinery problems to operators and other plant personnel . a specific example follows for further explaining the system 10 ( apparatus and method ) and how the system 10 solves the problems discussed hereinabove . to describe the solution by way of example , data was taken from a hydrogen compressor crosshead and valve cover using accelerometers such as transducers 20 , 22 coupled to the hydrogen compressor asset m . the data was gathered from these locations at a sample rate of 262 . 1 k samples per second . the machine was operating at 276 rpm so a single revolution is : 262 . 1 k samples / sec 276 rpm = 262100 * 60 samples / 276 rev = 56980 samples / rev this data was considered as the infallible truth and used as a guiding principle or base line for the system . fig3 shows a graphical view of the base line data for a single revolution of throw number 2 . the two plots on the graph represent the accelerometer data on the crosshead and on the suction valve . specifically , fig3 shows two plots 120 , 122 of two signals from respective transducers 20 , 24 being sampled at the base line sample rate of 262 , 100 samples per second or 56 , 980 samples per revolution and plotted with voltage values versus crank angle in degrees . the two plots 120 , 122 on the graph of fig3 represent , respectively , the accelerometer data on a crosshead and on a suction valve of the hydrogen compressor machine m . recognizing that the data sample rate of one typically used monitoring system is 64 , 000 samples per second , and that the base line data is sampled at a higher rate than the 64 , 000 samples per second rate resulted in the conclusion that the input data has to be decimated in order to represent the raw analog to digital samples that this typical monitor would have available to process . this data results in the plots shown in fig4 . particularly , fig4 is a graphical representation of two plots 124 , 126 from the two signals from the two respective transducers 20 , 24 which have been sampled at the 64 , 000 samples per second rate and plotted on a plot of voltage values versus crank angle in degrees . it can be seen from fig4 , in comparison with fig3 , that even at this sample rate , some of the high magnitude data around − 7 . 5 and − 9 . 5 volts does not show in the 64 , 000 samples per second data . if we were able to plot every sample for each revolution of the crankshaft , the plot in fig4 is what we would get , and represents the very best that this typical monitor could do if it could save every a / d sample for a revolution of the crankshaft . however , to accomplish this would require that the monitor support a 13 , 913 - point waveform . in contrast , data that is typically obtained from other measurement points in the reciprocating compressor application is set at 360 or 720 points per revolution . when set at 720 points , the waveforms are gathered by picking a sample every ½ degree of crankshaft rotation for a total of 720 points . so if we agree to only return 720 points for the cycle above , we can simulate this by performing the 720 - point sample picking from the 64 , 000 samples per revolution data and would result in the waveform shown in fig5 . fig5 is a graphical view of two 720 - point sample plots 128 , 130 respectively obtained by picking 720 samples from each of the two 64 , 000 samples per revolution plots 124 , 126 shown in fig4 . as can be seen , the data sample rate aliases the data so that the original waveform shape and content is severely changed . a requirement is that there will be an ability to correlate the impulse events to operational events in the compressor . comparing the two plots reveals that the peak magnitudes have been altered and much of the form of the waveform has been lost . this is primarily due to the aliasing effect of sampling . from this plot it is difficult to determine what is a real impulse event and when aliasing gives the impression of an event . this plot emphasizes our conclusion that we must consider enough samples such as all of the analog to digital base line samples in a revolution to adequately describe the data shape . remember that our intent is to determine the magnitude and location of an impulse event , but still be able to present the data in an abbreviated set of data points such as no more than 720 points of data . hence , in one aspect , the invention includes a method of preserving the information performing a process of looking at enough samples such as all base line samples , and for each degree ( or fraction thereof ) of crankshaft rotation determining the maximum and the minimum values and recording them . this gives us the highest and lowest points of the modulation to a 1 - degree resolution ( or fraction thereof ) so we can accurately assess the location to within 1 degree ( or fraction thereof ) and the magnitude of the impulse event . then , this data is alternatively ( e . g . first the maximum then the minimum ) stored in a waveform file in memory in monitor 30 and / or in computer 100 thereby resulting in a compressed 720 point data file . the result can then be plotted in the same fashion as other waveforms for comparison such as with other 720 points per revolution waveforms used in a reciprocating compressor plot group . fig6 shows the resulting plot . specifically , fig6 shows is a graphical view of two 720 - point sample plots obtained by 720 samples picked from results of the impulse monitoring system transforming each of the two 262 , 100 samples per revolution plots shown in fig3 . that is , the system 10 uses , for example , all the base line samples and for each degree ( or fraction thereof ) of crankshaft rotation it determines the maximum and the minimum value for obtaining a plurality of maximum and minimum sample or digital packets , and then , records them resulting in a modulation envelope which is preserved , as are as the impulse data locations or events in the cycle as shown in fig6 . hence , each maximum and minimum sample packet includes a unique location defined by each predefined degree of rotation of the rotating element such that the system 10 transforms analog transducer measurements into a plurality of maximum and minimum sample packets each having a unique location , and then continues to compress the analog transducer measurements by consecutively storing only the maximum and minimum packets and their associated locations , for example , first a maximum and then a minimum per each predefined degree of rotation for defining a waveform of maximum and minimum values for each unique predefined degree of rotation for further analysis such as comparing the max / min values to previously known values for determining any impulse events based on the comparison step such as by having the maximum and minimum meeting or exceeding a predefined criterion based on the previously known values . additionally , in one embodiment of the invention the system 10 is further comprised of the computerized condition monitor 100 operatively coupled to the monitoring system 30 for displaying for comparison the defined waveform with a known waveform and for determining any impulse events based on the comparison step such as by having the maximum and minimum meeting or exceeding a predefined criterion based on the known waveform . hence , impulse events can be determined visually and / or computationally via the computerized condition monitor 100 and monitor 30 . fig7 is a graphical view providing a better understanding of one embodiment of the invention by showing a selection of data from 270 to 300 degrees of rotation with the selection being an overlay of the sample picked data plots 128 , 130 shown in fig5 on the 64 , 000 sampled data plots 124 , 126 shown in fig4 . fig8 is a graphical view providing a better understanding of one embodiment of the invention by showing a selection of data from 270 to 300 degrees of rotation with the selection being an overlay of the transformed data plots 132 , 134 shown in fig6 overlaid on the 64 , 000 sampled data plots 124 , 126 shown in fig4 . the maximum and minimum values for each degree of rotation are reflected in the plot shown in fig9 . specifically , fig9 is a graphical view of a selection of data from 270 to 300 degrees of rotation with the selection being the transformed data plots 132 , 134 shown in fig6 without the 64 , 000 sampled data plots 124 , 126 shown in fig4 thereby more clearly showing the alternating maximum and minimum values plotted in fig8 by leaving out the 64 , 000 sampled data plots 124 , 126 shown in fig4 . one method embodiment of the invention for determining asset impulse events is to identify the sources of impulses so that action can be taken to manage machinery . much of the high frequency signal is generated as acoustic noise in the process flow through piping , valves and in the cylinder . the high frequency signal is transmitted through the case and can give valuable information on valve leaks , restrictions or metal - on - metal rubs . impulse events that excite the natural resonances occur at lower frequencies and can be masked by the high frequency acoustic noise . one method looks for the impulse events in a waveform that is filtered . resonance frequencies occur in the several hundred hertz range , so if we filter the data with a cutoff of 1 khz , the acoustic signals should be filtered out and the impulse events should be easier to locate . referring to fig1 , a graphical view is shown of two plots obtained from passing the same 64 , 000 sampled data plots shown in fig4 through a 1 khz low pass filter ( butterworth ). referring to fig1 , a graphical view is shown of two 720 - point sample plots obtained by picking 720 samples from each of the two 64000 samples per revolution plots which have been passed through the 1 khz low pass filter . referring to fig1 and 11 reveals that some events appear to be retained in the waveform after the filtering but when we apply the 720 - sample selection currently done in the monitors to this data the plot reveals differences between the plots ( on the crosshead curve ) around 50 degrees of rotation . referring to fig1 , a graphical view is shown of two 720 - point sample plots obtained by picking 720 samples from each of the two results from the impulse monitoring system transforming each of the two 262 , 100 samples per revolution plots which have been passed through a 1 khz low pass filter resulting in the data around 50 degrees being preserved better than in the sample picking methods . because the frequency content is lower , the aliasing is considerably less than when looking at the unfiltered signals . hence , the maximum / minimum transform will fit within the existing waveform data format of existing reciprocating compressor data presentations , gives a good representation of the modulation and allows event detection to the resolution needed to allow correlation between the max / min plot and others included in a reciprocating compressor plot group . the typical monitoring system employed in the above example is a 3500 monitoring system manufactured and sold by bently nevada , llc located in minden , nev . u . s . a . in use and operation , and referring to the drawings , one embodiment of the invention provides impulse monitoring system 10 : apparatus and method which can be embodied in a machinery protection system monitoring rotating and / or reciprocating machines or mechanical systems . in this embodiment , the system 10 is operatively coupled to at least the one transducer 20 operatively coupled to the rotating or reciprocating machine m for monitoring the machine and outputting an analog signal to the system 10 indicative of machine status . the monitor 30 of system 10 includes analog to digital converter 40 operatively coupled to at least the one transducer 20 for receiving , sampling , and digitizing the outputted analog signal into a digitized signal . in turn , the a / d converter 40 is operatively coupled to processor 50 including a filter 72 for filtering the digitized signal and further including a max / min transform 70 for transforming the filtered digitized signal into a plurality of maximum and minimum sample or digital packets each having a maximum and minimum value taken from values of a plurality of samples of the filtered digitized signal taken during predefined degrees of rotation of a rotating element of the asset for defining a location and a maximum and a minimum value to each of the plurality of digital packets wherein each digital packet location is defined by each predefined degree of rotation of the rotating element thereby transforming the analog signal outputted by at least the one transducer 20 into the plurality of maximum and minimum sample or digital packets each having a unique identified location . the processor device 50 can then continue to compress the analog signal outputted by the transducer 20 by only storing , preferably consecutively , each maximum and minimum value of each sample packet and its associated location , for example , first a maximum and then a minimum per each predefined degree of rotation for defining a waveform of maximum and minimum values associated to a unique predefined degree of rotation . the monitoring system 30 may be used to compare the maximum and minimum values at particular locations to previously known values at the same location for determining impulse events based on the comparison step for providing machine protection . the comparison step can also include displaying , for comparison , the defined waveform with a known waveform for visually or computationally determining impulse events via computerized condition monitor 100 . additionally , alarms can be generated based on determined impulse events in the form of , for example , automatically shutting down the machine being monitored by the transducer and / or automatically annunciating machinery problems to operators and other plant personnel . hence , in one aspect , the present invention provides a system 10 : apparatus and method for identifying impulse events on machines by using inertial sensors with monitor 30 and computerized condition monitor 100 for detecting the higher frequency magnitudes of the impulse events and the position in the rotation ( for rotating machinery ) or the location of the piston in its stroke ( for reciprocating machinery ) when impulse events occur . additionally , for the case of reciprocating compressors , individual alarm magnitude set point limits can be set for different banded crank angle increments . further , banded crank angle increments can be set to “ track ” other machine events , such as rod reversal , suction valve opening or closing , discharge valve opening or closing , et cetera . in another aspect , the present invention provides a system 10 : apparatus and method that determines impulse events which occur in the operational cycle of the machine and compares their relative magnitudes to other events of the machine and / or relative to their own history ( e . g . are they getting stronger or weaker ) such that emerging problems are identified , correlated to a probable cause , and alleviated by a formulated proactive action . in another aspect , the present invention provides a system 10 : apparatus and method for processing asset data for retaining event timing to be able to accomplish event correlation ( to other machine events such as suction and discharge valve operation , rod reversal , etc ), and retaining relative magnitudes of the events so they can be compared historically to previous records for monitoring impulse events . these aspects , among other things , demonstrate industrial applicability of this invention . moreover , having thus described the present invention , it should be apparent that numerous modifications and adaptations may be resorted to without departing from the scope and fair meaning of the present invention as set forth hereinabove and as described herein below by the claims .
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in general , the teachings herein provide for a label assembly that includes at least one or any combination of a base layer , an adhesive layer , a handling layer , a cut - out portion and a channel portion . the cut - out portion may extend through one or any combination of the base layer , the adhesive layer and the handling layer . the base layer may have first and second surfaces and may be in planar contact with one or more of the adhesive layer and the handling layer . the adhesive layer may be in planar contact with the second surface of the base layer . the handling layer may be in planar contact with the adhesive layer so that the adhesive layer is located between the base layer and the handling layer . the channel portion may be located so that it covers at least a portion of the cut - out portion . the present invention further provides for a label assembly that includes an adhesive label having a first surface and a second opposing surface that can be customized and modified while in use by placing a removable insert within a channel portion of the label assembly . the label assembly may include printed material on both the first and second opposing surface of the base layer . the adhesive layer may permit the label assembly to be adhered to a first surface , removed from the first surface , and adhered to a second surface . the adhesive layer may permit transfer to a plurality of surfaces without a substantial reduction in adhesion strength of the adhesive layer . the channel portion may or may not be covered with the adhesive layer . the channel portion may be located on the first surface of the base layer , the second surface of the adhesive label , or both the first and second surface of the base layer . the label assembly includes a base layer . the base layer may be substantially planar . the base layer includes a first surface and an opposing second surface . the base layer may include at least a portion that is substantially planar . the base layer may include a top edge , a bottom edge and one or more side edges . the base layer may include only three edges . the base layer may be circular , having only one edge . the top edge and bottom edge may be substantially parallel . the base layer may include a pair of substantially parallel side edges . the base layer may comprise a substantially continuous material layer . alternatively , the base layer may include one or more cut - out portions . the base layer may be formed of a flexible material . the base layer may be formed of a substantially rigid material . the base layer may be formed of a flexible material having a coating or additional material layer placed thereon to impart increased rigidity to the base layer . as discussed further herein , the base layer may be contacted with an adhesive layer that may provide increased rigidity to the base layer material . the base layer may also be contacted with a handling layer so that the handling layer provides increased rigidity to the base layer . the base layer may include one or more cut - out portions . the one or more cut - out portions may be formed by removing a portion of the base layer . the base layer material may be die - cut to remove a portion of the base layer , thus creating the cut - out portion . the one or more cut - out portions may be confined within the edges of the base layer so that the one or more cut - out portions do not contact any edges of the base layer . the cut - out portion may be formed so that a portion of the cut - out portion contacts one or more edges of the base layer so that an opening is created along one or more edges of the base layer . the cut - out portion may include one or more side edges . the cut - out portion may include at least two side edges that are substantially parallel to one another . the cut - out portion may include only one continuous side edge . the side edges of the one or more cut - out portions may be substantially parallel to one or more side edges of the base layer . each side edge of the cut - out portion may be substantially parallel to a side edge of the base layer . the one or more cut - out portions may have four side edges , each side edge being substantially parallel to at least one side edge of the base layer . the length of each side edge of the one or more cut - out portions may be shorter than the length of any side edge of the base layer . the length of each side edge of the one or more cut - out portions may be shorter than the length of at least one side edge of the base layer . the shape of the cut - out portion may be similar to that of the base layer . for example , both the base layer and cut - out portion may both have a rectangular shape . alternatively , the base layer and cut - out portion may have different shapes . as an example , the base layer may be rectangular in shape and the cut - out portion may be circular in shape . the cut - out portion may also encompass the majority of the base layer , so that only a small amount of base layer exists while the majority of the label assembly is comprised of the cut - out portion . each of the one or more cut - out portions includes a front face and a back face . the front face of the cut - out portion may be adjacent the first surface of the base layer , while the back face of the cut - out portion is adjacent the second surface of the base layer . the faces of the one or more cut - out portions may be covered by additional material layers that contact the base layer or that contact other additional material layers . as an example , one or both faces of the one or more cut - out portions may be covered by the handling layer . the one or more cut - out portions may be covered by the adhesive layer on one or more faces . one or more faces of the cut - out portion may remain exposed ( e . g ., uncovered ) by any additional material layer . the base layer may be contacted with an adhesive layer . the adhesive layer may allow the label assembly to adhere to a surface . the adhesive layer may be such that the label assembly can be adhered to a first surface , removed from the first surface , and adhered to a second surface and / or any number of additional surfaces . the adhesive layer may be a substantially permanent adhesive so that the label assembly is difficult to remove from a substrate , thus deterring theft of the label assembly . the adhesive layer may be located on the entire base layer . the adhesive layer may be located upon only a portion of the base layer . alternatively , the base layer may include one or more mechanical fasteners for fastening the label assembly to a surface . the base layer may include no means for attachment , but may be placed onto a substrate that includes an adhesive or mechanical fastening means to attach the label assembly to the substrate . any adhesive layer may be contacted with a handling layer so that a tacky surface of the label assembly is not exposed prior to use . as an example , the handling layer may cover any portions of the base layer that are contacted by the adhesive layer . the handling layer may be flexible to allow for bending of the label assembly . the handling layer may be substantially planar . the handling layer may be placed in direct planar contact with the adhesive layer . the handling layer may also lie substantially parallel in relation to the base layer . one or more faces of the cut - out portion may be covered by a channel portion . the channel portion may be formed so that it can receive an insert . the channel portion may be formed of a single continuous portion of material . the channel portion may be formed of multiple connected portions of material . the channel portion may include one or more folded edges . the one or more folded edges of the channel portion may be fastened to the base layer , the adhesive layer , the handling layer , or any material layer included within the label assembly . the one or more folded edges of the channel portion may be fastened to the base layer ( or any material layer included within the label assembly ) via an adhesive layer ( e . g ., adhesive tabs ). the adhesive layer ( e . g ., adhesive tabs ) may be located along the perimeter of the cut - out portion . the channel portion may be fastened via a mechanical fastener such as a pin , clip , staple or the like . the one or more folded edges may contact areas of the base layer that are adjacent ( e . g ., located at the perimeter of ) the one or more cut - out portions . the channel portion may include two folded edges so that two remaining edges are open and the open edges can receive the insert . the channel portion may be scored along the folded edges or at locations adjacent the folded edges to promote folding of the edges and prevent bowing of the channel portion . the scoring may be increased as the thickness of the intended insert decreases so that the folded edges form a thinner channel . alternatively , the scoring may be reduced to receive inserts having increased thickness . one open edge may include a stopper or may be adhered or mechanically fastened to the base layer to further prevent an insert from becoming dislodged from the channel portion . the folded side edges may be formed as channels located along the top and bottom edges of the cut - out portion . the channels may thus receive an edge of an insert . alternatively , the channel portion may also be formed of a continuous portion of material that is folded to form an envelope . the side edges of the envelope may be fastened ( e . g ., adhered ) together so that the channel portion includes only one open edge for receiving a removable insert . the only one open edge may be the top edge or may be a side edge . the envelope formed may be large enough so that it can hold a plurality of coupons , brochures , or other informational material that can be retrieved by consumers or other individuals to which information should be supplied . the removable insert may be planar so that it includes a top surface and a bottom surface . the top surface and bottom surface may include printed information so that the printed information can be viewed from both the first surface and second surface of the base layer . the printed information on the top surface and bottom surface of the removable insert may be identical . the removable insert may have a one or more side edges . the removable insert may have any shape or form so that it fits within the channel portion . the removable insert may include two substantially parallel side edges . the removable insert may include a top edge and a bottom edge . the top edge and bottom edge of the removable insert may be substantially parallel to one another . the lengths of each side edge and the top and bottom edge may correspond to the lengths of the channel portion so that the removable insert fits securely within the channel portion to prevent the removable insert from becoming unintentionally detached from the channel portion . the thickness of the removable insert may be such that the insert can slide into the channels created by the channel portion . however , the removable insert preferably has a thickness that prevents the insert from easily falling out of the channel portion during use . the base layer and removable insert discussed herein may be composed of a pliable material to provide flexibility to the label assembly . a particular feature of the material may be that it is durable enough to resist tearing during attempts to place and remove the label assembly . the base layer and removable insert may be formed of the same material , or of different materials . the base layer and removable insert may be formed of paper materials including but not limited to paperboard , chipboard , cardboard , fiberboard , natural fibers , mineral fibers or any combination thereof . the material may be a virgin material , a post - consumer recycled material , or both . the material may be a recyclable material and / or a biodegradable material . if the base layer and / or removable insert material includes paperboard , the paperboard may be a bleached or unbleached paperboard . for example it may be a solid bleached sulfate ( sbs ) paperboard . the base layer and removable insert may be formed of a more rigid material , such as a polymeric material including but not limited to thermoplastics , thermoset plastics , elastomer containing materials or any combination thereof . examples of polymeric materials that may be employed include polyamide , polyester , polystyrene , polyethylene ( including polyethylene terephthlate , high density polyethylene and low density polyethylene ), polypropylene , polyvinyl chloride , bio - based plastics / biopolymers ( e . g ., poly lactic acid ), silicone , acrylonitrile butadiene styrene ( abs ), or any combination thereof . the base layer and removable insert may also be composed of a paper - based material that includes a coating , which may be a polymeric coating , to enhance the strength and / or rigidity of the label assembly . the coating may be a film layer . common plastic films that may be used include nylon , polyvinyl chloride , polypropylene , high - density polyethylene , low - density polyethylene , linear low - density polyethylene , polyvinylidene chloride and combinations thereof . the film layer may be any material with sufficient transparency for viewing information printed onto the base layer and / or removable insert . the channel portion may be composed of any material having sufficient transparency so that any printed information located on the removable insert may be viewed through the channel portion . the channel portion may be formed of a more rigid material , such as a polymeric material including but not limited to thermoplastics , thermoset plastics , elastomer containing materials or any combination thereof . examples of polymeric materials that may be employed include polyamide , polyester , polystyrene , polyethylene ( including polyethylene terephthlate , high density polyethylene and low density polyethylene ), polypropylene , polyvinyl chloride , bio - based plastics / biopolymers ( e . g ., poly lactic acid ), silicone , nylon , acrylonitrile butadiene styrene ( abs ), or any combination thereof . the adhesive layer may include one or more adhesives for adhering at least a portion of base layer to a substrate . the adhesive may be capable of adhering to multiple types of substrates , including both rigid and flexible substrates . such substrates may include , but are not limited to glass , polymeric materials , metal , paper - based materials , woven materials and the like . suitable adhesives may include synthetic adhesives such as polymeric ( e . g ., thermoplastic , elastomeric , emulsion or thermosetting ) adhesives . the adhesive may also include a bioadhesive such as starch , casein or albumin based adhesives . the adhesive may also include a uv curing adhesive . the adhesive may be a pressure sensitive adhesive such as a fugitive adhesive . as shown for example in fig1 and 2 , the label assembly may include a base layer 10 , and adhesive layer 12 , and a handling layer 14 . the base layer 10 includes a first surface 16 and a second opposing surface 18 . the base layer further includes a top edge 20 , a bottom edge 22 , and two substantially parallel opposing side edges 24 ( shown at fig3 ). a cut - out portion 26 may be located within the base layer 10 . the cut - out portion 26 includes a top edge 28 , a bottom edge 30 and two substantially parallel side edges 32 ( shown at fig3 ). the cut - out portion 26 includes a front face 34 and a back face 36 ( shown at fig5 ). the front face 34 of the cut - out portion may be covered with a channel portion 38 . the channel portion 38 may be located onto the first surface 16 of the base layer 10 via adhesive tabs 40 . the channel portion 16 includes two folded edge portions 42 that create channels 44 for receiving an insert ( not shown ). the adhesive layer 12 may be located in planar contact with the second surface 26 of the base layer 10 . the handling layer 14 may be located in planar contact with the adhesive layer 12 . as shown for example in fig2 , the handling layer 14 may be removed so that the adhesive layer 12 is exposed and the base layer 10 may be adhered to a substrate . as shown in fig3 , the channel portion 38 is attached to the first surface 16 of the base layer 10 . the channel portion 38 is composed of a single continuous transparent sheet 46 that includes two folded edge portions 42 that create channels 44 for receiving a removable insert 48 . the removable insert has a top surface 50 and a bottom surface 52 ( shown in fig5 ). the top surface 50 of the removable insert 48 is arranged adjacent the first surface 16 of the base layer 10 . fig4 shows the base layer 10 attached to a substrate 54 via the adhesive layer 12 . the substrate may be a substantially transparent substrate having two opposing surfaces ( a front surface 56 and a rear surface 58 ( shown in fig5 )). note that the removable insert 48 can be removed from within the channel portion 38 while the base portion 10 is adhered to the substrate 54 . fig5 shows the base layer 10 adhered to a substrate 54 as viewed from the rear surface 58 of the substrate 54 . the back face 36 of the cut - out portion 26 remains uncovered and the bottom surface 52 of the removable insert 48 is visible and uncovered . note that prior to removal of the handling layer , the back face of the cut - out portion 26 and bottom surface 52 of any removable insert 48 located within the channel portion 38 may not be covered by the handling layer . fig6 shows the removal of the removable insert 48 from within the channel portion 38 so that a second removable insert 60 may be located within the channel portion 38 as shown in fig7 . the label assembly may be shipped to the customer in one assembled piece , whereby an adhesive layer is included and the channel portion is already attached to the base layer . alternatively , the label assembly may be shipped without an integrated adhesive layer , but may include a separate adhesive or mechanical fastener . the customer may provide a separate adhesive or mechanical fastener . the label assembly may be shipped to the customer in two pieces , whereby the channel portion is not attached to the base layer . again , an adhesive or mechanical fastener may be provided to the customer for attaching the channel portion to the base layer or the customer may provide the adhesive or mechanical fastener for attaching the channel portion to the base layer . the label assembly as disclosed herein provides a two - sided label assembly where the information can be frequently modified while the label is in use and the label can be viewed from two opposing surfaces of a transparent substrate during use . the label assembly may be beneficial in advertising or any other capacity where it is necessary to transmit information while still maintaining the ability to quickly modify the information as needed . the label assembly further provides such benefits at a minimal cost , whereas digital signage provides similar benefit at extremely high cost . the label assembly further provides a means to remove the assembly from one location and adhere the assembly to another location multiple times with little or no damage to the label assembly . any numerical values recited herein include all values from the lower value to the upper value in increments of one unit provided that there is a separation of at least 2 units between any lower value and any higher value . as an example , if it is stated that the amount of a component or a value of a process variable such as , for example , temperature , pressure , time and the like is , for example , from 1 to 90 , preferably from 20 to 80 , more preferably from 30 to 70 , it is intended that values such as 15 to 85 , 22 to 68 , 43 to 51 , 30 to 32 etc . are expressly enumerated in this specification . for values which are less than one , one unit is considered to be 0 . 0001 , 0 . 001 , 0 . 01 or 0 . 1 as appropriate . these are only examples of what is specifically intended and all possible combinations of numerical values between the lowest value and the highest value enumerated are to be considered to be expressly stated in this application in a similar manner . as can be seen , the teaching of amounts expressed as “ parts by weight ” herein also contemplates the same ranges expressed in terms of percent by weight . thus , an expression in the detailed description of the invention of a range in terms of at “‘ x ’ parts by weight of the resulting polymeric blend composition ” also contemplates a teaching of ranges of same recited amount of “ x ” in percent by weight of the resulting polymeric blend composition .” unless otherwise stated , all ranges include both endpoints and all numbers between the endpoints . the use of “ about ” or “ approximately ” in connection with a range applies to both ends of the range . thus , “ about 20 to 30 ” is intended to cover “ about 20 to about 30 ”, inclusive of at least the specified endpoints . the disclosures of all articles and references , including patent applications and publications , are incorporated by reference for all purposes . the term “ consisting essentially of ” to describe a combination shall include the elements , ingredients , components or steps identified , and such other elements ingredients , components or steps that do not materially affect the basic and novel characteristics of the combination . the use of the terms “ comprising ” or “ including ” to describe combinations of elements , ingredients , components or steps herein also contemplates embodiments that consist essentially of the elements , ingredients , components or steps . by use of the term “ may ” herein , it is intended that any described attributes that “ may ” be included are optional . plural elements , ingredients , components or steps can be provided by a single integrated element , ingredient , component or step . alternatively , a single integrated element , ingredient , component or step might be divided into separate plural elements , ingredients , components or steps . the disclosure of “ a ” or “ one ” to describe an element , ingredient , component or step is not intended to foreclose additional elements , ingredients , components or steps . it is understood that the above description is intended to be illustrative and not restrictive . many embodiments as well as many applications besides the examples provided will be apparent to those of skill in the art upon reading the above description . the scope of the invention should , therefore , be determined not with reference to the above description , but should instead be determined with reference to the appended claims , along with the full scope of equivalents to which such claims are entitled . the disclosures of all articles and references , including patent applications and publications , are incorporated by reference for all purposes . the omission in the following claims of any aspect of subject matter that is disclosed herein is not a disclaimer of such subject matter , nor should it be regarded that the inventors did not consider such subject matter to be part of the disclosed inventive subject matter .
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referring now to fig1 , self - checkout system 10 includes attendant computer 12 , self - checkout terminals 14 , and attendant communicator 40 . attendant computer 12 includes processor 16 , sound circuitry 18 , and wireless communication circuitry 20 . processor 16 executes lane management software 26 , speech generating software 28 , and speech recognition software 30 . lane management software 26 receives status information and automated intervention requests from self - checkout terminals 14 . lane management software 26 is configured to recognize and respond to messages from self - checkout terminals 14 . speech generating software 28 works with sound circuitry 18 to convert the requests to sound signals . speech recognition software 30 works with sound circuitry 18 to convert speech signals to digital or software instructions directed to lane management software 26 . wireless communication circuitry 20 wirelessly transmits the sound signals to attendant communicator 40 . wireless communication circuitry 20 wirelessly receives speech signals from attendant communicator 40 . the attendant wears attendant communicator 40 and may additionally carry portable scanner 48 . attendant communicator 40 includes wireless communication circuitry 42 , speakers 44 , and microphone 46 . attendant communicator 40 may include a headset worn by the attendant . wireless communication circuitry 42 wirelessly receives sound signals from wireless communication circuitry 20 and sends the sound signals to speakers 44 . wireless communication circuitry 42 further receives speech signals from microphone 46 and wirelessly transmits the speech signals to wireless communication circuitry 20 . wireless communication circuitry 20 and 42 may include radio frequency ( rf ) communication circuitry . wireless communication circuitry 42 additionally includes amplification circuitry and a battery for amplifying received sound signals and speech signals . portable scanner 48 preferable includes a wireless handheld scanner for scanning large items . portable scanner 48 may decode bar code labels or send undecoded bar code information to self - checkout terminals 14 via wireless communication circuitry 20 and attendant computer 12 . attendant computer 12 further includes display 22 and input device 24 . display 22 displays status information and intervention requests provided by lane management software 26 . input device 24 records attendant selections in response to intervention requests . attendant computer 12 and self - checkout computers 14 are preferably coupled together via a network . self - checkout terminals 14 execute self - checkout software 34 , which process self - service transactions . self - checkout software 34 generates intervention requests and sends the intervention requests to attendant computer 12 . in operation , an attendant wears communicator 40 so as to communicate remotely with attendant computer 12 . if the attendant is called to one of self - checkout terminals 14 by a customer or by self - checkout software 34 to verify an identification card , scan a large item , or provide other assistance , the attendant receives status information and intervention requests through speakers 42 . the attendant may speak a response into microphone 44 rather than walk back to attendant computer 12 . table i below illustrates typical tasks of a self - checkout attendant , information supplied to the attendant , and actions taken by the attendant . turning now to fig2 , example operation of attendant computer 12 is illustrated in detail beginning with start 50 . in step 52 , lane management software 26 waits for an intervention request from self - checkout software 34 . in step 54 , lane management software 26 receives a request from self - checkout software 34 in connection with an attempted purchase of a product . for example , suppose self - checkout software 34 at one of self - checkout terminals 14 determines that a scanned item is an alcohol product that can only be sold to persons aged 21 or older . self - checkout software 34 sends attendant computer 12 an intervention request . the attendant may be located at attendant computer 12 or may be walking among self - checkout terminals 14 , viewing what is happening or assisting customers with questions posed directly to the attendant . in step 56 , lane management software 26 sends a message to the attendant . lane management software 26 wirelessly sends the message to attendant communicator 40 and displays the message on display 22 . speech generating software 28 works with sound circuitry 18 to convert the requests to audio messages . preferably , audio messages and spoken responses from the attendant are standardized to make communication easier . wireless communication circuitry 20 wirelessly transmits the sound signals to attendant communicator 40 . the attendant receives the message through attendant communicator 40 and walks over to self - checkout terminal 14 and determines the age of the customer by checking his driver &# 39 ; s license . the attendant speaks into microphone 46 , “ lane one age 25 ”. in step 58 , lane management software 26 receives a response from the attendant either allowing or denying the purchase . wireless communication circuitry 20 wirelessly receives speech signals from attendant communicator 40 . speech recognition software 30 works with sound circuitry 18 to convert speech signals to software responses directed to lane management software 26 . in step 60 , lane management software 26 sends a response to self - checkout software 34 , in the same way as if the attendant were responding through input device 24 . operation returns to step 52 to wait for another intervention request from any of self - checkout terminals 14 . table i task audio messages attendant speech customer “ age validation attendant walks to lane one , purchases an required , lane looks at the customer &# 39 ; s age restricted one ” plays identification and speaks into item on lane through speakers microphone 44 “ lane one age 25 ” one 42 customer on lane “ unpurchased attendant walks to lane three three places an item in bag , lane and determines if an unpurchased three ” unpurchased item is in the bag . item in a bag the attendant can then remove the item . customer on “ unpurchased attendant walks to lane three lane three places item in bag . lane and asks the customer to remove a purse on a bag three ” the purse . attendant may then scale , triggering approve the transaction by an unpurchased speaking , “ lane three approve .” item violation customer bags an “ wrong item attendant walks to lane two , item after bagged , lane two ” and speaks , “ lane two approve ”, scanning it on if correct item is bagged . lane two , but lane management software 26 detects an incorrect weight on a bag scale customer at lane none . attendant walks to lane one , one appears and speaks , “ scan lane one ” to unable to lift and instruct the system that the scan a large item . next item scanned with the attendant &# 39 ; s handheld wireless scanner should be part of lane one &# 39 ; s transaction . the attendant then scans the item for the customer on lane one . advantageously , the attendant is able to walk among self - checkout terminals 14 while still being able to handle requests . the invention reduces transactions times and allows the attendant to process more customers . finally , the invention may reduce shrinkage . a headset communicator allows the attendant to operate in a “ hands - free ” mode , which makes tasks such as helping with a scan or validating an identification card easier . although the invention has been described with particular reference to certain preferred embodiments thereof , variations and modifications of the present invention can be effected within the spirit and scope of the following claims .
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the present invention may be used in the cervical , lumbar , or thoracic regions of the spine . some components of the embodiment described herein , such as the cage bodies , are preferably made of biocompatible oxpekk , a poly - ether - ketone - ketone sold under the registered trademark of oxford performance materials , inc ., enfeld , conn ., usa . alternative embodiments contemplate fabrication from biocompatible peek ( poly - ether - ether - ketone ). oxpekk has approximately one - and - a - half to two times the compressive strength of peek , and therefore may be suited for constructing the cage body . in addition to the foregoing , it should be noted that , while the embodiments described herein are solid bodies , they may also be formed as porous bodies , as described in u . s . application ser . no . 612 / 952 , 788 ( filed nov . 23 , 2010 ), entitled “ spinal cage device ” and incorporated by reference herein . while the terms “ upper ,” “ lower ,” “ front ,” “ rear ,” and similar terms are used throughout this document , it should be expressly understood that such are simply terms of convenience only to aid in description of the invention , and the orientation of the invention disclosed herein after during implantation is primarily within the surgeon &# 39 ; s discretion . a first embodiment 18 of the invention is shown in fig1 - 5 . fig1 is an assembly view of the first embodiment 18 , which comprises a cage body 20 having upper and lower walls 22 , 24 with ridges 26 . upper and lower walls 22 , 24 partially define a cavity 28 of the cage body 20 . openings 30 through the upper and lower walls 22 , 24 provide access to the cavity 28 to allow for bone growth thereinto from adjacent vertebrae . a piston 32 having upper and lower angled surfaces 34 , 36 is insertable into the cavity 28 through a piston opening in the posterior sidewall of the cage body 20 to engage and drive nails 56 . piston screws 38 may thereafter be inserted through a piston faceplate 40 and secured to screw mounts 42 located in the cavity 28 near the posterior opening . fig2 a - 2c show the cage body 20 is greater detail . upper and lower rails 44 , 46 extend along the length of , and protrude into the cavity 28 from , the upper and lower wails 22 , 24 , respectively . screw mounts 42 are located near the posterior side of the cavity 28 . openings 30 through the upper wall 22 and lower wall 24 provide access the cavity 28 to allow for bone growth thereinto from adjacent vertebrae . cylindrical channels 31 are located between the two openings 30 and provide a cylindrical path through the upper wall 22 to the cavity 28 . a pair of cylindrical channels ( not shown ) is disposed through the lower wall in similar fashion and aligned with the upper channels 31 . fig3 a - 3c show the piston 32 of the first embodiment in greater detail . the piston 32 has upper and lower angled planar surfaces 34 , 36 approximately sixty degrees apart . upper and lower grooves 48 , 50 are formed longitudinally along the piston 32 and extend between the faceplate 40 and the upper and lower angled planar surfaces 34 , 36 . the grooves 48 , 50 are alignable with , and during insertion guide the piston 32 along , upper and lower rails 44 , 46 ( see fig2 a ), respectively , of the cage body 20 . shoulders 52 are formed in the piston body having a thickness t1 . engagement surfaces 53 are located between the shoulders 52 and the angled surfaces 34 , 36 . fig4 a and 4b show a titanium nail 56 and bushing 58 of the first embodiment in greater detail . the nail 56 is generally cylindrical and has a nail head 60 of thickness ti at a proximal end and tapers to a point 62 at the distal end . the nail head 60 has an angled portion 64 corresponding to the angled surfaces 34 , 36 of the piston 32 ( see fig3 a - 3c ). the upper end 66 of the bushing 58 corresponds in shape to the upper wall 22 ( see fig2 a - 2c ) such that , when assembled , the bushing 58 is flush with the ridges 26 of the upper surface of the cage body 20 ( see , e . g ., fig5 a ). fig5 a and fig5 b are an isometric view and a top elevation view , respectively , of the first embodiment 18 with the nails 56 in a second engaged position . during implantation , the angled portions 60 of the nail heads 60 ( see fig4 a - 4b ) are contacted by and become flush with the angled surfaces 34 , 36 of the piston 32 ( see fig3 a - 3c ), which , as the piston 32 is inserted further into the cavity 28 , causes the nails 56 to move upwardly through the channels 31 . in this manner , engagement of the upper angled surface 34 with the nail head 60 causes movement of the piston 32 into the cavity 28 to drive the nail 56 into the adjacent vertebra above the embodiment 18 . similarly , engagement of the lower angled surface 36 with nail heads causes movement of the piston 32 into the cavity 28 to drive lower nails ( not shown ) into the adjacent vertebra below the embodiment . after complete insertion of the piston 32 , each nail head 60 becomes flush with the corresponding engagement surface 53 to prevent the nail 56 from receding back into the cavity 28 . this ensures fastening of the nail 56 to adjacent bone matter . the upper and lower rails 44 , 46 ( see fig2 a , 2 c ) occupy the upper and lower grooves 48 , 50 , respectively , to ensure proper alignment of the piston 32 within the cavity 28 . the ridged bushings 58 are fitted within the channels 31 in the annular space between the nail 56 and channel walls to facilitate slidable movement of the nail 56 therein . by threading the screws 38 through the faceplate 40 and the screw mounts 42 , the piston 32 is drawn into the cavity 28 and secured to the cage body 20 . a second embodiment 118 of the invention , shown in fig6 - 10 , comprises a cage body 120 having upper and lower walls 122 , 124 with ridges 126 . upper and lower walls 122 , 124 partially define a cavity 128 of the cage body 120 . openings 130 through the upper and lower walls 122 , 124 provide access to the cavity 128 to allow for bone growth thereinto from adjacent vertebrae . a piston 132 having upper and lower angled planar surfaces 134 , 136 is insertable into the cavity 128 through a piston opening in the posterior wall of the cage body 120 . screws 138 may thereafter be inserted through a piston faceplate 140 and secured to screw mounts 142 located in the cavity 128 proximal to the piston opening . fig7 a - 7c show the cage body 120 of the second embodiment is greater detail . fig7 a and 7c are bottom and top elevations , respectively , of the cage body 120 . fig7 b is a rear elevation of the cage body 120 . upper and lower rails 144 , 146 extend along the length of , and protrude into the cavity 128 from , the upper and lower walls 122 , 124 , respectively . screw mounts 142 are located near the rear side of the cavity 128 . openings 130 through the upper and lower walls 122 , 144 provide access to the cavity 128 to allow for bone growth thereinto from adjacent vertebrae . as shown in fig7 a , a channel 131 is located between the two openings 130 and provides a path through the lower wall 124 to the cavity . as shown in fig7 b , two channels 133 are located between the two openings 130 and provide a path through the upper wall 122 to the cavity 128 . fig8 a and 8b show the piston 132 of the second embodiment 118 in greater detail . the piston 132 has upper and lower angled surfaces 134 , 136 angled approximately sixty degrees apart . upper and lower grooves 148 , 150 are formed longitudinally along the piston 132 from the faceplate 140 to the upper and lower angled surfaces 134 , 136 . upper and lower grooves 148 , 150 are alignable with , and during insertion guide the piston 132 along , upper and lower rails 144 , 146 ( see fig7 b ) of the cage body 120 . shoulders 152 are formed in the piston body having a thickness t2 . engagement surfaces 153 are located between the shoulders 152 and the angled surfaces 134 , 136 . fig9 a and 9b show a titanium pin 156 and bushing 158 , respectively , of the second embodiment 118 in greater detail . each pin 156 has an angled engagement surface 160 that corresponds to the angle of the upper and lower angled surfaces 134 , 136 of the piston 132 ( see fig8 b ). each pin 156 tapers to a wedge 162 at the distal end . the upper end 166 of the bushing 158 corresponds in shape to the upper wall 122 ( see fig7 a - 7c ) such that , when assembled , the bushing 158 is flush with the ridges 126 of the upper surface of the cage body 120 ( see , e . g ., fig1 ). fig1 is a perspective view of the second embodiment 118 with the pins 156 in an engaged position . during implantation , the angled engagement surfaces 160 ( see fig9 a - 9b ) of the pins 156 are contacted by and become flush with the upper and lower angled surfaces 134 , 136 of the piston 132 , which , as the piston 132 is inserted further into the cavity 128 , causes the pins 156 to move through the channels 131 , 133 to an engaged position . in this manner , engagement of the upper and lower angled surfaces 134 , 136 with the pins 156 causes movement of the piston 132 into the cavity 128 to drive the pins 156 into the adjacent vertebra . the piston screw heads are positioned anterior of the posterior surface of the faceplate 140 . after insertion of the piston 132 is complete , each engagement surface 160 is flush with the engagement surfaces 153 of the piston to prevent the pins 156 from receding back into the cavity 128 and ensuring fastening of the pins 156 with adjacent bone matter . the upper and lower rails 144 , 146 ( see fig7 b ) occupy the upper and lower grooves 148 , 150 , respectively , of the piston 132 to ensure proper alignment of the piston 132 within the cavity 128 . the ridged bushings 158 are fitted within the upper and lower channels 131 , 133 in the annular space between the pin 156 and channel wails to facilitate movement between disengaged and engaged positions . a third embodiment 218 of the invention , shown in fig1 - 15 , comprises a cage body 220 having upper and lower walls 222 , 224 with ridges 226 . upper and lower walls 222 , 224 partially define a cavity 228 . openings 230 through the upper and lower wall 222 , 224 and sidewalls provide access to the cavity 228 to allow for bone growth thereinto from adjacent vertebrae . upper and lower lock openings 225 , 227 are formed through the upper and lower walls , 222 , 224 , respectively proximal to a piston opening in the posterior wall of the cage body 220 . a piston 232 having upper and lower angled surfaces 234 , 236 is insertable into the cavity 228 through the piston opening . a screw 238 may thereafter be inserted through a piston faceplate 240 and secured to a screw mount 242 located at the posterior of the cavity 228 . a locking plate 280 having a closed end 283 and an opened end 284 defined by upper and lower fingers 286 , 288 is rotatably attached to the faceplate 240 with a locking member screw 282 . fig1 a - 12c show the cage body 220 in greater detail . a screw mount 242 is located near the front of the cavity 228 . openings 230 through the upper wall 222 provide access to the cavity 228 to allow for bone growth thereinto from adjacent vertebrae . rectangular channels 231 , 233 are located between the openings 230 and provide paths through the upper wall 222 and lower wall 224 to the cavity . as shown in fig1 c , upper and lower rails 244 , 246 extend along the length of , and protrude into the cavity 228 from , the upper and lower walls 222 , 224 , respectively . fig1 a - 13c show the piston 232 , piston screw 238 , and locking plate 280 of the third embodiment in greater detail . the piston 232 has upper and lower angled surfaces 234 , 236 angled approximately sixty degrees apart . upper and lower grooves 248 , 250 are formed longitudinally along the piston 232 between the faceplate 240 and the upper and lower angled surfaces 234 , 236 . upper and lower grooves 248 , 250 are alignable with , and during insertion guide the piston 232 along , upper and lower rails 244 , 246 ( see fig1 c ) of the cage body 220 . shoulders 252 are formed in the piston body having a thickness t3 . engagement surfaces 253 are located between the shoulders 252 and the upper and lower angled surfaces 234 , 236 . fig1 a - 14d show a titanium pin 256 and bushing 258 , respectively , of the third embodiment 218 in greater detail . each pin 256 has an angled engagement surface 260 that corresponds to the angle of the upper and lower angled surfaces 234 , 236 of the piston 132 ( see fig1 c ). each pin 256 tapers to an angled wedge 262 at the distal end . the upper end 266 of the bushing 258 corresponds in shape to the ridged upper surface ( see fig7 a - 7c ) such that , when assembled , the bushing 258 is flush with the ridges 226 of the cage body 220 ( see , e . g ., fig1 ). fig1 a - 15c disclose rear , front , and side elevations , respectively of the third embodiment 218 . during implantation , the angled engagement surfaces 260 ( see fig1 a - 14c ) are contacted by and become flush with the upper and lower angled surfaces 234 , 236 of the piston 232 , which , as the piston 232 is inserted further into the cavity 228 , causes the pins 256 to move upwardly through the channels 231 , 233 to an engaged position . in this manner , engagement of the upper and lower angled surfaces 234 , 236 with the pin 256 causes movement of the piston 232 into the cavity 228 to drive the pins 256 into the adjacent vertebra . after insertion of the piston 232 is complete , each engagement surface 260 becomes flush with the engagement surface 253 to prevent the nail from receding back into the cavity 228 and ensuring fastening of the nail 256 with adjacent bone matter . the upper and lower rails 244 , 246 ( see fig1 a , 12 c ) occupy the upper and lower grooves 248 , 250 , respectively , to ensure proper alignment of the piston 232 within the cavity 228 . the ridged bushings 258 are fitted within the channels 231 , 233 in the annular space between the titanium pin 256 and channel walls to facilitate movement and retain the pins 256 in the channels 231 , 233 . operation of the locking plate for this embodiment is identical to operation of the locking mechanism described hereafter with reference to the fourth embodiment a fourth embodiment comprises a cage body 320 , shown in fig1 a - 16c , comprises upper and lower walls 322 , 324 with ridges 326 . upper and lower walls 322 , 324 partially define a cavity 328 . openings 330 through the upper wall 322 provide access to the cavity 328 to allow for bone growth thereinto from adjacent vertebrae . upper and lower lock openings 325 , 327 are formed in the upper and lower walls 322 , 324 , respectively near the piston opening 328 . a piston 332 having upper and lower angled surfaces 334 , 336 is insertable into the cavity 328 . a screw 338 may thereafter be inserted through a piston faceplate 340 and secured to a screw mount located in the cavity 328 . a locking plate 380 having a closed end 383 opened end 384 defined by upper and lower fingers 386 , 388 is rotatably attached to the faceplate 340 with a screw 382 . as shown in fig1 b , the fastening members of the fourth embodiment 318 comprises porous blades 356 with lateral passages 357 therethrough to allow bone growth . fig1 b and fig1 c , which both depict the piston in an engaged position within the cage body 320 , show the locking plate 380 in the unlocked and locked position , respectively . in the unlocked position , the screw 338 may be passed between the upper and lower fingers 386 , 388 , with the screw head accessible . once the piston 382 is engaged with the cage body 320 to support the blades 356 , the locking plate 380 is rotated around the locking plate screw 381 so that the lower finger 386 extends into the lower lock opening 325 and upper finger 386 covers the head of the piston screw 382 . in this position , the locking plate 380 prevents “ back out ” of the piston screw 382 and piston 332 , which assures engagement of the blades 356 with the adjacent vertebrae . although the embodiments of the present invention disclose titanium fastening members , alternative embodiments include stainless steel fastening members . for each of the above - described embodiments , the upper and lower walls are at least substantially parallel . in alternative embodiments , however , the upper and lower walls may be angled relative to one another to correspond to curvature of the spine ( e . g ., to correspond to a lordotic curvature ) at the targeted region of implantation . in such case , the front and rear sides will be of differing heights . in addition to the nail and / or pins described hereinabove , alternative embodiments of the present invention contemplate a fastening member with a blade - or knifelike appearance , such as the porous blades shown in fig1 and fig2 . the present invention is described in terms of preferred illustrative embodiments of specifically described stand - alone spinal cages . those skilled in the art will recognize that yet other alternative embodiments of such a device can be used in carrying out the present invention . other aspects , features , and advantages of the present invention may be obtained from a study of this disclosure and the drawings , along with the appended claims .
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