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referring now to the drawing , wherein the showings are for the purpose of illustrating the invention only and not for the purpose of limiting the same , a schematic diagram of a system for notifying a subscriber of time - critical events is shown , in accordance with an embodiment of the current invention . the exemplary system for notifying a plurality of subscribers comprises : a wireless carrier core ip network 100 , one or more wireless carrier systems 140 , a telematics unit 170 , and alert server 200 . telematics unit 170 may be fixedly installed into a motor vehicle , such as an automobile or truck , or other vehicles . alternatively , the telematics unit may comprise a hand - held device carried by an individual . the telematics unit 170 is preferably equipped with suitable hardware and software for transmitting and receiving voice and data communications . elements of the telematics unit 170 preferably comprise : a digital signal processor connected to a wireless modem ; a global positioning system (‘ gps ’) receiver or gps unit ; an electronic memory ; a microphone ; one or more audio speakers ; an embedded telephone or an email access appliance ; a real time clock ; a display ; and a software monitor for reading a time signal of real time clock . the gps unit provides longitude and latitude coordinates of the device , as well as a time stamp and a date stamp . the telephone preferably comprises a cellular communications device having push - to - talk - over - cellular (‘ poc ’) capability , and is operable to send and receive over - the - air messages , including those originating from the alert server 200 . the telematics unit 170 sends and receives radio transmissions from wireless carrier core ip network 100 via the one or more wireless carrier systems 140 which are operable to communicate using cellular systems . wireless carrier core ip network 100 includes a poc server 110 , a home agent 120 , and mobile contact manager 130 , which work in conjunction with the alert server 200 , to deliver timely and geographic position - appropriate messages to telematics unit 170 . the home agent 120 and mobile contact manager 130 are preferably operable to track and manage information about each subscriber , based upon communications through the wireless carrier systems 140 . wireless carrier core ip network 100 preferably includes services from mobile telephone switching offices , wireless networks , public - switched telephone networks , and internet protocol (‘ ip ’) networks . network 100 comprises a wired network , an optical network , a fiber network , another wireless network , or any combination thereof , and connects to telematics unit 170 via wireless carrier system 140 . wireless carrier core ip network 100 is operable to communicate with various public internet servers 150 to obtain localized location - specific time - critical information , such as traffic reports , road construction updates . wireless carrier core ip network 100 is operable to communicate with private intranet servers 160 to obtain similar information of interest . wireless carrier core ip network 100 sends and receives messages according to established protocols for cellular phone communications such as is - 637 standards for short message service ( sms ), is - 136 air - interface standards for sms , and gsm 03 . 40 and 09 . 02 standards . the alert server 200 may be incorporated as an element of a call center . the call center comprises a virtual location wherein many calls are received and serviced at the same time , or wherein many calls are sent at the same time . in one embodiment of the invention , the call center is a telematics call center , prescribing communications to and from telematics unit 170 . in another embodiment , the call center is a voice call center , providing verbal communications between a communication services advisor in the call center and one or more subscribers . in another embodiment , the call center contains each of these functions . in another embodiment , the call center serves as a fully automated center providing telematics service center data , including execution of the functions of the alert server 200 . communication services advisor may be a real advisor or a virtual advisor . a real advisor is a human being in verbal communication with a user or subscriber . a virtual advisor is a synthesized voice interface responding to requests from user or subscriber . in one embodiment , virtual advisor includes one or more recorded messages . in another embodiment , virtual advisor generates voice messages using a text to speech synthesis engine ( tts ). in another embodiment virtual advisor includes both recorded and tts generated messages . the system presented includes the alert server 200 operable to collect , aggregate , and communicate time - critical information over the wireless carrier core ip network 100 . the alert server comprises a location manager 210 , an alert notification manager 220 , and a message delivery notification manager 230 . the wireless communications system preferably comprises the poc communications system , as previously discussed . the location manager 210 is operable to identify and locate telematics units within a known geographical area . the term ‘ recipient ’ as used herein describes a telematics unit receiving the time - critical information . the time - critical information is communicated to the recipient via communications system described herein . the message delivery notification manager 230 is operable to schedule and format delivery of alert messages to the recipients , consistent with the specific communications system and telematics hardware and operating system . the message delivery notification manager 230 schedules and formats delivery of various time - critical alert messages to each recipient , based upon location and direction of travel of each of the recipients . the alert notification manager 220 receives and aggregates alert messages , including a geographic location of the source of the alert , and prepares the aggregated alert messages for delivery . the alert server 200 works with the alert notification manager 220 to collect time - critical information from various sources which is formed into the alert messages . collecting time - critical information includes identifying available services compatible with network latencies ; and , collecting appropriate time - critical messages consistent with the identified services . exemplary vehicle time - critical information that may be compiled , aggregated and communicated to subscribers in alert messages may include , for example , warning of approaching emergency vehicles ; warnings of approaching sharp curves , low or narrow bridges , or other non - obvious road features ; warnings of road surface changes due to ambient conditions , e . g . fog , ice , drifting snow , water , flooding ; warnings of approaching rail trains for collision avoidance ; amber alert details ; warnings of approaching work zones ; and , warnings of approaching traffic congestion or changed traffic patterns , and warning of vehicle approach to a school zone wherein speed limits are restricted at specific times of the day . other specific information may be developed and implemented according to needs of an individual network , consistent with the communications ability of the network system and the vehicles . other specific services compatible with network latencies currently comprise services able to accept a latency of approximately one second , due to current delay times of the poc cellular system . it is envisioned that additional alert messages may become appropriate for communication to subscribers when delay times of the poc cellular system decrease with the advent of new technology . in operation , the alert server 200 acts to push communications of alert messages to each subscriber , based upon each recipient &# 39 ; s location and direction of travel relative to location of each known time - critical event or location . each recipient &# 39 ; s location and direction of travel can be determinable using information from the gps transponder . the alert messages are preferably pushed to each subscriber through the subscriber &# 39 ; s telematics device 170 , and may take the form of a voice message heard audibly by the subscriber , or in the form of a written message printed on a visual display such as a vehicle information center , or in the form of an audible alert coupled with a written message , or in the form of a bank of lamps viewable by the subscriber , which are associated with various alert messages . the alert server 200 collects and receives time - critical information from a variety of sources , including information available on the internet 150 , and information developed on the server &# 39 ; s private intranet 160 . the information developed on the server &# 39 ; s private intranet 160 may comprise electronically available information , or information collected or captured and interpreted by a human operator who is able to encode the information in a manner suitable for use by the server . the subscriber may desire regular notification of specific events or kinds of events . one example of event notification is traffic conditions . in this case , the network may regularly capture traffic events from public and private sources that are relevant to the subscriber &# 39 ; s geographic location and direction of travel , and provide such information on a scheduled basis , including a notification that there are no incidences for which the subscriber has cause for concern . the invention has been described with specific reference to the preferred embodiments and modifications thereto . further modifications and alterations may occur to others upon reading and understanding the specification . it is intended to include all such modifications and alterations insofar as they come within the scope of the invention .
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the following description is provided to enable any person skilled in the art to make and use the invention and sets forth the best modes contemplated by the inventor of carrying out his invention . various modifications , however , will remain readily apparent to those skilled in the art , since the general principles of the present invention have been defined herein specifically to provide an effective treatment for lupus and other autoimmune and inflammatory joint diseases flavonoids are ubiquitous secondary products found in most land plants . flavonoids are oxygen based rather than nitrogen based like traditional pharmaceuticals plant compounds such as alkaloids . as such they are end terminus electron acceptors rather than electron donors . flavonoids inhibit 5 - lipoxygenase in the cytokine release pathways because hydroxyl groups at 4 ′, 3 , and 7 positions of the flavonoid molecules accept electrons . ( see , effects of flavonoids on arachidonic acid metabolism , a . f . welton , l . d . tobias , the biochemistry of cell activation related to the putative action of flavonoids , s . g . laychock , plant flavonoids in biology and medicine : biochemical , pharmacological , and structure - activity relationships , pg 231 - 242 , 1986 alan r liss , inc .). flavonoids modulate the immune response through sequestration of free radicals , which prevents formation of epoxide diols and subsequent attack on the dna . further , catalytic ion and signal transducers are sequestered by flavonoids ( see , structural dependence of flavonoid interactions with cu 2 + ions : implications for their antioxidant properties , brown j e , khodr h , hider r c , rice - evans c a , biochem . j . 1998 mar . 15 ; 330 ( pt 3 ): 1173 - 8 ). a number of biological effects of flavonoids have been elucidated . for example , flavonoids inhibit deiodinase , which is the enzyme that promulgates thyroid functions . iodothyronine deiodinase is oxygen bound and directly impacts basal oxygenation . flavonoids have the steric binding mimicry of ligands that bind the oxygen transport molecule iodothreonine deiodinase . (“ role of flavonoids in the oxygen - free radical modulation of immune responses ”, b . pignol , et . al ., role of flavonoids in the oxygen - free radical modulation of the immune response , plant flavonoids in biology and medicine ii : biochemical , cellular , and medicinal properties , pg . 173 - 182 , 1988 alan r . liss , inc . ; “ structure activity relationships of flavonoids deiodinase inhibitors and enzyme active site model ”, s . v . cody , plant flavonoids in biology and medicine : biochemical , pharmacological , and structure - activity relationships , 1986 alan r . liss , inc ., pg . 373 - 382 ). flavonoids thus “ turn down the thermostat ” of homeostasis . (“ iodothyronine deiodinase is inhibited by plant flavonoids ”, j . koehrle pg . 324 , structure activity relationships of flavonoids deiodinase inhibitors and enzyme active site model , s . v . cody , plant flavonoids in biology and medicine : biochemical , pharmacological , and structure - activity relationships , 1986 alan r . liss , inc ., pg . 373 - 382 ). it is believed that the effect of flavonoids in the present invention is mediated through the above - discussed effect on ion channels . however , the effect on the thyroid indicates that the flavonoids may be acting on more than one biological system in the present invention . the inventor included bromelain in the present invention because there is some indication that this enzyme can aid in the regeneration of cartilage in a damaged joint . generally , bromelain alone is not effective in ameliorating the joint pain in either osteoarthritis or lupus caused joint inflammation . it is logical that the compound is not effective in lupus because continued lupus - induced inflammation would mask any joint repairing effects of bromelain . it also seems apparent that osteoarthritis , at least in some cases , is mediated by an inflammatory process . this may explain why bromelain treatment of that disease has not been very effective . however , the flavonoid component of the present invention controls inflammation through its effects on ion channels and possibly through other biological effects not yet elucidated . white blood cells are deactivated by the changes in ion channels so that inflammatory attacks on the joints are decreased . down regulation of the immune system ( as 30 mediated by white blood cells ) results in lowered production of auto - antibodies . under these conditions bromelain appears to be able to help in joint repair . it does seem likely that bromelain is in some way synergistic with the flavonoids because treatment with flavonoids but without bromelain is clearly less effective than the combination . many natural foods contain flavonoids ; however , few , if any , contain bromelain combined with effective flavonoids . also , it is not known whether the combination of flavonoids in natural products might decrease the overall effectiveness of the “ correct ” flavonoids . for whatever reasons mere dietary treatments for lupus and related diseases has not been successful . while the present inventor believes that the addition of vitamin c to the flavonoid / bromelain mixture enhances the effect of the mixture , it is apparent that the mixture without vitamin c is also effective . however , because vitamin c is relatively innocuous , it has been used in the vast majority of tests . screening tests by experts in ion channel function have indicated that a number of flavonoids , especially certain flavonols have the correct charge structure to regulate the key ion channels . quercetin , which has been used in the majority of tests of the present invention , is very effective in tests of ion channel function . luteolin is even more effective than quercetin in such tests . limited tests have shown that replacing quercetin with luteolin in the inventive formula is somewhat more effective . however , at this time the inventor lacks a ready source of pharmaceutical grade luteolin to demonstrate whether luteolin is significantly more effective overall . quercetin and luteolin differ by a single hydroxyl group ( which luteolin lacks as compared to quercetin ). a limited number of tests have shown that myricetin is somewhat effective in the present ; this compound varies from quercetin in the addition of one hydroxyl . in addition , rutin is also moderately effective in the present invention . rutin is a glycoside ( rutinoside ) of quercetin so that metabolism of rutin is likely to make quercetin available . it is likely that other flavonoids with structural similarities to quercetin or luteolin , or glycosides of these flavonoids , will also function in the present invention . the results of treating actual patients with the inventive composition have been extremely dramatic . besides the cases described herein literally dozens of patients have shown similar results when treated with the quercetin / bromelain / vitamin c mixture . one of the first tested subjects was , bz , who had been bed ridden for nine months and could neither sit up or turn over . she showed the typical lupus butterfly rash and was diagnosed by a blood test showing a positive ana ( anti - nucleic acid antibody ) titer - criteria indicative of lupus . the subject &# 39 ; s mother had previously tested positive for lupus and has been treated with several medications , including plaquinel and cyclosporin . a second subject , ka , had also tested positive for lupus and had been being treated with plaquinel and cyclosporin . both of these test subjects experienced rapid relief from symptoms of fatigue and depression and pain , elimination of the associated rash and a return to normal life style within one to two months of beginning a regime of one pill ( 500 mg quercetin / 500 mg bromelain / 500 mg vitamin c ) three times per day at the above dosage . kidney flares ceased and pain abrogated . both subjects stated that they felt completely fine with no side effects and maintained a perfect state of health while on the inventive composition . both bz and ka stopped taking the medication after two months , since they reported that they were “ completely recovered .” as might be expected , symptoms begin to reappear within two weeks . upon reestablishment of treatment all symptoms again disappeared . this indicates that the inventive product is solely responsible for the amelioration of sle ( systemic lupus erythematosus ). additional patients have also shown similar positive results . mk was a 65 - year - old woman with seropositive rheumatoid arthritis . she developed side effects from methotrexate treatment at a dose of 22 . 5 mg weekly . her methotrexate was discontinued and she was started on the inventive composition . within one month she showed a dramatic decrease in synovitis . nm was a 37 - year - old woman with an inflammatory polyarthritis and positive ana ( antinuclear antibody ). she had sjogrens syndrome with a positive ssa ( anti - ro ) antibody . after three months of treatment with the inventive composition , she noticed decreased hair loss , and a lessening of joint pain and swellings . her serologies also improved . her initial ana titer was 170 and ssa titer was 584 , and occasionally much , much higher . her most recent serologies show an ana titer of 67 and ssa of 429 . ds was a 57 year old female with sle / sjogrens . her disease manifestations were pulmonary infiltrates and pulmonary effusions . despite high doses of prednisone , plaquenil , and imuran she had continued pulmonary symptoms , fevers , joint swellings , and elevated anti - dna antibody . after one - month treatment with the inventive composition , her anti - dna level decreased from 454 to 186 ( normal less than 30 ). lc was a 46 year old female with sle . her main manifestations have been joint inflammation and recurrent serositis . she has had recurrent chest pain and palpitations . her echocardiogram in 1999 showed valvular changes with trace mitral regurgitation and mild to moderate tricuspid regurgitation . she also had pulmonary hypertension with a rv systolic pressure of 45 . lc started the inventive compositions and after four months was tapered off prednisone of 20 - mg qd and plaquinel . her recent echocardiogram shows improvement - there was no longer any evidence of pulmonary hypertension . at this time more than 50 patients , most with some form of lupus , but others with various inflammatory joint diseases , have been treated with the inventive composition . virtually all patients have demonstrated a measurable amelioration of their disease state . the following claims are thus to be understood to include what is specifically illustrated and described above , what is conceptually equivalent , what can be obviously substituted and also what essentially incorporates the essential idea of the invention . those skilled in the art will appreciate that various adaptations and modifications of the just - described preferred embodiment can be configured without departing from the scope of the invention . the illustrated embodiment has been set forth only for the purposes of example and that should not be taken as limiting the invention . therefore , it is to be understood that , within the scope of the appended claims , the invention may be practiced other than as specifically described herein .
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supercontinuum generation in fibers is well known and has been demonstrated in numerous fiber waveguides . nonlinear interactions in such fibers are greatly affected by fiber properties such as effective area ( a eff ) and waveguide dispersion . waveguide dispersion governs how quickly a launched pulse will spread in the time domain and , as a result , how quickly the peak power of the pulse will decrease as it propagates along the fiber . in addition , the peak intensity of the pulse will be larger for fibers with a smaller a eff , and will determine the magnitude of the nonlinear interactions in the waveguide itself . however , as mentioned above , current supercontinua have limitations that are dictated by the dispersion and nonlinearity of the fiber . various applications currently exist ( for example , frequency metrology ) that would greatly benefit by broadening the continuum . in particular , broadening the supercontinuum would allow for a smaller length of hnlf to span an octave for a given pump power . other limitations in the currently available supercontinuum are associated with the shape of the spectrum , the wavelength range , noise figure , etc . generally speaking , therefore , it would be desirable to find a way to “ enhance ” the supercontinuum generation in fibers , where the enhancement may take the form of one or more of these desirable characteristics . fig1 contains a graph illustrating the relationship between the wavelength of a generating pulse and fiber dispersion for two different prior art supercontinuum - generating structures . the curve on the left is associated with using a ti : sapphire laser as the pulse generating device in conjunction with an air - silica microstructured ( or tapered ) fiber . the curve on the right is associated with using an erbium laser source in conjunction with a section of highly - nonlinear fiber ( hnlf ). numerical models show that the broadest continuum is generated when the wavelength of the laser light pulse is in the anomalous ( positive ) dispersion regime of the fiber . in particular , the pulse initially begins to self - raman split to longer wavelengths ; then , as higher - order solitons start to break up , parametric four - wave mixing causes frequencies to be generated at wavelengths shorter than the zero dispersion wavelength of the fiber , the combination resulting in the supercontinuum profile in the output power . comparing the two curves of fig1 , the curve associated with the hnlf is similar to that of the microstructured / tapered fiber , only shifted to longer wavelengths . indeed , recent experiments with hnlf have shown supercontinuum generation at wavelengths of from 1 . 1 μm to 2 . 1 μm in only a few centimeters of hnlf . in accordance with the teachings of the present invention , as will be discussed in detail hereinbelow , it has been found that continuum generation in hnlf can be enhanced ( for example , extended in bandwidth or improved in terms of spectral shaping ) by modifying the fiber characteristics after fabrication . for example , uv exposure , electromagnetic field treatment and thermal processes may all modify the dispersion characteristics of hnlf in a manner that results in enhancing its supercontinuum output . supercontinuum generation in optical fibers depends on an interplay between nonlinear optical interactions and the linear dispersion of the fiber itself . control of these dispersive properties has , to date , relied exclusively on the careful design and fabrication of an appropriate fiber waveguide , typically with very low dispersion , and a carefully - chosen zero dispersion wavelength value ( in order to maintain a narrow pulse shape and provide appropriate phase matching ). applications operating in the near - infrared regions ( approximately 800 nm to 1 micron ) typically use a high - δ microstructured fiber ( or tapered fiber ) in order to generate the desired supercontinuum ( as evident from the ti : sapphire graph of fig1 ). the use of hnlf in supercontinuum generation has been designed , as indicated by the plot of fig1 , to operate in the mid - infrared region ( around 1550 nm ). the prior art has demonstrated that octave - spanning supercontinua can be generated in fibers only a few centimeters in length . in accordance with the present invention , a section of hnlf is post - processed to be inscribed with at least one bragg grating ( using conventional grating - writing processes ) to modify the generated radiation by having a core - guided , forward propagating mode reflected back into a core - guided mode . bragg gratings ( also referred to as refractive index gratings ) have been used in association with optical waveguides for a number of years . a bragg grating is a structure that has a periodic pattern of alternating high and low optical refractive index values . conventionally , such gratings couple a forward - propagating core - guided mode at a predetermined wavelength in a single mode fiber ( defined by the grating period ) to the back - reflected core mode . supercontinuum radiation generated by a bragg grating / hnlf in accordance with the present invention results in the formation of an extended peak in the supercontinuum near the center wavelength of the grating , as well as enhanced light in a narrow band on the long wavelength side of the grating . fig2 illustrates an exemplary experimental arrangement used to observe the effects on generated supercontinuum for an hnlf that has been post - processed to include one or more bragg gratings in accordance with the present invention . in this example , a femtosecond erbium laser source 10 is coupled through an amplifier 12 and propagates along a section of single mode fiber 14 . a uv - exposed section 16 of hnlf including a bragg grating 18 is spliced to single mode fiber 14 , and the output is measured at an optical spectrum analyzer ( osa ) 20 . for one experiment , uv - exposed hnlf 16 comprised a 20 cm section of fiber that was loaded with deuterium to enhance its uv sensitivity . to create bragg grating 18 , the fiber was exposed to scanned , focused uv light at 242 nm from an excimer - pumped , frequency - doubled dye laser source through a phase mask having a period of 0 . 672 μm . the intensity of the beam was approximately 216 mj / cm 2 per pulse , with the dose at each point on the fiber being approximately 3 . 4 kj / cm 2 . the bragg grating was formed by a 22 mm uniform scan , with a reflectance at 990 nm . while bragg grating 18 is shown in this embodiment as formed within hnlf 16 , in an alternative embodiment a similar resonant structure may be formed at the termination of a section of hnlf , thus still providing the desired reflection back along the hnlf and supercontinuum generation in accordance with the present invention . fig3 contains a graph ( curve a ) of the supercontinuum generated from a uv exposed fiber in the arrangement of fig2 , prior to the inscription of a bragg grating in accordance with the present invention . curve b illustrates the difference in supercontinuum generation associated with the incorporation of a bragg grating in the uv - exposed hnlf structure . each curve has a similar average refractive index change ( with respect to a non - exposed hnlf fiber ) and thus exhibits a similar waveguide dispersion characteristic . in accordance with the present invention , the inclusion of a bragg grating structure in the hnlf results in generating a peak in supercontinuum radiation at the grating resonance ( in this case , at 990 nm ), with an additional large enhancement of the supercontinuum in the region on the long wavelength side of the grating resonance . the grating enhancement is illustrated as peak x on curve b , where peak x is shown as being approximately thirty times greater than the supercontinuum generated from a uv - exposed hnlf without a grating structure . fig4 contains simulation results for supercontinuum radiation generated in response to the resonant dispersion of a bragg grating , with fig4 ( a ) showing the resultant continuum for an hnlf with a 980 nm grating ( compared to a simulation result for an hnlf without a grating ). fig4 ( b ) is an expanded view in the region of the grating resonance . referring to fig4 ( b ), it is evident that a strong feature on the long wavelength side of the grating resonance is produced ( compare with prior art curve ) as a result of including a bragg grating in the structure . advantageously , well - known processing techniques can be used to form bragg gratings with any desired grating resonance ( for example , the period of the phase grating may be adjusted to change the grating resonance ). indeed , multiple bragg gratings may be “ written ” into the same section of fiber ( in this case hnlf ) so as to form multiple resonant wavelengths . bragg gratings with multiple resonances can also be fabricated by imposing a sampling function on a given grating structure . in particular , a sampling function ( usually a periodic function ) is a modulation of the basic grating index modulation and is usually longer in period than the basic grating modulation . the formation of a sampled grating structure results in forming many resonances that are spaced in wavelength by an amount that is inversely proportional to the sampling period . fig5 illustrates a graph of experimental results for supercontinua produced by bragg gratings with other center wavelengths , namely , 1080 nm and 1480 nm . as shown , the generated supercontinuum from such structures will experience an enhancement on the long wavelength side of each inscribed grating resonant wavelength . the possibility also exists , it should be noted , to generate enhancements on the short wavelength side of the resonance , or on both sides , for other grating and laser parameters . it is to be noted that spectrum of light being generated by the hnlf can be monitored as the grating is being inscribed into the fiber . in this way , the spectrum may be trimmed , shifted or shaped to an optimum value , with desired noise reduction figures , through incorporating a feedback mechanism into the grating writing process . moreover , various other well - known bragg grating “ features ” may be incorporated into a grating formed in hnlf . that is , an apodized grating , blazed grating , chirped , etc . may easily be formed and the modifications in the grating structure used to enhance various aspects of the generated supercontinuum generation . moreover , it is to be understood that various other highly - nonlinear waveguiding components , such as a microstructured fiber , may be processed to include the resonant features as discussed above . while the foregoing description represents a preferred embodiment of the present invention , it will be obvious to those skilled in the art that various modifications may be made without departing from the spirit and scope of the invention as pointed out by the following claims .
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the present invention is generally related to embedded memory compilers and read - only memories ( roms ). when a rom is compiled , a rom data file may be prepared , the data may be read into the compiler and the memory programmed accordingly . typically , a storage capacity of the rom exceeds an amount of data to be programmed . therefore , an upper end of an address range within the rom may remain un - programmed by the data . as such , the rom data file may be padded with predetermined data to account for the entire capacity of the rom . the predetermined data is generally selected to draw minimal dynamic power when coupled to pre - charged bitlines ( e . g ., program logical high padded bits for logically high pre - charged bitlines ). at a compile time , the padded data may be seen in the data file . the present invention generally alters a layout and / or fabrication process of the control logic and / or bit cells associated with accessing the padded data to minimize static leakage current . for instance , if a rom layout has many ( e . g ., 128 ) rows and one or more upper rows ( e . g ., 8 rows ) are programmed with only padded data , a row driver module associated with each of the padded rows may be optimized for static leakage current . any increased delay through the optimized row driver modules may be irrelevant as the padded data should never be access , or at least rarely accessed . leakage current optimization may be achieved in a number of ways ranging from completely removing some or all of the devices , lengthening some or all of the gate channel lengths within the control logic and / or changing a substrate doping ( e . g ., a higher threshold implant ) over the region of the control logic associated with the padded data . an overestimation of an anticipated memory size early in a design cycle generally amplifies the static power consumption problem . for example , if a rom design is originally targeted to have 3072 words , but the final rom code uses only ⅓ of the words , a majority of the rom memory adds to a leakage current overhead without storing useful data . to minimize the leakage current , a flag may be passed at compile time for any memory type signifying a maximum address that may be accessed and / or a list of locations that should never be accessed . for example , if an 8192 × 16 dual port memory is compiled for a chip and a system level designer flags that the last 512 words should never be accessed , the memory compiler may act accordingly and replace the control logic modules used to access such locations with lower - leakage - current versions . referring to fig1 , a flow diagram of an example method 100 of creating a leakage optimized memory is shown in accordance with a preferred embodiment of the present invention . the method ( or process ) 100 may be implemented in hardware and / or software executing on a computer system . the method 100 generally comprises a step ( or block ) 102 , a step ( or block ) 104 , a step ( or block ) 106 , a step ( or block ) 108 , a step ( or block ) 110 , a step ( or block ) 112 , a step ( or block ) 114 , a step ( or block ) 116 , a step ( or block ) 118 and a step ( or block ) 120 . in the step 102 , a register transfer level ( rtl ) design of a circuit having an embedded memory may be created in an initial design file . a preliminary layout of the circuit may be performed in the step 104 and stored in a preliminary layout file . during or after the preliminary layout of the circuit is performed , data to be stored in the memory may be generated in the step 106 and stored in a rom data file . the data may include instructions for one or more processors and / or information to be used within the circuit , such as programmable parameters , offsets , cryptography codes and the like . since the memory capacity is often established before the final programmed data is known , the memory is usually sized to meet a worst - case anticipated situation . after the final capacity of the memory is known , padded data may be included into the rom data file in the step 108 such that the size of data in the rom data file matches the memory capacity of the memory in the preliminary layout file . in the step 110 , the compiler may allocate the data ( both programmed and padded ) from the rom data file to the memory . in compiling the memory , many rows of bit cells within the memory may store the programmed data , some rows may store a mixture of programmed data and padded data , and one or more rows may store only padded data . rows containing only padded data may be flagged in the step 112 for further processing . the additional processing may involve ( i ) modifying a layout of the circuit and / or ( ii ) modifying one or more fabrication steps to be used in manufacturing the circuit . layout modifications may be performed in the step 114 . fabrication process modifications may be performed in the step 116 . after the adjustments to the layout / fabrication process have been made , a completed circuit definition may be generated and stored in a compiled file in the step 118 . the finished circuit , as defined in the compiled file , may be tested in the step 120 . testing may include , but is not limited to , design rule checking , layout vs . schematic check , timing analysis and the like . referring to fig2 , a detailed flow diagram of an example implementation of the layout modification step 114 is shown . the layout modification method ( or process ) 114 generally comprises a step ( or block ) 140 , a step ( or block ) 142 , a step ( or block ) 144 and a step ( or block ) 146 . the method 114 may be implemented in hardware and / or software executing on a computer system . layout modification may be accomplished in the step 140 by replacing one or more original modules in the unused rows of the memory ( e . g ., contain only padded data ) with substitute modules that have fewer components than the original modules . a lower gate count in the substitute modules compared with the original modules generally results in a lower leakage current . the gate count may be lowered by replacing one or more transistors and / or logic gates in the original modules with direct connections to a logical high voltage level and / or a logical low voltage level in the step 142 . by replacing active circuitry with direct connections to power rails , the leakage currents may be reduced even further . layout modifications may be accomplished by replacing one or more original modules in the unused rows of the memory with lower power versions of the original modules in the step 144 . the memory compilers generally build the memory module from tiling leaf cells . swapping in low leakage versions of the control logic and / or row drivers in the unused rows may be easily accomplished . since the lower power replacement modules generally have lower leakage currents than the original modules , the overall static power consumption of the memory may be reduced due to the swapping . another layout modification approach may involve lengthening a gate channel length of one or more transistors in one or more unused rows of the memory in the step 146 . per fig3 , the gate channel length is generally a distance ( e . g ., l ) between a source diffusion 150 and a drain diffusion 152 of the transistor . lengthening a gate channel length may reduce the leakage current of the transistor and therefore lower the static power consumed . referring to fig4 , a detailed flow diagram of an example implementation of the fabrication modification step 116 is shown . the fabrication modification method ( or process ) 116 generally comprises a step ( or block ) 160 , a step ( or block ) 162 , a step ( or block ) 164 and a step ( or block ) 166 . the method 116 may be implemented in hardware and / or software executing on a computer system . a fabrication modification may be accomplished in the step 160 by adjusting a doping level in particular areas of the substrate associated with the unused rows of the memory . the substrate doping adjustment may be adapted to increase a threshold voltage of the transistors formed in the adjusted areas of the substrate . increasing the transistor threshold voltages generally decreases the leakage current of such transistors , leading to a reduction in the overall power consumption of the memory . doping levels may be changed by one or more fabrication techniques , such as ion implantation , ion diffusion and the like . another fabrication modification may be accomplished by creating thicker gate oxides in one or more transistors in the unused rows of the memory per step 162 . per fig5 , the gate oxide thickness is generally a distance ( e . g ., t ) between a substrate 154 and a gate 156 . increasing the gate oxide thickness generally increases the transistor threshold voltage . as mentioned above , increasing the transistor threshold voltage generally decreases the static leakage current . the gate oxide thickness may be increased by one or more techniques , such as increasing a time and / or rate of oxide growth , depositing additional material over thin oxide layers , and the like . fabrication of the transistors in the unused rows of the memory may also be modified by adjusting the permittivity of the thin gate oxides 158 ( with or without increasing the gate oxide thickness t ). varying the permittivity may alter the transistor threshold voltage , and thus alter the static leakage current of the transistor . the permittivity may be adjusted by using different materials for the gate oxide 158 , altering the growth rate of the oxides 158 , altering the atmosphere in which the oxides 158 are grown and the like . the modifications to the fabrication process may result in ( i ) the introduction of one or more new fabrication steps , ( ii ) exposing the areas forming the unused rows of the memory to one or more fabrication steps that the areas would otherwise avoid and / or ( iii ) masking one or more fabrication steps from the unused row areas . to account for the changes in the fabrication , one or more new masking layers may be created and / or one or more existing masking layers may be modified . for example , a single new mask controlling a new ion implantation step may be created to adjust the transistor threshold voltages in the unused rows of the memory . if the ion implantation step is normally performed as part of the chip fabrication , an existing implant mask may be altered to expose the transistors in the unused rows to the ion implantation . referring to fig6 , a diagram of a first example application of an adjustment is shown . a memory 170 may be viewed as multiple columns of core cells ( or bit cells ) disposed around a central column of row driver modules . below each column of core cells , input / output ( i / o ) modules may be created to read / write the data from / to the cells . a control module may be formed below the row driver modules to control which particular row is accessed during a read cycle and a write cycle . after the rom data file has been generated , the padded data may be examined to identify the rows of the memory holding only padded data . a region ( or area ) 172 may be defined that covers all of the unused rows . within the region 172 , the fabrication process and / or layout may be adjusted to decrease the leakage current of some to all of the transistors in the unused core cells and in the unused row driver modules . when fabricated , the unused rows may remain functional . however , access times to the core cells in the region 172 may be slower than the access times to the rest of the core cells . in asynchronous designs incorporating a dummy “ self - timing ” column , the dummy bit cell used to establish the timing may be disposed within an unused row . to maintain proper timing of the dummy column , the region 172 may be modified to avoid the dummy column and the associated row driver module . referring to fig7 , a diagram of a second example application of an adjustment is shown . the leakage current consumed in the unused rows of the memory 170 may be reduced by adjusting the fabrication and / or layout of only the unused row driver modules ( e . g ., area 174 ). the fabrication and / or layout of the unused core cells may remain the same as the fabrication of the active core cells . as such , if the unused core cells are accessed , a response from the unused core cells may be similar to that of the used core cells . the techniques of the present invention may be used to customize the performance of rows in memory arrays holding programmed data . performance variations ( and leakage currents ) across the memory array rows may be used to shrink the data output hold parameter to match a data access time window in non - self - timed memories . for instance , in a memory implementing inverter sense modules , an access to low rows in the array may occur much faster than an access to upper row in the array . by applying the present invention to adjust the channel length and / or the threshold voltages , access to the lower rows may be slowed while access to the upper rows may remain as fast as possible . hence , in the inverter sensed architected memory , the data output hold time may be trimmed to closely match the data access time . the function performed by the flow diagrams of fig1 , 2 , 4 , 6 and 7 may be implemented using a conventional general purpose digital computer programmed according to the teachings of the present specification , as will be apparent to those skilled in the relevant art ( s ). appropriate software coding can readily be prepared by skilled programmers based on the teachings of the present disclosure , as will also be apparent to those skilled in the relevant art ( s ). the present invention may also be implemented by the preparation of asics , fpgas , or by interconnecting an appropriate network of conventional component circuits , as is described herein , modifications of which will be readily apparent to those skilled in the art ( s ). the present invention thus may also include a computer product which may be a storage medium including instructions which can be used to program a computer to perform a process in accordance with the present invention . the storage medium can include , but is not limited to , any type of disk including floppy disk , optical disk , cd - rom , magneto - optical disks , roms , rams , eproms , eeproms , flash memory , magnetic or optical cards , or any type of media suitable for storing electronic instructions . while the invention has been particularly shown and described with reference to the preferred embodiments thereof , it will be understood by those skilled in the art that various changes in form and details may be made without departing from the scope of the invention .
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although the disclosure hereof is detailed to enable those skilled in the art to practice the invention , the embodiments published herein merely exemplify the present invention . [ 0066 ] fig1 depicts a top view of accumulator or accumulation conveyer ( 20 ). as shown in this cutaway view , accumulator ( 20 ) discloses elements of zones ( 200 , 400 and 600 ), but those skilled in the art recognize that accumulation conveyor ( 20 ) can be , as represented in fig1 , engineered with a multitude of zones ( 200 , 400 , 600 , 800 , et cetera ) and their corresponding item carrying rollers ( 30 ). accumulators , within the scope of the present invention , can convey a plethora of items — ranging from such things as boxes , baggage and cartons to any vessel of sufficient size to travel over the item conveying rollers ( 30 ). in fig1 item carrying rollers ( 30 ) have been cutaway above zones ( 200 ) and ( 400 ) while item carrying rollers ( 30 ) are shown , in part , above zone ( 600 ). each zone ( 200 , 400 , 600 , et cetera ) of item carrying rollers ( 30 ) can be defined relative to its corresponding assembly embodiments of the present invention , pivoting tracking rollers may not incorporated into the rack . assembly ( 40 b ) is also provided with idler rollers ( 90 c ) and ( 90 d ). as depicted in zone ( 200 ), along with its pressure rollers ( 60 a ′, 60 b ′, 60 c ′ and 60 d ′), rack ( 50 a ) can include pivoting tracking roller ( 82 ) and idler rollers ( 90 a ′ and ( 90 b ′). upper portion ( 82 ) of pivoting tracking roller ( 82 ) extends above upper surface ( 66 ) of rack ( 50 a ). likewise the upper portions the rack &# 39 ; s ( 50 a ) pressure rollers ( 60 a ′, 60 b ′, 60 c ′ and 60 d ′) can also extend above the upper surface ( 66 ) of rack ( 50 a ) to engage the belt ( not shown ). [ 0069 ] fig2 is an exploded bottom view of assembly ( 40 a ) of zone ( 200 ) which does not show the narrow belt or the item carrying rollers ( 30 ). sidewalls ( 120 and 122 ) depend downward from upper surface or side ( 66 ) of rack ( 50 a ). upper side ( 66 ) has openings ( 68 a , 68 b , 68 c and 68 d ) fitted for pressure rollers ( 60 a ′, 60 b ′, 60 c ′ and 60 d ′). each pressure roller ( 60 a ′, 60 b ′, 60 c ′ and 60 d ′) turns about its corresponding axle ( 72 a , 72 b , 72 c and 72 d ). sidewalls ( 120 and 122 ) of rack ( 50 a ) are provided with apertures ( 74 ) for receiving axles ( 72 a , 72 b , 72 c and 72 d ). sidewall ( 120 ) has aperture ( 124 ) for receiving arm ( 110 a ) of non - pneumatic or electric actuator ( 100 a ) that is mounted to side rail ( 24 ) of accumulation conveyor ( 20 ). due to such a configuration , in select embodiments , the combination of aperture ( 124 ) of sidewall ( 120 ) and arm ( 110 a ) can provide support for rack ( 50 a ). as shown in fig2 and 3 , holder ( 86 ) is designed to fit between sidewalls ( 120 and 122 ) of rack ( 50 a ) as well as to hold pivoting tracking roller ( 82 ). pin ( 83 ) and its corresponding counterpart ( not shown ) of holder ( 86 ) protrude though apertures of sidewalls ( 120 and 122 ) to secure holder ( 86 ) to rack ( 50 a ). rack ( 50 a ) includes opening ( 96 ) corresponding to an upper portion of pivoting tracking roller ( 82 ). bolt ( 88 ) attaches rotable bracket ( 92 ) journaling pivoting tracking roller ( 82 ) such that pivoting tracking roller &# 39 ; s ( 82 ) upper portion can pivot substantially in a plane of contact with the narrow belt ( not shown ) and relative to sideways movements of the belt as the belt traverses about pressure rollers ( 60 a ′, 60 b ′, 60 c ′ and 60 d ′) and pivoting tracking roller ( 82 ) of rack ( 50 a ). in other words , upper portion of pivoting tracking roller ( 82 ) pivots in a plane that is substantially horizontal relative to the underneath side of its corresponding item transporting rollers ( 30 ), i . e ., pivoting roller ( 82 ) can move relative to the sideways movement of the belt . as best shown in fig2 and 5 , zone ( 200 ), mounting brackets ( 130 and 132 ) are attached , in any manner acceptable in the art , to side rail ( 24 ) of accumulation conveyor ( 20 ). shaft ( 140 a ) extends inward from mounting bracket ( 130 ) relative to side rail ( 24 ) of accumulation conveyor ( 20 ) and shaft ( 140 b ) extends inward from mounting bracket ( 132 ). at first end ( 152 ), movable linkage ( 150 a ) is attached to shaft ( 140 a ) and at second end ( 154 ), pin ( 156 ) hinges movable linkage ( 150 a ) to rack ( 50 a ). in a similar manner , first end ( 158 ) of movable linkage ( 150 b ) is attached to shaft ( 140 b ) and pin ( 155 ) hinges movable linkage ( 150 b ) to rack ( 50 a ). as disclosed , movable linkages ( 150 a and 150 b ) are four - bar linkages . however , those skilled in the art recognize other types of movable linkages or movable supports can also be utilized to maintain upper side ( 66 ) of rack ( 50 a ) in a substantially parallel spatial relationship to the underneath side ( 28 ) of the zone ( 200 ) of item transporting rollers . as shown , idler rollers ( 90 a ′) and ( 90 b ′) also extend inward from mounting brackets ( 130 and 132 ), but other idler roller configurations are can be utilized within the scope of the present invention . with a view toward fig4 zone ( 800 ) of item transporting rollers ( 30 ) is portrayed . assembly ( 40 d ) is attached to side rail ( 24 ) of frame ( 22 ) of accumulation conveyor ( 20 ). similar to assembly ( 40 a ) enabled in fig1 and 3 , assembly ( 40 d ), among other elements , has rack ( 50 d ) journaling a plurality of pressure rollers and pivoting tracking roller , actuator ( 100 d ) and arm ( 110 d ). and as will be disclosed more fully below , other embodiments can include one or more flanged pressure rollers . as shown in fig4 the length of rack ( 50 d ) of assembly ( 40 d ) approximates the length of its corresponding zone &# 39 ; s ( 800 ) item transporting rollers ( 30 ). attached laterally of assembly ( 40 d ) is end idler roller ( 172 ). end idler roller ( 172 ) can by supported by side rail ( 24 ) in any manner acceptable in the art . in this view , mounting bracket ( 174 b ) and shaft ( 176 b ) hold end idler roller ( 172 ) in operational relationship with assembly ( 40 d ) of zone ( 800 ) of accumulation conveyor ( 20 ). [ 0074 ] fig5 exhibits a belt ( 180 ) that can engage item transporting rollers ( 30 ) of zone ( 200 ). in the embodiment shown , the width of belt ( 180 ) approximates the length of pressure rollers ( 60 a ′, 60 b ′ and 60 c ′). end idler roller ( 170 ) and assembly ( 40 a ) are each mounted to side rail ( 24 ) of frame ( 22 ) of accumulation conveyor ( 20 ). cross tie ( 32 ) joins side rails ( 24 ) and ( 26 ). and movable linkages ( 150 a and 150 b ) maintain upper surface ( 66 ) of rack ( 50 a ) in substantially parallel spatial relationship with underneath side ( 28 ) of item transporting rollers ( 30 ) of zone ( 200 ). depending upon activation or deactivation of actuator ( 40 a ), rack ( 50 a ) of assembly ( 40 a ) can be stationary , or moving upward toward , or downward from item transporting rollers ( 30 ). upon engagement of pivoting tracking roller ( 80 ) with the narrow belt ( 180 ), pivoting tracking roller ( 80 ) can pivot relative to the sideways movement of belt ( 180 ) as the belt travels about the assembly &# 39 ; s ( 40 ) pressure rollers . arm ( 110 a ) is received by rack ( 50 a ). as disclosed in fig5 non - pneumatic actuator ( 100 a ) is a direct current electric actuator . however , other types of non - pneumatic actuators , such as solenoids or alternating current electric actuators can be incorporated to the practice of the present invention . and fig6 b shows the deactivated offset shaft ( 310 ). activated offset shaft ( 310 ) and roller bearing ( 312 ) vertically lift the rack to engage the narrow belt . in the deactivated mode , the offset shaft ( 310 ) has vertically lowered the rack away from the underneath side of its corresponding zone of item carrying rollers . with a view toward fig6 and 7 , arm ( 330 ) of actuator ( 300 ) includes housing ( 302 ), offset shaft ( 310 ), roller bearing ( 312 ) and nut ( 314 ). thus , in select embodiments arm ( 330 ) can provide support as well lift for its corresponding rack . however those skilled in the art recognize that offset shaft ( 310 ) alone can function as the actuator &# 39 ; s movable support or arm . lines ( 320 ) supply power to actuator ( 300 ) and connections ( 322 ) are for lines ( not shown ) running to the actuator &# 39 ; s sensor . with a view toward fig8 back ( 306 ) is exploded away from housing ( 302 ) of actuator ( 300 ) to reveal electrical motor ( 350 ) and controller ( 360 ). lines ( 320 ) supply power to stepped electrical motor ( 350 ). in this specific embodiment , stepped electrical motor ( 350 ) can generate a 180 degree rotation of offset shaft ( 310 ) of arm ( 330 ). as shown , controller ( 360 ) is a microprocessor that has been positioned inside housing ( 302 ) of actuator ( 300 ), but it is contemplated other types of controllers as well as their locations in relation to actuator ( 300 ) are within the scope of the present invention . [ 0078 ] fig9 is a close up of a type of pressure roller within the scope of the present invention . pressure roller ( 370 ) has a flanged edge ( 372 ) at its first lengthwise edge and flanged edge ( 374 ) at its opposite lengthwise edge . axle ( 376 ) runs the length of pressure roller and is sized for journaling pressure roller ( 370 ) in a rack such as one of those previously disclosed and enabled above . in select embodiments , one or more flanged pressure rollers can be incorporated into any rack to center the belt &# 39 ; s sideways movements . in other embodiments and as previously enabled , a pivoting tracking roller can be utilized to center the narrow belt . in still other embodiments , a combination of pivoting tracking rollers and flanged pressure rollers can be utilized to center the belt . among other things , along with providing non - pneumatic actuation of the accumulation conveyor &# 39 ; s assemblies and the subsequent elimination of the prior art &# 39 ; s pneumatic compressors , lines , bladders , tubing , et cetera , the practice of the present invention can meet the long felt but unfulfilled need of providing multiple means and / or combinations of structures to center the belt about the accumulation conveyor &# 39 ; s assemblies . as portrayed in fig1 , for zones ( 200 ), ( 400 ), ( 600 ) and ( 800 ), among other elements , each zone includes its corresponding assembly ( 40 a ), ( 40 b ), ( 40 c ) and ( 40 d ), as well as the zone &# 39 ; s sensor ( 190 a ), ( 190 b ), ( 190 c ) and ( 190 d ) for detecting the presence of items in each respective zone ( 200 ), ( 400 ), ( 600 ) and ( 800 ). any type of sensor , such as photoelectric or pressure , is within the scope of the present invention . and as previously set forth , the number of zones for accumulation conveyors in accordance with the present invention are limited only by space and engineering parameters . depending upon a predetermined paradigm , detection of an item or items in any zone can actuate its corresponding zone &# 39 ; s assembly to cause the narrow belt to engage the underneath side of the zone &# 39 ; s corresponding item transporting rollers . as previously enabled , logic can be incorporated on or about the actuators ( 100 a ), ( 100 b ), ( 100 c ) and ( 100 d ) of each zone ( 200 ), ( 400 ), ( 600 ) and ( 800 ) of accumulation conveyor ( 20 ). in one embodiment of the present invention , whenever possible , each actuator is linked ( not shown ) by any means convenient in the art with its immediate upstream and downstream actuator . by way of illustration , actuator ( 40 a ) is linked with actuator ( 40 b ); actuator ( 40 b ) is linked with actuators ( 40 a ) and ( 40 c ); actuator ( 40 c ) is linked with actuators ( 40 b ) and ( 40 c ), so forth and so on . in another embodiment , all actuators of the assemblies of accumulator can be linked to a logic circuit ( not shown ) so that each microprocessor can communicate with every other microprocessor of accumulation conveyor ( 20 ). under such a linked actuator concept , the logic circuit and the resultant activation or deactivation of the accumulator &# 39 ; s actuators can be controlled by a central processing unit . [ 0081 ] fig1 is a pictorial top view a type of a type of drive pulley unit ( 500 ) utilized to practice of the present invention . narrow belt ( 180 ) shown in phantom is driven by drive pulley ( 510 ) about accumulation conveyor ( 20 ). drive pulley ( 510 ) extends outward from gearbox ( 512 ) that is powered by electric motor ( 514 ). snub rollers ( 522 ), ( 524 ) and ( 526 ) are aligned with drive pulley ( 510 ) for engaging narrow belt ( 180 ) as the belt winds about accumulation conveyor ( 20 ). drive pulley ( 510 ), gearbox ( 512 ), electric motor ( 514 ) and snub rollers ( 522 ), ( 524 ) and ( 526 ) are attached to drive pulley unit ( 500 ) in any manner acceptable in the art . takeup pulley ( 530 ) is mounted to slide ( 532 ) which can slide along guide ( 540 ). members ( 542 ) and ( 544 ) form guide ( 540 ). as shown member ( 542 ) includes channel ( 548 ) for guiding slide ( 532 ) while member ( 544 ) also includes a channel ( not shown ) for guiding slide ( 532 ). cable ( 550 ) is connected to slide ( 532 ) via connector ( 534 ) and wound about pulleys ( 552 ) and ( 554 ); thereafter , cable ( 550 ) is connected to spring motor ( 560 ) via connector ( 556 ). as portrayed in fig1 , spring motor ( 560 ) is a constant force spring takeup . [ 0082 ] fig1 is a top view representation of a constant force spring takeup spring motor ( 560 ). housing ( 562 ) is cutaway to reveal storage drum ( 564 ) and takeup drum ( 566 ). spring ( 568 ) is wound about storage drum ( 564 ) and takeup drum ( 566 ). [ 0083 ] fig1 is a side view of spring motor ( 560 ) with housing ( 562 ) cutaway . in this specific embodiment , spring motor ( 560 ) includes constant force springs ( 568 a and 568 b ), but depending upon engineering parameters , spring ( 560 ) can comprise one , two , three or more constant force springs . takeup drum ( 566 ) and storage drum ( 564 ) are mounted inside housing ( 562 ) in any manner acceptable in the art . winding ( 570 ) of output drun ( 566 ) extends through aperture ( 572 ) of housing ( 562 ) to connect with cable ( 550 ). in operation , the combination of spring ( 560 ), cable ( 550 ), takeup pulley ( 530 ), slide ( 532 ), guide ( 540 ), etc . applies a constant force takeup to belt ( 180 ) as the belt winds about accumulation conveyor ( 20 ). steps associated with the practice of the methods of present invention utilizing select structural elements enabled above are set forth in fig1 - 19 . having disclosed the invention as required by title 35 of the united states code , applicants now pray respectfully that letters patent be granted for their invention in accordance with the scope of the claims appended hereto .
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by way of example , the present invention is illustrated in terms of a method and apparatus used in a self - checkout system in a retail store . the example application described herein is only one example application of the present invention and is provided for the purpose of better explaining the present invention . the present invention may be applied to any number of other data collection systems having a number of potential users employing a portable data collection terminal to update a centralized data file . thus , the present invention should not be limited to the specific example described herein . as illustrated in fig1 a customer is provided with a customer loyalty card 10 having encoded customer data stored thereon . corresponding customer information is also placed in a customer data file on a central storage system for the self - checkout system . once a customer loyalty card 10 has been issued and a corresponding customer data file is established on the central storage system , the customer may then use the system to perform self - checkout of merchandise distributed in a facility employing the self - checkout system . to use the system , a customer proceeds to an entrance unit 20 and inserts their customer card 10 into slot 22 . a card reader on the entrance unit 20 reads the information stored on the card and checks with the central storage system to confirm that a corresponding customer data file exists and that the customer is authorized to use the system . once system approval is obtained , a display unit 24 on the entrance unit 20 instructs the user to proceed to a designated area of a dispenser unit 30 to retrieve a designated data collection unit such as a bar code reader with integrated terminal features 40 . although not shown , the system could also be provided with a entry gate which is activated to permit the customer through upon the assignment of the bar code reader 40 and blinking lights 33 on the side of the dispenser and above the dispenser to direct the customer to the proper location . these systems are especially necessary in large stores having a high number of dispenser units . the bar code reader 40 is provided with a flashing light 42 to assist the customer in retrieving it after it has been assigned to the customer . the flashing light 42 is activated by the central processor ( shown in fig2 ) after it has been assigned to the customer and the assignment is recorded in the customer &# 39 ; s data file . in an alternative embodiment , the bar code reader is further provided with an audible signal generator to assist the user in finding it in the terminal dispenser and a visual display for displaying either the customer &# 39 ; s name or some other form of customer identifiable code . the bar code reader 40 is stored in one of a plurality of reader slots 34 in the dispenser unit 30 . each of the slots is physically and electronically marked and may be provided with locking means for locking the bar code reader 40 in place until the bar code reader is assigned for use to a customer . the physical marking is used to direct the customer to the proper location on the dispenser , i . e ., location &# 34 ; a9 ,&# 34 ; and the electronic marking is provide as a means for identifying the location of the bar code reader by the central processor . the electronic means may comprise a bar code located on the terminal dispenser 30 such that when the bar code reader 40 is locked in place , the bar code can be read by the bar code reader 40 and communicated to the central processor . once the bar code reader 40 is assigned to a customer , the locking means is disengaged . in the event the bar code reader is not removed from the slot 34 after a predetermined time period , it is again locked and the customer data file for the customer to whom it was assigned is updated to reflect that the customer did not take possession of the reader within the allotted time period . prior to issuance to a customer , the bar code reader 40 could also be required to scan the bar code located on the terminal dispenser as a self - diagnostic tool . in a preferred embodiment , the bar code is sufficiently degraded to test the outer boundaries of the bar code readers capabilities . thus , if the bar code reader is unable to read the bar code and communicate the bar code symbol top the central processor , it will not be assigned . the central processor will notify the supervising attendant that the terminal is not functioning properly . once a customer has been issued a bar code reader 40 , the customer proceeds through the retail facility and uses the bar code reader 40 to record purchases . preferably each item is either coded with a code which is recognizable to the bar code reader , or in the case of produce which is sold by weight , is provided with a machine for generating an adhesive bar coded ticket after the produce is weighed . upon scanning of the code on a selected merchandise item 60 , a display 44 on the bar code reader 40 displays product information such as price , product name , quantity and nutritional information . in a preferred embodiment of the present invention , the bar code reader 40 is provided with a processing means for recording all items selected by the customer . alternately , the bar code reader 40 acts as a dumb terminal with radio frequency communication means . in such case , all information is stored in a central location and the bar code reader 40 simply communicates data to the central location . in a preferred embodiment of the present invention , the reader permits a customer to add a product to their record through the selection of an &# 34 ; add &# 34 ; key 46 , return a scanned product previously selected by selecting a &# 34 ; minus &# 34 ; key 47 or simply to perform a price check or other information check by pressing an &# 34 ; equals &# 34 ; key 48 . in a preferred embodiment , the &# 34 ; equals &# 34 ; key 48 may also be used to provide the customer with a running total of the products selected . once the customer has completed their product selection , the customer returns the bar code reader 40 to the dispenser unit 30 where it is placed in an open slot 34 . upon return of the bar code reader 40 , information collected with the bar code reader 40 is downloaded to a central processing unit and a ticket for the items is issued to the customer from a printer 32 which is located near or on the dispenser . communication between the bar code reader 40 and the central processing unit is completed through a communication network which may consist of either a wired communication bus which coupled through a port on the bar code reader 40 when it is placed in the dispenser unit 30 , or through an rf network which is active when the bar code reader 40 is placed in the terminal dispenser 30 . in an alternative embodiment of the present invention , rather than issuing a ticket at the terminal dispenser location , a card reader and data entry device are provided at the cash register the customer may then enter their customer card and pin number at the cash register location . prior to updating any customer data files , the customer is requested to insert the customer loyalty card 10 and / or enter a pin code to ensure that the customer is in fact the same person who initially retrieved the scanner . this is especially important in the event the system provides for electronic fund transfers for payment and information for such transfers are stored wholly or partially in a customer data file . once the central processing system has successfully retrieved the customer information from the bar code reader 40 , the customer then proceeds to a checkout register 50 for payment of the products selected . in the event a debit operation was made at the dispenser unit 30 , confirmation of payment . the checkout system may be an automated system or a manually operated system . the ticket is either scanned or otherwise read at the checkout 50 and the customer is asked to pay for the goods selected if payment has not been previously made . recognizing that some goods may not be scanned due to coding damage or other issues , a customer may proceed to a manned checkout station for the addition of items to their receipt . at such point , additional payment made need to be made using traditional payment schemes , or if the central processing unit is being used to provide a debit function , customer card and pin code information may need to be entered at the checkout facility . after all items are selected and the transaction is complete , the customers data file is updated in the central processing unit to reflect the customer &# 39 ; s shopping activities . in an alternative embodiment of the present invention , the customer loyalty card is also used to selectively activate and deactivate the portable bar code reader by scanning the customer loyalty card with the bar code reader . thus , in the event the customer wishes to maintain the bar code reader but does not wish to have it activated , they simply scan their customer loyalty card . this deactivates the bar code reader from updating a session data record of items selected for purchase by the customer which is being generated with the bar code reader . when the customer wishes to reactivate the bar code reader , the customer simply re - scans their customer loyalty card . this function is useful in situations were the customer may not wish to maintain constant supervision over the scanner . for instance , in the event a customer with children wishes to stop at the store cafeteria or try on some clothes in a dressing room , the customer can deactivate the bar code reader in order to prevent the children from accidentally scanning or deleting items into the session data record . turning to fig2 the data processing functions of the system are controlled by a central processing system 100 . this central processing system could be either a single high capacity computer , or a distributed network of computers . the system is coupled to the entrance unit 20 , the dispenser unit 30 and may also be coupled through an rf network to each of the bar code readers 40 which are dispensed through the dispenser unit 30 . alternatively , the dispenser unit 30 is provided with a communication bus for communicating data from the bar code reader 40 the central processing system 100 once the bar code reader 40 is placed in the dispenser unit 30 . the central processing system 100 includes memory having a data file 150 , ( fig3 and 4 ) for each of the customers authorized to use the system . after the entrance unit 20 reads the information on a customer card 10 , the entrance unit 20 communicates the data retrieved from the customer card to the central processing system 100 . the central processing system searches for and confirms that the data on the customer card 10 corresponds to a person authorized to use the self - checkout system and that no blocking information is present which would prevent the user form using the system . in a preferred embodiment of the present invention , the central processor system maintains a data file 170 , fig3 and 4 for each customer . in a preferred embodiment , the data file 170 includes the following data fields : customer name 171 , address 172 , account information 173 ( such as amounts due ), purchase histories 174 ( last five shopping sessions ) and an account clear field 175 . the account clear field 175 is used to indicate that ( i ) the customer has not previously performed an illegal function such as ( ii ) not returning a bar code reader 40 , ( iii ) generated excessive account debits , or ( iv ) has deceased . the entry of the customer card in the entrance unit 20 results in the communication of the data stored in the customer card to the central processing unit . once the central processing system 100 determines that the customer card entered into the entrance unit 20 belongs to an authorized customer and that the corresponding customer is cleared to use the system , the central processor assigns a bar code reader 40 to the customer , communicates the assignment to the entrance unit 20 where it is displayed and to the bar code reader 40 in the dispenser unit 30 . upon receiving the assignment signal , the designation light 42 on the bar code reader is activated and the locking mechanism in the dispenser unit for the designated bar code reader 40 is disengaged . in addition , the account clear field 175 is changed to reflect that a bar code reader 40 has been issued and not returned . the central processor system 100 updates the customer data file 170 to reflect the time , date and the bar code reader 40 designation for this session . in the event the bar code reader 40 is a batch type system , all customer selections with the bar code reader 40 are stored locally in the memory of the bar code reader 40 . alternatively , the system 100 and the bar code reader 40 may be provided with a wireless communication network such as an rf communication network . if such a system is used , all central processing customer transactions may be stored remotely on a system controlled by the central processor system 100 . once the customer has completed the session and returns the bar code reader 40 to the dispenser unit 30 , the customer is prompted to enter the customer loyalty card 10 which was used to retrieve the bar code reader 40 upon entry and enter an additional credit card , authorization code and / or signature on a signature pad if the transaction requires a debit or eft transaction . once this data is received , the customer data file 170 is updated to reflect changes in the purchase history field 173 and account information field 173 . if the bar code reader 40 is returned to the dispenser and the transaction is completed without incident , i . e ., the payment is received , the account clear field 175 is then cleared permitting the user to permit subsequent use of the system . alternatively , all customer account credit and payment information is stored on a secure server and encoded . the encoding mechanism may be a forty bit key or higher depending on the amount of security required for the system and whether the information will be made available over a public network . in an alternative embodiment of the present invention , the locking mechanism of the dispenser 30 is used to engage the bar code reader 40 once it is returned into slot 34 for final processing . if the bar code reader 40 was returned by someone who stole or simply took some other customer &# 39 ; s bar code reader by mistake , the bar code reader 40 is kept in the system until it is released by the authorized person or a customer service employee . in a preferred embodiment , the service desk facility 200 performs three basic functions : ( 1 ) customer management ; ( 2 ) scanner management ; and ( 3 ) report processing . each of these functions is described below : the service desk facility 200 includes a customer service console 210 . the console 210 may comprise a pc having a display terminal , keyboard , data processing unit and a communication bus coupled to the central processing system 100 through either a local or wide area network . the customer service console 210 is used to enter customer information such as new customer information . the entry of such information will generate a customer data file for the new customer and designate a customer loyalty card to the new customer . customer data may be stored on the customer loyalty card using a card writer 230 . in the event a customer has a complaint regarding the record maintained by the bar code reader 40 or is for some reason locked out of the system or if some other hardware problem is presenting itself on the system , the service desk console 210 may also be used to retrieve the relevant customer data file from the central processing system 100 and information from the bar code reader 40 issued to the customer . in order to read the bar code reader 40 , the system console may be provided with a separate bar code receiver for communicating with the bar code reader 40 . the customer service attendant may then clear , correct or otherwise tend to any system malfunction or customer questions using the retrieved data . in order to assist the customer , the service facility 200 is provided with a card reader 220 and , if required , a numeric keypad on the console 210 to receive a security pin code . this will confirm that the customer seeking assistance is in fact an authorized customer . in the absence of such security measures , a person who finds a customer card could easily use the system to purchase items on an authorized customer &# 39 ; s account . the service facility also functions to control the activity of the dispenser unit 30 . the console 210 is connected to the central processing system 100 and may override the locking function of the dispenser so as to lock everyone out after a certain time , i . e ., 10 minutes before closing , and to reopen the system in the morning . in addition , the service console 210 may be used to maintain surveillance over bar code readers 40 which have been issued , returned without receipt of an authorization code and not retrieved after the system has designated a bar code reader for use by a customer , thus providing a mechanism for identifying customer misuse or errors in using the system . in the event a customer should lose a printed receipt or receive an illegible copy ( or require a copy from a prior shopping session ), a customer receipt printer 250 is also provided . in the event a line forms at the entry unit 20 , the service facility can also function as a supplemental entrance unit . the service facility is provided with a card reader 220 and a keypad on the console 210 for entry of a pin code . the customer service facility 200 may also be used to generate reports such as daily , weekly and annual sales report . these reports may be printed on a report printer 240 at predetermined times ( i . e ., every monday at 6 : 00 a . m .) or at the entry of a request on the console 210 . as shown in fig2 the self - checkout system of the present invention may be coupled directly to an existing point of sale ( pos ) system 500 which is connected to and supervises activities on existing checkout registers 50 . the existing pos system 500 could be used to maintain inventory histories , update product information and other system functions . the system requirements for the central processing system 100 are therefore diminished and the necessary system requirements are reduced . this effectively reduces the cost of implementing the self - checkout system in a retail facility having an existing system . in an alternative preferred embodiment of the present invention , in the event the existing pos system 500 has sufficient system resources available , the functions of the central processing system 100 are incorporated into the pos system 500 . based on the above disclosure , it would be obvious to those skilled in the art to make numerous modifications to the herein described embodiments without straying from the present invention . for instance , various modifications could be made to the customer data files to record various forms of additional customer information . in addition , various system components could be integrated to provide the same overall functions , i . e ., attaching the entrance unit 20 to the dispenser unit 30 . moreover , although certain embodiments of the present invention are described in the context of an rf network system , it would be understood by those skilled in the art that equivalent systems could be implemented using various wireless communication systems .
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fig1 a and 1b show the circuit construction of an electronic timepiece with alarm function . an oscillator 1 generates a reference clock signal which is coupled to and frequency divided by a frequency divider 2 to obtain a signal having a period of one second . this one second signal is supplied to a time counting circuit 3 and counted therein . the time counting circuit 3 provides time count data such as hour , minute and second data on the basis of the one second signal mentioned above . the time count data is fed through a display control section 4 to a display section 5 for analog or digital display . this data is also fed to first and second alarm circuits 6 and 7 in which desired alarm time data are preset . the first and second alarm circuits 6 and 7 include respective coincidence circuits ( not shown ) which generate an alarm signal al 1 or al 2 as a single pulse signal when they detect the coincidence of the aforementioned time count data and preset alarm time data . the preset alarm time data in the first and second alarm circuits 6 and 7 are provided through the display control section 4 to the display section 5 for analog or digital display . a switch s 1 is a display mode selection switch , and a signal generated when it is operated is coupled to a scale of 3 mode counter 8 , which changes its content to &# 34 ; 0 &# 34 ;, &# 34 ; 1 &# 34 ;, &# 34 ; 2 &# 34 ;, &# 34 ; 0 &# 34 ;, . . . every time the switch operation signal from the switch s 1 is coupled and provides signal &# 34 ; 1 &# 34 ;, &# 34 ; 1 &# 34 ;, &# 34 ; 2 &# 34 ;, &# 34 ; 0 &# 34 ;, . . . corresponding to its prevailing content as a display mode signal to the display control section 4 . when the content of the mode counter 8 is set to &# 34 ; 0 &# 34 ;, an ordinary time display mode in which the display control section 4 couples the time count data from the time counting circuit 3 to the display section 5 for display therein is selected . when the mode counter circuit is set to &# 34 ; 1 &# 34 ;, a first alarm time display mode in which the alarm time data in the first alarm circuit 6 is coupled through the display control section 4 to the display section 5 for display is selected . when the mode counter content is set to &# 34 ; 2 &# 34 ;, a second alarm time display mode in which the alarm time data in the second alarm circuit 7 is coupled through the display control section 4 to the display section 5 for display is selected . the signals &# 34 ; 1 &# 34 ; and &# 34 ; 2 &# 34 ; of the mode counter 8 are coupled as an enable signal through an or gate 9 to an and gate 10 . thus , when a recording switch s 2 is operated in the first or second alarm time display mode , the key operation signal from the switch s 2 is coupled through the and gate 10 to a delay circuit 11 . the delay circuit 11 delays the switch operation signal from the recording switch s 2 for a predetermined period of time . the signal &# 34 ; 1 &# 34 ; of the mode counter 8 is also coupled to and gates 12 and 13 , and the output signal from the delay circuit 11 is coupled directly to the and gate 12 and also coupled through an inverter 14 to the and gate 13 . the output of the delay circuit 11 is further coupled to a delay circuit 15 . the delay circuit 15 delays the output signal of the delay circuit 11 , and its output signal is coupled through an inverter 16 to the and gate 12 and is also coupled directly to the and gate 13 . thus , when the switch s 2 is operated while the mode counter 8 is set to &# 34 ; 1 &# 34 ;, an output of one - shot is provided from the and gate 12 from the rising of the output signal of the delay circuit 11 till the falling of the output signal of the inverter 16 ( i . e ., the rising of the output signal of the delay circuit 15 ). also , since the output signals of one - shot of the delay circuits 15 and 11 are coupled to the and gate 13 , when the switch s 2 is brought from the operated state to the non - operated state an output is provided from the and gate 13 from the rising of the output signal of the inverter ( i . e ., the falling of the output signal of the delay circuit 11 ) till the falling of the output signal of the delay circuit 15 . the output signals of the delay circuits 11 and 15 are also coupled to an and gate 17 , so that an output signal is obtained from the and gate 17 while both the delay circuits 15 and 11 are providing their outputs . when the content of the mode counter 8 is &# 34 ; 2 &# 34 ;, i . e ., in the second alarm time display mode , the signal &# 34 ; 2 &# 34 ; of the mode counter 8 is coupled to and gates 18 and 19 . to the and gate 18 , like the and gate 12 , the output signal from the delay circuit 11 and the output signal from the delay circuit 15 through the inverter 16 are coupled , so that when the switch s 2 is operated in the second alarm display mode , a single pulse signal is provided from the and gate 18 . to the and gate 19 , like the and gate 13 , the output signal from the delay circuit 11 through the inverter 14 and the output signal from the delay circuit 15 are coupled , so that when the switch s 2 is brought from the operated state to the non - operated state a pulse signal is provided from the and gate 19 . the signal provided from the and gate 12 is coupled through the or gate 20 to an address section 21 including an address counter ( not shown ) to reset the content thereof . the address section 21 is rendered operative when the output signal of the and gate 17 is coupled as an operation command signal through an or gate 22 , and the content of the address counter is incremented by &# 34 ;+ 1 &# 34 ; as each clock pulse signal at a predetermined frequency is provided from the frequency divider 2 while the and gate 17 is providing the output signal . the content of the address section 21 is coupled as address designation data to a ram 23 . thus , the specified address of the ram 23 is progressively shifted every time the content of the address section 21 is changed by &# 34 ;+ 1 &# 34 ;. the content of the address section 21 is preset in an address memory 25 through an and gate 24 . the address data preset in the address memory 25 is preset in the address section 21 again through an and gate 27 , to which the output signal from the and gate 18 is coupled as an enable signal . the output signal from the and gate 19 is coupled as reset signal through the or gate 20 to the address section 21 . the alarm signal al 1 provided from the first alarm circuit 6 mentioned above is coupled through the or gate 20 to the address section 21 to reset the content thereof , and it is also coupled to the set side input terminal s of an rs flip - flop 30 and further through an or gate 28 to the set side input terminal of an rs flip - flop 29 . the set signal of the flip - flop 29 is coupled as an operation command signal through the or gate 22 to the address section 21 . the set signal of the flip - flop 30 is coupled as an operation command signal to a coincidence circuit 31 , to which the address data from the address section 21 and the address data preset in the address memory 25 are coupled . when the coincidence circuit 31 detects the coincidence of the address data in the address section 21 and the address data in the address memory 25 , it generates a single pulse as a coincidence signal which is coupled through an or gate 32 to the reset input terminals r of the flip - flops 29 and 30 to reset these flip - flops . the alarm signal al 2 provided from the second alarm circuit 7 is coupled to the or gate 28 and also coupled as an enable signal through an or gate 26 to an and gate 27 . a carry signal c provided from the address counter of the address section 21 is coupled through an or gate 32 to the reset input terminals r of the flip - flops 29 and 30 . designated at 33 is a microphone provided in the timepiece . a voice signal provided from the microphone 33 is coupled to an a / d ( analog / digital ) converter 34 . the a / d converter 34 converts the voice signal from the microphone into a digital voice signal which is coupled to an encoder 35 . the encoder 35 encodes the digital voice signal into data representing the interval , volume , etc ., and this voice code is coupled to the ram 23 . the a / d converter 34 and encoder 35 are rendered operative when the recording signal from the and gate 17 is coupled as an operation command signal to them . the ram 23 receives the recording signal from the and gate 17 at its read / write input terminal w / r , and it is given a write designation when the recording signal is at a binary logic level &# 34 ; 1 &# 34 ; and a read designation when the signal is at a level &# 34 ; 0 &# 34 ;. the write or read out operation of the ram 23 is done in synchronism to the clock signal ( not shown ) provided from the frequency divider 2 and with respect to a memory region , whose address is specified by the address section 21 . the voice code written in the ram 23 is read out to a decoder 36 . the operation in the decoder 36 is converse to that in the encoder 35 , and the decoded signal output is coupled to an alarm signal synthesizing circuit 37 . the alarm signal synthesizing circuit 37 synthesizes a voice signal from the decoded signal output of the decoder 36 , and the voice signal thus obtained is coupled to a loudspeaker 38 for producing alarm sound . the decoder 36 and alarm signal synthesizing circuit 37 are rendered operative when the set signal of the flip - flop 29 is coupled as an operation command signal to them . now , the operation of the electronic timepiece having alarm function having the above construction will be described . when the content of the mode counter 8 is &# 34 ; 0 &# 34 ;, the time count data obtained in the time count circuit 3 is fed through the display control circuit 4 to the display section 5 for display as ordinary time data . when the mode selection switch s 1 is operated in the ordinary time data display mode , its content is incremented by &# 34 ; 1 &# 34 ;, so that the signal &# 34 ; 1 &# 34 ; is provided from the mode counter 8 and coupled to the display control circuit 4 . thus , the alarm time data preset in the first alarm circuit 6 is coupled through the display control circuit 4 to the display section 5 for display . now , the case of recording an alarm voice ( for instance &# 34 ; meeting &# 34 ;) corresponding to the alarm time ( for instance &# 34 ; 10 : 30 a . m .&# 34 ;) preset in the first alarm circuit 6 in the first alarm time display mode will be described . when the recording switch s 2 is operated in the &# 34 ; 1 &# 34 ; state of the mode counter 8 , its operation signal is coupled through the and gate 10 , which has been enabled by the signal &# 34 ; 1 &# 34 ; of the mode counter 8 , to the delay circuit 11 , so that the delay circuit 11 provides the output signal after a predetermined delay time . the output signal of the delay circuit 11 is coupled to the delay circuit 15 , which provides a delayed output signal after a predetermined delay time . thus , the single pulse signal is provided from the and gate 12 to clear the address counter in the address section 21 . while the recording switch s 2 is being operated , during which time the output signals of the delay circuits 11 and 15 are coupled to the and gate 17 , the and gate 17 provides the output signal while the delay circuits 11 and 15 are providing the output signals . with the appearance of the output signal from the and gate 17 , the a / d converter 33 and encoder 34 are rendered operative , while the ram 23 is given a write designation . further , the address section 21 is rendered operative to cause counting operation of the address counter which has been cleared as mentioned earlier . in this state , by pronouncing the alarm voice (&# 34 ; meeting &# 34 ;) which is the content to be executed at the alarm time preset in the first alarm circuit 6 , to the microphone 32 , the microphone 32 produces a voice signal which is converted through the a / d converter 34 into the digital voice signal , which is in turn encoded through the encoder 35 before being coupled to the ram 23 . the voice code coupled to the ram 23 is written therein in the memory region thereof , whose address is specified by the address data from the address section 21 . since the content of the address counter in the address section 21 is cleared prior to the recording operation by the output signal from the and gate 12 , at the time of the start of the recording operation the first address of the ram 23 is first specified , and then the specified address of the ram 23 is progressively shifted every time the content of the address counter in the address section 12 is incremented by &# 34 ;+ 1 &# 34 ;, whereby the voice codes representing the voice &# 34 ; meeting &# 34 ; are written in the memory region of the specified addresses . when the pronounciation of the sound &# 34 ; meeting &# 34 ; is ended , the recording switch s 2 is released , whereupon a single pulse signal is provided from the and gate 13 . by this pulse signal the and gate 24 is enabled , whereby the content of the address section 21 , i . e ., the address data therein at the time of the releasing of the switch s 2 , is coupled through the and gate 24 to the address memory 25 and registered therein . when the mode selection switch s 1 is subsequently operated to set the content of the mode counter 8 to &# 34 ; 2 &# 34 ;, the signal &# 34 ; 2 &# 34 ; is provided therefrom and coupled to the display control section 4 . thus , the display mode is switched over to the second alarm time display mode , and the alarm time data preset in the second alarm circuit 7 is coupled through the display control section 4 to the display section 5 . if an alarm voice ( for instance &# 34 ; a telephone call for mr . a &# 34 ;) corresponding to the alarm time ( for instance &# 34 ; 3 : 30 p . m .&# 34 ;) preset in the second alarm circuit 7 is to be recorded in the second alarm time display mode , the recording switch s 2 is operated again . the switch operation signal thus provided from the switch s 2 is coupled through the and gate 10 , which has been enabled by the signal &# 34 ; 2 &# 34 ; of the mode counter 8 , to the delay circuit 11 , and the delay circuit 11 provides the output signal after a predetermined delay time . the output signal of the delay circuit 11 is coupled to the delay circuit 15 . thus , the aforementioned case with the and gate 12 , the and gate 18 provides a single pulse signal , which is coupled as an enable signal through the or gate 26 to the and gate 27 , whereby the address data set in the address memory 25 is coupled through the and gate 27 to the address section 21 and preset therein . the address data that is set in the address section 21 this time is what has been in the address counter in the address section 21 at the time of the end of the recording of the alarm voice (&# 34 ; meeting &# 34 ;) corresponding to the alarm time (&# 34 ; 10 : 30 a . m .&# 34 ;) set in the first alarm circuit 6 . since this address data is coupled to the ram 23 , the ram 23 is given address designation at this time from the address next to the memory region in which the voice codes for the alarm voice &# 34 ; meeting &# 34 ; are recorded . with the appearance of the recording signal from the and gate 17 , the ram 23 , a / d converter 34 , encoder 35 and address section 21 are set to the recording enable state as described previously . by pronouncing &# 34 ; a telephone call for mr . a &# 34 ; to the microphone 32 in this state , the voice codes regarding the voice &# 34 ; a telephone call for mr . a &# 34 ; are recorded in the ram 23 in a memory region thereof next to the region in which the voice codes for &# 34 ; meeting &# 34 ; are recorded . when the recording is ended , the recording switch s 2 is released , whereupon a single pulse is provided from the and gate 19 and coupled through the or gate 20 to the address section 21 to clear the content thereof . when the alarm time (&# 34 ; 10 : 30 a . m .&# 34 ;) set in the first alarm circuit 6 is reached , the alarm signal al 1 as a single pulse is provided from the first alarm circuit 6 , and it is coupled through the or gate 20 to the address section 21 to clear the content thereof . while the content of the address section 21 is cleared when the recording of the voice corresponding to the alarm time set in the second alarm circuit 7 is ended as mentioned previously , in case if the recording of the voice corresponding to the alarm time of the second alarm circuit 7 is not made , the last address data at the time of the recording of the voice corresponding to the alarm time of the first alarm circuit 6 remains memorized in the address section 21 . with the appearance of the alarm signal al 1 the content of the address section 21 is thus cleared for specifying the first address in the ram 23 . the alarm signal al 1 is also coupled through the or gate 28 to the flip - flop 29 to set this flip - flop . thus , the flip - flop 29 provides the set signal which is coupled through the or gate 22 to the address section 21 , whereby the content of the address counter in the address section 21 is progressively incremented by &# 34 ;+ 1 &# 34 ; after another . since the output of the and gate 17 is at the binary logic level &# 34 ; 0 &# 34 ;, the ram 23 is given the read designation , while the address section 21 is given address progressive designation from the first address , whereby the voice codes regarding the voice &# 34 ; meeting &# 34 ; are progressively read out from the memory region in which they are recorded . as these voice codes are read out , they are successively coupled through the decoder 36 , alarm signal synthesizing circuit 37 , these circuits being set to the operative state by the set signal of the flip - flop 29 . thus , they are each decoded in the decoder 36 and inverted in the alarm signal synthesizing circuit 37 into a voice signal which is coupled to the loudspeaker 38 for producing sound . in this way , the alarm voice sound &# 34 ; meeting &# 34 ; is produced at the alarm time &# 34 ; 10 : 30 a . m .&# 34 ;. the alarm signal al 1 mentioned above is further coupled to the set input terminal s of the flip - flop 30 to set this flip - flop , and the set signal therefrom is coupled as an operation command signal to the coincidence circuit 31 . the coincidence circuit 31 is thus rendered operative for detecting the coincidence of the address data from the address section 21 and the address data from the address memory 25 . when the coincidence circuit 31 detects the coincidence of data , i . e ., when the memory region in the ram 23 in which the voice codes regarding the voice &# 34 ; meeting &# 34 ; has been entirely specified , a coincidence signal is provided from the circuit 31 and coupled through to the reset input terminal r of the flip - flop 29 to reset this flip - flop , thus stopping the sound producing operation . when the alarm time (&# 34 ; 3 : 30 p . m .&# 34 ;) set in the second alarm circuit 7 is reached , the alarm signal al 2 is provided from the second alarm circuit 7 , and it is coupled through the or gate 28 to the flip - flop 29 to set this flip - flop and also coupled through the or gate 26 to the and gate 27 to enable this and gate . with the setting of the flip - flop 29 the address section 21 , encoder 35 and alarm signal synthesizing circuit 37 are set to the operative state , while the address data in the address memory 25 is coupled through the and gate 27 to the address section 21 and preset therein . with the address section 21 rendered operative , the ram 23 is given address designation for addresses after the address specified by the address data preset in the address section 21 . thus , the voice codes regarding the voice &# 34 ; a telephone call for mr . a &# 34 ; are read out from the ram 23 , and the voice sound &# 34 ; a telephone call for mr . a &# 34 ; is produced from the loudspeaker 37 . when the carry signal is provided from the address section 21 , it is coupled through the or gate 32 to the reset input terminal r of the flip - flop 29 , thus stopping the sound producing operation . as has been described in the foregoing according to the invention , what is scheduled to be done at an alarm time is informed of by the voice sound at the alarm time . in addition , since the voice corresponding to the alarm time set in the second alarm circuit 7 can be recorded in a recording region immediately following the recording region in which the voice corresponding to the alarm time set in the first alarm circuit 6 is recorded , that is , since any blank memory region in the ram 23 without any voice codes recorded therein between adjacent memory regions where voice codes are recorded can be eliminated , it is possible to minimize the recording capacity of the ram 23 , that is , make the most effective use of the ram capacity . while in the above embodiment of the electronic timepiece with alarm function two alarm circuits have been provided , it is possible to provide three or more alarm circuits . further , while the above embodiment has applied to the electronic timepiece having the alarm function of producing an alarm sound at a preset alarm time , the invention is also applicable for use in connection with a time informing function of producing a sound at the exact time corresponding to an integral number on a time keeper or a calendar alarm function of producing a sound on a preset day of the month , year , etc .
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according to fig1 , the system for producing and handling sausage - shaped products s , e . g . sausages s , comprises as main components a schematically shown production unit 10 for producing sausages s and storing them on rod - like elements r , e . g . smoking rods , a robotic device 20 having a control unit 22 for controlling the movement of robotic device 20 and a storage frame 30 , into which the sausages s hung up at the smoking rods r are to be moved . production unit 10 comprises a control unit 12 , a sausage production device 14 and an automatic hanging line 16 . at least automatic hanging line 16 is peripherally arranged inside an operation range 40 of robotic device 20 described below . in production unit 10 , sausages s are produced in a known manner by filling sausage meat through a filling pipe into a tubular casing and closing the casing by a clipping machine attaching and closing clips at both ends . a flexible suspension loop is fed to one of the closing clips to be attached together with said clip to the respective end of the sausages s . thereafter sausages s will be placed in regular intervals at smoking rod r in automatic hanging line 16 . robotic device 20 is positioned in the centre of its operation range 40 to reach all units and stations peripherally arranged inside operation range 40 by its pivotally attached arms 24 , 25 . at front end of arm 25 , a gripping unit 26 is arranged for gripping the rod - like element r with the sausage products s hanging thereon inside production unit 10 , in particular from automatic hanging line 16 , and moving it to movable storage frame 30 . storage frame 30 is positioned in operation range 40 of robotic device 20 . inside storage frame 30 tray rails , e . g . in the form of horizontally aligned bars , are arranged for positioning smoking rods r thereon . in fig2 , an automatic hanging line 110 is schematically and partially shown . amongst others , said automatic hanging line 110 comprises a transportation device in the form of a horizontally arranged conveyor 120 and a clamping device 130 for clamping a smoking rod r on which sausages s are to be hung up . sausages s are transported from sausage production device 14 to automatic hanging line 16 . conveyor 120 includes a conveyor belt or chain 122 which circulates in a vertical plane and on which hook elements 124 are arranged in regular intervals . conveyor chain 122 circulates about two turning points in a direction identified by arrow t . hooks 125 of hook elements 124 at the carrying side of chain 122 are in a delivering position , where hooks 125 are pivoted into an approximately horizontal position parallel to chain 122 . hooks 125 of hook elements 124 at the return side of chain 122 are in a receiving position , where hooks 125 are perpendicularly aligned to chain 122 . below conveyor chain 122 , a smoking rod r is arranged parallel to conveyor chain 122 and in a distance which corresponds almost to the vertical height of a hook element 124 . smoking rod r is held by a holding device 130 at its right end . holding device 130 comprises an only schematically shown clamping unit 132 , which may be known in the art . at the left end of smoking rod r , a further bearing 134 for smoking rod r is shown so that smoking rod r is borne on both ends . it is principle possible to hold smoking rod r only on one end , for example , the right end by a respective clamping unit . in the region of the left end of smoking rod r , a delivery unit 140 can be arranged . delivery unit 140 is part of the mechanism for feeding an actually produced sausage s out of the clipping machine , which is not shown and which may also be known in the art . delivery unit 140 is arranged to be passed by a hook element 124 , whereby a sausage s positioned in delivery unit 140 is caught by hook element 124 . the delivery unit can also be formed by a conveyor belt or a guiding means for the loops of sausages s . between conveyor chain 122 and smoking rod 130 , a weighing device 150 is arranged at the end of transport path , in particular in the region of the right end of smoking rod r which is the distal end of smoking rod r referred to the clipping machine . weighing device 150 is attached to production unit 10 by fasteners 151 ( see fig3 and 4 ) and is positioned in such a way between conveyor chain 122 and smoking rod r that at least one sausage s can be transferred by hooks 125 to weighing device 150 . in particular , a loop of sausage s may abut on a stud - like projection 152 of weighing device 150 , stud - like projection 152 being arranged substantially parallel to smoking rod r and conveyor chain 122 . as can be seen in detail in fig3 and 4 , stud - like projection 152 comprises a circular cross - section and a tapered end 154 facing the clipping machine . projection 152 is attached through an essentially l - shaped beam 155 with a two - part beam 156 being substantially parallel to projection 152 , beam 156 accommodating a sensing element 157 . sensing element 157 is only schematically shown , but corresponds to sensing elements being already known from prior art . the part of weighing device 150 consisting of projection 152 , l - shaped beam 155 and beam 156 is linearly or reciprocally movable in a direction identified by arrow a relative to a fastened part 158 of weighing device 150 . in the following , the part consisting of projection 152 , l - shaped beam 155 and beam 156 is also called movable part 159 of weighing device 150 . movable part 159 , especially the beam 156 , comprises a substantially c - shaped element 163 , c - shaped element 163 interacting with a corresponding rail 163 of fastened part 158 of weighing element 150 . a piston 160 is attached to movable part 159 , in particular to beam 156 , interacting with a cylinder 161 being connected with fastened part 158 of weighing device 150 . the piston - cylinder - assembly allows a limited movement of a part of weighing device 150 , the direction being substantially parallel to a smoking rod r positioned on the holding device 130 . weighing device 150 can take a weighing position in which at least one sausage s is positioned on projection 152 ( see fig3 ) and a retracted position in which no sausage s is positioned on projection 152 ( see fig4 ). in particular , a sausage s is transferred from a hook 125 to projection 152 as it is explained in detail below . sausage production device 14 comprises a filling pipe on which a tubular casing for the sausage s is stored . the tubular casing is closed at its front end at the opening of the filling pipe by a closing clip constituting the first end of the sausage s . filling material like sausage meat is filled into the casing via the filling pipe . if a predetermined length of the sausage s is reached , the clipping machine gathers the filled casing , whereby a plait free from sausage meat is provided , and stacks at least one clip at the plait for closing the second end of the sausage s . together with the clip , a flexible hanging means , like a loop , is secured to the second end of the sausage product s for hanging up the sausage product s thereon . at the same time , a second clip may be stack and closed around to the plait , constituting the first end of the subsequent sausage s . alternatively to the length of the sausage s , the size of the sausage meat portion filled into the casing may be predetermined or the duration of the filling process . upon closing the tubular casing and securing a loop to the second end of the sausage s , the sausage meat free plait is cut between the second clip of the sausage s and the first clip of the first end of the subsequent sausage s . the actually produced sausage is than fed out of the clipping machine by a suitable conveyor like a belt conveyor . the loop is thereby caught by a guide for placing the sausage s at delivery unit 140 . conveyor 120 turns in the direction t , whereby a hook element 124 passes delivery unit 140 . hook 125 of hook element 124 engages the loop of sausage s and transfers sausage s to smoking rod r or to weighing device 150 . at a predetermined position , hook 125 is pivoted from the receiving position into the delivering position ( the receiving position of a hook element 124 is shown with the left lower hook element 124 , whereas the delivery position of a hook element 124 is shown with the middle lower and right hook elements 124 ). thereby , the sausage s is placed on smoking rod r or on weighing device 150 . after passing the second turning point , which is the right one in fig2 , hook element 124 enters the return side , whereby hook 125 is pivoted into the receiving position . in particular , at least the first sausage s which is placed from the left side onto smoking rod r is placed on projection 152 of weighing device 150 when weighing device 150 is in its weighing position ( see fig2 and 3 ). the sausage s placed on projection 152 causes a force . said force is detected by sensing element 157 . based on the position of sausage s on projection 152 , that means based on the distance between sausage s and l - shaped beam 155 , the weight of sausage s is calculated according to the lever principle in a respective calculation device in control unit 12 of sausage production unit 10 . the lever principle allows calculating the weight of a sausage s from its known distance to the sensing element 155 , which , in this case , is the “ lever ”, and the force acting on sensing element 155 via the moment caused by the weight of the sausage s and the length of the “ lever ”. according to the result of said calculation , the size of the actually produced sausage s or the subsequent sausage s may be altered . if the calculated weight exceeds a predetermined value , the length of the following sausages s may be reduced . alternatively , the duration of the filling process may be reduced or a smaller amount of sausage meat is filled into the casing . the calculation device of control unit 12 calculates the weight of the sausage s actually hung up on projection 152 of weighing device 150 and , in the case that the weight of the sausage s exceeds or falls under a predetermined threshold value , control unit 12 acts on the clipping machine and / or the pump of the filling machine and / or other suitable devices , like the casing breaking device , for altering the weight of the sausage s still to be produced . after measurement of sausage s , movable part 159 of weighing device 150 is linearly moved in its retracted position ( see fig4 ) by a drive ( not shown ). thereby , sausage s is urged from projection 152 and rests onto smoking rod r . since weighing device 150 and smoking rod r are close to each other , sausage s is not damaged when it is urged from projection 152 onto smoking rod r . for urging sausage s from projection 152 , a deflector 162 ( schematically shown in fig2 ) can be provided . stud - like deflector 162 is positioned between projection 152 of weighing device 150 and smoking rod r . when projection 152 of weighing device is moved from weighing position into retracted position , loop of weighed sausage s is held by deflector 162 and is not moved together with weighing device , but is urged from projection 152 . in placing sausage s onto projection 152 of weighing device , the position of deflector 162 defines the position of sausage s on projection 152 , as deflector 162 stops the movement of sausage s . that means the lever for calculating the weight of sausage s is always the same . deflector 162 can stationary fixed onto or movably attached to automatic hanging line 16 . then , deflector 162 is for example pivotable . alternatively , not only the first sausage s 1 but also a second sausage s 2 can be positioned onto projection 152 and the weights of both sausages s are measured . after a certain number of sausages s has been placed on smoking rod r , a respective signal is sent from control unit 12 of sausage production device 10 to control unit 22 of robotic device 20 . robotic device 20 controlled by control unit 22 , is moved towards automatic hanging line 16 and grips a smoking rod r . for gripping a smoking rod r , at the front end of arm 25 of robot device 20 , a gripping unit 26 is arranged . gripping unit 26 may comprise at least one jaw for gripping a smoking rod r . in a simplified embodiment , gripping unit 26 may only provided with hook - like elements , in which a smoking rod r rests . robotic device 20 , which may be a so called joined - arm robot , removes a smoking rod r together with the sausage products s hanging thereon from automatic hanging line 16 and moves it towards storage frame 30 . smoking rods r will be placed at predetermined positions on the tray rails inside storage frame 30 according to the size of the sausage products s . for security reason , it is possible to derive safety signals from sensing element 157 , e . g . in the case that the weight of a sausage s exceeds a maximum value or falls under a minimum value . in that case , a weighing error has been occurred and the sausage production may be stopped by control unit 12 . to rise up the productivity and to reduce costs , the present system for producing sausage - shaped products s may be simplified by merging control units 12 and 22 into a common control unit . said single control unit allows an easier and effective data input and a connection between control units 12 and 22 , e . g . by wire , will be redundant .
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a preferred embodiment of the workpiece holding device for use in a polishing apparatus will be presented in the following with reference to fig1 to 4 . the workpiece holding device comprises a top ring member 10 of an overall disc shape , a drive shaft 12 for supporting the top ring member 10 and transmitting rotational and pressing forces to the top ring member 10 , and a universal joint 14 joining the drive shaft 12 to the top ring member 10 in such a way as to accommodate tilting motion of the top ring member 10 relative to the drive shaft 12 . in the following presentation , horizontal surfaces of various component parts are referenced such that a lower surface closer to the workpiece is the front surface and an upper surface away from the workpiece is the back surface . upper and lower surfaces thus correspond to back and front surfaces , respectively . each of these sections will be explained in more detail in the following . in this embodiment , the top ring member 10 comprises a holder plate 16 of a generally disc shape for holding a workpiece such as a wafer by means of a suction force , a cover plate 18 of a generally disc shape fixed to the holder plate 16 so as to form a space s on the upper side of the holder plate 16 , and a fixing plate 20 of a hollow disc shape for covering the cover plate 18 and fixing the same to the holder plate 16 . a guide ring 22 is attached to the lower outer periphery of the holder plate 16 for surrounding the outer periphery of the workpiece when the holder plate 16 holds the wafer on its lower surface . a depression or depression section 24 is formed in the upper surface ( back surface in relation to the front surface which holds the workpiece ) of the holder plate 16 and a step surface 26 is formed around the outer periphery of the holder plate 16 . on the other hand , a protrusion or protrusion section 28 for fitting into the depression section 24 is formed in the center region of the front surface of the cover plate 18 , and a thin flange or flange section 30 , to be fixed to the step surface 26 with bolts , is provided around the periphery or peripheral section of the cover plate 18 . the upper ( back ) surface of the cover plate 18 has a central depressed area 32 and a ring shaped shoulder or shoulder section 34 surrounding its periphery , and an outer region forms a step surface 36 for attaching the fixing plate 20 . the depth of the depression section 24 in the holder plate 16 is made to be larger than the height of the protrusion section 28 in the cover plate 18 , thereby forming a spacing s of a certain thickness between the depression section 24 and the protrusion section 28 . the holder plate 16 has a large number of flow holes 38 formed vertically through the plate 16 , and they are communicated with a fluid hole 40 in the fixing plate 20 by way of the space s formed between the cover plate 18 and the holder plate 16 . the flow holes 38 are communicated with the back surface of the workpiece held on the front surface of the holder plate 16 . the space s , as described in more detail later , is for retaining a back side pressure therein , and when it is connected to an evacuation device , it produces a suction force , and when it is connected to a pressure fluid source , it produces a pressing force . the drive shaft 12 is supported by top ring head section 42 , which is fixed to the polishing apparatus , so as to be freely rotatable and vertically movable , and is coupled to an output shaft of the drive source ( motor with reduction gears , not shown ) through a pulley belt device 44 . the vertical movement is produced by the action of a piston rod 48a in top ring cylinder 48 disposed between the top ring head section 42 and drive shaft holder 46 ( refer to fig2 ). specifically , the main body of the top ring cylinder 48 is fixed to a shoulder section of the drive shaft holder 46 , and the tip of the piston rod 48a is fixed to the lower surface of the top ring head section 42 . the drive shaft 12 is formed as a hollow member , and a through hole 50 formed in its center section is communicated with an external pressure source apparatus 54 via a rotary joint 52 . a corrosion resistant fluid tube 56 , made of a polymeric resin such as teflon or polypropylene , is inserted inside the through hole 50 . the top end of the fluid tube 56 is connected to rotary joint 52 and the bottom end thereof is divided into separate tubes 56a , 56b ( fig3 ) which are connected to fluid holes 40 in the fixing plate 20 . in this design , the pressure fluid is supplied through the rotary joint 52 to the top end of the through hole 50 so that there is no need to provide a horizontal hole on the lateral side of the drive shaft 12 , thus resulting in a simplified construction and a lower production cost . the external pressure source apparatus 54 , in this embodiment , is provided with an evacuation device 58 , a pressurized air source 60 and pure water supply source 62 , each of which can be selectively connected to the flow holes 38 in the holder plate 16 through selection valves 64a , 64b , 64c , rotary joint 52 , delivery tubes 56 , 56a and 56b . a polishing solution supply nozzle ( not shown ) is disposed above the turntable to enable a polishing solution to be supplied to the surface of the polishing cloth on the turntable . a driver plate 68 having an outwardly extending flange or flange section 66 is fixed to the bottom end of the drive shaft 12 . the universal joint 14 is provided between the driver plate 68 and the cover plate 18 of the top ring member 10 for tiltably supporting the top ring member 10 and transmitting the pressing force thereto . the universal joint 14 has a spherical bearing mechanism 70 and a rotation transmission mechanism 72 for transmitting the rotational force of the drive shaft 12 to the top ring member 10 . the spherical bearing mechanism 70 will be explained first . in the center of the front surface of the driver plate 68 , there is a protruded area 76 formed in such a way that the lower surface makes a gentle spherical surface , and in the center of this protruded area 76 , there is a spherical cavity 80 for freely slidingly retaining a bearing ball 78 made of a high hardness material such as ceramics . the depressed area 32 in the center of the upper surface of the cover plate 18 has width and depth dimensions sufficient to house the protruded area 76 of the driver plate 68 , and in the center of the depressed area 32 , there is also a spherical cavity 82 to pair with the spherical cavity 80 to contain the bearing ball 78 . the bottom end of the bearing ball 78 is positioned inside the depression section 24 of the holder plate 16 , i . e ., below the level of the step surface 26 . by forming the depression section 24 in the holder plate and the protruded area 76 in the cover plate 18 so as to make the top ring thin , and by locating at least a part of the spherical bearing unit within the depression section 24 of the holder plate 16 , it becomes possible to bring the spherical bearing unit close to the turntable . the distance l between the center of the bearing ball 78 and the front surface of the holder plate 16 is designed to be less than 26 mm . as shown in fig1 and 4 , the shoulder section 34 protruding around the depressed area 32 of the cover plate 18 is provided with several pins 84 , 86 ( six in this embodiment ) spaced at equal angles , which are inserted into respective holes 88 , 90 provided at corresponding locations in the flange section 66 of the driver plate 68 . these pins 84 , 86 are distributed such that suspending pins 84 for suspending the top ring member 10 and driven pins 86 for transmitting the torque to the top ring member 10 are placed alternately . the suspending pins 84 are protruded out of the upper surface of the driver plate 68 , and a spring 94 is placed between a stopper plate 92 disposed at the top end of the pin and the driver plate 68 so as to support ( a part of ) the load exerted by the top ring member 10 with the elastic force of the spring 94 . with reference to fig3 and 4 , two parallel driver pins 98 are horizontally embedded in holes 90 of the driver plate 68 on opposite circumferential sides of the driven pins 86 . that is , as shown in fig4 two fine holes 99 are provided in such a way to open at a side surface of the flange section 66 and into hole 90 located on the flange section 66 of the driver plate 68 , and the driver pins 98 are inserted and fixed in these fine holes 99 . as illustrated in fig4 the driven pin 86 is provided with a cushion 96 , made of an elastic material such as rubber , around the periphery , and each cushion 96 has a cushion cover 97 on its periphery . each driver pin 98 touches the outer periphery of the cushion cover 97 . the rotation transmission mechanism 72 thus comprises the driver pins 98 and the driven pins 86 to transmit the torque smoothly and with certainty from the drive shaft 12 to the top ring member 10 . next , the operation of the polishing apparatus having the construction presented above will be explained . by connecting the evacuation device 58 of the external pressure source apparatus 54 to the rotary joint 52 , the workpiece is held on the lower surface of the holder plate 16 by the suction at the flow holes 38 in the holder plate 16 , and drive power is applied to the drive shaft 12 to rotate the holder plate 16 . in this case , because the fluid tube 56 is made of teflon or polypropylene , it is sufficiently strong so as not to collapse under the stress of evacuation . with reference to fig2 the top ring cylinder 48 is operated so that the piston rod 48a is pulled into the top ring cylinder 48 , then , because the top ring head 42 is fixed to the polishing apparatus frame , the top ring cylinder 48 is descended together with the drive shaft holder 46 . the workpiece is made to touch the turntable first , and then , it is further pressed against the turntable . the pulling force exerted by the piston rod 48a is transmitted to the workpiece in the form of a pressing force by way of the drive shaft 12 , bearing ball 78 , flange section 30 of the cover plate 18 and the holder plate 16 . the workpiece is thus pressed onto the polishing cloth on the turntable with a given pressure . in the meantime , when the top ring member 10 begins to descend , the turntable rotation had already been started and the polishing solution is being supplied through the supply nozzle onto the polishing cloth on the turntable . the surface to be polished ( bottom surface ) of the workpiece is polished under the existence of the polishing solution so that the polishing process is commenced . in this polishing operation , because the pressing force from the drive shaft 12 is transmitted through the spherical bearing 70 provided between the drive shaft 12 and the top ring member 10 , even if the vertical alignment of the drive shaft 12 to the cloth surface of the turntable is impaired , for example , the holder plate 16 can tilt about a center at the bearing ball 78 so that the workpiece is kept in close contact with the cloth surface . also , because the depression section 24 and the protrusion section 28 are formed to mate with each other in an opposing manner on the respective holder plate 16 and the cover plate 18 , the thickness of the center region of the holder plate 16 is reduced . also , because a part of the spherical bearing structure resides within the depression section 24 , the distance between the center of the spherical bearing 70 and the workpiece surface is made short . therefore , the rotational moment about the spherical bearing 70 is also reduced so that the attitude of the workpiece is stabilized . the result is that stable polishing can be carried out without sacrificing the stiffness of the holder plate while maintaining all the essential polishing requirements , such as securing the space necessary for supplying the polishing solution to the top ring member 10 and keeping the workpiece in close contact with the polishing cloth on the turntable . furthermore , the distance between the center of the spherical bearing 70 and the workpiece surface is also made short because the bearing ball 78 is provided between the depressed area 32 in the cover plate 18 and the protruded area 76 provided at the bottom end of the drive shaft 12 , which also promotes a stable alignment of the workpiece . further , the peripheral section of the top ring member 10 has been given a sufficient thickness to provide the shoulder section 34 and the step surface 36 , so as not to sacrifice either the stiffness or the space required for fabricating the connection hole 40 or implanting the driven pins 86 . in this design of the workpiece holder device , even if the holder plate 16 becomes tilted , the driven pins 86 and the driver pins 98 are relatively movable in the vertical direction so that the rotational torque of the drive shaft 12 is reliably transmitted to the holder plate 16 by simply relocating the contacting points to each other . also , because the driven pins 86 and the driver pins 98 are in point contact at right angles to each other , friction is low and the freedom of tilting is maintained . in this embodiment , each driven pin 86 is surrounded with an elastic cushion 96 such as rubber to absorb vibration between the drive shaft and the top ring . further , the outer surface of the cushion 96 is covered with a tube shaped cushion cover 97 , and the driver pins 98 contact the cushion cover 97 at opposite peripheral sides . therefore , the driven pins 86 and the driver plate 68 are able to freely move vertically relative to each other while maintaining an elastic contact . also , the bottom end surface of the protruded area 76 of the driver plate 68 is formed as a spherical surface ( flank ) 74 of a large radius of curvature , so that the separation distance from the top surface of the cover plate 18 progressively increases from the center towards the circumference , therefore , even if the spherical cavity 82 is made sufficiently large , there is no mechanical interference between the curved surface 74 and the depressed area 32 , so that the pressing force is transmitted reliably from the drive shaft 12 to the bearing ball 78 . to assure reliable contact of the workpiece to the polishing cloth , the fluid tube 56 may be switched to air pressure source 60 so that compressed air may be supplied to the back surface of the workpiece through the flow holes 38 and the spacing s . when the polishing operation is completed , the drive shaft 12 is raised , and the drive plate 68 integral with the drive shaft 12 is also raised , and the cover plate 18 and the top ring member 10 are elastically supported approximately horizontally by way of the springs 94 and the suspending pins 84 . in this state , the top ring member 10 is retracted away from the turntable , and is operated the pressure source apparatus 54 as needed to hold / detach the workpiece from the top ring member 10 to handle the workpiece between the top ring member 10 and some external device . by connecting the evacuation device 58 of the external pressure source apparatus 54 to the rotary joint 52 , the workpiece is held on the lower surface of the holder plate 16 , and by connecting the pure water supply source 62 of the external pressure source apparatus 54 to the rotary joint 52 , pure water is made to flow through the fluid tube 56 , space s , and the flow holes 38 in the holder plate 16 to push the back surface of the workpiece to detach the workpiece readily from the holder plate 16 . in this embodiment , because the holder device is designed so that the pressing force is transmitted from the flange section 30 of the cover plate 18 to the step surface 26 of the holder plate 16 , a uniform pressure can be applied to the holder plate 16 on the total surface of the workpiece , compared with the conventional arrangement in which the pressure is applied through the center of the holder plate through the bearing ball , because the forces are distributed around the periphery of the holder plate 16 to reduce the amount of deflection of the holder plate 16 . in the present polishing apparatus , the fluid tube 56 is made of a corrosion resistant material , therefore , even when water or air is supplied through the through hole , no rust is formed on its interior . contamination is thus prevented , and polishing precision as well as the final quality of the polished workpiece can be improved . also , in the present embodiment , the driver section and the driven section to transmit the rotational torque from the drive shaft 12 to the holder plate 16 are based on pin contacts . however , the invention is not necessarily limited to such designs . other possible designs such as plate form and other special forms are also employable . also , the driver pins 98 to engage the driven pin 86 are disposed parallel in the present embodiment , but they may not be parallel , nor be limited to two pins . conversely , for example , driver pins may be protruded from the side of a plate 68 and several driven pins may be provided on the top surface of the driven plate 18 so as to hold the driver pin . also , in the present embodiment , the drive shaft 12 has a separate fixed driver plate 68 , but the drive plate 68 may be formed integrally with the drive shaft 12 .
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2 . 3 programmable state machine , counters , cpu core and off - chip trigger interfaces the present invention may be applied beneficially in a wide variety of different kinds of microprocessors . for purposes of illustration , the invention will be described herein with reference to a particular kind of microprocessor , namely a four - way superscalar reduced instruction set (&# 34 ; risc &# 34 ;) microprocessor . it is believed that this form of description will enable persons having ordinary skill in the art not only to make and use the invention , but also readily to perceive any modifications or adaptations necessary to apply the invention to microprocessors other than the one specifically described herein . this section one will describe the illustrative host microprocessor first without having any of the components of the invention added to it . the remaining sections will describe a preferred implementation of the invention within the context of the exemplary host microprocessor discussed in this section one . fig1 is a block diagram of an exemplary risc microprocessor 100 before the addition of any of the components of the invention . microprocessor 100 is coupled to an instruction cache 102 , a data cache 104 and a system bus 106 . microprocessor 100 includes system bus interface unit 108 , instruction fetch unit 110 , sort unit 112 , instruction queue unit 114 , functional units 116 , data cache interface unit 118 , retire unit 120 , rename register blocks 122 , 124 , architected register block 126 , test access port (&# 34 ; tap &# 34 ;) controller 128 , scan chain 129 and clock generator 146 . functional units 116 include dual integer alus 130 , dual shift / merge units 132 , dual floating point multiply / accumulate units 134 , and dual floating point divide / square root units 136 . instruction queue unit 114 includes alu instruction queue 138 , memory instruction queue 140 , address reorder buffer 142 , and dual load / store address adders 144 . system bus 106 is a 64 - bit multiplexed address / data split transaction bus that uses the same protocol as the system bus of the well - known pa - 7200 microprocessor manufactured and sold by hewlett packard company . system bus interface 108 is provided to implement the protocol necessary for microprocessor 100 to communicate with memory subsystem 208 and input / output subsystem 210 over system bus 106 . instruction fetch unit 110 is provided to retrieve instructions from instruction cache 102 or , in the case of cache misses , from main memory subsystem 208 . during normal operation , instruction fetch unit 110 is capable of retrieving up to four quadword - aligned instructions per cycle from single - level instruction cache 102 . cache lines can also be loaded into instruction queue 114 by sort unit 112 at the rate of four instructions per cycle , thus keeping pace with instruction fetch unit 110 . when instruction fetch unit 110 indicates a cache miss , system bus interface 108 initiates instruction cache prefetches by fetching the next sequential line of instructions from main memory subsystem 208 . high - bandwidth connections are provided both to instruction cache 102 and to data cache 104 to enhance performance . data cache 104 is preferably dual - ported , with each port having access to a double word per cycle . because the overall objective behind the design of a microprocessor such as microprocessor 100 is to enhance performance by reducing the ratio of clock cycles per instruction executed , it is desirable that more than one instruction may be executed concurrently ( thus the nomenclature &# 34 ; super - scalar &# 34 ;). in the example of microprocessor 100 , duplicate functional units are provided so that as many as four separate instructions may be started during any one clock cycle . however , in order to keep these functional units fully occupied , it is necessary to find four instructions that may be executed simultaneously . this task is known as instruction scheduling and sometimes involves executing instructions out of program order . while instruction scheduling may be left to the compiler , any four sequential instructions are likely to contain data dependencies that cannot be resolved at compile time . therefore , in microprocessor 100 , a large instruction queue 114 is provided so that instruction scheduling may be achieved in hardware to extract maximum parallelism from the instruction stream . alu queue 138 and memory queue 140 are each 28 - entries deep . alu queue 138 holds instructions destined for functional units 116 , while memory queue 140 holds memory load / store instructions . certain instruction types such as load - and - modify instructions and branch instructions go into both queues . as a result , microprocessor 100 has the ability to examine up to 56 recently - fetched instructions in order to find four instructions that may be executed simultaneously . once a group of instructions has been fetched , insertion of the instructions into instruction queue 114 is handled by sort unit 112 . specifically , sort unit 112 receives four instructions from instruction fetch unit 110 and determines which of the four were actually requested by the cpu . ( sometimes a fetched bundle of four instructions contains superfluous instructions simply because instructions are fetched four at a time .) this determination is called instruction validation . sort unit 112 then routes the valid instructions to one or both of alu queue 138 and memory queue 140 . each of the queues 138 and 140 can handle up to four instructions per cycle , so an arbitrary collection of four instructions may be inserted into the queues simultaneously . as was mentioned previously , queues 138 and 140 each have entries or &# 34 ; slots &# 34 ; for 28 different instructions . once a new instruction has been placed into a slot within one of the queues , hardware monitors the previous instructions that are then launching from the queues to functional units 116 and address adders 144 . this is done in order to determine whether any of the now - launching instructions will supply an operand needed by the new instruction . once the last instruction upon which the new instruction depends has been launched to functional units 116 or address adders 144 , then the slot containing the new instruction begins to arbitrate for its own launch to functional units 116 or address adders 144 . up to two instructions may be launched simultaneously from each of alu queue 138 and memory queue 140 . because the hardware within functional units 116 and address adders 144 is duplicated , arbitration in each of the queues is handled in two groups . for example , even - numbered slots within alu queue 138 arbitrate for launch to alu0 , and odd numbered slots arbitrate for launch to alu1 . arbitration proceeds similarly among the slots within memory queue 140 . in each queue , the even - numbered slot with the oldest instruction and the odd - numbered slot with the oldest instruction win arbitration and are launched to functional units 116 or address adders 144 . address reorder buffer 142 is provided to help eliminate performance penalties that are associated with load - store dependencies . when a load or store instruction in a slot of memory queue 140 has received all of its operands , it requests to be dispatched just like an alu instruction . the destination of the load / store instruction , however , will be one of address adders 144 instead of one of functional units 116 . address adders 144 are provided so that the effective address for the load / store instruction may be calculated before executing the instruction . once calculated , the effective address is stored into one of 28 slots within address reorder buffer 142 . ( each of the 28 slots within address reorder buffer 142 is associated with one of the slots in memory queue 140 .) the effective address also goes to the translation look - aside buffer ( not shown ), which returns a physical address that is placed into the same slot of address reorder buffer 142 . with its address stored in address reorder buffer 142 , the load / store instruction begins arbitrating for access to one of the banks of synchronous sram that make up dual - ported data cache 104 . the instruction tries again on each successive cycle until it wins access . ( arbitration is based on the age of the original load / store instruction , not the time its address has been in address reorder buffer 142 . priority is given to the oldest instruction .) address reorder buffer 142 also checks for store - to - load dependencies as follows : whenever a store instruction has its effective address calculated , the address is compared to the addresses of any younger load instructions that have completed their cache accesses by executing out of order . if the addresses are the same , then the load and all younger instructions are flushed from address reorder buffer 142 and reexecuted . similarly , whenever a load instruction has its address calculated , the addresses of all older stores in address reorder buffer 142 are compared with it . in the event of a match , the load waits until the store data becomes available . these mechanisms are provided to ensure that out - of - order execution cannot cause stale data to be read . retire block 120 is provided to remove instructions from instruction queue 114 in program order after they have successfully executed or after their trap status is known . up to four instructions may be retired per cycle -- two from alu queue 138 and two from memory queue 140 . if an instruction needs to signal a trap , the trap parameters are recorded in the architected state , and the appropriate trap vector is forwarded to instruction fetch unit 110 , which then begins fetching from the new address . microprocessor 100 employs register renaming to execute ( but not retire ) instructions speculatively . rename register blocks 122 and 124 contain a total of 56 rename registers , one for each slot within alu queue 138 and memory queue 140 . in addition , architected register block 126 contains 32 integer and 32 floating point architectural registers . at retire time , the contents of the rename register associated with a given instruction are committed to the appropriate architectural register , and any store data is forwarded to a buffer ( not shown ) that holds data to be written to data cache 104 . test access port (&# 34 ; tap &# 34 ;) controller 128 is provided to implement a serial off - chip interface in accordance with the well - known institute of electrical and electronics engineers ( ieee ) standard 1149 . 1 , &# 34 ; test access port and boundary scan architecture , &# 34 ; also known as the joint test action group (&# 34 ; jtag &# 34 ;) standard . tap controller 128 is coupled to numerous test nodes located adjacent to the chip pads of microprocessor 100 . such an arrangement of test nodes is commonly called a &# 34 ; scan chain , &# 34 ; as is indicated in the drawing at 129 . tap controller 128 may be commanded to latch the state of the various test nodes constituting scan chain 129 , and the data thus captured may then be shifted serially off - chip via the test access port for analysis by external equipment . further information about the structure and operation of microprocessor 100 may be found in the engineering and user documentation supplied with the pa - 8000 microprocessor manufactured and sold by hewlett packard company . as shown in fig2 a complete computer system may be constructed using one or more microprocessors 100 , 200 coupled via system bus 106 to a memory subsystem 208 and an input / output subsystem 210 . in a multi - processor implementation such as that shown in fig2 each of microprocessors 100 , 200 would preferably have its own instruction cache 102 , 202 and its own data cache 104 , 204 . fig3 is a block diagram illustrating host microprocessor 100 having a preferred embodiment of the invention implemented therein . state machine block 300 includes programmable state machine 302 , counters 304 , off - chip trigger interface 306and cpu core interface 308 . off - chip trigger interface 306 provides a three - bit interface to components external to microprocessor 100 . cpu core interface 308 provides a trig -- trap signal to fetch unit 110 , a control signal i to tap controller 128 , and two control signals j to clock generator 146 . off - chip data interface 310 provides a 63 - bit interface to components external to microprocessor 100 . its data inputs comprise 603 total signals coming from various points located throughout microprocessor 100 . system bus interface 108 is provided with system bus interface comparators 312 and performance signal generation logic 314 . system bus interface comparators 312 take six bits of input from within system bus interface 108 and provide two output bits a to programmable state machine 302 . performance signal generation logic 314 provides six output bits b to programmable state machine 302 . fetch unit 110 is provided with fetch unit comparators 316 . fetch unit comparators 316 take as inputs four instructions i0 - i3 , certain address bits adr and a cache index ci . address bits adr and cache index ci correspond to the virtual address and the cache index for the fetched bundle of four instructions comprising instructions i0 - i3 . fetch unit comparators 316 provide four output bits d to programmable state machine 302 and sixteen output bits 318 to sort unit 112 . sort unit 112 is provided with validate logic 320 . validate logic 320 takes as inputs four bits from within sort unit 112 , and the sixteen bits 318 that were generated by fetch unit comparators 316 . validate logic 320 provides four output bits e to programmable state machine 302 and sixteen output bits 322 to instruction queue 114 . data cache interface 118 is provided with data cache interface comparators 324 . recall that data cache 104 is preferably organized as a dual - port unit . thus , an even and an odd port exist for data loads . in this implementation , data stores share a common 64 - bit data bus . correspondingly , data cache interface comparators 324 have two sets of inputs for loads -- one set for even loads and one set for odd loads . a third set of inputs is provided for stores , as shown . data cache interface comparators 324 provide six total output bits f , g to programmable state machine 302 . the four output bits f are also provided to instruction queue 114 . data flow is provided from validate logic 320 and data cache interface comparators 324 to retire unit 120 via instruction queue 114 . to accomplish this , new bit fields 326 , 328 and 330 are added to each of the slots within alu queue 138 , memory queue 140 and address re - order buffer 142 , respectively . the sixteen output bits 322 from validate logic 320 are stored in bit fields 326 , 328 . output bits 322 include four bits per instruction ( regardless of whether the instruction is an alu - type or a memory - type instruction ), and there is a potential maximum of four instructions entering instruction queue 114 from sort unit 112 during a given clock cycle . thus , output bits 322 comprise a maximum of four different 4 - bit sets . each of the 4 - bit sets is placed in the same slot of instruction queue 114 as the instruction to which it corresponds . similarly , the four output bits f from data cache interface comparators 324 comprise a maximum of two different 2 - bit sets . these 2 - bit sets are stored in bit field 330 in the same slot of instruction queue 114 as the instructions to which they correspond . because results f from data cache interface comparators 324 always pertain to load - type memory instructions , and because even and odd load instructions are allowed to execute simultaneously in the architecture of microprocessor 100 , one of these 2 - bit sets will always correspond to an even load instruction , and the other will always correspond to an odd load instruction . therefore , in order to represent this information properly in address re - order buffer 142 , two bits in each slot of bit field 330 are reserved for one of the 2 - bit sets produced by data cache interface comparators 324 , and one additional bit in each slot of bit field 330 is reserved to indicate whether the 2 - bit set just stored there derived from an even or an odd load instruction . consequently , although outputs f comprise a maximum of four total bits ( two result bits for each simultaneously - executing load instruction ), a maximum of six bits may actually be stored in address - re - order buffer 142 during a given clock cycle . ( in a preferred embodiment , the even / odd indicator need not be independently generated and stored in address re - order buffer 142 with the comparison results . this is because , in such an embodiment , the address of the load instruction will already be stored in address re - order buffer 142 ; therefore , the even / odd bit may be determined from this previously - stored address whenever it is needed .) retire unit 120 is provided with retiring instruction comparator matrix 332 and overall match generation matrix 334 . retiring instruction comparator matrix 332 takes , as its inputs , 24 bits of &# 34 ; retire - time information &# 34 ; from instruction queue 114 . these 24 bits comprise six bits of retire - time information for each of the four instructions retiring during a given clock cycle . ( some of these bits will be null if fewer than four instructions actually retire during that clock cycle .) retiring instruction comparator matrix 332 provides sixteen output bits to overall match generation matrix 334 . overall match generation matrix 334 takes these sixteen bits as inputs , as well as 22 other bits from instruction queue 114 . the latter 22 bits include the 16 bits 322 from validation logic 320 that were previously placed in bit fields 326 , 328 , and the 6 bits deriving from data cache interface comparators 324 that were previously placed in bit field 330 . based on these inputs , overall match generation matrix 334 provides 12 output bits h to programmable state machine 302 . tap controller 128 is provided with sample - on - the - fly circuitry 336 . sample - on - the - fly circuitry 336 takes as an input the control signal i generated by cpu core interface 308 , and is coupled to numerous test nodes 0 - n located throughout microprocessor 100 . its purpose is to latch , in a conventional manner , the state of test nodes 0 - n whenever control signal i is asserted . after the state of the test nodes is so latched , tap controller 128 may then be used to clock the latched information serially off - chip in a conventional manner via the test access port . the information may then be analyzed by components external to microprocessor 100 . staging register circuitry 338 is provided , and is coupled to architected registers 126 via parallel data bus 340 . this enables data to be transferred between architected registers 126 and staging register 338 by executing an instruction on microprocessor 100 . serial data and control lines 342 form a serial loop comprising staging register circuitry 338 , fetch unit comparators control register circuitry 344 , state machine / counters control register circuitry 346 , system bus interface comparators control register circuitry 348 , off - chip data interface control register circuitry 350 , data cache interface comparators control register circuitry 352 and retire unit comparators control register circuitry 354 . staging register circuitry 338 and control register circuitries 344 - 354 , as well as how data communication is achieved between them and architected registers 126 , will now be described with reference to fig4 - 10 . as can be seen in fig4 a serial loop is formed by remote register circuitries 344 - 354 and staging register circuitry 338 . staging register circuitry 338 has a serial data output 400 , a serial data input 402 , and a control signal output 404 . the staging register circuitry control signal output 404 is coupled via control line 406 to a corresponding control signal input 408 of remote register circuitry 344 . likewise , the staging register circuitry serial data output 400 is coupled via serial data line 410 to a corresponding serial data input 412 of remote register circuitry 344 . each of remote register circuitries 344 - 352 has a serial data input 412 , a serial data output 414 , a control signal input 408 and a control signal output 416 . remote register circuitry 354 has a serial data input 412 , a serial data output 414 and a control signal input 408 . thus , the signal on serial data line 410 may be propagated in serial fashion from the serial data output 400 of staging register 338 , through each of remote register circuitries 344 - 354 and back into the serial data input 402 of staging register circuitry 338 . similarly , the signal on control line 406 may be propagated from the control signal output 404 of staging register circuitry 338 to remote register circuitry 354 through each of the intervening remote register circuitries . staging register circuitry 338 is coupled to general purpose register circuitry 126 via parallel data bus 340 . fig5 is a block diagram illustrating staging register circuitry 338 and general purpose register circuitry 126 in more detail . general purpose register circuitry 126 is coupled to staging register 500 via a parallel data bus 340 . data bus 340 is shown in fig5 in the form of conventional switching circuitry appropriate for directing read and write data between staging register 500 and one of the general purpose registers within microprocessor 100 &# 39 ; s general purpose registers 126 . also shown in fig5 is clock generation logic 146 , counter 502 , header generation register 504 , multiplexer 506 , comparators 508 , 510 and 512 , and rom 514 . for the purpose of explaining the concept and preferred implementation of staging register circuitry 338 and control register circuitries 344 - 354 in this section 2 . 2 , we will assume that the control registers contained in remote register circuitries 344 - 354 are each 64 bits deep . it will be apparent with reference to sections 2 . 3 et seq ., however , that the number of actual bits contained in these control registers varies . also , in actual implementations , the staging register need not be the same length as the remote registers . moreover , the remote registers need not all be the same length as one another . ( multiple operations may be used to read and write remote registers that are longer than the staging register .) rom 514 may be implemented simply as hardwired connections to power supply and ground as required to present the binary equivalent of decimal &# 34 ; 77 &# 34 ; to the parallel data load inputs of counter 502 . counter 502 should be configured to count down whenever it receives a clock and its control input indicates count . when its control input indicates load , counter 502 will be reset to the value &# 34 ; 77 . &# 34 ; clock generation logic 146 generates clock signal 516 , which may be used to drive clock inputs throughout the chip . comparator 508 will assert control line 406 whenever the output of counter 502 exceeds decimal 6 . comparator 510 will assert main serial data multiplexer control line 520 whenever the output of counter 502 exceeds decimal 70 . and comparator 512 will assert a signal to control logic 522 within microprocessor 100 whenever the output of counter 502 exceeds 0 . as is indicated in the drawing , the control signals for counter 502 , header generation register 504 and staging register 500 may be provided by control logic 522 within microprocessor 100 . also , the parallel data load inputs of header generation register 504 are provided by instruction decode logic 524 within microprocessor 100 . fig6 is a block diagram illustrating a representative one of remote register circuitries 344 - 354 . ( it should be understood that remote register circuitry 600 is representative of all remote register circuitries 344 - 354 shown in fig3 and 4 , with the exception that remote register circuitry 354 does not include a control signal output .) remote register circuitry 600 includes a header capture register 602 , a remote register 604 , an input multiplexer 606 and an output multiplexer 608 . control signal input 408 is coupled to control signal output 416 through one - bit latch 610 . serial data input 412 is coupled to one input of output multiplexer 608 through one - bit latch 612 . the other input of output multiplexer 608 is coupled to the data shift output of remote register 604 . serial data output 414 is provided by the output of output multiplexer 608 . the control input of output multiplexer 608 is provided by the output of a combinational logic system comprising and gates 614 and 616 , comparator 618 and rom 620 . rom 620 stores the address that remote register circuitry 600 will respond to . ( preferably , each of remote register circuitries 344 - 354 will be configured to respond to a unique address .) comparator 618 compares this address with bits ad0 - 4 from header capture register 602 and asserts one input of and gate 616 if they are the same . a match is indicated on the output of and gate 616 if the output of comparator 618 is asserted and the valid bit in header capture register 602 is also asserted . if match is asserted and the r / w bit in header capture register 602 indicates a read , then the output of and gate 614 will be asserted and the &# 34 ; 1 &# 34 ; inputs of both multiplexers 608 and 606 will be selected ; otherwise , the &# 34 ; 0 &# 34 ; inputs of those multiplexers will be selected . or gate 622 and load control logic 624 are provided to enable input data to be loaded into remote register 604 whenever desired . serial data input 412 is coupled to the &# 34 ; 0 &# 34 ; input of input multiplexer 606 and to the serial input of header capture register 602 . the serial input of remote register 604 is coupled to the output of input multiplexer 606 . the shift input of remote register 604 is coupled to the match signal , while its load input is supplied by load control logic 624 . control input 408 is coupled to a clear input of header capture register 602 via inverter 626 . the shift input of header capture register 602 is driven by the output of and gate 628 , whose first input is coupled to the control input 408 , and whose second input is coupled to the valid bit through inverter 630 . it is contemplated that microprocessor 100 will include within its instruction set certain opcodes for writing data to and reading data from specific remote registers . for example , one instruction may be designed to move the contents of a specified one of general purpose registers 126 into staging register 500 . another instruction may be designed to load header generation register 504 with the address of the desired remote register , to set the r / w bit in header generation register 504 to &# 34 ; r &# 34 ; in the case of a read or to &# 34 ; w &# 34 ; in the case of a write , and to shift the header out onto serial data line 410 . a third instruction might be designed to move the contents of staging register 500 into a specified one of general purpose registers 126 . fig7 illustrates a preferred method for writing a data value to a remote register using the apparatus just described . in step 702 , a microprocessor instruction is executed to load the data into general purpose register grx . in step 706 , using another microprocessor instruction , the contents of grx are loaded into staging register 500 . in step 708 , a &# 34 ; shift to diagnose &# 34 ; instruction is executed . preferably , this instruction should contain the address of the target remote register as immediate information . the effect of the instruction is to load the address into bits ad0 - 4 of header generation register 504 , and to set the r / w bit of that register to w . ( the valid bit in header generation register 504 always loads with valid .) then , after loading counter 502 with the number 77 , the contents of header generation register 504 and staging register 500 are shifted onto serial data line 410 by supplying appropriate control signals to the two registers . the shifting ceases when counter 502 counts down to zero . because , when initially loaded , the value in counter 502 exceeds both 6 and 70 , control signal 406 and multiplexer control line 520 are both asserted ( as indicated at count = 77 in fig8 ). thus , main serial data multiplexer 506 routes the serially shifting output from header generation register 504 onto serial data line 410 . as soon as the seven header bits from header generation register 504 have been shifted onto serial data line 410 , the count in counter 502 will have fallen to 69 . at this time , main serial data multiplexer control line 520 is unasserted ( as shown at count = 69 in fig8 ). thus , the data from staging register 500 is selected and begins to be shifted serially out onto serial data line 410 . at the same time , data from serial data input 402 is shifted serially into staging register 500 . although the write data will have been completely shifted out of staging register 500 when count = 5 ( as shown in fig8 ), the write operation continues for several additional clock cycles until count = 0 . this is necessary because each of remote register circuitries 344 - 354 interposes a one - bit latch on serial data line 410 and on control line 406 . in the example being discussed , there are six remote registers . thus , six additional shifts are necessary to assure that all bits are communicated to the 6th remote register in the serial loop before shifting ceases . activity at the remote registers can best be understood with reference to fig6 . it can be seen that header capture register 602 will have been cleared while control was unasserted . when control is asserted , header capture register will begin clocking bits in serially from serial data input 412 . as soon as the valid bit is clocked in , the shift input is disabled and no further shifting occurs in header capture register 602 . instantaneously , a comparison is then made with address 620 . if the address matches the header address bits , then remote register 604 begins clocking bits in serially from serial data input 412 until control is no longer asserted . the result will be that 64 data bits will have been written into remote register 604 . reading data from a particular remote register is very similar procedurally to writing data to the register , except that microprocessor 100 sets the r / w bit in header generation register 504 to r , and need not load any data value into staging register 500 before executing the read operation . fig9 illustrates a preferred method for reading data from a remote register . in step 902 , a &# 34 ; shift from diagnose &# 34 ; instruction is executed to load counter 506 with 77 , load address bits ad0 - 4 of header generation register 504 with the address specified in the instruction , and set the r / w bit of that register to &# 34 ; r . &# 34 ; the header is then shifted out onto serial data line 410 , and at the same time serial data is shifted back into staging register 500 from serial data input 402 . the shifting ceases when counter 502 counts down to zero . in step 904 , another microprocessor instruction is executed to move the contents of staging register 500 into a specified one of architected registers 126 , thus completing the read operation . as can be seen in fig1 , the 6 - bit latency caused by the latches in the serial loop of remote register circuitries causes the last of the read data to be clocked into staging register 500 from serial data input 402 when count = 0 . as the header is propagated through the loop of remote register circuitries 344 - 354 , each of the remote register circuitries compares bits ad0 - 4 in the header with its own address to determine if it has been selected . if the addresses are the same , then match is asserted . the r / w having been set to r causes read also to be asserted . the result is that multiplexer 608 routes data from remote register 600 onto serial data line 414 , enabling the data to be shifted serially back into serial data input 402 of staging register circuitry 338 as desired . the control inputs of remote register 604 are also controlled so that data shifted out of the register is recirculated to the serial input , thus making non - destructive reads possible if the remote register is either 64 bits long or an evenly divisible submultiple of 64 . when implementing the invention on a die that is already dense with other circuitry , the reader will find that the apparatus and procedures discussed in this section 2 . 2 provide important advantages . for example , the remote registers can be quite large ( on the order of 1 , 000 bits or more ) and very numerous , and yet only two interconnect lines are necessary to access all of them . also , the apparatus can be expanded to include many more or less than the six remote registers used in the example discussed herein , simply by adding to or subtracting from the number of bits used in the header address field ( bits ad0 - 4 ). moreover , addition of a remote register , no matter its size , adds only one bit of latency to the serial loop . 2 . 3 programmable state machine , counters , cpu core and off - chip trigger interfaces programmable state machine 302 , counters 304 , off - chip trigger interface 306 and cpu core interface 308 will now be described with reference to fig1 - 21 . fig1 illustrates the contents of block 300 in detail . block 300 contains programmable state machine 302 , counters 304 , cpu core interface 308 and off - chip trigger interface 306 . programmable state machine 302 includes input conditioning logic 1100 , programmable state machine entries 1102 , multi - bit present state latch 1104 and and gate 1106 . the inputs to input conditioning logic 1100 include thirty - eight bits from on - chip results a - h , four bits from counters 304 ( via counter overflow bus 1108 ), and one bit from off - chip trigger interface 306 . input conditioning logic 1100 provides twenty - three total output bits . eleven of these are provided to programmable state machine entries 1102 as state machine inputs 1110 . the other twelve are provided to counters 304 via increment data bus 1112 . as can be seen in the drawing , the inputs of each of programmable state machine entries 0 - n are coupled to multi - state latch 1104 via present state bus 1114 and also to state machine inputs 1110 . the outputs of each of programmable state machine entries 0 - n are coupled to next state bus 1116 , state machine output bus 1118 and hit bus 1120 . the hit signal is combined with clk by and gate 1106 to derive a signal that is used to control multi - state latch 1104 . fig1 illustrates a representative one of programmable state machine entries 0 - n . it is contemplated that storage elements 1201 - 1210 would be included within state machine / counters control register circuitry 346 . thus , storage elements 1201 - 1210 would be loaded with data by writing to state machine / counters control register circuitry 346 using the method and apparatus described above in section 2 . 2 . the four bits of present state bus 1114 are provided to one of the inputs of comparator 1212 so that they may be compared with the contents of storage element 1201 , which specifies the present state during which entry 1200 will become active . the four bits that are output from comparator 1212 are anded together at and gate 1216 , yielding a one - bit match result for present state . similarly , the contents of storage element 1202 ( bit - wise select ) are compared with the eleven bits of state machine input bus 1110 by comparator 1214 . or gate 1218 is used to mask the output bits of comparator 1214 with the contents of storage element 1204 ( bit - wise mask ). the results of this masking operation are anded together using and gate 1220 , resulting in a match result for the state machine input bus . exclusive or gate 1221 couples the output of and gate 1220 to one of the inputs of and gate 1222 as shown , and also provides a selectable inversion function . that is , when negate bit 1206 is set to &# 34 ; 0 ,&# 34 ; the output of exclusive or gate 1221 follows the output of and gate 1220 ; but when negate bit 1206 is set to &# 34 ; 1 ,&# 34 ; the output of exclusive or gate 1221 is the opposite to the output of and gate 1220 . the match results for present state and for the state machine input bus are anded together by and gate 1222 to produce the hit signal , which is coupled to hit bus 1120 . if hit happens to become asserted as a result of the match results for present state and the state machine input bus , then tri - state buffers 1224 and 1226 are enabled , allowing the contents of storage elements 1208 and 1210 to drive next state bus 1116 and state machine output bus 1118 , respectively . fig1 illustrates counters 304 in detail . as can be seen in the drawing , counters block 304 includes four separate counters labeled counter 0 - 3 . on the input side , each of counters 0 - 3 is coupled to increment data bus 1112 , state machine output bus 1118 and hit bus 1120 . specifically , bits 0 - 2 of increment data bus 1112 are coupled to counter 0 , bits 3 - 5 are coupled to counter 1 , bits 6 - 8 are coupled to counter 2 , and bits 9 - 11 are coupled to counter 3 . bit 7 of state machine output bus 1118 is coupled to counter 0 , bit 8 to counter 1 , bit 9 to counter 2 , and bit 10 to counter 3 . the hit signal is coupled to each counter . each of counters 0 - 3 also generates an overflow bit , labeled ov 0 - 3 in the drawing . these four overflow bits constitute counter overflow bus 1108 . fig1 illustrates counter 0 in detail . ( counter 0 is representative of each of counters 0 - 3 .) it is contemplated that storage elements 1406 and 1407 would be included within state machine / counters control register circuitry 346 . thus , storage element 1406 would be loaded with data by writing to state machine / counters control register circuitry 346 using the method and apparatus described above in section 2 . 2 . storage element 1407 may be loaded from latches 1414 and 1416 using logic such as load control logic 624 , and may be read by reading from state machine / counters control register circuitry 346 using the method and apparatus described above in section 2 . 2 ( section 2 . 2 . 2 in particular ). counter 0 contains a thirty - two bit adder 1400 , which has two addend inputs 1401 and 1403 . addend input 1401 is coupled to the output of multiplexer 1402 . one input of multiplexer 1402 is coupled to a latched copy of the sum output ( rslt ) of adder 1400 , as shown . the other input of multiplexer 1402 is coupled to the output of storage element 1406 ( initial value ). thus , depending on the state of the init signal , addend input 1401 will be coupled either to rslt or to the initial value stored in storage element 1406 . ( preferably , the init signal is generated whenever storage element 1406 is written to .) the least significant three bits of addend input 1403 are coupled to three - bit latch 1404 . the twenty - nine most significant bits are coupled to ground . the input of latch 1404 is coupled to the output of multiplexer 1408 . one input of multiplexer 1408 is coupled to ground , yielding an input value of &# 34 ; 000 .&# 34 ; the other input of multiplexer 1408 is coupled to bits 0 - 2 of increment data bus 1112 . thus , depending on the output of and gate 1410 , the input of latch 1404 is provided either by bits 0 - 2 of increment data bus 1112 or by ground . the former will be selected whenever hit is asserted and bit 7 of state machine output bus 1118 is asserted . thus , counter 0 may be incremented by any value between 0 and 7 depending on the content of increment data bus bits 0 - 2 . &# 34 ; 1 - detector &# 34 ; 1412 ( constructed by conventional means ) is provided to catch asynchronously any assertions of the overflow signal ov by adder 1400 . in turn , this signal is latched by latch 1414 . &# 34 ; 1 - detector &# 34 ; 1412 will be cleared upon the assertion of the init signal . the sum output rslt of adder 1400 is latched by latch 1416 . the contents of latches 1414 and 1416 are preferably stored by storage element 1407 for later retrieval as previously discussed . overflow signal ov is also supplied to counter overflow bus 1108 . referring now to fig1 , cpu core interface 308 includes 4 - bit latch 1500 , whose inputs are coupled to the output of 4 - bit multiplexer 1502 . one 4 - bit input of multiplexer 1502 is coupled to ground , yielding the input value &# 34 ; 0000 .&# 34 ; the other input is coupled to bits 3 - 6 of state machine output bus 1118 . the select input of multiplexer 1502 is provided by the hit signal . when trig -- trap is asserted , fetch unit 110 will preferably begin fetching instructions from the address associated with the trap routine . when trig -- hch ( trig -- hcl ) is asserted , clock generator 146 will hold the system clock high ( low ). when trig -- sof is asserted , sample - on - the - fly logic 336 will latch the state of test nodes 0 - n for later retrieval by an external system via conventional tap controller 128 . referring now to fig1 , off - chip trigger interface 306 includes 3 - bit latch 1600 , whose inputs are coupled to the output of 3 - bit multiplexer 1602 . one 3 - bit input of multiplexer 1602 is coupled to ground , yielding the input value &# 34 ; 000 .&# 34 ; the other input is coupled to bits 0 - 2 of state machine output bus 1118 . the select input of multiplexer 1502 is provided by the hit signal . the outputs of latch 1600 are called ext -- trig -- out a , b and c . ext -- trig -- out a , b and c are coupled to chip pads 1604 , 1606 and 1608 , respectively , via output driver buffers 1610 , 1612 and 1614 . while chip pads 1604 and 1606 constitute output signals for microprocessor 100 , chip pad 1608 is bidirectional by virtue of the fact that it is coupled not only to output driver buffer 1614 , but also to receive buffer 1616 . the output of receive buffer 1616 is designated ext -- trig -- in and constitutes one of the inputs of input conditioning logic 1100 ( which will be discussed next ). fig1 illustrates input conditioning logic 1100 in detail . the chief purpose of input conditioning logic 1100 is to allow the programmer to select which information will be used as inputs to programmable state machine 302 . a secondary purpose of input conditioning logic is to determine which increment values will be used to increment counters 0 - 3 . input conditioning logic 1100 includes conditioning logic blocks 0 - 3 and cmp generation blocks 4 - 6 . signal sets c , d , e , f , g and h are provided to conditioning logic blocks 0 - 3 as shown . signal sets a and b are provided to cmp generation blocks 4 and 5 as shown . the only input for cmp generation block 6 is the ext -- trig -- in signal previously discussed in relation to fig1 . counter overflow bus 1108 is fed straight through to the output of input conditioning logic 1100 without manipulation . each of conditioning logic blocks 0 - 3 provides three of the twelve total bits that comprise increment data bus 1112 , as shown . also , each of input conditioning logic blocks 0 - 3 provides one of the seven total bits that comprise comparator result bus 1700 . the other three bits of comparator result bus 1700 are provided by cmp generation blocks 4 - 6 . together , comparator result bus 1700 and counter overflow bus 1108 comprise state machine input bus 1110 . fig1 illustrates the contents of conditioning logic 0 in detail . ( conditioning logic 0 is representative of conditioning logic 0 - 3 ). it is contemplated that storage elements 1800 - 1812 would be included within state machine / counters control register circuitry 346 . thus , storage elements 1800 - 1812 would be loaded with data by writing to state machine / counters control register circuitry 346 using the method and apparatus described above in section 2 . 2 . the purpose of the circuitry within sub - block 1814 is to produce one of the four 3 - bit increment values that are placed on increment data bus 1112 . the rom value &# 34 ; 001 &# 34 ; is coupled to the &# 34 ; 1 &# 34 ; input of multiplexer 1818 so that , by storing a &# 34 ; 1 &# 34 ; in storage element 1802 , the increment value can be forced to &# 34 ; 001 .&# 34 ; otherwise , the increment value will be determined by the state of overall match generator output bits 0 , 1 and 2 , as shown . these overall match generator output bits are gated by and gates 1820 - 1824 . in this manner , they may be enabled or disabled by setting the value in storage element 1800 as desired . store -- match is also provided to and gates 1820 - 1824 to enable the programmer to focus exclusively on store - type instructions . if this is not desired , then store -- match may be forced to a &# 34 ; 1 &# 34 ; in a manner to be explained below in relation to fig3 . as can be seen in fig1 , the programmer is free to generate cmp [ 0 ] by using various combinations of the following : overall match generator results , load match information from data cache interface comparators 324 , validated instruction match information from validate logic 320 , unvalidated instruction match information from fetch unit comparators 316 , and user - selected signals taken from a variety of possible locations within microprocessor 100 by off - chip data interface 310 . these combination possibilities are provided by and gates 1834 , 1836 , 1828 , 1830 and 1832 ; or gates 1831 , 1833 and 1835 ; and the enable bits stored in storage elements 1800 - 1812 . fig1 and 20 illustrate the generation logic for cmp 4 and 5 , respectively . it is contemplated that storage elements 1900 - 1912 and 2000 - 2012 would be included within state machine / counters control register circuitry 346 . thus , storage elements 1900 - 1912 and 2000 - 2012 would be loaded with data by writing to state machine / counters control register circuitry 346 using the method and apparatus described above in section 2 . 2 . once again , the purpose of this circuitry is to enable the programmer to select which information will be used as an input to programmable state machine 302 . as can be seen in fig1 and 20 , the programmer may use and / or gates 1928 - 1934 ( 2028 - 2034 ) and storage elements 1900 - 1912 ( 2000 - 2012 ) to construct an or term using any or all of the following signals : system bus writeback , system bus i - flush , system bus d - flush , system bus private - to - shared , system bus interface prefetch buffer hit , system bus interface misprediction buffer hit , and the outputs from system bus address / data comparators 312 . ( the meaning of the six system bus performance signals just mentioned will be discussed below in connection with fig2 - 25 .) the generation options for cmp5 are identical to those for cmp 4 except that , in the case of cmp5 , the output of system bus address / data comparator 1 is used instead of the output of system bus address / data comparator 0 . ( system bus address / data comparators 0 and 1 are discussed in the next section .) fig2 illustrates the generation logic for cmp6 . latch 2100 is provided to store the state of the ext -- trig -- in signal . cmp6 tracks the state of the output of latch 2100 . system bus interface comparators 312 and performance signal generation logic 314 will now be discussed with reference to fig2 - 25 . as shown in fig2 , system bus interface comparators block 312 includes system bus address / data comparators 0 and 1 . each of system bus address / data comparators 0 and 1 is coupled to the 64 - bit system address / data bus 2200 , an address valid bit 2202 , a master id bus 2204 , a chip id bus 2206 , a transaction id bus 2208 , a data valid bit 2210 and a status register bit 2212 stored in storage element 2214 . the outputs of the two system bus address / data comparators are labeled sba / dcmp 0 and 1 , and are coupled to programmable state machine 302 at a . as was discussed above , system bus 106 operates according to the protocol of the well - known pa - 7200 microprocessor manufactured and sold by hewlett packard company . consequently , address and data pertinent to a given bus transaction may be presented on address / data bus 2200 in non - contiguous bus cycles . thus , a transaction id is associated with each bus transaction and is presented on transaction id bus 2208 in conjunction with each presentation of address or data so that the components interfaced to the bus can determine to which transaction the address or data belongs . in addition , a master id is presented on master id bus 2204 to indicate which microprocessor or other chip in the computer system is initiating the bus transaction . a chip id for microprocessor 100 is stored in a storage element and is communicated to system bus interface 108 via chip id bus 2206 . system bus interface 108 uses the chip id to determine , based on a comparison between the chip id and the information present on master id bus 2204 , whether the information then - present on the bus is intended for microprocessor 100 . fig2 illustrates system bus address / data comparator 0 in detail . it is contemplated that storage elements 2300 - 2308 , as well as storage element 2214 , would be included within system bus interface comparators control register circuitry 348 . thus , storage elements 2300 - 2308 , as well as storage element 2214 , would be loaded with data by writing to system bus interface comparators control register circuitry 348 using the method and apparatus described above in section 2 . 2 . system bus address / data comparator 0 is operable in two different modes , depending on the state of status register bit 2212 . ( status bit 2212 determines the mode by selecting which signal will be presented on the output of multiplexer 2310 .) when status register bit 2212 is &# 34 ; 0 ,&# 34 ; system bus address / data comparator 0 operates in a &# 34 ; normal &# 34 ; mode . when status register bit 2212 is &# 34 ; 1 ,&# 34 ; system bus address / data comparator 0 operates in an &# 34 ; alternate &# 34 ; mode . in the normal mode , the output of address / data comparator 0 indicates whether a match has occurred on both the expected address stored in storage element 2300 and the expected data stored in storage element 2304 . to accomplish this , the output of and gate 2312 is presented on the output of multiplexer 2310 . the inputs of and gate 2312 are addr match 2314 and data match 2316 . addr match 2314 is asserted when and gate 2325 is asserted . and gate 2325 is asserted when : ( 1 ) the information present on addr / data bus 2200 matches the expected address information stored in storage element 2300 , as indicated by the output of comparator 2318 which output is bit - wise masked by or gate 2334 , the results of which are anded by multiple - input and gate ( 2323 ); ( 2 ) address valid bit 2202 is asserted , indicating that the information present on addr / data bus 2200 is in fact a valid address ; and ( 3 ) comparator 2320 indicates that there is a match between master id 2204 and chip id 2206 . when all three of these conditions occur , the match is stored by conventional &# 34 ; 1 detector &# 34 ; 2322 for later use by and gate 2312 in determining the overall addr / data match . also , because the data corresponding to the address of interest may not be presented on addr / data bus 2200 on the next bus cycle , the transaction id is stored in latch 2324 for later use by comparator 2326 . once the transaction id is stored in latch 2324 , a recurrence of the same transaction id on transaction id bus 2208 ( which presumably will occur when the awaited data is presented on address / data bus 2200 ) will cause xaction id match 2328 to be asserted by virtue of the fact that the bit - wise outputs of comparator 2326 and anded by multiple - input and gate 2327 . data match 2316 is asserted when and gate 2339 is asserted . and gate 2339 is asserted when : ( 1 ) xaction id match 2328 is asserted ; ( 2 ) comparator 2330 indicates that the information present on addr / data bus 2200 matches the expected data stored in storage element 2304 ; and ( 3 ) data valid bit 2210 is asserted , indicating that the information present on addr / data bus 2200 is in fact valid data . the operations of multiple - input and gate 2337 , bit - wise or gate 2336 and comparator 2330 are analogous to those of and gate 2323 , or gate 2334 and comparator 2318 , discussed above . once both addr match 2314 and data match 2316 are asserted , the overall addr / data match signal 2332 is asserted . when this occurs , &# 34 ; 1 detector &# 34 ; 2322 is cleared . additional flexibility is provided by or gates 2334 and 2336 , which allow the programmer to mask certain of the bits from the comparisons made by comparators 2318 and 2330 , respectively . also , exclusive or gate 2338 is provided , allowing the programmer optionally to negate the output of or gate 2336 . in the alternate mode , expected data is stored not only in storage element 2304 , but also in storage element 2300 , and the output of system bus address / data comparator 0 is indicative of data matches only . moreover , in the alternate mode , no consideration is given to the transaction id . ( in this mode , multiplexer 2310 presents only the data match 2340 signal on the output of system bus address / data comparator 0 .) the out put of and gate 2323 is coupled to one input of or gate 2342 . the output of exclusive or gate 2338 is coupled to the other input of or gate 2342 . one input of and gate 2344 is provided by the output of or gate 2342 . the other input of and gate 2344 is provided by data valid signal 2210 . the output of and gate 2344 is the data match signal 2340 . fig2 illustrates system bus address / data comparator 1 in detail . as is apparent from the drawing , system bus address / comparator 1 is constructed and operates exactly like system bus address / data comparator 0 , except for the following : in the alternate mode , address / data comparator 1 is used for address comparisons only ( as opposed to data comparisons only ). thus , in the alternate mode for system bus address / data comparator 1 , expected address is stored not only in storage element 2400 , but also in storage element 2404 . again , in the alternate mode , transaction id information is disregarded , and address matches are reported on addr match signal 2440 whenever they have occurred in both comparators 2418 and 2430 . fig2 illustrates in detail the signals that are generated by performance signal generation logic 314 . it is contemplated that the generation of the signals shown in fig2 may be accomplished by conventional means , and that numerous alternative methods for doing so will be apparent to those having ordinary skill in the art based on the following signal descriptions : bus writeback : this signal is asserted when a &# 34 ; dirty &# 34 ; cache line is being written back to main memory 208 . bus i - flush : this signal is asserted when a line from instruction cache 102 has just been flushed in response to a command received over system bus 106 from another component in the computer system . this activity is commonly done in connection with maintaining cache coherency with main memory 208 . bus d - flush : this signal is asserted when a line from data cache 104 has just been flushed in response to a command received over system bus 106 from another component in the computer system . this activity is commonly done in connection with maintaining cache coherency with main memory 208 . bus p & gt ; s : this signal is asserted when a previously - private cache line is changed to shared ( or is flushed , if dirty , to main memory ). bus prefetch buffer hit : system bus interface 108 is equipped with a buffer for instructions that have been prefetched from main memory 208 but not yet requested by fetch unit 110 . once fetch unit 110 does request such a prefetched instruction , a hit occurs on the prefetch buffer , and the bus prefetch buffer hit signal is asserted at this time . bus mispredicted buffer hit : system bus interface 108 is also equipped with a buffer for instructions that have been fetched speculatively , but turn out to have been mispredicted . in the event fetch unit 110 eventually requests such an instruction while it is still in the mispredicted instruction buffer , a hit occurs on the buffer . when this happens , bus mispredicted buffer hit is asserted . all six of the signals generated by performance signal generation logic 314 are coupled to programmable state machine 302 at b . fetch unit comparators 316 will now be discussed with reference to fig2 - 30 . fig2 illustrates the content of fetch unit comparator block 316 . as each bundle of four instructions i0 - i3 is fetched by fetch unit 110 , the instructions are provided to instruction comparator matrix 2600 . simultaneously , the cache index and certain bits of the virtual address for the bundle of four instructions are provided to address comparator matrix 2602 . as will be discussed in more detail below , instruction comparator matrix 2600 contains four instruction comparators called instruction comparators a - d . each of instruction comparators a - d provides one result for each of the four instructions in the bundle ( four results total ). thus , instruction comparator matrix 2600 provides sixteen total results for each bundle of instructions . for convenience , the results for instruction comparator a are called icmpa [ i0 ], icmpa [ i1 ], icmpa [ i2 ], and icmpa [ i3 ]. the four complete sets of results from instruction comparator matrix 2600 are labeled as follows in fig2 : icmpa [ i0 - i3 ], icmpb [ i0 - i3 ], icmpc [ i0 - i3 ] and icmpd [ i0 - i3 ]. address comparator matrix 2602 contains four bundle address comparators a - d . because there is only one address associated with each bundle of four instructions , bundle address comparator matrix 2602 provides only one set of results for each bundle of instructions . in the drawing , these results are labeled bacmp [ a - d ]. as is shown , the result from bacmp [ a ] is anded with all four of the results from icmpa . likewise , the result from bacmp [ b ] is anded with all four of the results from icmpb ; the result from bacmp [ c ] is anded with all four of the results from icmpc ; and the result from bacmp [ d ] is anded with all four of the results from icmpd . the sixteen results from these and operations are provided to validate logic 320 via bus 318 . in addition , each group of four and results is ored together by or gates 2604 - 2610 . the resulting four bits , labeled fetcha - d in the drawing , are provided to programmable state machine 302 at d . fig2 illustrates instruction comparator matrix 2600 in detail . it is contemplated that storage elements 2700 - 2706 would be included within fetch comparators control register circuitry 344 . thus , storage elements 2700 - 2706 would be loaded with data by writing to fetch comparators control register circuitry 344 using the method and apparatus described above in section 2 . 2 . as is shown , instructions i0 - i3 are provided to each of instruction comparators a - d . but each of instruction comparators a - d compares instructions i0 - i3 with different expected instructions a - d stored in storage elements 2700 - 2706 , respectively . for additional flexibility , each instruction comparator is also provided with a separate set of mask , negate and enable bits , as shown . fig2 illustrates in detail a representative one of instruction comparators a - d . instruction comparator 2800 contains four 32 - bit comparators 2802 - 2808 . one 32 - bit input of each comparator 2802 - 2808 is coupled to 32 - bit expected instruction 2810 . the other input of each comparator 2802 - 2808 is coupled to a different one of the four instructions i0 - 3 . a thirty - two bit mask 2812 is provided to each of or gates 2814 - 2820 , allowing the programmer the option of bit - wise masking certain of the bits from each instruction comparison result . a negate bit 2822 is provided to exclusive or gates 2824 - 2830 , allowing the programmer the option of negating each of the instruction comparison results . finally , a set of enable bits 2832 - 2838 is provided to and gates 2840 - 2846 , allowing the programmer the option of individually enabling or disabling each of the instruction comparison results . fig2 illustrates address comparator matrix 2602 in detail . it is contemplated that storage elements 2900 - 2906 would be included within fetch comparators control register circuitry 344 . thus , storage elements 2900 - 2906 would be loaded with data by writing to fetch comparators control register circuitry 344 using the method and apparatus described above in section 2 . 2 . as mentioned above , bundle address comparator matrix 2602 contains four bundle address comparators a - d . each of bundle address comparators a - d is coupled to selected bits 2908 of the virtual address for the bundle of instructions i0 - i3 . each of bundle address comparators a - d is also coupled to the cache index 2910 for the bundle of instructions i0 - i3 . but each of bundle address comparators a - d compares the virtual address bits 2908 and the cache index 2910 with different expected addresses a - d stored in storage elements 2900 - 2906 , respectively . for additional flexibility , each address comparator is also provided with a separate set of mask , negate and enable bits , as shown . fig3 illustrates in detail a representative one of bundle address comparators a - d . bundle address comparator 3000 contains comparators 3002 and 3004 . comparator 3002 is used to compare bundle virtual address bits 2908 with expected bundle virtual address bits 3006 . comparator 3004 is used to compare bundle cache index 2910 with expected bundle cache index 3008 . a mask 3010 is provided to or gate 3012 , allowing the programmer the option of masking certain of the bits from the bundle virtual address comparison . a negate bit 3014 is provided to exclusive or gate 3016 , allowing the programmer the option of negating the result of the bundle virtual address comparison . and a disable bit 3018 is provided to or gate 3020 , allowing the programmer the option of enabling or disabling the result of the bundle virtual address comparison . similarly , a mask 3022 is provided to or gate 3024 , allowing the programmer the option of masking certain of the bits from the bundle cache index comparison . a negate bit 3026 is provided to exclusive or gate 3028 , allowing the programmer the option of negating the result of the bundle cache index comparison . and a disable bit 3030 is provided to or gate 3032 , allowing the programmer the option of enabling or disabling the result of the bundle cache index comparison . finally , the results of the bundle virtual address comparison and the bundle cache index comparison are anded by and gate 3034 , yielding a bundle addr match signal 3036 . this latter signal corresponds to the bacmp signals shown in fig2 . data cache interface comparators 324 will now be discussed with reference to fig3 - 34 . fig3 illustrates the content of data cache interface comparators 324 in detail . as is shown , data cache interface comparators block 324 contains even cache port comparators 3100 and odd cache port comparators 3102 . even cache port comparators block 3100 contains dual load address / data comparators 3104 and store data comparator 3106 . odd cache port comparators block 3102contains dual load address / data comparators 3108 and store data comparator 3110 . sixty - four bit data cache store data bus 3112 is provided to both store data comparators 3106 and 3110 . ( microprocessor 100 is designed to be capable of executing two load operations simultaneously -- one odd and one even . store operations , on the other hand , may only be executed one at a time .) even loads bus 3114 includes even data cache index bus 3116 , even data cache tag bus 3118 and even data cache load data bus 3120 . all three of these busses are provided to dual load address / data comparators 3104 . odd loads bus 3122 includes odd data cache index bus 3124 , odd data cache tag bus 3126 and odd data cache load data bus 3128 . all three of these buses are provided to dual load address / data comparators 3108 . dual load address / data comparators 3104 provide two output signals , eloadmatch0 and eloadmatch1 . dual load address / data comparators 3108 provide two output signals , oloadmatch0 and oloadmatch1 . these four bits are provided to programmable state machine 302 at f . in addition , these four bits are also stored in address reorder buffer 330 , as will be discussed in more detail below in relation to fig3 . store data comparator 3106 provides one output signal , estorematch . store data comparator 3110 provides one output signal , ostorematch . these two bits are provided to programmable state machine 302 at g . fig3 illustrates in detail a representative one of store data comparators 3106 and 3110 . it is contemplated that storage elements 3200 and 3202 would be included within data cache interface comparators control register circuitry 352 . thus , storage elements 3200 and 3202 would be loaded with data by writing to data cache interface comparators control register circuitry 352 using the method and apparatus described above in section 2 . 2 . each 32 - bit word of 64 - bit data bus 3112 is sent to a different one of comparators 3204 and 3206 . comparator 3204 compares word 0 with expected word 0 , and comparator 3206 compares word 1 with expected word 1 . the results of the bit - wise comparison for word 0 are anded by multiple - input and gate 3205 , the output of which may be masked by or gate 3208 and negated by exclusive or gate 3210 , at the option of the programmer . the results of the bit - wise comparison for word 1 are anded by multiple - input and gate 3207 , the output of which may be masked by or gate 3212 and negated by exclusive or gate 3214 , at the option of the programmer . additional flexibility is provided by multiplexer 3216 , or gate 3218 , and gate 3220 and or gate 3222 . select bits 3224 may be set by the programmer so that storematch ( the output of the store data comparator ) reflects any one of the following : ( 0 ) the logical or of store data match 0 and store data match 1 ; ( 1 ) just store data match 1 ; ( 2 ) just store data match 0 ; or ( 3 ) the logical and of store data match 0 and store data match 1 . moreover , by setting disable bit 3226 appropriately , the programmer may choose to override all of the previously mentioned results , effectively &# 34 ; forcing &# 34 ; a match . fig3 illustrates in detail a representative one of dual load address / data comparators 3104 and 3108 . as is shown , dual load address / data comparator 3300 contains load comparators 3302 and 3304 . each is coupled to data cache index bus 3306 , data cache tag bus 3308 and data cache load data bus 3310 . the outputs of load comparators 3302 and 3304 are loadmatch0 and loadmatch1 , respectively . fig3 illustrates in detail a representative one of load comparators 3302 and 3304 . it is contemplated that storage elements 3402 - 3412 would be included within data cache interface comparators control register circuitry 352 . thus , storage elements 3402 - 3412 would be loaded with data by writing to data cache interface comparators control register circuitry 352 using the method and apparatus described above in section 2 . 2 . comparator 3414 compares data cache index 3426 with expected data cache index 3427 . comparator 3416 compares data cache tag 3428 with expected data cache tag 3429 . for additional flexibility , mask bits 3430 are provided to or gate 3432 , allowing the programmer to mask individual bits from the data cache index comparison results . the bit - wise outputs of or gate 3432 are anded by and gate 3433 , and the result is provided to one input of exclusive or gate 3436 . negate bit 3434 is provided to the other input of exclusive or gate 3436 , allowing the programmer to negate the data cache index comparison result . in respect of the data cache tag comparison results , the same flexibility is provided to the programmer by mask bits 3438 , or gate 3442 , and gate 3443 , negate bit 3440 and exclusive or gate 3444 . comparators 3418 and 3422 and multiplexer 3446 are used to produce data match in exactly the same manner as comparators 3204 and 3206 and multiplexer 3216 are used to produce storematch , with one exception : comparators 3420 and 3424 are added to consider whether there is also a match between the parity bits for cache load data words 0 and 1 and the corresponding expected parity bits . the results of the parity comparisons are merged with the data comparisons by and gates 3448 and 3450 . mask bits 3452 and 3454 are provided for parity word 0 and 1 comparisons , respectively , providing the programmer with additional flexibility . the optional masking functionality is provided by or gates 3447 , 3451 , 3455 and 3459 . the optional negating functionality is provided by exclusive or gates 3449 and 3457 . multiple - input and gates 3445 and 3453 are provided to and the bit - wise results of comparators 3418 and 3422 , respectively . or gate 3461 and and gate 3463 are configured to provide several logical permutations of the match w0 and match w1 signals at the inputs to multiplexer 3446 , as shown . the output of multiplexer 3446 may be overridden via the disable signal applied to or gate 3465 . ultimately , indexmatch , tagmatch and datamatch are anded together by and gate 3456 to produce loadmatch . fig3 illustrates validate logic 320 in detail . as was discussed above , one of the functions of sort unit 112 is to determine which of the four instructions in a fetched bundle were actually requested and are therefore &# 34 ; valid , &# 34 ; versus which of them were not requested and are therefore &# 34 ; invalid . &# 34 ; it is contemplated that four bits ( one &# 34 ; valid / invalid &# 34 ; bit for each instruction ) will be produced by conventional means within sort unit 112 in order to convey this information to validate logic 320 . in fig3 , these bits are labeled i0valid , i1valid , i2valid and i3valid . bus 318 carries sixteen result bits from fetch unit comparators 316 over to validate logic 320 . the valid bits are anded with the corresponding fetch unit comparator results , as shown , resulting in the validate logic results . for example , all of the fetch unit comparator results for instruction 0 ( fai0 , fbi0 , fci0 and fdi0 ) are anded with the iovalid bit . the resulting four bits are called vai0 , vbi0 , vci0 and vdi0 . sixteen bits result from this anding operation . they are provided via bus 322 to instruction queue 114 for storage along with the instructions to which they correspond . in addition , the validated results for each fetch unit comparator a - d are ored together , instruction by instruction , by or gates 3502 - 3508 . the outputs of these or gates are provided to programmable state machine 302 at e . a maximum of four instructions may retire from instruction queue 114 during any given clock cycle -- two from alu queue 138 and two from memory queue 140 . for the remainder of this discussion , these retiring instructions will be referred to as alu instructions 0 and 1 , and mem instructions 0 and 1 ( hereinafter denoted alu [ 0 ], alu [ 1 ], mem [ 0 ] and mem [ 1 ]). the reader should note that these retiring instructions do not necessarily correspond to the instructions i0 - i3 discussed previously . rather , during any given clock cycle , a bundle of four instructions i0 - i3 may be fetched , and at the same time a group of four instructions alu [ 0 ], alu [ 1 ], mem [ 0 ] and mem [ 1 ] may be retired . fig3 illustrates the components of the invention that reside within retire unit 120 . as was discussed previously , retiring instruction comparator matrix 332 takes , as its inputs , 24 bits of &# 34 ; retire - time information &# 34 ; from instruction queue 114 . retiring instruction comparator matrix 332 provides sixteen output bits 3600 to overall match generation matrix 334 . overall match generation matrix 334 takes these sixteen bits as inputs , as well as 22 other bits from instruction queue 114 . the latter 22 bits include validated instruction comparison results 3602 ( which correspond to the 16 bits 322 from validation logic 320 that were previously placed in bit fields 326 , 328 ), and data cache load comparison results 3604 ( which correspond to the 6 bits deriving from data cache interface comparators 324 that were previously placed in bit field 330 ). based on these inputs , overall match generation matrix 334 provides 12 output bits h to programmable state machine 302 . fig3 illustrates retiring instruction comparator matrix 332 in detail . retiring instruction comparator matrix 332 contains four retiring instruction comparators 3700 - 3706 , one for each of the four possible retiring instructions . because a maximum of two alu - type instructions and a maximum of two mem - type instructions may retire at once , retiring instruction comparators 3700 and 3702 are dedicated to alu - type retiring instructions , while retiring instruction comparators 3704 and 3706 are dedicated to mem - type retiring instructions . six bits of retire - time info are supplied to each retiring instruction comparator . each set of six bits corresponds to one of the retiring instructions , as shown . within each of the four retiring instruction comparators are four retire match generators a - d . ( this will be discussed in more detail below in relation to fig3 and 39 .) thus , each of the retiring instruction generators 3700 - 3706 produces four retire match bits . it follows that the total output for matrix 332 is sixteen total bits of match results presented as four different 4 - bit sets -- one set for each of the possible retiring instructions . in the drawing , these sets are denoted retire -- cmp [ alu0 ] [ a - d ], retire -- cmp [ alu1 ] [ a - d ], retire -- cmp [ memo ] [ a - d ] and retire -- cmp [ mem1 ] [ a - d ]. fig3 illustrates in detail a representative one of alu - type retiring instruction comparators 3700 and 3702 . it is contemplated that storage elements 3800 - 3826 would be included within retire unit comparators control register circuitry 354 . thus , storage elements 3800 - 3826 would be loaded with data by writing to retire unit comparators control register circuitry 354 using the method and apparatus described above in section 2 . 2 . the generation of the six &# 34 ; retire - time info &# 34 ; signals shown in fig3 may be accomplished by any conventional means . numerous alternative methods for doing so will be apparent to those having ordinary skill in the art based on the following signal descriptions : stores : this bit indicates whether the associated retiring instruction was a store - type memory instruction . ( this information is pertinent only to mem - type instructions .) ptaken : for every conditional branch or jump - type instruction encountered , microprocessor 100 makes a prediction about whether the ( upcoming ) evaluation of the condition will cause the branch or jump to be taken . this bit indicates whether the associated instruction was a branch instruction whose branch was predicted to be taken . dcmiss : this bit indicates whether the associated instruction caused a data cache miss . ( this information is pertinent only to mem - type instructions .) icmiss : this bit indicates whether the associated instruction caused an instruction cache miss . nullified : the instruction set of microprocessor 100 includes the capability to &# 34 ; nullify &# 34 ; certain instructions in the instruction stream based on the outcome of other instructions or conditions within microprocessor 100 . this bit indicates whether the associated instruction was nullified for any reason . takenbranch : this bit indicates whether the associated instruction was a branch instruction whose branch was actually taken . ( this information is pertinent only to alu - type instructions .) bits 3800 - 3826 are provided for the programmer &# 39 ; s flexibility . by setting them appropriately , the programmer may configure the retiring instruction comparator to produce a variety of different kinds of results at its outputs . four stores enable bits 3800 - 3806 are provided . each is coupled to one of the inputs of one of and gates 3836 - 3842 through inverters 3828 - 3834 . ( this is done so that the alu - type retiring instruction comparator will not produce any match indications when the programmer is interested in store - type memory instructions .) storage elements 3808 - 3814 contain ptaken negate and enable bits for each of and gates 3836 - 3842 , respectively . the negate function is achieved by exclusive or gates 3844 - 3850 . the enable function is achieved by or gates 3852 - 3858 ( each of which has an inverted input for the enable bit ). two dcmiss enable bits are provided . one is provided to an input of and gate 3840 through inverter 3860 . the other is provided to an input of and gate 3842 through inverter 3862 . storage elements 3820 - 3822 contain icmiss negate and enable bits for each of and gates 3836 - 3838 , respectively . the negate function is achieved by exclusive or gates 3864 - 3868 . the enable function is achieved by or gates 3866 - 3870 ( each of which has an inverted input for the enable bit ). storage element 3824 contains a nullified enable bit for and gate 3840 . the enable function is performed by exclusive or gate 3872 , which has an inverted input for the enable bit . storage element 3826 contains a taken -- branch enable bit for and gate 3838 . the enable function is performed by exclusive or gate 3874 , which has an inverted input for the enable bit . fig3 illustrates in detail a representative one of mem - type retiring instruction comparators 3704 and 3706 . the same bits contained in storage elements 3800 - 3826 that were provided to comparators 3700 - 3702 are also provided to comparators 3704 - 3706 , as shown . the stores enable bits 3800 - 3806 are used for all four of and gates 3936 - 3942 . the enable function is provided by or gates 3928 - 3934 , all of which have an inverted input for the enable bit . the ptaken negate and enable bits 3808 - 3814 are used in exactly the same manner as they are used in the alu - type comparator shown in fig3 , as are the icmiss negate and enable bits 3820 - 3822 and the nullified enable bit 3824 . the two sets of dcmiss negate and enable bits are used for and gates 3940 and 3942 . the negate function is provided by exclusive or gates 3959 and 3963 . the enable function is provided by or gates 3961 and 3965 , each of which has an inverted input for the enable bit . the taken -- branch enable bit 3826 is provided to one input of and gate 3938 through inverter 3973 . fig4 illustrates overall match generator matrix 334 in detail . overall match generator matrix 334 includes overall match generators a - d . a total of thirty - eight input bits are provided to overall match generator matrix 334 . for each of the four possible retiring instructions mem [ 0 ], mem [ 1 ], alu [ 0 ] and alu [ 1 ], there are the following inputs : 4 bits from retiring instruction matrix 332 , labeled r [ a - d ]; and 4 bits from validated instruction comparison results 3602 , labeled v [ a - d ]. in addition , the 6 bits from data cache load comparison results 3604 are distributed as follows : the load -- match a / b result bits for instructions mem [ 0 ] and mem [ 1 ] go to overall match generators a and b . the load -- match c / d result bits for instructions mem [ 0 ] and mem [ 1 ] go to overall match generators c and d . the even / odd bits for instructions mem [ 0 ] and mem [ 1 ] go to each of overall match generators a - d . based on these inputs , each of the overall match generators produces one overall match bit for each of instructions alu [ 0 ], alu [ 1 ], mem [ 0 ] and mem [ 1 ], as shown . these four sets of overall match results are provided to adders 4000 - 4006 . the purpose of each adder is to determine how many of its four input bits were asserted . thus , sum a indicates how many retiring instructions produced a match at the end of comparator chain a . sum b indicates how many retiring instructions produced a match at the end of comparator chain b , and so on . the twelve bits comprising sums a - d are provided to the input of programmable state machine 302 at h . each of overall match generators a - d is slightly different from the others . fig4 illustrates overall match generator a in detail . it is contemplated that storage elements 4100 would be included within retire unit comparators control register circuitry 354 . thus , storage element 4100 would be loaded with data by writing to retire unit comparators control register circuitry 354 using the method and apparatus described above in section 2 . 2 . overall match generator a contains and gates 4102 - 4108 . the output of each one of these four and gates provides the &# 34 ; a &# 34 ; overall match result for one of the four retiring instructions . thus , these outputs are labeled overall -- match -- a [ alu0 ], overall -- match -- a [ alu1 ], overall -- match -- a [ mem0 ] and overall -- match -- a [ mem1 ]. an inverted version of data cache enable a is provided to and gates 4102 and 4104 directly , and to and gates 4106 and 4108 through or gates 4110 and 4112 . this is done so that , when data cache enable a is asserted ( meaning the programmer is interested in mem - type instructions on comparator chain a ), there will be no overall match results generated for alu - type instructions on comparator chain a . results for mem - type instructions , on the other hand , will be enabled . the even / odd bits for mem [ 0 ] and mem [ 1 ] are provided to and gates 4114 and 4116 without inversion . thus , overall match generator a is configured to derive its mem [ 0 ] and mem [ 1 ] match results from the load -- match a / b comparison result of even memory load instructions only . fig4 illustrates overall match generator b in detail . as can be seen , its structure is completely analogous to that of overall match generator a . the difference is that overall match generator b is configured to derive its mem [ 0 ] and mem [ 1 ] match results from the load -- match a / b comparison result of odd memory load instructions only ( by virtue of the inverted input on and gates 4214 and 4216 ). fig4 illustrates overall match generator c in detail . as can be seen , its structure is completely analogous to that of overall match generator a . the difference is that overall match generator c is configured to derive its mem [ 0 ] and mem [ 1 ] match results from the load -- match c / d comparison result of even memory load instructions only ( as opposed to deriving them from the load -- match a / b result for even memory load instructions ). fig4 illustrates overall match generator d in detail . as can be seen , its structure is completely analogous to that of overall match generator c . the difference is that overall match generator c is configured to derive its mem [ 0 ] and mem [ 1 ] match results from the load -- match c / d comparison result of odd memory load instructions only ( as opposed to even ones ), by virtue of the inverted inputs on and gates 4414 and 4416 . fig4 illustrates the contents of off - chip data interface 310 in detail . it is contemplated that storage elements 4500 - 4508 would be included within off - chip data interface control register circuitry 350 . thus , storage elements 4500 - 4508 would be loaded with data by writing to off - chip data interface control register circuitry 350 using the method and apparatus described above in section 2 . 2 . five hundred and seventy - six test nodes from various points within microprocessor 100 are routed to the inputs of multiplexer 4510 in groups of 36 . the programmer uses the value in storage element ( s ) 4508 to select which set of 36 test nodes will be coupled to chip pads 4512 . in addition to the 36 signals so selected , 27 additional signals ( preselected and fixed ) are always routed to chip pads 4512 , as shown , so as to be visible off - chip under all circumstances . of the 36 selected signals 4522 and the 27 fixed signals 4524 , 32 of them ( 4526 ) are routed to multiplexers 4514 - 4520 in four groups of eight , as shown . the programmer uses the values in storage elements 4500 - 4506 to select one bit from each of these four groups to be routed back to programmable state machine 302 at c . fig4 illustrates a second preferred implementation of the functionality just described . in the implementation of fig4 , multiplexer 4510 is replaced by 32 different 16 : 1 multiplexers , indicated generally in the drawing by multiplexers 4602 - 4610 . the various 16 : 1 multiplexers are physically located at various remote locations around microprocessor 100 . each has its inputs coupled to a set of test nodes , indicated generally in the drawing at 4612 - 4620 . each has its select inputs coupled to storage elements , indicated generally in the drawing at s0 - s31 . the outputs of the 16 : 1 multiplexers comprise bus 4522 . bus 4524 is coupled to 27 fixed nodes 4622 . preferably , fixed nodes 4622 are chosen as those nodes that a programmer would most likely want to see at chip pads 4512 under all circumstances . for example , fixed nodes 4622 may correspond to the minimum set of signals from which the state of microprocessor 100 can be reconstructed by external equipment . it is further contemplated that storage elements s0 - s31 would either be included within off - chip data interface control register circuitry 350 , or would constitue a new set of control registers that may be coupled into the serial loop of control registers 344 - 354 . in yet another variation , the same four bits 4508 may be used as select inputs for each of the 16 : 1 multiplexers throughout the chip . one advantage of the implementation of fig4 is that , by multiplexing closer to the test nodes , fewer interconnect traces need to be run across the chip to multiplexers 4514 - 4520 and to chip pads 4512 . in yet another preferred embodiment , any combination of storage elements 4500 - 4508 and s0 - s31 may be implemented as latches whose inputs are coupled to state machine output bus 1118 . in this manner , the selection of which signals are routed to chip pads 4512 and to state machine inputs c may be changed automatically and &# 34 ; on the fly &# 34 ; by state machine 302 in response to user - defined events having occurred . while the present invention has been described in detail in relation to a preferred embodiment thereof , particularly in relation to fig3 and 46 , the described embodiment has been presented by way of example and not by way of limitation . it will be understood by those skilled in the art that various changes may be made in the form and details of the described embodiment , resulting in equivalent embodiments that will remain within the scope of the appended claims .
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the present invention provides a shunt system having endoscopic placement features which allow the system to be surgically implanted and easily assembled using minimally invasive techniques . turning now to the drawings and particularly to fig1 a and 1b , a shunt system 10 in accordance with the present invention is shown . in an exemplary embodiment of the present invention , the shunt system 10 comprises a shunt device 20 contained within a housing 12 . the shunt device 20 includes a valve mechanism 22 for regulating fluid flow into and out of the shunt device 20 . the valve mechanism 22 can comprise any typical valve mechanism , such as the ball - in - cone valve illustrated and as described in u . s . pat . nos . 3 , 886 , 948 , 4 , 332 , 255 , 4 , 387 , 715 , 4 , 551 , 128 , 4 , 595 , 390 , 4 , 615 , 691 , 4 , 772 , 257 , and 5 , 928 , 182 , all of which are hereby incorporated by reference . of course , it is understood that the valve mechanism 22 can also comprise other suitable valves including programmable valves for controlling fluid flow in a shunt device as are known in the art . also included in the shunt device 20 is a pump chamber 24 that is connected to and in fluid communication with the valve mechanism 22 . the pump chamber 24 can comprise a flexible diaphragm 26 that enables selective occlusion of fluid flow into and out of the pump chamber 24 , thereby allowing bidirectional pumping of fluid between the pump chamber 24 and an attached reservoir 30 that is in fluid communication with the pump chamber 24 . the reservoir 30 comprises a top section 32 and a base section 34 which terminates in a catheter connector 36 . a portion of the base section 34 including the connector 36 extends out of the housing 12 as shown in fig1 b . however , it is understood that only the connector 36 need be located outside of the housing 12 for ease of assembly , and the base section 34 itself may be wholly contained within the housing 12 if desired . the top section 32 of the reservoir 30 which connects to the pump chamber 24 serves as a second pump chamber . preferably , the reservoir 30 can be a “ domed ” reservoir . that is , the top section 32 of the reservoir 30 is situated under a domed cap 14 that forms a part of the housing 12 , much like in the prior art rickham pump chamber 2 of fig3 in which there is shown a pump chamber 4 attached to a reservoir 6 seated underneath a domed housing 8 . in the present invention , both the top section 32 of the reservoir 30 and the pump chamber 24 are each configured to handle approximately 0 . 08cc of fluid volume , thereby allowing in total about four times the fluid volume as compared to the rickham pump chamber 2 of the prior art . however , the length of the housing 12 itself is approximately 4 cm so the overall dimensions of the shunt device 20 are still relatively small . to form the complete fluid flow pathway , catheters 40 , 60 are connected to the shunt device 20 of the present invention . provided with the shunt system 10 is an inflow catheter 40 having a first end 42 , a second end 44 , and a channel 46 extending between the first end 42 and second end 44 . the first end 42 of the inflow catheter 40 is configured to attach to the base section 34 of the reservoir 30 by way of the catheter connector 36 , while the second end 44 serves as the fluid uptake end , thereby providing a pathway for fluid to enter the shunt system 10 . in a hydrocephalus shunt system , the inflow , or ventricular , catheter 40 is placed in a ventricle of the patient so that cerebrospinal fluid can enter the shunt device 20 . after the cerebrospinal fluid enters the shunt device 20 , the fluid is regulated by the valve mechanism 22 and , according to the patient &# 39 ; s physiological condition , excess cerebrospinal fluid is released from the shunt device 20 through an outflow , or drainage , catheter 60 . the excess fluid is carried out through a channel 66 extending between a first end 62 of the outflow catheter 60 , which first end 62 is configured to attach to the valve mechanism 22 , and a second , fluid release end 64 where the fluid exits the shunt system 10 . as shown in fig1 b , the catheter connector 36 includes a flange 38 at its free end . the first , attachment end 42 of the inflow catheter 40 has an inner diameter id which is slightly smaller than the largest outer diameter of the flange 38 . this inner diameter id can be the diameter of the channel 46 extending from the first , attachment end 42 to the second , fluid uptake end 44 of the inflow catheter 40 provided the channel 46 has a consistent diameter throughout the inflow catheter 40 . however , it is understood that the inner diameter id of the channel 46 need only be smaller than the largest outer diameter of the flange 38 at a section near the first , attachment end 42 of the inflow catheter 40 . this smaller inner diameter id enables the attachment end 42 to form a tight , interference fit with the connector 36 when the attachment end 42 is urged onto the connector 36 and flange 38 . the inflow catheter 40 can be formed from a resilient and flexible material such as medical - grade silicone to allow the first , attachment end 42 to deform and fit over the connector 36 and flange 38 as the inflow catheter 40 is advanced towards the base section 34 . to secure the first , attachment end 42 of the inflow catheter 40 to the connector 36 , a selectively engageable locking mechanism 50 is provided with the inflow catheter 40 . the locking mechanism 50 can comprise a retaining ring 52 for maintaining the attachment end 42 of the inflow catheter 40 onto the connector 36 . in one exemplary embodiment , the retaining ring 52 is able to move , or slide over the inflow catheter 40 and beyond the flange 38 when the inflow catheter 40 is attached to the connector 36 . as illustrated in fig1 c , the retaining ring 52 can be situated adjacent to the attachment end 42 in an unlocked state . after the attachment end 42 is urged onto the connector 36 and flange 38 , the retaining ring 52 can be moved towards the attachment end 42 such as by sliding , twisting , or other similar advancing action until the retaining ring 52 passes over the flange 38 held within the attachment end 42 . in this locked state as shown , the retaining ring 52 compresses the flexible attachment end 42 over the connector 36 . the retaining ring 52 is configured such that the inner diameter is smaller than the largest outer diameter of the attachment end 42 with the flange 38 therein , thereby preventing the retaining ring 52 from sliding out of its locked state back to its unlocked state . it is contemplated that the retaining ring 52 can be formed of a suitable biocompatible material such as titanium or titanium alloy , while the connector 36 and flange 38 are formed of a semi - deformable material such as nylon to allow enough compression for the retaining ring 52 to slide over the flange 38 . with this locking mechanism 50 , the inflow catheter 40 is able to be assembled to the shunt device 20 quickly and easily , without the need for sutures or adhesives . the retaining ring 52 also provides a more consistent joining force than current suturing methods . the inflow catheter 40 of the present invention also provides features that enable its customization to a particular patient . on the outer surface of the inflow catheter 40 are marks or indicia 54 which correspond to the length of the inflow catheter 40 . these marks 54 can aid the surgeon in pre - sizing the inflow catheter 40 to the individual patient once the specific size of the ventricular tube needed has been determined by either ct scan or other known imaging techniques . this way , the surgeon can adjust the length , i . e ., by cutting the catheter 40 to the required size , intraoperatively . if it is desirable to cut the inflow catheter 40 to size , the retaining ring 52 can be slid away from the area to be cut , near the second , fluid uptake end 44 . alternatively , the retaining ring 52 can be taken off the inflow catheter 42 entirely , and placed back on after the inflow catheter 40 has been cut to size . once the inflow catheter 40 has been cut to the desired size , the retaining ring 52 is advanced near the first , attachment end 42 prior to assembly . in addition , the inflow catheter 40 can have either an open or a closed second end 44 for surgeon modification to allow visualization with an endoscope . if the second end 44 is closed , a pre - formed slit 56 can be provided so as to allow the endoscope to pass through the second end 44 . since the second end 44 serves as the fluid uptake end , a series of apertures 58 can be provided near the closed second end 44 to facilitate fluid entry into the inflow catheter 40 . rather than having a sliding retaining ring 52 on the inflow catheter 40 , fig2 a shows another exemplary embodiment of a locking mechanism 50 ′ comprising a retaining ring 52 ′ that is firmly secured to the inflow catheter 40 of the present system 10 at its attachment end 42 . the retaining ring 52 ′ can resemble the retaining ring 52 of fig1 b and 1c in size , shape , and composition , except that the retaining ring 52 ′ is bonded to the outer diameter of the inflow catheter 40 . fig2 b shows yet another exemplary embodiment of a locking mechanism 50 ″ for use with the inflow catheter 40 of the present system 10 , in which a retaining ring 52 ″ is firmly secured such as by bonding to the inner diameter id of the inflow catheter 40 at its attachment end 42 . the retaining ring 52 ″ can be formed from a semi - deformable material such as nylon . the retaining rings 52 ′, 52 ″ of the present invention can be used with pre - cut fixed length inflow catheters 40 . during assembly , the bonded retaining rings 52 ′, 52 ″ pop over the flange 38 of the connector 36 when the inflow catheter 40 is urged onto the connector 36 , thus retaining the inflow catheter 40 and the connector 36 together without the need for sutures or adhesives . to allow pumping of the valve mechanism 22 distally while preventing occlusion of the shunt device 20 proximally , the base section 34 of the reservoir 30 can include a check valve mechanism 70 as illustrated in fig4 . within the base section 34 are partitions 76 that form a funnel entrance 82 leading into a constricted region or central flow channel 78 that extends into the main chamber 84 . the partitions 76 can be held a distance apart from the base section 34 to thereby create peripheral flow channels 80 as well . the peripheral flow channels 80 lend anti - siphon properties to the check valve mechanism 70 by creating narrow structures that restrict fluid flow distally . a free floating ball 72 is provided with the check valve mechanism 70 to occlude fluid flow into the base section 34 from the inflow catheter 40 during distal pumping or anti - reflux as shown in fig4 . the free floating ball 72 can be pushed aside or manipulated aside by positioning the patient , such as in fig . sa where normal flow conditions are present and fluid flows from the inflow catheter 40 through the base section 34 of the reservoir 30 and to the valve mechanism 22 as indicated by the arrows . the free floating ball 72 can also be pushed aside using an endoscope 90 such as in fig5 b during endoscopic placement of the shunt system 10 or during ventricular injection . to provide the endoscope 90 with access to the check valve mechanism 70 , the domed cap 14 of the housing 12 can include an endoscope port 16 . the endoscope port 16 can comprise a pre - formed slit comprising a resealable silicone and can extend into a portal 18 that connects to the top section 32 of the reservoir . once the endoscope 90 has passed through the portal 18 , the endoscope can continue through the top section 32 and into the base section 34 past the central flow channel 78 . the endoscope 90 can extend all the way out through the catheter connector 36 to facilitate placement of the shunt device 20 with respect to the pre - inserted inflow catheter 40 and allow endoscopic visualization as needed . the endoscope port 16 can also include radiopaque markings to assist the surgeon in locating and targeting the port 16 . additionally , the peripheral flow channels 80 of the base section 34 can be made more tortuous with surface features such as helical ridges 86 as illustrated in fig6 a which shows the flow dynamics during distal pumping or anti - reflux . the helical ridges 86 within the peripheral flow channels 80 provide the shunt system 10 with higher resistance and even more anti - siphoning capabilities . fig6 b shows the flow dynamics during normal erect flow , while fig6 c shows the flow dynamics during anti - siphon flow in which fluid traveling distally is forced through the tortuous path of the peripheral flow channels 80 and is thereby drained from the shunt system 10 at a reduced rate . finally , the flow dynamics during prone flow , or during distal pumping is illustrated in fig6 d , while fig6 e shows the use of an endoscope 90 with the present shunt system 10 during endoscopic placement or ventricular injection . the present invention also provides an instrument 100 for assembling the inflow catheter 40 quickly and easily to the shunt device 20 . the instrument 100 has a first arm 110 having a proximal end 112 and a distal end 114 including a handle portion 118 . pivotally connected to the first arm 110 at pin 130 is a second arm 120 having a proximal end 122 and a distal end 124 including a handle portion 128 . the proximal end 112 of the first arm 110 includes a gripping section 116 that is configured to hold a portion of the housing 12 . as illustrated in fig7 the gripping portion 116 is configured to seat against the domed cap 14 of the housing 12 . the proximal end 122 of the second arm also includes a platform section 126 that is configured to sit around the inflow catheter 40 and against the retaining ring 52 while resting on the patient &# 39 ; s scalp . upon compressing the handle portions 118 , 128 together , the gripping section 116 and platform section 126 advance towards each other , in the process forcing the retaining ring 52 up towards the first , attachment end 42 of the inflow catheter 40 . the platform section 126 is configured to slide along the inflow catheter 40 . the use of the instrument 100 to connect these components enables the retaining ring 52 to slide over the attachment end 42 of the ventricular catheter 40 and over the flange 38 of the connector 36 without over advancement . typically , the outflow catheter 60 can be assembled to the shunt device 20 prior to implantation , while the inflow catheter 40 is assembled to the shunt device after the two components are separately implanted . in one exemplary embodiment of the shunt system 10 , when fully assembled the inflow catheter extends at approximately 90 ° with respect to the outflow catheter . the endoscopic placement features just described for the shunt system 10 of the present invention allow the system 10 to be easily assembled and implanted using endoscopic placement so as to require only minimally invasive surgery . the assembly process for the present invention minimizes surgery time and avoids leakage at the connection sites , since the retaining ring eliminates the need for suturing methods . the endoscopic placement features of the present invention also provides the added benefits of revision on a minimally invasive basis , such as clearing or draining obstacles to improve cerebrospinal fluid flow , without major surgical intervention . finally , the check valve mechanism of the reservoir also provides easy occlusion for distal flushing . all of these features make endoscopic placement more convenient for the surgeon , and provide a better and more effective shunt system for the patient . it will be understood that the foregoing is only illustrative of the principles of the invention , and that various modifications can be made by those skilled in the art without departing from the scope and spirit of the invention . all references cited herein are expressly incorporated by reference in their entirety .
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referring initially to fig1 a , 1b , and 2 of the drawings , the bed loader of this invention is generally illustrated by reference numeral 10 . the bed loader 10 comprises a front guide 12 , a top forward guide 14 , and a top rear guide 16 . the bed loader 10 may be mounted on a four - wheel recreational vehicle 18 , fitted with a roof 20 , a roll cage 21 , a bed 22 and a winch 24 . the winch 24 is mounted on a front end 23 a of the recreational vehicle 18 , generally on a bumper 23 d , and the front guide 12 , the top forward guide 14 , and the top rear guide 16 are spaced on the recreational vehicle 18 in alignment with a winch line 33 running along a vehicle longitudinal axis 25 running from the front end 23 a to a rear end 23 b of the recreational vehicle 18 as shown in fig2 . the winch line 33 is fitted with a typical cable hook 34 and wound on a winch drum 32 that is as illustrated in fig1 a . the winch line 33 is of a sufficient length to allow the cable hook 34 to engage loads or a game animal , such as a deer 34 a in a bag 34 b , off the rear end 23 b of the recreational vehicle 18 . referring again to fig1 a , the front guide 12 of the bed loader 10 is mounted on the bumper 23 d of the recreational vehicle 18 above the winch 24 and the front guide 12 operates to receive the winch line 33 from the winch drum 32 and guide the winch line 33 to the top forward guide 14 which guides the winch line 33 to the top rear guide 16 when the winch drum 32 a is winding and unwinding the winch line 33 . accordingly , the winch line 33 extends from the winch 24 upwardly to the front guide 12 , and then upwardly across a front view area , such as a windshield 23 c to the top forward guide 14 and then to the top rear guide 16 and then may extend to the rear end 23 b of the recreational vehicle 18 as illustrated in fig1 a , 1b , and 2 . the bed 22 may be placed in a tilted position 22 a as shown by the dashed outline in fig1 b to more easily load the game animal , such as the deer 34 a . accordingly , the winch line 33 may be extended farther rearwardly from the top rear guide 16 by operation of the winch 24 and rotating the winch drum 32 in reverse direction , to lead out the winch line 33 from the winch drum 32 . the winch line 33 is guided downwardly from the top rear guide 16 in position such that the cable hook 34 on the winch line 33 , as illustrated in fig1 a and 1b , is then extended to the game animal , such as the deer 34 a in the bag 34 b . the winch 24 can then be operated to rotate the winch drum 32 in the opposite direction rewinding the winch line 33 on the winch drum 32 to load the game animal in the bed 22 . referring now to fig2 of the drawings , in a preferred embodiment of the invention the front guide 12 , the top forward guide 14 , and the top rear guide 16 each comprise at least a guide means 40 a , a guide support 40 b , and a retaining means 40 b as shown in for front guide 12 . referring to fig3 a , 3b , 4a , and 4b , the guide means 40 a may comprise an hourglass roller 41 a and a shaft bolt 49 . looking again to fig2 and more specifically to the front guide 12 , the guide support 40 b may be two “ l ” brackets 43 , each of the two “ l ” brackets 43 having a first leg 45 a running laterally traverse to the vehicle longitudinal axis 25 opposite the first leg 45 a of the other , and the guide means 40 b , an hourglass roller 41 a , disposed between the second leg 45 b of the one “ l ” bracket 43 and the second leg 45 b of the other “ l ” bracket 43 . referring to fig2 a and 4b , the retaining means 40 b of the front guide 12 , the top forward guide 14 , and the top rear guide 16 may be two retaining bars 42 a with each having a long leg 42 a 1 disposed parallel to the shaft bolt 49 and a short leg 42 a 2 that is parallel and adjacent to the second leg 45 b and perpendicular to the first leg 45 a . looking to fig3 a and 3b , the retaining means 40 c may also be a retaining pin 42 b , such as a ⅝ inch quick - release pin commonly available at vendors like mcmaster - carr . the retaining pin 42 b can easily be removed to place the winch line 33 in the guide , such as the front guide 12 . the retaining pin 42 b is disposed placed through the second leg 45 b of each “ l ” bracket 43 of each guide , such as front guide 12 , to hold the winch line 33 in the guide . looking to fig3 a , 3b , 3c and 3d , the front guide 12 is attached to a front mount 12 a . the front mount 12 a may be rectangular and comprises a top bar 13 a , two identical side bars 13 b , a front plate 13 c , and a bottom plate 13 d . the front plate 13 c and the bottom plate 13 d are rectangular and are attached to each other forming a base channel 13 e that is “ l ” shaped . the side bars 13 b are parallel to each other and run vertically , and are located between the top bar 13 a and the bottom plate 13 d that are running horizontally . looking at fig3 a and 4a , one side bar 13 b forms one side of the rectangular front mount 12 a and the other side bar 13 b forms the opposite side of the rectangular front mount 12 a and the side bars 13 b extend upward from an upper face 13 d 4 of the bottom plate 13 d , and are adjacent to a back face 13 c 3 of the front plate 13 c . the top bar 13 a is mounted to an upper end 13 b 1 of each of the top side bars 13 b . the base channel 13 e is attached to the two side bars 13 b along the back face 13 c 3 of the front plate 13 c and the upper face 13 d 4 of the bottom plate 13 d 4 . the top bar 13 c and the side bars 13 b may be made of square tubing , preferably 1 . 5 inch steel tubing between 0 . 15 and 0 . 25 inches thick , preferably 0 . 125 inches thick . the top bar 13 c is between 1 - 3 feet long , preferably 2 feet long , and the side bars are between 1 - 3 feet long , preferably 1 . 5 feet long . the front plate 13 c an the bottom plate 13 d are equal to the length to the top bar 13 a and generally 0 . 2 to 0 . 75 of an inch thick , preferably 0 . 25 inches , and 2 . 5 inches wide . the front plate 13 c runs horizontally and has a back face 13 c 3 that is oriented vertically and attached , preferably wielded , to the side bars 13 b , and to the upper face 13 d 4 of the bottom plate 13 d is attached , preferably welded , to the two side bars 13 b . the front guide 12 is attached , preferably welded , to a front face 13 a 4 of the top bar 13 a . fig5 a shows an enlarged side view of the top forward guide 14 and the top rear guide 16 on a base plate 44 as shown in fig1 a , 1b , and 2 but without the retaining means 40 c , such as the retaining bars 42 a or the retaining pin 42 b . fig5 b shows an enlarged top view of the top forward guide 14 and the top rear guide 16 of fig2 . fig6 a shows a top view of the top forward guide 14 with an hourglass roller 41 a and without the retaining means 40 c . fig6 b shows an end view of the top forward guide 14 of fig6 a , illustrating the shaft bolt 49 secured by a shaft nut 47 b . the shaft bolt ( 49 ) is inserted though the second leg ( 45 b ) of the each the two “ l ” brackets of the guide support ( 40 b ). looking again to fig6 a , the first leg 45 a of the “ l ” bracket 43 is drilled for a roof bolt 38 that secures the “ l ” bracket 43 to the roof 20 . the roof bolt 38 is 0 . 25 to 5 inches long and 0 . 25 to 0 . 5 inches in diameter allowing the roof bolt 38 to penetrate the first leg 45 a , the base plate 44 where used , and the roof and be secured by a fastener , such as a nut . the second leg 45 b may be a plate 2 to 6 inches long , 1 to 5 inches wide , and ½ inch thick . the first leg 45 a is 2 to 6 inches long , 1 to 5 inches wide and 0 . 25 to 0 . 75 inches thick . the second leg 45 b may be welded to the first leg 45 a . the first leg 45 a and the second leg 45 b may are made of a high strength material such as carbon steel . looking to fig6 c and 6d , the guide means 40 a of the top forward guide 14 may comprise a roller , such as the hourglass roller 41 a , and a shaft bolt 49 , with the hourglass roller 41 a rotating on the shaft bolt 49 that is inserted through the second leg 45 b of the each “ l ” bracket 43 and the hourglass roller 41 a . the shaft bolt 49 is secured on one end by a head 47 a and the other end by shaft nut 47 b , allowing the hourglass roller 41 a to rotate as the winch line 33 in fig2 moves over the hourglass roller 41 a to the rear end 23 b of the recreational vehicle 18 and is retracted back towards the front end 23 a . referring to fig6 a and 6b , the “ l ” brackets 43 can be mounted to a base plate 44 and secured to the roof 20 and the roll cage 21 of fig1 a and 1b by a roof bolt 38 through the first leg 45 a of each ‘ l ” bracket 43 . looking to fig2 , the base plate 44 is centered on the vehicle longitudinal axis 25 and the base plate 44 runs from the roof forward edge 23 e to the roof rear edge 23 f . looking again to fig6 c , the hourglass roller 41 a comprises a first disc portion 70 adjacent to a first portion 72 that is conically shaped and adjacent to a uniform circular middle portion 74 that is adjacent to a conically shaped second portion 76 that is adjacent to a second disc portion 78 ; the middle portion 74 being cylindrical and running from the first portion 72 to the second portion 76 ; the first portion 72 and the second portion 76 configured to cradle the winch line 33 of fig2 onto the middle portion 74 . the first portion ( 72 ) and the second portion ( 76 ) tapering down from the first disc portion ( 70 ) and the second disc portion ( 78 ), respectively , to the middle portion ( 74 ). referring to fig7 , an elongated cylindrical rod , the cylindrical roller 41 b , may be mounted between the two “ l ” brackets 43 of the guide support 40 b of the each guide , such as the top forward guide 14 , and the cylindrical roller 41 b disposed placed to rotate on the shaft bolt 49 . the cylindrical roller 41 b may also be removed and the winch line 33 allows to slide over the shaft bolt 49 . looking to fig8 a , 8b , 9a , and 9b , and more particularly 9 c , the retaining means 40 c may be a two retaining bars 42 a that are “ l ” shaped each having a long leg 42 a 1 , a short leg 42 a 2 and a distal end 42 c . the short leg 42 a 2 is mounted on the “ l ” bracket adjacent to the second leg 45 b and perpendicular to the first leg 45 a . when the retaining means 40 c is two retaining bars 42 a , the retaining bars 42 a can be mounted on the front guide 12 and the top rear guide 16 as shown in the top forward guide 14 in fig9 c disposed placed so that the winch line 33 to be inserted around the distal end 42 c of each retaining bar 42 a to ride on the hourglass roller 41 a of the guide means 40 a . when the two retaining bars 42 a are used , one on each “ l ” bracket 43 as shown in fig9 a and 9c , the retaining bars 42 a are mounted parallel to each other with the distal end 42 c of the each retaining bar pointed opposite the distal end 42 c of the other retaining bar 42 a . this allows the winch line 33 to be inserted around the distal end 42 c of the each retaining bar 42 a . fig1 shows the retaining bars 42 a used with the top forward guide 14 of fig7 . referring again to fig1 a , 1b , and 2 , the bed loader 10 of this invention is made to use of the winch 24 , winch drum 32 a , winch line 33 , and cable hook 34 provided on many recreational vehicles 18 . the winch 24 performs a key role and is an indispensable component for operating the bed loader 10 . it will be further appreciated that the bed loader 10 can be used for many purposes other than loading game animal in the bed 22 . for example , the winch 24 on the front end 23 a of the recreational vehicle 18 can be used with the bed loader 10 to load / pull items such as sacks of sand and the like and other objects , by utilizing the winch 24 and the winch line 33 in combination with the front guide 12 , the top forward guide 14 , and the top rear guide 16 of the bed loader 10 , in the same manner described above with regard to the handling and loading the deer 34 a . since the top rear guide 16 between the front wheels 25 a and the rear wheels 25 b of the recreational vehicle 18 , the recreational vehicle 18 is relatively stable when a heavy load , such as the deer 34 a is attached to the winch line 33 . the recreational vehicle 18 that has four wheels is much more stable and is a preferred vehicle for installation and use of the bed loader 10 , although the bed loader 10 may be mounted on a three wheel recreational vehicle ( not shown ). although the present invention has been described in considerable detail with reference to preferred versions thereof , other versions are possible . therefore , the spirit and scope of the appended claims should not be limited to the description of the preferred versions contained herein . various deviations and modification may be made within the spirit and scope of this invention without departing from the main theme thereof .
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the pipeline leak detector is a “ pig ” type device adapted for robotic travel within a fluid pipeline for the detection of fluid leaks in the pipeline wall . the device accomplishes this with a minimal number of sensors . the sensors rotate within the pipe to cover the entire interior surface of the pipe wall as the device travels through the pipe . the pipeline leak detector is particularly well suited for use in water pipelines , but may be adapted for use in pipes carrying oil , gas , and / or other fluids as well . fig1 of the drawings provides an elevation view in section of the pipeline leak detector 10 disposed within a pipe p . the leak detector 10 has a rotationally stationary drive component 12 having a central housing 14 . the drive component and its housing are restrained from axial rotation within the pipe p by a series of supporting wheels , described in detail further below . a rotary driveshaft 16 extends axially from the drive component 12 and its housing 14 . the driveshaft 16 has a drive component end 18 disposed within the housing 14 and an opposite sensor array end 20 . a leak detector component 22 is disposed upon the sensor array end 20 of the driveshaft 16 . the leak detector component 22 has a single leak sensor array 24 extending radially therefrom that subtends a limited arc ( e . g ., thirty degrees , more or less ) about the leak detector component 22 . the sensor array 24 comprises a plurality of pressure sensors 26 extending radially from a sensor array support wheel 46 , which is installed concentrically about the central body of the leak detector component 22 . the sensors 26 are adapted for the detection of minor pressure changes along the wall of the pipe p as the device 10 travels through the pipe . the leak detector component 22 and the sensor array 24 extending radially therefrom are driven in axial rotation within the pipe p as the rotary driveshaft 16 rotates . the leak sensors are force sensors , having either a gate or a membrane that moves and generates an electronic signal when a leak is detected . two different pressure sensor embodiments are described herein , which are illustrated in fig4 and 5 , respectively , and described in detail further below . fig2 and 3 also illustrate sensor arrays 24 . the array of fig2 has four sensors 26 , and the array of fig3 shows three such sensors 26 . the precise number of sensors is adjusted in consideration of the diameter of the pipe p , the diameters of the sensors 26 , and the axial and radial velocities of the sensors as they travel through the pipe p . the drive component 12 and central housing 14 of the leak detector 10 are supported by three radially disposed wheels . the wheels travel along the interior surface of the pipe wall as the device 10 travels through the pipe . the three wheels are distributed evenly about the circumference of the leak detector 10 and are separated by substantially equal angular arcs a of about 120 ° each , as shown in fig2 of the drawings . a rotationally powered drive wheel 28 rolls along the interior surface of the pipe p wall . the drive wheel 28 provides motive power for the leak detector 10 to drive the device 10 through the interior of the pipe p . the drive wheel 28 may be powered by a small electric motor disposed within the wheel hub . the motor receives electrical power from an on - board electrical storage battery disposed within the drive component 12 . such motors and electrical power battery systems are well known , and accordingly are not described in further detail herein . a driven wheel 30 extends radially from the central housing 14 and rolls along the interior of the pipe p . the driven wheel 30 has a concentric first bevel gear 32 a at its hub . the first bevel gear 32 a drives a second bevel gear 32 b disposed upon the distal end portion 34 b of a driven wheel shaft . the shaft has a proximal end portion 34 a disposed within the central housing 12 and extending radially therefrom . the distal end portion 34 b telescopes within the proximal end portion 34 a to allow the driven wheel shaft assembly to lengthen and shorten according to the diameter of the pipe p . the two driven wheel shaft portions 34 a and 34 b are locked rotationally to one another by splines , key and keyway , non - circular sections , or other conventional means . a third bevel gear 36 a is affixed to the proximal end portion 34 a of the driven wheel shaft assembly . a fourth bevel gear 36 b is affixed to the drive component end 18 of the leak detector component driveshaft 16 and meshes with the third bevel gear 36 a , as shown in fig1 . this gear train drives the leak detector component driveshaft 16 and the leak detector component 22 extending therefrom rotationally as the driven wheel 30 rotates due to its frictional engagement with the wall of the pipe p as the leak detector 10 travels through the pipe . alternative means of transmitting the rotary motion of the driven wheel 30 to the driveshaft 16 may be provided , e . g ., a flexible shaft , hydraulics , etc . the third wheel is an idler or stabilizer wheel 38 extending radially from the drive component 12 , or more properly from its central housing 14 , and serves primarily as a third point defining the transverse span of the drive component 12 across the interior of the pipe p . the idler or stabilizer wheel 38 is a passive support wheel with no drive means , i . e ., no means of propelling the leak detector 10 through the pipe p , and has no means of driving the rotation of the driveshaft 16 and its leak detector 12 . however , the stabilizer wheel 38 may include means for transmitting its rotary motion to a central processor ( discussed further below ) for translation to distance traveled by the pipeline leak detector 10 as it travels through the pipe p . this function may alternatively be handled by one of the other two wheels 28 or 30 , particularly the driven wheel 30 , as it is already imparting rotary motion to the driveshaft 16 that is connected to the drive component 18 of the device . the driven wheel shaft can adjust inward and outward to adjust for different pipe diameters by means of its mutually telescoping proximal and distal portions 34 a and 34 b , as noted above . accordingly , the positions of the three wheels 28 , 30 , and 38 may be adjusted for different pipe diameters . each of the wheels is supported by an adjustable length strut that extends radially from the drive component 12 , or more properly , from the housing 14 of the drive component . the drive wheel 28 is supported by a drive wheel strut having a proximal portion 40 a and a distal portion 40 b that telescopes in and out of the proximal portion 40 a to adjust its length . the driven wheel 30 is supported in the same manner by a driven wheel strut having a proximal portion 42 a and a distal portion 42 b that telescopes in and out of the proximal portion 42 a . the idler or stabilizer wheel 38 is also supported in the same manner by a stabilizer wheel strut having a proximal portion 44 a and a distal portion 44 b that telescopes in and out of its proximal portion 44 a . the pipeline leak detector 10 may thus be adjusted for use in different diameters of pipes p by adjusting the lengths of the driven wheel shaft , the three wheel struts , and the radial spans of the sensors 26 of the sensor array 24 . the longitudinal or axial motion of the pipeline leak detector 10 through the pipe p results in a rotary motion of the leak detector component 22 and its sensor array 24 by means of the drive wheel 30 and its driveshaft and gearing , as described in detail further above . the drive component 12 of the leak detector is restricted from rotating about its longitudinal axis within the pipe p due to the alignment of the wheel rotation or tracks parallel to the longitudinal axis of the pipe . however , the combination of the longitudinal motion of the leak detector 10 and the rotary motion of the leak detector component 22 and its sensor array 24 results in the sensor array 24 describing a helical path h immediately adjacent the inner surface of the pipe wall , as shown in fig6 of the drawings . ( the helical path illustrated in fig6 is shown in its complete appearance through 360 ° of rotation within the inner circumference of the pipe p .) the diameter of the drive wheel 30 and the gear ratios of the first through fourth bevel gears 32 a , 32 b , 36 a , and 36 b are selected to provide complete coverage of the interior of the pipe wall as the sensor array 24 travels along its helical path h . it will be seen that by increasing the rotational speed of the leak detector component 22 relative to the longitudinal speed of the device 10 through the pipe p , it is possible to use only a single leak detector array 24 . the pipeline leak detector 10 is adapted to travel through a pipeline p carrying water , oil , gas , or other fluid in search of leaks l , as shown in fig7 of the drawings . any leak l will result in a pressure drop across the leak , as the fluid flows from the relatively higher pressure within the pipe p to the lower pressure outside the pipe ( or vice versa ) and the flow accelerates through the leak aperture . fig7 provides a representation of this phenomenon . the pressure is represented by a series of isobars i1 through i8 ( with other closely spaced isobars being shown within the leak aperture ). the more closely spaced the isobars are over a given distance or span , the greater the pressure drop over the given distance . the pressure drop within the pipe p , represented by the isobars i1 through i4 , is of primary interest here . it will be noted that in order to detect this pressure drop , the detector or sensor must be quite close to the leak l , as the pressure does not change significantly at some distance from the leak , as indicated by the relatively widely spaced isobars i1 and i2 . accordingly , the helical path h traveled by the sensor array 24 assures that complete coverage of the interior of the pipe wall will occur as the pipeline leak detector 10 travels through the pipe p so that at least one of the pressure sensors 26 passes nearly directly over the leak to register the pressure drop . returning to fig1 of the drawings , it will be noted that each of the pressure sensors 26 is connected to a central processor 48 by a wiring harness 50 . the central processor 48 receives pressure drop signals from each of the pressure sensing elements 26 whenever such a pressure drop is sensed by an individual sensor or sensors . the central processor 48 also communicates electronically with the rotationally stationary drive component 12 , e . g ., via slip rings or other conventional means . the central processor 48 registers both the location of the leak detector 10 within the pipe p by means of the odometer information provided by one of the three wheels 28 , 30 , or 38 , and also registers the angular relationship between the leak detector component 22 and its sensor array 24 relative to the drive component 12 . thus , whenever a leak is detected , the central processor 48 records this information to enable a technician or other person to determine not only the axial location of the leak along the length of the pipe p , but also the circumferential location of the leak about the pipe . this information may be recorded by the central processor 48 , and / or may be transmitted to a remote external receiver 52 by an on - board transmitter 54 communicating with the receiver 52 , if desired . fig4 and 5 illustrate two different pressure differential leak sensors , or more precisely , two different detectors that may be installed within the pressure differential leak sensor 26 . the pressure differential leak sensor 26 essentially comprises a radially disposed tube 56 having a support wheel attachment end 58 and an opposite outer end 60 , with a frustoconical mouth 62 extending from the outer end 60 . in the embodiment of fig4 , a flexible valve 64 extends across the juncture of the mouth 62 and the outer end 60 of the tube 56 . the valve 64 includes a strain gauge 66 thereon . the strain gauge 66 is electrically connected to the central processor 48 by a wiring harness 50 , as shown in fig1 of the drawings . as the mouth 62 of the sensor 26 passes over a leak , the drop in pressure at the leak results in fluid flow through the tube 56 , thus flexing the valve 64 outward as shown in fig4 as the fluid flows therethrough and altering the electrical characteristics of the attached strain gauge 66 to send a signal to the processor 48 . the pressure differential leak sensor 26 of fig5 has an identical outer structure , i . e ., tube 56 with its inboard attachment end 58 and opposite outer end 60 and frustoconical mouth 62 extending from the outer end 60 . however , rather than having an opening valve within the juncture of the outer end 60 of the tube and the frustoconical mouth 62 , a closed or sealed flexible diaphragm 68 is applied across this juncture . a strain gauge 66 , which may be substantially identical to the strain gauge illustrated in the embodiment of fig4 , is installed upon the flexible diaphragm 68 . the strain gauge 66 may be installed either outward or inward on the diaphragm 68 or the valve 64 of the embodiment of fig4 , as desired . as the mouth 62 of the sensor 26 of fig5 passes over a leak , the drop in pressure at the leak results in a differential pressure between the interior of the tube 56 and the mouth 62 of the tube , thus distending the sealed diaphragm 68 outward as shown in fig5 and altering the electrical characteristics of the attached strain gauge 66 to send a signal to the processor 48 . it is to be understood that the present invention is not limited to the embodiments described above , but encompasses any and all embodiments within the scope of the following claims .
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it is to be understood that the figures and descriptions of the present invention have been simplified to illustrate elements that are relevant for a clear understanding of the present invention , while eliminating , for purposes of clarity , other elements that may be well known . those of ordinary skill in the art will recognize that other elements are desirable and / or required in order to implement the present invention . however , because such elements are well known in the art , and because they do not facilitate a better understanding of the present invention , a discussion of such elements is not provided herein . the detailed description of the present invention and the preferred embodiment ( s ) thereof is set forth in detail below with reference to the attached drawings . though many hardware and software approaches for implementing the present invention are feasible , a preferred embodiment of the present invention comprising a system for protecting individual stored data objects — at times referred to herein as files — is a software implementation for a general - purpose computing system . referring now to the drawings , wherein like reference numerals designate corresponding structure throughout the views , fig5 illustrates one possible preferred hardware configuration 90 of a general - purpose computing system according to the present invention . the system hardware comprises networking components 100 such as ethernet adapters , non - volatile secondary memory 102 such as magnetic disks , input / output devices 104 such as keyboards and visual displays , volatile main memory 106 , and a processor 108 . all of these system hardware components can be connected via a common system bus 110 . the processor 108 comprises processing units 112 and on - chip storage devices 114 such as memory caches . a preferred embodiment is application software that is stored in non - volatile memory devices 102 while not in use ; when the software is needed , the software is loaded into volatile main memory 106 . after being loaded into main memory 106 , the processor 108 can read software instructions from main memory 106 and perform useful operations by executing sequences of the software instructions on data that is read into the processor 108 from volatile main memory 106 . upon completion , certain data results of the instructions are written to volatile main memory 106 . alternatively , the steps of the present invention might be performed by specific hardware components that contain hardwired logic for performing the steps , or by any combination of programmed computer components and custom hardware components . it is to be understood that various terms and techniques are used by those knowledgeable in the art to describe communications , protocols , applications , implementations , mechanisms , etc . one such technique is the description of an implementation of a technique in terms of an algorithm or mathematical expression . that is , while the technique may be , for example , implemented as executing code on a computer , the expression of that technique may be more aptly and succinctly conveyed and communicated as a formula , algorithm , or mathematical expression . thus , one skilled in the art would recognize a block denoting d + e = f as an additive function whose implementation in hardware and / or software would take two inputs ( d and e ) and produce a summation output ( f ). thus , the use of formula , algorithm , or mathematical expression as descriptions is to be understood as having a physical embodiment in at least hardware and / or software ( such as a computer system in which the techniques of the present invention may be practiced as well as implemented as an embodiment ). fig6 illustrates a preferred logical location of a preferred software program of the present invention in a general - purpose computing system . the boxes in fig6 represent software code modules , and the arrows represent file input / output ( i / o ) operations . as shown in fig6 , a software implementation according to the present invention is preferably contained within a microsoft windows file system filter driver ( or the equivalent of such a filter driver in other operating systems ). a file system filter driver intercepts file system i / o to perform certain operations prior to sending file data to the underlying file system or subsequent to retrieving data from the underlying file system , and such a preferred software implementation and / or a file system filter driver may communicate with other software code modules in the general purpose computing system . furthermore , in many systems in which it is installed , such a preferred software implementation of the present invention does not require changes to the software applications or to the operating system kernel . in reference to fig6 , other preferred software implementations of the present invention may be contained in the software application ( s ), the operating system code , and / or the file system driver . a file f to be protected consists of n bits . in a preferred embodiment of the present invention , the file is logically divided into m b - bit blocks , as shown in fig7 . the size of b can be adjusted as needed , but in a preferred embodiment , the size of b is 8192 bytes , which equals 65536 bits . if f is not aligned to b bits ( i . e ., the last block consists of a number of bits x that is fewer than b bits because n is not evenly divisible by b ), then the minimal number of zero bits is appended to the logical representation of the file such that the size of the appended file is evenly divisible by b . the last block in fig7 illustrates the appended zeroes . in alternative embodiments of the present invention , the file is not required to be padded with zeroes when n is not evenly divisible by b . in one or more preferred embodiments of the present invention , software is utilized to protect file data and to perform security operations on protected file data . prior to the execution of any of these operations , unprotected file data must be converted into protected file data . given an n - bit b - bit - aligned file f , the file is protected on a block - by - block basis to obtain a protected file f ′ of size n ′ bits . fig8 illustrates the logical structure of the protected file f ′. the initial contents of f ′, which compose the protected file header , contains per - file metadata such as the protected file identifier , access right information , and certain cryptographic key material that is associated with the protected file . the remainder of the protected file consists of m protected blocks that are interleaved with per - block metadata . the jth protected block , where j is an integer between 1 and m , corresponds to the jth block of the file f . the jth protected block of f ′ is simply the jth block of file f in encrypted form . in one or more preferred embodiments of the present invention , a symmetric - key cipher is used to encrypt blocks , and an encrypted block is the same size as an unprotected block , b bits . preferably , a region of per - block metadata may include information such as hash fingerprints and cryptographic key material that is associated with the corresponding protected block . preferably , the per - file metadata and the per - block metadata may be of fixed size or of a size that varies over time or that varies between protected blocks . in one or more preferred embodiments of the present invention , the protected file preferably is structured to interoperate with a preferred cryptographic key hierarchy . a preferred hierarchy for a single file consists of per - block keys ek j and hk j , a file encryption key fek , a file hashing key fhk , and possibly one or more intermediate encryption keys iek x . fig9 illustrates a preferred cryptographic key hierarchy of the present invention . all keys except for the fhk are represented in a logical tree ( henceforth called the “ key tree ”), in which the nodes represent cryptographic keys , and the arrows between nodes represent an encryption operation . for any node in the tree , the key associated with that node is encrypted with the key associated with its parent node , and the encrypted key is stored in either per - block or per - file metadata within the protected file . in a preferred embodiment , both the encryption and decryption algorithms can employ fek to encrypt and decrypt data using a symmetric - key cipher . however , alternative embodiments of the present invention may employ separate encryption and decryption keys in conjunction with other types of algorithms ( such as public - key ciphers ) to perform encryption and decryption operations . similarly , instead of using a single key to perform encryption and decryption steps in various operations described below , alternative embodiments of the present invention may employ separate encryption and decryption keys as well as different types of ciphers ( such as asymmetric - key ciphers ) to implement those steps .” referring to fig8 , each of the m protected blocks is associated with a unique key for encryption and a unique key for keyed hash computation . the encryption key for the jth block is ek j , and the hashing key for the jth block is hk j . ek j is the secret key employed by a symmetric - key cipher to encrypt / decrypt the jth file block . hk j is applied as an input to an hmac generation function along with the encrypted jth block and possibly other identifying information regarding the jth block ( such as the value of j ) to produce an hmac g j . g j and other relevant information associated with the jth block ( such as initialization vectors or counters needed to facilitate the desired encryption mode of operation ) are stored in the per - block metadata in unencrypted ( i . e ., plaintext ) form . preferably , the keys used to encrypt the per - block keys are the intermediate encryption keys iek x , which are stored in a protected file in encrypted form . the plaintext versions of the keys in lowest tree level of intermediate keys are used to encrypt the per - block keys . ek j and hk j are stored in the per - block metadata in encrypted form ( i . e ., encrypted with the keys corresponding to the parent node ). if there are several levels of intermediate keys , then intermediate keys in all levels except for the highest ( topmost ) level are encrypted using other intermediate keys that are their parents in the logical tree . the highest level of intermediate keys preferably are encrypted with the file encryption key fek . in one or more preferred embodiments of the present invention , the intermediate keys may be stored in encrypted form in per - file metadata or per - block metadata . in addition , the intermediate keys may be encrypted and distributed across the per - block metadata associated with multiple protected blocks . depending on the characteristics of access patterns to protected files , a preferred cryptographic key hierarchy of the present invention may comprise a deep tree of intermediate keys , i . e ., a tree with many levels . in addition , another preferred cryptographic key hierarchy of the present invention may comprise a broad tree of intermediate keys , i . e ., a tree where intermediate key nodes have many children . also , in a basic implementation of yet another preferred cryptographic key hierarchy of the present invention , no intermediate keys are employed , and the file encryption key fek would be used to encrypt the per - block keys . preferably , the file encryption key fek and the file hash key fhk , in one or more preferred embodiments of the present invention , are stored in the per - file metadata ( possibly along with other access control information that is modifiable only by an authority ) in encrypted form . in one or more preferred embodiments of the present invention , other system components that interoperate with a system utilizing one or more methods or software implementations according to the present invention may be relied upon to allow only authorized users to successfully obtain the fek and the fhk in unencrypted forms ( for use by such a system utilizing the present invention ) through interaction with an authority . in a preferred embodiment , the fhk is used in concert with the per - block hash keys hk j and a merkle hash tree to provide integrity for the file data and file metadata . however , as known to those skilled in the art , several other methods can be employed to achieve data integrity and data freshness verification goals ; examples of such methods include but are not limited to digital signature schemes , simple per - file or per - block hmacs , and modes of operation for encryption algorithms that provide both confidentiality and integrity capabilities . fig1 illustrates a preferred , simplified structure of a hashing implementation of the present invention . a single root hash for all of the file data is computed using a merkle hash tree , as shown in the left side of fig1 . the leaf nodes of the tree are the per - block hmac values g j ( as described above ), and a given intermediate node ( or the root node ) of the tree represents the output of a hash function computed over the hash values represented by the child nodes of that given node . similarly to the handling of the intermediate keys iek x , the hash values corresponding to the nodes of the merkle tree are encoded and efficiently distributed across the per - block metadata associated with several protected file blocks . preferably , in the per - file metadata for the protected file , a per - file hash g file is stored . the computation of g file , as shown in fig1 , is the output of an hmac function using the file hash key fhk and performed over the root hash of the merkle tree , optionally over the hash of certain bits from the per - file metadata , and optionally over a file version number ver . the value of g file and the intermediate hashes can be used by the operations described below to efficiently verify the freshness and integrity of protected file data blocks and certain file metadata . given the structure of the protected file and the cryptographic key hierarchy , one or more preferred embodiments of the present invention comprise ( s ) the performance of one or a plurality of the following four operations : protected file reading , protected file writing , protected file access modification , and forced expiration of protected files . though the following descriptions of preferred methods of the present invention for protected file reading and protected file writing relate only to a single protected block to be read / written , these operations can be easily modified , within the scope of the present invention , to accommodate multiple protected block reads / writes . a preferred method of protected file reading according to the present invention comprises reading bits from the jth protected file block by an authorized user . given fhk and fek in plaintext form , certain per - file metadata ( including g file and ver ), the entire protected file block , and the corresponding per - block metadata are read from the storage device . additionally , any per - block metadata is read from the storage device that is associated with the nodes in the key tree along the path of the fek to the per - block keys for the desired protected file block . this path is called the key path . also , any per - block metadata is read that is associated with the nodes in the merkle hash tree along the path from the root hash to the desired protected file block hmac . this path is called the hash path . next , the per - block values of ek j and hk j are obtained by decrypting the keys along the key path one by one . this process begins by decrypting the first intermediate key from the key path via a decryption algorithm using the key fek , and the chain of decryption continues along the key path until ek j and hk j are deciphered . then , the protected file block can be decrypted using ek j and possibly certain information from the per - block metadata . now , the integrity and freshness of the desired file block ( and certain other file information ) is verified as follows . the hmac value g j is computed for the desired block using the key hk j over at minimum the ( encrypted ) file data block read from storage . then , the expected value of g file is computed as follows . beginning with the computed value of g j , the nodes read from storage along the hash path are used to compute the root hash of the merkle tree . then , as shown in fig1 , this root hash is inputted to an hmac function along with certain per - file metadata , the version ver read from storage ( or that is obtained from a trusted party or a secured point of reference ), and the key fhk , which enables the generation of an expected value of g file . if this expected value differs from the value of g file read from storage , an error may be reported , as either the file has been modified in an unauthorized manner or certain file data has been rolled back to an earlier version of that data in an unauthorized manner . optimizations can be applied to this process to accelerate the verification process and to distinguish between unauthorized file modification and unauthorized file rollback . a preferred method of the present invention of writing bits to a protected file block by an authorized user comprises one or more of the following methods : overwriting data in an existing file block , writing data to a new protected block to the end of the file , or deleting data from the protected block at the end of a file . a preferred method of overwriting data according to the present invention , wherein bits are to be written to existing protected data block j , comprises the initial steps of reading , decrypting and verifying the protected block j using the steps described above . then , by replacing certain bits in the existing plaintext block with the plaintext bits to be written , a new plaintext block is generated . the new plaintext block is then encrypted with a new , randomly or pseudorandomly generated per - block key ek j , and a new hmac value g j is computed for the protected block is generated using a new , randomly or pseudorandomly generated per - block key hk j . using the values from the key path and the hash path obtained during the protected block reading process , the key tree and the merkle tree are updated from the leaf node to the root node . specifically , for each node in the key tree along the key path between the new ek j and the child of the key fek ( not including ek j and fek ), a new encryption key is randomly generated , and all of the children of that node are encrypted using the new encryption key . each of the updated keys is written to its appropriate location in the file metadata . for each node in the merkle tree along the hash path from the new g j and the root hash ( excluding g j but including the root hash ), new hashes are generated and written to their appropriate locations in the file metadata . next , the value of ver is incremented by 1 and written back to the file ( and possibly transmitted to a trusted party or a secured point of reference ). then , the new value of g file is generated by computing the hmac using the key fhk over certain per - file metadata , the new value of ver , and the root hash . the new value of g file is then written to the protected file . in alternative embodiments of the present invention , depending on the security goals , the initial steps of overwriting protected block data recited above may not require reading , decrypting , and verifying the existing protected block in the event that the entire protected data block is to be overwritten . in a preferred method of writing data to a new protected block at the end of a file , wherein b or fewer new bits are to be appended to the end of the protected file by creating a new protected file block at the end of the file , if the number of bits to be written is fewer than the preferred protected file block size b , then the bits to be written are appended with zeroes such that the number of bits to be written is b . next , the key path and the hash path are read ( as described above ), but no block is decrypted or verified . now , as in the preferred method of overwriting data in existing file blocks as described above , new keys ek j and hk j are created , and the protected file block is encrypted and hashed . the resulting encrypted block and associated per - block metadata are then written to the protected file . the key tree , the merkle hash tree , the value of ver , and the file hash g j are then updated as described with respect to the preferred method of overwriting data in existing file blocks as described above , but depending on the number of blocks in the file , the number of nodes in the two trees may be expanded to ensure that the trees remain balanced . a preferred method of deleting data according to the preset invention , wherein b or fewer bits are to be deleted from the protected block at the end of the protected file , if the number of bits to be deleted is fewer than the number of data bits ( not including zero padding bits ) in the protected block at the end of the file , then a new protected block is written to the file using the preferred method of overwriting data described above . the new protected plaintext block would simply be the original plaintext blocks in which certain bits are replaced with zeroes . if the number of bits to be deleted is equal to the number of data bits in the protected block at the end of the file , the entire block is to be deleted . in this scenario , the key tree and the hash path are read ( as performed in the first preferred operation ). the merkle hash tree , the value of ver , and the file hash g j are then updated as described above with respect to the preferred method of overwriting data described above , but depending on the number of blocks in the file , the number of nodes in the merkle tree and in the key tree may be reduced to ensure that the trees remain balanced . in a preferred method of the present invention for modifying an entity &# 39 ; s access rights to a protected file , given the values of fek and fhk in unencrypted form , the authorized entity requests an access control rights modification from an authority using certain information that may be obtained from the protected file . if the authority grants the request , new keys fek new and fhk new ( and in some cases , new metadata ) are provided to the authorized requesting entity in plaintext and ciphertext forms . if new metadata is provided , the requesting entity writes that metadata to the appropriate location ( s ) with the protected file . in a system utilizing a software implementation according to the present invention , other system components that interoperate with such software implementation may be relied upon to obtain new keys fek new and fhk new in encrypted and unencrypted forms ( for use by such software implementation according to the present invention ). next , the authorized entity reads the following information from the stored file : the root hash of the merkle tree and the existing per - file metadata ( which includes the value of ver ). the authorized entity increments the value of ver by 1 , and then the entity generates a new g file by using the key fhk new to compute the hmac over the root hash of the merkle tree , the incremented value of ver , and certain per - file metadata . furthermore , the children of the key fek in the key tree are read from the file metadata , decrypted with fek , re - encrypted with fek new , and the new encrypted values of those keys are written to the file metadata . next , the new value of g file , the fhk new in ciphertext form , the fek new in ciphertext form , and possibly other per - file metadata ( including the new value of ver ) are written to the file . lastly , new value of ver may be transmitted to a trusted party or a secured point of reference . because of the manner in which the merkle tree and the key tree are updated during a protected file write operation , this access right modification operation may virtually ensure that entities cannot access new data written to a file after their access rights are revoked , and the operation may virtually ensure that entities cannot access data that is not currently stored in the file but was stored in the file prior to the time at which those entities obtained access to that file . a preferred method of the present invention for disabling access allows for the prevention of future access to the plaintext data of a protected file or certain protected file blocks without explicitly deleting all copies the protected file or the protected file blocks . with respect to this preferred method of the present invention for disabling access , a set of possible data classifications exist wherein each classification is associated with a unique encryption key , and all copies of that key are maintained , protected , and tracked by a trusted authority ( such as a centralized administration server ) that may exist inside or outside of the software and supporting hardware of a system in which preferred methods of protected data accesses are performed . at the time when a file is initially protected or at the time when a new protected file is created , the protected file can be associated with one or more classifications . for a file associated with y classifications , the ciphertext versions of the fek and fhk generated by a trusted authority are equivalent to the values of fek and fhk recursively encrypted at least y times , at least once with each encryption key corresponding to any of the y classifications . when an authorized entity requests the decryption of the fek and the fhk in order to read , write , or change access to the file , the trusted authority performs the y recursive decryptions using the y classification keys without releasing the key to the authorized entity or to an untrusted environment . in order to permanently disable access to all files with a particular classification , the authority simply deletes all copies of the encryption key associated with that classification from its volatile and non - volatile storage . by the properties of strong symmetric - key encryption algorithms , if any entity ever requests the decryption of the fek or fhk for a file that possesses a classification associated with a deleted key , then no entity — including the trusted authority — will be able to decrypt the fek and fhk for that file . however , alternative embodiments of the present invention may employ separate encryption and decryption keys in conjunction with other types of algorithms ( such as public - key ciphers ) to perform encryption and decryption operations conducted by the trusted authority , and a preferred embodiment described herein can be easily extended to disable access to both encryption keys and decryption keys associated with data objects . this preferred method of disabling access can be extended as follows to prevent all future access to individual blocks within files instead of only to files as a whole . an individual block may be classified in the same way that a file can be classified . during a protected block write operation , in addition to encrypting the block encryption and hashing keys ek j and hk j corresponding to that block using keys from the key tree , the encrypted results are provided to the trusted authority and are encrypted again using one or more classification keys . the trusted authority then returns the doubly encrypted results , and these results are stored in the protected file . similarly , during a protected block read operation , the relevant block encryption and hashing keys are first provided to the trusted authority for decryption using a classification key prior to being decrypted using keys from the file &# 39 ; s key tree . as in the file classification case , if a classification key is destroyed by the trusted authority , then the encrypted blocks associated with that classification will not be accessible in the future by any entity . additional steps may be added and optimizations may be performed to each of these preferred operations to provide additional security services and improve performance , respectively . while embodiments and applications of this invention have been shown and described , it would be apparent to those skilled in the art having the benefit of this disclosure 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 .
| 7 |
referring now to fig1 a , an expanding liquid barrier 1 is shown according to one embodiment of the present invention . the expanding liquid barrier 1 is substantially flat and low profile when no liquid is present . the barrier 1 preferably has tape - like or narrow sheet - like geometry . when liquid 2 contacts the barrier 1 , the barrier 1 heightens to create a barrier 1 or dyke as shown in fig1 b . according to one embodiment of the present invention shown if fig2 a and 2b , the barrier 1 may include an adhesive layer 10 which holds the barrier to a base surface 3 . the base surface 3 may be any surface which may benefit from a barrier of this type , for example , a floor , walkway , entranceway , lab table , equipment platform or other surface . in one embodiment the adhesive layer 10 is a one - sided tape . the adhesive layer 10 has a bottom face 11 and a top face 12 . the bottom face 11 is adhered to the base surface 3 . the bottom face 11 of adhesive layer 10 prevents horizontal and vertical movement of the barrier 1 . the bottom face 11 also creates a seal preventing liquid from passing under the barrier 1 . the top face 12 is opposite the bottom face on the adhesive layer and is connected to an expanding layer 20 . the expanding layer 20 is affixed to the top surface 12 of the adhesive layer 10 along a longitudinal edge of the barrier at a front end 5 and rear end 6 . the expanding layer 20 may be affixed to the adhesive layer 10 by adhesive or by mechanical seal . the expanding layer 20 may be made of two or more sections , a liquid permeable section 40 and liquid impermeable section 30 . the impermeable layer 30 may be made from any liquid impervious material , for example , vinyl , rubber , acrylonitrile butadiene styrene ( abs ), materials found under the tradename sanoprene , polyethylene and polypropylene . the permeable section 40 may be made of perforated sheet and solid materials and woven and non - woven materials . the permeable layer 40 may be made from a material which allows fluid to pass through like a woven material or the liquid permeable layer 40 may be what is considered an impermeable material with various holes throughout the segment to allow liquid to pass as seen in fig3 . again referring to fig2 a and 2b , an expandable fill 50 may be disposed between the adhesive layer 10 and the expanding layer 20 . the expandable fill 50 is capable of increasing in size or swelling when it comes in contact with a liquid . as the expandable fill 50 swells the expanding layer 20 fills and increases in height . the expandable fill 50 may also absorb some amount of liquid . in one embodiment the expandable fill is a super absorbent polymer . in another embodiment the expandable fill 50 may comprise compressed sponges , foam or any other compressible absorbent . for example , isocyanate - based foams , pyranyl foams , syntactic foams , and / or elastomeric foams may be used . certain absorbents may be compressed through the use of a water - soluble binder , i . e . the absorbent may be wetted with the binder compressed and dried into a thin configuration . referring now to fig3 , a section of barrier 1 is shown . the arrow indicates the direction from which liquid would approach the barrier 1 . in a preferred orientation , the permeable section 40 is positioned nearest the approach of the fluid . in this embodiment , permeable section 40 is typically made from the same material as impermeable section 30 . the permeable section 40 allows fluid to pass by way of apertures 41 . referring now to fig4 , the same preferred arrangement is shown with the permeable section nearest the approach of fluid . however , in this embodiment , the permeable section 40 and impermeable section 30 comprise different materials . the impermeable section 30 comprising a material impervious to the flow of liquid while the permeable section 40 utilizes and inherently permeable material to allow liquid to pass . the impermeable section 30 and permeable section 40 are joined by any common means . in the embodiment shown in fig5 a - 5d , the barrier 1 includes an adhesive layer 10 affixed at one end to an expanding layer 20 . the expanding layer 20 includes only an impermeable section 30 . the expanding layer 20 and adhesive layer 10 open at one end but are connected by flexible members 21 . the flexible members 21 allow the expanding layer to open partially but not fully . for example , the flexible members 21 may restrict opening of the expanding layer 20 to less than 90 °. as seen in fig5 b expandable fill 50 is disposed between the expanding layer 20 and adhesive layer 10 . the expandable fill 50 swells when in contact with a liquid causing the expanding layer 20 to lift at its open end . the expanding layer 20 raises until the flexible members 21 are fully extended , as shown in fig5 c and fig5 d . flexible members 21 may be made of any suitable material , which is flexible yet , substantially inelastic . another embodiment of an expanding liquid barrier according to the present invention is shown in fig6 a and 6b . in this embodiment the barrier 1 has an adhesive layer 10 affixed to the floor and an expanding layer 20 . the expanding layer 20 is made of an impermeable and highly resilient material , for example , rubber , abs , materials found under the tradename sanoprene , polyethylene , and polypropylene . as seen in fig6 a , the expandable layer 20 is held in a generally flat and low profile configuration by being compressed and held together with a water - soluble adhesive 22 . when a water based liquid 2 comes into contact with the barrier 1 the water soluble adhesive 22 dissolves and releases the expanding layer so that the liquid may be contained as seen in fig6 b . the water soluble adhesive 22 may be , for example , cellulose ether , polyvinylpyrrolidone , or polyvinyl alcohol . it is also contemplated that the soluble adhesive 22 may be oil based where the barrier 1 is used to contain oil based liquids . suitable oil soluble adhesives include , for example , ethoxylated nonylphenol and transitions metal alkyl sulfonates . referring now to fig7 a and 7b , an expanding liquid barrier 1 according to one embodiment of the present invention is shown . in this embodiment , the barrier 1 has an adhesive layer 10 affixed to the floor . adjacent the adhesive layer 10 is a contracting portion 25 also adjacent the floor . the expanding layer 20 is affixed at its ends to the contracting portion 25 as shown in fig7 a . in one embodiment the expanding layer 20 may have a front end attached to the contract section 25 and a rear end attached to the adhesive layer 10 . the expanding layer 20 may be wholly made of liquid impermeable material or may have a portion which is permeable nearest the approach of the liquid 2 to be contained . when liquid 2 comes into contact with the contracting portion 25 , the contracting portion 25 shrinks along dimension d is shown in fig7 a and 7b . as the contracting portion 25 decreases along dimension d , the expanding layer 20 raises to contain the liquid 2 as shown in fig7 b . referring now to fig8 a and 8b , a switch 60 may be incorporated with the barrier 1 . the switch may be mounted so that the switch 60 is in one position when no liquid 2 is present and the barrier 1 is in a substantially flat arrangement . when liquid 2 is present the barrier 1 expands and activates the switch 60 as shown in fig8 b . the expanding barrier 1 and associated activation of switch 60 may send a signal to an alarm such as an audible alarm , beacon , strobe light or other indicator to alert personnel that a leak has been detected . it is also contemplated that the switch 60 could be tied into other equipment such as automatic valves , pumps , etc to stop the flow of liquid . this communication may be direct or through a computer or plc . while the switch 60 shown in fig8 a and 8b is a standard limit switch affixed with a metal lever 61 and wheel 62 , it is contemplated that the switch 60 may be of any type suitable for this application . for example , the switch 60 could be a plunger type , proximity switch or other suitable switch . referring now to fig9 , a beneficial aspect of the present invention is illustrated . while it should be apparent that the expanding barrier 1 may provide containment it should also be appreciated that the barrier 1 may also be used as a diverter of liquid . the expanding barrier may be installed around a container 70 or other spill source , such as piping or equipment . under normal conditions the barrier 1 is low profile and not an obstacle or impediment to pedestrian or wheeled traffic . however , it will be appreciated that should a leak in the container develop , the barrier will expand and divert the liquid to the drain 80 or other receptacle . whereas particular embodiments of this invention have been described above for purposes of illustration , it will be evident to those skilled in the art that numerous variations of the details of the present invention may be made without departing from the invention as defined in the appended claims .
| 8 |
fig1 illustrates a view of a deaerator shaft 102 and pump assembly 104 within an integrated drive generator ( idg ) housing 106 in accordance with one embodiment of the invention . the idg may include the deaerator shaft 102 , a deaerator drive gear 108 , the pump assembly 104 , and pump drive gear 109 . in operation , the pump assembly 104 is driven the pump drive gear 109 . the pump drive gear 109 may be mated with a deaerator drive gear 108 surrounding the deaerator shaft 102 . as the pump drive gear 109 turns , the deaerator shaft 102 may rotate . fluid flowing into the deaerator shaft 102 may be centrifuged , causing a supply of oil to be transferred and siphoned by the pump assembly 104 . in operation , a sufficient amount of oil is processed and flows through the deaerator shaft 102 so that the pump assembly 104 ( in particular a charge pump component of the pump assembly ) may be provided with a full supply of oil . a sufficient amount of oil may be supplied to components of the idg for cooling and lubrication purposes by the charge pump component . fig2 illustrates the deaerator shaft 102 in more detail . the deaerator shaft 102 comprises a plurality of tubular segments that may extend axially along an axis 202 . the axis 202 may extend the length of the deaerator shaft 102 . a tubular intake segment 204 is disposed along the axis 202 , forming an intake end 206 of the deaerator shaft 102 . the tubular intake segment 204 is configured to receive fluid and has a diameter of approximately 1 . 175 in . ( 2 . 9845 cm ). the tubular intake segment 204 has a length of approximately 0 . 684 in . ( 1 . 737 cm ) extending along the axis 202 . the end of the tubular intake segment 206 that forms the intake end 206 is chamfered in one embodiment . the chamfered edge can form a 45 degree angle with respect to an outer wall of the tubular intake segment 204 . the deaerator shaft 102 further comprises a tubular sleeve attachment segment 208 that is adjacent to the tubular intake segment 204 . the tubular sleeve attachment segment 208 extends along the axis 202 and has a diameter that is greater than the diameter of the tubular intake segment . in one embodiment , the diameter of the tubular sleeve attachment segment 208 is approximately 1 . 195 in . ( 3 . 0353 cm ). the tubular sleeve attachment segment 208 has a length of approximately 0 . 684 in . ( 1 . 737 cm ) extending along the axis 202 . the deaerator shaft 102 further comprises a central segment 210 extending along the axis 202 . the central segment 210 may be adjacent to the tubular sleeve attachment segment 208 , and located on an opposite side of the tubular sleeve attachment segment 208 from the tubular intake segment 204 . a protruding ring 212 extends radially from the central segment 210 about a circumference of the central segment 210 . the protruding ring 212 divides the central segment 210 , forming a shortened central segment portion 214 and a lengthened central segment portion 215 . the protruding ring 212 may have opposing flat surfaces 216 on an outer radial surface of the protruding ring 212 . in one embodiment , the shortened central segment portion 214 and lengthened central segment portion 215 measure 0 . 347 in . ( 0 . 881 cm ) and 0 . 69 in . ( 1 . 75 cm ) along the axis 202 , respectively . the diameters of the shortened central segment portion 214 and the diameter of the lengthened central segment portion 215 may be 1 . 3215 in . ( 3 . 355 cm ). the protruding ring 212 may measure 0 . 584 in . ( 1 . 483 cm ) along the axis 202 in one embodiment . the deaerator shaft 102 may further comprise a tubular discharge segment 218 extending along the axis 202 , forming a discharge end 219 of the deaerator shaft 102 . the tubular discharge segment 218 may be adjacent to the shortened central segment portion 214 . the tubular discharge segment 218 has a diameter of approximately 1 . 175 in . ( 2 . 984 cm ), which is approximately equal to the diameter of the tubular intake segment 204 . the tubular discharge segment 218 may comprise a plurality of openings 220 . the plurality of openings 220 is disposed about a circumference of the tubular discharge segment 218 . the plurality of openings 220 may be spaced equally around a circumference of the tubular discharge segment 218 . each opening extends in an axial direction for approximately 0 . 88 in . ( 2 . 2352 cm ) along the axis 202 . as described in more detail below , the plurality of openings 220 can act as a primary discharge point for fluid flowing through the deaerator shaft 102 . the discharge end 219 may act as a secondary discharge point for fluid , and the tubular discharge segment 218 may be chamfered at the discharge end 218 . fig3 and 4 illustrate a rotated view of the deaerator shaft 102 . a plurality of vanes 302 may extend from a radial center of the deaerator shaft 102 to an interior wall 303 of the deaerator shaft 102 . the plurality of vanes 302 may extend axially along a length of the deaerator shaft 102 , forming channels within the interior of the deaerator shaft 102 . the channels may assist with accelerating the fluid from longitudinal flow to rotating flow as the deaerator shaft 102 rotates , and as the fluid travels from the intake end 206 to the discharge end 219 . each channel may terminate at a respective opening of the plurality of openings 220 . in one embodiment , three vanes extend from a radial center of the deaerator shaft 102 , forming three channels of equal capacity . each vane terminates at the inner wall at a point 120 degrees apart from an adjacent vane . the plurality of vanes 302 may be axially recessed within the tubular intake segment 206 and the tubular discharge segment 219 . accordingly , the plurality of vanes 302 may not extend the entire length of the deaerator shaft 102 . as shown in fig3 , the intake edges 304 of the plurality of vanes 302 are recessed with respect to the intake end 206 of the deaerator shaft 102 . the distance from the intake edges 304 of the plurality of vanes 302 to the intake end 206 may be 0 . 125 in . ( 0 . 318 cm ), in one embodiment . in fig4 , the plurality of vanes 302 are axially recessed relative to the discharge end 219 of the deaerator shaft 102 . in particular , discharge edges 402 of the plurality of vanes 302 are recessed with respect to the discharge end 219 of the deaerator shaft 102 . the length of the recess between the discharge end 219 and the discharge edges 402 can vary , but in one embodiment the length of the recess is 0 . 376 in . ( 0 . 955 cm ). furthermore , the discharge edges 402 may be cupped , with a central part of the plurality of vanes 302 further recessed with respect to the discharge edges 402 . fig5 illustrates a cross - sectional view of the central segment 212 . each vane of the plurality of vanes 302 may form a rounded surface 502 with the inner radial wall of the central segment 212 . the rounded surface 502 may promote ease of manufacture of the vanes . the diameter of the protruding ring 212 as measured between outer radial walls of the protruding ring 212 may be 1 . 562 in . ( 3 . 967 cm ) in one embodiment . the distance between opposing flat surfaces 504 , 506 of the protruding ring 212 may be approximately 1 . 374 in . ( 3 . 48 cm ). the opposing flat surfaces 504 , 506 may run parallel to one another . fig6 illustrates a cross - sectional view of the tubular discharge segment 218 . the configuration of the plurality of vanes 302 extending through the tubular discharge segment 218 is illustrated in more detail . in particular , the plurality of vanes 302 is cupped , forming a central discharge opening 602 between fins 604 of the plurality of vanes 302 . the central discharge opening 602 may extend 1 . 183 in . ( 3 . 005 cm ) from the discharge end 219 , and radially 0 . 4 in . ( 1 . 016 cm ). the plurality of vanes 302 may be recessed 0 . 376 in . ( 0 . 955 cm ) from the discharge end . accordingly , each fin 604 of the plurality of vanes 302 may extend 0 . 807 in . ( 2 . 05 cm ) along the axis 202 . although an edge 606 of the fin 604 is squared in fig6 , the edge 606 of each fin 604 may have a rounded edge . referring to fig7 with continuing reference to fig2 and 5 , an isometric view of a gear 700 is shown in accordance with the subject invention . the gear 700 is ring - shaped with opposing tabs 702 , 704 that extend axially from an inner side 706 of the gear 700 . as described in more detail below , the opposing tabs 702 , 704 are configured to lock with the opposing flat surfaces ( not shown ) of the protruding ring ( not shown ). the opposing tabs 702 , 704 are used to provide a positive transfer of torque from the gear 700 to the deaerator shaft . the gear 700 is axially mounted on protruding ring 212 . the opposing tabs 702 , 704 drive on opposing flat surfaces 504 , 506 of the deaerator shaft , transmitting torque to the deaerator shaft . fig8 illustrates a cross - sectional view of the gear 700 . the gear 700 is disposed along an axis 802 . the gear 700 has a central ring 804 with a diameter of approximately 1 . 3254 in . ( 3 . 366 cm ) between inner radial walls of the central ring 804 . the gear 700 has a plurality of teeth 806 circumferentially disposed about an outer radial surface of the central ring 804 . the plurality of teeth 806 extend along the axial length of the central ring 804 . the plurality of teeth 806 provide a thrust surface by which a mating gear ( not shown ) may transmit torque to gear 700 . in one embodiment , the central ring 804 and the plurality of teeth 806 have an axial length of 0 . 35 in . ( 0 . 889 cm ). the gear 700 has a shouldered ring 808 with a diameter between inner radial surface 810 of the shouldered ring 808 of 1 . 195 in . ( 3 . 035 cm ), and a diameter between outer radial surface 814 of the shouldered ring 808 of 1 . 513 in . ( 3 . 843 cm ). the shouldered ring 808 may extend axially from the central ring 804 for a distance of 0 . 84 in . ( 2 . 133 cm ). the shouldered ring 808 also provides a thrust surface when mounted to the deaerator shaft and helps to axially locate the deaerator shaft within the idg . the opposing tabs 702 , 704 of gear 700 extend in a direction opposite to the shouldered ring 808 . the opposing tabs 702 , 704 may extend 0 . 2 in . ( 0 . 508 cm ) in an axial direction . fig9 illustrates an axial view of the gear 700 . the opposing tabs 702 , 704 have a length of 0 . 35 in . ( 0 . 889 cm ) extending along the cross - sectional axis 802 . radially - inward facing surfaces 806 , 807 of the opposing tabs 702 , 704 are flat . however , the radially - outward facing surfaces 808 , 810 of the opposing tabs 702 , 704 may be arced , similar to the circumference of the central ring 804 . while the invention has been described in detail in connection with only a limited number of embodiments , it should be readily understood that the invention is not limited to such disclosed embodiments . rather , the invention can be modified to incorporate any number of variations , alterations , substitutions or equivalent arrangements not heretofore described , but which are commensurate with the spirit and scope of the invention . additionally , while various embodiments of the invention have been described , it is to be understood that aspects of the invention may include only some of the described embodiments . accordingly , the invention is not to be seen as limited by the foregoing description , but is only limited by the scope of the appended claims .
| 5 |
referring to fig5 the form of a tooth 28 of an external gear 11 cut by a rack - type tool 16 with straight - sided teeth having a pressure angle α o ( as shown in fig4 ) assumes an involute curve 19 that has a pressure angle α o on a pitch circle 18 . when considering the tooth form of the tool and the external gear , chamfering at the edges of the tooth tip and the corners of tooth root as well as the radius of fillet are excepted . assuming that the involute curve 19 and the pitch circle 18 intersect at point 20 , the length of a circular arc 20 - 20 &# 39 ; is equal to the virtual thickness lo of the tooth 2 of the belt 1 on the pitch line 7 . the virtual thickness lo is a constant value that is determined by belt size expressed by pitch length between adjacent teeth of a belt or the like . there arises a deflection δ 1 k between points 22 and 23 where the tangent 21 of the involute curve 19 at point 20 and the involute curve 19 intersect the outside diameter 25 of the external gear 11 , and a deflection δ 1 f between points 26 and 27 where said tangent 21 and involute curve 19 intersect the bottom land 24 of the external gear 11 . the absolute values δ 1 k and δ 1 f become smaller with an increase in the number of teeth in the external gear 11 ; that is , δ 1 k and δ 1 f become zero when the number of teeth becomes infinite . assuming now that δ 1 k and δ 1 f of an external gear having a minimum number of teeth are dk and df , the values of δ 1 k and δ 1 f become smaller than the absolute values of dk and df as the number of teeth of the external gear increases . δ 1 k and δ 1 f are calculated from the following equations : ## equ1 ## where d = 1 / 2 of the difference between the outside diameter 25 of the external gear 11 and the diameter of the pitch circle 18 dp = the diameter of the pitch circle 18 of the external gear 11 h = the depth of the tooth space 13 of the external gear 11 αo = the pressure angle of the rack - type tool 16 used for tooth cutting it must be additionally noted that , within the range of the practically usable number of teeth on the external gear 11 , a tooth surface 28 of the external gear 11 becomes totally consistent with the involute curve 19 , owing to the tooth form conditions , including a pressure angle αo , of the tool . in fig6 a tooth form 30 of an external gear 11 &# 39 ; cut by a rack - type tool having straight - sided teeth with a pressure angle αo + δα coincides with an involute curve 29 . there arise a deflection δ &# 39 ; 1 k between points 22 and 31 where the tangent 21 of the involute curve 19 and the involute curve 29 intersect the outside diameter 25 of the external gear 11 &# 39 ;, and a deflection δ &# 39 ; 1 f between points 26 and 32 where said tangent 21 and involute curve 29 intersect the bottom land 24 of the external gear 11 &# 39 ;. δ &# 39 ; 1 k and δ &# 39 ; 1 f are calculated from the following equations , with the extent of each deflection being adjustable by δα : ## equ2 ## the involute curve 29 increases its curvature and deviates more and more from the tangent 21 of the involute curve 19 , as it approaches the bottom land 24 of the external gear 11 &# 39 ;. it is therefore effective , for making small the value of δ &# 39 ; 1 f as well as the curvature at the root of the tooth form 30 of the external gear 11 &# 39 ;, to form the greater part of the tooth surface of a rack - type tool 33 shown in fig7 with a straight line 34 and the remaining small part , for instance , about one - third from the tip of the tooth , with a curve 35 . to be more precise , the tooth form of the external gear 11 &# 39 ; generated by the straight - lined portion 34 of the rack - type tool 33 forms the involute curve 29 , whereas the tooth form generated by the curved portion 35 presents a curve deflected in such a direction as to relatively narrow the width 32 - 32 &# 39 ; of the bottom land 24 , compared with the tooth form generated by an all straight - sided rack - type tool . the curved portion 35 of the tool 33 may be substituted by an arc of a circle . assuming that the maximum values which said δ &# 39 ; 1 k can take is d &# 39 ; k and that said δ &# 39 ; 1 f can take is d &# 39 ; f , the maximum amount of relief ε at the tooth tip of the tool 33 must be expressed by ε = d &# 39 ; f - d &# 39 ; k . if the angle formed between points 20 and 20 &# 39 ; on the pitch circle 18 of the external gear 11 in fig5 is 20 , the pressure angle of the involute curve 19 on the pitch circle 18 is αo . therefore , the angle of intersection of the tangents 21 and 21 &# 39 ; of the involute curve 19 and 19 &# 39 ; becomes 2 ( αo + θ ), which is twice as great as the pressure angle αo of the tool , plus 20 . θ is calculated from the following equation : ## equ3 ## in fig8 let us consider two straight - sided tooth forms 36 and 37 , having a pressure angle αo and αo + θ , respectively , at point 20 on the pitch circle 18 . then there arise deflections δ 2 k and δ 2 f between points 38 and 23 and points 39 and 27 where said tooth forms 36 and 37 intersect the outside diameter 25 and the bottom land 24 . δ 2 k and δ 2 f are calculated from the following equations : δ . sub . 2 f = ( d + h ) { tan ( αo + θ ) - tanαo } assuming that the aforesaid δ 2 k and δ 2 f become δ &# 39 ; 2 k and δ &# 39 ; 2 f when the pressure angle αo is changed to αo + δα , δ &# 39 ; 2 k and δ &# 39 ; 2 f are calculated from the following calculation : δ &# 39 ;. sub . 2 k = d { tan ( αo + δα + θ ) - tan ( αo + δα )} δ &# 39 ;. sub . 2 f = ( d + h ) { tan ( αo + δα + θ ) - tan ( αo + δα )} from the above , δ &# 39 ; k and δ &# 39 ; f are defined as follows : 2δ &# 39 ; k shows a difference between tooth thickness l 1 at the root of the tooth of the belt 1 with a straight - sided tooth 2 having a virtual tooth thickness lo and pressure angle αo on the pitch line 7 and tooth space 31 - 31 &# 39 ; on the outside diameter 25 of the external gear 11 &# 39 ; cut by a rack - type straight - sided tooth - cutting tool having a pressure angle αo + δα . 2δ &# 39 ; f shows a difference between tooth thickness l 2 at the tip of the tooth of the same belt and tooth space 32 - 32 &# 39 ; at the bottom land 24 of the external gear 11 &# 39 ;. with the assumption that 2δ &# 39 ; k - 2δ &# 39 ; f - 2δ &# 39 ;, 2δ &# 39 ; is defined as showing a dimensional error permissible for an ideal tooth space ( 31 - 31 &# 39 ; - 2h tanαo ) at the bottom land 24 of the external gear 11 &# 39 ;, which determines the tooth tip thickness of the belt to be cut thereby , with respect to the tooth space 31 - 31 &# 39 ; on the outside diameter 25 of said external gear 11 &# 39 ;. the thickness l &# 39 ; 1 and l &# 39 ; 2 at the tooth root and tip of the belt 46 ( fig9 ) cut by the external gear 11 &# 39 ; having the aforementioned 2δ &# 39 ; k and 2δ &# 39 ; f differ with the number of teeth in the external gear 11 &# 39 ;. at the same time , the tooth surface 47 of the belt 46 made by the external gear 11 &# 39 ; forms a concave involute curve , because the external gear 11 &# 39 ; has a convex involute tooth form 30 . the belt 1 and the toothed wheels 40 and 40 &# 39 ; are considered to engage with each other as in the case of a rack and a pinion . if a belt 46 is considered a rack , the aforesaid 2δ &# 39 ; k is a value affecting the back - lash existing between the tooth 48 of the belt 46 and the teeth 41 and 41 &# 39 ; of the toothed wheels 40 and 40 &# 39 ;. also , 2δ &# 39 ; calculated from equation 2δ &# 39 ; k - 2δ &# 39 ; f = 2δ &# 39 ; and the concave curve on the tooth surface 47 of the belt 46 are considered tooth form errors . the aforementioned δ &# 39 ; k and δ &# 39 ; f were calculated with regard to the belt tooth forms of every pitch specified in british standards 4548 - 1970 , specifications for synchronous belt drives , assuming that δα is approximately one degree . for the belts having great pitch dimensions , the tooth form of external gears cut by a partly curved , straight - sided rack - type tool were considered . it was then found out about the tooth form of every pitch that the amount of change in δ &# 39 ; k ( that is , the range of values which δ &# 39 ; k can take ) with the number of teeth in the external gear was small , and all such values were positive . it was also found that the amount of change in δ &# 39 ; with the number of teeth in the external gear was small too , and , furthermore , the value of δ &# 39 ; could be kept within a range between a very small positive value to a small negative value or between zero and a small negative value , depending on how ε in fig7 was determined . the positive δ &# 39 ; for the tooth tip space of the belt 46 becomes the amount of interference in the engaging mechanism of rack and pinion , while the negative δ &# 39 ; becomes that of relief . in the engagement of the belt 46 and the toothed wheels 40 and 40 &# 39 ;, the presence of a very small positive δ &# 39 ; does not constitute an obstacle to such engagement , because the tooth 48 of the belt 46 , made of rubber - like elastic material , can permit some extent of transformation different from gears of hard metal . if the presence of such positive δ &# 39 ; is undesirable , it can be changed to negative regardless of the number of teeth of the belt , by changing the value of δα or ε of the tool 33 shown in fig7 or the interrelationship therebetween . when the above - described belt 46 , which differs , in tooth tip thickness slightly from the base dimention and has a concave tooth surface 47 , is placed over the wheels 40 and 40 &# 39 ; and moved , the belt smoothly engages the wheels . the moment the teeth 2 and 48 of the belts 1 and 46 , respectively , engage with the wheels 40 and 40 &# 39 ;, the tooth surfaces 3 and 47 of the belts 1 and 46 receive from the tooth surfaces 42 and 43 reactive force originated from power transmission . for the transmission of power , it is more advantageous to engage the belt 46 , having the concave tooth surface 47 , of this invention with the wheels having the convex tooth surface 42 and 43 , than to do so with the belt 1 with the straight - sided teeth 3 , since the former produces less contact stress between both tooth surfaces ( see fig1 and 11 ). its superiority in durability has also been experimentally proven . as described above , this invention permits cutting of external gears for the manufacture of timing belts having various numbers of teeth of the same pitch , using one rack - type gear - cutting tool . this means that one tool is enough for each pitch , thus eliminating the necessity of preparing many costly rack - type tools and facilitating the maintenance and keeping of such tools . because the tooth form of this rack - type tool is straight - sided or partly curved , it can be more easily manufactured than a rack - type tool with totally curved teeth . also the belt is designed with concave teeth so as to properly engage with convex - surfaced wheel teeth , which decreases contact stress during the transmission of power between both teeth and increases the durability of the teeth or the belt . these are the examples of remarkable results expected from this invention . although a particular preferred embodiment of the invention has been disclosed in detail for illustrative purposes , it will be recognized that variations or modifications of the disclosed apparatus , including the rearrangement of parts , lie within the scope of the present invention .
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the invention and the various features and advantageous details thereof are explained more fully with reference to the nonlimiting 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 not to unnecessarily obscure the invention in detail . it should be understood , however , that the detailed description and the specific examples , while indicating preferred embodiments of the invention , are given by way of illustration only and not by way of limitation . various substitutions , modifications , additions and / or rearrangements within the spirit and / or scope of the underlying inventive concept will become apparent to those skilled in the art from this detailed description . the entire contents of u . s . ser . no . 60 / 173 , 232 , filed dec . 28 , 1999 , are hereby incorporated by reference for all purposes as if set forth herein in their entirety . the clock recovery scheme can be extended with additional circuitry to ascertain whether the following two events occur . first is the notion of “ excess zeros ”. second is the notion of a rapid phase change in the incoming t 1 reference signal . if t 1 - sig had no missing pulses then there would be ( very approximately ) one rising edge in every 18 clock cycles of the reference local clock signal ( 30 mhz ). a simple counter arrangement , where a counter is clocked by the local oscillator and reset by ( any ) every rising edge of t 1 - sig would never show a count much larger than 18 if the t 1 signal was “ all - 1s ”. a count of about 36 could be observed if the t 1 signal has one isolated “ 0 ”. a count of about 750 would indicate the presence of a string of about 40 “ 0 ” s in the t 1 signal . thus , by setting a suitable threshold it can be ascertained if there has been a long string of “ 0 ” s in the t 1 signal . this mechanism has been used quite widely in symmetricom designs . the technique depicted in fig1 - 2 can be extended to detect a rapid change in the phase / frequency of the incoming signal . this provides an important function in synchronization equipment . this extension was developed to handle the “ unipulse ” problem and a brief exposition of this problem is also provided . detection of a rapid change in the incoming t 1 signal in all synchronization equipment , the clock recovered from the incoming t 1 signal is then used to discipline a stable oscillator using a narrow - band phase / frequency lock technique ( pll is an acronym for phase locked loop ; fll stands for frequency locked loop ). the timing output signal provided by the equipment is derived from the disciplined oscillator . the ( final ) output signal follows the input reference , albeit sluggishly . a phase step in the input signal will be reflected in a phase change ( over time ) of roughly the same magnitude . this behavior is expected and the equipment is not considered to have malfunctioned and in fact if the phase change of the output is less than the phase step introduced in the input signal then the equipment is considered to be well - behaved . now consider the case where the input signal has a rapid phase change of almost + 180 degrees . this is a phase jump corresponding to one - half of a clock cycle or 0 . 5 ui ( ui stands for unit interval and is equivalent to one bit - period in time or 360 degrees in phase ). the output will try to follow this phase step and , after some time , will have moved ( almost ) + 180 degrees . now suppose the input signal phase reverted back to its original phase state via the introduction of a phase step of ( almost ) − 180 degrees . the equipment output is expected to return to its original phase state . this expectation is problematic because an instantaneous phase step of + 180 degrees is indistinguishable from an instantaneous phase step of − 180 degrees . at times the equipment output phase change may thus be a net 360 degrees . this is the “ unipulse ” problem , the nomenclature stemming from the fact that the output seems to have moved 1 ui even though the ( net ) change in the input was 0 ui . to protect against this so - called malfunction , it is necessary to monitor the input signal for a rapid change in phase state . this is achieved by the method described here . this method can be implemented as an extension of the clock recovery scheme described above . to see how this method works , first note the following observations related to the clock recovery method . for convenience we will assume that the incoming t 1 signal was “ all - 1s ” and thus t 1 - sig has no missing pulses ( this assumption can be relaxed later ). the signal q 4 is a mixture of two different frequencies which can be called ƒ 13 and ƒ 14 which are nominally 1 . 538461 . . . mhz and 1 . 547619 . . . mhz , respectively . the feedback arrangement causes the alternation between the two which are present for p 13 and p 14 fractional time , respectively . the feedback is such that the fractional quantities p 13 and p 14 are roughly constant regardless of the time interval over which they are observed providing , of course , that the input frequency is constant . that is , the ff output , which controls the selection of the modulo - 13 or modulo - 14 operation , is quite oscillatory in nature and long strings of high or low will not be present . if there is a slow variation in phase of the input signal then the fractional quantities will change to allow q 4 to “ maintain phase tracking ” of t 1 - sig , but the oscillatory nature will be retained . if the nominal frequency of t 1 - sig is constant but , for some reason or another , one period is shortened by + x ui ( x is a small fraction ) then the mechanism will choose the higher frequency ( modulo - 14 selection ) in a sustained manner till q 4 “ catches up ” with t 1 - sig . similarly , if one period of t 1 - sig is lengthened by + y ui ( again , y is a small fraction ) then the mechanism will choose the lower frequency ( modulo - 13 selection ) in a sustained manner till q 4 realigns with t 1 - sig . a rapid change in phase of the incoming t 1 signal is , roughly , equivalent to the shortening or lengthening of one period of t 1 - sig . in actuality , a few consecutive periods will be shortened / lengthened to get the overall shift corresponding to the phase change introduced . to see how many ui elapse for the mechanism to realign the phase of q 4 and t 1 - sig , note that the “ high ” and “ low ” frequencies ( in fractional units ) are + 2 . 343943e - 3 and − 3 . 587086e - 3 relative to the ( nominal ) t 1 clock frequency of 1 . 544 mhz . if the incoming signal has a precession of x ui , then the “ high ” frequency must be selected for 426 . 6x ui ( approximately ), in a sustained manner , for the phase of q 4 to realign (“ catch up ”) with t 1 - sig . if the incoming signal has a delay of + y ui then the “ low ” frequency must be selected for 278 . 8y ui ( approximately ), in a sustained manner , for phase realignment . the last point provides the basis for the method for detecting a rapid change in phase . referring to fig3 two counters , clocked by t 1 - sig ( or a clock derived from either t 1 - sig or q 4 ), are maintained . a first counter 110 , hi - count , counts ( up ) when modulo - 14 is selected and a second counter 120 , lo - count counts ( up ) when modulo - 13 is selected . hi - count is reset when modulo - 13 is selected and lo - count is reset when modulo - 14 is selected . thus hi - count is reflective of the number of ui that have elapsed since the last time modulo - 13 was selected and lo - count reflects the number of ui since modulo - 14 was selected . if either of these counts exceeds a predetermined threshold then it can be stated that the input t 1 signal included a rapid phase change . a suitable threshold would correspond to about 0 . 25 ui ( use the value 0 . 25 for x and y ). comparing fig3 to fig1 it can be appreciated that in fig1 there is one signal labeled dwn +/ up − which controls the selection of the modulo - 13 or modulo - 14 operation . when dwn +/ up − is high , the modulo - 13 operation is selected . this corresponds to the signal shown in fig3 as sel . mod - 13 being “ true ” or high . when dwn +/ up − is low the modulo - 14 operation is selected , corresponding to the signal sel . mod - 14 of fig3 being true or high . when either the lo - count or hi - count counter value exceeds its threshold , a signal alarm 130 is true , indicative of a rapid phase change detection event . this rapid - phase - change - event detection can be used to supplement the pll / fll arrangement used to discipline the local oscillator such that the oscillator does not “ follow ” the recovered clock during transition phases . techniques for implementing such a “ don &# 39 ; t - follow - during - transients ” scheme have been implemented in several symmetricom products and are not described here . using t 1 - sig as the clock for the counters is advantageous since if there is a missing pulse then the counters do not change reflective of the fact that no decision is made when a pulse is missing . nco is an acronym for numerically controlled oscillator . essentially , as the name would imply , an nco is a device that generates a frequency , derived from a ( hopefully stable ) local oscillator , that can be programmed via a numerical value in a ( control ) register . a “ conventional nco ” is depicted in fig4 . it comprises an accumulator 200 which is the combination of an adder 210 and a register 220 . the local oscillator has a frequency ƒ 0 and is used to load the results of the addition into the accumulator - register . the “ increment ” is what controls the frequency of the output signal . in a simple implementation , the carry - out ( c out from the adder is loaded by ƒ 0 into a flip - flop ( one - bit register ). the flip - flop output will be a pulsed waveform with a pulse repetition rate of ƒ out . the frequency of this output is related to the clock frequency , ƒ 0 , by the simple equation f out ≅ f 0 δ 2 n in this equation the quantity n represents the wordlength of the accumulator ( the register / adder size ) and δ is the numerical value of the increment and is an integer ( often called an unsigned binary number ). typical values of n are between 16 and 48 . the larger the value of n , the more precision can be achieved for the synthesized frequency . the above equation holds when the “ carry - in ” signal to the accumulator is always “ 0 ”. the effective value of δ can be augmented by forcing the carry - in to alternate between 0 and 1 . if the carry - in is 1 for x % of the time , then the impact is similar to increasing δ ( an integer ) by ( x / 100 ) ( a fractional part ). for convenience , it is assumed that the carry - in is held at 0 . referring now to fig5 the nco form can be used quite advantageously to perform the function of clock recovery . to see how , recognize that the prior art achieves clock recovery by alternating between two frequencies . likewise , the nco form can be controlled by having two choices for increment , δ . consider two values for δ , say δ h and δ l , which satisfy the relationship . f 0 δ l 2 n & lt ; f t1 & lt ; f 0 δ h 2 n or f l & lt ; f t1 & lt ; f h then an nco 310 can be controlled in much the same way as the divider scheme in the clock recovery method ( prior art ) described before . to emphasize the relationship , the output signal is labeled as q 4 . as a first implementation , the conventional nco 310 can be modified by making the choice of increment , δ , based on the relative phase of the rising edge of q 4 and t 1 - sig in much the same manner as the conventional method . this is illustrated in fig5 . the output of the flip - flop 320 clocked by t 1 - sig will be high if the rising edge of q 4 occurs before the rising edge of t 1 - sig and will be low if the rising edge of q 4 occurs after the rising edge of t 1 - sig . this explains the nomenclature that the flip - flop 320 , ff , performs the action of a phase detector in terms of an early / late decision . a multiplexer 330 sends either δ h or δ l to the nco 310 . considering the similarity between the conventional scheme and the nco form , the question arises as to which is superior , if at all . the nco form is superior for the following reasons : note that the conventional method requires the selection of three divider modulo quantities , a , n , and m , which depend on the choice of the local oscillator frequency , ƒ 0 , and the t 1 frequency ( 1 . 544 mhz ). in the scenario described , the local oscillator is ( nominally ) 30 mhz and the choices are a = 18 , n = 13 , and m - 14 . it is not uncommon to specify m =( n + 1 ). with this choice , the “ high ” frequency is + 2344 ppm and the “ low ” frequency is − 3587 ppm ( relative to the t 1 frequency ). these are not symmetric about 0 and are quite large . it turns out that there is not much leeway in the choice of the dividers and these large variations are not easily avoided . the drawback of these large variations is the intrinsic jitter in the recovered clock signal . this large jitter is exacerbated if the t 1 signal has an appreciable number of missing pulses ( i . e . data bits =“ 0 ”). the nco form , on the other hand , provides much more leeway in the selection of δ l and δ h that can be tailored to the quality of the local oscillator . consider the case when the local oscillator is nominally 30 mhz and has an intrinsic accuracy of 100 ppm . the t 1 clock recovery specification requires a clock recovery even when the t 1 signal is off - frequency by as much as 50 ppm . clearly , if the high and low frequencies are of the order of ± 200 ppm then there is adequate margin to recover the clock frequency and yet have an intrinsic jitter of much less than if the high and low frequencies were ± 2300 ppm . for example , if the nco wordlength is 16 bits , then one could choose δ h = 3374 and δ l = 3372 and obtain a “ high ” frequency which is + 320 . 4 ppm and a “ low ” frequency which is − 272 . 6 ppm . clearly with a longer wordlength one could obtain frequencies that are more symmetric about the nominal . nevertheless , even with such a short wordlength ( 16 bits ) the jitter performance of the nco form will still be clearly superior to the conventional method described . the frequency of the incoming t 1 signal relative to the local oscillator can be expressed in terms of the percentage of time each of the two frequencies are selected . denote by p l the fraction of time the lower frequency , ƒ l , is selected and by p h the fraction of time the higher frequency , ƒ h is selected . then clearly p l =( 1 = p h ) and or f t1 ≅ f 0 ( p l δ l 2 n + p h δ h 2 n ) thus , as in the case of the conventional clock recovery method , the fraction of time the “ low ” frequency ( or “ high ” frequency ) is selected is a measure of the relative frequency difference between the local oscillator and the incoming t 1 signal timebase . because using the nco form allows one to keep the “ high ” and “ low ” frequencies much closer to the nominal , it is clear that the reliability and quality of the estimate of frequency difference is much better than in the conventional case ( prior art ). the addition of a mechanism to detect rapid phase changes to the nco form of clock recovery is quite straightforward . in fact , the same scheme depicted in fig3 is applicable . by replacing the signal named “ sel . mod - 14 ” with “ sel - δ h ” and “ sel . mod - 13 ” with “ sel - δ l ”, the requisite detection mechanism is obtained . that is , the dwn +/ up − signal of fig5 is used as was the signal dwn +/ up − signal of fig1 . however , the calculation of thresholds would be based on 320 . 4 ppm vs . 2344 ppm and − 272 . 6 ppm vs . − 3587 ppm because the high and low frequencies are now closer to the nominal value . the example of the nco form described above used a wordlength of 16 bits for the accumulator and δ h = 3374 and δ l = 3372 to obtain a “ high ” frequency which is + 320 . 4 ppm and a “ low ” frequency which is − 272 . 6 ppm . now suppose a wordlength of 18 bits and δ h = 13496 and δ l = 13488 . one would obtain a “ high ” frequency which is + 320 . 4 ppm and a “ low ” frequency which is − 272 . 6 ppm ( the same as before ). if one modified δ l to 13487 then the “ low ” frequency would be − 347 ppm providing a somewhat more symmetrical operation . clearly , the larger the wordlength , the greater is the freedom of choice to obtain “ high ” and “ low ” frequencies that are reasonably symmetric about the nominal . now with an 18 - bit accumulator one can consider δ to be any ( integer ) value between δ h = 13496 and δ l = 13487 . then the nominal frequency of q 4 will be between + 320 . 4 ppm and − 347 ppm . in contrast with the earlier situation of just two choices , “ low ” or “ high ”, one can now provide 10 choices in the same range and thus one can expect to get a much improved granularity which in turn translates to much reduced jitter in the recovered clock signal . a simple control mechanism to adjust δ is depicted in fig6 . the phase detection scheme is as before and detects whether the rising edge of q 4 is early or late . this controls a multiplexer 330 (“ mux ”) that selects an increment of + 1 or − 1 to be added to the current value of δ . the adder 340 includes circuitry to ensure that the range of outputs is kept to between δ h and δ l . the “ δ register ” 350 is most advantageously clocked by t 1 - sig since if there is no pulse in t 1 - sig the phase detector cannot make a determination of early / late and the current value for δ is “ held ”. thus , the rate of change of the output phase can be increased or decreased . this acceleration or deceleration , as the case may be , can be made available for either advancing or retarding the output phase relative to the incoming signal . when the register 350 is saturated ( i . e ., either δ h and δ l as the case may be ) the rate of change can only be held constant or decreased . the frequency of the incoming t 1 signal relative to the local oscillator can be determined by observing the “ increment ” δ . denote by & lt ; δ & gt ; the average value of δ taken over a reasonable length of time . then the average frequency of the incoming t 1 signal in terms of the local oscillator frequency is given by f t1 ≅ f 0 & lt ; δ & gt ; 2 n the precision of this average is much better than the case where one used just two selections for the instantaneous frequency of q 4 . furthermore , because of the finer granularity of choices for the instantaneous frequency of q 4 , the overall jitter performance is vastly improved . while not being limited to any particular performance indicator or diagnostic identifier , preferred embodiments of the invention can be identified one at a time by testing for the presence of accurate rapid phase shift detection . the test for the presence of accurate rapid phase shift detection can be carried out without undue experimentation by the use of a simple and conventional bench top experiment where sig - t 1 is rapidly shifted in a controlled manner and the response of the system is evaluated . the invention can also be included in a kit . the kit can include some , or all , of the components that compose the invention . the kit can be an in - the - field retrofit kit to improve existing systems that are capable of incorporating the invention . the kit can include software / firmware and / or hardware for carrying out the invention . the kit can also contain instructions for practicing the invention . the components , software , firmware , hardware and / or instructions of the kit can be the same as those used in the invention . the term approximately , as used herein , is defined as at least close to a given value ( e . g ., preferably within 10 % of , more preferably within 1 % of , and most preferably within 0 . 1 % of ). the term coupled , as used herein , is defined as connected , although not necessarily directly , and not necessarily mechanically . the term deploying , as used herein , is defined as designing , building , shipping , installing and / or operating . the term means , as used herein , is defined as hardware , firmware and / or software for achieving a result . the term program or phrase computer program , as used herein , is defined as a sequence of instructions designed for execution on a computer system . a program , or computer program , may include a subroutine , a function , a procedure , an object method , an object implementation , an executable application , an applet , a servlet , a source code , an object code , a shared library / dynamic load library and / or other sequence of instructions designed for execution on a computer system . the terms including and / or having , as used herein , are defined as comprising ( i . e ., open to additional elements ). the terms a or an , as used herein , are defined as one or more than one . the term another , as used herein , is defined as at least a second or more . all the disclosed embodiments of the invention disclosed herein can be made and used without undue experimentation in light of the disclosure . although the best mode of carrying out the invention contemplated by the inventor is disclosed , practice of the invention is not limited thereto . accordingly , it will be appreciated by those skilled in the art that the invention may be practiced otherwise than as specifically described herein . variation may be made in the steps or in the sequence of steps composing methods described herein . further , although the invention described herein can be a separate module , it will be manifest that the invention may be integrated into the system with which it is ( they are ) associated . furthermore , all the disclosed elements and features of each disclosed embodiment can be combined with , or substituted for , the disclosed elements and features of every other disclosed embodiment except where such elements or features are mutually exclusive . it will be manifest that various substitutions , modifications , additions and / or rearrangements of the features of the invention may be made without deviating from the spirit and / or scope of the underlying inventive concept . it is deemed that the spirit and / or scope of the underlying inventive concept as defined by the appended claims and their equivalents cover all such substitutions , modifications , additions and / or rearrangements . the appended claims are not to be interpreted as including means - plus - function limitations , unless such a limitation is explicitly recited in a given claim using the phrase ( s ) “ means for ” and / or “ step for .” subgeneric embodiments of the invention are delineated by the appended independent claims and their equivalents . specific embodiments of the invention are differentiated by the appended dependent claims and their equivalents .
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referring now to the discussion that follows and also to the drawings , illustrative approaches to the disclosed systems and methods are shown in detail . although the drawings represent some possible approaches , the drawings are not necessarily to scale and certain features may be exaggerated , removed , or partially sectioned to better illustrate and explain the disclosed device . further , the descriptions set forth herein are not intended to be exhaustive or otherwise limit or restrict the claims to the precise forms and configurations shown in the drawings and disclosed in the following detailed description . while the device is described with respect to an exemplary cross - track constant velocity joint ( cvj ) for use in a vehicle , the following apparatus is capable of being adapted for various purposes including automotive vehicles drive axles , motor systems that use a propeller shaft , or other vehicles and non - vehicle applications that require cvj &# 39 ; s for torque transmission . an exemplary drive system 10 for a typical four - wheel drive vehicle is shown in fig1 . while a four - wheel drive system is shown and described , the concepts here presented could apply to a single drive unit system or multiple drive unit system , including rear wheel drive only vehicles , front wheel drive only vehicles , all wheel drive vehicles , and four - wheel drive vehicles . the exemplary drive system 10 includes an engine 12 that is connected to a transmission 14 and a power take - off unit ( ptu ) 16 . a front differential 18 has a front right hand side half shaft 20 and front left hand side half shaft 22 , each of which are connected to a wheel 24 and deliver power to the wheels . attached to the ends of the right hand side half shaft 20 and left hand side half shaft 22 are constant velocity joints 26 . a propeller shaft 28 connects the transmission 18 to a rear differential 30 . the rear differential 30 includes a rear right hand side shaft 32 and a rear left hand side shaft 34 , each of which has a wheel 24 attached to one end thereof . constant velocity joints 26 are located on both ends of the half shafts 32 , 34 that connect to the wheels 24 and the rear differential 30 . the propeller shaft 28 may be a two piece propeller shaft that includes several high - speed constant velocity joints 26 and a high - speed shaft support bearing 36 . the propeller shaft 28 includes first and second interconnecting shafts 38 , 40 . the shafts 20 , 22 , 38 , 40 , 32 , 34 may be solid or tubular with ends adapted to attach each shaft to a particular constant velocity joint 26 , as appropriate for the particular application . the constant velocity joints 26 transmit power to the wheels 24 through the propeller shaft 28 even if the wheels or the propeller shaft 28 have changed angles due to steering or raising and lowering of the suspension of the vehicle . the constant velocity joints 26 may be any of a variety of joint types , including but not limited to a plunging tripod , a cross groove joint , a fixed joint , a fixed tripod joint , or a double offset joint , all of which are recognized terms for identifying different varieties of constant velocity joints 26 . the constant velocity joints 26 allow for constant velocity torque transmission within the joint at operating joint angles that are typically encountered in every day driving of automotive vehicles in both the half shafts and propeller shafts of these vehicles . optionally , each constant velocity joint may be replaced with any other types of joint . thus , any of the constant velocity joints identified in fig1 at 26 or 36 may include a constant velocity joint . because the torque transfer capability of the constant velocity joint is influenced by its moment of inertia , which is a function of the maximum radii of the constant velocity joint parts , and is less effected by the mass of the constant velocity joint parts , it may be beneficial to have a cross - track constant velocity joint with optimized ratios that benefits from the torque / radius transfer relationship in order to reduce the mass of the system or to optimize its performance . with reference to fig2 and 3a thru 3 c , an exemplary cross - track constant velocity joint 42 may include an annular outer race 44 having a generally cylindrical inner face 46 defining an inner diameter d bore , and a generally cylindrical outer face 48 defining an outer diameter d or . outer race 44 has a front face 50 and a rear face 52 that define an axial outer race length or l . arranged on inner face 46 of outer race 44 are first and second outer ball tracks 54 and 56 . each outer ball track 54 and 56 has a track depth t d corresponding to a radial distance measured from inner face 46 to a bottom 58 and 60 of outer ball tracks 48 and 50 , respectively . outer ball tracks 54 , 56 have substantially the same track depth t d . outer ball tracks 54 , 56 extend over the entire length or l of outer race 44 from front face 50 to rear face 52 . outer race 44 may be secured to a drive shaft of a drive unit , for example , ptu 16 , front differential 18 and rear differential 30 , as illustrated in fig1 , or any other member capable of transmitting a torque to or from constant velocity joint 42 . various means may be used to attach outer race 46 to the corresponding drive shaft . for example , outer race 46 may be bolted to the drive shaft using a plurality of bolts received in corresponding bolt holes 62 extending lengthwise through outer race 46 from front face 50 to rear face 52 . other connection means may also be employed depending on the requirements of the particular application . referring to fig2 and 5a thru 5 d , arranged within outer race 44 is an inner race 64 having an outer face 66 and inner first and second ball tracks 68 and 70 . outer face 66 of inner race 64 has , as seen in longitudinal section ( fig5 a ), a generally roof - shaped contour that is interrupted by the inner ball tracks 68 , 70 . outer face may also have any of a variety of other contours , including but not limited to circular , elliptical , parabolic , and linear , to name a few . the roof - shaped outer face 66 includes a generally cylindrical midsection region 72 flanked by generally conical surface portions 74 adjoining the latter tangentially . midsection region 72 defines a maximum outer diameter d ir of inner race 64 . inner race 64 has a front face 76 and a rear face 78 that define an axial inner race length ir l . inner ball tracks 68 and 70 have a track depth t d corresponding to a radial distance measured from midsection region 72 of outer face 66 of the inner race to a bottom 80 , 82 of inner ball tracks 68 and 70 , respectively . inner ball tracks 68 , 70 have substantially the same track depth t d . inner ball tracks 68 , 70 extend over the entire length ir l of inner race 64 from front face 76 to rear face 78 . inner race 64 may include a central orifice 86 extending lengthwise through the inner race from front face 76 to rear face 78 . an inner surface of orifice 86 includes a series of longitudinal toothing 88 defining a spline 91 having a length ls . orifice 86 is configured for rotationally fixed insertion of a correspondingly configured drive shaft , such as a journal shaft of a drive unit or any other member capable of transmitting a torque to or constant velocity joint 42 . the contact points between the spline 91 of inner race 64 and the spline of the drive shaft received in orifice 86 define a spline pitch circle diameter pcd spline . the distance from an outer diameter of the spline to the bottom 80 , 82 of inner ball tracks 68 , 70 corresponds to a spline inner distance s ir . referring to fig2 thru 5 d , multiple balls 90 having a diameter “ d ” are guided in pairs of ball tracks consisting in each case of one outer first ball track 54 and one inner first ball track 68 , and one outer second ball track 56 and one inner second ball track 70 . a cage 92 is arranged between the outer race 44 and the inner race 64 , and includes circumferentially distributed windows 94 in which the balls 90 are received . with particular reference to fig4 a and 4b , cage 92 includes a set of long windows 96 and short windows 98 alternately arranged over the circumference of the cage . large windows 96 have a circumferential length lc and receive balls 90 guided in the track pairs consisting of outer second ball tracks 56 and inner second ball tracks 70 . small windows 98 have a circumferential length l s and receive balls 90 guided in the track pairs consisting of outer first ball tracks 54 and inner first ball tracks 68 . long and shorts windows 96 , 98 each have a width w c producing a ball window clearance 100 between a circumferential inside surface 102 of the window and an outer circumference of ball 90 received in the window . cage 92 has an inner face 104 and an outer face 106 . inner face 104 includes , as seen in longitudinal section ( fig4 a ), a generally cylindrical recessed midsection region 108 flanked by generally cylindrically shaped surface portions 110 adjoining the latter tangentially . midsection region 108 defines a maximum cage inner diameter d i and the adjoining cylindrically shaped surface portions 110 define a minimum cage inner diameter d i . outer face 106 of cage 92 has , as seen in longitudinal section ( fig4 a ), a generally peaked contour that is interrupted by the windows 94 . the outer face 106 includes a generally arcuate midsection region 112 flanked by generally conical surface portions 114 adjoining the latter tangentially . midsection region 112 defines a maximum outer diameter do of cage 92 . cage 92 has a front face 116 and a rear face 118 that define an axial cage length b . cage 92 has a side cross sectional area 120 , as seen in longitudinal section ( fig4 a ), bounded by conical region 114 of cage outer face 106 , cylindrical region 110 of cage inner face 104 , window circumferential edge 102 , and front and rear faces 116 , 118 of cage 92 . cage 92 also has a center cross - sectional area 122 , as seen in circumferential section ( fig4 b ), bounded by midsection region 112 of cage outer face 106 , midsection region 108 of cage inner face 104 , and a peripheral end surface 124 of adjacent long and short windows 96 , 98 . continuing to refer to fig3 a thru 5 d , the first pairs of tracks that include outer and inner first ball tracks 54 , 68 , and the second pairs of tracks that include outer and an inner second ball tracks 56 , 70 , are alternately arranged over the circumference of the respective inner and outer races 64 , 44 . multiple webs 126 are formed between each two inner first and second ball tracks 68 , 70 that are arranged adjacent to one another in the circumferential direction . similarly , multiple webs 128 are formed between each two outer first and second ball tracks 54 , 56 that arranged adjacent to one another in the circumferential direction . in each case , two first pairs of ball tracks 54 , 68 and two balls 90 lie diametrically opposite one another with respect to a joint longitudinal mid - axis a - a . likewise , in each case , two second pairs of ball tracks 56 , 70 and two balls 90 lie diametrically opposite one another with respect to the joint longitudinal mid - axis a - a . with the joint aligned , such that a longitudinal mid - axis b - b of the outer race 44 is substantially aligned with a longitudinal mid - axis c - c of the inner race 64 , only the balls 90 guided in the pairs of first ball tracks 54 , 68 transfer a torque , whereas an axial force for controlling ball cage 92 occurs at the balls 90 guided by the pairs of second ball tracks 56 , 70 . when the joint articulates , the balls 90 guided in the pairs of second ball tracks 56 , 70 may also transfer torque . the amount of torque transferred is a function of the articulation angle of the joint . outer first and second ball tracks 54 , 56 have a generally elliptical shaped cross - sectional profile , as shown in fig3 c . the balls 90 guided in the outer first and second ball tracks 54 , 56 engage the tracks at two points 93 , 95 located at a radius r cor . center points 97 of a pair of balls 90 seated in diametrically opposite ball tracks 54 , 56 define an outer race pitch circle diameter pcd o . similarly inner first and second ball tracks 68 , 70 have a generally elliptical shaped cross - sectional profile , as shown in fig5 d . the balls 90 guided in the inner first and second ball tracks 68 , 70 engage the tracks at two points 99 , 101 located at a radius r cir . center points 97 of a pair of balls 90 seated in diametrically opposite ball tracks 68 , 70 define an inner race pitch circle diameter pcd i . for purposes of discussion , the constant velocity joint 42 is shown to include four axially parallel pairs of ball tracks 54 , 68 and four joint axis - intersecting pairs of ball tracks 56 , 70 . the pairs of ball tracks are alternately arranged over the circumference of the respective inner and outer races 64 , 44 , and receive a total of eight balls 90 . it shall be appreciated , however , that constant velocity joint 42 may also be configured to include three or five axially parallel pairs of ball tracks 54 , 68 , and a corresponding number of joint axis - intersecting pairs of ball tracks 56 , 70 that alternate over the circumference of the inner and outer races and receive a total of either six or ten balls 90 depending on the number of pairs of ball tracks employed . with the joint aligned , the outer first ball tracks 54 and the inner first ball tracks 68 have axially parallel center lines 130 , 132 , respectively . the first ball tracks 54 , 68 operate in conjunction with balls 90 to transfer torque between inner race 64 and outer race 44 , while providing little or no control of the ball cage 92 . the outer second ball tracks 56 form an outer track angle ta or with the joint longitudinal mid - axis a - a in a radial view , with the joint aligned . the corresponding opposite inner second ball tracks 70 have , with respect to the joint longitudinal mid - axis a - a , an equal and opposite inner track angle ta ir in a radial view , with the joint aligned . this arrangement results in a centerline 136 , 134 of the respective inner and outer second ball tracks 58 , 50 intersecting one another in a radial view . the balls 90 received by each pair of inner and outer second tracks 70 , 56 have their center points 97 located at the intersection point of the centerlines 134 , 136 of the second pairs of ball tracks 56 , 70 . the second inner ball tracks 70 of the inner race 64 arranged at an inner track angle ta ir relative to the joint longitudinal mid - axis a - a are all obliquely inclined co - directionally with respect to one another . similarly , the corresponding opposite second outer ball tracks 56 of the outer race 44 are all obliquely inclined co - directionally with respect to one another . the balls 90 received in the windows 94 of the ball cage 92 control the positioning of ball cage 92 within constant velocity joint 42 . the centrally symmetrical arrangement of the balls 90 received in the first ball track pair 54 , 68 , and the balls 90 received in the second ball track pair 56 , 70 , results in two torque - transferring balls 90 and two controlling balls 90 lying diametrically opposite one another when the joint is aligned . the operating and performance characteristics of constant velocity joint 42 may be affected by a variety of parameters . several of these parameters are listed in the tables shown in fig6 a and 6b . for example , the torque transfer capability of a cross - track constant velocity joint is a function of its mass , material properties and the maximum radii of the constant velocity joint &# 39 ; s parts . thus , the performance characteristics of constant velocity joint 42 may be enhanced by maximizing the torque transfer to radius relationship in order to reduce the mass of the constant velocity joint . maximizing the performance parameters identified in fig6 a and 6b may provide additional benefits , such as weight reduction , package size control , reduced part envelop and / or part runout , improved vibration deadening , increased strength per package size , and increased torque transfer capability per unit weight . thirty - four parameters are identified in the tables in fig6 a and 6b . each parameter includes an identified range that may maximize one or more of the performance characteristics of constant velocity joint 42 . with regard to the processes , systems , methods , heuristics , etc . described herein , it should be understood that , although the steps of such processes , etc . have been described as occurring according to a certain ordered sequence , such processes could be practiced with the described steps performed in an order other than the order described herein . it further should be understood that certain steps could be performed simultaneously or generally simultaneously , that other steps could be added , or that certain steps described herein could be omitted . in other words , the descriptions of processes herein are provided for the purpose of illustrating certain embodiments , and should in no way be construed so as to limit the claimed invention . it is to be understood that the above description is intended to be illustrative and not restrictive . many embodiments and applications other than the examples provided would be apparent to those of skill in the art upon reading the above description . the scope of the invention should 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 . it is anticipated and intended that future developments will occur in the arts discussed herein , and that the disclosed systems and methods will be incorporated into such future embodiments . in sum , it should be understood that the invention is capable of modification and variation and is limited only by the following claims . all terms used in the claims are intended to be given their broadest reasonable constructions and their ordinary meanings as understood by those skilled in the art unless an explicit indication to the contrary is made herein . in particular , use of the singular articles such as “ a ,” “ the ,” “ said ,” etc . should be read to recite one or more of the indicated elements unless a claim recites an explicit limitation to the contrary .
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for the purposes of promoting an understanding of the principles of the invention , reference will now be made to preferred embodiments and specific language will be used to describe the same . it will nevertheless be understood that no limitation of the scope of the invention is thereby intended , such alterations and further modifications of the invention , and such further applications of the principles of the invention as illustrated herein , being contemplated as would normally occur to one skilled in the art to which the invention relates . as indicated above , the present invention relates to cysteine protease inhibitors which contain heterocyclic leaving groups . in one aspect of the invention , a group of cysteine protease inhibitors which have been shown to be particularly effective for in vivo applications is disclosed . the cysteine protease inhibitors described herein function as the sum of two portions . the first portion defines the specificity of a particular inhibitor to an enzyme by the spacial , hydrophobic or hydrophilic and ionic interactions of a particular composition that either imitates or improves upon the nature of the enzyme &# 39 ; s natural substrate . the second portion is a trap that covalently binds the enzyme in a two - step mechanism : the first step involves the nucleophilic attack of the enzyme thiolate on the carbonyl of the inhibitor to form a hemithioketal . it is then energetically favorable for this intermediate to undergo a 1 , 2 migration of the thiolate in which a heterocyclic leaving group is simultaneously released . the enzyme has now become irreversibly bonded to the inhibitor . with the inhibitors of the present invention the leaving group is a heterocyclic leaving group . accordingly , the cysteine proteinase inhibitors of the present invention are preferably constructed with an activated carbonyl which bears a suitable α - leaving group which is fused to a programmed peptide sequence that specifically directs the inhibitor to the active site of the targeted enzyme . ( for example , z - phe - phechn 2 preferentially inhibits cathepsin l over catheosin b .) once inside the active site , this inhibitor carbonyl is attacked by a cysteine thiolate anion to give the resulting hemiacetal form . if the α - leaving group then breaks off , the bond between enzyme and inhibitor becomes permanent and the enzyme is irreversibly inactivated . the selectivity of the inhibitor for a particular enzyme depends not only on the “ lock and key ” fit of the peptide portion , but also on the reactivity of the bond binding the leaving group to the rest of the inhibitor . it is very important that the leaving group must be reactive only to the intramolecular displacement via a 1 , 2 - migration of sulfur in the breakdown of the hemithioacetal intermediate . the preferred inhibitors of the present invention can be described generally by the formula : wherein b is an amino acid blocking group for the n - terminal amino acid , each ( p ) x is an optionally protected α - amino acid residue , x is an integer between zero and 5 , inclusive , and het is the heterocyclic portion of the leaving group . as is conventional in the art , and as used herein , amino acid residues may be designated as p 1 , p 2 , etc ., wherein p 1 refers to the amino acid residue nearest the leaving group , p 2 refers to the amino acid residue next to p 1 and nearer the blocking group , etc . in dipeptide inhibitors therefore , p 2 is the amino acid residue nearest the blocking group . more specifically , the compounds employed in the present invention are of the formula : b is h or an amino acid blocking group for an n - terminal amino acid nitrogen ; r 1 is the amino acid side chain of the p 1 amino acid residue ; r 2 is the amino acid residue of the p 2 amino acid ; r 3 is the amino acid residue of the p 3 amino acid ; het is the heterocyclic portion of the leaving group ; wherein the heterocyclic leaving group includes a four -, five -, six - or seven - membered ring having at least one c and at least one of n , o or s in the ring . concerning the amino acid blocking group b for the n - terminal amino acid nitrogen , many suitable peptide end - blocking groups are known in the art . for example the end - blocking groups identified in e . gross and j . meienhofer ( eds . ), the peptides , vol . 3 are generally suitable for use in the present invention . preferred blocking groups include n - morpholine carbonyl and derivatives of propionic acid derivatives that have intrinsic analgesic or anti - inflammatory action . examples of blocking groups having intrinsic analgesic or anti - inflammatory action may be found in gilman , goodman , gilman , the pharmacological basis of therapeutics , sixth ed . macmillan , chapter 29 . as defined herein , the peptide end - blocking group is attached to either an amino acid or a peptide chain . one particularly effective blocking group is the 4 - morpholinylcarbonyl (“ mu ”) blocking group shown below : the peptide portion of the inhibitor may include any pep , ide appropriate for targetting a desired cysteine protease . preferably , the side chain on the p 1 amino acid is selected according to the enzyme being targetted . for cathepsin b or l , this might include side chains such that the linked p 1 amino acid is a member of the group consisting of alanyl ( ala ), arginyl ( arg ), aspartic acid ( asp ), glutamic acid ( glu ), histidyl ( his ), homophenylalanyl ( hphe ), phenylalanyl ( phe ), ornithyl ( orn ), seryl ( ser ) and threonyl ( thr ), and optionally substituted analogues thereof such as thiazoles and amino thiazoles . preferably the side chain on the p amino acid is selected so that the linked p 2 amino acid is a member of the group consisting of phenylalanyl ( phe ), leucyl ( leu ), tyrosyl ( tyr ) and valyl ( val ) amino acid residues and substituted analogues thereof , particularly including tyr ( ome ). as indicated above , each of the cysteine protease inhibitors of the present invention includes a heterocyclic leaving group . the heterocycle of the leaving group is a ring of variable size ( 4 - 7 members ) containing one or more heteroatoms and n double bonds where n = 0 - 3 . this ring is bonded through an oxygen atom which becomes part of the leaving group during inhibition of the targeted enzyme . in the absence of the targeted active site , the inhibitor construction is an ether that is very stable in the physiological environments of the stomach , lysosome , or disease state arthritic joint . the heterocycles of the present invention may be derived from the group that includes pyridine n - oxides , uracils , cytosines , pyrones , pyridones , pyrimidines , pyraziznes , furans , thiophenes , pyrroles , oxazoles , thiazoles , pyrazoles , imidazoles , triazoles , tetrazoles and their optionally - substituted derivatives such as benzo - fused derivatives . for oral bioavailability , the most preferred leaving groups have at least one heteroatom for each four carbon atoms in the leaving group . the ability of the leaving group to protonate at physiological ph is directly related to its inability to cross cell membranes which can be advantageous in certain applications . in the same context , the ability of a heterocycle to chelate with a metal ion may ( 1 ) impede crossing of membranes and / or ( 2 ) target metalloproteases such as calpains . in the environment of the active site protonation and / or hydrogen bonding of ring heteroatoms will accentuate its role as a leaving group . it is to be appreciated that the heterocycle may be chosen specifically in accord with the function of the enzyme to be inhibited . for example , the inhibitor would use a derivative of hydroxyproline ( a major constituent of collagen ) to target a collagenase : or the natural substrate ( hydroxyproline ) may be improved upon by a suitable replacement such as a hydroxyfuran which upon displacement from the inhibitor can and does tautomerize to a more stable keto form increasing its efficiency as a leaving group . it is also to be aporeciated that during the course of the reaction of enzyme with inhibitor , the carbonyl of the inhibitor rehybridizes to sp3 and forms a ketal intermediate with the thiol function of the enzyme . under the acid conditions of this reaction , other ketals can exchange with this intermediate either by going through the ketone or by ketal - ketal exchange . accordingly , ketals can be substituted for carbonyls in the peptidyl inhibitors of the present invention . similarly , other compounds such as hydrazones , hemiketals , oximes , imines , cyanohydrins , enolethers , enamines , hemithioketals , and the like are to be considered carbonyl equivalents and may be substituted for a carbonyl or to give a carbonyl under the acidic conditions of these inhibition reactions . utilization of such derivatives can also be vehicles to either improve the bioavailability of the inhibitor drug or keep it from crossing a cellular membrane depending upon the hydrophobic nature of the masking function . finally , it is to be appreciated that the development and synthesis of compounds having isosteric replacements of amide bonds is now a standard practice in the development of biologically active peptides once the optimum peptide sequence has been identified . accordingly , the present invention includes compounds having one or more modified amide bonds in the peptide sequence so long as conformation and binding are maintained while secondary enzymatic hydrolysis is prevented . for a list of such modifications see kaltenbronn , 33 , j . med . chem ., 838 . in addition , inhibitors having a hydrazine replacement for the p 1 nitrogen as reported by giordano for other halogen methyl ketones are also intended to be claimed . reference will now be made to specific examples using the processes described above . it is to be understood that the examples are provided to more completely describe preferred embodiments , and that no limitation to the scope of the invention is intended thereby . in a 100 ml round bottom flask equipped with an argon line was placed mu - phe - h ~ he - br ( 1 . 0 g , 1 . 94 mmol ), potassium fluoride ( 449 . 5 mg , 7 . 75 mmol ), potassium carbonate ( 534 . 9 mg , 3 . 87 mmol )- k 2 co 3 was added to control the acidic environment , and 4 - hydroxy - 6 - methyl - 2 - pyrone ( 488 . 0 mg , 3 . 87 mmol ). about 5 ml of dmf was added to dissolve the solid mixture . the reaction flask was immersed in a 50 ° c . oil bath . the reaction was allowed to run for 40 minutes in order to ensure the completion of the reaction . the reaction mixture was diluted with ethyl acetate , and potassium fluoride was removed by a small silican gel column . the solvent ethyl acetate was stripped by a water vacuum pump , and dmf was removed by an oil vacuum pump . the next day the light yellow product was recrystallized in hexane : diethyl ether ( 50 %: 50 %). the white precipitate was filtered and a nmp spectrum was obtained . m . p . 94 - 98 ° c . in a 100 ml round bottom flask equipped with an argon line as placed mu - phe - hphe - br ( 300 mg , 0 . 581 mmol ), potassium fluoride ( 134 . 8 mg , 2 . 33 mmol ) potassium carbonate ( 321 . 4 mg , 2 . 33 mmol )- k 2 co 3 was added to control the acidic environment , and 5 , 6 - dihydro - 4 - hydroxy - 6 - methyl - 2h - pyran - 2 - one ( 298 . 0 mg , 2 . 33 mmol ). about 5 ml of dmf was added to dissolve the solid mixture . the reaction flask was immersed in a 50 ° c . oil bath . the reaction was allowed to run for 40 minutes in order to ensure the completion of the reaction . the reaction mixture was diluted with ethyl acetate , and potassium fluoride was removed by a small silica gel column . the solvent ethyl acetate was removed by a water vacuum pump , and dmf was removed by an oil vacuum pump . the next day the light yellow product was recrystallized in 50 : 50 hexane : diethyl ether . the white precipitate was filtered and a nmr spectrum was obtained . m . p . 74 - 7 ° c . in a 100 ml round bottom flask equipped with an argon line was placed mu - phe - hphe - br ( 1 g , 1 . 94 mmol ), potassium fluoride ( 0 . 45 g , 7 . 75 mmol ), potassium carbonate ( 1 . 07 g , 7 . 75 mmol )- k 2 co 3 was added to control the acidic environment , and 2 - hydroxy - 3 - methylcarboxypyridine ( 0 . 59 g , 3 . 87 mmol ). about 5 ml of dmf was added to dissolve the solid mixture . the reaction flask was immersed in a 50 ° c . oil bath . the reaction was allowed to run for 40 minutes in order to ensure the completion of the reaction . the reaction mixture was diluted with ethyl acetate , and potassium fluoride was removed by a small silica gel column . the solvent ethyl acetate was removed by a water vacuum pump , and dmf was removed by an oil vacuum pump . the next day the light yellow product was recrystallized in 50 : 50 hexane : diethyl ether . the white precipitate was filtered and a nmr spectrum was obtained . m . p . 100 - 102 ° c . in a 100 ml round bottom flask equipped with an argon line was placed mu - he - hphe - br ( 500 mg , 0 . 969 mmol ), potassium fluoride ( 224 . 8 mg , 3 . 876 mmol ), potassium carbonate ( 267 . 8mg , 1 . 938 mmol )- k 2 co 3 was added to control the acidic environment , and 3 - hydroxypyridine ( 184 . 3 mg , 1 . 938 mmol ). about 5 ml of dmf was added to dissolve the solid mixture . the reaction flask was immersed in a 50 ° c . oil bath . the reaction was allowed to run for 40 minutes in order to ensure the completion of the reaction . the reaction mixture was diluted with ethyl acetate , and potassium fluoride was removed by a small silica gel column . the solvent ethyl acetate was removed by a water vacuum pump , and dmf was removed by an oil vacuum pump . the next day the light yellow product was recrystallized in 50 : 50 hexane : diethyl ether . the white precipitate was filtered and a nmr spectrum was obtained . m . p . 112 - 115 ° c . in a 100 ml round bottom flask equipped with an argon line was placed mu - phe - hphe - br ( 300 mg , 0 . 581 mmol ), potassium fluoride ( 135 . 1 mg , 2 . 33 mmol ), potassium carbonate ( 322 . 0 mg , 2 . 33 mmol )- k2co3 was added to control the acidic environment , and 2 - hydroxypyrimidine ( 111 . 7 mg , 1 . 938 mmol ). about 5 ml of dmf was added to dissolve t - he solid mixture . the reaction flask was immersed in a 50 ° c . oil bath . the reaction was allowed to run for 40 minutes in order to ensure the completion of the reaction . the reaction mixture was diluted with ethyl acetate , and potassium fluoride was removed by a small silica gel column . the solvent ethyl acetate was removed by a water vacuum pump , and dmf was removed by an oil vacuum pump . the next day the light yellow product was recrystallized in 50 : 50 hexane : diethyl ether . the white precipitate was filtered and a nmr spectrum was obtained . m . p . 95 - 100 ° c . in a 100 ml round bottom flask equipped with an argon line was placed mu - phe - hphe - ch - br ( 500 mg , 0 . 969 mmol ), potassium 2fluoride ( 224 . 8 mg , 3 . 876 mmol ), potassium carbonate ( 535 . 7 mg , 3 . 876 mmol )- k 2 co 3 was added to control the acidic environment , and 2 - furanone ( 275 μl , 3 . 876 mmol ). about 5 ml of dmf was added to dissolve the solid mixture . the reaction flask was immersed in a 50 ° c . oil bath . the reaction was allowed to run for 40 minutes in order to ensure the completion of the reaction . the reaction mixture was diluted with ethyl acetate , and potassium fluoride was removed by a small silica gel column . the solvent ethyl acetate was removed by a water vacuum pump , and dmf was removed by an oil vacuum pump . the next day the light yellow product was recrystallized in 50 : 50 hexane : diethyl ether . the white precipitate was filtered and a nmr spectrum was obtained . m . p . 90 - 93 ° c . in a 100 ml round bottom flask equipped with an argon line was placed mu - phe - hphe - br ( 200 mg , 0 . 388 mmol ), potassium fluoride ( 89 . 9 mg , 1 . 55 mmol ), potassium carbonate ( 214 . 3 mg , 1 . 55 mmol )- k 2 co 3 was added to control the acidic environment , and 2 - hydroxypyrimidine ( 205 . 5 mg , 1 . 55 mmol ). . bout 4 ml of dmf was added to dissolve the solid mixture . the reaction flask was immersed in a 50 ° c . oil bath . the reaction was allowed to run for 40 minutes in order to ensure the completion of the reaction . the reaction mixture was diluted with ethyl acetate , and potassium fluoride was removed by a small silica gel column . the solvent ethyl acetate was removed by a water vacuum pump , and dmf was removed by an oil vacuum pump . the next day the light yellow product was recrystallized in 50 : 50 hexane : diethyl ether . the white precipitate was filtered and a nmr spectrum was obtained . m . p . 82 - 85 ° c . in a 100 ml round bottom flask equipped with an argon line was placed mu - phe - hphe - br ( 500 mg , 0 . 969 mmol ), potassium fluoride ( 224 . 8 mg , 3 . 876 mmol ), potassium carbonate ( 535 . 7 mg , 3 . 876 mmol ) was added to control the acidic environment , and boc - l - hydroxyproline - methylester ( 475 . 2 mg , 1 . 938 mmol ). about 6 ml of dmf was added to dissolve the solid mixture . the reaction was left at the room temperature and periodical tlc was checked to monitor the progress of the reaction . according to tlc , the reaction was completed after about one hour . the reaction mixture was diluted with ethyl acetate , and potassium fluoride was removed by a short silica gel column . the solvent ethyl acetate was stripped by a water vacuum pump , and dmf was removed by an oil vacuum pump . the product was dried under the vacuum pump . the next day the light yellow oily product was recrystallized in hexane . the precipitate was filtered and a nadir spectrum was obtained . de - boc : about 5 ml of methylene chloride was used to dissolve 100 mg of the boc product . then about 5 ml of hcl . dioxane was put into the 50 ml flask , and the reaction was allowed to proceed for about 45 minutes under argon . carbon dioxide was released from the flask ; bubbles came up to the surface of the reaction mixture . after the completion of the reaction , the mixture was slowly dropped into six test tubes filled with diethyl ether . the precipitation came out and was allowed to continue for about half hour . the product was quickly removed through suction filtration and it was put in a dry box overnight . in a 100 ml round bottom flask equipped with an argon line was placed nu - phe - hphe - ch 2 - br ( 300 mg , 0 . 582 mmol ), potassium fluoride ( 150 mg , 2 . 4 mmol ), and potassium carbonate ( 150 mg , 1 . 2 mmol ), and 8 ml of 200 proof ethanol . the reaction was stirred 3 hours , filtered and the solvents were removed under vacuum and the residue chromatographed on a short silica gel column ( chcl 3 : mleoh 95 : 5 ) and then recrystallized from ether . general procedure for the preparation of hcl - hphe - ch 2 - o - substituted heterocyclic inhibitors . to boc homophenylalanine ( 18 mmol ) in 150 ml distilled thf at − 20 ° c . was added one equivalent of n - methylmorpholine followed by one equivalent of isobutylchloroformate . after 10 minutes , the mixture was poured through filter paper into 200 ml etheral solution of diazomethane which was made according to the suppliers directions from 8 . 6 g of diazald ( aldrich ). the reaction was allowed to stir overnight , and then poured into 100 ml water . the organic portion was washed with nahco3 ( ag ) ( 2 × 50 ml ), brine ( 2 × 50 ml ); dried over mgso 4 ; concentrated to give the diazoketone 5 . 38 9 ( 99 %) of a yellow oil that crystalizes on standing . to the above diazoketone ( 5 . 38 g , 0 . 018 mol ) in 20 ml of methylene chloride at − 5 ° c . is added dropwise 30 % hbr in acetic acid which is diluted three - fold with methylene chloride . the addition is made at a rate that allows the monitoring of the evolved nitrogen and until all yellow color of the starting material has disappeared . the reaction is poured into 50 ml water and diluted with another 100 ml of methylene chloride . the organic layer is separated , washed with nahco 3 ( aq ) ( 50 ml ), brine ( 50 ml ), dried over mgso and concentrated to give a white solid which is characterized by its nmip . in a 100 ml round bottom flask equipped with an argon line was placed boc - hphe - ch br ( 1 . 4 mmol ), potassium fluoride ( 5 . 5 mmol ) and the substituted phenol ( 5 . 6 mmol ). about 1 ml or dmf is added and the mixture is stirred at 50 ° c . for 40 min . the reaction is then diluted with ethyl acetate and run through a silica gel plug to remove the potassium salts . the solvents are removed ( low then high ) vacuum to give a solid product . when purification is needed , a silica gel column is used . in this way the following compounds were prepared : to the boc - phhe ch 2 - o - substituted aromatic ( 2 . 6 mmol ) in 3 ml of methylene chloride was placed 8ml of 2n hcl — dioxane . the reaction was stirred about 40 min and the resulting mixture was added dropwise to about 600 ml of ether and then filtered to give the peptide inhibitor . evaluation of heterocyclic - methyl , peptidyl ethers by the in vitro inhibition of purified enzymes cathepsin b and h enzyme : cathepsin b , purified from human liver , is from enzyme systems products ( dublin , calif .). the activity is 50 mu per ml at 30 ° c ., in 52 mm sodium phosphate , ph 6 . 2 , 31 mm dtt , 2 . 1 mm edta , with 0 . 2 mm z - arg - arg - 7 - amino - 4 - trifluoromethyl - coumarin as a substrate . specific activity is 8330 mu per mg protein . ( 1 mu = 1 nmol per min .) substrate : boc - leu - arg - arg - 7 - amino - 4 - triflouromethyl - coumarin - 2hbr is from enzyme systems products . a 20 mm solution is made in dmf and stored at − 200 c . inhibitors : candidate inhibitors are synthesized by pcrototek , inc ., dublin , calif . 20 mm stock solutions are made in dmf and stored at − 20 ° c . dilutions are made in assay buffer . method : the percent inhibition and the inhibitor concentration at which the enzyme is 50 % inhibited ( ic50 ) are determined as follows : five μl of enzyme are activated by pre - incubation in three 480 μl aliquots and one 485 μl aliquot of assay buffer ( 50 mm potassium phosphate ph 6 . 2 , 2 mm edta , 5 mm dtt ) on ice for 30 min . the inhibition is initiated by the addition of 5 μl or 200 μm , 20 μm , and 2 μm inhibitor each to the 480 μl aliquots . the 485 μl aliquot zenith enzyme is used as a control and thus receives no inhiibitor . the enzyme / inhibitor mixtures are incubated 10 min . on ice and assayed for cathepsin b activity as follows . cathepsin b assay : to 490 μl of ore - incubated inhibitor / enzyme mixtures in assay buffer in 0 . 5 ml cuvette at 37 ° c . is added 10 μl or the s , ubstrate . final inhibitor concentrations become 2000 mm , 200 mm , and 20 mm for the 200 μm , 20 μl and 2 μm stock concentrations , respectively . activity is followed by release of free afc over 5 min . ( where ( fluorescence units at t = 6 )—( fluorescence units at t = 1 )) with a perkin - elmer ls - 5b spectrofluorometer ( ex = 400 nm , em = 505 nm ). the percent inhibition is determined by comparing the change in fluorescence units of the three sample concentrations of inhibited enzyme to the change in fluorescence units off the control enzyme . 100 −( fl . units · of sample / f 1 . units of control × 100 ) gives percent inhibition . the ic50 is ascertained by plotting percent inhibition vs . inhibitor concentration on the log scale . the ic50 is the concentration of inhibitor ( nm ) at which the enzyme is inhibited by 50 %. the materials and methods were as disclosed above for example 12 — cathepsin b kinetics — except as follows : water solutions of inhibitor using either ethanol or dmso as a cosolvent were made at 8000 nm , 800 nm and 160 nm concentrations with a minimum of solvent . each rat was given a dose at time 0 and then individuals were sacrificed at 6 hrs , 12 hrs and 24 hrs . doses were given either by injection or stomach tube . the livers and kidneys were harvested and analyzed for cathepsin b activity . in some individuals the urine was collected at 6 , 12 , 24 hrs and analyzed for the presence of inhibitor . the results for examples 14 and 15 are shown in tables 14 and 15 below . dba / lac mice mere injected with 200 μg of type ii chick collagen emulsified in freund &# 39 ; s complete adjuvant on day 0 and on day 21 . mu - phe - hphe - o - prolite methyl ester was suspended in an ethanol solution which was then diluted to 10 % ( aq ) and administered by garage at a dose of 10 mg / kg / day to day 21 until sacrifice at day 49 . the of joint inflammation was evaluated grossly at seven day intervals beginning on day 21 . the effect of oral administration of nu - phe - hphe - o - proline methyl ester on the severity of bone lesions in adjuvant - induced arthritis was determined by evaluating osseous mineralization , periostat proliferation , bone erosion , joint space narrowing and osseous fragmentation . all lesions were scored on a scale of 0 ( normal architecture ) to 3 ( severe or marked changes ). values calculated were mean values ± std . error of the mean . the “ bone lesion severity ” values of mu - phe - hphe - o - proline methyl ester treated animals were significantly ( p & lt ; 0 . 05 ) lower than the values of control animals for each parameter tested . the effect of oral administration of mu - phe - hphe - o - proline methyl ester on the histological aspects of adjuvant - induced arthritis was determined by evaluating inflammation , focul ulcers , tibiotarsal joint cartilage destruction , bone destruction and periosteal proliferation . inflammation was scored on a scale of 0 ( no inflammation ) to 3 ( severe ) based on the extent of edema and cell infiltration . focul ulcer cartilage destruction was measured as the percent of articular cartilage surfaces with focal destruction which exposed underlying subchondral bone . tibiotarsal joint cartilage destruction was measured as the percent of articulating surfaces with destruction of the subchondral bone . values calculated were mean values 1 std . error of the mean . the “ histological aspects ” values of mu - phe - hphe - o - proline methyl ester treated animals were significantly ( p & lt ; 0 . 05 ) lower than the values of control animals for each parameter tested . dba / lac mice were injected with 200 μg of type ii chick collagen emulsified in complete freund &# 39 ; s adjuvant on day 0 and on day 21 . mu - phe - hphe - o - proline methyl ester was suspended in phosohate buffered saline and administered by gavage from day 21 until sacrifice at day 35 . doses of between 3 mg / kg / day and 25 mg / kg / day were used , with the daily dosage being held constant over time for each test . the severity of joint inflammation was evaluated grossly as seven day intervals beginning on day 21 . the effect of oral administration of mu - phe - hphe - o - proline methyl ester on the severity of bond lesions in adjuvant - induced arthritis was determined by evaluating osseous mineralization , periostat proliferation , bone erosion , joint space narrowing and osseous fragmentation . all lesions were scored on a scale of 0 ( normal architecture ) to 3 ( severe oc marked changes ) values calculated were mean values ± 1 std . error of the mean . the “ bone lesion severity ” values of mu - phe - hphe - o - proline ethyl ester treated animals were significantly ( p & lt ; 0 . 05 ) lower than the values of control animals for each parameter tested . rats were injected with adjuvant on day 0 and were treated with mu - tyr -( ome )- hphe - o - proline methyl ester in ground diet from the time of adjuvant injection until sacrifice at day 32 . over the course of the disease , animals were evaluated in terms of a mean clinical score , a derived series of clinically observed parameters normalized to facilitate graphical presentation . lean paw volumes were also measured using ! normalized units throughout the course of the disease . at the end of the study , the animal groups were sacrificed and evaluated by x - ray analysis . the mean clinical scores of mu - tyr -( ome )- hphe - o - proline methyl ester treated rats were significantly lower than the scores for untreated animals . similarly , mean paw volumes were also significantly reduced . the example demonstrates the beneficial effect of nu - tyr -( ome )- hphe - o - proline methyl ester on adjuvant - induced arthritis . effectiveness of heterocyclic methyl ketones on human and murine malaria paracytes . the effect of the inhibitor on gingival inflammation was studied by investigating its ability to prevent the development of experimental gingivitis . twenty human subjects with healthy gingiva and no periodontal disease were recruited . the subjects received oral hygiene instruction and scaling prior to baseline . the test sites were the mesibuccal crevices on the upper first and second molars and premolars ( bicuspids ). acrylic shields were made to cover the gingival margins of these teeth and were worn during oral hygiene to prevent brushing of the test and control sites . during the test period of three weeks the subjects were told to brush only the lower teeth and upper anteriors and to wear the shields during brushing . the left side was used as the test side and the right was the control side in 10 subjects . the sides were reversed in the other 10 subjects so the subjects could act as their own controls . thirty second gcf samples were taken prior to clinical measurements at baseline and at 1 , 2 , 3 and 4 weeks . these were assayed for cathepsins b and l - like activities . clinical measurements of gingival index ( gi ), gingival bleeding index ( gbi ) and plaque index ( pli ) were taken at test and control sites at zero , one , two , three and four weeks . following the baseline measurements the inhibitor and placebo were placed at test 2nd control sites and sealed in with coe - pak for a week . the inhibitor and placebo were coded so that the study was blind . the gi , gbi and pli and cysteine proteinase levels were compared at test and control sites . it was observed that the use of mu - phe - mphe - o - furan reduced all parameters tested at the test sites . mu - phe - hphe - o - furan can therefore be seen to be effective in treating periodontal diseases such as gingivitis . in the following examples 21 - 27 , the active ingredient is the compound moroholine carbonyl - l - phenylalanyl - l - homophenyl alanyl methyl furanyl ether ( see example 6 ). however , other compounds of the present invention can be substituted thereof . an injectable preparation buffered to a ph of 7 is prepared having the following composition the above ingredients are mixed intimately and pressed into single scored tablets . the above ingredients are mixed and introduced into a hard - shell gelatine capsule . the above ingredients are mixed and introduced ; into a hard - shell gelatine capsule . all of the above ingredients , except water , are combined and heated to 60 ° c . with stirring . a sufficient quantity of water at 60 ° c . is then added with vigorous stirring to emulsify the ingredients , and water then added q . s . 100 g . as previously indicated , the compositions of the present invention may be useful in treating disease states which are associated with cathepsins b , l , h or c . for example , the cathepsin c inhibitors of the present invention may be used to inhibit dipeptidyl peptidase i (“ dpp - i ”) found in cytotoxic t lymphocytes , or to inhibit the processing enzyme of bone marrow serine proteases like elastase and granzyme a . it is to be appreciated that vinylogous homologs of heterocycles ( benzo - derivatives ) would also be considered by those skilled in the art to be reactive in this context . for example , because a hydroxy pyridine derivative works as a leaving group , a hydroxyquinoline ( 5 , 6 , 7 or 8 - hydroxy ) would also work . other examples of this principle of vinylogy in synthetic organic chemistry include : ( 1 ) a michael reaction is a vinylogous analog of an aldol condensation ; and ( 2 ) an sn 2 reaction is a vinylogous analog to an sn 2 reaction . it is also to be appreciated that because sulfur falls below oxygen in the periodic table that s may replace o in the compositions and methods of the present invention and an effective cysteine protease inhibitor would result . finally , it is to be appreciated that the processing of viral proteins by virally encoded proteases plays a central role in the maturation of many viruses . examples of viruses which have been associated with cysteine proteases are polio virus ( 3c proteases ) encephalomycarditis virsu , rhinovirus and foot - and - mouth virus . accordingly , the compositions of the present invention are believed to be useful therapeutic agents for the treatment of viral diseases . while the invention has been illustrated and described in detail in the drawings and foregoing description , the same is to be considered as illustrative and not restrictive in character , it being understood that only the preferred embodiment has been shorn and described and that all changes and modifications that come within the spirit of the invention are desired to be protected .
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the eyewear or eyeglasses of the present invention are particularly useful for athletic activity because they are lightweight and the prescription lenses are inserted and can be impact resistant in accordance with the f803 astm standard and other similar standards , with respect to protective or sport glasses . with respect to sport glasses , many athletes choose less bulky frames that maximize their field of vision with the least amount of frame support around lenses . referring to fig1 and 2 , a pair of eyeglass frames with a mechanical lock lens attachment includes a frame 1 , a nosepiece 4 , and two lenses 3 . the frame includes a horizontal arm 17 positioned between first and second temple pieces 2 , temple pieces 2 extending behind the frame 1 , and a channel 5 formed in the horizontal arm 17 and around the outer edges of the nosepiece 4 . the mechanical lock lens attachment includes a slideable lock clip 7 , a locking pin 8 , and two slots 6 for accommodating the slideable lock clip in the channel 5 . the frame 1 is a conventional winged frame designed so that there are no rims surrounding the lower arcuate surfaces of the lenses 3 . in other words , the lenses 3 look like wings hanging down from the horizontal arm 17 . only the upper sections of the lenses 3 are engaged by the frame 1 . the points of contact between the frame 1 and the lenses 3 comprise a first section of a channel 5 located in the horizontal arm 17 of the frame 1 and a second section of the channel 5 located in the side wall adjacent to the nosepiece 4 . the nosepiece 4 is located at the center of the horizontal arm 17 . it protrudes below the horizontal arm 17 of the frame 1 to support the eyeglasses on the user &# 39 ; s nose . the nosepiece 4 is further defined by two channels 5 for receiving the lenses 3 , one on each side of the nosepiece 4 . both the channel 5 of the horizontal arm 17 of the frame and the channels 5 surrounding the nosepiece 4 are of a suitable size to slidably receive and tightly wrap around the sides of the lenses 3 . as seen in fig3 through 6 , the frame 1 further includes the mechanical lock lens attachment . the lock clip 7 is a slidable bar , captured in two inwardly facing slots 6 of the channel 5 of the horizontal arm 17 of the frame 1 . the lock clip 7 has an i - shaped cross section as seen in fig6 including two outwardly facing rails 9 . the rails 9 arc slidably received in two inwardly facing slots 6 in the channel 5 of the frame 1 to prevent the lock clip 7 from moving vertically relative to the frame 1 . the inwardly facing slots 6 in the channel 5 supports the lock clip 7 and allows the lock clip 7 to move along the channel 5 , once the lens 3 is positioned in the channel 5 . once the lock clip 7 is slid into place over the lens 3 , thereby securing the lens 3 to the frame 1 , a locking pin 8 is secured in the inwardly facing slots 6 between the lock clip 7 and the temple or endpieces . the locking pin 8 thereby prevents the lock clip 7 from sliding away from the lens and releasing it . this process will be described in further detail below . the lenses 3 are located adjacent opposite sides of the nosepiece 4 and below the horizontal arm 17 of the frame 1 . the lenses 3 are blade - style lenses defined by a first protrusion or tab 20 and a second protrusion or tab 21 on the upper portion of the lens 3 , closest to the horizontal arm 17 of the frame 1 , as seen in fig2 . the lens 3 is positioned in the frame channel 5 and includes first outwardly protruding tab 20 and second outwardly protruding tab 21 , the tabs facing opposite directions . the first tab 20 is directed towards the interior section of the frame 1 , specifically , towards the nosepiece 4 . the second tab 21 is directed towards the outer portion of the frame , specifically , towards the temple pieces 2 and end pieces . the lenses 3 are secured to the frame via a sliding lock clip 7 and a locking pin 8 received by the slot 6 in the channel 5 that passes along the horizontal arm 17 . the lenses 3 are placed into the channel 5 that passes through the horizontal arm 17 . the first protruding tab 20 of the lens 3 slides into a portion of the channel 5 shaped to receive it , at the top of the frame 1 towards the nosepiece 4 . the second protruding tab 21 is secured to the frame by sliding the lock clip 7 along the channel 5 of the frame 1 and over the second protrusion 21 of the lens 3 to allow room in the channel 5 for receiving the locking pin 8 . the lock clip 7 is prevented from dislodging by the insertion of the locking pin 8 , thereby restricting movement in the assembly , also illustrated in fig2 . as illustrated in fig2 through 6 , to lock the lens 3 to the frame 1 , the protrusions of each lens 3 is placed into the channel 5 of the horizontal arm 17 . the first protruding tab 20 is received in a first recess in the channel 5 . then , the lock clip 7 is slid from the outer edge of the horizontal arm 17 , closest to the temple pieces 2 , towards the nose piece 4 until the recess 10 in the lock clip 7 engages the second tab 21 . finally , the locking pin 8 is placed into the channel 5 between an end of the lock clip 7 and the outer end of the channel 5 . the locking pin 8 engages the lock clip 7 , and securely locks the lens 3 to the frame , thus preventing the lens 3 from being dislodged and preventing the lock clip 7 from moving out of engagement with the second tab on the lens 3 , as seen in fig3 . the lens 3 is secured between the upper section of the frame 1 , the nosepiece 4 , and the lock clip 7 . to aid in rigidly supporting the lock clip 7 in place , it can have a wedge - shaped configuration or can have serrated sides for engagement with corresponding serrated sides of the lock clip 7 and the end of the channel 5 . the lock clip may be shaped to fit into the slots 6 to ensure its stability , but those skilled in the art will appreciate that there are other ways to secure the locking pin 8 in place so that it prevents lock clip 7 from sliding back toward temple or end piece 2 . fig7 - 10 illustrate additional embodiments of the invention wherein the mechanical lock lens attachment can be selected from the group comprising a screw , a pin , or a bar clip , as well as a single bar support or a double bar support . the frame 1 is a winged frame , similar to the frame in the above described embodiments . the lenses 3 are also similar to those in the above described embodiments . they are blade style lenses 3 defined by a first protrusion 20 and a second protrusion 21 on the upper portion of the lens 3 , closest to the horizontal arm 17 of the frame 1 . only the upper sections of the lenses 3 are engaged by the frame 1 . further , the protrusion includes first outwardly protruding tab 20 and second outwardly protruding tab 21 facing opposite directions . a channel or recess 5 in the horizontal arm 17 of the frame 1 is shaped to receive the first protrusion 20 and the second protrusion 21 of the lens 3 . the embodiments illustrated show a lens with two protruding tabs . those skilled in the art will recognize that protrusions of different numbers or shapes may also be used . as seen in fig7 and 8 , eyeglasses with a mechanical lock lens attachment includes a frame 1 , a nosepiece 4 , two lenses 3 , and two pivotable bars or levers 18 and 19 . first and second levers 18 and 19 form a double bar support 12 that traps the lenses 3 between the levers 18 and 19 and the frame 1 . the levers are located on opposite sides of the nosepiece 4 , behind the frame 1 . the levers 18 and 19 are pivotally attached to the frame 1 , near the nosepiece 4 , with a screw or pin 23 . the levers or bars may also be affixed in different manners recognizable to a person having ordinary skill in the art , such as a sliding bar or a clip - over bar instead of a pivoting bar . a lever could be a bar or any other suitable means for securing the lenses to the frames . a single bar or lever spanning both lenses could also be used instead of multiple levers . fig7 depicts the double bar support 12 in a closed position . the first 18 and second 19 levers are locked to the outer edges of the frame 1 , furthest from the nosepiece 4 , with an additional screw or pin 11 . fig8 illustrates the structure of the double bar support 12 in an open position . a channel 5 is located in the horizontal arm 17 of the frame to receive the lenses 3 . the channel 5 is shaped to receive the protrusion on the upper portion of the lens 3 . the first and second protruding tabs 20 and 21 of the lenses 3 are received into the channel 5 . once the lenses 3 are placed in the frame 1 , the levers 18 and 19 close over the lenses 3 , creating a wall and layering the lenses 3 between the levers 18 and 19 and the frame 1 . finally , a retaining mechanism 11 such as a screw or pin engages each lever 18 and 19 and frame 1 to mechanically lock the lenses 3 to the frame 1 . the outer edge of each lever 18 and 19 comprises an opening 22 for receiving the retaining mechanism 11 . the inner screw or pin 23 is tightly attached to the frame 1 , enough such that it cannot slip out of the frame 1 , but the inner pin 23 is attached loosely enough to allow the levers 18 and 19 to pivot . this pivoting motion of the levers opens like a drawbridge , each lever pivoting upwardly , away from the lens 3 . this allows enough space for the frame to receive the lens 3 . turning to fig9 through 12 , eyeglasses with a mechanical lock lens attachment include a frame 1 , a nosepiece 4 , two lenses 3 , a single bar support 14 , and a bar clip 15 . a single bar support 14 is a lengthwise bar comprising curved sections that follow the substantially arched sections of the frame . the single bar support 14 comprises first and second protrusions 24 and 25 attached to the inner wall of the bar , each protrusion adjacent to the nosepiece 4 and endpiece . the single bar is shaped to replicate the curvature of the lens , creating the channel that secures the frame and lenses together . additionally , the single bar support comprises of protrusions at the bar ends , and a recess in the nasal area , that allows the bar to slide down and nest into the frame endpieces and a slot in the center of the bar for receiving the bar clip . the nosepiece 4 , located in the middle of the frame 1 , comprises a substantially rectangular shaped recess 27 for receiving a bar clip 15 . the nosepiece 4 is further defined by an inlet on the upper surface of the nosepiece 4 , perpendicular to the bar clip 15 for receiving the single bar support 14 . once the lenses 3 are placed into the frame 1 , as described in the above embodiments , the single bar support 14 is slidably received in the frame 1 and over the lenses 3 thereby securing the lenses to the frame . a bar clip 15 , comprising first and second legs 28 and 29 on each end of the bar clip 15 , engages the recess 27 in the nose piece 4 . the legs 28 and 29 pass through the recess 27 and hook into the slot 26 of the single bar support 14 . the legs 28 and 29 aid to securely lock the bar clip 15 into the single bar support 14 . when the single bar support 14 is in a closed position ( not shown ), overhang the bar support completes the channel for the lens and the securing of the lens to the frame . fig1 illustrates the single bar support 14 as described above with an additional securing or locking mechanism . this embodiment includes the use of double sided adhesive tape 16 to further secure the lenses 3 to the frames 1 , strengthening the connection between the lenses and the front inner wall of the lens channel . other adhesives may be used in addition to double sided adhesive tape . double sided adhesive tape 16 is used to attach the lenses 3 to the inner wall of the frame channel . one side of the tape 16 attaches to the frames 1 , against the channel 5 wall . the opposite side of the tape 16 attaches to the lens 3 . the tape 16 helps to maintain the lenses 3 in place before the single bar support 14 is placed over the lenses 3 and frames 1 and further secures the lens and frame together . the adhesive or double sided tape 16 can be applied to any surface of channel 5 . fig9 through 12 show an embodiment of the invention using lenses 3 having a first notch 20 and second notch 21 . the locking bar or lever , in combination with adhesive or double sided tape , provides sufficient support for a lens with no protrusions to adequately withstand impact . fig1 a shows a pair of eyeglass frames 1 having a horizontal arm 17 and a nose piece 4 . a lens 3 is secured to the frame 1 using double sided tape or other adhesive . the frame 1 is of a conventional winged design . fig1 b shows the eyeglass assembly of fig1 a disassembled . there is a channel 5 in the horizontal arm 17 of the frame 1 . double sided tape or adhesive 16 is secured to the inside of the channel 5 . the lens 3 has a first protrusion 20 and a second protrusion 21 . double sided tape or adhesive 16 is secured to the lens 3 . the channel 5 is shaped to receive the first protrusion 20 of the lens 3 near the nosepiece 4 of the frame 1 . the channel 5 is also shaped to receive the second protrusion 21 of the lens 3 near the temple or end piece of the frame 1 . the combination of double sided tape or adhesive with the protrusions on the lens received in the recess of the horizontal arm will prevent the lens from ejecting out of the frame or breaking under impact . fig1 a shows another embodiment of the present invention . the frame 1 has a double bar support 12 in an open position . a channel 5 is located in the horizontal arm 17 of the frame 1 to receive the lenses 3 . the lens 3 has a surface with no protrusions 31 that is received by the channel 5 of the lens 1 . double sided tape or adhesive 16 is used to assist in securing the lens to the frame . once the lenses 3 are placed in the frame 1 , the levers 18 and 19 close over the lenses 3 , creating a wall and layering the lenses 3 between the levers 18 and 19 and the frame 1 . finally , a retaining mechanism ( not shown ) such as a screw or pin engages each lever 18 and 19 and frame 1 to mechanically lock the lenses 3 to the frame 1 . the outer edge of each lever 18 and 19 comprises an opening 22 for receiving the retaining mechanism . the inner screw or pin 23 is tightly attached to the frame 1 , enough such that it cannot slip out of the frame 1 , but the inner pin 23 is attached loosely enough to allow the levers 18 and 19 to pivot . this pivoting motion of the levers opens like a drawbridge , each lever pivoting upwardly , away from the lens 3 . this allows enough space for the frame to receive the lens 3 . fig1 b shows another embodiment of the present invention . fig1 b shows a frame 1 , a nosepiece 4 , two lenses 3 , a single bar support 14 , and a bar clip 15 . a single bar support 14 is a lengthwise bar comprising curved sections that follow the substantially arched sections of the frame . the single bar support 14 comprises first and second protrusions 24 and 25 attached to the inner wall of the bar , each protrusion adjacent to the nosepiece 4 and endpiece . the single bar is shaped to replicate the curvature of the lens , creating the channel that secures the frame and lenses together . additionally , the single bar support comprises of protrusions at the bar ends , and a recess in the nasal area , that allows the bar to slide down and nest into the frame endpieces and a slot in the center of the bar 26 for receiving the bar clip 15 . the nosepiece 4 , located in the middle of the frame 1 , comprises a substantially rectangular shaped recess 27 for receiving a bar clip 15 . the nosepiece 4 is further defined by an inlet on the upper surface of the nosepiece 4 , perpendicular to the bar clip 15 for receiving the single bar support 14 . the lenses 3 have a surface without protrusions 31 that is received in the channel 5 of the horizontal arm 17 . double sided tape or adhesive 16 is used to aid in securing the lens 3 to the channel 5 . the single bar support 14 is slidably received in the frame 1 and over the lenses 3 thereby securing the lenses to the frame . a bar clip 15 , comprising first and second legs 28 and 29 on each end of the bar clip 15 , engages the recess 27 in the nose piece 4 . the legs 28 and 29 pass through the recess 27 and hook into the slot 26 of the single bar support 14 . the legs 28 and 29 aid to securely lock the bar clip 15 into the single bar support 14 . fig1 c shows another embodiment of the present invention . a recess 5 in the horizontal arm 17 of the frame 1 receives a detached lens 3 . the upper surface of the lens 3 has no protrusions , but does have two recesses 34 for receiving a screw or pin . similar recesses are also present in the channel 5 of the horizontal arm 17 of the frame 1 . fig1 d shows the embodiment illustrated in fig1 c with the lens 3 and frame 1 assembled . screws or pins 33 are used to secure the lens 3 to the frame 1 . fig1 e shows a cross - section of the embodiment of the present invention illustrated in fig1 d . the screw or pin 33 extends through the lens 3 and into the frame 1 to secure the lens 3 to the frame 1 . when a particular embodiment has been chosen to illustrate the invention , it will be understood by those skilled in the art that various changes and modifications can be made therein without departing from the scope of the invention as defined in the appended claims .
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the invention is hereinafter described in detailed with reference to the accompany drawings and specific embodiments . if ue and a ca adopt different protocols , support and deal with the protocols in different ways , processing procedures of the ue and the ca are different . in the diff - serv model with a separate bearer control layer , the sip is usually adopted . in the following embodiment , a method for forwarding traffic is described , in which the sip is adopted . the following embodiment is described by an example in which bi - directional service connection is established . the edge device in the embodiments of the invention may be an er or a network element device with the function of a label edge router ( ler ). fig2 shows a flow chart illustrating a method for forwarding traffic in a bearer network in accordance with an embodiment of the invention . as shown in fig2 , the processing procedure is included in the process of establishing a service call connection and includes the steps as follows . step 201 : each of cas related to the current call instructs the cm managed by the ca to allocate a qos policy and reserve resources for the current call , and sends a resource reserving success message to other cas related to the current call after successfully allocating the qos policy and reserving the resources . step 202 ˜ 204 : each of the cas determines whether the cms managed by other cas related to the current call successfully allocate qos policies and reserve resources for the current call , that is , determines whether each of the cas receives the resource reserving success messages sent by other cas ; if yes , the cm managed by the ca issues the qos policy to an edge device in the management domain managed by the cm ; otherwise , the cm removes the qos policy and releases the resources . step 205 : the edge device receiving the qos policy starts to forward traffic matching the received qos policy . fig3 shows a flow chart illustrating a method for forwarding traffic in a bearer network in accordance with another embodiment of the invention . as shown in fig3 , the processing procedure is included in the process of established a service call connection and includes the steps as follows : step 301 : each of the cas related to the current call instructs the cm managed by the ca to allocate a qos policy and reserve resources for the current call , and sends a resource reserving success message to other cas related to the current call after the cm managed by the ca successfully allocates the qos policy and reserves the resources . step 302 : each of the cas instructs the cm managed by the ca to issue the qos policy and an instruction forbidding forward traffic to an edge device in the management domain managed by the cm , and the edge device receiving the qos policy and the instruction forbidding forward traffic does not forward traffic matching the received qos policy . steps 303 ˜ 305 : each of the cas determines whether to receive the resource reserving success messages sent by other cas related to the current call ; if yes , the ca instructs the cm managed by the ca to issue an instruction allowing forward traffic to the edge device in the management domain managed by the cm ; otherwise , the ca removes the qos policy and releases the resources . step 306 ; the edge device determines whether to receive the instruction allowing forward traffic ; if yes , starts to forward traffic matching the received qos policy . fig4 shows a flow chart illustrating a process of establishing a service connection and forwarding bi - directional traffic in a bearer network in which the service layer adopts the sip in accordance with an embodiment of the invention . as shown in fig4 , ca 1 is a calling ca , ca 2 is a called ca , er 1 is in the management domain managed by cm 1 and may import the traffic of this call to the bearer network , and cm 1 is the calling cm managed by ca 1 , er 2 is in the management domain managed by cm 3 and may export the traffic of this call from the bearer network , and cm 3 is the called cm managed by ca 2 . cm 2 is a midway cm by which this call request passes . as shown in fig4 , the process includes the steps as follows . step 401 : ca 1 receives a call request ( invite ) sent by ue 1 . step 402 ˜ 403 : ca 1 sends to ca 2 a call request carrying negotiation parameters of the communication capability of the calling side , such as the type of ue , decoding method of traffic and qos parameters . after receiving the call request , ca 2 returns to ca 1 a 200 ok response carrying negotiation parameters of the communication capability of the called side . after receiving the 200 ok response , ca 1 acquires the communications capabilities of the calling side and the called side , that is , ca 1 acquires the resource requirements and qos parameters including a delay parameter , a packet loss rate and a jitter . step 404 : ca 1 sends a forward resource request carrying the negotiated resource requirements and qos parameters to cm 1 . after receiving the forward resource request , cm 1 sends the forward resource request downward hop by hop till the path calculation of this separate operating network is completed or till the home cm of ue 2 , e . g ., cm 3 in this embodiment , is reached . each cm receiving the forward resource request selects a forward qos policy meeting the resource requirements and the qos parameters for the call , e . g ., a forward intra - domain policy route and a forward inter - domain policy route , and reserves the forward path resources . the forward intra - domain policy route is a forward policy route in the management domain managed by the cm while the forward inter - domain policy route is a forward policy route between the management domain managed by the cm and the management domain managed by the cm of the next hop . each of the cms forwards the selected forward qos policy to the cm 1 with a response message after selecting the forward qos policy and reserving the forward path resources . in step 404 , if a cm reserves the forward path resources successfully , the response message includes information of successfully reserving forward path resources ; otherwise , the response message includes information of unsuccessfully reserving forward path resource . in addition , the calculating method for each cm selecting the forward intra - domain policy route and the forward inter - domain policy route in step 404 may be referred to in chinese patents 03126471 . 9 , 03160068 . 9 and 03156821 . 1 , and will not be described herein . step 405 : cm 1 determines whether the received response message includes the information of successfully reserving forward path resources ; if yes , cm 1 issues the forward qos policy and traffic state information to er 1 and performs step 406 ; otherwise , cm 1 returns a resource reserving failure response to ca 1 and step 407 is performed . in the invention , a qos policy gated switch is set in the er in the bearer network for managing the er whether to forward traffic matching the forward qos policy or the backward qos policy . when the qos policy gated switch is turned on , the er forwards traffic matching the qos policy ; when the qos policy gated switch is turned off , the er does not forward traffic matching the qos policy . the traffic state information carries instruction information for managing the qos policy gated switch and a traffic identifier . the instruction information includes an instruction allowing forward traffic and an instruction forbidding forward traffic for turning on and turning off the qos policy gated switch , respectively . the traffic identifier is 5 - tuple information corresponding to the qos policy and the 5tuple information corresponding to the qos policy matches 5 - tuple information of the traffic allowed or forbidden to be forwarded . in step 405 , the traffic state information carries information for turning off the qos policy gated switch , e . g ., the instruction forbidding forward traffic , and the 5 - tuple information corresponding to the qos policy is the 5 - tuple information of the forward qos policy . after receiving the forward qos policy and the traffic state information , er 1 reads the traffic state information and acquires the instruction forbidding forward traffic and the 5 - tuple information of the forward qos policy , and then turns off the qos policy gated switch . thus , even if receiving forward traffic matching the 5 - tuple information of the forward qos policy , er 1 does not forward the forward traffic . alternatively , step 405 may include the steps of : cm 1 does not issue the qos policy but performs step 406 directly . step 406 : cm 1 returns a resource reserving success response to ca 1 . step 407 : ca 1 determines whether the received resource reserving response is a resource reserving success response ; if yes , ca 1 sends to ca 2 a update ( update ) message indicating that ca 1 agrees with the negotiation parameters of communication capability of ca 2 and carrying a forward path resource reserving result , which is equivalent to a resource reserving success message and indicates that ca 1 successfully reserves resources for the current call ; otherwise , ca 1 removes the qos policy and releases the reserved forward path resources . step 408 : after receiving the update message , ca 2 sends a backward resource request carrying the negotiated resource requirements and qos parameters to cm 3 . after receiving the backward resource request , cm 3 sends the backward resource request to the cm of the last hop till cm 1 is reached . each cm receiving the backward resource request selects a backward qos policy meeting the resource requirements and the qos parameters for the current call and reserves the backward path resources . the backward qos policy includes a backward intra - domain policy route and a backward inter - domain policy route . the backward intra - domain policy route is a backward policy route in the management domain managed by the cm , and the backward inter - domain policy route is a backward policy route between the management domain managed by the cm and the management domain managed by the cm of the last hop . each of the cms forwards the selected backward qos policy to the cm 3 with a response message after selecting the backward qos policy and reserving the backward path resources . in step 408 , if the cm reserves the backward path resources successfully , the response message includes information of successfully reserving backward path resources ; otherwise , the response message includes information of unsuccessfully reserving backward path resources . in addition , the calculation method for each cm selecting the backward qos policy in step 408 may be referred to in chinese patents 03126471 . 9 , 03160068 . 9 and 03156821 . 1 , and will not be described herein . step 409 : cm 3 determines whether the received response message includes information of successfully reserving backward path resources ; if yes , cm 3 issues the backward qos policy and traffic state information to er 2 and performs step 410 ; otherwise , cm 3 returns a resource reserving failure response to ca 2 and step 411 is performed . step 410 : cm 3 returns a resource reserving success response to ca 2 . in step 410 , the traffic state information carries an instruction allowing forward traffic for turning on the qos policy gated switch and the 5 - tuple information matching the backward qos policy . if er 2 receives backward traffic matching the backward qos policy , er 2 forwards the backward traffic after receiving the traffic state information . step 411 : ca 2 determines whether the received resource reserving response is a resource reserving success response ; if yes , ca 2 sends to ca 1 a 200 ok message indicating that ca 2 agrees with the negotiating parameters of communication capability of ca 1 and a forward path resource reserving result in the update message and carrying a backward path resource reserving result , which is equivalent to a resource reserving success message , and sends a 200 ok response to ue 2 ; otherwise , ca 2 removes the qos policy and releases the reserved backward path resources , and returns a resource reserving failure message to ca 1 . step 412 : ca 1 receives the response message of ca 2 ; if the response message is a 200 ok message , ca 1 instructs cm 1 to issue to er 1 traffic state information carrying an instruction allowing forward traffic for turning on the qos policy gated switch and the 5 - tuple information matching the forward qos policy , and cm 1 returns an execution response to ca 1 after issuing the traffic state information . after receiving the traffic state information , er 1 forwards forward traffic matching the 5 - tuple of the forward qos policy based on the route of the forward qos policy if er 1 receives the forward traffic . alternatively , if cm 1 does not issue the forward qos policy , ca 1 instructs cm 1 to issue the forward qos policy and traffic state information carrying an instruction allowing forward traffic to er 1 . cm 1 returns an execution response to ca 1 after issuing the forward qos policy and the traffic state information . after receiving the forward qos policy and the allowing forward instruction . er 1 forwards forward traffic matching the forward qos policy based on the forward qos policy if er 1 receives the forward traffic . ca 1 removes the qos policy and releases the reserved forward path resources if ca 1 receives a resource reserving failure response . step 413 : ca 1 sends a 200 ok message to ue 1 to notify ue 1 to start communicating after receiving the execution response of cm 1 , and the traffic sent by ue 1 is forwarded to ue 2 through the bearer network . in the embodiments of the invention , if the resource manager supports applying for bi - directional path resources only once , ca 1 sends a bi - directional resource request to cm 1 in step 404 . after receiving the bi - directional resource request , cm 1 sends the bi - directional resource request downward hop by hop till cm 3 is reached . each cm receiving the bi - directional resource request selects a bi - directional qos policy meeting the resource requirements and the qos parameters for the current call and reserves bi - directional path resources . after selecting the bi - directional qos policy and reserving the bi - directional path resources , each cm forwards the information of the selected forward qos policy and the reserved forward path resources to cm 1 hop by hop with a response message , and forwards the information of the selected backward qos policy and the reserved backward path resources to cm 3 hop by hop . cm 1 performs steps 405 and 406 , cm 3 performs steps 40 i and 410 , and the operation of ca 1 and ca 2 is the same as that in the above process . in the embodiment shown in fig4 , the multiple bearer network resource managers are in a single separate operating network . if a service connection crosses multiple separate operating networks and relates to multiple cas , the level number of cas in the embodiments of the invention increases correspondingly . however , the processing of the cas , the cms and the edge devices in the bearer network is the same as that in the embodiment shown in fig4 . in the embodiments of the invention , after a connection is established for a service call request , a ca may instruct the cm at any moment as demanded by the service to issue to the er traffic state information for managing the qos policy gated switch , and the traffic state information carries an instruction allowing forward traffic or an instruction forbidding forward traffic , and the 5 - tuple information of the traffic allowed or forbidden to be forwarded . after receiving the traffic state information , if the traffic state information carries an instruction allowing forward traffic , the er forwards the traffic based on the qos policy matching the 5 - tuple of the traffic after receiving traffic matching the 5 - tuple information of the traffic allowed to be forwarded . if the traffic state information carries an instruction forbidden forward traffic , the er does not forward the traffic after receiving traffic matching the 5 - tuple information of the traffic forbidden to be forwarded . with the above method of the embodiments of the invention , in an end - to - end service connection , the bearer network may be managed to forward or stop forwarding traffic at any moment . therefore , the embodiments of the invention provides a more flexible resource reserving method for the service layer , and are convenient for the development of an ngn value added service with demand for qos . for example , the call hold service in the ngn allows ue to suspend the current call during the call , initiate a new call , and switch between the two calls after the new call is established . for the call hold service , when keeping the information of the original service connection , ca 1 and cm need to only issue an instruction of turning on or off the qos policy gated switch of the original service connection to the er in the bearer network so as to switch the call of the service connection between being turned on and being turned off and thus meet the demand of the call hold service . with the embodiments of the invention , the qos policy of an original service connection may also be prevented from being usurped . for example , once the 5 - tuple information of a service connection is blabbed , another ue may use the 5 - tuple information to send traffic to a called , and when the traffic reaches an er in the bearer network , the er forwards the traffic based on the original qos policy since the 5tuple information is the same as that of the original service connection . thus , the qos policy of the original service connection is usurped . in the embodiments of the invention , a qos policy gated switch is provided for a qos policy , and the qos policy of the original service connection will not be usurped if the qos policy gated switch is in the state of “ off ”. when the service connection is disconnected for the moment , traffic state information for managing the qos policy gated switch of the service connection is issued to the er in the bearer network to set the qos policy gated switch corresponding to the service connection as the state of “ off ”, and thus the bearer network does not forward the traffic of the service connection . when the service connection is put through , traffic state information for managing the qos policy gated switch of the service connection is issued to the er in the bearer network to set the qos policy gated switch of the service connection as the state of “ on ”, and the bearer network continues to forward the traffic of the service connection using the original qos policy instead of applying a new qos policy , and thus the resource utilization efficiency of the bearer network may be improved . while the qos policy of original service connection is kept , a new service connection may apply for resources based on the process of the embodiments of the invention . the above process is a flow for establishing a bi - directional service connection . for the flow for establishing a unidirectional service connection , if multiple cas reserve resources for the call of the service connection , the above method of the embodiments of the invention may also be applied only if the process of allocating the backward qos policy and reserving the resources is omitted . the foregoing is only preferred embodiments of the invention . the protection scope of the invention , however , is not limited to the above description . any change or substitution , within the technical scope disclosed by the invention , easily occurring to those skilled in the art should be covered by the protection scope of the invention .
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in various implementations , different blades of the razor have different tip radii and thus different relative sharpness . the blade sharpness may be quantified by measuring cutter force , which correlates with sharpness . cutter force is measured by the wool felt cutter test , which measures the cutter forces of the blade by measuring the force required by each blade to cut through wool felt . the cutter force of each blade is determined by measuring the force required by each blade to cut through wool felt . each blade is run through the wool felt cutter 5 times and the force of each cut is measured on a recorder . the lowest of 5 cuts is defined as the cutter force . the combination and positioning of sharper and duller blades can be selected so as to provide a razor with desired performance characteristics . generally , the sharper the blade the lower the engagement time in the hair . increased engagement time , achieved with relatively duller blades , will result in hairs being pulled from the follicle during cutting . however , the manner in which a particular blade functions will depend on its exposure as well as on its sharpness . the blades may also have different coefficients of friction , which will affect how the blade interacts with the shaver &# 39 ; s skin and hair . for example , a blade having a higher coefficient of friction will tend to pull hair from the follicle while cutting it , as will be discussed in further detail below . these two variables ( tip radius and coefficient of friction ) will be discussed in turn below . referring to fig1 , a blade unit of a razor cartridge includes a frame 1 defining a guard 2 , and a cap 3 . as shown the cap comprises a lubricating strip 4 mounted on the frame . the strip may be of a form well known in the art . carried by the frame are primary , secondary and tertiary blades 11 , 12 , 13 having parallel sharpened edges . the blades may be supported firmly by the frame to remain substantially fixed in the positions in which they are depicted ( subject to any resilient deformation which the blades undergo under the forces applied against the blades during shaving ). alternatively the blades may be supported for limited movement against spring restoring forces , e . g . in a downward direction as viewed in the drawings . in the blade unit of fig1 , the edges of all three blades lie in a common plane p . the blade exposure is defined to be the perpendicular distance or height of the blade edge measured with respect to a plane tangential to the skin contacting surfaces of the blade unit elements next in front of and next behind the edge . therefore , for the three - bladed blade unit shown in fig1 , the exposure of the first or primary blade is measured with reference to a plane tangential to the guard and the edge of the second blade , and the exposure of the third or tertiary blade is measured with reference to a plane tangential to the edge of the second blade and the cap . blade exposure may be neutral , if the tip is in the plane ; positive , if the tip extends beyond the plane towards the user ; or negative , if the tip is recessed behind the plane , away from the user . generally , the greater the exposure , the closer the blade will tend to shave , but also the more likelihood that the blade will nick or cut the user . blades with negative exposures will nonetheless cut hair , due to the deformable nature of skin and thus the tendency of the skin bulge to flow into the recessed area and towards the blade . in the embodiment shown in fig1 , the primary blade 11 has a negative exposure ( e . g ., − 0 . 04 mm ), the exposure of the secondary blade 12 is zero , and the exposure of the tertiary blade 13 is positive ( e . g ., + 0 . 06 mm ), with the edges of all three blades lying in plane p . thus , there is a progressive increase in blade exposure from the leading blade 11 to the trailing blade 13 . razor cartridges having blades with progressively different exposures are described in u . s . pat . no . 6 , 212 , 777 , the complete disclosure of which is hereby incorporated by reference herein . in one embodiment , the primary blade 11 , which has a negative exposure , has a smaller tip radius and therefore is sharper and exhibits a lower cutter force than the secondary blade 12 . preferably , the tertiary blade 13 has a smaller tip radius than the secondary blade , e . g ., a tip radius approximately equal to the tip radius of the primary blade or in between the tip radii of the primary and secondary blades . in this case , the primary blade will tend to cut hair , and the tertiary blade will cut the hair that is pulled by the secondary blade . the inclusion of the relatively dull secondary blade tends to reduce the incidence of nicks and cuts , without compromising shaving closeness . the primary blade may be quite sharp without significant risk of nicks and cuts due to its negative exposure . in some alternative embodiments , the tertiary blade , which has the highest level of exposure , may have a tip radius that is equal to or greater than that of the secondary blade . this option is advantageous for users who have a high propensity for nicking and cutting . in some instances , the primary blade has a tip radius of less than 300 angstroms , e . g ., about 235 to about 295 , resulting in a cutter force of less than about 1 . 15 lbs , preferably less than about 1 . 05 lbs . this is considered herein to be a relatively sharp blade . if it is desired that the primary blade be sharper than the secondary blade , the tip radius of the primary blade may be selected to provide a cutter force of at least about 0 . 1 lbs lower , preferably at least about 0 . 4 lbs lower , than the cutter force of the secondary blade . in general , the tip radius of the secondary blade may be from about 600 to about 1000 angstroms , if a quite dull secondary blade is desired , or from about 350 to about 450 angstroms , if it is desired that the secondary blade be only slightly less sharp than the primary blade . a tip radius of 600 to 1000 angstroms will generally produce a cutter force of about 1 . 75 to 2 . 0 lbs , whereas a tip radius of 350 to 450 angstroms will generally produce a cutter force of about 1 . 3 to 1 . 6 lbs . the tertiary blade may have a tip radius of about 235 to about 1000 angstroms , depending on whether it is desired that the tertiary blade be relatively sharper or duller than the other blades . in other embodiments , it may be desirable to have the primary blade be less sharp than the secondary blade . if the primary blade is less sharp than the secondary blade , the primary blade will tend to pull the hairs further out of the follicle during cutting than a normally sharp blade , so that after cutting the hairs will be further out of the follicle than with a normally sharp blade and thus be cut further down the shaft by the second blade so that when they retract into the follicles their ends will be beneath the skin surface . for example , the primary blade may have a tip radius of from about 350 to about 450 angstroms , while the secondary blade has a tip radius of from about 235 to about 295 angstroms . in these implementations , the tertiary blade may have the same sharpness as the secondary blade , may be sharper or duller than the secondary blade , or may even be as dull as or duller than the primary blade . having a relatively dull tertiary blade will tend to give a very safe shave , with little danger of nicking or cutting , while having a relatively sharp tertiary blade will provide a very close shave . the tip radius r may be varied by controlling the properties of the coatings applied to the blade tip , for example by adjusting the sputtering conditions . the bias on the blades , prior to and / or during sputter deposition , can be varied to effect the etch rate . generally , blades processed with high bias voltage ( e . g ., greater than − 1000 vdc ) yield smaller tip radii and thus lower cutter forces than blades processed at low bias voltages ( e . g ., less than − 200 volts direct current ( vdc )). the ion to atom ratio can also be varied to control the deposition and etch rates . alternatively , the blades may be ion etched post - sputtering to reduce the tip radius . in this case the sputtering conditions would be controlled to provide a high tip radius and then the tip radius would be reduced to a desired level using ion etching . suitable processes are described in u . s . pat . no . 4 , 933 , 058 , the disclosure of which is incorporated herein by reference . another alternative would be to vary the tip radius by controlling the sharpening process so as to obtain a desired tip radius during sharpening . if desired , the razor can include four , five or more blades . the blades may have various combinations of sharpness . for example , in a razor having four blades , two blades with higher cutter forces may be positioned to alternate with two blades having lower cutter forces . the blades with the higher cutter forces may be the primary and tertiary blades , or in an alternate embodiment may be the secondary and quaternary blades . in these and other embodiments , the blade ( s ) having a higher cutter force may in some cases have a tip radius of from about 350 to about 450 angstroms , while the blade ( s ) having a lower cutter force has a tip radius of from about 235 to about 295 angstroms . in determining the desired degree of sharpness of the various blades , the principles discussed above apply , i . e ., a duller blade generally will provide greater safety and will apply tension to hair and pull it from the follicle allowing it to be cut more closely by subsequent blades , while a sharper blade will cut hair more closely and with less cutter force . generally , providing duller blades in more exposed positions will reduce the incidence of nicks and cuts , while providing sharper blades in these positions will provide a closer , more comfortable shave . it has also been noted by the inventors that for certain women &# 39 ; s razors it is generally desirable to provide a sharp blade in the primary position , regardless of the number of blades used . a desired combination of blades of differing sharpness can be determined based on the desired performance attributes of the razor . referring again to fig1 , primary blade 11 may have a higher coefficient of friction ( measured as a higher cutter force ) than secondary blade 11 . when the razor is in use , the primary blade 11 will contact the hair before the secondary blade 12 . as blade 11 passes the user &# 39 ; s skin , it engages a hair , pulling it and thereby extending the hair outside of the hair follicle , and cutting the hair to a first length . as the secondary blade 12 passes the user &# 39 ; s skin it cuts the hair again , to a shorter length . subsequent to cutting , the hair settles back into the hair follicle below the surface of the skin . the tertiary blade can have any desired cutter force , typically within a 0 . 8 to 1 . 5 pound range . many other combinations of blades having different coefficients of friction may be used , e . g ., a blade having a relatively low coefficient of friction in the primary position , a blade having a relatively higher coefficient of friction in the secondary position , and a blade having a relatively low coefficient of friction in the tertiary position . in some instances , the blade ( s ) having relatively low coefficients of friction have cutter forces ( as measured using a wool felt cutter ) at least about 0 . 1 lbs greater than the cutter forces of the blade ( s ) having relatively high coefficients of friction . in general , the cutter force of the low coefficient of friction blade ( s ) is between about 0 . 1 and 1 . 0 lbs . ( e . g ., at least about 0 . 2 , 0 . 3 , 0 . 4 , or 0 . 5 lbs . and at most about 1 . 0 , 0 . 9 , 0 . 8 , 0 . 7 or 0 . 6 lbs .) less than that of the blades having relatively higher coefficients of friction . providing a blade having higher cutter forces can be accomplished in a variety of ways . in some instances , it is desirable to provide a first blade having a modified polymer coating . for example , the blade may include a teflon coating that is modified , for example using plasma etching , to incrementally increase its surface friction . exposure of the coated blade to plasma under suitable conditions can cause both chemical and physical changes to occur on the polymer coating . the changes can affect a variety of properties of the coating , including but not limited to roughness , wettability , cross - linking , and molecular weight , each of which can affect the cutter force of the blade . suitable methods of modifying the polymer coating are described in u . s . ser . no . 11 / 392 , 127 filed mar . 29 , 2006 and entitled razor blades and razors , the complete disclosure of which is hereby incorporated herein by reference . in some instances , a blade can be used that is substantially free of polymer coating . however , a blade without any polymer coating can result in an undesirable decrease in comfort . for example , it may pull the hair too aggressively . many different combinations of these three parameters are contemplated with different combinations yielding different razor performance characteristics . for example , in some cases , it is desirable to have a relatively sharp ( small tip radius ) blade that has a relatively high coefficient of friction ( high cutter force due to the surface characteristics of the blade rather than the tip radius ). such a blade will tend to cut hair comfortably , while also providing a hysteresis effect ( pulling the hair from the follicle so that the next blade can cut it more closely before it retracts into the follicle ). thus , it may be desirable to have the primary blade have a small tip radius and relatively high coefficient of friction . the secondary blade may have a larger tip radius , due to its relatively higher blade exposure , and a lower coefficient of friction , since it is not necessary that this blade pull hair . the characteristics of the tertiary blade may be selected to suit the needs of a particular user group , e . g ., avoidance of nicking and cutting ( large tip radius ) or closeness ( small tip radius ; high coefficient of friction if a fourth blade is used ). 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 .
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before the present methods and treatment methodology are described , it is to be understood that this invention is not limited to particular methods , and experimental conditions described , as such methods and conditions may vary . it is also to be understood that the terminology used herein is for purposes of describing particular embodiments only , and is not intended to be limiting , since the scope of the present invention will be limited only in the appended claims . as used in this specification and the appended claims , the singular forms “ a ”, “ an ”, and “ the ” include plural references unless the context clearly dictates otherwise . thus , for example , references to “ the method ” includes one or more methods , and / or steps of the type described herein and / or which will become apparent to those persons skilled in the art upon reading this disclosure and so forth . unless defined otherwise , 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 any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the invention , the preferred methods and materials are now described . all publications mentioned herein are incorporated herein by reference . the terms used herein have the meanings recognized and known to those of skill in the art , however , for convenience and completeness , particular terms and their meanings are set forth below . “ agent ” refers to all materials that may be used to prepare pharmaceutical and diagnostic compositions , or that may be compounds , nucleic acids , polypeptides , fragments , isoforms , variants , or other materials that may be used independently for such purposes , all in accordance with the present invention . the term “ antibody ” as used herein includes intact molecules as well as fragments thereof such as fab and f ( ab ′) 2 , which are capable of binding the epitopic determinant . antibodies that bind the proteins of the present invention can be prepared using intact polypeptides or fragments containing small peptides of interest as the immunizing antigen attached to a carrier molecule . commonly used carriers that are chemically coupled to peptides include bovine serum albumin and thyroglobulin . the coupled peptide is then used to immunize the animal ( e . g , a mouse , rat or rabbit ). the antibody may be a “ chimeric antibody ”, which refers to a molecule in which different portions are derived from different animal species , such as those having a human immunoglobulin constant region and a variable region derived from a murine mab . ( see , e . g ., cabilly et al ., u . s . pat . no . 4 , 816 , 567 ; and boss et al ., u . s . pat . no . 4 , 816 , 397 .). the antibody may be a human or a humanized antibody . the antibody may be a single chain antibody . the antibody may be prepared in mice , rats , rabbits , goats , sheep , swine , dogs , cats , or horses . “ analog ” as used herein , refers to a chemical compound , a nucleotide , a protein , or a polypeptide that possesses similar or identical activity or function ( s ) as the chemical compounds , nucleotides , proteins or polypeptides having the desired activity and therapeutic effect of the present invention ( eg . to inhibit cellular proliferation and to sensitize for , or potentiate chemotherapy or radiation therapy for treatment of mammals having cancer or hyperproliferative disorders ), but need not necessarily comprise a sequence that is similar or identical to the sequence of the preferred embodiment , or possess a structure that is similar or identical to the agents of the present invention . as used herein , a nucleic acid or nucleotide sequence , or an amino acid sequence of a protein or polypeptide is “ similar ” to that of a nucleic acid , nucleotide or protein or polypeptide having the desired activity if it satisfies at least one of the following criteria : ( a ) the nucleic acid , nucleotide , protein or polypeptide has a sequence that is at least 30 % ( more preferably , at least 35 %, at least 40 %, at least 45 %, at least 50 %, at least 55 %, at least 60 %, at least 65 %, at least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 90 %, at least 95 % or at least 99 %) identical to the nucleic acid , nucleotide , protein or polypeptide sequences having the desired activity as described herein ( b ) the polypeptide is encoded by a nucleotide sequence that hybridizes under stringent conditions to a nucleotide sequence encoding at least 5 amino acid residues ( more preferably , at least 10 amino acid residues , at least 15 amino acid residues , at least 20 amino acid residues , at least 25 amino acid residues , at least 40 amino acid residues , at least 50 amino acid residues , at least 60 amino residues , at least 70 amino acid residues , atea amino acid residues , at least 90 amino acid residues , at least 100 amino acid residues , at least 125 amino acid residues , or at least 150 amino acid residues ) of the aapi ; or ( c ) the polypeptide is encoded by a nucleotide sequence that is at least 30 % ( more preferably , at least 35 %, at least 40 %, at least 45 %, at least 50 %, at least 55 %, at least 60 %, at least 65 %, at least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 90 %, at least 95 % or at least 99 %) identical to the nucleotide sequence encoding the polypeptides of the present invention having the desired therapeutic effect . as used herein , a polypeptide with “ similar structure ” to that of the preferred embodiments of the invention refers to a polypeptide that has a similar secondary , tertiary or quaternary structure as that of the preferred embodiment . the structure of a polypeptide can determined by methods known to those skilled in the art , including but not limited to , x - ray crystallography , nuclear magnetic resonance , and crystallographic electron microscopy . “ derivative ” refers to either a protein or polypeptide that comprises an amino acid sequence of a parent protein or polypeptide that has been altered by the introduction of amino acid residue substitutions , deletions or additions , or a nucleic acid or nucleotide that has been modified by either introduction of nucleotide substitutions or deletions , additions or mutations . the derivative nucleic acid , nucleotide , protein or polypeptide possesses a similar or identical function as the parent polypeptide . it may also refer to chemically synthesized organic molecules that are functionally equivalent to the active parent compound , but may be structurally different . it may also refer to chemically similar compounds which have been chemically altered to increase bioavailability , absorption , or to decrease toxicity . “ fragment ” refers to either a protein or polypeptide comprising an amino acid sequence of at least 5 amino acid residues ( preferably , at least 10 amino acid residues , at least 15 amino acid residues , at least 20 amino acid residues , at least 25 amino acid residues , at least 40 amino acid residues , at least 50 amino acid residues , at least 60 amino residues , at least 70 amino acid residues , at least 80 amino acid residues , at least 90 amino acid residues , at least 100 amino acid residues , at least 125 amino acid residues , at least 150 amino acid residues , at least 175 amino acid residues , at least 200 amino acid residues , or at least 250 amino acid residues ) of the amino acid sequence of a parent protein or polypeptide , or a nucleic acid comprising a nucleotide sequence of at least 10 base pairs ( preferably at least 20 base pairs , at least 30 base pairs , at least 40 base pairs , at least 50 base pairs , at least 50 base pairs , at least 100 base pairs , at least 200 base pairs ) of the nucleotide sequence of the parent nucleic acid . any given fragment may or may not possess a functional activity of the parent nucleic acid or protein or polypeptide . a “ therapeutically effective amount ” is an amount sufficient to decrease or prevent the symptoms associated with the cancer or hyperproliferative disorders or other related conditions contemplated for therapy with the compositions of the present invention . “ treatment ” refers to therapy , prevention and prophylaxis and particularly refers to the administration of medicine or the performance of medical procedures with respect to a patient , for either prophylaxis ( prevention ) or to cure or reduce the extent of or likelihood of occurrence of the infirmity or malady or condition or event in the instance where the patient is afflicted . “ combination therapy ” refers to the use of the agents of the present invention with other active agents or treatment modalities , in the manner of the present invention for treatment of cancers or hyperproliferative disorders . these other agents or treatments may include drugs such as other anti - cancer drugs such as those that are standardly used to treat various cancers , radiation therapy , anti - viral drugs , corticosteroids , non - steroidal anti - inflammatory compounds , other agents useful in treating or alleviating pain , growth factors , cytokines , or colony stimulating factors . the combined use of the agents of the present invention with these other therapies or treatment modalities may be concurrent , or the two treatments may be divided up such that the agent of the present invention may be given prior to or after the other therapy or treatment modality . “ local administration ” means direct administration by a non - systemic route at or in the vicinity of the site of an affliction , disorder , or perceived pain . “ slow release formulation ” refers to a formulation designed to release a therapeutically effective amount of a drug or other active agent such as a polypeptide or a synthetic compound over an extended period of time , with the result being a reduction in the number of treatments necessary to achieve the desired therapeutic effect . in the matter of the present invention , a slow release formulation would decrease the number of treatments necessary to achieve the desired effect in terms of inhibiting cellular proliferation and decreasing the tumor burden or metastatic potential of a cancer or hyperproliferative disorder . the term “ clonogenic potential ” refers to the ability of single cells to divide and grow into a cluster of cells . this is a characteristic of metastatic cancer cells in the body . in the lab , it is a reflection of many factors , including viability , health of the cell , injury , and ability to divide on the support provided in the tissue culture dish or in suspension “ egf ” is epidermal growth factor ; a protein that binds to cell surface receptors and initiates signals that tell the cell to divide , crawl and survive . “ igf ” is insulin - like growth factor ; a protein that binds to the insulin - like growth factor receptor that initiates signals that tell the cell to do perform a variety of function from cell division survival , depending on the cell type . “ fgf - 2 ” is fibroblast growth factor 2 , basic fibroblast growth factor ; a protein that binds to cell surface receptors that initiates a variety of signals that tell different cells to perform different functions . in breast cancer , it can act as a differentiation factor , inhibiting growth and motility . the term “ hyperproliferative disorders ” refers to diseases that result from the abnormal growth of cells . these can include cancers , pre - malignant states as well as inflammatory states such as rheumatoid arthritis or conditions such as psoriasis . “ integrins ” are intrinsic cell surface proteins . they mediate cell adhesion by binding with components of the extra cellular matrix , such as fibronectin . this adhesion process is closely tied to the cells ability to survive and reproduce . many different integrins have been discovered and most have similar structural features eg . they are heterodimeric transmembrane proteins and contain an alpha subunit and a beta subunit . the major fibronectin receptor on most cells is the alpha 5 , beta 1 integrin , also referred to in the present application as α5β1 . this integrin interacts with the rgd site of the fibronectin molecule . a kinase is a protein that acts as an enzyme to transfer a phosphate group onto another protein . a “ kinase inhibitor ” blocks the action of such a protein a “ transcription inhibitor ” is a chemical or biological that interferes with the synthesis of messenger rna from a dna template . “ atra ” refers to all - trans retinoic acid ; a member of a family of compounds called retinoids that act by binding to nuclear receptors called retinoic acid receptors and retinoid x receptors that , when bound to their retinoid ligands , act as transcription factors . atra inhibits cell proliferation , induces cell death and potentiates chemotherapy agents in breast cancer cells . as used herein , the term “ modified peptide ” may be used to refer to a peptide that is capable of binding to a protein and modulating its activity ( e . g ., a cell surface receptor ). modified peptides may possess features that , for example , modulate ( increase or decrease ) binding , alter the half - life of the peptide , decrease renal clearance , or improve absorption . as used herein , the term “ amino acid ” and any reference to a specific amino acid is meant to include naturally occurring proteogenic amino acids as well as non - naturally occurring amino acids such as amino acid analogs . one of skill in the art would know that this definition includes , unless otherwise specifically indicated , naturally occurring proteogenic ( d ) or ( l ) amino acids , chemically modified amino , acids , including amino acid analogs such as penicillamine ( 3 - mercapto - d - valine ), naturally occurring non - proteogenic amino acids such as norleucine and chemically synthesized compounds that have properties known in the art to be characteristic of an amino acid . as used herein , the term “ proteogenic ” indicates that the amino acid can be incorporated into a protein in a cell through well - known metabolic pathways . the choice of including an ( l )- or a ( d )- amino acid into a peptide of the present invention depends , in part , on the desired characteristics of the peptide . for example , the incorporation of one or more ( d )- amino acids can confer increasing stability on the peptide in vitro or in vivo . the incorporation of one or more ( d )- amino acids also can increase or decrease the binding activity of the peptide as determined , for example , using the binding assays described herein , or other methods well known in the art . in some cases it is desirable to design a peptide which retains activity for a short period of time , for example , when designing a peptide to administer to a subject . in these cases , the incorporation of one or more . ( l )- amino acids in the peptide can allow endogenous peptidases in the subject to digest the peptide in vivo , thereby limiting the subject &# 39 ; s exposure to an active peptide . as used herein , the term “ amino acid equivalent ” refers to compounds which depart from the structure of the naturally occurring amino acids , but which have substantially the structure of an amino acid , such that they can be substituted within a peptide which retains is biological activity . thus , for example , amino acid equivalents can include amino acids having side chain modifications or substitutions , and also include related organic acids , amides or the like . the term “ amino acid ” is intended to include amino acid equivalents . the term “ residues ” refers both to amino acids and amino acid equivalents . as used herein , the term “ peptide ” is used in its broadest sense to refer to compounds containing amino acid equivalents or other non - amino groups , while still retaining the desired functional activity of a peptide . peptide equivalents can differ from conventional peptides by the replacement of one or more amino acids with related organic acids ( such as paba ), amino acids or the like or the substitution or modification of side chains or functional groups . it is to be understood that limited modifications can be made to a peptide without destroying its biological function . thus , modification of a peptides of the present invention that does not completely destroy its activity are within the definition of the compound claims as such . modifications can include , for example , additions , deletions , or substitutions of amino acids residues , substitutions with compounds that mimic amino acid structure or functions , as well as the addition of chemical moieties such as amino or acetyl groups . the modifications can be deliberate or accidental , and can be modifications of the composition or the structure . an exemplary cell surface receptor envisioned for targeting by a peptide or “ modified peptide ” of the invention is a member of the integrin receptor family . in an embodiment of the invention , a “ modified peptide ” may be used to inhibit integrin receptor activity , including , without limitation , the ability of integrin - expressing cells to bind to extracellular matrix proteins and surrounding cells . modified peptides capable of inhibiting integrin binding / activity have been described in u . s . pat . nos . 5 , 536 , 814 ; 5 , 627 , 263 ; 5 , 912 , 234 ; 5 , 922 , 676 ; 5 , 981 , 478 ; 5 , 912 , 234 ; and 6 , 177 , 542 , the entire contents of each of which is herein incorporated in its entirety by reference . retinoids are a class of compounds consisting of four isoprenoid units joined in a head - to - tail manner . all retinoids may be formally derived from a monocyclic parent compound containing five carbon - carbon double bonds and a functional group at the terminus of the acyclic portion . derivatives of retinoids may be generated by means known to skilled artisans to render the retinoid derivative more therapeutically effective . a retinoid derivative may be , for example , an aldehyde derivative , a carboxylic acid derivative , a substituted derivative , a hydrogenated derivative , or it may be derivatized by functional substitution of a basic hydrocarbon . retinoid derivatives may , for example , be generated that are more specifically targeted to hyperproliferative cells . as used herein , the term “ retinoid derivative ” may also be used to refer to a compound or agent having retinoid activity , but which does not necessarily act through a retinoid receptor . as used herein , the term “ biological therapy ” refers to a therapeutic regimen designed to enhance a subject &# 39 ; s or patient &# 39 ; s response to treatment administered to reduce the number of cancer cells and / or symptoms associated with cancer . in general , “ biological therapy ” involves the use of a variety of cytokines , including , but not limited to , growth factors , interferons , colony stimulating factors , tumor necrosis factors , and interleukins . as used herein , the term “ sensitization ” or “ sensitizing ” refers to treating a subject so as to render the subject or cells therein more susceptible to the effects of a therapeutic regimen ; a number of sensitizing agents have been characterized that render cancer cells , for example , more susceptible to therapeutic modalities designed to eradicate cancer from a subject . such sensitizing agents have been previously described in , for example , u . s . pat . no . 5 , 436 , 337 , the entire contents of which is incorporated herein by reference in its entirety . as used herein , the phrase “ disrupting survival signaling from the microenvironment ” refers to a situation in which interactions between integrins and their ligands are reduced or decreased . such interactions may be physically blocked using antibodies or peptides ; or may be prevented by decreasing the cell surface expression levels of integrins via transcriptional inhibition ; or by blocking survival signaling initiated by integrin receptor ligation by proteins in the microenvironment . the present invention relates to the novel finding that increased expression of the alpha - 5 beta - 1 integrin on metastasized breast cancer cells in the bone marrow transmit a survival signal from matrix proteins in the bone marrow . ligation of the integrin to fibronectin interrupts integrin - mediated cell death signaling and initiates the cell survival signaling that leads to dormancy , protection from chemotherapy and ultimately relapse in the breast cancer patient . the invention provides for a method to inhibit the expression of the integrin and to interrupt specific elements of the survival pathway that will allow traditional chemotherapy or radiation therapy to be utilized to kill the remaining cells in the bone marrow and avoid a relapse and ultimately resistance by the cells and the death of the patient suffering from a hyperproliferative disorder such as but not limited to breast cancer , or prostate cancer . the over expression of alpha - 5 beta - 1 is down regulated through the use of kinase or transcription inhibitors such as demonstrated in fig1 . the schema of fig1 demonstrates the fate of metastatic cells in the bone marrow and the effect of fibronectin ligation through its integrin receptor alpha 5 beta 1 on maintaining survival and chemoresistance . disruption of this interaction by decreasing synthesis of the integrin or disruption of its interaction with its ligand would allow the cells to become sensitive to chemotherapy and undergo cell death . in the present invention , evidence is provided which supports a paradigm in which fgf - 2 initiates a more differentiated , dormant state in well - differentiated micrometastatic breast cancer cells . this encompasses cell cycle arrest and changes in the integrin repertoire . cells with improperly ligated integrins such as α5β1 , upregulated by fgf - 2 in fibroblasts and endothelial cells undergo cell death , likely due to ligand incompatibility . ligation of integrin α5β1 by fibronectin , a component of bone marrow stroma , which can initiate survival signaling ( matter , m . l , & amp ; ruoslahti , e . ( 2001 ) j . biol . chem . 276 , 27757 - 27763 ; lee , j . w . & amp ; juliano , r . l . ( 2000 ) molecular biology of the cell 11 , 1973 - 1987 ), promotes survival of fgf - 2 - responsive cells . in particular , the present invention is directed to methods for disrupting survival signaling from the microenvironment in cancer cells , wherein said disrupting results in sensitizing cells to chemotherapy , biological therapies or radiation therapy of cancer micrometastases and hyperproliferative disorders in a mammal . the method comprises blocking the interaction of an integrin with an extracellular matrix protein of the microenvironment . a preferred embodiment includes the alpha 5 beta 1 integrin and the preferred extracellular matrix protein is fibronectin . the invention is directed to treating primary tumors , tumor metastasis , micrometastases and hyperproliferative disorders . a further preferred embodiment is treating breast cancer or prostate cancer . a further preferred embodiment comprises administration of an antibody specific for an integrin or a blocking peptide or modified peptide that disrupts interaction of the integrin with the extracellular matrix . a yet further preferred embodiment comprises administration of all trans retinoic acid or a retinoic acid derivative . a yet further preferred embodiment comprises decreasing expression of cell surface integrins with a transcription inhibitor . the method also comprises treatment with an inhibitor of a kinase , said kinase selected from the group consisting of mep / map kinase , p38 , rhoa , rho kinase , pi3 kinase , pkc , and pka . the methods further comprise blocking survival signaling initiated by ligation of integrins by microenvironment proteins . the method also comprises use of the inhibitors selected from the group consisting of ly294002 , uo126 , ag82 , y27632 , sb203580 , pd169316 , pd98059 , ro318220 , and a c3 transferase inhibitor . thus , methods of treating primary cancers , metastatic cancers , micrometastases , and hyperproliferative disorders are encompassed by the present invention . combination therapy is also envisioned with other standard forms of chemotherapy , radiation therapy and biological therapies and other anti - neoplastic regimens . it is envisioned that the therapies described in the present invention can be used as adjunct therapy with other anti - neoplastic treatment modalities . the roles of various stromal proteins and growth factors that are relevant to the bone marrow microenvironment in inducing breast cancer dormancy were studied using a panel of breast cancer cell lines . to test the potential role of fgf - 2 in inducing growth arrest of breast cancer cells in the bone marrow microenvironment , the clonogenic potential of mcf - 7 , t - 47d and mda - mb - 231 breast cancer cells on stromal proteins in the presence of fgf - 2 was measured . clonogenic potential is the ability of single cells to grow into multi - cell clusters , that is a hallmark of metastatic growth of malignant cells . the presence of fgf - 2 , but not egf , significantly blocked clonogenic growth of relatively well - differentiated mcf - 7 and t - 47d cells but had no effect on the highly dedifferentiated aggressive mda - mb - 231 cells . fgf - 2 arrested cells failed to survive on collagen - 1 and laminin - 1 , while they survived on fibronectin for many days . to study the molecular basis for the long - term survival of growth arrested cells , a comparison was made between the expression levels of various integrins in breast cancer cells that remained dormant on fibronectin for 3 and 5 days in the presence of fgf - 2 , to that of actively growing cells on fibronectin . microarray analysis showed increased expression levels of the alpha 5 beta 1 integrin , a fibronectin receptor . western blots demonstrated that fgf - 2 induced an increased expression of both the alpha 5 and beta 1 subunits , which together make up the fibronectin receptor in their naturally paired state , in mcf - 7 and t - 47d cells but had no effect on constitutively very high levels of the alpha 5 subunit in mda - mb - 231 cells . the block in growth of fgf - 2 - treated cells on fibronectin was further accentuated by pre - treatment of the cells with an anti alpha 5 subunit antibody , strongly suggesting a role for fibronectin in supporting the survival of dormant breast cancer cells in bone marrow . blocking peptides that disrupt the interaction of fibronectin with its integrin receptor that downregulated the expression of the alpha 5 beta 1 integrin also reversed the survival effects of fibronectin binding to cells in the presence of fgf - 2 . fgf - 2 also induced the phosphorylation of the kinase akt involved in survival signaling . all trans retinoic acid was able to reverse akt phosphorylation induced by egf and reversed fgf - 2 induced increases in total and phosphorylated akt , suggesting an additional mechanisms of disrupting survival in these cells . the administration of kinase or transcription inhibitors or antibodies or blocking peptides or modified peptides as a pre - treatment to sensitize the dormant or metastatic cells for chemotherapy or radiation therapy . the inhibitor could be administered in a variety of methods including but not limited to injectable , oral , liquid , tablet or suppository . the present invention also provides pharmaceutical compositions used in the method of the invention . such compositions comprise a therapeutically effective amount of the agents of the present invention , and a pharmaceutically acceptable carrier . in a particular embodiment , the term “ pharmaceutically acceptable ” means approved by a regulatory agency of the federal or a state government or listed in the u . s . pharmacopeia or other generally recognized pharmacopeia for use in animals , and more particularly in humans . the term “ carrier ” refers to a diluent , adjuvant , excipient , or vehicle with which the therapeutic is administered . such pharmaceutical carriers can be sterile liquids , such as water and oils , including those of petroleum , animal , vegetable or synthetic origin , such as peanut oil , soybean oil , mineral oil , sesame oil and the like . water is a preferred carrier when the pharmaceutical composition is administered intravenously . saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers , particularly for injectable solutions . suitable pharmaceutical excipients include starch , glucose , lactose , sucrose , gelatin , malt , rice , flour , chalk , silica gel , sodium stearate , glycerol monostearate , talc , sodium chloride , dried skim milk , glycerol , propylene , glycol , water , ethanol and the like . the composition , if desired , can also contain minor amounts of wetting or emulsifying agents , or ph buffering agents . the therapeutic agent , whether it be a polypeptide , analog or active fragment - containing compositions or small organic molecules , are conventionally administered by various routes including intravenously , intramuscularly , subcutaneously , as by injection of a unit dose , for example . the term “ unit dose ” when used in reference to a therapeutic composition of the present invention refers to physically discrete units suitable as unitary dosage for humans , each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with the required diluent ; i . e ., carrier , or vehicle . the compositions are administered in a manner compatible with the dosage formulation , and in a therapeutically effective amount . the quantity to be administered depends on the subject to be treated , capacity of the subject &# 39 ; s immune system to utilize the active ingredient , and degree of inhibition or neutralization of binding capacity desired . precise amounts of active ingredient required to be administered depend on the judgment of the practitioner and are peculiar to each individual . suitable regimes for initial administration and subsequent injections are also variable , but are typified by an initial administration followed by repeated doses at intervals by a subsequent injection or other administration . these compositions can take the form of solutions , suspensions , emulsion , tablets , pills , capsules , powders , sustained - release formulations and the like . the composition can be formulated as a suppository , with traditional binders and carriers such as triglycerides . oral formulation can include standard carriers such as pharmaceutical grades of mannitol , lactose , starch , magnesium stearate , sodium saccharine , cellulose , magnesium carbonate , etc . examples of suitable pharmaceutical carriers are described in “ remington &# 39 ; s pharmaceutical sciences ” by e . w . martin . such compositions will contain a therapeutically effective amount of the compound , preferably in purified form , together with a suitable amount of carrier so as to provide the form for proper administration to the subject . the formulation should suit the mode of administration . the compounds of the invention can be formulated as neutral or salt forms . pharmaceutically acceptable salts include those formed with free amino groups such as those derived from hydrochloric , phosphoric , acetic , oxalic , tartaric acids , etc ., and those formed with free carboxyl groups such as those derived from sodium , potassium , ammonium , calcium , ferric hydroxides , isopropylamine , triethylamine , 2 - ethylamino ethanol , histidine , procaine , etc . administration of the compositions to the site of injury , the target cells , tissues , or organs , may be by way of oral administration as a pill or capsule or a liquid formulation or suspension . it may be administered via the transmucosal , sublingual , nasal , rectal or transdermal route . parenteral administration may also be via intravenous injection , or intramuscular , intradermal or subcutaneous . due to the nature of the diseases or conditions for which the present invention is being considered , the route of administration may also involve delivery via suppositories . this is especially true in conditions whereby the ability of the patient to swallow is compromised . the plant compositions or extracts may be provided as a liposome formulation . liposome delivery has been utilized as a pharmaceutical delivery system for other compounds for a variety of applications . see , for example langer ( 1990 ) science 249 : 1527 - 1533 ; treat et al . ( 1989 ) in liposomes in the therapy of infectious disease and cancer , lopez - berestein and fidler ( eds . ), liss : new york , pp . 353 - 365 ( 1989 ). many suitable liposome formulations are known to the skilled artisan , and may be employed for the purposes of the present invention . for example , see : u . s . pat . no . 5 , 190 , 762 . in a further aspect , liposomes can cross the blood - brain barrier , which would allow for intravenous or oral administration . many strategies are available for crossing the blood - brain barrier , including but not limited to , increasing the hydrophobic nature of a molecule ; introducing the molecule as a conjugate to a carrier , such as transferrin , targeted to a receptor in the blood - brain barrier ; and the like . transdermal delivery of the plant compositions or extracts is also contemplated . various and numerous methods are known in the art for transdermal administration of a drug , e . g ., via a transdermal patch . it can be readily appreciated that a transdermal route of administration may be enhanced by use of a dermal penetration enhancer . controlled release oral formulations may be desirable . the plant composition or extract may be incorporated into an inert matrix which permits release by either diffusion or leaching mechanisms , e . g ., gums . slowly degenerating matrices may also be incorporated into the formulation . some enteric coatings also have a delayed release effect . another form of a controlled release of this therapeutic is by a method based on the oros therapeutic system ( alza corp . ), i . e . the drug is enclosed in a semipermeable membrane which allows water to enter and push drug out through a single small opening due to osmotic effects . pulmonary delivery may be used for treatment as well . contemplated for use in the practice of this invention are a wide range of mechanical devices designed for pulmonary delivery of therapeutic products , including but not limited to nebulizers , metered dose inhalers , and powder inhalers , all of which are familiar to those skilled in the art . with regard to construction of the delivery device , any form of aerosolization known in the art , including but not limited to spray bottles , nebulization , atomization or pump aerosolization of a liquid formulation , and aerosolization of a dry powder formulation , can be used in the practice of the invention . ophthalmic and nasal delivery may be used in the method of the invention . nasal delivery allows the passage of a pharmaceutical composition of the present invention to the blood stream directly after administering the therapeutic product to the nose , without the necessity for deposition of the product in the lung . formulations for nasal delivery include those with dextran or cyclodextrins . for nasal administration , a useful device is a small , hard bottle to which a metered dose sprayer is attached . in one embodiment , the metered dose is delivered by drawing the pharmaceutical composition of the present invention solution into a chamber of defined volume , which chamber has an aperture dimensioned to aerosolize and aerosol formulation by forming a spray when a liquid in the chamber is compressed . the chamber is compressed to administer the pharmaceutical composition of the present invention . in a specific embodiment , the chamber is a piston arrangement . such devices are commercially available . the compositions and extracts of the present invention are also suited for transmucosal delivery . in particular , the compositions and extracts are particularly suited for sublingual , buccal or rectal delivery of agents that are sensitive to degradation by proteases present in gastric or other bodily fluids having enhanced enzymatic activity . moreover , transmucosal delivery systems can be used for agents that have low oral bioavailability . the compositions of the instant invention comprise the plant extract dissolved or dispersed in a carrier that comprises a solvent , an optional hydrogel , and an agent that enhances transport across the mucosal membrane . the solvent may be a non - toxic alcohol known in the art as being useful in such formulations of the present invention and may include , but not be limited to ethanol , isopropanol , stearyl alcohol , propylene glycol , polyethylene glycol , and other solvents having similar dissolution characteristics . other such solvents known in the art can be found in “ the handbook of pharmaceutical excipients ”, published by the american pharmaceutical association and the pharmaceutical society of great britain ( 1986 ) and the handbook of water - soluble gums and resins , ed . by r . l . davidson , mcgraw - hill book co ., new york , n . y . ( 1980 ). any transmucosal preparation suitable for administering the components of the present invention or a pharmaceutically acceptable salt thereof can be used . particularly , the mixture is any preparation usable in oral , nasal , or rectal cavities that can be formulated using conventional techniques well known in the art . preferred preparations are those usable in oral , nasal or rectal cavities . for example , the preparation can be a buccal tablet , a sublingual tablet , and the like preparation that dissolve or disintegrate , delivering drug into the mouth of the patient . a spray or drops can be used to deliver the drug to the nasal cavity . a suppository can be used to deliver the mixture to the rectal mucosa . the preparation may or may not deliver the drug in a sustained release fashion . a specific embodiment for delivery of the components of the present invention is a mucoadhesive preparation . a mucoadhesive preparation is a preparation which upon contact with intact mucous membrane adheres to said mucous membrane for a sufficient time period to induce the desired therapeutic or nutritional effect . the preparation can be a semisolid composition as described for example , in wo 96 / 09829 . it can be a tablet , a powder , a gel or film comprising a mucoadhesive matrix as described for example , in wo 96 / 30013 . the mixture can be prepared as a syrup that adheres to the mucous membrane . suitable mucoadhesives include those well known in the art such as polyacrylic acids , preferably having the molecular weight between from about 450 , 000 to about 4 , 000 , 000 , for example , carbopol ™ 934p ; sodium carboxymethylcellulose ( nacmc ), hydroxypropylmethylcellulose ( hpmc ), or for example , methocel ™ k100 , and hydroxypropylcellulose . the delivery of the components of the present invention can also be accomplished using a bandage , patch , device and any similar device that contains the components of the present invention and adheres to a mucosal surface . suitable transmucosal patches are described for example in wo 93 / 23011 , and in u . s . pat . no . 5 , 122 , 127 , both of which are hereby incorporated by reference . the patch is designed to deliver the mixture in proportion to the size of the drug / mucosa interface . accordingly , delivery rates can be adjusted by altering the size of the contact area . the patch that may be best suited for delivery of the components of the present invention may comprise a backing , such backing acting as a barrier for loss of the components of the present invention from the patch . the backing can be any of the conventional materials used in such patches including , but not limited to , polyethylene , ethyl - vinyl acetate copolymer , polyurethane and the like . in a patch that is made of a matrix that is not itself a mucoadhesive , the matrix containing the components of the present invention can be coupled with a mucoadhesive component ( such as a mucoadhesive described above ) so that the patch may be retained on the mucosal surface . such patches can be prepared by methods well known to those skilled in the art . preparations usable according to the invention can contain other ingredients , such as fillers , lubricants , disintegrants , solubilizing vehicles , flavors , dyes and the like . it may be desirable in some instances to incorporate a mucous membrane penetration enhancer into the preparation . suitable penetration enhancers include anionic surfactants ( e . g . sodium lauryl sulphate , sodium dodecyl sulphate ), cationic surfactants ( e . g . palmitoyl dl camitine chloride , cetylpyridinium chloride ), nonionic surfactants ( e . g . polysorbate 80 , polyoxyethylene 9 - lauryl ether , glyceryl monolaurate , polyoxyalkylenes , polyoxyethylene 20 cetyl ether ), lipids ( e . g . oleic acid ), bile salts ( e . g . sodium glycocholate , sodium taurocholate ), and related compounds . the administration of the compositions and extracts of the present invention can be alone , or in combination with other compounds effective at treating the various medical conditions contemplated by the present invention . also , the compositions and formulations of the present invention , may be administered with a variety of analgesics , anesthetics , or anxiolytics to increase patient comfort during treatment . the compositions of the invention described herein may be in the form of a liquid . the liquid may be delivered as a spray , a paste , a gel , or a liquid drop . the desired consistency is achieved by adding in one or more hydrogels , substances that absorb water to create materials with various viscosities . hydrogels that are suitable for use are well known in the art . see , for example , handbook of pharmaceutical excipients , published by the american pharmaceutical association and the pharmaceutical society of great britain ( 1986 ) and the handbook of water - soluble gums and resins , ed . by r . l . davidson , mcgraw - hill book co ., new york , n . y . ( 1980 ). suitable hydrogels for use in the compositions include , but are not limited to , hydroxypropyl cellulose , hydroxypropyl methyl cellulose , sodium carboxymethyl cellulose and polyacrylic acid . preferred hydrogels are cellulose ethers such as hydroxyalkylcellulose . the concentration of the hydroxycellulose used in the composition is dependent upon the particular viscosity grade used and the viscosity desired in the final product . numerous other hydrogels are known in the art and the skilled artisan could easily ascertain the most appropriate hydrogel suitable for use in the instant invention . the mucosal transport enhancing agents useful with the present invention facilitate the transport of the agents in the claimed invention across the mucosal membrane and into the blood stream of the patient . the mucosal transport enhancing agents are also known in the art , as noted in u . s . pat . no . 5 , 284 , 657 , incorporated herein by reference . these agents may be selected from the group of essential or volatile oils , or from non - toxic , pharmaceutically acceptable inorganic and organic acids . the essential or volatile oils may include peppermint oil , spearmint oil , menthol , eucalyptus oil , cinnamon oil , ginger oil , fennel oil , dill oil , and the like . the suitable inorganic or organic acids useful for the instant invention include but are not limited to hydrochloric acid , phosphoric acid , aromatic and aliphatic monocarboxylic or dicarboxylic acids such as acetic acid , citric acid , lactic acid , oleic acid , linoleic acid , palmitic acid , benzoic acid , salicylic acid , and other acids having similar characteristics . the term “ aromatic ” acid means any acid having a 6 - membered ring system characteristic of benzene , whereas the term “ aliphatic ” acid refers to any acid having a straight chain or branched chain saturated or unsaturated hydrocarbon backbone . other suitable transport enhancers include anionic surfactants ( e . g . sodium lauryl sulphate , sodium dodecyl sulphate ), cationic surfactants ( e . g . palmitoyl dl camitine chloride , cetylpyridinium chloride ), nonionic surfactants ( e . g . polysorbate 80 , polyoxyethylene 9 - lauryl ether , glyceryl monolaurate , polyoxyalkylenes , polyoxyethylene 20 cetyl ether ), lipids ( e . g . oleic acid ), bile salts ( e . g . sodium glycocholate , sodium taurocholate ), and related compounds . when the compositions and extracts of the instant invention are to be administered to the oral mucosa , the preferred ph should be in the range of ph 3 to about ph 7 , with any necessary adjustments made using pharmaceutically acceptable , non - toxic buffer systems generally known in the art . for topical delivery , a solution of the agent of the invention in water , buffered aqueous solution or other pharmaceutically - acceptable carrier , or in a hydrogel lotion or cream , comprising an emulsion of an aqueous and hydrophobic phase , at a concentration of between 50 μm and 5 mm , is used . a preferred concentration is about 1 mm . to this may be added ascorbic acid or its salts , or other ingredients , or a combination of these , to make a cosmetically - acceptable formulation . metals should be kept to a minimum . it may be preferably formulated by encapsulation into a liposome for oral , parenteral , or , preferably , topical administration . the invention provides methods of treatment comprising administering to a subject a therapeutically effective amount of at least one of the agents described herein . in one embodiment , the compound is substantially purified ( e . g ., substantially free from substances that limit its effect or produce undesired side - effects ). the subject is preferably an animal , including but not limited to animals such as cows , pigs , horses , chickens , cats , dogs , etc ., and is preferably a mammal , and most preferably human . in one specific embodiment , a non - human mammal is the subject . in another specific embodiment , a human mammal is the subject . the amount of the agent of the invention which is optimal in treating cancers and hyperproliferative disorders can be determined by standard clinical techniques based on the present description . in addition , in vitro assays may optionally be employed to help identify optimal dosage ranges . the precise dose to be employed in the formulation will also depend on the route of administration , and the seriousness of the disease or disorder , and should be decided according to the judgment of the practitioner and each subject &# 39 ; s circumstances . however , suitable dosage ranges for intravenous administration are generally about 20 - 500 micrograms of active compound per kilogram body weight . suitable dosage ranges for intranasal administration are generally about 0 . 01 pg / kg body weight to 1 mg / kg body weight . effective doses may be extrapolated from dose - response curves derived from in vitro or animal model test systems . a subject in whom administration of the agents of the present invention is an effective therapeutic regiment is preferably a human , but can be any animal . thus , as can be readily appreciated by one of ordinary skill in the art , the methods and pharmaceutical compositions of the present invention are particularly suited to administration to any animal ; particularly a mammal , and including , but by no means limited to , domestic animals , such as feline or canine subjects , farm animals , such as but not limited to bovine , equine , caprine , ovine , and porcine subjects , wild animals ( whether in the wild or in a zoological garden ), research animals , such as mice , rats , rabbits , goats , sheep , pigs , dogs , cats , etc ., avian species , such as chickens , turkeys , songbirds , etc ., i . e ., for veterinary medical use . furthermore , the administration of the agent may be given at the time of or after the identification of a cancer or hyperproliferative disorder , alone , or in combination with other agents known to be beneficial for ameliorating the symptoms or decreasing tumor load or enhancing the number or activity of immune cells in patients having cancer or a hyperproliferative disorder . in one embodiment , the subject suitable for treatment by the method of the invention is a subject determined to be suffering from cancer or hyperproliferative disorder . this determination may be made clinically by methods known to one of skill in the art . the following examples are intended to illustrate the invention not limit it . fgf - 2 inhibits single cell growth of well differentiated breast cancer cells mcf - 7 and t - 47d cells incubated with fgf - 2 have markedly diminished clonogenic potential in colony assays in tissue culture on laminin -, collagen i - and iv - coated and uncoated plates ( fig2 , 3 , 4 and 12 ). the clones that did form in the presence of fgf - 2 were arrested in the 8 cell stage . fgf - 2 had no effect on the growth of the highly de - differentiated mda - mb - 231 cells . efg had no effect and served as a negative control in all three cell types . fgf - 2 induces expression of cell integrins including integrin α5 and restricts growth of differentiated single breast cancer cells incubation of well differentiated cells with fgf - 2 induces the expression of a variety of cell adhesion molecule genes , including α5 , α6 , β1 and β3 , that contribute to cell death when expressed in an unligated state ( fig5 , 6 , and tables 1 and 2 ). fig6 is a western blot demonstrating induction of integrin α5 expression in mcf - 7 and t - 47d cells growing on either plastic tissue culture dishes or fibronectin - coated dishes . the increase in integrin α5 expression was assayed for up to five days and remained sustained . no effect is demonstrated on baseline high levels of integrin α5 in mda - mb - 231 cells . inhibition of colony formation by fgf - 2 can be rescued by incubation of cells 6n fibronectin - coated plates ( fig2 b , 4 , 8 , 9 , 15 and 16 ). the protection of colonies in mcf - 7 cells treated with fgf - 2 was sustained by incubation on fibronectin for up to 15 days ( fig8 ). fibronectin is a ligand for integrin α5β1 while collagens i and iv are not . these data suggests an association between unligated integrin α5β1 and inhibition of growth and rescue of clonogenic potential by providing a specific ligand for integrin α5β1 . fibronectin supports long - term survival of fgf - 2 arrested cells , potentially through a p13k pathway antibody to integrin α5 inhibits the clonogenic potential of mcf - 7 cells on fibronectin both with and without fgf - 2 treatments ( fig7 ). antibody to integrin α3 was used as a negative control . to provide a potential mechanism for survival signaling by integrin α5 on fibronectin in the presence of fgf - 2 , initial experiments were conducted to determine the phosphorylation of akt by fgf - 2 in the presence of fibronectin . fig1 demonstrates that fgf - 2 induced phosphorylation of akt in mcf - 7 and t - 47d . phosphorylation was sustained for the five days of assay ; highly de - differentiated mda - mb - 231 cells , however , express constitutively higher levels of integrin α5 and phospho - akt , implicating these molecules in their unlimited growth potential on fibronectin . disruption of fibronectin / integrin α5β1 interaction can reverse protection from cell death our data suggest that stromal proteins in the bone marrow microenvironment , such as fibronectin , provide protection of metastatic cancer cells from cell death induced by physiologic factors in the bone marrow microenvironment and from exogenous toxicity such as chemotherapy or radiation therapy . the ability to disrupt the interaction between fibronectin / integrin α5β1 with blocking antibodies to integrin α5 ( fig7 ) and β1 ( experiments in progress ), peptides to the fibronectin binding site ( fig8 , 9 and 14 ), antisense phosphorothioated oligonucleotides to integrins α5 or β1 or downregulation of integrins α5 or β1 in a dose dependent manner , other transcription inhibitors or retinoids , can result in disruption of the survival signal initiated by fibronectin / integrin α5β1 interaction and thereby become sensitive to chemotherapy and radiation therapy or other biologic therapy - mediated cell death . this approach may sensitize both well - differentiated cells that are non - cycling and dormant in the bone marrow that receive survival protection from ligation to fibronectin in the microenvironment and highly de - differentiated cells that are actively proliferating in the bone marrow that also receive survival signaling from interaction with fibronectin through a constitutively upregulated integrin α5 . disruption of the pi3k / akt signal pathway may disrupt support for breast cancer colony growth by fibronectin fgf - 2 - induced phosphorylation of akt may be disrupted in a number of ways by disrupting the interaction of fibronectin with integrin α5β1 by downregulating the expression of the α5 and β1 subunits , with other transcription factor inhibitors , retinoids , antisense oligonucleotides , disruption of their interaction with blocking antibodies to the integrin α5 β1 or fibronectin , or kinase inhibitors that inhibit activation of pi3k or akt . examples of akt inhibition are shown in fig1 , where incubation of mcf - 7 cells with atra reversed the egf - mediated phosphorylation of akt , as demonstrated on a western blot , and fig1 and 16 where inhibition of akt and pi3k , the upstream activation of akt inhibits survival of dormant clones . this approach may also provide an array of mechanisms for disruptive survival signaling through the pi3k pathway to breast cancer cells at metastatic sites initiated by interaction of integrin α5β1 with fibronectin . disruption of signaling pathways , kinases and gtpases may disrupt signaling initiated by interaction of fibronectin with the integrins alpha 5 beta 1 in cancer cells that can support survival in these cells . examples are included which were conducted with inhibitors of rhp , rho kinase and mep / map kinase , p38 , pkc and pka resulting in the survival of dormant clones on fibronection ( fig1 a and b ). mcf - 7 , sk - br - 3 , mda - mb - 231 , pc - 3 and lncap cells were purchased from the american type culture collection ( atcc ), ( rockville , md .). cells were cultured in dulbecco &# 39 ; s modified eagle &# 39 ; s medium ( dmem ) ( gibco brl , gaithersburg , md .) with phenol red 15 mg / l , 2 mm glutamine , 10 % heat inactivated fetal calf serum ( fcs ) and penicillin 50 units / ml and streptomycin 50 micrograms μg / ml ( gemini bioproducts , calabasas , calif .). one to ten thousand cells were incubated on 24 well tissue culture plates that were either commercially coated for tissue culture ( uncoated ) or coated with 20 g fibronectin , laminin i , collagen i or collagen iv , depending on the cell type or experimental conditions described in the figure legends . colonies were manually counted at 100 × magnification after variable days in culture as described in the figure legends after removing the media and staining cells with crystal violet . proliferation kinetics were performed as before 1 using 2 % trypan blue counts on trypsinized cells on the days indicated in the figure in triplicate plates . recombinant human fgf - 2 and egf were purchased from r & amp ; d systems , minneapolis , minn .). atra was purchased from sigma . neutralizing mouse monoclonal antibody to integrin α5 or integrin β3 were purchased from chemicon , inc . ( temecula , calif .). fibronectin - blocking peptide grgdsp and control peptides were purchased from american peptide co ., inc . ( sunnyvale , calif .). cells were harvested and lysates were prepared as described 2 and analyzed as before 3 . mcf - 7 cells were incubated with and without fgf - 2 10 ng / ml for 5 days on tissue culture dishes coated with fibronectin 20 μg . messenger rna was prepared using solutions provided in a nonrad gearray q series kit and analyzed using a human extracellular matrix and adhesion protein chip and a human pathway finder chip ( super array , bethesda , md .). * exoenzyme c3 transferase is an adp ribosyl transferase that selectively ribosylates rho proteins on asparagine residue 41 , it has extremely low affinity for other members of the rho family such as cdc42 and rac1 . adp ribosylation does not appear to affect the gtpase activity of rho , rather , it appears to block downstream funtions of the protein . ribosylation of rho effectively renders rho inactive , hence , c3 transferase is a very useful protein in the study of rho activity .
| 2 |
formation of the microjet and its acceleration are based on the abrupt pressure drop associated with the steep acceleration experienced by the gas on passing through the orifice . this results in a large pressure difference between the liquid and gas , which in turn produces a highly curved zone on the liquid surface near the orifice and in the formation of a cuspidal point from which a steady microjet flows provided the amount of liquid withdrawn through the orifice is replenished . the parameter window used ( i . e . the set of special values for the liquid properties , flow - rate used , feeding needle diameter , orifice diameter , pressure ratio , etc .) should be large enough to be compatible with virtually any liquid ( dynamic viscosities in the range from 10 − 4 to 1 kg m − 1 s − 1 ); in this way , the capillary microjet that emerges from the end of the feeding needle is absolutely stable and perturbations produced by breakage of the jet cannot travel upstream . downstream , the microjet splits evenly shaped drops simply by effect of capillary instability ( see , for example , raileigh , “ on the instability of jets ”, proc . london math . soc ., 4 - 13 , 1878 ), similarly to a laminar capillary jet falling from a half - open tap . when the stationary , steady regime is reached , the capillary jet that emerges from the end of the drop at the outlet of the feeding point is concentrically withdrawn into the nozzle . after the jet emerges from the drop , the liquid is accelerated by tangential sweeping forces exerted by the gas stream flowing on its surface , which gradually decreases the jet cross - section . the forces exerted by the gas flow on the liquid surface should be steady enough to prevent surface oscillations . therefore , any turbulence in the gas motion should be avoided : even if the gas velocity is high , the characteristic size of the orifice should ensure that the gas motion is laminar ( similarly to the boundary layers formed on the jet and on the inner surface of the nozzle or hole ). in summary , the gas flow , which effects the liquid withdrawal and its subsequent acceleration after the jet is formed , should be very rapid , but also uniform , in order to avoid perturbing the fragile capillary interface ( the surface of the drop that emerges from the jet ) and hence its breaking . therefore , the dynamic forces exerted by the gas should never exceed the surface tension ( drop and microjet ) at any time during the process . in terms of non - dimensional fluid dynamics numbers , the weber number ( i . e . the dynamic to surface tension force ratio ) should not exceed unity during the process . the weber number for the microjet will inevitably be unity because the pressure drop in the gas is similar in magnitude to the effect of the surface tension : 2 γ d j ∼ 1 2 ρ v g 2 where γ and ρ are the surface tension and liquid density , respectively ; and d j and ν g are the characteristic diameter of the jet and characteristic velocity of the gas . also , the velocity of the gas around the drop that produces the jet must be related to that across the orifice via the areas , i . e . v g d 0 2 ˜ ν g d 0 2 , where v g is the velocity of the gas around the drop , and d 0 and d 0 are the diameters of the feeding point and orifice , respectively . since the maximum possible gas velocity at the orifice is similar to the speed of sound , one has v g ∼ ( d 0 d 0 ) 2 × 320 m / s and , for the jet diameter , d j ∼ 4 γ ρ g v g 2 ∼ 4 × 2 × 10 2 1 . 2 × 320 2 ∼ 5 μ m ( γ = 2 × 10 2 n / m 2 for n - heptane ) at the smallest diameters possible with this system ( similar to the thickness of the boundary layer ), the kinetic energies per unit volume of the liquid and gas should be of the same order . the resulting liquid velocity will be v l ∼ ( ρ g ρ 1 ) 1 / 2 v g ∼ 10 m / s where ρ l is he liquid density . from the previous equation , the liquid flow - rate turns out to be q l ˜ d j 2 ν l ˜ 10 − 11 m 3 / s the gas flow should be laminar in order to avoid a turbulent regime — turbulent fluctuations in the gas flow , which has a high frequency , would perturb the liquid - gas interface . the reynolds reached at the orifice are re = v g d 0 v g ∼ 4000 where ν g is the kinematic viscosity of the gas . even though this number is quite high , there are large pressure gradients downstream ( a highly convergent geometry ), so a turbulent regime is very unlikely to develop . the essential difference from existing pneumatic atomizers ( which possess large weber numbers ) is that the aim is not to rupture the liquid - gas interface but the opposite , i . e . to increase the stability of the interface until a capillary jet is obtained . the jet , which will be very thin provided the pressure drop resulting from withdrawal is high enough , splits into drops the sizes of which are much more uniform than those resulting from disorderly breakage of the liquid - gas interface in existing pneumatic atomizers . the proposed procedure for atomizing liquids can be used for electronic fuel injection as well as in inhalers for delivery of drugs or anaesthesia and in nebulizers for chemical analyses , among others . also , it affords mass production of ceramic powders and sintering semiconductors used to manufacture ceramic materials , semiconductors , plastics , etc . in order to complement the above description and facilitate understanding the invention , this report includes an illustrative rather than limitative plan for a prototype model . 2 . end of the feeding needle used to insert the liquid to be atomized . 5 . end of the feeding needle used to evacuate the liquid to be atomized . d 0 = diameter of the feeding needle ; d o = diameter of the orifice through which the microjet is passed ; e = axial length of the orifice through which withdrawal takes place ; h = distance from the feeding needle to the microjet outlet ; p 0 = pressure inside the chamber ; p α = atmospheric pressure . the proposed atomization system obviously requires delivery of the liquid to be atomized and the gas to be used in the resulting spray . both should be fed at a rate ensuring that the system lies within the stable parameter window . multiplexing is effective when the flow - rates needed exceed those on an individual cell . the flow - rates used should also ensure the mass ratio between the flows is compatible with the specifications of each application . obviously , the gas can be externally supplied at a higher flow - rate in specific applications ( e . g . burning , drug inhalation ) since this need not interfere with the atomizer operation . the gas and liquid can be dispensed by any type of continuous delivery system ( e . g . a compressor or a pressurized tank the former and a volumetric pump or a pressurized bottle the latter ). if multiplexing is needed , the liquid flow - rate should be as uniform as possible among cells ; this may entail propulsion through several capillary needles , porous media or any other medium capable of distributing a uniform flow among different feeding points . each individual atomization device should consist of a feeding point ( a capillary needle , a point with an open microchannel , a microprotuberance on a continuous edge , etc .) 0 . 05 - 2 mm ( but , preferentially 0 . 1 - 0 . 4 mm ) in diameter , where the drop emerging from the microjet can be anchored , and a small orifice 0 . 05 - 2 mm ( preferentially 0 . 1 - 0 . 25 mm ) in diameter facing the drop and separated 0 . 1 - 2 mm ( preferentially 0 . 2 - 0 . 5 mm ) from the feeding point . the orifice communicates the withdrawal gas around the drop , at an increased pressure , with the zone where the atomizate is produced , at a decreased pressure . the atomizer can be made from a variety of materials ( metal , plastic , ceramics , glass ); the choice is dictated by the projected application . fig1 depicts a tested prototype where the liquid to be atomized is inserted through one end of the system ( 2 ) and the propelling gas in introduced via the special inlet ( 4 ) in the pressure chamber ( 3 ). the prototype was tested at gas feeding rates from 100 to 2000 mbar above the atmospheric pressure p α at which the atomized liquid was discharged . the whole enclosure around the feeding needle ( 1 ) was at a pressure p 0 & gt ; p α . the liquid feeding pressure , p 1 , should always be slightly higher than the gas propelling pressure , p 0 . depending on the pressure drop in the needle and the liquid feeding system , the pressure difference ( p 1 − p 0 & gt ; 0 ) and the flow - rate of the liquid to be atomized , q , are linearly related provided the flow is laminar — which is indeed the case with this prototype . the critical dimensions are the distance from the needle to the plate ( h ), the needle diameter ( d 0 ), the diameter of the orifice through which the microjet ( 6 ) is discharged ( d 0 ) and the axial length , e , of the orifice ( i . e . the thickness of the plate where the orifice is made ). in this prototype , h was varied from 0 . 3 to 0 . 7 mm on constancy of the distances ( d 0 = 0 . 45 mm , d 0 − 0 . 2 mm ) and e − 0 . 5 mm . the quality of the resulting spray ( 7 ) did not vary appreciably with changes in h provided the operating regime ( i . e . stationary drop and microjet ) was maintained . however , the system stability suffered at the longer h distances ( about 0 . 7 mm ). the other atomizer dimensions had no effect on the spray or the prototype functioning provided the zone around the needle ( its diameter ) was large enough relative to the feeding needle .
| 1 |
fig1 is a block diagram of a power conversion unit ( pcu ) and permanent magnet generator ( pmg ) that illustrates the electrical interface . the pmg 101 is connected to the pcu 102 by a plurality of pairs of wires 103 . each pair of the wires carries a different phase of voltage between the pmg 101 and pcu 102 . the voltage is derived in the pmg 101 and converted to the desired output voltage by the pcu 102 when the starter / generator subsystem is operating as a generator . the voltage is derived from a power source connected to the pcu 102 output ( labeled “ 28 . 5vdc output ” and “ 28 . 5vdc return ” in fig1 ), converted by the pcu 102 to an ac voltage of the desired form , and provided to the pmg 101 , when the starter / generator subsystem is operating as a starter . the ac voltage derived in the pcu 102 while operating in the start mode , is specifically regulated in amplitude , frequency and phase angle so as to control the speed , direction of rotation and the torque produced by the pmg 101 . one embodiment of a pmg 101 is a general dynamics ( gd ) part number 1209 pmg . the gd part number 1209 pmg 101 is a brushless and bearingless machine . further , the part number 1209 pmg 101 is designed in accordance with the fault tolerant architecture described herein and is constructed with windings that are electrically isolated from machine structure and from the other windings of the pmg 101 . one embodiment of a pcu 102 is a general dynamics ( gd ) part number 1208 pcu and is described below . the gd part number 1208 pcu 102 includes three converter modules 104 , 105 , 106 . each converter module is connected a single phase of the pmg 101 through a single pair of wires . the converter modules each include a transformer which is connected to an output filter 107 . the output filter 107 attenuates high frequency components of the voltage that leaves the pcu 102 and is provided to the aircraft loads . the voltage that leaves the part number 1208 pcu 102 is regulated to 28 . 5 vdc ( but other generator mode output voltages are possible ). the part number 1208 pcu 102 also includes a connection for the 28 . 5vdc output return current that is isolated from the pcu 102 chassis . the converter modules , each operate as a bi - directional converter and each provide an electrically isolated interface to the pmg 101 . when the starter / generator subsystem is operated as a generator , the converter modules 104 , 105 , 106 convert the ac voltage from the pmg 101 , to a dc voltage of the desired form . when the starter / generator subsystem is operated as a starter , the converter modules 104 , 105 , 106 convert a dc voltage , that is derived from a source ( typically a battery ) connected to the pcu 102 output , to an ac voltage of the desired form . the ac voltage is applied to the pmg 101 , to operate the pmg 101 as a motor and cause the engine to rotate and thus begin an engine start operation . the converter modules 104 , 105 , 106 are connected to the pmg by the plurality of pairs of wires 103 . additionally , the pcu 102 typically includes a control module 108 connected to the converter modules 104 , 105 , 106 which provides various control and synchronization functions including monitoring of various operating conditions which enable the pcu 102 to achieve the sensorless control of the pmg 101 during engine starts , as well as performing various fault monitoring and built - in - test functions . the control module 108 is typically configured to monitor various internal pcu 102 operating functions and external system operating functions are performing correctly . fig2 is a functional block diagram of a typical power conversion unit 102 . this block diagram illustrates a more detailed overview of the functional elements of the pcu 102 . the converter modules 104 , 105 , 106 of fig1 are represented by a combination of three blocks in fig2 , the ac / dc bi - directional power factor corrected full wave bridge 201 , the dc / dc isolated bi - directional converter 202 , and the feedback control 203 blocks . the control module 108 of fig1 is represented by five blocks in fig2 , the speed / phase detection and control module 204 , the ground fault detector module 205 , control logic module 206 , the equalizer and phase balance control module 207 , and the auxiliary converters module 208 . the output filter module 107 of fig1 is represented by the emi filter module 209 in fig2 and performs essentially the same function . the interface between the pmg 101 and the pcu 102 is represented by the three signals labeled “ phase a ,” “ phase b ” and “ phase c ” in fig2 . the pmg 101 and pcu 102 interface is a two conductor interface for each phase , as previously described . in the pcu 102 embodiment illustrated in fig2 , the bi - directional power factor corrected full wave bridge ac - dc module 201 performs two functions ; in the generator mode , this module converts the variable ac voltage from the pmg 101 to a regulated dc voltage ( approximately 400 volts in this example ), and in the starter mode , this module inverts a dc voltage to an ac voltage that is provided to the pmg 101 to drive it as a motor . the isolated bi - directional converter dc - dc module 202 of fig2 also performs two functions ; in the generator mode , the dc voltage derived by the bridge module 201 is converted to a dc voltage of the desired form through an isolation transformer , and in the starter mode , the voltage that is present on the pcu 102 output bus (“ the voltage labeled “ 28v bus ” in fig2 , which is the output voltage filtered by the filter module 209 ) is converter to a dc form as desired for proper operation of the bridge module 201 . the dc - dc converter module 202 utilizes a high frequency switching converter with an isolation transformer to ensure that the input / output labeled “ 400v rail ” and the input / output labeled “ 28v bus ” of fig2 are always electrically isolated . the feedback control module 203 of fig2 ensures that dc - dc converter modules 202 operate at approximately the same power level as the converter modules for the other phases . the feedback control module 203 also ensures that each dc - dc converter module 202 is synchronized as desired to enhance pcu 102 performance , improve operating efficiency and reduce electromagnetic interference ( emi ). each bridge module 201 is connected to one phase of the pmg 101 and to the associated dc - dc converter module 202 for that phase of the pcu 102 . each dc - dc converter module 202 is connected to the associated bridge module 201 for that phase of the pcu 102 , and to the common “ 28v bus ” ( note that a 28vdc output for the pcu 102 is just one embodiment , and that other output forms can also exist ). the feedback control module 203 is connected to the dc - dc converter module 202 and to the balance control module 208 . the speed / phase detection and control module 204 of fig2 provides the speed and phase detection of the ac voltage from the pmg 101 . the speed and phase information is needed to properly implement start mode control in the pcu 102 . the ground fault detector module 205 of fig2 monitors the phase voltages of the pmg 101 and the associated circuits in the pcu 102 to detect a fault conduction path from one phase to ground or aircraft structure . a conduction path fault of very low current can be detected by the ground fault module 205 and that information is used to ensure that appropriate action can be taken to correct the fault condition . the control logic module 206 of fig2 ensures that proper start and generator mode operation is performed by the pcu 102 and that appropriate action is taken in the event a fault is detected . the equalizer and phase balance control module 207 of fig2 ensures that each dc - dc converter module 202 provides approximately equivalent power during generate and start mode operation , as well as insuring the converters are synchronized as desired . the auxiliary converters module 208 of fig2 provides general control power to the various pcu 102 subsystems , and may be comprised of one or more converters . the speed / phase detection module 204 is connected to all three phases of the ac voltages from the pmg 101 and to the associated circuits in the bridge module 201 . the speed / phase detection module 204 is also connected to the control circuits of all three bridge modules 201 . the ground fault detector module 205 is connected to all three phases of the ac voltages from the pmg 101 and to the control circuits of all three bridge modules 201 and all three dc - dc converter modules 202 . the control logic module 206 is connected to ground fault detector module 205 , the equalizer control module 207 , all three phases of the ac voltages from the pmg 101 and to the control circuits of all three bridge modules 201 and all three dc - dc converter modules 202 . the auxiliary converter modules 208 are connected to all circuits within the pcu 102 to provide control power . the emi filter module 209 of fig2 is a low pass filter that reduces ripple frequency and high frequency emissions that are a natural result of the switching function within the dc - dc converter modules 202 . in the embodiment of the pcu illustrated in fig2 , two input / output connectors are utilized , j 1 210 and j 2 211 . the j 1 connector 210 and associated cable provides the electrical interface between the pmg 101 and the pcu 102 . this interconnecting cable is typically shielded to reduce high frequency radiated emissions and mechanically protected to reduce the probability of shorts on these conductors to aircraft structure . the j 1 interface 210 is typically not connected to other vehicle systems . the j 2 connector and associated cable 211 provides the input / output electrical interface for control signals from other subsystems on the vehicle , such as a flight control computer , to the pcu 102 . the j 2 interface 211 typically includes control signals that are used to control the various operating modes of the pcu 102 , such as standby , generate and start operating modes . the pcu 102 output bus 212 which is illustrated in fig2 as the “ battery bus ” and associated “ return bus ”. in the pcu 102 embodiment of fig2 , this output is regulated to 28 . 5vdc by the pcu 102 when operating as a generator , and a 24 vdc battery is typically connected directly to this output bus ( hence the title “ battery bus ”). the current return conduction path for the battery bus 212 is typically electrically isolated from the pcu 102 chassis and hence a “ return bus ” is typically provided by the pcu 102 . the “ return bus ” is typically electrically connected to the vehicle structure in a specific location as part of a single point ground design for the vehicle . the various bus voltages within the pcu 102 are typically selected to optimize the overall system performance , including weight , reliability , output voltage regulation and starter torque . in the pcu 102 embodiment of fig2 , the output battery bus 212 voltage is regulated at 28 . 5vdc , the bus voltage labeled “ 400v rail ” is regulated to approximately 400 vdc . this voltage is the output voltage of the bridge module 201 when the pcu 102 is operating in the generator mode , and the output voltage of the dc - dc converter module 202 when the pcu 102 is operating in the start mode . the pmg 101 is designed so that the voltage produced in the generator mode is compatible with the pcu 102 bus voltages . the power stage for each bridge module 201 and each dc - dc converter module 202 is electrically and physically isolated . the pcu 102 when configured in the fault tolerant architecture of this invention , can provide generate mode power even in the presence of faults on the pmg 101 and / or pcu 102 feeder cables or the faults within the bridge modules 201 or dc - dc converter modules 202 . since each phase of the pmg 101 is electrically isolated from the other phases and from the vehicle structure , a feeder cable that has a conductor shorted to the vehicle structure will have no impact upon pmg 101 or pcu 102 operation . in fact , up to three simultaneous conductors or components within the bridge modules 201 or dc - dc converter modules 202 , can be tolerated without any deleterious impact upon the starter / generator subsystem performance . the pmg 101 is also designed so that a shorted phase winding or a short within a phase pair of feeder cable wires will not cause the pmg 101 to overheat or produce an unsafe operating condition . a short condition within a phase of the pmg 101 or within a phase of the pcu 102 bridge modules 201 or dc - dc converter modules 202 , will not result in complete loss of the generator mode output power for this fault tolerant architecture . a loss of one phase will result in an approximate 33 % reduction in generator mode output power capacity and a loss of two phases will result in an approximate 67 % reduction in generator mode output power capacity . fig3 is a flow diagram of the start mode control logic utilized for a typical embodiment of the permanent magnet starter / generator subsystem . the pmg 101 in the diagram of fig3 is designed for a maximum drive speed of approximately 20 , 000 revolutions per minute . the pcu 102 incorporates a sensorless , vector control method for controlling the speed and torque produced by the pmg 101 while operating as a starter , in this embodiment of the permanent magnet starter / generator subsystem . an open loop and closed loop control method are utilized with this embodiment of the pmg 101 start mode control . this method provides for automatic transitions form open to closed loop control in a normal start sequence . the method also allows for the pcu 102 to check for incorrect engine rotation and correct phasing of the pmg 101 output voltage during an engine start . if a fault is encountered during the engine start , the pcu 102 terminates the start sequence and initiates a failed start indication , in this embodiment of the start mode logic implementation . the implementation of start mode control logic is application specific and can be tailored as necessary in the pcu 102 . the torque versus speed profile in start mode typically includes a starter assist to approximately 40 % maximum pmg drive speed which incorporates a soft start characteristic . the starter assist may vary by 20 % of maximum pmg drive speed and can operate in any range from 0 %- 100 % of maximum pmg drive speed . a “ motoring start ” is when the rotational speed of the pmg is measured prior to initiating an engine start and the pcu automatically adjusts the ac control excitation to “ lock - in ” on the initial rotational speed of the pmg and start accelerating from that speed instead of beginning the pmg speed control from a lower speed . fig4 is an illustration of a typical permanent magnet generator 101 . this embodiment of the pmg 101 is an illustration of the gd part number 1209 pmg 101 and is a brushless , bearingless machine . in this embodiment , the pmg 101 includes two assemblies , a stator assembly 401 and a rotor assembly 402 . the stator assembly contains the magnetic core material and the three isolated windings . the rotor assembly contains an array of permanent magnets that are mounted to a bobbin and secured in a suitable fashion to ensure structural integrity at high rotational speeds . the pmg 101 can also be designed for operation as an integral assembly on an engine shaft ( i . e ., pmg rotates at same speed as a main or auxiliary engine shaft ; no bearings are required ) or a shaft mounted , gearbox integrated assembly such as the gd part number 1209 pmg 101 ( i . e ., pmg rotor is mounted directly to driveshaft on engine accessory gearbox ( agb )). further , the pmg may be designed for operation as an agb mounted assembly ( i . e ., the pmg incorporates a spline and bearings so that the assembly interfaces to engine agb in similar or identical fashion to conventional brushed s / gs ). additionally , an optional contactor or circuit breaker can be added in series with the pmg output to remove power from the feeder cables and / or pcu input . the use of this contactor or circuit breaker is optional with the “ fault tolerant ” architecture . other embodiments and uses for the invention also exist . the fault tolerant architecture applications include aircraft and / or automotive applications requiring engine start operation and generation of dc electrical power . the applications also include aircraft and / or automotive applications requiring engine start operation and generation of ac electrical power . further applications include aircraft and / or automotive applications requiring engine start operation and generation of dc and ac electrical power . the pcu 102 can be designed for operation as a single assembly located adjacent to or remote from pmg 101 . the pcu 102 may also be designed for operation as multiple assemblies located adjacent to or remote from pmg 101 . further the pcu 102 and pmg 101 may be interconnected with a low current feeder cable ( i . e ., the pmg 101 is designed to produce a voltage that is greater than the average pcu 102 output voltage ) or interconnected with a high current feeder cable ( i . e ., the pmg 101 is designed to produce a voltage that is equal or less than the average pcu 102 output voltage ).
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the treadmill assembly of the present invention is shown in fig1 indicated generally at 1 . treadmill 1 is shown in greater detail in fig2 - 4 . referring first to fig1 and 2 it may be seen that treadmill assembly 1 has a front end 2 and a rear end 3 and generally includes as its main components ; a substantially planar trihedral main frame indicated generally at 4 which comprises a left and a right side - rail 5 and 6 , a front transverse mounting bracket 16 and a platform support frame 21 affixed transversely to the side - rails 5 and 6 ; a slider bed 26 ; a front roller 31 ; a rear roller 41 ; an endless tread - belt 49 ; a first flywheel and first pulley arrangement indicated generally at 52 ; a second flywheel and second pulley arrangement indicated generally at 55 ; a flexible endless drive belt 53 ; a one - piece u - shaped tubular rail indicated generally at 61 including a grasp - rail 62 , a left and right tubular arm 63a and 63b respectively and left and right tubular ends 64a and 64b respectively ; a pair of adjustable tubular front legs 70a and 70b and a pair of back legs 75 . referring now more particularly to fig2 - 4 , it may be seen that the main frame 4 of treadmill 1 comprises a left and a right spaced side - rail 5 and 6 respectively , extending generally lengthwise of the treadmill 1 . the side - rails 5 and 6 of the main - frame 4 are formed as a hollow rectangular shaped channel member , preferably made of a suitable metal or plastic material extruded or stamped however , other suitable materials such as wood may be used . more specifically , the side - rails 5 and 6 include a front end 7 , a rear end 8 , a vertical lateral wall 9 , a vertical medial wall 10 , a top wall 11 , and a lower wall 12 . the medial walls 10 of the side - rails 5 and 6 include a central slot 13 which extends approximately six inches from the rear end 8 toward the front end 7 of the left and right side - rails 5 and 6 . a bore 14 is provided through the lateral wall 9 and the medial wall 10 spaced approximately six inches from the front end 7 of the left side - rail 5 . side - rails 5 and 6 are retained in a spaced apart relation at their front ends by the mounting bracket 16 having a top flange 17 and a bottom flange 18 which are screwed , bolted or otherwise rigidly connected transversely to the top walls 11 at the front end 7 of the side - rails 5 and 6 . side - rails 5 and 6 are further retained in a spaced apart relation , along their length , by the platform support frame 21 which includes a front end 22 , a back end 23 and a left and right side 24 . sides 24 are bolted , welded or otherwise rigidly affixed along the length of the medial walls 10 of rails 5 and 6 . side - rails 5 and 6 , bracket 16 and platform support frame 21 provide the main frame 4 with the platform support frame 21 positionally supporting and retaining the slider bed 26 in relation to the main frame 4 . mounting bracket 16 is preferably formed from metal or plastic and includes a left and right spaced threaded boss 19a and 19b respectively , which are bolted or welded to , or integrally formed in , a front wall 20 of the bracket 16 to generally mount , in a spaced apart relation , the left and right arms 63a and 63b respectively , of the u - shaped tubular rail 61 to the main frame 4 . the slider bed 26 substantially supports a upper reach 50 of the endless tread - belt 49 and is preferably formed of a stationary metal , wood or plastic plank having a length extending substantially between the front roller 31 and the rear roller 41 . slider bed 26 is preferably of a width somewhat greater than the width of the tread - belt 49 and extends out beyond a left and a right outer edge 52 of the tread - belt 49 with the outer edges 52 terminating short of a left and a right side edges 29 of the slider bed 26 . a gap b is provided by the slider bed 26 between the outer edges 52 of the tread - belt 49 and a inner left and right edges 15 of the left and right side - rails 5 and 6 to thereby prevent a binding or rubbing of the edges 52 of the tread - belt 49 with the edges 15 of the side - rails 5 and 6 . slider bed 26 is secured by screws 30 to a top surface 25 of the side members 24 of the platform support frame 21 . the slider bed 26 is maintained in close proximity to the upper reach 50 of the tread - belt 49 to thereby prevent sagging or yielding of the tread - belt 49 in response to the user walking or running thereon . alternatively , the slider bed 26 , the platform support frame 21 , side - rails 5 and 6 , and the bracket 16 , or any combinations thereof , may be integrally formed as a unitary plastic injected member . the front and rear rollers 31 and 41 respectively , are preferably formed of a plastic or metal hollow cylindrical tube . the front roller 31 includes a left and a right fitted end cap 33 having a conventional roller - bearing 34 integrally formed , or rigidly affixed , at their centers . the end caps 33 , including the roller - bearings 34 , are press fit , glued , riveted or otherwise rigidly secured in a respective left and right end 32a and 32b respectively , of the front roller 31 . a left and a right front roller mounting angle bracket 34a and 35 respectively , include short shafts 38 which project substantially horizontally and medially from the center of the lower leaf 36 of the brackets 34a and 35 . the shafts 38 are journaled in the roller - bearings 34 mounted in the end caps 33 of the front roller 31 so that the front roller 31 is free wheeling . a upper leaf 37 of the roller mounting angle brackets 34a and 35 is adapted to be bolted , welded or otherwise rigidly affixed forwardly on the top wall 11 of the left and right side - rail members 5 and 6 respectively , to thereby mount the front roller 31 near the front end 7 of the main frame 4 of the treadmill 1 . the front roller 31 is adapted to include a first flywheel 39 integrally formed , or otherwise rigidly connected , to the left end 32 of the roller 31 . the rear roller 41 includes a left and a right fitted end cap 42 having a conventional roller - bearing 43 integrally formed in , or otherwise rigidly affixed , at their centers . the end caps 42 , including the roller - bearings 43 , are press fit , glued , riveted , or otherwise rigidly secured , to a left and a right end 40a and 40b of the rear roller 41 . the rear roller 41 includes a axle 44 projecting substantially horizontally through the length of the rear roller 41 and extending approximately one inch lateral to the left and right roller end caps 42 to form a left and a right mounting shaft 44 , so that the rear roller 41 is free wheeling . a threaded bore 45 is provided in the left and right mounting shafts 44 , and the shafts 44 , are journaled within the slots 13 provided at the rear end 8 of the left and right side - rail members 5 and 6 . a flat roller mounting plate 46 is sized and shaped to fit snugly against the left and right ends 8 of the left and right side - rail members 5 and 6 . the mounting plate 46 includes a threaded bore 47 which engages an adjustment bolt 48 . the adjustment bolt 48 threads through the bore 47 of the mounting plate 46 to engage with the threaded bore 45 of the left and right mounting shafts 44 , of the rear roller 41 . the rear roller 41 may be positionally adjusted to thereby loosen or tighten the tread - belt around the rollers of the treadmill by the simultaneous screwing or unscrewing of the adjustment bolt 48 in a clockwise or in a counter - clockwise direction , respectively . the endless tread - belt 49 is preferably formed of a rubber , vinyl or other suitable flexible material and is entrained around the front and rear rollers 31 and 41 and includes an upper reach 50 and a lower reach 51 . the upper reach 50 moves from front to rear so that a user standing on the upper operative surface of the upper reach 50 of the tread - belt 49 may walk or run in a forward direction , as indicated by arrow a of fig3 and remain stationary relative to the main frame 4 of the treadmill 1 . referring now more specifically to fig4 it may be seen that the first flywheel and first pulley arrangement generally indicated at 52 includes a first flywheel 39 which is integrally formed , but may be otherwise rigidly connected to , the left end 32a of the front roller 31 . the first flywheel 39 is preferably formed from a machined , cast or molded steel plate but may alternatively be formed of a sand filled vinyl casting or of any other suitable material having a weight substantially sufficient to function for the intended purpose of the flywheel . the first flywheel 39 includes a groove 76 about its perimeter so as to function as a flywheel and pulley in combination forming the first flywheel and first pulley arrangement indicated generally at 52 . the flexible endless drive belt 53 is preferably formed from a flexible elastomer or rubber material and is entrained about the first flywheel and first pulley arrangement 52 and about a second pulley 54 of the second flywheel and second pulley arrangement 55 . the second pulley 54 is formed preferably of metal or plastic materials and has a diameter four to five times smaller than the first flywheel and first pulley arrangement 52 . pulley 54 is rigidly connected to an inside projection 57 of the axle 56 and is positionally aligned with the first flywheel and first pulley arrangement 52 to thereby prevent excessive wear of the drive belt 53 , or slippage of the drive belt 53 out from the first flywheel and first pulley arrangement 52 and / or out from the second pulley 54 during use of the device . the axle 56 is preferably formed of a metal or plastic material and is retained in a bushing 58 which is press fit or otherwise rigidly affixed in the bore 14 provided through the lateral and medial walls 9 and 10 respectively , near the front end 7 , forward of the first flywheel and first pulley arrangement 52 , of the left side rail 5 of the main frame 4 . the axle 56 passes through the bushing 58 to form an outside projection 59 of the axle 56 having the second flywheel 60 rigidly connected thereto . the second flywheel 60 is of a similar construction to flywheel 39 . the u - shaped tubular rail 61 is formed from a one - piece bent metal or molded plastic tube and includes ; a substantially horizontal upper u - shaped portion which forms the grasp - rail 62 centrally and extending peripherally to form the left and right arms 63a and 63b respectively which terminate in the left and right tubular ends 64a and 64b respectively . the left and a right tubular arms 63a and 63b include a bore 65a and 65b respectively , through their respective sidewalls . bores 65a and 65b are spaced approximately ten inches proximal to the free ends of the left and right tubular ends 64a and 64b of rail 61 . bores 65a and 65b align and engage with the respective bosses 19a and 19b provided on the front wall 20 of bracket 16 to generally mount the left and right arms 63a and 63b of u - shaped rail 61 , in a spaced apart relation , to the bracket 16 at the front end 2 of the treadmill 1 . nuts 66 are threaded on bosses 19a and 19b and tightened against the arms 63a and 63b to positionally retain u - shaped rail 61 on bracket 16 at the front end 2 of the main frame 4 of the treadmill 1 . u - shaped rail 61 extends approximately thirty - six inches upwardly from the upper edge of bracket 16 at the front end 4 of the treadmill 1 providing the user with the grasprail 62 for stability . bores 67a and 67b are provided in the respective sidewalls of the tubular ends 64a and 64b spaced approximately five inches proximal to the free ends of the tubular ends 64a and 64b of rail 61 . with rail 61 mounted on bracket 16 the tubular ends 64a and 64b project approximately four inches below the lower edge of the bracket 16 of the main frame 4 and bores 67a and 67b project approximately one inch below the lower edge of the bracket 16 of the main frame 4 . a bottom end 68 of the tubular ends 64a and 64b slidingly receives a top end 69 of the tubular front legs 70a and 70b respectively . the tubular front legs 70a and 70b having a overall length of approximately ten inches and formed of a plastic or metal tube of a smaller diameter than the diameter of the tubular ends 64a and 64b of the rail 61 . tubular front legs 70a and 70b include a plurality of spaced bores 71a and 71b through their respective sidewalls , along their respective length . the tubular front legs 70a and 70b and tubular ends 64a and 64b are uniformly secured and retained , with respect to each other respectively , by the alignment of the bore 67a of the left tubular end 64a with one of the bores 71a of left tubular leg 70a and by aligning bore 67b of the right tubular end 64b with the matching bore 71b of right tubular leg 70b having a detachable pin 72a and 72b disposed respectively , therethrough . legs 70a and 70b are uniformly raised or lowered by selecting a particular matching bore 71a and 71b provided in each of the front legs 70a and 70b and aligning the selected bores 71a and 71b with the bores 67a and 67b and securing their alignment with the pins 72a and 72b to thereby selectively raise or lower the front end 4 of treadmill 1 to increase or decrease the intensity of the exercise as desired . as shown in fig5 a plastic or rubber foot 73 is press - fit or otherwise attached to a bottom end 74 of legs 70a and 70b to protect the floor surface . a pair of static back legs 75 , formed of plastic , rubber or other suitable material , are screwed , bolted , glued or otherwise rigidly connected to the lower wall 12 of the left and right side - rails 5 and 6 at the rear end 8 of the side - rails 5 and 6 of the treadmill 1 . back legs 75 and are of a sufficient height so as to ensure that the main frame 4 is substantially horizontally supported above the floor when the front legs 70a and 70b are maximally disposed within the tubular ends 64a and 64b and the front end 4 of the treadmill 1 so that the frame 4 is supported at its lowest height , as best illustrated in fig1 . during operation of the treadmill 1 the user manipulates the tread - belt 49 into a front to back motion by walking or running on the upper reach 50 of the tread - belt 49 . the front to back movement of the tread - belt 49 causes the front roller 31 and the first flywheel and first pulley arrangement 52 to rotate in a clockwise direction . the second pulley 54 , having a diameter smaller than the first flywheel and first pulley arrangement 52 , connected thereto by the drive belt 53 , and further connected by the axle 56 to the second flywheel 60 causes the second flywheel 60 to rotate at a faster speed than the first flywheel and first pulley arrangement 52 rotates . the faster rotating second flywheel 60 generates a centrifugal force which is transmitted back through the first flywheel and first pulley arrangement 52 to impart a controlled inertia and momentum to the tread - belt 49 , thereby improving the momentary reaction of the tread - belt 49 in response to a user increasing or decreasing his or her stride speed thereon . by using an endless belt drive by way of example it is not intended to limit the present invention to driving the second flywheel by way of an endless belt , any conventional means for stepping - up the rotational speed at a driving flywheel is considered to be within the slope of the present invention . for example , use of chains and sprockets are considered to be equivalent means . similarly , use of directly engaging gears or friction drives such as rubber wheels , in which case the second flywheel would counter - rotate with respect to the first flywheel , are considered to be equivalent means . in the foregoing description , certain terms have been used for brevity , clearness and understanding ; but no unnecessary limitations are to be implied therefrom beyond the requirement of the prior art , because such terms are used for descriptive purposes and are intended to be broadly construed . moreover , the description and illustration of the invention is by way of example , and the scope of the invention is not limited to the exact details shown or described . having now described the features , discoveries and principles of the invention , the manner in which the improved treadmill assembly is constructed and used , the characteristics of the construction , and the advantageous , new and useful results obtained ; the new and useful structures , devices , elements , arrangements , parts and combinations , are set forth in the appended claims .
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certain terminology is used in the following description for convenience only and is not limiting . the words “ right ”, “ left ”, “ lower ” and “ upper ” designate directions in the drawings to which reference is made . the words “ inwardly ” or “ distally ” and “ outwardly ” or “ proximally ” refer to directions toward and away from , respectively , the geometric center of the fracture mobility testing system and related parts thereof . the words , “ anterior ”, “ posterior ”, “ superior ,” “ inferior ” and related words and / or phrases designate preferred positions and orientations in the human body to which reference is made and are not meant to be limiting . the terminology includes the above - listed words , derivatives thereof and words of similar import . referring to fig2 - 3 , a fracture mobility testing system 100 is provided that includes a first syringe 110 , a second syringe 120 , a three - way stop - cock coupling unit 130 , and a balloon catheter 140 , the balloon catheter 140 further including a shaft 142 , the distal end of which terminates in a balloon 144 . the three - way stopcock coupling 130 provides a selective coupling for fluid or gas communication between the balloon catheter 140 and the first and second syringes 110 , 120 . fig2 - 3 further include a working cannula 150 that provides an access corridor to the interior of a vertebral body . the first syringe is configured for inflating or expanding the balloon while the second syringe is configured for creating a vacuum within the balloon catheter 140 . in some implementations , the first syringe and / or the second syringe may be replaced with a pressure syringe , such as the vertebral body stenting ( vbs ) inflation system , available from synthes . the vbs inflation system may be connected to the three - way stopcock coupling unit 130 to pressurize the balloon 144 or to create a vacuum within the interior of the fracture mobility testing system 100 . in a first embodiment , the balloon 144 is a non - elastic balloon but , in alternate embodiments , may be elastic . the balloon 144 may be essentially spherical or elliptical or may assume a range of alternate geometries that are well - configured for imparting a distraction force to the vertebral endplates , and may include flattened superior and inferior surfaces . balloon 144 may be designed to have particular properties that are beneficial to diagnosing fracture mobility . for example , balloon 144 may be designed to withstand high pressures and large volume increases thereby providing for height restoration , as opposed to conventional curette type cavity creation devices that provide no height restoration . in addition , balloon 144 may have an expansion ratio ( beginning diameter / ending diameter ) much greater than that provided by a curette . balloon 144 may also expand while keeping a large surface contact 360 ° around the circumference ( increasing with continued inflation ) versus the point contact of a curette ( which must be rotated and longitudinally shifted to reliably and completely check for 360 ° all - round fixation mobility ). further , balloon 144 may be designed to create a larger volume than a volume - constant tipped curette (& lt ; 200 %), resulting in a larger and more radiopaque body . in operation , and in continuing reference to fig2 - 4 , a transpedicular access corridor is created using the working cannula 150 ( block 302 ). in a first embodiment , the procedure begins by placing the patient in a prone position . if a general anesthesia is used , the patient can be placed in hyperextension . the surgical field of interest is then checked with a c - arm to ensure free access for the c - arm in the a - p and lateral directions at the level of pathology . the area to be treated is then draped and cleaned . the vertebral body 25 to be augmented is then identified using the c - arm , which is adjusted exactly in the ap projection so that the view is parallel to the endplates and in order that the pedicles appear symmetric . a second c - arm may be used in order to obtain a bi - planar projection and gain control of both planes simultaneously . otherwise , the c - arm can be switched into the other projection when necessary . with the c - arm installed in the ap projection , the incision site is planned . the c - arm is then used to localize a stab incision into the skin . a guide wire is then pushed through the soft tissue until the bony surface of the spine is touched , while the c - arm is used for controlled placement ( block 304 ). a wire holder can be used in order to avoid radiation exposure to the surgeon &# 39 ; s fingers . the orientation of the guide wire is then made with the c - arm in the ap view . once the bony surface is touched , the tip of the guidewire is positioned lateral of the eye of the pedicle at its upper third . at the thoracic spine , the guide wire is made to sit on the costo - transverse process and at the lumbar spine , the guide wire is made to sit in the edge of the lateral facet and the transverse process . the guide wire is then advanced convergent in the projection of the pedicle . guide wires are then preliminarily inserted at all levels where cement augmentation is planned , with each vertebrae &# 39 ; s position stored in the image intensifier of the c - arm display . the working cannula 150 is then placed over the guidewire and the guidewire is removed . a vacuum is drawn within the interior of the fracture mobility testing system 100 by manipulating the stop cock 130 into a position configured for enabling the second syringe 120 to create or maintain a vacuum within the interior of the balloon catheter 140 by manipulating the plunger with respect to the second syringe 120 . the fracture mobility testing system 100 is then utilized by inserting the balloon catheter 140 through the working cannula 150 such that the balloon 144 is placed into the interior of the vertebral body 25 ( block 306 ). with the c - arm in a lateral or a - p position ( or both , if two c - arms are being utilized ), the balloon 144 is then filled ( e . g ., with saline solution , other biocompatible material , contrast agents , combinations thereof , etc .) by manipulating the stop cock 130 into a position configured to enable fluid communication between the contents of the first syringe 110 and the interior of the balloon catheter 140 and plunging the contents of the first ( injection ) syringe 110 through the balloon catheter 140 and into the interior of the balloon 144 , thereby causing the balloon 144 to expand in volume ( block 308 ). mobility of the vertebral body 25 may now be detected ( block 310 ). for example , because no cavity has been created within the interior of the vertebral body 25 , expansion of the balloon 144 will either force one or more of the vertebral body endplates to distract from one another . this may be the case when the cortical surfaces of the vertebral body 25 have not fused to one another over the fracture lines of the collapsed vertebral body 25 ( block 312 : yes ). in such a case , cement augmentation and height restoration of the collapsed vertebral body 25 is achievable using any of a variety of subsequent augmentation steps known in the art and as described in the background section ( block 316 ). in the case in which the mobility of the fractured portions of the vertebral body has been confirmed , the surgeon may elect to deflate and re - inflate the balloon 144 several times after adjusting slightly the position of the balloon ( block 318 ). this may be performed to determine where the fault line ( s ) or hot spot ( s ) for optimal balloon expansion and cancellous bone compression are located in the fractured vertebral body 25 to better plan the next steps of the procedure ( block 320 ). however , when the cortical bone surfaces or cancellous bone portions of a collapsed vertebral body 25 have begun to fuse to one another over the fracture lines , the increasing volume and pressure of the expanding balloon 144 will not be sufficient to force the one or more endplates of the collapsed vertebral body 25 to become displaced with respect to one another ( block 312 : no ). any mobility or lack thereof can easily be perceived by the surgeon by viewing the c - arm images during the injection of contrast agent to expand the volume of the balloon 144 . in the case in which the fracture mobility step has proven that there is no mobility to the fractured portions , the surgeon may elect to perform a simple kyphoplasty , in which cement is injected inside the cavity defined by the access corridor using known techniques through the working cannula 150 without achieving height restoration of the vertebral body , but such that the boney structure is prevented from further collapse and stabilized as is ( block 314 ). alternately , the surgeon may decide to attempt to manually distract the endplates of the collapsed vertebral body 25 using instruments such as curettes or other more resilient cavity creation tools . such a decision may be based upon the age and health and pathology of the patient , as the height of an elderly and osteoporotic patient &# 39 ; s recently collapsed vertebral body may be more readily restored than a young , relatively healthy individual who underwent trauma such as a car accident and whose treatment was neglected for some time , allowing the cortical surfaces of his collapsed vertebral body to begin to heal and fuse over the fracture lines . in an alternate embodiment , an extrapedicular approach may be utilized instead of the transpedicular approach described above . a bipedicular procedure , in which two balloon catheters 140 are inserted , one through each pedicle , may be utilized . the same balloon catheter 140 can further be sequentially utilized through each of the bipedicular access corridors and into the interior of the vertebral body 25 and inflated , deflated , and removed . in the transpedicular and extrapedicular approaches described above , the guide wire or trocar may be initially inserted into a treatment area until they reach a treatment area of the vertebral body . the working cannula 150 may positioned over the guide wire or trocar to for insertion and proper positioning of the balloon catheter 140 . in some embodiments , the fracture mobility testing system 100 may further include sensing elements for determining the volume and / or pressure within the interior or the pressure upon the exterior of the balloon 144 . such a volume and / or pressure sensing element may sense the force applied to the plunger of the first and / or second syringes 110 , 120 . in an alternate embodiment , and in reference to fig4 , the fracture mobility testing system 100 is configured , with or without minor modifications , for use in testing the mobility and healing status of long bone fractures as well , to assist in preoperative planning for the reduction of the long bone fracture . it will be appreciated by those skilled in the art that changes could be made to the preferred embodiment described above without departing from the broad inventive concept thereof . it is understood , therefore , that this invention is not limited to the particular embodiment disclosed , but it is intended to cover modifications within the spirit and scope of the present invention as defined by the present description .
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the present invention is directed to an apparatus to provide cushioning for a cantilevered component mounted to a rigid frame and will be described as being used with a vertical tillage implement , but it is understood that the invention could be used in other agricultural and non - agricultural applications . referring to fig1 , a vertical tilling implement 10 is shown . an agricultural vehicle ( not shown ) pulls the vertical tilling implement 10 in a direction of motion a . the vertical tilling implement 10 includes a main frame 12 . the wing frame 12 has a hitch 14 on the front end that may be used to connect the vertical tilling implement 10 to an agricultural vehicle such as a tractor . additionally , a set of wheels 16 are connected to the wing frame 12 . the set of wheels 16 are oriented in a direction that is in general alignment with the direction of motion a . the set of wheels 16 includes a set of center wheels 18 and a set of pivoting wheels 20 . the set of center wheels 18 is attached across the wing frame 12 at positions , for example , roughly midway between the front and rear ends of the wing frame 12 . the set of center wheels 18 may include a system for adjusting the distance between the main frame 12 and the set of center wheels 18 . this system for adjusting may permit the set of center wheels 18 to be statically fixed during the movement of the vertical tilling implement 10 or to be dynamically adjustable as the vertical tilling implement 10 travels . the set of pivoting wheels 20 are connected to the front distal ends of the wing frame 12 . as will be described , the set of pivoting wheels 20 may include at least two pivoting wheels that reduce the amount of lateral movement of vertical tilling implement 10 as it is pulled . the vertical tilling implement 10 also includes a plurality of rows of fluted - concave disc blades 22 attached to the main frame 12 . in accordance with one configuration , the plurality of rows of fluted - concave disc blades 22 is indexed . in particular , the plurality of rows of fluted - concave disc blades 22 includes a front left row 24 , a front right row 26 , a rear left row 28 , and a rear right row 30 . when indexed , the front left row 24 and the front right row 26 are aligned with the rear left row 28 and the rear right row 30 such that areas of ground between the blades in the front left rows 24 and the front right row 26 are engaged by the blades in the rear left row 28 and the rear right row 30 as the tilling implement is pulled forward . the fluted - concave disc blades will induce lateral and vertical forces in the vertical tilling implement 10 . the fluted - concave disc blades on the plurality of rows of fluted - concave disc blades 22 have surface features , as will be described below . the rotation of the fluted - concave disc blades and the engagement of the surface features of the blades will displace soil during the tilling operation . however , the engagement of the surface features of the blades with the soil will also apply a force to the blades . the blades engagement with the soil will displace the fluted - concave disc blades in a direction perpendicular to the blades direction of rotation . the front left row 24 is symmetric about a centerline 32 of the vertical tilling implement 10 with the front right row 26 . likewise , the rear left row 28 is symmetric about the centerline 32 of the vertical tilling implement 10 with the rear right row 30 . additionally , the front left row 24 is substantially symmetric about a line perpendicular to the direction of motion a with the rear left row 28 . likewise , the front right row 26 is substantially symmetric about a line perpendicular to the direction of motion a with a rear right row 30 . these general symmetries may involve some of the rows being offset relative to the others to achieve the indexing of the blades as described above . when the plurality of rows of fluted - concave disc blades 22 are arranged in a symmetrical arrangement about the centerline 32 , such as illustrated in fig1 , a gap between each side of symmetrical rows may be created . a center tilling member 34 may be placed in this gap to ensure that all the soil passing under the vertical tilling implement 10 is tilled as the tilling implement is pulled forward . the center tilling member 34 may be a coulter , as shown in fig1 , another fluted disc blade , or the like . it should be observed that although fig1 only shows four rows included in the plurality of rows of fluted - concave disc blades 22 , there may be fewer or more rows of fluted - concave disc blades . additionally , while the illustrated embodiment shows the plurality of rows of fluted - concave disc blades 22 having an x - shaped configuration based on the described symmetry , the plurality of rows of fluted - concave disc blades 22 may have a different configuration . for example , the plurality of rows of fluted - concave disc blades 22 may have a diamond configuration , a k - shaped configuration , or all may be parallel with each other in a direction perpendicular to the direction of motion a . furthermore , it is contemplated that some or all of the rows may be configured in asymmetric arrangements . it should be further observed that the rows may be at oriented at angles of about 18 degrees from a direction perpendicular to the direction of pull . as described above , known tillage implements utilizing typical smooth concave blades would not operate properly under such an aggressive angle and achieve satisfactory results . historically , flat blades mounted in rows at this aggressive of an angle would break as a result of the massive side pressure of the soil as the tillage implement was pulled and would tend to leave large clods of soil that require a second tilling pass . however , in the disclosed embodiments , the fluted blades are unexpectedly capable of one - pass tilling at this aggressive gang angle despite only having a shallow concavity . rolling basket or reel assemblies 36 are connected to the rear end of the main frame 12 to provide downward pressure . although fig1 shows three rolling basket assemblies 32 , two of which having rotational axes which are not collinear with the third , the rolling basket assemblies 32 may include fewer or more members providing downward force . referring now to fig2 , a detailed view of the rear left row 28 and the rolling basket assemblies 36 are shown . the rolling basket assemblies 36 are connected to the main frame 12 by an adjustable pressure assembly 38 . the adjustable pressure assembly 38 includes a set of arms 40 extending rearwardly from the main frame 12 and downwardly to engage the rolling basket assemblies 36 . the set of arms 40 includes a pair of fixed beams 42 which have a set of spring connection points 44 positioned frontwardly on the fixed beams 42 and a set of links 46 that is hingedly connected to the fixed beams 42 near the midpoints of the fixed beams 42 . a set of springs 48 run between the set of spring connection points 44 and the set of links 46 . the set of links 46 also connect in the rearward direction to a set of l - shaped bars 50 . the set of l - shaped bars 50 are positionally adjustable but are also connected to and restricted in movement by a pair of slide bearings 52 located on the set of fixed beams 42 at a point near the rearward ends of the set of fixed beams 42 . the adjustable pressure assembly 38 applies a downward force on the rolling basket assemblies 36 . the set of springs 48 may be selected to apply a desired force on the set of links 46 . this force will cause the set of links 46 to rotate about their hinged connections to the fixed beams 42 such that the set of l - shaped bars 50 exert more or less downward force into the rolling basket assemblies 36 . the rolling basket assemblies 36 includes a frame 54 extending between the set of arms 50 and about the ends of a rolling basket 56 . to this end , the frame 54 engages the rolling basket 56 through a rotational coupling 58 , such that the rolling basket 56 is capable of rotating about a rotational axis 60 . although multiple rolling basket assemblies 36 are not required , in the case where there are multiple rolling basket assemblies 36 , their respective rotational axes , as illustrated , may be non - collinear . however , it is contemplated that in some applications , it may be desirable for the rotational axes to be collinear . the rolling basket 56 is formed by a plurality of bars 62 that extend between end caps 64 and around a set of supporting framework rings 66 . the end caps 64 engage the rotational coupling 58 to allow the rolling basket assemblies 36 to rotate . as illustrated , it is contemplated that the plurality of bars 62 may have a helical configuration , such that the plurality of bars 62 twists around the cylindrical face of the rolling basket assemblies 36 . however , in some configurations , straight or other varied arrangements may be utilized . the plurality of bars 62 may have flat or rounded surfaces . in the illustrated configuration , the plurality of bars 62 has flat surfaces and a rectangular - shaped cross - section . furthermore , the plurality of bars 62 are mounted between the end caps 64 such that the outermost edge of the diameter of the rolling basket assemblies 36 are the sharp corners of the plurality of bars 62 . as such , as the rolling basket assemblies 36 rotate , a sharp corner is designed to impact the ground surface and , thereby , penetrate , and preferably , explode , the clumped soil and / or residue . that is , as the soil passes under the rolling basket assemblies 36 the rolling basket 56 rotates and the edge of the plurality of bars 62 act to both crush the remaining large chunks of earth as well as to level the soil . a section view of the rotational coupling 58 , taken along line 3 - 3 of fig2 , is shown in fig3 . corresponding isometric view of the rotational coupling 58 are shown in fig4 and 5 . the rotation coupling 58 , as noted above , couples the basket 56 to the frame 12 . more particularly , the frame 12 includes an arm 67 that carries a rigid , generally cylindrical shaped member 68 . the rotational coupling 58 includes a spindle 70 that is coupled to the rigid member 68 by a pin 73 . as shown in fig3 , the spindle 70 is cantilevered from the arm 66 via the connection to the rigid member 68 . the spindle 70 carries a hub 74 to which a basket hub mount 76 ( or end cap ) is coupled by fasteners 78 , 80 , such as bolts . the hub 74 is free to rotate around the spindle 70 by interfacing bearings 82 , 84 . as such , the basket hub mount 76 , and thus basket 56 , may passively rotate around spindle 70 as the implement 10 is pulled along the field surface . additionally , as shown in the figure , the hub 74 is carried by the spindle 70 such that a small gap 86 is present between the rigid member 68 and the hub 74 , which allows the hub mount 74 to rotate relative to the rigid member 68 . bushings 88 , 90 are interposed between the shaft of the spindle 70 and the inner surface of the rigid member 68 . the bearings are comprised of a composite material that flexes to provide cushioning for the spindle 70 when the spindle is loaded due to bending moments . thus , when the basket 56 is being operated at higher speeds or increased loads , the spindle 70 will be cushioned by the bushings 88 , 90 to reduce stress placed on the spindle during such operation . additionally , as noted above , the spindle 70 is allowed to float relative to the frame 12 , which also reduces the stress that would otherwise be placed on the spindle during high speed and / or high load conditions . while the rotational coupling 58 for only one of the baskets 56 has been described in detail , it is understood that the other rotational couplings , such as the rotational coupling at the opposite end of the basket 56 is similarly constructed . additionally , while the invention has been described with respect a cantilevered spindle for coupling a reel or a basket to an implement frame , the invention is not limited to such an application . many changes and modifications could be made to the invention without departing from the spirit thereof . the scope of these changes will become apparent from the appended claims .
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in the following , a particular embodiment of the invention will be described by way of example only . fig1 is a perspective view of a system unit 10 for use in a rack - mountable system . in a particular example described herein , the system unit is a computer system unit for forming a computer server for a telecommunications application , for example an internet server . as shown in fig1 the unit 10 has a front surface 12 formed by a front wall , a rear surface 14 formed by a rear wall , a left end surface 16 formed by a left side wall , a right end surface 18 formed by a right side wall , a lower surface 20 formed by a base wall and an upper surface 22 , in the present example formed by a cover 30 . as shown in fig1 the system unit 10 is provided with sacrificial transport flanges 24 , which extend above and below the system unit . this optional feature is removed before installation of the system unit 10 in a rack . the system unit 10 is constructed with an extremely robust chassis 11 , with the various walls 12 - 20 and the cover 30 forming the casing of the chassis 11 as well as internal walls ( not shown ) being formed of heavy gauge steel . the walls of the chassis can be made , for example , from electroless nickel - plated mild steel with a thickness of , for example , 1 . 5 to 2 . 0 - mm . the steel chassis 11 is pre - formed with mounting holes for the attachment of mounting flanges or a slide mechanism to enable the system unit 10 to be provided with a wide variety of mounting options and rack sizes . mounting flanges can be provided to suit standard 19 - inch , 23 - inch , 24 - inch or 600 - mm nominal frame widths . ( one inch = approximately 25 . 4 mm ). fig2 a is a plan view of the unit 10 showing the upper surface 22 / cover 30 and various options for flanges 26 with the displacements from the front surface indicated in mm . fig2 b is a front view of the unit 10 showing the front surface 12 and two different examples of mounting flanges 26 . the mounting flange shown to the left ( as seen in fig2 b ) is provided with a handle to facilitate insertion and removal of the unit 10 from the racking system , whereas the flange 26 to the right ( as viewed in fig2 b ) is not provided with a handle . in the present example , the mounting flanges can be attached using screws which pass through the mounting flange into threaded holes in the end walls 14 , 16 at either side of the chassis 11 of the unit 10 . fig2 c is a side view of the system unit 10 , showing the holes in the side of the system unit 10 for the mounting of flanges or a slide mechanism . vertical rows of holes are for the attachment of flanges to be attached to vertical rack components , and horizontal rows of holes provide for the attachment of a runners for permitting a slideable mounting of the system unit in a rack . fig3 is a perspective rear view of the unit 10 showing the cover 30 that forms the top surface 22 of the unit 10 . as can be seen , the cover 30 is provided with front locating flanges 32 that , in use , engage a co - operating front flange 31 of the body of the chassis 11 . side flanges 33 engage either side of the end walls forming the left and right ends 16 and 18 of the chassis 11 . detents 34 on those end walls engage within l - shaped slots 35 in the side flanges 33 so that the cover may be lowered onto the top of the chassis 11 and then moved forwards so as to cause the detents 34 to latch within the slots 35 . at the rear of the cover 30 , a rear flange 36 with a lower lip 37 engages over an abutment 38 at the top of the rear end wall 14 of the casing 10 . the cover can be secured to the remainder of the chassis 11 by means of a screw 39 that passes through this rear flange into a threaded hole in the abutment 38 . fig4 is an exploded perspective view from the front of the system unit 10 . this shows a motherboard 40 that is mounted on a horizontal mounting plane 41 within the chassis 11 . mounted on the motherboard 40 are between one and four processor modules 42 . a riser card 44 can receive a plurality of dual in - line memory modules ( dimms ) 46 . further dimms 46 can be received directly in slots in the motherboard . a slideable carriage 48 is provided for receiving one or more media drives . as shown in fig4 the slideable carriage 48 can receive up to two media drives . in the present instance , two media drives including a digital audio tape ( dat ) drive 50 and a cd - rom drive 52 are provided . appropriately configured metal cover plates 54 and 56 are provided for the media drives 50 and 52 . a disc bay assembly 58 provides a small computer system interface ( scsi ) backplane and cables for receiving one or more scsi media drives , such as a scsi disc drive 60 . although , in the present instance , the drives are controlled via a scsi - type interface , it will be appreciated that another media drive interface ( e . g ., ide ) could be used . a scsi card ( not shown ) is located within the chassis to the front of the motherboard . a bezel ( decor panel ) 62 is provided for covering ventilation holes 63 in the front wall 12 of the chassis 11 . a bezel 64 is provided for covering the media drives 50 , 52 and 60 . a fan control module 66 controls the operation of processor fans 68 and system fans 70 . a power sub - assembly that includes a power sub - frame 72 with a power distribution board assembly , is provided for receiving three separate power supply units 74 . an alarms module in the form of an alarms card 78 enables the signalling of alarms to the outside world , and is also connected to an led card 2 for signalling alarms locally on the front of the unit 10 . a power switch 82 is also provided on the front surface of the unit 10 . fig4 also illustrates one pci card 84 to be received within a pci slot 85 on the motherboard 40 . fig5 is a front view of the unit 10 showing the bezels 62 and 64 , a power and alarm panel 90 which includes the power switch 82 and a number of status light emitting diodes ( leds ) 92 . fig5 also illustrates the slots 86 and 88 for the media drives such as media drives 50 and 52 shown in fig4 . fig6 is a rear view of the unit 10 in a configuration with three dc power supply units 74 a , 74 b and 74 c . each of the power supply units 74 a , 74 b and 74 c is the same , and provides redundant power for the unit 10 . however , as will be seen later , one or more of the dc power supply units could be replaced by ac ( mains ) power supply units . the power supplies are hot swappable ( i . e ., while the system is running ), as long as they are swapped one at a time . with regard to power supply unit 74 a , it can be seen that this is provided with a handle 94 that is used for inserting and removing the power supply unit 74 a . the handle 94 includes a flange portion that is able to receive a screw 95 for securing the power supply unit to the chassis 11 . first and second power cable sockets 96 and 98 are shown . also shown is a grounding plate 100 that is secured by knurled nuts 102 , 104 and 106 to grounding studs 103 , 105 and 107 . grounding stud 103 provides a connection directly to the chassis 11 of the unit 10 . grounding studs 105 and 107 , on the other hand are electrically isolated from the chassis by an insulating board and are instead connected to logic ground ( i . e . the ground of the electronic circuitry ). by means of the grounding plate 100 , logic ground can be connected directly to chassis ground . the provision of this grounding plate provides for optional tying of logic ground to chassis ground . it will be noted that each of the power supply units 74 is provided with a similar grounding plate 100 , for connection to corresponding grounding studs . if it is desired to isolate logic ground from chassis ground , it is necessary to remove the grounding plate 100 from each of the power supply units 74 a , 74 b and 74 c . an isolated ground system is needed in some telco applications when operating in a regional bell operating company ( rboc ) mode . when operating in such a mode , the chassis and logic ground are connected at a remote location to provide , for example , lightning protection . in this case two - hole lugs 101 having a pair of holes 111 to fit over the pair of grounding studs 105 and 107 are provided for each of the power supply units 74 and are secured over the studs using nuts 104 and 106 . a similar two - hole lug 101 is secured to the grounding studs 108 and is secured with similar nuts . earthing wires 109 from each of the two - hole lugs 101 on the power units and the chassis then are taken to the remote , earthing location . the studs 103 105 , 107 and 108 are of a standard thread size ( m 5 ). the studs 105 / 107 and the studs 108 are at a standard separation ( 15 . 85 mm ). the studs 105 / 107 are self - retaining in the insulated board on the power supply units . the stud 103 is self - retaining in the casing of its power supply unit 74 . the suds 108 are also self - retaining in the system unit chassis . in a non - isolated ground situation , chassis ground can simply be tied to a desired ground potential ( for example , to the racking system ) by connecting a grounding cable to grounding studs 108 provided on the rear of the chassis . a further earth connection is provided via the power cables for the power supplies . fig6 also illustrates rear ventilation holes 110 through which air is vented from the system . fig6 also shows the alarms module 78 with a serial connector 112 enabling connection of the alarms module to a network for the communication of faults and / or for diagnostic operations on the unit 10 to be performed from a remote location . fig6 also shows a number of pci cards 84 received within respective pci slots 116 . a number of further external connections 114 are provided for connection of serial connections , parallel connections and scsi connections , and for the connection of a keyboard or a twisted - pair ethernet ( tpe ) connector . fig7 is a plan view of the motherboard 40 shown in fig4 . four cpu module slots 120 are provided . each of these slots is able to receive one processor module 42 , and any number between one and four slots may be occupied by a processor module 42 . a connector arrangement 122 is provided for receiving a riser card 44 as shown in fig4 . also , connectors 124 ( in four banks ) are provided for receiving dimms 46 as mentioned with reference to fig4 . edge connectors 126 are provided for connecting the motherboard to connectors mounted on the mounting plane 41 . also shown in fig7 is the slot 128 for the alarms module 78 and various ports 130 for the connectors 114 shown in fig6 . fig8 is a schematic overview of the computer architecture of the system 10 . as shown in fig8 various components within the system are implemented through application - specific integrated circuits ( asics ). the system is based round a ultrasparc port architecture ( upa ) bus system that uses a peripheral component interconnect ( pci ) protocol for an i / o expansion bus . the cpu modules 40 . 0 , 40 . 1 , 40 . 2 , 40 . 3 , and a upa - to - pci ( u2p ) asic 154 communicate with each other using the upa protocol . the cpu modules 40 and the u 2 p asic 154 are configured as upa master - slave devices . an address router ( ar ) asic 154 routes upa request packets through the upa address bus and controls the flow of data to and from memory 150 using a data router ( dr ) asic 144 and a switching network 148 . the ar asic 154 provides system control . it controls the upa interconnect between the major system components and main memory . the dr asic 144 is a buffered memory crossbar device that acts as a bridge between six system unit buses . the six system unit buses include two processor buses , a memory data bus and to i / o buses . the dr asic 144 provides crossbar functions , memory port decoupling , burst transfer and first - in - first - out ( fifo ) data read functions . clock control for the operation of the processor is provided by a reset , interrupt , scan and clock ( risc ) asic 152 . the pci bus is a high performance 32 - bit or 64 - bit bus with multiplexed address and data lines . the pci bus provides electrical interconnection between highly integrated peripheral controller components , peripheral add - on devices , and the processor - memory system . a one - slot pci bus 155 connects to a pci device 156 . 0 . a three - slot pci bus connects to three pci slots 156 . 1 , 156 . 2 and 156 . 3 . two controllers are also connected to the second pci bus 157 . these include a scsi controller 174 and a pci - to - ebus / ethernet controller ( pcio ) 158 . the scsi controller 174 provides electrical connection between the motherboard and separate internal and external scsi buses . the controller also provides for scsi bus control . the pcio 158 connects the pci bus to the ebus . this enables communication between the pci bus and all miscellaneous i / o functions as well as the connection to slower , on board functions . thus , the pcio enables the connection to an ethernet connection via a transmit / receive ( tx / rx ) module 161 and a network device ( nd ) module 162 . an ebus2 159 provides a connection to various i / o devices and internal components . super i / o 164 is a commercial off - the - shelf component that contains two serial port controllers for keyboard and mouse , an ieee 1284 parallel port interface and an ide disk interface . the super i / o drives the various ports directly with some electromagnetic interference filtering on the keyboard and parallel port signals . the alarms module 78 interfaces with the motherboard and provides various alarm functions . the nvram / tod 168 provides non - volatile read only memory and the time of day function . serial port 170 provides a variety of functions . modem connection to the serial port 170 enables access to the internet . synchronous x . 25 modems can be used for telecommunications in europe . an ascii text window is accessible through the serial port on non - graphics systems . low speed printers , button boxes ( for computer aided design applications ) and devices that function like a mouse are also accessible through the serial port . the serial port includes a serial port controller , line drivers and line receivers . a one - mbyte flash programmable read only memory ( prom ) 172 provides read only memory for the system . fig9 is a perspective rear view of the system 10 showing the withdrawal and / or insertion of a power supply unit 74 in a non - isolated ground situation . in this example , ac power supply units 74 are shown . it can be seen that the power supply unit 74 is provided with the handle 94 . as shown in fig9 the handle 94 is provided with a grip 184 , a pivot 182 and a latch 180 . to insert the power supply unit 74 it is necessary to slide the power supply unit into the power sub - frame 72 with the grip 184 of the handle 94 slightly raised so that the detent 180 can be received under the top 184 of the power sub - frame 72 . as the power supply unit 74 reaches the end of its movement into the power sub - frame 72 , connectors ( not shown ) provided on the power supply unit 74 make connection with a corresponding connector on the power distribution board at the rear of the power sub - frame 72 . also , at this time , the handle can be pushed down into the position shown in fig9 . this causes the detent 180 to latch behind the upper portion 184 of the power sub - frame 72 . the handle 94 can then be secured in place by tightening the screw 95 . the ac power supply unit 74 shown in fig9 has a single power socket 97 , whereas the dc power supply units 74 shown in fig6 have two power sockets 96 and 98 . irrespective of whether the arrangement is as shown in fig6 with two dc power sockets 96 and 98 , or as shown in fig9 with one ac power socket 97 , the configuration of the power socket ( s ) and the lever 94 is such that the lever cannot be moved , and therefore the power supply unit cannot be released from the power sub - frame 72 and the chassis 11 with a plug 186 of a power cable 188 in place in one of the power sockets 96 / 97 / 98 . the removal operation is achieved by releasing the screw 95 , removing the power plug , and lifting and pulling on the handle 94 . in an isolated ground situation , in order to hot - swap a power supply unit 74 , it is merely necessary to remove the two - hole lug 101 with its connecting earth wire 109 from the studs 105 , 107 of the power supply unit to be removed , to remove the old power supply unit 74 , to replace a new power supply unit 74 and then to reconnect the two - hole lug 101 and connecting earth wire 109 to the studs 105 , 107 of the new power supply unit 74 . these operations can all be performed with the system under power from the other power supply units 74 and with the two - hole lugs 101 and earth wires 109 in place over the chassis studs 108 and the studs 105 , 107 of the other power supply units 74 . the isolated ground situation is not shown in fig6 and 9 . in the non - isolated ground situation shown in fig6 and 9 , hot - swapping of a power supply unit is even easier , as it is merely necessary to remove the selected power supply unit 74 and to replace it with the new power supply unit 74 . fig1 a , 10 b , 10 c and 10 d are rear , top , front and perspective views of a power sub - frame for receiving three power supply units : the power sub - frame 72 comprises a rectangular , box - shaped frame 191 , with four exterior walls on four sides ( the top , bottom and two lateral surfaces ), one open side 195 for receiving three power supply units and a power distribution circuit board 190 opposite to the open side . in the present instance , the walls are made of electroless nickel - plated mild steel . fig1 a shows the power distribution board at the “ rear ” of the power sub - frame ( i . e . opposite to the open side ). when inserted in the chassis of the system unit , this “ rear ” of the power sub - frame is actually the forward - most side of the power sub - frame when viewed with respect to the system unit . the power distribution board 190 is formed with ventilation holes 194 and carries circuit tracks and components ( not shown ). fig1 a also illustrates the flanges 198 with screw holes 199 for securing the power sub - frame to the rear chassis wall . fig1 b shows the top of power sub - frame . it will be noted that the power sub - frame body 196 is provided with apertures 197 for lightness and for ventilation purposes . fig1 c shows the open ( front ) side 195 ( see fig1 b ) of the power sub - frame . when inserted in the chassis of the system unit , this “ front ” of the power sub - frame is actually the rear - most side of the power sub - frame when viewed with respect to the system unit . within the power sub - frame 72 , connectors 192 a , 192 b and 192 c for the three power supply units 74 a , 74 b and 74 c , respectively , can be seen . these connectors are mounted on the power distribution board 190 inside the power sub - frame 72 . fig1 c also shows the flanges 198 with screw holes 199 for securing the power sub - frame to the rear chassis wall . fig1 d is a perspective view of the power sub - frame 72 , which shows that this in fact forms part of a power sub - assembly 71 . internal walls 200 separate three compartments , each for a respective one of the three power supply units 74 . cables 202 connect standby power and signal lines from the power distribution board 190 to a connector 204 for connection to an alarms module . cables 206 connect main power and signal lines from the power distribution board 190 to various connectors 208 , 210 , 212 and 214 . fig1 e shows the various connector types 192 , 204 , 208 , 210 , 212 and 214 and the electrical signal connections thereto . fig1 is a schematic representation of some of the logic connections on the power distribution board . for ease of explanation , only those connections relevant for an understanding of the present invention are described . at the left of fig1 , the three connectors 192 a , 192 b and 192 c for the three power supply units 74 a , 74 b and 74 c are shown . for reasons of clarity and convenience only those connections relevant for an understanding of the present invention as shown . for example , as illustrated with respect to fig1 e , the connectors 192 have many pins and pass many signals via respective lines . however , as not all of these lines are necessary for an understanding of the present invention , and as it would be confusing to illustrate all of the signal pathways on a diagram , only selected pathways are shown in fig1 . it is to be noted from fig1 e , that the power supply units output ground , + 3v3 , + 5v , + 12v , − 12v and + 5v standby potentials as well as control signals such as psu ok , psu on , etc . the + 5v standby voltage is used for powering the alarm module 78 . the other voltages are for powering the motherboard and other main system components . the various lines could be configured using bus bars , wires , printed circuit or thick film conductors as appropriate . firstly , the two - of - three circuit 232 will be explained . this circuit is powered by the + 5v standby voltage 231 provided from each of the power supply units 74 . each of the power supply units outputs a psu ok signal via a pin on its respective connector to a corresponding psu ok line 230 a , 230 b and 230 c when the power supply unit is operating correctly . each of these psu ok lines 230 is connected to the two - of - three circuit 232 . this comprises three and gates 234 , 236 and 238 , each for comparing a respective pair of the psu ok signals . the outputs of the and gates are supplied to an or gate 240 . if the output of this or gate is true , then at least two of the power supply units 74 are operating correctly , and power can be supplied to the motherboard of the computer system . this can be achieved by closing the main power line 245 . an output signal 242 could be supplied to a gate 244 ( for example a power fet ) to enable current to pass to the motherboard and other system components . additionally , or alternatively , a power ok signal 246 for controlling some other form of switch mechanism ( not shown ). if alternatively the output of the or gate 242 is false , then this indicates less than two of the power supply units 74 are operative . in this case power is prevented from being passed to the motherboard 40 of the computer system . this can be achieved by interrupting the main power line 245 . an output signal 242 could be supplied to a gate 244 ( for example a power fet ) to prevent current being passed to the motherboard and other system components . additionally , or alternatively , a power fault signal 246 could be passed to the alarms module and / or for controlling some other form of switch mechanism ( not shown ). one - of - three power control is effectively provided by the alarms module 78 to be described later . however , with reference to fig1 , input a / b signals 268 and output sense signals 270 are passed to the alarms module for standby operation , and control signals 272 could be returned for turning off of a power supply unit , if required . fig1 further illustrates a protection circuit 256 that is able to detect an overcurrent representative of a current greater than 2 * imax , where imax is the maximum current that can be output by a power supply , 2 * imax being the maximum current which should be required by the system unit . if a current greater than 2 * imax is detected , this is representative of a fault in the system unit . in accordance with telco requirements , in such a situation the system should be powered down . by providing for overcurrent detection on the power distribution board , where the maximum drawable current should be 2 * imax , it is possible to test for a fault at a lower overall current than if this test were made within each power supply unit . if the test were made in each power supply unit , each power supply unit would need to be tested for an overcurrent in excess of imax , whereby one would be testing for a total current drain of 3 * imax . this could lead to faults not being detected or not detected early enough and the system could incorrectly be drawing up to 3 * imax , which could damage components and traces ( tracks ). thus , as shown in fig1 , each of the main power lines ( e . g ., + 12v ) 250 a , 250 b and 250 c from the power supply units 74 a , 74 b and 74 c , respectively is connected to form a common power supply line 254 . an overcurrent detector 258 detects a current in excess of 2 * imax . if such a current is detected ( for example as a result of a fault represented by the box 266 ), then a signal 261 is provided to the connectors 192 , a , 192 b and 192 c for shutting down the power supplies 74 a , 74 b and 74 c , respectively . also , a signal 262 is passed to a switchable shunt 260 ( e . g ., a silicon controlled rectifier ( scr ), a metal oxide semiconductor field effect transistor ( mosfet ), an insulated gate bipolar transistor ( igbp ), etc ) to shunt the power supply line 254 to ground . this will cause any energy stored in the power supplies and also in the system ( for example as represented by the capacitor 264 ) to drain to ground , thus protecting the system . the use of the two - of - three circuit described above means that redundant power supply operation is provided in that the system can remain powered even if one of the three power supply units fails . as only two - of - three power supply units are needed to power the system the third power supply unit can be hot swapped while the other two power supply units power the system . fig1 illustrates the location of an alarms card forming the alarms module 78 in the rear of the system unit 10 . fig1 is a functional block diagram for illustrating the alarm sub - system on the alarms module 78 . the alarms sub - system provides lights out management or remote management of the system over a serial connection . the alarms module 78 interfaces with the motherboard through an ebus edge connector slot 298 ( connected to ebus2 as shown in fig8 ). a pci - style bracket is attached to one edge of the alarms module ( as seen in fig1 ) and provides the external interfaces at the rear of the chassis 11 . internal interfaces provide connections to the power supply assembly and to the led card 80 located at the front panel of the system unit 10 . the alarms module is powered by the standby , or reserve , power supply . the alarms module only requires power from a single power supply to remain operable . accordingly , the alarms module can remain operable even in a situation where the system has been powered down due to there being only one power supply unit operable . the alarms sub - system comprises a logic device 280 which receives inputs 298 from the ebus , inputs 286 from the fans , input 290 from general purpose events , input 270 from the power supply unit output rails and inputs 268 from the a and b power inlets . the logic circuit samples , or multiplexes , the inputs to the microcontroller 296 in response to multiplex signals from the microcontroller 296 . the microcontroller 296 processes the sampled ( multiplexed ) inputs . the microcontroller 296 provides power control signals 272 for controlling the power supply units , and alarm outputs for the output of alarm signals . the microcontroller 296 also outputs power supply unit status signals 304 and fault signals 306 . the micro controller 296 can further output a system reset signal 310 , when required . alarm signals to be passed to a remote location can pass via a remote serial connection 112 . diagnostic and remote control signals can be passed from the network via the serial connection 112 to the microcontroller 296 . control signals can thus be provided via the remote serial connection over the network for powering on and powering off the system . examples of other commands that can be sent to the microcontroller via the remote serial connection 112 are to turn alarms off , to reset the monitoring of all failures , to display the status of all fans , power supply units , alarms and fault light emitting diodes ( leds ), to display an event log , etc . the microcontroller is programmed to report any fan failures or changes in power supply units status by means of the leds 92 ( fig5 ) on the system front and optionally to report the faults via the remote serial connection 112 . the microcontroller 296 is programmed to maintain the event log that was referenced above . fig1 illustrates the configuration of the fan control module 66 shown in fig4 . the fan control module is subdivided into two halves 66 a and 66 b . one half 66 a handles one processor fan 68 a and one system fan 70 b and the other half 66 b handles the other processor fan 68 band the other system fan 70 b . the fans are connected to the fan control module 66 by respective power lines 320 so that the fans receive their power via the fan control module . the fan control module receives + 12v power via power lines 324 a / b from the power distribution board 190 and supplies voltages to the fans via the power lines 320 in a controlled manner . for convenience , tacho ( speed ) signals 322 a 1 , 322 a 2 , 3221 b 1 , and 322 b 2 from the fans pass via the fan control module 66 . the speed signals are not processed by the fan control module , but are instead forwarded via tacho sense 326 to the power distribution board 190 . the power distribution board then routes the tacho sense signals to the alarms module 78 to form the signals 286 shown in fig1 . this routing is convenient as it enables simpler wiring looms to be used . also , when replacing a fan unit , the maintenance engineer only needs to remove a single bundle of wires from the fan to the fan control module 66 , rather than having to locate a number of different connectors connected to the fan . the fan control module thus has four fan connectors , each for receiving a connector connected to a bundle of wiring from a respective fan , plus a further connector for receiving a connector with a bundle of wires from the power distribution board . module , but are instead forwarded via tacho sense 326 to the power distribution board 190 . the power distribution board then routes the tacho sense signals to the alarms module 78 to form the signals 286 shown in fig1 . this routing is convenient as it enables simpler wiring looms to be used . also , when replacing a fan unit , the maintenance engineer only needs to remove a single bundle of wires from the fan to the fan control module 66 , rather than having to locate a number of different connectors connected to the fan . the fan control module thus has four fan connectors , each for receiving a connector connected to a bundle of wiring from a respective fan , plus a further connector for receiving a connector with a bundle of wires from the power distribution board . as shown in fig1 , each half 66 a / 66 b of the fan control module receives respective power lines 324 a / b from the power distribution board . each half of the fan control module includes electrical noise isolation circuitry 340 a / b . this electrical noise isolation circuitry 325 a / b , which can be of conventional construction , prevents dirty power signals on the lines 320 a / b caused by electrical noise from the fans being passed back along the power lines 324 a / b and potentially contaminating the otherwise clean power supply to the electronics of the system unit ( e . g ., the components on the scsi bus . the provision of clean power supply signals in a telco application is important in order to ensure reliability of operation . although in the present example the noise isolation circuitry is located in the fan control module , it could be located elsewhere as long as it is effective to isolate the main power lines from fan - related electrical noise . as further shown in fig1 , each side 66 a / b of the fan control module comprises control logic 342 a / b which receives a temperature signal from a temperature sensor 344 and adjusts the speed of the fans by adjusting the voltage supplied thereto in accordance with pre - programmed parameters in order to provide a desired degree of cooling . the control logic 342 a / b can be implemented by an asic , a programmable logic array , or any other appropriate programmable logic . alternatively , it could be implemented by software running on a microcontroller or microprocessor module . it should be noted that the fan control module could be implemented in a unitary manner , rather than being divided into two halves . although in the present instance the fan control module is preferably configured on a single circuit board , this need not be the case . also , although the temperature sensor is also mounted on the same circuit board , it could be mounted elsewhere . moreover , although it is preferred that a single temperature sensor is used , with the advantage that the fan speeds of the respective fans can be ramped up in parallel in a controlled manner , more than one temperature sensor could be used . ideally , in this case they would be located close together and control of the individual fans could be dependent on individual signals but would more preferably be dependent on a function of some or all of the temperature signals . as a further feature , the control logic could be provided with different sets of programmed parameters depending on the number of processors present and could be responsive to the number of processors present . it will be appreciated that although particular embodiments of the invention have been described , many modifications / additions and / or substitutions may be made within the spirit and scope of the present invention . accordingly , the particular example described is intended to be illustrative only , and not limitative .
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referring in detail to fig1 the novel barbecue cooking apparatus of the present invention is illustrated in the general direction of arrow 10 which includes a fire bowl 11 on which a lid 12 is disposed so as to act as a cover either during the cooking procedure or when the device is not in use . the lid is detachably connected to the upper edge marginal region of the fire bowl 11 and a tether cord 13 movably couples the lid 12 to the apparatus such as at a support brace 14 . therefore , the lid may be released from the fire bowl 11 but cannot be separated therefrom due to the connection by the tethering cord . the apparatus 10 is outwardly cantilevered from a supporting structure by a rod 15 . one end of the rod may be attached to a support while its free end carries a fitting 16 which is coupled to the brace 14 by means of a nut and bolt fastener . also , it is noted that a pipe 17 outwardly radiates from the support brace 14 and includes a band which enters the apparatus at its center . the opposite end of the tube 17 is connected to a gas supply as will be described later . it is to be noticed that immediately adjacent to the bottom of the fire bowl 11 , there is provided a baffle 18 which serves as a wind deflector to prevent gusts of wind from entering the fire bowl from any vent openings . furthermore , the lid 12 includes a knob 20 and a pair of flanges separated by the thickness of the tub of the lid 12 . however , a flange 21 of the pair is spaced from the underside of the lid a sufficient amount to accommodate the thickness of the edge marginal region of the fire bowl . in this manner , the lid may be used as a wind deflector when not covering the entire fire bowl . referring now in detail to fig2 it can be seen that the apparatus 10 is outwardly cantilevered from a support rod or tube 23 which may , for example , be the aft or stern stanchion on a power or sailboat . a coupling 24 of a c - shaped configuration serves to connect the rod 15 to the tube or rod 23 . the extreme end of the rod 15 is threaded as seen at numeral 25 and a flanged member 26 is threadably engaged therewith . by rotating the flanged member on the threads 25 , a portion of the flanged member is drawn against the c - shaped clamp and securement is effected . it is to be understood that the support member 23 may be vertically disposed or horizontally disposed whereby the cooking apparatus 10 can be suitably supported in a cantilevered position . it can also be seen in fig2 that the supply of fuel is carried in a pressurized vessel 26 for holding a sufficient quantity of gas . therefore , the cooking apparatus of the present invention has all of the great features of conventional charcoal versions but adds the convenience of instant gas cooking . the canister or cylinder 26 is refillable or disposable as desired and adapts to existing lpg and cng systems . the cylinder 26 includes a pressure head 27 for dispensing gas into the tube 17 via manual controls 28 that may be readily set at the convenience of the user . a quick disconnect arrangement indicated in general by the numeral 30 releasably couples the cylinder 26 to the end of gas tube 17 and a shield 31 covers a release mechanism for detachably connecting the cylinder to the gas tube . the fire bowl 11 includes an internal cavity which is occupied by a substantially concave liner illustrated in general by numeral 32 that supports a concave screen 33 . the screen is covered by a grill 34 taking the form of a circular rod having crosspieces 35 and 36 which support a plurality of rods arranged in fixed parallel , spaced - apart relationship so that the opposite ends of each of the rods is fastened to a portion of the ring 37 . the grid or grill 34 is releasably coupled to the edge marginal region of the fire bowl by means of clips 38 and 40 which are carried on opposite sides of the fire bowl and include openings which receive selected rods in the midsection of the grid as will be described later . fig2 also discloses that the screen 33 holds a plurality of briquettes such as identified by numeral 41 which may be used to enhance the heating effect of the gas burner . the number of briquettes depends on the user and the manner of cooking . the lid 12 in addition to the flange 21 includes a central plate 42 which is provided with a plurality of holes so that venting is accomplished when the lid is used to cover the fire bowl and the grill as shown in fig1 . referring now in detail to fig3 an exploded view is illustrated of the apparatus where it can be seen that the fire bowl 11 includes a reinforced opening 43 provided in the center of its bottom and an outer ring of openings , such as opening 44 which serve as venting apertures the reinforced opening 43 is used to insertably receive a threaded portion 45 of a base 46 . the base 46 includes a circular portion having the bottom of the fire bowl placed on top thereof while the wind deflector or baffle 18 is located on the underside of the anchor or base portion 46 . a lower threaded portion ( not shown in fig3 ) extends downwardly from the portion 46 of the base and is attached to a nut coupler 47 carried on the end of tube 17 . inasmuch as the threaded connection portions 45 and the lower portion ( not shown in fig3 ) are tubular , gas flow will pass from the tube 17 through the base into a burner portion indicated by numeral 50 . the burner 50 is of conventional design including a plurality of apertures for releasing gas for ignition however , the burner does include an eyelet 51 intended to project through a central opening or hole 52 in the reinforced center of screen 33 . once so disposed , a retaining clip 53 is inserted through the eyelet for retention purposes . fig3 also discloses that the liner 32 is of similar shape and construction to the fire bowl 11 ; however , the liner includes a plurality of openings , such as opening 54 , that are in spaced - apart relationship with respect to a central opening 55 . the openings 54 are vent holes while the central opening 55 is intended to be coaxially disposed with respect to the opening 43 on the fire bowl so as to insertably receive the upper threaded portion 45 of the base 46 . also , it can be seen that the upper edge of the liner includes the clips 38 and 40 and that the center rod identified by numeral 56 of the grill 34 is longer than the other rods so as to outwardly project beyond the perimeter of the ring . the projecting opposite ends of the rod are intended to fit into the retainers 38 and 40 in order to hold the grill in position so that it will not slide or inadvertently move during the cooking procedure . it is to be noted that the wind deflector or baffle 18 includes a central portion which is dome shaped and indicated in general by the numeral 57 . the outer periphery of the deflector includes an upturned lip identified by numeral 58 . therefore , the deflector is substantially dish shaped with a high inner crown or dome . the center portion of the deflector is similar to the screen 33 , liner 32 , and bowl 11 in that the center opening is reinforced in thickness so that ready support on the base 46 can be attained . referring now in detail to fig4 it can be seen that all of the components of the barbecue cooking apparatus 10 are coaxially related and that all the components are substantially mounted on the base 46 which is held on angle member 58 carried on the brace 14 . the base 46 includes the upper threaded portion 45 which mounts the bowl 11 , and the inner liner 32 . it is to be particularly noted that the burner 50 includes a lower plate having a threaded aperture indicated broadly by the numeral 61 which threadably engages with the threaded upper portion 45 . by this means , the burner 50 is rotated and presses the liner downward into engagement with the reinforced central section of the bowl 11 . thus , assembly is achieved . the screen is retained by insertion of the hole over the eyelet 51 so that the clip 53 can be installed . the bottom or underside of the bowl 11 is conical shaped in order to conform and mate with the dome shape 57 of the deflector 18 . such an arrangement ensures that a certain amount of space will be available for airflow through the vents 44 between the underside of the bowl and the outer lip 58 of the deflector . by employing the liner which is of substantial conformal configuration to the configuration of the bowl 11 , the bowl will never receive any of the debris , ash , or food substances that would normally occur in a barbecue situation . the liner 32 serves to catch such ingredients should any pass through the screen 33 . therefore , the liner device is very convenient and clean . referring now in detail to fig5 and the gas supply portion of fig4 it can be seen that a simple pin attachment and release mechanism are provided for attaching the control head 27 of the fuel supply to the tube 17 . in fig4 a nozzle 63 is provided with a reduced groove 64 so that when inserted into a receiver 65 , the groove 64 will be open through a notch 66 . such a circumstance is shown in fig5 and , in this view , a pin 67 is positioned through the opening 66 and through the groove 64 for releasable retention purposes . a cover 31 may be pulled back as shown in fig4 during the installing or removing of pin 67 . however , during the operation of the gas system , the cover 31 is disposed over the entire connection so that the pin cannot be advertently displaced . the cover 31 is manually removed and includes a forward stop indicated by numeral 68 and a rear back - up ring 70 . 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 may be made without departing from this invention in its broader aspects and , therefore , the aim in the appended claims is to cover all such changes and modifications as fall within the true spirit and scope of this invention .
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since the present invention concerns atomic force microscopy ( afm ) as well as scanning tunneling microscopy ( stm ) and near field scanning optical microscopy ( nsom ), a shod description of the physical apparatus used in afm , stm and nsom is provided for those not familiar with this prior art . referring to fig1 there is shown a conceptual diagram of an atomic force microscope 100 incorporating both afm and near field optical sensors . a microminiature cantilever arm 102 with a sharp tip 104 at its free end is used to probe the surface of a sample 110 . in some preferred embodiments the tip 104 is simply the apex of the cantilever 102 and does not project out from the cantilever . furthermore , as will be described below , the tip 104 may be substantially transparent , or may be doped so as to function as a photodiode . in the preferred embodiments , the sample 110 is mounted on an xyz scanning stage 113 . this is a &# 34 ; piezo scanning tube &# 34 ; type of stage , which uses piezoelectric actuators to precisely move the sample 110 in the x , y and z directions . the cantilever 102 is kept stationary while an xyz scanning stage 113 moves the sample 110 so as to scan the sample &# 39 ; s surface . those ordinarily skilled in the art will recognize that a separate z translator apparatus for moving the probe 102 up and down relative to the sample 110 may also be utilized in lieu of a three axis scanning stage 113 . alternately , the sample &# 39 ; s surface can be scanned using a probe holder 112 that functions as an xyz scanner to move the cantilever 102 while keeping the sample 110 stationary . regardless of whether the sample holder 113 of the probe holder 112 or both are used to move the probe relative to the surface of the sample , scanning is controlled by a programmed microcontroller or computer 114 , which also analyzes measurement data and displays measurement information on display 116 . the afm has a &# 34 ; contacting mode &# 34 ; of operation and a &# 34 ; non - contacting mode &# 34 ; of operation . in the &# 34 ; contacting mode &# 34 ; of operation , the tip 104 rides on the surface of a sample with an extremely light tracking force , on the order of 10 - 5 to 10 - 10 n . profiles of the surface topography are obtained with extremely high resolution . images showing the position of individual atoms are routinely obtained . in the second non - contacting mode of operation , the tip 104 is held a short distance , on the order of 5 to 500 angstroms , from the surface of a sample and is deflected by various forces between the sample and the tip ; such forces include electrostatic , magnetic , and van der waals forces . in either mode of operation , measurements of the sample &# 39 ; s surface topography or other characteristics are obtained by measuring deflection of the cantilever 102 . deflection of the cantilever is usually measured using precisely aligned optical components 120 coupled to a deflection measurement circuit 122 , although other techniques are sometimes used . atomic force microscopy is capable of imaging conductive as well as insulating surfaces with atomic resolution . typical afm &# 39 ; s have a sensitivity of 0 . 1 angstrom in the measurement of displacement . the microscope 100 shown in fig1 combines nsom and afm measurement modalities . near field scanning optical microscopy is an analysis tool that can be used either alone , or in conjunction with afm to analyze the topography and material characteristics of a substrate or other target object . the microscope is operable with both conducting and insulating surfaces , and can be used to detect impurity atoms in a sample near the surface , such as those placed in a sample using ion implantation . as noted above , this microscope assembly 100 has a scanning and measurement controller 114 , a cantilever 102 with a substantially transparent or photosensitive sharp tip probe 104 positioned over a sample 110 , cantilever deflection measurement optics 120 and a cantilever deflection measurement circuit 122 for afm operation . the cantilever 102 in assembly 100 differs from conventional afm cantilevers in that it includes a photodiode 130 ( also herein called a photosensor or photosensitive region of the cantilever ) in the vicinity of the tip 104 and an electrode 132 or equivalent low impedance connector that couples the photodiode 130 to a photodiode current measurement circuit 140 . alternately , the tip can itself be part of the photodiode . referring to fig2 conventional scanning tunneling microscopes ( stms ) are used primarily to monitor the electronic character of the surfaces being scanned . the stm / nsom assembly 200 has a cantilever 202 with a conductive tip 204 . in this example the tip 204 is the apex of the cantilever 202 and is also used as the point at which tunneling current enters the stm probe from the sample 110 . in other embodiments of the present invention the tip can be a projecting , conductive tip that projects away from the cantilever 202 . tunneling currents in conductive or semiconductor samples are induced by placing a conductive tip 204 one to ten angstroms above the sample 110 , and introducing a low voltage electric field ( typically less than one volt ) between a conductive tip 204 and the sample 110 , which is mounted on a metal plate 222 for ease of electrical connection to the sample . tunnelling current , drawn from the tip through the one to ten angstrom gap 150 between the tip 204 and sample 110 , is indicative of the size of the gap 150 . stms typically have two modes of operation . the first is constant height mode , for very flat samples , in which the tip is scanned at a constant height and the tunneling current is measured to determine the topography of the sample . the second mode is constant current mode , in which tunneling current is kept constant by varying the height of the cantilever until a preselected current level is restored . a tunneling current measurement circuitry 220 , coupled to both the tip 204 and the sample 110 , controls the assertion of a current inducing voltage on the tip 204 and measures the magnitude of the resulting tunneling current . the measurement data , or images generated from that data , are displayed on display device 116 after appropriate processing by the controller 114 . the cantilever 202 includes a photodiode 230 at its end . the doping required to form the photodiode 230 also makes the apex of the cantilever conductive . as a result , the photodiode 230 is can be used both as a photodiode for near field scanning optical microscopy and as a conductor for scanning tunneling microscopy . as a result , the photodiode 230 region of the cantilever 202 is coupled to both a tunneling current measurement circuit 220 and a photodiode current measurement circuit 140 , only one of which is used at any one time depending on the type of measurements being taken . referring now to fig3 a , the substantially &# 34 ; l &# 34 ;- shaped afm / nsom cantilever 102 includes an upper surface 300 and lower surface 302 . the cantilever in a first preferred embodiment is made from a silicon substrate in order to take advantage of its transparency and semi - conductor properties . a photodiode 130 is disposed at a first end 306 of the cantilever 102 . in the preferred embodiment , the photodiode is a pn junction diode created by doping a n - type substrate with boron , or by doping a p - type substrate with phosphorous . when a silicon substrate is used to make the cantilever 102 , the photodiode 130 may be formed directly in the silicon substrate . alternatively , a silicon nitride or silicon dioxide substrate ( either alone or formed on top of an underlying glass support substrate ) can be used with a polysilicon or amorphous silicon film on the surface of the cantilever for forming the pn junction of the photodiode 130 . the silicon nitride or silicon dioxide variations can be manufactured less expensively than the pure silicon cantilevers and as such are ideal for manufacturing large arrays of photosensitive cantilevers . disposed on the photodiode 130 and extending away from the cantilever 102 is the probe tip 104 . as shown in fig3 a and 3b , in one preferred embodiment the photo diode 130 encircles and includes an extended region 308 ( see which extends radially beyond the probe tip base region 309 . the probe tip 104 is constructed out of transparent materials and serves to transmit the scattered light induced by the probe &# 39 ; s presence in an evanescent field through the probe 102 to the photodiode 130 directly . the scattered light transmitted through the probe 102 will induce current flow in the photodiode 130 , transforming the optical energy into an electrical signal which may be transmitted through an electrode 132 for processing by a data collection system . those ordinarily skilled in the art will recognize that with the photodiode of the present invention , the adjustment and screening pin - hole configuration of the prior art is not required . this is because of the close proximity between the photodiode and the sample as provided in the present invention . however , if reflections from the optical positioning system result in measurement errors in the photodiode system , means for differentiating the light sources may be employed . the optical cantilever positioning system ( including cantilever deflection measurement optics 120 and a cantilever deflection measurement circuit 122 ) discussed above may utilize a different color light than detectable by the photodiode 130 . in addition , time division or frequency division multiplexing may be utilized to differentiate the light sources . an alternative embodiment cantilever 400 is shown in fig4 . the cantilever 400 includes an offset photodiode 402 adjacent to the probe tip 404 . in this configuration , scattered light is collected due to the probe tip &# 39 ; s interference with the induced surface field over the sample . in this configuration , light is not required to be directly transmitted through the probe tip 404 , and instead is directly collected by means of the photodiode 402 . this offset photodiode configuration is well suited for stm / nsom applications in which the two modes of operation are a scanning tunneling mode and a near field optical mode . thus , in the configuration of fig4 the probe &# 39 ; s tip 404 may be metal coated or doped so as to render the tip 404 semi - opaque and conductive . in this configuration , light scattered by the probe may still be collected due to the close proximity of the photodiode 402 to the sample surface . the photodiode 402 is connected to a photodiode current measurement circuit via an electrode 410 while the conductive probe tip 404 is connected to a tunneling current measurement circuit 220 . fig5 shows a cantilever 500 including a photodiode 501 and electronics 502 formed on the same substrate as the cantilever . electronics 502 include amplifiers and signal conditioning apparatus for pre - processing the photodiode signals generated as the photodiode 501 is exposed to scattered light . in this embodiment , improved signal to noise ratios can be achieved by boosting and / or processing the photodiode signals prior their exposure to extraneous noise , allowing for better system performance . the electronics 502 are disposed in and / or on the cantilever substrate material and are in electrical communication with the photodiode 501 by means of electrode 503 . those ordinarily skilled in the art will recognize that any of a variety of semiconductor devices may be formed in the cantilever structure disclosed thereby maintaining the electronics in close proximity to the photodiode 501 for signal processing purposes . alternatively , other means for detecting the deflections in the cantilever arm in lieu of the optical positioning system disclosed above may be selected . one such means , shown in fig6 a and 6b , includes a piezoresistive sensor 520 embedded into a cantilever 521 as described in pct patent document wo 9212398 , published jul . 23 , 1992 ( pct application no . 91us9759 ) which is incorporated herein by reference . the piezoresistive sensor 520 is coupled to a resistance measurement circuit 522 by a pair of electrodes 524 , while the photodiode region is coupled to a distinct electrode 526 . a second cantilever deflection detection apparatus , shown in fig7 uses capacitive sensing wherein a double level cantilever 550 forms a capacitive sensor for monitoring the deflections in the cantilever . capacitor plates 551 on the two arms are coupled by electrodes to a capacitance measurement circuit 552 . the resistance measurements for the apparatus shown in fig6 a - 6b and the capacitance measurements for the apparatus shown in fig7 correspond directly to deflections of the cantilever by either physical contact with a sample or by van der waals forces . these and other means may be utilized as is known in the art without departing from the spirit of the present invention . referring to fig8 a , the first step of the manufacturing process is to provide a substrate 602 , such as a lightly doped p -& lt ; 100 & gt ; silicon wafer . silicon epitaxy is used to grow an etch stop layer 604 as well as a lightly doped epitaxial layer 606 used for fabrication of electronic devices . the etch stop layer is 1 μm thick and doped to 3 × 10 20 cm - 3 with boron and germanium . boron doping in excess of 10 20 cm - 3 reduces the etch rate of silicon in ethylene diamine pyrocatecol ( edp ) by approximately 300 times . germanium is included to reduce the residual stress caused by the mismatch of lattice constants of silicon and boron . a 5 μm thick layer of lightly p - boron doped ( 3 × 10 15 cm - 3 ) silicon is grown over the etch stop layer . a pn junction photodiode is fabricated by ion implanting 10 18 cm - 3 phosphorus into the lightly doped p - type surface epitaxial layer to form an n - region 608 . the cross - section of the photodiode is approximately 50 μm 2 . the wafer is then thermally oxidized to create an oxide film 610 which serves as both an anti - reflection coating for the photodiode as well as a passivation layer . openings in the oxide layer are created and contact vias are formed . after annealing , windows are patterned in the back side of the wafer using a dual - sided aligner . the back side windows are used in the final stages of the manufacturing process to completely etch away the silicon under the cantilevers to yield free - standing structures . then 500 nm of aluminum are sputtered on the wafer and patterned into contact pads 612 and metal lines ( not shown ). this gets us to the configuration shown in fig8 a . next , the actual shape of the cantilever is created by patterning a 6 μm thick film of az 4620 photoresist . the resist is baked for over 2 hours at up to 200 ° c . and acts as a masking material with 5 μm of silicon are etched in a sf 6 plasma . after dry etching , the cantilever shape is completely defined and the photodiodes are fully functional . in order to free the cantilever from the substrate , the front of the wafer is coated with approximately 50 μm of hitachi pix3500 polyimide and baked over six hours at temperatures up to 400 ° c . a cross section view of the wafer at this point in the manufacturing process is shown in fig8 b . the wafer is then etched in edp at 105 ° c . until the etch stop layer 604 is reached , leaving 5 μm thick cantilevers resting on the 1 m thick silicon membranes . this is an anisotropic etch that leaves the remaining portion of the supporting wafer with walls sloped along the ( 100 ) crystallographic plane . fig8 c shows the wafer after the anisotropic etch . the silicon membranes are removed by dry etching from the back side . the polyimide film is removed in an oxygen plasma . individual cantilevers are then broken off the wafer , producing cantilevers as shown in fig8 d . the resulting cantilevers are typically bonded to support posts for ease of mounting to a probe holder . a four inch wafer using the above process yields several hundreds of cantilevers . for simplicity , the tips for the cantilevers produced by the above described process are the apex of the cantilevers themselves . in alternate embodiments , a protruding sharp tip can be manufactured separately and bonded to the cantilevers , or can be fabricated directly on the wafer substrate ( prior to the photodiode doping step of the manufacturing process described above ) at positions that will subsequently become the ends of cantilevers . the cantilever &# 39 ; s tip should have a radius of curvature less than 500 angstroms and preferably less than 250 angstroms . the final sharpness of the tip is typically determined by the sharpening effect of a low temperature oxidation . while the present invention has been described with reference to a few specific embodiments , the description is illustrative of the invention and is not to be construed as limiting the invention . various modifications may occur to those skilled in the art without departing from the true spirit and scope of the invention as defined by the appended claims .
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referring to fig1 returning air from various temperature control zones is drawn into a return duct 10 by a fan 12 for subsequent flow over a cooling coil 14 . the chilled air is thereafter provided to a number of temperature control zones via dampers 16 , 18 , and 20 . these dampers are controlled by a system controller 22 which receives temperature readings from each zone via remote temperature sensors 24 , 26 , and 28 . the system controller 22 also receives a temperature reading of the chilled air leaving the cooling coil 14 via a temperature sensor 30 . referring now to fig2 various elements of a two stage cooling system associated with the cooling coil 14 are illustrated relative to control elements of the system controller 22 . in particular , the cooling coil 14 is seen to include two stages of cooling 32 and 34 which chill refrigerant which subsequently passes through the cooling coil 14 before returning to the cooling stages via a condensing coil 36 . the two stages of cooling 32 and 34 are activated by relay logic 38 receiving appropriate voltage signals from a power source 40 . the relay logic 38 causes the various voltage levels to be applied to the respective stages of cooling 32 and 34 in response to control signals from a microprocessor 42 received via a communication bus 44 . the microprocessor 42 also controls the relay logic 38 so as to provide appropriate voltage activation signals to the fan 12 . the microprocessor 42 also communicates with motor drive circuitry 46 via the communication bus 44 . the motor drive circuitry interfaces with damper motors 48 , 50 and 52 that position the dampers 16 , 18 , and 20 . the microprocessor 42 also communicates with an a / d converter 54 which receives temperature signals from the remote room sensors 24 , 26 , and 28 as well as the temperature sensor 30 downstream of the cooling coil 14 . the microprocessor 42 executes various control processes stored in a memory 56 associated therewith . one such stored process monitors the temperature sensed by the temperature sensor 30 and provides appropriate control signals over the bus 44 to either the relay logic 38 , or the motor driver circuitry 46 so as to thereby control the two stages of compression 32 and 34 as well as the dampers 16 , 18 , and 20 . this stored process executable by the microprocessor 42 is illustrated in fig3 a , 3b , and 3c . referring to fig3 a , the stored process begins with a step 60 wherein the duct temperature t d is read from the sensor 30 . it is to be appreciated that the duct temperature t d is a reading of the temperature of the air leaving the cooling coil 14 . as will be explained in detail hereinafter , this sensed temperature will be compared with three separate threshold temperature conditions stored in memory 56 . these threshold temperatures will be referred to as t a , t b and t c . t a is the lowest threshold temperature whereas t c is the highest . t b is a threshold temperature between t a and t c . normally , the duct temperature sensed by the sensor 30 should be above the highest threshold temperature t c . this will be the assumed initial temperature condition . referring now to step 62 , inquiry is first made as to whether the duct temperature t d is less than t a . since the duct temperature will be above t a , the microprocessor will proceed to a step 64 and inquire as to whether the duct temperature t d is less than the threshold temperature t b . since the duct temperature will be above t b , the microprocessor will proceed to a step 66 and clear a &# 34 ; time 1 &# 34 ; flag . the microprocessor will next proceed to a step 68 and inquire as to whether the duct temperature is less than the threshold temperature t c . since the duct temperature will be above the highest threshold temperature t c , the microprocessor will proceed along the no path to a step 70 and set a &# 34 ; proceed &# 34 ; flag in a step 70 . the microprocessor will next clear a &# 34 ; damper -- offset &# 34 ; variable in a step 72 . another variable &# 34 ; old 13 t d &# 34 ; will be set equal to the threshold temperature t b . the microprocessor next proceeds to clear a &# 34 ; lat -- trip &# 34 ; flag in a step 76 . following the setting of the various variables in steps 70 through 76 , the microprocessor proceeds to a step 78 and inquires as to whether the cooling stage 32 of the two stage cooling system is on . if stage 32 has not been activated by the microprocessor 42 , then an inquiry is made in a step 80 as to whether there is a demand for this cooling stage . this is essentially a check of the results of other programs that may have been run by the microprocessor 42 to ascertain whether there is a demand to activate this stage of cooling . activation of this stage of cooling is subject to the setting of the &# 34 ; lat -- trip &# 34 ; flag . in this regard , the microprocessor proceeds from step 80 to a step 82 to inquire as to whether the &# 34 ; lat -- trip &# 34 ; flag has been set if a cooling demand has been noted in step 80 . since the &# 34 ; lat -- trip &# 34 ; flag was cleared in step 76 , the microprocessor will proceed along the no path to a step 84 and turn on cooling stage 32 . the microprocessor will next proceed to a step 86 and inquire as to whether a &# 34 ; reduce -- stages &# 34 ; flag is set . it is to be appreciated that this flag will initially not be set when the process is first executed . the microprocessor will accordingly proceed from step 86 to a step 88 and set a zone index &# 34 ; i &# 34 ; equal to one . it is to be appreciated that the zone index is an identifier of the various temperature zones having remote room sensors 24 , 26 and 28 and dampers 16 , 18 and 20 associated therewith . the microprocessor will proceed to a step 90 and read the temperature &# 34 ; t i &# 34 ; for the room sensor identified by the particular numerical value of the zone index . the microprocessor will thereafter fetch the set point for that particular identified zone in step 92 . an inquiry will next be made in step 94 as to whether the thus read zone temperature is greater than the set point temperature for that particular zone . if the zone temperature is less than the zone set point temperature , the microprocessor will proceed to a step 96 and set the damper position for the particular zone d i equal to the value of damper -- offset . since damper -- offset is initially cleared in step 72 this will mean that the damper for the particular zone will be closed since a cleared damper offset is zero . the microprocessor will proceed from step 96 to a step 98 and inquire as to whether the zone index , &# 34 ; i &# 34 ;, equals &# 34 ; n &# 34 ;. it is to be appreciated that &# 34 ; n &# 34 ; equals the total number of zones for a given configuration . assuming another zone is to be checked , the microprocessor increments the zone index &# 34 ; i &# 34 ; in step 99 and returns to read the temperature t i and set point s i for the new zone index value . in the event that the zone temperature t i is above set point , the microprocessor proceeds to a step 100 and calculates a new damper position d i for the particular damper associated with the identified zone . this calculation will include multiplying a constant k times the temperature difference t i minus s i plus adding the damper offset value thereto . the constant k is the number of incremental positions per degree that the dampers 16 , 18 and 20 are to move . the microprocessor proceeds to a step 102 and inquires as to whether the calculated damper position d i is greater than the maximum allowable position . the damper position is set equal to the maximum allowable in step 104 in the event that the calculated damper position is greater than the maximum allowable . the microprocessor proceeds to step 98 and inquires whether all zone indexes have been checked for temperatures and appropriate damper position calculations performed . when all zone indexes have been thus addressed , the microprocessor proceeds to a step 106 and exits the particular process of fig3 a through 3c . it is to be appreciated that the microprocessor will preform other tasks before returning to the process of fig3 a through 3c . the re - execution of the process of fig3 a through 3c will preferably occur within a time period that allows for the process of fig3 a through 3c to be re - executed in a timely manner . it is to be appreciated that this time may vary from system to system . repeating the process every ten seconds is sufficient for the configuration of fig1 and 2 . referring again to step 60 , following the appropriate time interval , the microprocessor will again read the value t d of the sensor 30 . for purposes of discussion , the duct temperature t d will be assumed to be less than the threshold temperature t c but greater than the threshold temperature t b . this will prompt the microprocessor to proceed through steps 62 , 64 and 66 to step 68 . since the duct temperature is less than the threshold temperature t c , the microprocessor will proceed from step 68 to a step 108 and clear a &# 34 ; proceed &# 34 ; flag . the microprocessor will move from step 108 to step 78 and inquire as to whether the cooling stage 32 is on . since the cooling stage 32 is now on , the microprocessor will proceed to a step 110 and inquire as to whether cooling stage 34 is on . since cooling stage 34 is not yet on , the microprocessor will proceed to a step 112 and inquire as to whether a demand is present for cooling stage 34 . this is a check as to whether another control process that has been run by the microprocessor 42 has demanded an activation of cooling stage 34 . assuming a demand to be present , the microprocessor will proceed to a step 114 and inquire as to whether the &# 34 ; proceed &# 34 ; flag has been set . it will be remembered that the &# 34 ; proceed &# 34 ; flag will have been cleared in step 108 since the duct temperature is now less than the threshold temperature t c . since the duct temperature is less than this threshold temperature , the microprocessor will proceed along the no path and not allow the cooling stage 34 to be activated . it is however to be appreciated that if the duct temperature were greater than the threshold temperature t c , then the &# 34 ; proceed &# 34 ; flag would have been appropriately set in step 70 and the microprocessor would proceed from step 114 to a step 116 and turn on cooling stage 34 . the microprocessor proceeds from either step 114 along the no path or from step 116 to step 86 and inquires as to whether the &# 34 ; reduce -- stages &# 34 ; flag is set . since the &# 34 ; reduce -- stages &# 34 ; flag has yet to be set , the microprocessor proceeds to step 88 and reads temperature and set points and updates any damper positions in steps 90 through 104 before exiting in step 106 . the microprocessor again executes other control processes before again returning to step 60 to read the temperature sensor 30 . it will now be assumed that the duct temperature has dropped below the threshold temperature t b . the microprocessor accordingly pursues the yes path out of step 64 and inquires in a step 118 as to whether the present duct temperature t d is greater than an old duct temperature value stored in the variable &# 34 ; old -- t d &# 34 ;. it will be remembered that the value of the variable &# 34 ; old -- t d &# 34 ; is equal to the threshold temperature t b as result of step 74 . since the duct temperature will have dropped below this value of &# 34 ; old -- t d &# 34 ;, the microprocessor will proceed along the no path from step 118 to a step 120 and inquire as to whether a &# 34 ; time -- 1 &# 34 ; flag has been set . this particular flag will initially be clear when the microprocessor 42 is first powered up . this means that the microprocessor will proceed from step 120 to a step 122 and set this &# 34 ; time -- 1 &# 34 ; flag . the microprocessor will proceed through the various steps that have been heretofore described and eventually exit from the process in step 106 . the process of fig3 a through 3c will again be executed in a timely fashion and the duct temperature t d will again be read in step 60 . assuming that the duct temperature remains below the threshold temperature t b , the microprocessor will proceed along the yes path out of step 64 and along the no path out of step 118 to step 120 . this time , the &# 34 ; time -- 1 &# 34 ; flag will have been set prompting the microprocessor to proceed along the yes path out of step 122 a step 124 wherein the &# 34 ; reduce -- stages &# 34 ; flag is set . the &# 34 ; time -- 1 &# 34 ; flag is cleared in step 126 and the variable &# 34 ; old -- t d &# 34 ; is set equal to the current value of duct temperature in step 128 . the microprocessor will next proceed to step 78 and again inquire as to whether the cooling stage 32 is on . in the event that stage 32 is on , the microprocessor will proceed to step 110 and inquire as to whether cooling stage 34 is also on . if the answer is yes , the microprocessor proceeds to a step 130 and inquires as to whether the &# 34 ; reduce -- stages &# 34 ; flag has been set . since &# 34 ; reduce -- stages &# 34 ; flag was set in step 124 , the microprocessor will proceed to a step 132 and turn off cooling stage 34 . it is to be appreciated that this will only occur when the temperature drops below the threshold temperature t b causing the &# 34 ; time -- 1 &# 34 ; flag to be set and thereby causing the microprocessor to completely execute the process of fig3 a through 3c an other time before again returning to step 120 . following deactivation of the cooling stage 34 in step 132 , the microprocessor proceeds to step 134 and clears the &# 34 ; reduce -- stages &# 34 ; flag . the microprocessor will again execute steps heretofore described and exit the process of fig3 a through 3c in step 106 . assuming the duct temperature , t d , remains below the threshold temperature t b when the microprocessor again executes the control process of fig3 a through 3c , the microprocessor will proceed along the yes path out of step 64 to step 118 . assuming that the duct temperature has furthermore dropped relative to its previous value stored in &# 34 ; old -- t d &# 34 ; the microprocessor will proceed along the no path out of step 118 and the no path out of step 120 so as to again set the &# 34 ; time -- 1 &# 34 ; flag . following the setting of the &# 34 ; time -- 1 &# 34 ; flag , the microprocessor will proceed through the various steps as have been theretofore described and exit from the step 106 . assuming the temperature remains below the threshold temperature t b and also drops relative to &# 34 ; old -- t d &# 34 ;, the microprocessor will again execute the process of reading the duct temperature in step 60 and proceed through step 64 and through step 118 and proceed along the yes path out of step 120 to set the &# 34 ; reduce -- stages &# 34 ; flag in step 124 . the &# 34 ; time -- 1 &# 34 ; flag will again be cleared in step 126 and the variable &# 34 ; old -- t d &# 34 ; will be set equal to the value of the current duct temperature in step 128 . the microprocessor will proceed through steps 68 through 78 and along the yes path out of step 78 to step 110 wherein it will be noted that the cooling stage 34 has already been turned off . the no path will be pursued to a step 112 and inquiry will be made whether there is a demand for the cooling stage 34 . if demand is present , the microprocessor proceeds to step 114 and inquires whether the &# 34 ; proceed &# 34 ; flag is set . it is to be appreciated that the only way the &# 34 ; proceed &# 34 ; flag would be set is if the temperature t d were equal to or above the threshold temperature t c . the microprocessor will hence proceed along the no paths out of either step 112 or step 114 without turning the cooling stage 34 on . the microprocessor proceeds to step 86 and inquires as to whether the &# 34 ; reduce -- stages &# 34 ; flag is set . since the &# 34 ; reduce -- stages &# 34 ; flag will have been set in step 124 as a result of the second time through of executing the process following the deactivation of the second cooling stage , the microprocessor will proceed to step 136 and first clear the &# 34 ; reduce -- stages &# 34 ; flag . the microprocessor will proceed to step 138 and increment the current value of &# 34 ; damper -- offset &# 34 ;. the increment will preferably be one damper position . inquiry is next made in step 140 as to whether the value of &# 34 ; damper -- offset &# 34 ; is greater than a maximum allowable value . it is to be appreciated that the maximum allowable value for this variable can be any arbitrary number of incremental damper positions . this maximum value should be the amount that the damper is allowed to be opened to compensate for the denoted temperature condition that has prompted the damper offset calculation to be initiated . this maximum value could for instance be set equal to one half of the total incremental damper positions possible for any one of the dampers 16 , 18 or 20 . if this number is exceeded in step 140 , the microprocessor proceeds to a step 142 and sets the &# 34 ; damper offset &# 34 ; variable equal to the maximum allowed value . the microprocessor either proceeds out of step 140 or step 142 with an appropriate offset damper value and proceeds to step 88 wherein the zone index &# 34 ; i &# 34 ; is set equal to one . the temperature for the zone indicated by the particular index setting &# 34 ; i &# 34 ; is compared with the set point temperature for that zone in step 94 . if the temperature t i for the particular zone is below set point , then the damper position will be set equal to the calculated damper offset value in step 96 . on the other hand , if the zone temperature t i is greater than set point , then the microprocessor will proceed to calculate the new damper position based on the noted temperature differential as well as adding the damper -- offset value previously calculated . the microprocessor will proceed to inquire as to whether the damper position is at its maximum allowable open position and make the appropriate correction if necessary in step 104 before inquiring as to whether the last zone has been updated for damper position in step 98 . when each zone has thus been updated , the microprocessor will exit the process in step 106 . it is to be appreciated that the &# 34 ; damper -- offset &# 34 ; variable may be incremented every other time the process of fig3 a through 3c is executed . this is of course due to the necessity of first setting the &# 34 ; time -- 1 &# 34 ; flag and then subsequently setting the &# 34 ; reduce -- stages &# 34 ; flag the next time through as long as &# 34 ; t d &# 34 ; continues to drop relative to &# 34 ; old -- t d &# 34 ;. providing the above conditions continue , the microprocessor will proceed to calculate a new value for &# 34 ; damper -- offset &# 34 ; in steps 138 through 142 . in this manner , the value of damper -- offset may potentially increment to the maximum allowable damper -- offset value in an attempt to correct the declining temperature condition sensed by the temperature sensor 30 . the thus opened dampers will allow more air to enter each zone than would otherwise be permitted by a normal damper control response to the room temperature versus the set point for that particular room . this damper opening should eventually alleviate the duct temperature condition occurring at the cooling coil 14 . if the duct temperature however continues to drop and more over drops below the threshold temperature t a , then the microprocessor will so note this situation in step 62 . the microprocessor will proceed from step 62 to a step 144 and turn off both cooling stages 32 and 34 . after the cooling stages 32 and 34 have been turned off the microprocessor proceeds to a step 146 and sets a &# 34 ; lat trip &# 34 ; flag in a step 146 before proceeding to the exit step 106 . it is to be appreciated that the process of fig3 a through 3c will be executed repeatedly with no further action taken until the duct temperature rises about the threshold temperature t a . at such time , the microprocessor will implement the various courses of action dictated by the duct temperature being first less and than greater than the threshold temperature t b . if the air temperature finally rises above the threshold temperature t c , the microprocessor will so note in step 68 . the &# 34 ; damper offset &# 34 ; will subsequently be cleared in step 72 and the &# 34 ; lat -- trip &# 34 ; flag will be cleared in step 76 . it is to be appreciated that the two stage cooling system and associated dampers will be allowed to operate in a normal fashion as long as the duct temperature downstream of the cooling coil remains greater than the threshold temperature t c . at such temperatures , the microprocessor will be allowed to turn on the second cooling stage 34 in the event that it is not presently running . if the duct temperature again drops below the threshold temperature t b , the microprocessor will deactivate the second stage of cooling one at a time following at least a second execution of the process due to the &# 34 ; time -- 1 &# 34 ; flag setting routine . the microprocessor will also begin to open the dampers 16 , 18 and 20 after having deactivated the second cooling stage in the event the sensed temperature downstream of the cooling coil continues to drop . if the temperature drops below threshold temperature t a , then the microprocessor immediately deactivates both stages of cooling . it is to be appreciated that a particular embodiment of the invention has been described . alterations , modifications and improvements thereto will readily occur to those skilled in the art . such alterations , modifications and improvements are intended to be part of this disclosure even though not expressly stated herein and are intended to be within the scope of the invention . accordingly the foregoing description is by way of example only and the invention is to be limited only by the following claims and equivalents thereto .
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the invention may be more particularly understood by having reference to the following examples wherein examples 1 to 5 and 7 set out methods of preparing particular ion exchangers according to the invention . example 6 relates to the preparation of an exchanger which has not been hydroxy - propylated for comparison as to the degree of sulphation . example 8 relates to the determination of the extent of sulphation . example 9 is an examination of flow rates of the resin according to the invention and examples 10 and 11 relate to adsorptive capacities of the resin according to the invention . granular regenerated cellulose ( 20 g ) ( 75 - 125μ ), with a moisture content of 5 - 7 %, was mixed with cold 30 % ( w / v ) aqueous sodium hydroxide ( 30 ml ), 2 ml epichlorohydrin ( 10 % v / w based on cellulose ) and 10 ml propylene oxide ( 50 % v / w based on cellulose ). the mixture was stirred thoroughly until the cellulose had finished swelling and all the liquid had been absorbed . the damp cellulose was then placed in a container and sealed before heating it at 60 ° without further mixing . after 2 hours the reaction vessel was cooled to room temperature , opened and the contents were transferred into a large volume of stirred water ( 500 ml ). the particles of hydroxylpropyl cellulose were collected on a buchner funnel , washed well with water and finally dried by either method ( i ) or ( ii ) below . the product ( 20 g ) was stored in a closed container until required for sulphation . ( i ) the product was dewatered by solvent exchange into methanol through a graded series of methanol -- water mixtures . excess methanol was removed and then the product was heated at 60 ° c . under reduced pressure . ( ii ) the product was freeze - dried . the last 1 % moisture could be removed by air - drying at 60 ° c . without affecting the reactivity of the product . using this method hydroxypropylated regenerated celluloses can be prepared with a range of swollen volumes . examples of these are given in table 1 . they were measured after the products had been dried by method ( i ). table i______________________________________settled bed volumes of hydroxypropyl regeneratedcelluloses in water ( ml / g ) 6 8 10 20 % epichlorohydrin______________________________________ 30 8 9 8 . 5 % propylene 50 12 . 5 11 . 0 9 . 5 8 . 1oxide 100 17 . 4 16 . 0 11 . 6 8 . 4______________________________________ the yields of water insoluble product decreased as the amount of cross - linking decreased and with 1 % epichlorohydrin only amounted to 40 % of the initial weight of cellulose used . with 6 , 8 and 10 % they amounted to 84 , 94 and 100 % respectively . granular regenerated cellulose ( 10 g ) was suspended in 50 ml of toluene . to the suspension there was then added 10 ml of 60 % aqueous sodium hydroxide followed by 8 ml of ethylene chlorohydrin and 0 . 5 ml of epichlorohydrin . the temperature of the mixture was then raised to 60 ° and the reaction allowed to proceed for 2 hours with agitation . after decanting the toluene , the product was dispersed in rapidly stirred water and collected on a sintered glass buchner funnel . it was washed thoroughly with water , dewatered with acetone and dried under reduced pressure at 50 ° c . the product had a settled bed volume of 8 ml / g in water . hydroxypropyl regenerated cellulose - 10 - 50 ( 1 g ) dried by method ( i ) in example 1 above , pyridine - sulphur trioxide complex ( 1 g ) and dry pyridine ( 10 ml ) were placed in an erlenmeyer flask , protected with a drying tube and heated on an oil bath at 80 ° for 1 . 5 hours . the flask was shaken periodically by hand during the course of the reaction and then cooled before transferring the reaction mixture into 20 ml of deionized water . the sulphated product was collected on a sintered glass funnel and washed thoroughly with more deionized water . to convert it from the pyridinium to the sodium ion form it was titrated in 1 m sodium chloride with 0 . 1 m sodium hydroxide to a phenolphthalein end point and then recollected and washed on the filter again . the hydroxypropyl - regenerated cellulose sulphate had an ion exchange capacity of 2 . 37 meq / g . and a settled bed volume of 8 . 5 ml / g in water . 1 g of freeze - dried hydroxypropyl regenerated cellulose - 8 - 50 , pyridine - sulphur trioxide complex ( 2 g ) and dry dimethylformamide ( 10 ml ) were placed in a tube , stoppered and gently shaken at 20 °- 25 ° for 2 hours . the sulphated product was obtained as described in ( a ) above and had ion - exchange capacity of 4 . 3 meq / g . and a settled bed volume of 12 ml / g in water . capacities up to 5 . 5 meq / g were obtained by this method by using up to 4 g of pyridine - sulphur trioxide complex and reaction times up to 4 hours . the sulphated product was stored in deionized water in the presence of 0 . 025 sodium azide as preservative , for 6 months at 25 ° c . without detachable loss of sulphate groups . the product may also be dewatered by solvent exchange into e . g . methanol and dried under reduced pressure at 20 ° c . without affecting its ability to reswell on wetting and its ability to bind lipoproteins . the yield of product was greater than 98 % allowing for the increase in weight resulting from the introduction of the charged groups (- oso 3 - na + ) in place of hydroxyls . microgranular cellulose ( 20 g ) ( whatman cellulose powder cc31 from w & amp ; r balston ltd ., england ) was mixed with cold 20 % ( w / v ) aqueous sodium hydroxide ( 30 ml ), epichlorohydrin ( 2 ml ) and propylene oxide ( 10 ml ). after the reactants had been thoroughly mixed in , the damp powderly cellulose was enclosed in a container and left at 20 ° c . for 24 hours . it was then transferred into 4 liters of stirred water . the product was washed , dewatered and dried in the same way as the hydroxypropyl regenerated cellulose ( example 1a ) to give 18 . 7 g of product with a settled bed volume of 7 . 6 ml / g in water . this was accomplished in the same way as set out in example 2a using hydroxypropyl cellulose prepared as in example 3 . by using 0 . 5 , 1 and 2 g of pyridine - sulphur trioxide complex products were obtained with ion - exchange capacities of 0 . 56 , 2 . 24 and 4 . 31 meq / g respectively . dry hydroxypropyl cross - linked dextran ( 1 g ) ( sephadex lh - 20 , from pharmacia fine chemicals ab , sweden ), pyridine - sulphur trioxide complex ( 2 g ) and dry pyridine ( 10 ml ) were placed in an erlenmeyer flask protected from atmospheric moisture with a drying tube and heated on an oil bath at 80 ° for 1 . 5 hours . the flask was shaken periodically during the course of the reaction and then cooled before transferring the reaction mixture into 200 ml of deionized water . the sulphated product was collected on a sintered glass funnel and washed thoroughly with more deionized water . it was finally neutralized with 0 . 1 m sodium hydroxide and then recollected and washed again on the filter . the cross - linked dextran matrix after sulphation had an ion - exchange capacity of 4 . 1 meq / g and a settled bed volume of 5 . 0 ml / g in water . dry cross - linked dextran ( 1 g ) ( sephadex g - 25 , from pharmacia fine chemicals ab , sweden ) was sulphated in 10 ml of dry formamide with 2 g of pyridine - sulphur trioxide as described in example 5 . the product has an ion - exchange capacity of 2 . 47 meq / g and a settled bed volume of 8 . 3 ml / g . an aqueous slurry of cross - linked agarose ( sepharose cl - 6b from pharmacia fine chemicals ab , sweden ) was transferred to a sintered glass buchner funnel and the excess water was removed by suction . 15 g of the moist agarose was exchanged into dmf through a graded series of dmf / water mixtures and finally washed with dry dmf . the cl - agarose beads suspended in dmf were then sulphated by adding 1 . 4 g of pyridine - so 3 complex and gently shaking the mixture for 4 hours at 20 °- 25 ° c . the product after dispersion in deionized water was collected on a sintered glass buchner funnel , washed thoroughly with deionized water . on titration it was found to contain 5 . 4 mmoles of sulphate groups ( 3 . 1 meq / g ). this ion exchanger was found to bind 5 . 2 mg of cholesterol / g when tested with lipoprotein solution as described in example 11 below . the extent of sulphation was determined from the volume of 0 . 1 m sodium hydroxide used to neutralize the pyridinium ion displaced from the sulphated matrix and by assuming a 100 % yield of matrix from the reaction . the validity of this was shown in many cases where the product was dried . the yield was greater than 98 % of that calculated from the weight of matrix used and the number of - oso 3 na groups introduced in place of hydroxyl groups . this method of analysis was further verified by a sulphur analysis on the dried product . ______________________________________comparison of analysis methodsmeq / g % sulphur % sulphur ( by titration ) ( calculated ) ( micro analysis ) ______________________________________1 . 42 4 . 55 4 . 653 . 67 11 . 75 11 . 61______________________________________ the flow rates measured for several of the sulphated matrices were as follows : in each case the bed depth was 10 cm and flow was maintained with a 70 cm hydrostatic pressure differential across the columns using 0 . 5 m nacl as eluant . although granular regenerated cellulose itself and ion - exchangers prepared from it u . s . pat . no . 3 , 573 , 277 granted mar . 30 , 1971 ) are known to have excellent flow rates when packed into a column , ( 240 cm / hr under the same conditions as described above ) it is surprising that such high flow rates are still possible after the regenerated cellulose particles have been substituted with hydroxypropyl groups giving rise to softer and more swollen grains . a column was packed with the ion - exchanger , hydroxylpropyl regenerated cellulose - 8 - 50 sulphate ( 1 meq / g ) prepared as herein described in example 2a . it was equilibrated with one column volume of 0 . 5 m magnesium chloride containing 0 . 01 m sodium bicarbonate and adjusted to ph7 . 4 . when serum diluted 1 : 1 with 1 m magnesium chloride and adjusted to ph7 . 4 with 0 . 1 m sodium hydroxide , was passed through the column two of the lipoprotein fractions , the very low density lipoproteins ( vldl ) and the low density lipoproteins ( ldl ) were selectively and quantitatively removed . all other proteins including the third lipoprotein fraction , the high density lipoproteins ( hdl ) passed straight through the column and were washed out with a further column volume of the 0 . 5 m magnesium chloride ( ph 7 . 4 ) solution as used initially to equilibrate the column . the lipoproteins ( vldl and ldl ) bound to the column were eluted with a solution 0 . 25 m in sodium chloride and 0 . 25 m in trisodium citrate which had been adjusted to ph 8 . 4 with 1 m hydrochloric acid . ( alternatively these lipoproteins can be eluted rapidly with 1 m sodium chloride ). the eluted lipoproteins were shown to be uncontaminated with other serum proteins by immunoelectrophoresis and agarose electrophoresis . similarly the serum proteins which passed straight through the column were shown to be devoid of vldl and ldl by immunoelectrophoresis and agarose electrophoresis . the hdl fraction may also be retained on the column if a more highly substituted ion - exchanger is used , e . g . 3 - 5 meq / g but this is not always necessary as it is usually the ldl and vldl which are the main cause of the trouble in serum protein fractionations . the flow rate of serum through the ion exchange column was such that the lipoproteins can be removed from 5 ml of serum inside a 15 minute period and also larger columns can be used still with good flow characteristics . thus quite unexpectedly from previous methods of selectively removing the lipoprotein components from serum , the use of this ion - exchange achieved it quantitatively and with speed . consequently if such a procedure is used first , it can facilitate the isolation of other serum proteins . for example in the preparation of igg from serum , all other proteins are adsorbed onto a column of qae - sephadex leaving igg to pass straight through the column ( protides of the biological fluids ; proceedings of the 17th colloquim , 1969 , p . 511 - 515 ). however the volume of diluted serum loaded onto the column cannot exceed 75 % of the volume of the column or ldl &# 39 ; s and vldl &# 39 ; s also break through the column and contaminate the igg . by removing the ldl &# 39 ; s and vldl &# 39 ; s first on a column of sulphated ion - exchanger and then carrying out the preparation of igg as outlined in the references above , up to three times as much serum may be loaded onto the qae - sephadex column without contamination of the igg being isolated . in order to measure the capacity of the sulphated ion - exchangers for binding lipoproteins each of them was packed in a pasteur pipette to make a small column of volume 1 . 5 ml . their lipoprotein binding capacities were determined using a low density lipoprotein fraction ( vldl plus ldl ) prepared on the ultracentrifuge and thence dialyzed against 0 . 01 m sodium bicarbonate buffer , ph 7 . 4 . the lipoprotein fraction was made up to its original serum volume with the same buffer and then diluted 1 : 1 with a solution containing sodium chloride , magnesium chloride and 0 . 01 m sodium bicarbonate adjusted also to ph 7 . 4 so that the diluted lipoprotein solution has a final salt concentration of 0 . 05 m and a magnesium chloride concentration of 0 . 5 m . the following method was used for each column . the column was equilibrated with 10 ml of solution ( a ) containing 0 . 05 m sodium chloride , 0 . 5 m magnesium chloride , 0 . 01 m sodium bicarbonate and adjusted to ph 7 . 4 . 5 ml of the lipoprotein solution was passed through the column and washed out with 5 ml of solution a followed by 2 ml of 0 . 01 m sodium bicarbonate buffer , ph 7 . 4 . the lipoproteins were then eluted from the column with 1 m sodium chloride and collected in 2 ml . the cholesterol content of this 2 ml was determined as a quantitative measure of the amount of lipoprotein bound to the column . the ion exchanger in the column was finally washed and oven dried at 60 ° c . to determine its dry weight . the results of capacity measurements of selected sulphated ion exchangers made in accordance with this procedure are set out in table ii . table ii______________________________________sulphated ion exhangers lipoprotein capacitymatrix meq / g mg cholersterol / g______________________________________micrograular cellulose10 - 50 2 . 24 25 &# 34 ; 10 - 00 2 . 11 18 &# 34 ; 50 - 00 2 . 06 2regenerated cellulose8 - 50 2 . 11 7 . 5 &# 34 ; 10 - 00 low not tested &# 34 ; 50 - 00 2 . 32 0 . 6 &# 34 ; 100 : 00 1 . 53 0 . 2cross - linked dextran lh - 20 2 . 65 2 . 2 g - 25 2 . 38 0 . 7cross - linked agarose 3 . 1 5 . 2______________________________________ the procedure was repeated using the serum from which the low density lipoproteins had been removed on the ultracentrifuge . this gave a measure of the ion exchanger &# 39 ; s capacity for hdl as none of the other serum proteins bound under these conditions . cellulose was employed in its native fibrous , microcrystalline , microgranular or regenerated forms which was cross - linked and had attached hydroxyalkyl groups . the regenerated cellulose was obtained from either the xanthate or cuprammonium process in a variety of forms such as granular , powder or rounded beads produced by known methods . powder -- by spraying the cellulose solution into the regenerating bath ( n . z . pat . no . 167 , 838 ). bead forms -- by dispersing the cellulose solution into microdrops by vigorous stirring in the presence of an organic solvent immiscible with water before regeneration . ( journal of polymer science : part c 36 , 1971 , page 280 ). ( british pat . no . 1 , 293 , 611 ). the cross - linking agent used can in principle be any bifunctional compound of formula x - r - y wherein x and y are each halo or epoxy groups and r is an aliphatic residue . typical cross - linking agents are set out herein below in table iii . cross - linking was achieved by reacting cellulose or regenerated cellulose in the presence of a base and water . alkali metal hydroxides , primarily sodium hydroxide and potassium hydroxide , were used for the base . however other alkaline reacting substances such as quanternary ammonium compounds could also be used . the properties of the finished product depended on the degree of cross - linking used . this could be controlled in accordance with the final properties required . the degree of cross - linking was from 1 to 50 %, but more especially from 4 to 20 %, expressed in terms of the volume of cross - linking reagent to the dry weight of cellulose . it will be appreciated that the degree of cross - linking used in any given case will depend on the particular matrix used and the number of activating hydroxy alkayl groups substituted on to it . levels of cross - linking above this range were sometimes required , for example , if the cross - linking was carried out prior to regeneration of the cellulose . the hydroxyalkyl groups could be added to the cellulose or regenerated cellulose at the same time as the crosslinking was carried out by adding an alkylene - oxide or alkylenehalohydrin to the alkali metal hydroxide , water and cross - linking agent . for example hydroxypropyl groups could be added by the use of propylene oxide or propylene chlorohydrin and hydroxyethyl groups by using ethylene oxide or ethylene chlorohydrin . preferably the amount used was between 20 and 200 %. the amount of water present in the reaction was sufficient to dissolve the base and swell the matrix , but not so great as to cause excessive side reactions with the hydroxyalkylating reagent . in order to minimize these side reactions , the reaction could be suitably carried out in the presence of a solvent not miscible with water , e . g . toluene . this solvent may also serve as a heat removing medium , and provide a more uniform distribution of the reactants as well as allow a higher reaction temperature to be used if one of the reactants is of low boiling point . alternatively in the case of regenerated cellulose , the cross - links and / or the hydroxyalkyl groups could be incorporated before the final regeneration of the cellulose by methods known in the art ( n . z . pat . no . 167838 ). the invention may be more fully understood by having reference to the accompanying drawings wherein : the fig1 and 2 are plots of the degree of sulphation expressed in meq / g against time for seven different samples of regenerated cellulose . the number labels , 100 - 0 , etc . have the same meaning as explained in relation to example 1 . fig3 and 4 are plots of the adsorption capacity of the ion exchanger for low density and high density lipoproteins respectively , as explained in example 11 , against the extent of sulphation of the ion exchanger expressed as meq / g . the number labels 6 . 40 etc , have the meaning explained in example 1 . &# 34 ; lh - 20 &# 34 ; refers to sephadex lh - 20 sulphated as described in example 5 . fig1 shows that the reactivity of the cross - linked regenerated cellulose towards sulphation decreases as the amount of cross - linking decreases . conditions of reaction are those given in example 2a using 2 g of pyridine - sulphur trioxide complex . similar reactivities were observed by presoaking in dmf for 16 hours and then carrying out the reaction in dmf at 20 °- 25 ° c . although regenerated cellulose prepared using 50 % and 100 % could be sulphated satisfactorily it has inferior binding capacities for binding lipoproteins , especially when expressed in terms of the dry weight of sulphated ion - exchanger required ( see fig3 and 4 ). fig2 shows how the reactivity of the cross - linked regenerated cellulose towards sulphation is dramatically improved by the presence of added hydroxypropyl groups . conditions of reaction are those given in example 2a using 2 g of pyridine - sulphur trioxide complex . fig3 and 4 show the improved capacity of the sulphated ion - exchangers prepared from hydroxypropylated matrices compared with that obtained using high levels of crosslinking ( 100 %) but no propylene oxide .
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the following description is provided to enable any person skilled in the art to make and use the invention and sets forth the best modes contemplated by the inventor of carrying out their invention . various modifications , however , will remain readily apparent to those skilled in the art , since the general principles of the present invention have been defined herein specifically to provide a low aspect ratio flow angle probe for an aircraft with no moving parts . the present invention is shown generally in fig1 to 4 . it comprises a cantilevered airfoil shaped member 10 extending perpendicularly from an arched mounting base 110 . it may be constructed of any suitable material , such as 2024 - t351 aluminum . the span of the airfoil member 10 is approximately 2 inches , although as described below much smaller probes are possible . for the two inch span airfoil member , the chord 120 is approximately one inch and the airfoil member has a thickness 130 of approximately one - eighth of an inch . a suitable wedge angle θ of the airfoil member is approximately twelve degrees ( semi - apex ). in a preferred embodiment , the airfoil member 10 includes a shaped fin 100 comprising a generally flat surface 180 and a parallel flat lower surface 190 which extend to the neck portion 160 . the fin 100 will typically be symmetric with respect to both x and y axes , and comprise leading and trailing edges of two inclined planes 200 a - b , 210 a - b , respectively . the leading edge inclined planes 200 a , b converge to form an apex angle θ , which is preferably symmetric with the apex angle formed by the inclined planes 210 a , b of the trailing edge . the fin 100 narrows at a first end to form a neck portion used to support the strain gauges and to transition from the load bearing surfaces to a mounting base 110 . the neck portion 160 may be rectangular in cross - section and of sufficient thickness to support the cantilevered fin 100 without deformation under the most adverse load conditions . the airfoil member 10 mounts to a base 110 which may have a curved first surface and a flat mounting surface . the flat mounting surface can be used to mount the base 110 flush against an aircraft component or a location on a ship hull . the curved first surface provides thickness to the base 110 to support four holes 220 sized to accept a fastener to secure the base 110 . the holes have a recessed annular shoulder to receive the end of the fasteners to keep the fasteners from interfering with the flow regime . other means for securing the base are possible , such as adhesives . the juncture between the neck portion of the airfoil member and the base include rounded transitions to reduce stress concentrations and promote flow over the neck portion of the probe . the probe includes four strain gauges 150 a - d located on the upper and lower surfaces of the neck portion 160 of the airfoil member 10 . the strain gauges output a voltage signal indicative of the load on the probe . the voltage signals from the strain gauges 150 a - d are conditioned and amplified by a signal conditioning component ( not shown ). a power source ( not shown ) is also preferably cooperating with the strain gauges 150 a - d to provide an excitation voltage . calibration of the flow angle measurement is achieved utilizing in - flight data or wind tunnel data . verification of the present invention has been confirmed with measured angle of flow data acquired by a symmetric angle of flow weather vane probe . fig5 illustrates the conversion from force to angle of attack ( represented in the figure as the greek letter alpha ). aerodynamic loads on the probe due to the movement of air over the probe will produce a stress at the load bearing portion of the probe where the strain gauges are positioned . at a zero angle of attack , the airfoil member will experience a bending stress as the force on the airfoil member is applied to the leading edge of the airfoil member . at a non - zero angle of attack , the aerodynamic force on the airfoil will produce both a bending stress and a torque at the base of the probe , due to the tendency for the airfoil member to twist and bend as a result of the uneven application of aerodynamic forces on the upper and lower surfaces . the strain gauges measure the stresses as a function of millivolts ( mv ), and outputs the signal in millivolts to a first conversion step . in this conversion , which is a thermal calibration , the millivolts are converted to newtons ( n ) for a given temperature ( t 1 , t 2 , t 3 , etc .). the output of this conversion is then provided to a second step where the load in newtons is converted to a flow angle ( α ) for a given dynamic pressure ( q ). fig6 is a composite graph of the steps shown in fig5 correlating strain measured by the probe with angle - of - attack for a given dynamic pressure . to reduce the size of the probe , conventional strain gauges can be replaced with fiber optic wires much more sensitive to strain . the use of fiber optic wires would allow for the fabrication of a very small probe . a probe with strain - detecting fiber optic wires can be used to perform tests on individual streamlines in an airflow , rather than gross airflow behavior . further , the use of a plurality of miniature probes could be used to perform quantitative tufting tests , as opposed to mere qualitative testing by conventional probes . those skilled in the art will appreciate that various adaptations and modifications of the just - described preferred embodiment can be configured without departing from the scope and spirit of the invention . therefore , it is to be understood that , within the scope of the appended claims , the invention may be practiced other than as specifically described herein .
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referring now to the drawings in detail , and particularly to fig1 , there is shown the present invention , which comprises a method and apparatus for generating , depositing and forming an accurate array of solder bumps on a substrate such as a wafer of for example silicon , or on a layer of plate glass . these solder bumps are utilized to form an array of electrical contacts on that substrate , wafer of plate , for use in the electronics industry . the initial apparatus of the present invention , represented in fig1 thus comprises a solder - loading assembly 20 consisting of a first or lower support compression plate 22 and a second or upper compression plate 24 ( only partially shown , for clarity ). the first or lower support plate 22 of the assembly 20 may be movably supported on lower plate drive 26 and the second or upper plate 24 may be supported by an upper plate drive 28 , wherein each drive 26 and 28 may be movable for compressably advancing the lower and upper plates 22 and 24 toward and apart from one another . the lower plate arrangement 22 of the assembly may be removably disposed within a liquid solder bath 30 or received within a solder deposition application arrangement . one or both of the drives 26 and 28 may have an energy field vibration or agitation generator arrangement therewith , ( not shown for clarity ), to enhance the process of filling the holes 34 , described hereinbelow , with molten solder . a mold plate or pattern plate 32 is arranged in proper alignment on the first or lower plate 22 during operation of the solder - loading assembly 20 . the pattern plate 32 has a plurality of properly aligned “ through - holes ” 34 disposed thereon . the pattern plate 32 is disposed on the first or lower plate 22 in the solder bath 30 or solder - deposition arrangement so as to supply completely void - free molten solder 36 in those through - holes 34 thereon . the first or lower plate 22 and the second or upper plate 24 are then brought pressingly together facing one another with the now solder - filled pattern plate 32 sandwiched therebetween , as represented in fig1 a . during this compression stage between the first or lower plate 22 and the second or upper plate 24 , the excess molten solder 39 is pressed away or “ squeegeed ” off of the pattern plate 32 , that pattern plate 32 then being preferably chilled by a chill means 38 in the lower plate 22 or within the assembly 20 , to a temperature sufficient to solidify the solder 36 in the through - holes 34 in that now “ excess - solder - free ” pattern plate 32 . a vibration means , an ultrasound means or an electromechanical energy field generator 41 may , in a further embodiment , be utilized to help effect void - free solder - filling the through - holes 34 in a step in this process , and also as a further embodiment in the separation of the pattern plate 32 from those solder bumps 36 in a further step in this inventive process . the now solidified , void - free solder 36 in the now excess - solder free pattern plate 32 is transferred to an awaiting substrate 40 such as a silicon wafer , or a plate glass substrate , in proper alignment therewith , as represented in fig2 . the wafer or substrate 40 to which the pattern plate 32 is alignably disposed , may be resting upon or in contact with a wafer supporting base 42 with a heater and / or chill means 44 arranged therewithin . the wafer substrate 40 and pattern plate 32 may then be heated to a temperature above the melting point of the solder 36 within the through - holes 34 of the pattern plate 32 . the now aligned through - holes 34 adheringly deposit their bumps of solder 36 onto the aligned wafer 40 therebeneath , as represented in fig3 . the pattern plate 32 is preferably then liftably removed ( as represented by arrow “ r ”) from the wafer substrate 40 , the through - holes 34 , now empty , and with the solder bumps 36 now adheringly disposed on their particular pads 46 on the now cooled wafer or substrate 40 therebeneath , as is represented in fig4 . that substrate or wafer 40 with the appropriate free - standing solder bumps 36 which are now aligned and secured thereon , and separated from its chill plate base 42 for subsequent further processing , is represented in fig5 . in a further embodiment of the assembly 20 of the present apparatus as shown in fig6 , the first or lower compression plate 22 may have a slightly spherically convex or cylindrically shaped uppermost surface 50 thereon and the second or upper plate 24 may have a corresponding cylindrically or a somewhat convex shaped surface 52 thereon , as represented in figure 6 , so as to provide a rollable or rockable “ squeegee ” effect to a pattern plate 32 supportably compressed therebetween . such a curved upper plate 24 and correspondingly curved lower support plate 22 could be articulated side - to - side by an articulable upper and lower support 54 and 56 to provide a squeezing and excess solder - removal action to a pattern plate 32 with its associated through - holes 34 with temporarily molten solder 36 therein . such articulable excess solder removal would thus shorten the manufacturing process by combining several steps into one operation of filling those through - holes 34 after the “ bath ” 30 , and subsequently compressively and / or squeegingly cleaning the surface of the pattern plate 32 almost simultaneously . a further embodiment of the assembly 20 utilized in the compression operation as applied to a pattern plate 32 , is represented in fig7 , which assembly comprises the advancement of a pattern plate 32 with its respective aligned through - holes 34 therewith being pulled preferably vertically or “ near vertical ” movement from a solder bath 58 , while being rolled or “ squeegeed ” between a pair of compressive roller members 60 and 62 . such compressive members 60 and 62 in one preferred embodiment thereof , would comprise a pair of biasedly - opposed roller 60 and 62 compressing and advancing a pattern plate 32 therebetween , thus compressing each individual through - hole 34 therebetween and simultaneously squeegeeing would thus foreshorten such a through - hole 34 solder filling manufacturing method . the biasedly opposed pair of roller apparatus or squeegee roller members 60 and 62 may be correspondingly chilled by a chill means 66 therein , so as to chill the molten solder 36 in those througth - holes 34 in that particular pattern plate 32 , or by adjacent chill means 69 acting upon the plate 32 upon its movement . the particular through - holes 34 may have various cross - sectional configurations to suit particular wafer requirements . such a pattern plate 32 in one embodiment , may have a straight through - bore or hole 34 therethrough , as is represented in the sectional view shown in fig8 . in another further embodiment of that pattern plate 32 , the through - hole 34 may be a tapered solder - fillable through - hole 70 , so as to create a tapered or conical shape to a solder bump subsequently applied to a substrate . in yet a further embodiment of the through - hole configuration in a pattern plate 32 , as represented in fig1 , a generally hemispherical - shaped depression 72 is arranged on one side of the pattern plate 32 , with a through - hole 74 in the other side of that pattern plate 32 in communication with the hemispherical depression 72 . a yet further embodiment of the through - hole configuration for a pattern plate 32 would be a hour - glass or pinched - waist 76 configuration to the through - hole , as represented in fig1 , wherein that pattern plate 32 may be subsequently etched - away on deposition of that pinched - waist configuration 76 of solder 36 applied to a wafer or substrate . a still further configuration of that through - hole in a pattern plate 32 may be a straight bore 78 therethrough with a slot arrangement 80 disposed on both the top side and the lower side of the patterned plate to provide a “ keyway ” effect therewithin , as is represented in fig1 . alignment of a pattern plate 32 and a wafer or substrate 40 in the prior art is often prior art is often an operation which consumes time and expense . one such apparatus for minimizing the expense , the time and the possible inaccuracies associated therewith , would be to present an apparatus 94 for supporting the patterned plate 32 in a hinged - correspondence to a base 92 for supporting the wafer 40 . pivotably moving the support 91 for the pre - aligned pattern plate 32 and the pre - aligned wafer 40 on a hinged support arrangement 94 , to provide automatic and prompt pivatable self - alignment therebetween , preceding a heating and chilling operation of the pattern plate 32 with its solder 36 filled through - holes 34 therewith for the ultimate deposition of those solder 36 as “ bumps ” onto that wafer 40 is presented herewith , in fig1 .
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in the following , exemplary embodiments are described of the method and device according to the present invention . these concrete examples are used to explain the realization of the invention , but do not limit the scope of the basic idea of the invention . one aspect of the method according to the present invention is the synchronization of the two circuits on the transmission line , the synchronization taking place via the transmission of a clock signal by the receiver . this is shown as an example in fig1 . in the upper part of the drawing , the signal sent onto the line by the transmitter is shown , and in the lower part the signal sent by the receiver is displayed opposite . the time axes of the two representations agree with one another . as is shown in fig1 , the receiver module sets an approximately rectangular clock signal on the transmission line . the transmitter module detects this clock signal and sets its signal to be transmitted in each of the recessive phases of the clock signal coming in from the receiver . analogously to the can bus , the transmit signals of the two modules are made up of dominant and recessive signals . this means that , when there is simultaneous transmission by a plurality of modules on the line , and thus in the present case simultaneous transmission by the transmitter and receiver , then due for example to the physical boundary conditions of the signal generation the dominant signal “ wins .” the bus remains at the recessive level only if both participants , i . e . transmitter and receiver , send a recessive signal . if at least one participant sends a dominant signal , the bus is at dominant level . if the dominant line level is interpreted as a logical true condition and the recessive line level is interpreted as a logical false condition , then the signal actually present on the line is an or linkage of the two signals sent by transmitter and receiver . in this way , the transmitter sends its data bit - by - bit in the gap between the dominant clock bits of the receiver , these data representing an item of logical information that is to be transmitted to the receiver . as already described , the transmitter observes the transmission line and places its bits to be transmitted in the “ recessive gaps ” of the clock signal . in the recessive phases of the clock signal that the receiver module sends , the receiver module checks the line for a change of edge from recessive to dominant . if the receiver module detects such a change of edge , this is for example interpreted as a logical one . if the receiver does not measure a change of edge up to the beginning of the next dominant clock bit , this is evaluated as a transmitted logical zero . depending on the physical realization of the bus and the particularities of the transmission protocol , recessive bits may also be represented or interpreted as one and dominant bits as zero ( inversion ). the bits transmitted from the transmitter to the receiver can be put together according to any arbitrary method to form data words , can be used to describe registers in the receiver , or can be processed and / or stored in some other way in the receiver . as shown in fig1 , the clock signal can be made up of equally long dominant and recessive phases , but a clock signal is also possible in which the dominant phases are shorter or longer than the recessive phases . an irregular signal having alternating dominant and recessive levels is also suitable for the method , because the receiver always knows whether an observed dominant bus level was set by the receiver or by the transmitter . only this factor is decisive for whether the bit is a bit belonging to the logical item of information or is an element of the clock signal , i . e . a clock bit . fig2 shows , as an example , the schematic configuration of the associated circuit , based on an open - drain interface having pull - up resistors : via the represented pull - down transistors 203 , 206 , transmitter 201 or receiver 204 can pull the transmission line to ground . if this does not happen , at least one pull - up resistor pulls the line to potential vdd 1 . here the state “ potential of the transmission line is ground ” is dominant , and the state “ potential of the transmission line is vdd 1 ” is recessive . receiver 204 produces the clock signal in that digital logic unit 205 that it contains periodically changes pull - down transistor 206 between blocking and transmission . in the blocking phase ( when the transmission line is raised to potential vdd 1 ), transmitter 201 can pull the line to ground by opening its pull - down transistor 203 using digital logic unit 202 . this change of the line level , caused by transmitter 201 , is recognized by receiver 204 as a logical one for example at times during which it interprets the absence of the change of line level in the blocking phase of its pull - down transistor 206 as a logical zero . as already mentioned , the representation of one and zero can also be inverted . the method or the circuit can be used to transmit logical information , in particular configuration information , for initializing a control device or component or a bus connection unit during a system start , the information being transmitted to this device or component or unit . that is , in this case after activation the receiver can begin to continuously specify the clock signal , and can wait for the scattering in of dominant bits by the transmitter . when the expected or required number of bits has been received , the receiver can terminate the transmission of the clock signal . however , the method can of course also be realized in such a way that the receiver continuously transmits a clock signal . also possible is a transmission as needed , i . e . in such a way that the receiver begins to send the clock signal whenever it requires a particular item of information from the transmitter . in the continuous case , the transmitter can begin the transmission of the logical information for example at a time selected by the transmitter itself , or also immediately after having being switched on and having determined the presence of the clock signal from the receiver on the line . if the transmitter does not transmit continuously , but rather for example in packets or in an event - controlled manner , then it makes sense that at the beginning of the transmitted logical information there is transmitted an item of packet start information , for example a leading dominant bit or also a sequence of defined bits , in order to signal to the receiver that a transmission is beginning . it is also conceivable that at the beginning of the logical information there is additionally transmitted an item of length information that indicates how many following logical bits are to be evaluated by the receiver . in the case in which the receiver places the clock signal onto the line only as needed , it makes sense for the transmitter to begin its transmission of the logical information when it has received a number of clock signals that is prespecified , or is prespecifiable , or also is not determined in more detail . it can terminate its transmission when the data provided for transmission have been completely transmitted . in this case , the receiver can resume the sending of the clock signal at a prespecified , prespecifiable , or not more precisely determined point in time or number of clock signals after it has received the last expected datum .
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the present invention will be understood from the following detailed discussion of the exemplary embodiments which is presented in connection with the accompanying drawings . the present invention provides a method of forming a mosfet transistor , and the resulting structure . in the following description , specific details such as layer thicknesses , process sequences , material compositions , are set forth to provide a complete understanding of the present invention . however , it will be obvious to one skilled in the art that the present invention can be employed with variations without departing from the spirit or scope of the invention . the term “ substrate ” used in the following description may include any supporting structure including , but not limited to , a semiconductor substrate that has an exposed substrate surface . semiconductor substrates should be understood to include silicon , silicon - on - insulator ( soi ), silicon - on - sapphire ( sos ), doped and undoped semiconductors , epitaxial layers of silicon supported by a base semiconductor foundation , and other semiconductor structures . when reference is made to a substrate or wafer in the following description , previous process steps may have been utilized to form regions or junctions in or over the base semiconductor or foundation . in addition , the semiconductor need not be silicon - based , but could be based on silicon - germanium , silicon - on - insulator , silicon - on - saphire , germanium , or gallium arsenide , among others . initially , as shown in fig1 , a gate oxide layer 201 is grown to a desired thickness on a semiconductor substrate 200 , e . g . a silicon substrate . the substrate can be doped to a predetermined conductivity , or as described below , channel region implants may be formed in lieu of or in addition to the substrate doping . the gate oxide layer 201 can be for example , a sio 2 ( silicon dioxide ) layer formed by thermal oxidation of the underlying silicon substrate region 200 or by any other conventional techniques well - known in the art . for purposes of a simplified description , silicon dioxide is employed as the gate oxide layer 201 ; however , other gate oxides well - known in the art can also be utilized . next , a polysilicon conducting layer 202 is formed by deposition on top of the gate oxide layer 201 . then , a first insulating layer 203 , such as a nitride layer is deposited on top of the polysilicon conducting layer 202 . typically , the nitride layer 203 is formed on the polysilicon layer 202 by chemical vapor deposition ( cvd ). however , other techniques well - known in the art can also be utilized , such as sputtering , ald processes , and pecvd to name a few . in addition , alternative - materials besides silicon nitride , possessing the properties of a dielectric can also be utilized for layer 203 . although the gate insulator material is described herein is referred to as silicon nitride , it is to be understood that the present invention also applies to gates that also contain other nitrides , such as oxynitride gate dielectrics , or silicon dioxide , or are solely comprised of nitrides , or that include other possible gate insulator materials , such as , tantalum pentoxide for example . the methods of the present invention can also be employed when high - k ( high dielectric constant ) gate materials are used . in general , the nitride layer 203 acts as an etch stop for later chemical mechanical planarization processes ( cmp ) or any other processes well - known in the art . the gate oxide layer 201 , polysilicon layer 202 , and nitride layer 203 are used to form a gate stack . referring now to fig2 , a gate stack 205 is formed by masking and etching layers 201 , 202 , and 203 . referring now to fig3 a - 3b , self - aligned source / drain implants can then be fabricated . depending on the type of source / drain implants ultimately desired , the source / drain implants can be angled , as shown in fig3 a , to produce angled implant regions 206 a , 206 b , which at this stage , can be of the type that produces ldd implants in the final transistor structure . thus , the doping can partially extend beneath the gate stack 205 , as in fig3 a , or can be vertical 207 a , 207 b , as shown in fig3 b , in which case source / drain regions 207 a , 207 b do not significantly extend beneath the gate stack 205 . for instance , source / drain regions 207 a and 207 b can be self - aligned to the gate stack structure 205 . other well - known ldd implant techniques can also be used in accordance with desired operating characteristics of the transistor under fabrication . alternatively , implanting can also be omitted at this stage if ldd implants are not desired ( not illustrated ). next , as shown in fig4 a , an insulating layer , e . g ., an oxide layer 208 is deposited , for example , by cvd techniques . however , other techniques well - known in the art can also be used to deposit oxide layer 208 ( e . g ., a spacer - forming layer ). for instance , sputtering , ald processes , or pecvd to name only a few . for instance , oxide layer 208 is deposited conformally over the surface of the silicon substrate 200 and gate stack structure 205 . although the present invention utilizes an oxide layer 208 , alternative materials such as tetraethylorthosilicate ( teos ), a high density plasma ( hdp ) oxide , borosilicate glass ( bpg ), phosphosilicate glass ( psg ), borophosphosilicate glass ( bpsg ), or other materials suitable for constructing sidewall spacers adjacent to the gate stack structure 205 can be used in lieu of or in combination with oxide layer 208 . oxide layer 208 ( e . g ., a spacer - forming layer ) is then anisotropically etched , resulting in two oxide sidewall spacers 209 a , 209 b located adjacent to the sidewalls of the gate stack structure 205 as illustrated in fig4 b . after the formation of sidewall spacers 209 a , 209 b , conventional source / drain implants 250 a , 250 b can be formed as illustrated in fig4 b if previous implants were not formed . as noted previously , if earlier ldd implants were formed , as in fig3 a , the source / drain regions 251 a , 251 b , are ldd regions as shown in fig4 c . for purposes of a simplified description , the illustrated structures show source / drain regions 250 a , and 250 b ; however , it should be understood that the invention has equal applicability to transistors having ldd source / drain regions . a second insulating layer 211 is next blanket deposited over the substrate 200 , and gate stack 205 having spacers 209 a , 209 b , as shown in fig5 a . the second insulating layer 211 can also be formed from the group consisting of hdp , bpg , psg , bpsg , teos , and other alternative materials that are well - known in the art which may be used in lieu of or in combination to form the second insulating layer 211 . referring now to fig5 b , the second insulating layer 211 undergoes a chemical mechanical planarization process ( cmp ) down to the first insulating layer 203 , e . g ., nitride layer 203 . as a result , the surface of the second insulating layer 211 becomes substantially planar with the surface of the exposed nitride layer 203 . again , other techniques that are well - known in the art can be used to form the surface of the second insulating layer 211 so that it becomes smooth and substantially planar with the surface of the exposed nitride layer 203 . next , as shown in fig5 c , the nitride layer 203 ( e . g ., first insulating layer ) is etched away using a wet nitride etch , e . g ., h 3 po 5 ( hot phosphoric ), with a good selectivity to oxide . other techniques that are well - known in the art can also be used to etch away the first insulating layer so that the conducting layer 202 is exposed . as a result , the nitride layer 203 is completely etched away exposing the surface of the conducting layer 202 as fig5 c illustrates . after this processing step , if channel implants are desired ( and have not been performed previously ), they can now be formed . thus , optional channel implant region 301 can be formed by implanting dopant through the polysilicon layer 202 and the gate oxide layer 201 of the gate stack structure 205 . the optional channel implant region 301 is formed beneath and is self - aligning to the gate stack 205 . spacers 209 a and 209 b at least in part , define optional channel implant region 301 . it is to be appreciated , that additional channel implant regions can be fabricated if desired . fabrication of additional channel implant regions utilizing the methods of the present invention are described below . many channel implant variations are possible for channel implant regions in addition to optional channel implant region 301 illustrated in fig5 c . for example , another exemplary embodiment is illustrated in fig6 a - 6c . a first implant can be conducted , as illustrated in fig6 a , to form a first channel implant region 301 ( similar to methods described in fig5 a - 5c ). then , a nitride layer 271 ( e . g ., a third insulating layer ) can be blanket deposited as shown in fig6 b , and subsequently etched and planarized as shown in fig6 c , to produce nitride spacers 212 a , 212 b adjacent to the sides of the insulating layer 211 and covering at least a portion of the exposed conducting layer 202 . although the present invention utilizes a nitride layer 271 , other materials well - known in the art that are suitable for constructing spacers adjacent to the sides of the insulating layer 211 and covering at least a portion of the exposed conducting layer 202 , can be used in lieu of or in combination with the nitride layer 271 . a second optional channel implant can then be conducted to produce a channel implant region 303 smaller in size ( e . g ., smaller in width compared to the gate stack &# 39 ; s 205 width and optional channel implant region 301 &# 39 ; s width ) than channel implant region 301 , as depicted in fig6 c . nitride spacers 212 a and 212 b , at least in part , define optional channel implant region 303 . if nitride spacers 212 a and 212 b cover a greater portion of the conducting layer 202 ( e . g ., less surface area of the conducting layer 202 is exposed ), the optional channel implant region 303 will be accordingly smaller in width . if nitride spacers 212 a and 212 b cover a smaller portion of the conducting layer 202 ( e . g ., more surface area of the conducting layer is exposed ), the optional channel implant region 303 will be accordingly wider . further , channel implant region 303 can possess a higher or smaller dopant concentration than channel implant region 301 , depending upon the characteristics of the desired fabricated device . as a result , the construction of nitride spacers 212 a and 212 b can define the width of channel implant region 303 depending upon the desired device &# 39 ; s operating characteristics . alternatively , in another embodiment of the present invention , the processing sequences forming optional channel implant region 301 , shown in fig6 a , can be omitted in which case only channel implant region 303 is formed ( not illustrated ). the optional channel implant region 303 is narrower than the gate stack 205 due to the presence of the optional nitride spacers 212 a , 212 b , as shown in fig6 c , and is self - aligning to the gate stack structure 205 . as described previously , channel implant region 303 is at least in part defined by nitride spacers 212 a and 212 b . as can be appreciated from the various embodiments , optional spacers 212 a , 212 b ( comprised of nitride or other materials well - known in the art ) can be fabricated to any desired size above the conducting layer 202 to create different sizes for channel implant region 303 . even more additional channel implant variations are depicted in fig7 a - 7d . referring now to fig7 a , and as discussed previously in fig5 c , the nitride layer 203 ( e . g ., first insulating layer ) is etched away using a wet nitride etch , e . g ., h 3 po 5 ( hot phosphoric ), with a good selectivity to oxide . then , portions of the second insulating layer 211 adjacent to the gate stack 205 , are selectively etched to produce the structure in fig7 b , which possesses a wider channel implant region 305 than the width of the gate stack 205 . as a result , a first channel implant region 305 can then be implanted as shown in fig7 b . as illustrated in fig7 b , channel implant region 305 is wider than the width of the gate stack structure 205 . thus , the degree of etching of the insulating layer 211 defines at least in part , the width of channel implant region 305 . additionally , if desired , formation of channel implant region 305 can be omitted . assuming channel implant region 305 is provided , following this , a nitride layer 273 , e . g ., an optional third insulating layer , can be blanket deposited as shown in fig7 c , and selectively etched to produce nitride spacers 275 a , 275 b as illustrated in fig7 d . although the present invention utilizes a nitride layer 273 as the insulating layer , other materials well - known in the art that are suitable for constructing spacers adjacent to the sides and covering at least a part of the second insulating layer 211 , and covering at least a - part of the exposed conducting layer 202 , can be used in lieu of or in combination with the nitride layer 273 . a second optional channel implant region 307 can then be formed as shown in fig7 d that is self - aligning to the gate stack 205 . the second channel implant region 307 is at least in part defined by spacers 275 a and 275 b . as a result , the width of the optional channel implant region 307 , illustrated in fig7 d , can be substantially controlled , and it can have a different concentration of dopant when compared to optional channel implant region 305 . the width of the optional channel implant region 307 is controlled by the manner in which the nitride layer 273 ( e . g ., third insulating layer ) is selectively etched . selective etching of the nitride layer 273 , as shown in fig7 c , can result in nitride spacers 275 a , 275 b , shown in fig7 d , which can form an optional channel implant region 307 that is substantially smaller than the width of the gate stack 205 , and can also be self - aligning to the gate stack 205 depending upon the desired device &# 39 ; s operating characteristics . the width of the channel implant region 307 , as illustrated in fig7 d , can be narrower or wider than illustrated . furthermore , the dopant concentration of channel implant region 307 can be greater or less than the dopant concentration found in channel implant region 305 . as can be appreciated from the various embodiments , nitride spacers 275 a , 275 b can be fabricated to any desired size located above the conducting layer 202 or layer 211 , to create different optional channel implant regions 305 and 307 that can be different in width and dopant concentration than depicted in fig7 b . in addition , the step of forming channel implant region 305 , as illustrated in fig7 b , can be omitted if desired . as a result , only channel implant region 307 is formed utilizing nitride spacers 275 a and 275 b . fig7 a - 7d illustrate only a small number of different possibilities that can be achieved when utilizing the methods of the present invention . many different embodiments and variations are possible by creating additional spacers such as 275 a and 275 b . additional spacers can also be used and created in conjunction or in lieu of spacers 275 a , 275 b to create even more different channel implant regions than is illustrated in fig7 a - 7d . for example , an additional insulating could be provided over spacers 275 a , 275 b and subsequently selectively etched to form additional spacers ( not illustrated ). the additional spacers could again define , at least in part , a third channel implant region within channel implant region 307 , assuming that it was previously formed . for instance , a third channel implant region can be formed within channel implant region 307 if desired ( not illustrated ) that possesses a greater or lesser dopant concentration than channel implant implant region 307 . further , even more additional channel implant regions ( e . g ., a plurality of channel implant regions ) are possible with the construction of additional spacers which at least in part , would define the width of the plurality of channel implant regions . another variation of channel implants which can be produced is described below with reference to fig8 a - 8e . in this variant , after removal of the first insulating layer 203 , portions of the second insulating layer 211 adjacent to the gate stack 205 , are selectively etched to produce the structure in fig8 b , which possesses a wider implant area 305 than the width of the gate stack 205 ( similar to the structure disclosed in fig7 b ). in this exemplary embodiment , a clean is conducted after formation of channel implant region 305 . if channel implant region 305 is not formed , a clean is conducted after selectively etching portions of the second insulating layer 211 . an additional optional etch is next conducted on sidewall spacers 209 a and 209 b as shown in fig8 c , recessing them to a pre - determined depth ( e . g ., selectively etching them to a predetermined height ). the depth of the etch should not extend to the gate oxide layer 201 . after the clean and etch , a nitride layer 273 ( e . g ., third insulating layer as described in reference to fig7 a - 7d ) can be blanket deposited as shown in fig8 d , and selectively etched to produce nitride spacers 275 a , 275 b of fig8 e . a second channel implant region 307 can then be formed as shown in fig8 e that is self - aligning to the gate stack 205 at least in part defined by spacers 275 a , 275 b . as discussed previously with respect to fig7 a - 7d , the width of the channel implant region 307 can be narrower or wider than illustrated and possess a higher or smaller dopant concentration than channel implant region 305 . further , a third channel implant region can be formed within channel implant region 307 if desired . still further , a plurality of channel implant regions can be formed within each previously formed channel implant region utilizing the methods of the present invention , at least in part defined by additionally formed spacers . the purpose of conducting an optional etch on sidewall spacers 209 a , 209 b , is to allow a second set of spacers , such as 275 a and 275 b , to protect the edges of the conducting layer 202 from shorts , as illustrated in fig8 e . spacers 275 a and 275 b can also provide further enhancement for future sac ( self - aligned contact ) etching processes . this exemplary embodiment finds particular utility in fabricating dram devices . as described above , additional channel implant regions can also be formed within channel implant region 307 is desired ( not illustrated ). these additional channel implant regions can also possess a different dopant concentration and have different widths than optional channel implant regions 305 and 307 . after the optional channel implants are fabricated , spacers 212 a , 212 b as depicted in fig6 c , or 275 a , 275 b as depicted in fig7 d and fig8 e , are present over or adjacent to the gate stack 205 . referring now to fig9 a - 9b which illustrates spacers 212 a , 212 b following the methods of fig6 a - 6c implantation steps , a thin layer of tungsten nitride ( wn x ) 216 a is first blanket deposited followed next by a layer of tungsten ( w ) 216 b . these metal layers 216 a and 216 b , e . g . refractory metal layers , are planarized using cmp as shown in fig9 b . other techniques that are well - known in the art can also be utilized to create a substantially planar surface for the metal layers 216 a and 216 b . in addition , other conductive layers that are well - known in the art can be used in lieu of the w / wn x layer combination . for example , a w / tin combination can be deposited in place of the w / wn x layer combination . still further , only one conductive layer can deposited if desired rather than a combination of metal layers . after the metal deposition steps , a silicide process is conducted to form a metallic silicide on the polysilicon 202 region of the gate stack 205 . for purposes of a simplified description , the silicide process is not described . the formation of a metallic silicide is well - known in the art . the process described above of layering in w / wn x or w / tin with reference to fig9 a and 9b , can also be applied with equal success to the structures described in reference to fig7 a - 7d or fig8 a - 8e ( or any other variants which are not illustrated ), to form a silicide from the refractory metal in layers 216 a , 216 b and the polysilicon layer 202 . the addition of the refractory metal layers after implantation allows fabrication of a structure that does not etch the metal layers . as described previously , the presence of metal layers during device fabrication can have deleterious effects . since the metal layers are deposited after implantation and etching are completed , the deleterious effects are avoided . accordingly , the methods of the present invention find particular utility anytime a structure is fabricated and one wishes to avoid etching the last formed layers during the fabrication process . referring now to fig9 c , additional insulating layers and other structures can be fabricated over the thus formed transistor . for example , an insulating layer 281 , e . g ., bpsg , can be deposited over the fig9 b structure and openings 291 etched through layers 281 and 211 to the source / drain regions , which are filled with a conductor 293 , e . g ., polysilicon , to provide contacts to source / drain regions 250 a , 250 b . an opening in insulator 281 , can also be etched to conductive layer 216 b which is filled with a conductor to provide contact to the transistor gate . fig1 is a block diagram of a processor system : having many electronic components which may be fabricated as an integrated circuit chip having a transistor structure produced as described above . the processor system 900 includes one or more processors 901 coupled to a local bus 904 . a memory controller 902 and a primary bus bridge 903 are also coupled the local bus 904 . the processor system 900 may include multiple memory controllers 902 and / or multiple primary bus bridges 903 . the memory controller 902 and the primary bus bridge 903 may be integrated as a single device 906 . the memory controller 902 is also coupled to one or more memory buses 907 . each memory bus accepts memory components 908 which include at least one memory device 100 . the memory components 908 may be a memory card or a memory module . examples of memory modules include single inline memory modules ( simms ) and dual inline memory modules ( dimms ). the memory components 908 may include one or more additional devices 909 . for example , in a simm or dimm , the additional device 909 might be a configuration memory , such as a serial presence detect ( spd ) memory . the memory controller 902 may also be coupled to a cache memory 905 . the cache memory 905 may be the only cache memory in the processing system . alternatively , other devices , for example , processors 901 may also include cache memories , which may form a cache hierarchy with cache memory 905 . if the processor system 900 include peripherals or controllers which are bus masters or which support direct memory access ( dma ), the memory controller 902 may implement a cache coherency protocol . if the memory controller 902 is coupled to a plurality of memory buses 907 , each memory bus 907 may be operated in parallel , or different address ranges may be mapped to different memory buses 907 . the primary bus bridge 903 is coupled to at least one peripheral bus 910 . various devices , such as peripherals or additional bus bridges may be coupled to the peripheral bus 910 . these devices may include a storage controller 911 , an miscellaneous i / o device 914 , a secondary bus bridge 915 , a multimedia processor 918 , and an legacy device interface 920 . the primary bus bridge 903 may also coupled to one or more special purpose high speed ports 922 . in a personal computer , for example , the special purpose port might be the accelerated graphics port ( agp ), used to couple a high performance video card to the processor system 900 . the storage controller 911 couples one or more storage devices 913 , via a storage bus 912 , to the peripheral bus 910 . for example , the storage controller 911 may be a scsi controller and storage devices 913 may be scsi discs . the i / o device 914 may be any sort of peripheral . for example , the i / o device 914 may be an local area network interface , such as an ethernet card . the secondary bus bridge may be used to interface additional devices via another bus to the processor system . for example , the secondary bus bridge may be an universal serial port ( usb ) controller used to couple usb devices 917 via to the processor system 900 . the multimedia processor 918 may be a sound card , a video capture card , or any other type of media interface , which may also be coupled to one additional devices such as speakers 919 . the legacy device interface 920 is used to couple legacy devices , for example , older styled keyboards and mice , to the processor system 900 . any or all of the electronic and storage devices depicted in fig1 may employ a transistor constructed in accordance with the invention . for example , the processors 901 and / or memory devices 100 may contain transistors fabricated in accordance with the invention . the processor system 900 illustrated in fig1 is only an exemplary processing system with which the invention may be used . while fig1 illustrates a processing architecture especially suitable for a general purpose computer , such as a personal computer or a workstation , it should be recognized that well - known modifications can be made to configure the processor system 900 to become more suitable for use in a variety of applications . for example , many electronic devices which require processing may be implemented using a simpler architecture which relies on a cpu 901 coupled to memory components 908 and / or memory devices 100 . these electronic devices may include , but are not limited to audio / video processors and recorders , gaming consoles , digital television sets , wired or wireless telephones , navigation devices ( including system based on the global positioning system ( gps ) and / or inertial navigation ), and digital cameras and / or recorders , as well as other electronic devices . the modifications may include , for example , elimination of unnecessary components , addition of specialized devices or circuits , and / or integration of a plurality of devices . although exemplary embodiments of the present invention have been described and illustrated herein , many modifications , even substitutions of materials , can be made without departing from the spirit or scope of the invention . accordingly , the above description and accompanying drawings are only illustrative of exemplary embodiments that can achieve the features and advantages of the present invention . it is not intended that the invention be limited to the embodiments shown and described in detail herein . the invention is limited only by the scope of the following claims .
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turning now to the drawings , and in particular to fig1 a vehicle seat assembly 10 is illustrated as comprising a seat cushion assembly 12 , a seat back 14 pivotally mounted to the seat cushion assembly 12 , a support frame 16 , a linkage assembly 18 pivotally mounted between the seat cushion assembly 12 and the support frame 16 , and a latch assembly 20 . the seat cushion assembly 12 necessarily includes a conventional cushion member 22 secured in a known manner to a generally rectangular horizontally positioned frame 24 . the seat cushion frame 24 includes laterally spaced sidewalls 26 , 28 which may be formed of a double - walled construction and front and rear walls 30 , 32 . a laterally extending brace 34 is positioned between the inner sides of the sidewalls 26 , 28 . the seat back 14 , which similarly includes a cushion portion 36 , is pivotally mounted through pins 38 to the sidewalls 26 , 28 . a plurality of journal members 40 extend rearwardly from the inner face 41 of the front wall 30 , as may best be seen in fig2 . the support frame 16 is preferably formed as a pair of laterally spaced upstanding brackets or plates 42 , 44 . each plate 42 , 44 has a flat base portion 46 which is conventionally secured to the floor ( not shown ) of the vehicle by cooperation with known fasteners or the like . the plates 42 , 44 further include generally rectangular imperforate outer shield plates 48 and generally triangular upstanding latch plates 50 spaced laterally inwardly from the shield plates 48 . each latch plate 50 includes at least one latching detent , as indicated by the forwardly positioned hole 52 . the linkage assembly 18 is simply constructed to include a pair of laterally outwardly positioned elongated link members 54 , 56 , each of which is pivotally mounted to the seat cushion frame 24 as indicated at a pivot pin 58 at its top end , and to the latch plate 50 as through a pin indicated at 60 at its bottom end . the linkage assembly 18 further includes a generally u - shaped bar member 62 having laterally spaced legs 64 , 66 positioned laterally inwardly with respect to the rear links 54 , 56 and pivotally mounted as through pins indicated at 68 , 70 and upstanding trunnion mounts 72 , 74 carried with the plates 42 , 44 , respectively of the support frame 16 . a bridge portion 76 joins the leg 64 , 66 being pivotally received through bores 78 in journal members 40 connected to the front wall 30 of the seat frame 24 . the latch assembly 20 consists of an actuator plate 80 rotatably mounted in known fashion such as by a journalled pin as indicated at 81 to the front face of the support brace 34 . a pair of pin guides 82 , 84 carried in depending fashion from the sidewalls 26 , 28 of the seat cushion frame 24 are provided to carry latching pins 86 , 88 . the latching pins 86 , 88 are resiliently biased outwardly in known fashion and are connected to the latch plate 80 by cables 90 , 92 . another cable 94 connects through an eyelet 96 to the latch plate 80 at one end , and at the other end to a ring pull actuator 98 . a coil spring 100 is fixed between the latch plate 80 and the brace 34 to bias the latch plate 80 toward the position shown in fig1 in which the latch pins 86 , 88 are urged outwardly into their latching positions . the operation of the seat assembly 10 to fold down to lowered positions can be readily appreciated by reference to fig2 - 4 . in these views the link pivotally connecting the seat back 14 to the seat cushion assembly 12 through the pin indicated at 38 in fig1 is eliminated to simplify the graphical presentation . it will be understood that any known mounting arrangement that permits pivotal movement of the seat back forwardly into a position in which its front surface f abuttingly engages the top surface t of the cushion member 22 may be employed . it will also be understood that the motion of components only on the left side of the seat assembly as it faces forward are described since the symmetrically positioned components on the other side of the seat operate identically . in the upright position of fig2 the latch pin 88 is biased outwardly to abuttingly engage a rear surface 102 of support plate 42 . this holds the rear link 54 and the front leg 64 , which are illustrated as being arranged in parallel fashion and being of equal length , in the operative position for occupant seating . drawing on the ring pull 98 rotates the latch plate 80 to withdraw the latch pin 88 from abutting engagement with the surface 102 and permits the seat cushion assembly 12 to be moved forward and downwardly as shown in fig3 to a position where the latch pin 88 registers with the hole 52 in the latch plate 50 , the link 54 and the leg 64 pivoting counterclockwise in parallelogram fashion to control this movement . such movement of the seat is particularly useful when it is utilized in a vehicle position in which an occupant entering the vehicle may desire such forward movement of the seat to facilitate ingress or egress to or from the rear of the seat assembly 10 . a subsequent actuation of the latch assembly 20 can withdraw the pin 88 and permit further movement of the seat cushion assembly 12 to the position shown in fig4 . in any of the illustrated positions , the seat back 14 may be moved pivotally to rest upon the seat cushion assembly 12 as shown in fig4 . downward movement of the seat cushion assembly may be stopped by abutting engagement of the latch pin holder 84 with the floor of the vehicle ( not shown ) or by providing other mechanical stop means . it will be particularly noted in fig4 that the fully stowed downward positioning of the seat assembly 10 is enhanced by the arrangement of the link 54 and the leg 64 in laterally spaced positions with respect to the seat cushion frame 24 . the linkage structure effecting the stowing movement of the seat assembly 10 does not obstruct full downward movement of the frame 24 . it will also be noted that the shield plate 48 substantially covers the linkage assembly 18 and provides for direct engagement with the latch pin 88 . in some vehicle applications , it may also be useful to utilize the nonmovable support frame as a mount for components associated with the use of the seat , such as occupant restraints . turning now to fig5 an alternative embodiment 580 of the latch plate is shown in which an offset ramp surface 104 terminating in a detent formed by an abutment surface 106 is positioned extending in arcuate fashion near the top of the plate 550 . a locking notch 108 is positioned at the forward bottom edge of the plate 550 . in this alternative embodiment , no depending latch pin guide members are utilized and a spring loaded guide pin 588 extends directly outwardly from the seat frame 524 . the seat assembly 510 , similar to the seat assembly 10 of fig1 - 4 provides a latch assembly 520 , having a latch plate 580 carried for horizontal rotative movement on a brace member 534 is resiliently biased into position by a return spring 500 carried on the seat cushion frame 524 . cables 590 connect with cable pulls 598 for rotating the actuator plate 580 and withdrawing outwardly spring biased pins 586 , 588 slidably mounted in the seat cushion frame 524 as by brackets 587 , 589 . those skilled in the art will appreciate that the number of alternatives to the latch assemblies 20 and 520 disclosed are possible and readily available . any mechanism for selectively withdrawing and replacing a latch pin from the seat cushion frame 24 or 524 or guide structure associated with it , such as the guide members 82 , 84 may be employed with the stowable seat assembly of the present invention . when the pin 588 is withdrawn by operation of a pull , such as 598 , the outer end of the pin 588 slides along the ramp surface 104 , which serves as a release mechanism , until it engages the abutment 106 establishing the intermediate folded position . the seat may be restored to the upright position simply by pushing it to move rearwardly without operating the cable pull 598 to withdraw the pin 588 . the fully stowed position of this seat can be established by withdrawal of the pin 588 from the position of engagement with abutment 106 and moving the seat forwardly until the pin 588 engages in the notch 108 . motion reversal from this position , of course , required operation of the cable pull 598 to withdraw the pin 588 . while only certain embodiments of the stowable seat assembly of the present invention have been described , others may be possible without departing from the scope of the appended claims .
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the particulars shown herein are by way of example and for purposes of illustrative discussion of the embodiments of the present invention only and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the present invention . in this regard , no attempt is made to show structural details of the present invention in more detail than is necessary for the fundamental understanding of the present invention , the description taken with the drawings making apparent to those skilled in the art how the several forms of the present invention may be embodied in practice . fig1 depicts a conventional prior art piston 2 for an internal combustion engine . the piston has a cylindrical shape with a head 4 ( or top ) and is generally hollow inside . the lower end of the cylindrical wall of the piston 2 is known as the skirt 8 . internally disposed within the piston 4 is a pair of pin bosses 6 which each have a pin bore 7 adapted to receive a wrist pin ( not shown ) in which a connecting rod ( not shown ) is rotatably attached . formed within the outer cylindrical wall of the piston 2 proximate the head 4 are three ring grooves , including a first ( or top ) ring groove 10 , a second ring groove 12 , and an oil ring groove 14 . fig2 is detail view of the ring grooves from fig1 taken along cross - section 2 - 2 . the head 4 of the piston 2 also forms the top land 16 which provides the top surface of the top ring groove 10 . a second land is disposed between the top ring groove 10 and the second ring groove 12 , thereby providing the lower surface of the top ring groove 10 and the upper surface of the second ring groove 12 . a third land is disposed between the second ring groove 12 and the oil ring groove 14 , thereby providing the lower surface of the second ring groove 20 and the upper surface of the oil ring groove 14 . also shown in phantom lines are the top ring 30 , the second ring 40 , and the third ring 50 . the present invention , various aspects thereof , and various embodiments thereof are shown in fig3 - 15 . to overcome the unwanted dissipation of coatings and dry - films from the flat surfaces of the ring due to friction and high temperatures , one aspect of the present invention is the incorporation of replenishment pockets 32 , 42 , 52 or 62 on the flat surfaces of the ring 30 , 40 , 50 or 60 ( i . e ., the upper 24 and lower 26 surfaces ). such pockets may vary in size , depth , the number used , and the arrangement or orientation in which the pockets are formed in the upper and lower flat surface of the ring . the pockets 32 , 42 , 52 or 62 may be formed by a various known metal removal techniques , for example mechanical removal by milling tools , laser removal , or by chemical etching . a depth of 0 . 001 thousandths of an inch is an exemplary preferred depth ; however , it is appreciated that the depth of the pocket may vary according to each application . for instance , if it desired that the replenishment pockets store more lubricant , than the depth can be increased in any desired increment . thus , it is foreseeable that a depth ranging from about 0 . 001 thousandths to 0 . 010 thousandths ( or even larger ) may be implemented depending on the overall thickness of the ring , so long as the overall strength of the ring is not greatly effected . it is preferred that the number and shape ( i . e ., total area covered ) of the replenishment pockets 32 , 42 , 52 or 62 be correlated to a percentage of total coverage of the surface of the ring 30 , 40 , 50 or 60 . for instance , it is preferred that a range between about 30 percent to about 10 percent of the ring surface be covered by replenishment pockets . and it is even more preferable that the replenishment pockets cover about 20 percent of the ring surface . thus , it can be seen , that the size of the replenishment pockets ( i . e ., the diameter size or shape ) and the number of replenishment pockets disposed on the ring surface , and depths thereof , can be adjusted and / or vary to meet a specific total replenishment pocket coverage requirement . hence , it is foreseeable that pocket size and volume can be correlated directly to a desired life period for the rings . the lubricant disposed within the replenishment pockets may comprise a variety of materials and / or compositions , for example , various dry - film lubricants or any other composition which may be disposed within a replenishment pocket . the lubricant may be for example , graphite tungsten disulfide or molybdenum disulfide . it is noted , however , that the aforementioned list of lubricants is merely exemplary and is not intended to be comprehensive . rather , it is well - known that from time to time , preferred dry film compositions or lubricants which may be ideally adapted to be disposed within the replenishment pockets may be invented or developed , and that such advancements in compositions or lubricants may also be utilized in the replenishment pockets in the foreseeable future . the manner in which the replenishment pockets function is now explained . as already discussed , the replenishment pockets 32 , 42 , 52 or 62 act as reservoirs which contain lubricant , such as a dry - film or a coating . furthermore , at least one of the upper 24 and lower 26 surfaces of the ring may be further coated with lubricant or a coating . as the pistons move up and down , the upper and lower ring surface may typically contact portions of the grooves 10 , 12 , 14 and lands 16 , 18 , 20 formed in the piston 2 . moreover , the rings may slightly rotate within the groves 10 , 12 , 14 . such surface to surface contact ( i . e . friction ) under extreme heat tends to remove and dissipate the lubricant from the top and bottom surfaces of the ring . when the lubricant , such as dry film has been worn from the top and bottom surfaces of the ring , the dry - film from the replenishment pockets is displaced and migrates from the pockets ( from friction ) and is redeposited onto the flat surfaces of the ring . following are several examples of ring designs which utilize the exemplary replenishment pockets . fig3 is a first exemplary embodiment of a ring 30 having slot - shaped replenishment pockets 32 disposed on at least one of the flat surfaces of the ring , according to an aspect of the present invention . the ring 30 is defined by an inner side 23 , and outer ring face side 23 , and substantially flat top and bottom surfaces 24 , 26 . the ring 30 further is defined by a width w ( see fig4 ) and a thickness t ( see fig6 ). fig4 is a detail view taken from detail 4 of fig3 which shows an exemplary arrangement of the slot - shaped replenish pockets 32 on at least one of the surfaces of the ring 24 , 26 , according to an aspect of the present invention . in this embodiment , a plurality of slot - shaped pockets 32 are radially aligned ( i . e ., spanning the width w of the ring ) and equally spaced around the ring 30 . in the particular example , there are eighteen pockets 32 disposed on the top surface 24 of the ring 30 , wherein each pocket 32 is spaced apart by about 20 degrees , and wherein the pockets 32 start at about 10 degrees from the end gap of the ring 30 . it is noted that the slot - shaped pockets 32 may be arranged and / or oriented in many different ways , and therefore , the present invention should not be limited merely to the first exemplary embodiment depicted in fig3 - 6 . for example , the slot - shaped pockets 32 need not be radially aligned ; as an alternative , the slot - shaped pockets 32 may be slanted at angles , or the spacing may also vary depending on the number of pockets desired to be formed on the surfaces 24 , 26 of the ring 30 . fig5 is a detail view taken from detail 5 of fig4 which shows a close - up view of an exemplary slot - shaped replenishment pocket 32 , according to an aspect of the present invention . this exemplary embodiment of a slot - shaped pocket 32 has the dimensions of 0 . 080 inches in length , about 0 . 15 inches in width , and a radius of about 0 . 0075 inches . however , it is noted that the shape and dimensions of the slot - shaped pocket 32 may vary , and thus the present invention should not be limited to merely to the first exemplary embodiment shown in the fig3 - 6 fig6 is a detail view taken from fig4 which shows a cross - section of the ring 30 taken along cross - section 6 - 6 , according to an aspect of the present invention . as discussed , the slot - shaped pockets 32 may be formed either on the top surface 24 ( as shown in fig6 ), the pockets 32 may be formed on the bottom surface 26 ( not shown in fig6 ), or the pockets 32 may be formed on both flat sides of the ring 30 . fig7 is a second exemplary embodiment of a ring 40 having a plurality of radial - spaced pairs of circular - shaped replenishment pockets 42 disposed on at least one of the flat surfaces of the ring 40 , according to an aspect of the present invention . the ring 40 is defined by an inner side 23 , an outer ring face side 22 , and substantially flat top and bottom surfaces 24 , 26 . the ring 40 further is defined by a width w ( see fig8 ) and a thickness t ( see fig9 ). fig8 is a detail view taken from detail 8 of fig7 which shows an exemplary arrangement of the circular - shaped pairs replenishment pockets 42 on at least one of the surfaces of the ring 24 , 26 , according to an aspect of the present invention . in this exemplary embodiment , a plurality of circular - shaped pairs pockets 42 are radially aligned ( i . e ., spanning the width w of the ring ), circumferentially aligned , and equally spaced around the ring 40 . in the particular example , there are a plurality of pairs of pockets 42 disposed on the top surface 24 of the ring 40 , wherein each pair of pockets 42 is spaced apart by about 5 degrees , and wherein the pockets 42 start at about 12 degrees from the end gap of the ring 40 . furthermore , each circular - shaped pocket 42 is spaced about 0 . 020 inches from the ring face 22 or the inner side 23 . the exemplary embodiment of a circular - shaped pocket 42 has the dimensions of 0 . 015 inches in diameter ; however , it is appreciated that the size of the pocket 42 may vary according to the application . it is noted that the circular - shaped pockets 42 may be arranged and / or oriented in many different ways , and therefore , the present invention should not be limited merely to the exemplary embodiment depicted in fig7 through 9 . for example , the circular - shaped pair of pockets 42 need not be radially aligned ; as an alternative , the circular - shaped pair of pockets 42 may be slanted at angles , or the spacing may also vary depending on the number of pair pockets desired to be formed on the surfaces 24 , 26 of the ring 40 . moreover , the overall diameter , depth and / or shape of the circular - shaped pockets 42 may vary , and thus the present invention should not be limited to merely to the second exemplary embodiment shown in fig7 - 9 . fig9 is a detail view taken from fig8 which shows a cross - section of the ring 40 taken along cross - section 9 - 9 , according to an aspect of the present invention . as discussed , the circular - shaped pockets 42 may be formed either on the top surface 24 ( as shown in fig9 ), the pockets 42 may be formed on the bottom surface 26 ( not shown in fig9 ), or the pockets 42 may be formed on both flat sides of the ring 40 . furthermore , the depth of the pocket 42 may vary depending on the amount of lubricant that is desired to be disposed within the pockets 42 . fig1 is a third exemplary embodiment of a ring 50 having a plurality of sets of stepped or staggered circular - shaped replenishment pockets 52 disposed on at least one of the flat surfaces of the ring 50 , according to an aspect of the present invention . the ring 50 is defined by an inner side 23 , and outer ring face side 22 , and substantially flat top and bottom surfaces 24 , 26 . the ring 50 further is defined by a width w ( see fig1 ) and a thickness t ( see fig1 ). fig1 is a detail view taken from detail 11 of fig1 which shows an exemplary arrangement of the plurality of sets of stepped or staggered circular - shaped replenishment pockets 52 on at least one of the surfaces of the ring 24 , 26 , according to an aspect of the present invention . in this exemplary embodiment , a plurality of circular - shaped pockets 52 are arranged in stepped or staggered sets , which have the appearance of a zig - zagging pattern . in particular , there are a plurality of pockets 52 disposed on the top surface 24 of the ring 50 , wherein each pockets 52 is spaced apart by about 7 degrees , and wherein the pockets 52 start at about 7 degrees from the end of the ring 50 . the three pocket pattern is then repeated every 21 degrees around the circumference of the ring 50 . the pockets 52 closest to the ring face 22 and inner side 23 are spaced from the ring face 22 and inner side 23 by about 0 . 030 inches . the exemplary embodiment of a circular - shaped pocket 52 has the dimensions of 0 . 020 inches in diameter ; however , it is appreciated that the size of the pocket 42 may vary according to the application . it is noted that the circular - shaped pockets 52 may be arranged and / or oriented in many different ways , and therefore , the present invention should not be limited merely to the second exemplary embodiment depicted in the figures . for example , the circular - shaped pockets 52 need not be in a three pocket pattern ; as an alternative , the circular - shaped pockets 52 may be in a two pocket zig - zagging pattern , or the spacing may also vary depending on the number of pockets 52 desired to be formed on the surfaces 24 , 26 of the ring 50 . moreover , the overall diameter , depth and / or shape of the circular - shaped pockets 52 may vary , and thus the present invention should not be limited to merely to the second exemplary embodiment shown in fig1 - 12 . fig1 is a detail view taken from fig8 which shows a cross - section of the ring 40 taken along cross - section 12 - 12 , according to an aspect of the present invention . as discussed , the circular - shaped pockets 52 may be formed either on the top surface 24 ( as shown in fig1 ), the pockets 52 may be formed on the bottom surface 26 ( not shown in fig1 ), or the pockets 52 may be formed on both flat sides of the ring 50 . furthermore , the depth of the pocket 52 may vary depending on the amount of lubricant that is desired to be disposed within the pockets 52 . fig1 is a fourth exemplary embodiment of a ring 60 having a plurality circular - shaped replenishment pockets 62 uniformly spaced about a centerline of one of at least the upper and lower surfaces of the ring 60 , according to an aspect of the present invention . the ring 60 is defined by an inner side 23 , and outer ring face side 22 , and substantially flat upper and lower surfaces 24 , 26 . the ring 60 further is defined by a width w ( see fig1 ) and a thickness t ( see fig1 ). fig1 is a detail view taken from detail 14 of fig1 which shows an exemplary arrangement of the plurality circular - shaped replenishment pockets 62 , each of which have the same diameter , and of which are also uniformly spaced on at least one of the surfaces of the ring 24 , 26 , according to an aspect of the present invention . in this exemplary embodiment , it is preferred that the number and diameter ( d ) of the pockets 62 be correlated to a percentage of total coverage of the surface of the ring 60 . for instance , it is preferred that about a range between about 30 percent to 10 percent of the ring surfaces 24 , be covered by replenish pockets 62 . and it is even more preferred that the replenish pockets 62 cover about 20 percent of the ring surface 24 . thus , it can be seen , that the size of the replenish pockets 62 ( i . e ., the diameter d ) and the number of replenish pockets 62 disposed on the ring surfaces 24 , 26 ( i . e ., the spacing s ), and depths thereof , can be adjusted / vary to meet a specific total replenishment pocket coverage requirement . it is further noted that the circular - shaped pockets 62 may be arranged and / or oriented in many different ways , and therefore , the present invention should not be limited merely to the fourth exemplary embodiment depicted in fig1 - 15 . for example , the circular - shaped pockets 62 need not be uniformly disposed and evenly spaced on the surface 24 ( and / or surface 26 ) of the ring 60 ; as an alternative , the circular - shaped pockets 62 may be in a zig - zagging pattern . moreover , the overall diameter , depth and / or shape of the circular - shaped pockets 62 may vary , and thus , the present invention should not be limited to merely to the fourth exemplary embodiment shown in fig1 - 15 . fig1 is a detail view taken from fig1 which shows a cross - section of the ring 40 taken along cross - section 15 - 15 , according to an aspect of the present invention . as discussed , the circular - shaped pockets 62 may be formed either on the top surface 24 ( as shown in fig1 ), the pockets 62 may be formed on the bottom surface 26 ( not shown in fig1 ), or the pockets 62 may be formed on both flat sides of the ring 60 . furthermore , the depth of the pocket may vary depending on the amount of lubricant that is desired to be disposed within the pockets 62 . it is noted that the aforementioned exemplary embodiments of the shapes and arrangement of the replenishment pockets should not be limited only to the disclosed examples . for instance , the pockets may be formed in other shapes such as squares , rectangles , ovals , small microgrooves , or any other means which may be formed in a surface of a ring and in which lubricant ( e . g ., dry - film ) may be deposited therein . it is further noted that the pockets may be formed with various manufacturing processes besides laser , such as etching . although the invention has been described with reference to several exemplary embodiments , it is understood that the words that have been used are words of description and illustration , rather than words of limitation . changes may be made within the purview of the appended claims , as presently stated and as amended , without departing from the scope and spirit of the invention in its aspects . although the invention has been described with reference to particular means , materials and embodiments , the invention is not intended to be limited to the particulars disclosed ; rather , the invention extends to all functionally equivalent structures , methods , and such uses are within the scope of the appended claims .
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the vehicle seat outlined in fig1 in a schematic longitudinal sectional view , in a known manner , has a seat part 11 adjustably held on the vehicle floor and a backrest 12 which , for adjusting the inclination , is connected with the seat part 11 by a swivel locking . the seat part 11 and the backrest 12 each have a cushion 13 which is fastened on a cushion carrier 14 . in the embodiment of fig1 the cushion carrier 14 is constructed as a spring core made of spring wire which is in each case fastened in a frame . in the seat part 11 , the frame is indicated by the reference number 15 . for reasons of clarity , the frame in the backrest 12 is omitted . the cushion 13 is constructed the same for the seat part 11 and the backrest 12 and comprises an air - permeable cushion support 16 made of a coarsely structured nonwoven material , such as rubberized hair , or of a spaced knit , and an air - impermeable pressure distribution layer 17 made of a nonwoven or rubberized - hair material of a high density which rests directly on the cushion carrier 14 and completely covers the cushion support 16 on its underside in the seat part 11 and on its back side in the backrest 12 . the top side or front side of the cushion 13 , which faces away from the pressure distribution layer 17 , is covered by an air - permeable cushion cover 18 made of a textile fabric , perforated leather or synthetic material , and a cover stuffing 19 made of cushion padding , nonwoven wool , an open - pore or at least partially perforated foamed material , or of a padding - foam combination is worked in between the cushion support 16 and the cushion cover 18 . if an electric seat heater ( not shown here in detail ) is present , then its heating wires are embedded in the cover stuffing 19 . the air - permeable cushion support 16 represents a so - called ventilation layer , through which an electrically driven fan or ventilator 20 can cause air to flow . for providing an air flow path with a low flow resistance , the pressure distribution layer 17 is provided with an inflow opening 21 and an outflow opening 22 which , viewed in the longitudinal direction of the seat part 11 or of the backrest 12 , are arranged at the largest possible distance from one another . the ventilator 20 is placed directly on the air inflow opening 21 below the pressure distribution layer 17 and is fastened to the latter . in the area of the air inflow opening 21 , the cushion support 16 is covered on its top side facing away from the pressure distribution layer 17 by an air - impermeable blocking layer 23 , such as a foil . at this point , therefore , the air flowing in by way of the air inflow opening 21 is deflected and flows in the longitudinal direction through the cushion support 16 and cannot exit directly by way of the air - permeable cushion cover 18 . as not shown here in detail , the blocking layer 23 can additionally continue beyond the direct area of the air inlet opening 21 and can be at least partially perforated so that different cushion areas are ventilated at different intensities ; this is not shown here in detail . in the embodiment of fig1 the air inflow opening 21 in the seat part 11 is arranged in the rear close to the backrest 12 and the air outflow opening 22 is arranged in the front on the seat part 11 so that the air taken in by the ventilator 20 from the vehicle interior below the seat part 11 flows through the cushion support 16 from the rear to the front . the air inflow opening 21 is provided in the lower area of the backrest 12 and the air outflow opening 22 is provided in the upper area of the backrest 12 so that air flow through the cushion support 16 takes place upwards from below . as is generally customary , and also in this case , the backrest 12 is covered on its backside facing away from the cushion cover 18 with a backrest covering 24 . a hollow space 25 remains between the cushion carrier 14 and the rearward backrest covering 24 . in this case , the cushion cover 18 is pulled over the upper edge of the backrest 12 into the upper part of the backside of the backrest 12 and is held in a tensioned manner there by the backrest covering 24 which , in turn , is fastened to the underside of the backrest 12 on the backrest frame . on the underside of the backrest 12 , an air inlet opening 26 is constructed in the backrest covering 24 , and , in the upper area of the backrest 12 , an air outlet opening 27 is worked into the area of the cushion cover 18 extending on the backside of the backrest 12 . the air outlet opening 27 is connected , by way of an air duct 28 penetrating the hollow space 25 , to the air outflow opening 22 in the pressure distribution layer 17 . in the embodiment of fig1 the air duct 28 is constructed as a flexible bellows . the ventilator 20 , which is still assigned to the air inflow opening 21 , is accommodated in the hollow space 25 and takes in air by way of the air inlet opening 26 on the bottom side of the backrest 12 . when the vehicle seat is occupied , the air which is taken in flows through the cushion support 16 upwards from below and , by way of the air outflow opening 22 , the air duct 28 and the air outlet opening 27 at the top side of the backrest is discharged again into the vehicle interior . within the cushion support 16 , the air sweeps along parallel to the front side of the backrest under the cushion cover 18 , as well as on the seat surface of the seat part 11 , and , in the process , generates an air humidity gradient so that air moistened by the seat user is discharged . when the seat is unoccupied , the air flowing in the cushion support 16 also flows through the cushion cover 18 into the air space in front of the backrest or above the seat part surface and causes rapid cooling of the vehicle seat heated , for example , by sun radiation . in order to utilize this effect , it is useful to couple the switch - on operation of the two ventilators 20 in the seat part 11 and in the backrest 12 with unlocking of the vehicle doors by a remote - controlled locking system so that the cooling of the vehicle seat starts before the vehicle is entered . since the air is taken in from the area below the vehicle seat , the cooling effect is intensified because , in a vehicle which is heated when parked , the temperature is lowest in the area below the vehicle seat . in comparison to the vehicle seat according to fig1 described above , the vehicle seat outlined in fig2 is modified to such an extent that the air flow in the cushion support 16 of the cushion 13 in the seat part 11 is guided from the front toward the rear and , in the cushion support 16 of the cushion 13 in the backrest , is guided downward from above . for this purpose , the air inflow opening 21 in the pressure distribution layer 17 is arranged close to the forward end of the seat part 11 and the air outflow opening 22 is arranged close to the rearward end of the seat part 11 in the pressure distribution layer 17 . in the forward area of the seat part 11 , the cushion 13 is supported by way of an elastic foam body 29 on a so - called anti - submarining wedge 30 constructed in the seat part frame 15 and does not rest on springs . the elastic foam body 29 provides the required spring deflection performance of the seat in the event of a strong braking operation or in the event of a crash and simultaneously forms an air duct 31 which connects the air inflow opening 21 in the pressure distribution layer 17 with the ventilator 20 fastened on the underside of the anti - submarining wedge 30 . if the cushion support 16 is not supported on the anti - submarining wedge 30 by the foam body 29 and the spring core has a continuous construction as in fig1 then the air inflow opening 21 is connected by way of bellows to the ventilator fastened from below to the anti - submarining wedge 30 . in order to supply the cushion support 16 of the backrest 12 with cool air from the lower area of the occupant compartment , the air inlet opening 26 is again constructed in the lower area of the backrest 12 in the backrest covering 24 ; specifically , this time , the air inlet opening is on the backside of the backrest 12 and not on its underside , and the hollow space 25 between the backrest covering 24 and the cushion 13 is used as an air guiding duct in which the air taken in by way of the air inlet opening 26 flows upwards and enters , by way of the air inlet opening 26 , into the air - permeable cushion support 16 . the air intake again takes place by way of the ventilator 20 which is arranged in the same manner in the air inflow opening 21 and is fastened to the air - impermeable pressure distribution layer 16 . the air outflow opening 22 is placed on the underside of the backrest 12 . fig3 illustrates a seat part 11 which is modified with respect to fig2 . here , the cushion carrier 14 is constructed as a seat bucket , in which an anti - submarining wedge 30 rather than a spring core is also constructed . the air - impermeable pressure distribution layer 17 here is not constructed as a thin layer made of a nonwoven or a rubberized - hair material of a high density ; instead , the air - impermeable pressure distribution layer is constructed as a dense foam cushion which is supported on the seat bucket and contains the air inflow opening 21 and the air outflow opening 22 as ducts , each of which penetrates the foam cushion . as in the seat part shown in fig2 the air inflow opening 21 is arranged close to the forward end of the seat part 11 , and the air outflow opening 22 is arranged close to the rearward end of the seat part 11 . therefore , the air flow generated in the cushion support 16 by the ventilator 20 , which is fastened on the underside of the anti - submarining wedge 30 , is guided from the front to the rear . a similar construction of the backrest in fig2 with such a foam cushion is conceivable . although the invention has been described and illustrated in detail , it is to be clearly understood that the same is by way of illustration and example , and is not to be taken by way of limitation . the spirit and scope of the present invention are to be limited only by the terms of the appended claims .
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fig1 shows a representative ( but blank ) image 10 ( composed of rows and columns of pixels , not particularly shown ). for purposes of discussion , image 10 may be an aerial photo of land , but it should be recognized that imagery 10 is not so limited . due to various factors ( e . g ., camera lens artifacts , and the perspective from which the photo was taken , etc . ), the rectangular photo typically does not depict a rectangular area of land . instead , the area of land depicted may actually be trapezoidal , or of other shape . overlaid on the fig1 image are sample latitude and longitude lines 12 , 14 . these are virtual and do not appear in the actual image . ( the straightness of the lines is unusual . in most landscape images , the receding horizon tends to curve any latitude or longitude projections that are not parallel to the image boundaries .) each point depicted in the image 10 has a unique position that may be expressed by latitude and longitude ( and , if 3d accuracy is desired , elevation ) coordinates . in accordance with an illustrative embodiment of the invention , such position data for a single location depicted in the image is determined . ( various techniques can be employed , e . g ., reference to a pre - existing map or database , ground - truth measurements using gps equipment , etc .) this location , and the pixel 16 corresponding thereto in the image , are termed the “ arbitrary origin ” in the discussion that follows . ( for expository convenience , the arbitrary origin in this discussion is the upper - left - most pixel in the image , and the ground point corresponding thereto .) the image 10 is digitally watermarked across its extent with a payload that includes the coordinates of the arbitrary origin ( e . g ., latitude / longitude / elevation ). in addition , the watermark payload also includes a parameter ( e . g ., angle 18 ) identifying the orientation of a vector pointing from the arbitrary origin to a known direction ( e . g ., true north ). the watermark payload can also include a scale datum , e . g ., indicating that 100 pixels to the right ( along the row ) from the arbitrary origin corresponds to a distance — on land — of 250 yards . as noted , a rectangular image generally does not depict a rectangular piece of land . moreover , even if a photo is taken from directly overhead — using a lens that introduces no aberrations — there is the slight complication posed by the fact that longitudinal lines are not parallel , but meet at the poles . accordingly , if high accuracy is desired , the watermark can additionally convey coefficients for one or more polynomials ( e . g ., one for each coordinate axis ), which model the apparent warp of the photographic depiction along different axes . ( in an exemplary arrangement 5 coefficients of 8 bits each are provided for the latitude and longitude polynomials , and 6 coefficients of 8 bits each are provided for the elevation polynomial .) thus , in an exemplary embodiment , the watermark payload may comprise the following ( 196 bits total ): digital watermarking is not belabored in this specification because such technology is well understood by artisans in the field of steganography . briefly , however , watermarking typically works by making subtle changes to the brightness of image pixels , conveying message payloads that can be detected by suitable detector software or hardware . the embedding process generally adjusts to the unique characteristics of the image , placing a stronger watermark signal in areas with rich detail and a weaker watermark signal in areas with little detail . because the payload is carried by the image &# 39 ; s pixels , it is file - format independent . the payload can survive most normal processing operations , such as compression , edits , file format transformations , copying , scanning and printing . some watermarking techniques are also robust against rotation and scaling , e . g ., through use of embedded calibration data , or auto - correlation techniques . any watermarking technique can be employed in the present invention , provided the requisite number of watermark payload bits can be embedded without introducing objectionable corruption into the image . suitable watermarking technologies are disclosed , e . g ., in patent publications u . s . pat . no . 6 , 122 , 403 u . s . pat . no . 6 , 044 , 182 , and wo 99 / 45705 , and in pending u . s . application ser . no . 09 / 503 , 881 ( now u . s . pat . no . 6 , 614 , 914 ). in a particular embodiment , the watermark payload is represented in a single 128 × 128 pixel patch 20 , which is then tiled across the image ( with local scaling to reduce visibility ). each patch comprises 16 , 384 pixels . in fig1 , one of the patches 20 is indicated by cross - hatching for ease of identification . to enhance robustness , the watermark payload may be processed , e . g ., by bch , reed - solomon , convolutional , or turbo coding , or the like , to provide error detecting / correcting capability . such coding has the effect of transforming the 196 bit payload bits into , e . g ., 320 bits (“ raw bits ”). each of the 16 , 384 pixels in the patch is encoded with one of these raw bits , so that each such bit is represented about 50 times per patch . the pixels corresponding to a single raw bit are desirably distributed across the patch , so that severe corruption of a small area of the watermarked image does not irretrievably lose certain raw bits . on the detection side , the image is processed to retrieve the 320 raw bits , and then the 196 payload bits are determined from the raw bits . from these payload bits , a user of the image knows the geographical coordinates of the point at the arbitrary origin and , through use of the other encoded parameters , can deduce the geographical location of any other point depicted in the image . in other embodiments , more elaborate watermark encoding can be used . for example , instead of tiling the identical watermark patch over and over across the image , each patch can be slightly different , e . g ., encoding the position of that tile within the array of tiles . in one arrangement the tile position data is a pair of numbers indicating tile - row / tile - column offsets from the tile containing the arbitrary origin . referring to fig1 , the tile containing the arbitrary origin 16 may be designated { 0 , 0 }. the tile next to it in the row may be designated { 0 , 1 }, etc . these index values may be encoded as 5 bits each , which bits are included in the watermark payload . this arrangement offers advantages in environments in which image cropping , rotation , or other image transformations may occur . by decoding the payload from a watermark tile , its location relative to the arbitrary origin can be determined , and the location of the arbitrary origin 16 can thus be inferred ( even if that point has been cropped out of the image ). in still other embodiments , information about the image perspective can be conveyed through a watermark . various forms of representation are possible . in one , the image perspective data can comprise the compass angle at which the camera is pointing ( θ ), and the elevation angle between the arbitrary origin point and the camera ( φ ). the former may be represented , e . g ., by 10 bits , the latter by 8 . additionally or alternatively , the perspective data can identify the lens or its attributes , so that optical distortion of the image can be characterized . in an index - based system , a six - bit code can be used to identify one of 64 different lenses . with different types of imaging systems , different forms of perspective information may be appropriate . for example , in so - called “ whisk broom ” cameras ( i . e ., those that repeatedly acquire line scans from a moving viewpoint ), the perspective information may additionally include the starting and ending positions ( the latter may be expressed as an offset from the former , allowing some payload conservation ). in yet other embodiments , elevation data for different points in the image can be encoded through watermarks . in one such arrangement , elevation data is determined for points at 64 - pixel gridded spacings across the image . these points are designated in fig1 by the stars labeled 22 . ( only a few such stars are shown in fig1 . the arbitrary origin 16 is also such a point .) the elevation may be expressed in absolute terms ( e . g ., feet above sea level ), or relative to another reference ( e . g ., the elevation of the arbitrary origin ). again , 16 bits per elevation may be used . ( or if difference in elevation from the arbitrary origin is used , then 8 - 12 bits may suffice .) in one such arrangement , the elevation data for each starred point is watermark - encoded in a 64 pixel by 64 pixel subpatch 24 centered around the star . again , one such sub - patch 24 is shown in fig1 by cross - hatching for ease of identification . more generally , these sub - patches 24 are the regions bounded by the fine , dotted lines in fig1 . again , sub - patches 24 are tiled across the image , but each one conveys a ( typically ) different elevation payload . ( in the fig1 arrangement , each patch 20 encompasses one full sub - patch 24 , and parts of eight others . by this arrangement , elevation data is encoded for the points at each corner of each patch 20 , as well as for the point at the center of the patch , and at points mid - way along each patch side boundary . in other embodiments , of course , sub - patches 24 can be sized and positioned differently relative to patches 20 .) the elevation watermark , based on patches 24 , may be simply overlaid on the main watermark , based on patches 20 . desirably , however , there is some coordination between the two watermarks , so as to avoid extreme changes in any pixel values ( as may occur , e . g ., if both watermarks try to change a pixel by a maximum amount permitted by the respective watermarking technique ). in one such coordination arrangement , each pixel in the image is assigned to one of the two watermarks . for example , 50 - 80 % of the pixels in the image may be assigned to the main watermark , and 50 - 20 % may be assigned to the elevation watermark . the assignment may be done based on a regular array , or a stochastic assignment may be used . in some cases , it may be prudent to allocate extra pixels to carry the elevation payload where — as in the upper right — the sub - patch 24 extends beyond the boundary of the image , limiting the number of pixels to convey elevation data ( e . g ., for arbitrary origin point 16 ). ( this coordination technique has applicability beyond the present context , and is generally applicable to a variety of watermarking applications in which plural watermarks are used .) by techniques such as the foregoing , an image can be provided with extensive photogrammetric information that travels with the image , notwithstanding distortion , cropping , format conversion , etc . this data can be exploited in various ways . one utilizes a computer system on which the image is displayed , e . g ., on a monitor or screen . an operator uses an input device , such as a mouse , light pen , graphics tablet , or the like , to designate a particular point in the displayed image . in response to selection of the point ( by clicking or other known selection technique ), the computer processes the embedded watermark information and displays to the operator the precise latitude , longitude and elevation of the selected point . using the elevation data , the computer system can also generate , and render , a 3d view of the depicted landscape , from an arbitrary viewing angle . surfaces that are hidden in the original image may be extrapolated using known techniques , and presented in a different color or texture to indicate their synthetic basis . in embodiments in which the camera perspective is known , the projections of latitude and longitude lines on the depicted terrain can be adjusted , e . g ., in accordance with variations in elevation . if the camera perspective is such that it is viewing down a downwardly - inclined slope , for example , the latitude or longitude lines that traverse this slope can be virtually placed more closely spaced together than would be the case if the camera view were orthogonal to the slope . the mathematical manipulations associated with such operation are somewhat complex , but well within the skills of those working in the photogrammetric and mapping arts . to determine elevation at an arbitrary point and to generate 3d models , for example , the elevations at the starred points 22 are provided to an algorithm that applies a bi - cubic spline - fitting model so as to estimate the elevation at any point on the image . ( the computer system can take various forms , but most include conventional computer components such as one or more cpus , volatile storage ( e . g ., ram ), non - volatile storage ( e . g ., rom , fixed and removable magnetic disks , fixed and removable optical disks ), interfaces ( e . g ., wan , lan , usb , modem , serial ), input / output devices ( e . g ., monitor , keyboard , mouse , tablet , joystick , light pen ), etc . associated with the computer system is various software , including operating system software and applications software — the latter being programmed to perform the data processing and presentation operations detailed above . naturally , such programming can be stored on fixed or removable computer storage media . in some embodiments , parallel or distributed computer architectures may be employed , e . g ., with different components of the computer system being located remote from each other .) a variety of aerial mapping and associated image database techniques can be used in conjunction with the present invention . representative systems are shown , e . g ., in patents u . s . pat . nos . 5 , 608 , 405 , 5 , 926 , 581 , 5 , 974 , 423 , 6 , 023 , 278 , 6 , 177 , 943 , 5 , 995 , 681 , 5 , 550 , 937 and 6 , 150 , 972 . to provide a comprehensive disclosure without unduly lengthening this specification , applicant incorporates by reference the patents publications and applications cited above . having described and illustrated the principles of the invention with reference to illustrative embodiments , it will be recognized that the invention can be modified in arrangement and detail without departing from such principles . for example , while the “ arbitrary origin ” was the pixel in the upper - left corner of the image in the illustrative example , this placement is not critical . the arbitrary origin can be moved to any location , with relative measurements being adjusted accordingly . likewise , while the detailed embodiment contemplated that the coordinates of the arbitrary origin are literally encoded as part of the digital watermark payload , in other embodiments this need not be the case . instead , e . g ., the watermark payload can be an arbitrary identifier that identifies an entry in a data structure ( e . g ., table or database ) in which the coordinate data is stored . the same index - a - remote - store approach can be used with any of the other payload data . although latitude / longitude / elevation were used as exemplary coordinates , it will be recognized that other coordinate geometries can alternatively be employed . the main watermark payload is described as including coordinate , orientation , scale , and polynomial correction data . depending on the application , certain of this data may be omitted , and / or certain additional information may be included in the watermark payload . the payload length is exemplary . some embodiments can employ a payload that is considerably shorter ( e . g ., by abbreviating the bits dedicated to each data and / or omitting certain data ). other embodiments may employ a payload that is longer . while elevation may be expressed in height above sea level , this need not be the case . height relative to any other measure can alternatively be employed . the illustrative embodiments &# 39 ; encoding of plural data ( e . g ., coordinate data , and lens data ) in a single watermark payload is not essential . in other embodiments , the different elements of embedded information can be conveyed through distinct watermarks , e . g ., layered over each other , interspersed between each other , coordinated with each other in the manner of the elevation watermark , etc . in many embodiments , lossless data compression techniques ( e . g ., lempel - ziv based ) can be employed to reduce the number of payload bits that are encoded in a watermark . although described in the context of watermarking for mapping and photogrammetric purposes , the principles detailed herein find application in many other watermarking applications , not limited to the purposes particularly detailed . in view of the many embodiments to which the principles of the invention may be applied , it should be recognized that the detailed embodiments are illustrative only and should not be taken as limiting the scope of the invention . rather , i claim as my invention all such embodiments as fall within the scope and spirit of the following claims , and equivalents thereto .
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with reference now to the drawings , and in particular to fig1 through 6 thereof , a new bed device embodying the principles and concepts of an embodiment of the disclosure and generally designated by the reference numeral 10 will be described . as best illustrated in fig1 through 6 , the pet bed assembly 10 generally comprises a clamp 12 . the clamp 12 may releasably engage a footboard 14 of a conventional bed 16 and extends above the footboard 14 . the clamp 12 includes a bottom section 18 and a top section 20 movably coupled to each other such that varying sizes of the footboard 14 are accommodated . each of the bottom section 18 and top section 20 include a leg 22 that has a first end 24 and a second end 26 . a foot 28 is coupled to and extends away from the leg 22 . the foot 28 has a distal end 29 with respect to the leg 22 . additionally , the foot 28 is positioned adjacent to the first end 24 . the second ends 26 of the bottom section 18 slidably receives the second end 26 of the top section 20 . the legs 22 frictionally engage one another such that the feet 28 are retained a selected distance from each other . alternatively or in addition to the above , the leg 22 of the bottom section 18 may include a lock 30 . the lock 30 may engage the leg 22 of the top section 20 . the lock 30 may retain the feet 28 at the selected distance apart from each other . the lock 30 may comprise a pin or the like to removably engage the leg 22 of the top section 20 . a lip 32 is provided . the distal end 29 has the lip 32 coupled thereto and extending upwardly therefrom . the lip 32 defines a receiving channel 34 between the lip 32 and the leg 22 . the lip 32 on the top section 20 and bottom section 18 extend toward each other . the receiving channel 34 in each of the top section 20 and bottom section 18 receives the footboard 14 . a platform 36 has a top surface 38 , a bottom surface 40 and an outer edge 42 extending therebetween . the platform 36 has an arm 44 extending downwardly from the bottom surface 40 . the first end 24 of the leg 22 on the top section 20 slidably receives the arm 44 . the platform 36 is spaceable a selected distance above the foot 28 on the top section 20 . the arm 44 frictionally engages the leg 22 on the top section 20 . thus , the platform 36 is retained at the selected distance from the top section 20 . alternatively , a locking mechanism may be used to retain the arm 44 at a selected position relative to the top section 20 . the arm 44 on the platform 36 is positioned adjacent to a back side 46 of the outer edge 42 . the platform 44 extends over the bed 16 when the clamp 12 is coupled to the footboard 14 . the top surface 38 may support a pet 48 . the pet 48 may be a dog or cat or the like . a backboard 50 is coupled to and extends upwardly from the back side 46 . the backboard 50 is coextensive with the back side 46 . in an alternative embodiment 52 as shown in fig5 and 6 , the clamp 12 may comprise a first section 54 hingedly coupled to a second section 56 . the arm 44 on the platform 36 may slidably engage a free end 58 of the first section 54 . the first 54 and second 56 sections are positionable to form a right angle with each other . the second section 56 may be positionable between the bed 16 and a frame 60 of the bed 16 so the first section 54 extends upwardly from the frame 60 . the first section 54 may be positionable in a stored position having the first section 54 being coextensive with the second section 56 . the hinge may be a locking hinge or the like . in use , the clamp 12 is coupled to the footboard 14 when the pet 48 is to sleep near the bed 16 . the pet 48 sleeps on the platform 36 so as not to disturb the bed 16 . the assembly 10 allows the bed 16 to be slept in without being disturbed by the pet 48 . with respect to the above description then , it is to be realized that the optimum dimensional relationships for the parts of an embodiment enabled by the disclosure , to include variations in size , materials , shape , form , function and manner of operation , assembly and use , are deemed readily apparent and obvious to one skilled in the art , and all equivalent relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by an embodiment of the disclosure . therefore , the foregoing is considered as illustrative only of the principles of the disclosure . further , since numerous modifications and changes will readily occur to those skilled in the art , it is not desired to limit the disclosure to the exact construction and operation shown and described , and accordingly , all suitable modifications and equivalents may be resorted to , falling within the scope of the disclosure . in this patent document , the word “ comprising ” is used in its non - limiting sense to mean that items following the word are included , but items not specifically mentioned are not excluded . a reference to an element by the indefinite article “ a ” does not exclude the possibility that more than one of the element is present , unless the context clearly requires that there be only one of the elements .
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an exemplary business architecture 10 is illustrated in fig1 in accordance with a preferred embodiment of providing vision correction to a patient 12 . the patient 12 presents herself at a practitioner &# 39 ; s facility 14 . the practitioner &# 39 ; s facility is suitably equipped with apparatus ( not shown ) for obtaining , in particular , wavefront aberration information 16 from the patient . the apparatus is preferably one of a variety of wavefront measuring instruments ( e . g ., zywave ™ wavefront aberration sensor from bausch & amp ; lomb surgical / technolas , munich ) or other suitable devices and associated procedures for obtaining wavefront aberration information such as , e . g ., phase diversity and / or topography . fig4 is an exemplary display of a patient &# 39 ; s wavefront aberration information . this information may take a variety of forms which are most suitably useable by a practitioner for diagnosis , prescribing , etc . ; by the patient for informed consent , information , subjective evaluation , etc . ; by an ordering and / or billing platform 18 , and particularly , for a custom lens supply platform 20 where a custom lens based upon the wavefront measurement information can be made and packaged for shipment to the practitioner or the patient . in addition , other refractive data and patient data may be obtained and transmitted . as such , different platforms may be interconnected . the selected diagnostic equipment is preferably designed to automatically output the appropriate information in suitable form to the custom lens supply platform 20 . it is well known in the art how to convert a wavefront measurement into data that a laser , lathe or other suitable surface modifying equipment can use to create a desired surface modification ; therefore , that exercise need not be discussed at length herein , nor does it constitute a material part of the invention described herein . for illustration , however , an exemplary process is shown with reference to fig6 . fig6 is a flow chart of an exemplary aspect of the invention for a custom contact lens produced by lathing . starting at block 1 , zernike polynomial data is output by a wavefront measuring apparatus . the data is input at block 2 to an optical design program that in its most basic capacity designs the shape of the anterior surface ( optical zone and / or peripheral zone ) of the proposed contact lens . a second set of zernike data is generated at block 3 . this data is preferably in the form of a mini - file or other suitable format that is readable by a lens turning lathe . the mini - file data is input into the lathe processor at block 4 and a custom contact lens is produced at block 5 . referring again to fig1 as illustrated , some information is transmitted from one platform to another platform via the internet , however , any supporting transmission mode and transmission medium can be used . it is contemplated that some or all of the platforms will be located remote from the practitioner &# 39 ; s facility but this need not be so . the supply platform 20 is suitably equipped to produce an appropriate custom lens . accordingly , a custom contact lens , a custom inlay , a custom onlay , or a custom iol can be made . the manufacturing process will preferably entail shaping a surface of the custom lens . this may be accomplished by one or more of the processes including laser ablation , lathing , casting / molding , or other known processes . a specific quantity of custom lenses , e . g ., contact lenses , may be produced for the patient so as to be used over an extended period of time . the lenses will preferably be packaged in a customized manner 22 ( as they are custom lenses ) for the patient . an exemplary representation of a customized package is shown in fig7 . the package can then be shipped to the patient or practitioner as appropriate . in an aspect of the embodiment , it may be desirable to show the patient , to the extent possible , what their improved vision could be as provided by the custom lens . an instrument much like a wavefront sensor device equipped with a phase compensator such as a deformable mirror , as shown in u . s . pat . no . 5 , 777 , 719 , can provide an indication of wavefront corrected vision . an exemplary aberration corrected wavefront display is shown in fig5 resulting from the corrected wavefront aberrations shown in fig4 . it will be appreciated that the customization aspect of the present invention is primarily attributed to the measurement and correction of higher - order wavefront aberrations . these are generally considered to consist of monochromatic aberrations associated with third and higher order zernike polynomials and particularly fifth to tenth order zernike modes . an exemplary business practice used in the laser vision correction industry involves per procedure fees . this practice is illustrated by the sale of non - reusable laser interlock cards to the doctor that were inserted into the laser and , without which , the laser would not operate . this model is also appropriate , for example , as applied to obtaining a wavefront aberration measurement . it is envisioned that a per use fee may be implemented each time the wavefront sensor is used to obtain aberration information . likewise , any of the processes constituting portions of the method of the invention , particularly those occurring between different or third party - controlled platforms , may be crafted as business activities that carry a royalty or other income generation for their use . accordingly , it is contemplated to automatically transmit various data and information between platform constituents for this purpose with an intent of enhancing the value of the products and / or services provided . part of this enhanced value stream includes improved vision to the patient exceeding the improvements expected or obtained over conventional refraction practice , and enhanced value to the practitioner . fig2 is a block diagram illustrating an alternative business architecture 400 to that shown in fig1 and is the basis of a semi - intelligent interactive system . a practitioner &# 39 ; s platform 140 comprises the practitioner &# 39 ; s facility 14 where the patient 12 is engaged to generate vision diagnostic information 200 , including wavefront measurement data , personal history , practitioner information and whatever other information may be useful for constructing or maintaining one or more databases for future use . the vision diagnostic information 200 is sent via the internet to a service platform 300 that illustratively includes an information storage server 201 , a lens design interface 202 , and a lens manufacturing interface 204 . two types of information are generated from service platform 300 : order , billing , and optional demographic information , 180 , for example , are sent to and received by an order / billing platform 18 ; and lens design and manufacturing information 210 is sent to and received by a custom lens platform 20 . ordering / billing information 180 can be transmitted to the practitioner , the patient , or both . custom lens information 210 is used by lens platform 20 to produce custom packaged lens products 22 for the patient which can be shipped to the patient at home 24 , for example , or to the practitioner &# 39 ; s facility 14 for fitting and / or delivery to the patient 12 . simultaneous to the transfer of patient and lens information 180 , 210 , respectively , various royalty information 206 , 208 , may be transmitted between various platforms , for example , as shown . moreover , the illustrated architecture 400 may be considered a semi - intelligent interactive system in that the system provides for database feedback in real time between various platforms . for example , based upon the patient &# 39 ; s wavefront measurement and / or other vision data and / or demographic information , the service platform 300 and / or the lens platform 20 and / or the billing platform 18 may generate feedback 500 to the practitioner and / or the patient that influences the decisions about type of treatment , type of lens , quantity , payment , etc . to illustrate this , a patient may seek to obtain vision correction ( or improvement ) by laser vision correction . certain ocular characteristics of the patient will be measured , preferably wavefront aberration and possibly , in conjunction therewith , topography measurements will be obtained . a practitioner or , alternatively , a computer determined evaluation , for example , may conclude that the patient &# 39 ; s prospective vision correction could be better accomplished not by laser vision correction but , foe instance , by a custom contact lens . the evaluation may be in the form of an option matrix so to speak wherein information about prospective vision correction and cost , among other things , can be compared against different types of eye treatment or no treatment at all . an eye treatment option can then be selected by the patient and / or the practitioner , and upon selection , the appropriate information such as wavefront aberration data and patient financial information , for example , can be automatically sent to the appropriate platform ( in the illustrated case , a custom lens supply platform and an order / billing platform , respectively ) for processing . in another embodiment of the invention for providing vision correction to a patient , the patient situates himself in a practitioner &# 39 ; s facility . at the facility , a diagnostic lens is selected and fitted to the eye . the diagnostic lens will be of similar design to that which will eventually be prescribed as the custom contact lens . the power of the lens preferably should be spherical ( defocus ) only , similar in magnitude to that of the patient &# 39 ; s eye . however , if the patient &# 39 ; s spherical power is not known , a standard plano powered lens could be used . base curve selection is based on central corneal curvature readings made with a keratometer or a corneal topographer . if neither is available , the trial lens can be fitted empirically by observation of the movement , centration and rotation of the lens . regardless of the methodology used to select the lens , the lens is placed on the eye , allowed to equilibrate for up to 10 minutes , and then the centration , movement and rotation is assessed using a biomicroscope . the lens should show movement when blinking but remain relatively stable between blinks . ideally it should return to its primary gaze position between blinks , with little variation in horizontal or vertical centration . if excessive movement or decentration is present , a steeper base curve diagnostic lens should be fitted . the patient &# 39 ; s wavefront will then be measured with the diagnostic lens in place . ideally , the patient will have a large pupil ( greater than 5 mm ) under the illumination conditions that the wavefront is measured . if the conditions are not such that the patient &# 39 ; s pupil is dilated to 5 mm naturally , then a pharmacological agent may be instilled to ensure adequate pupil size under the illumination conditions used for wavefront measurement . by correcting the patient &# 39 ; s wavefront over a large pupil size , the patient would be wavefront corrected over a wide range of pupil sizes , and pupillary axes , since this axis shifts in many patients in relation to pupil size . measurement in this fashion eases lens fabrication since some methods of manufacture , particularly those which are lathe based , are easier to control if the optical surface is centered symmetrically on the lens . the wavefront measurement should be made along the geometric central axis of the lens , this axis being defined by viewing the edge of the lens or by viewing particular marks made on the diagnostic lens which define the geometric center of the lens ( e . g . a circle ) while viewing the lens through a camera mounted in the wavefront sensor instrument . using a hartmann - shack type aberration sensor , an image of the lenslet array images is captured on the wavefront sensor ccd camera , and converted by software algorithms into a series of zernike coefficients which describe the wavefront aberration of the eye and diagnostic lens system . if so equipped , the rotation of the diagnostic lens on the eye will be measured by the wavefront sensor , by sensing of specific marks made on the diagnostic lens and capturing an image of the lens in its stable primary gaze position with the camera mounted in the wavefront sensor instrument . if this capability is not available , the clinician will measure the rotation of the lens on the eye using an eyepiece reticle , and the specific marks of the diagnostic lens . in an alternative aspect of this embodiment for measuring wavefront aberrations along an axis passing through the geometric center of the lens , an axis shift is introduced . once the resting position of the trial ( diagnostic ) lens on the patient &# 39 ; s eye is determined , the patient &# 39 ; s visual axis is aligned to the measurement axis of the metrology system , preferably an aberration sensor . this is typically a self - alignment by the patient accomplished by looking at a target presented by the metrology system . the measurement axis is then shifted from the visual axis to a parallel axis that passes through the geometric center of the lens . this can be accomplished by the operator of the aberrometer by shifting the optical axes of the pupil camera and wavefront sensor to an axis that is parallel to the visual axis of the patient and passes through the center of the trial lens . the pupil camera and wavefront sensor are conveniently mounted on the same x - y translation stage such that they are moved in unison . the geometric center of the diagnostic lens is now the reference feature for the wavefront aberration when the lens is in the resting position on the patient &# 39 ; s eye . optical modification to the trial lens can now be made with respect to its geometric center by any of the techniques disclosed herein . the zernike coefficients are then converted into another series of zernike coefficients describing the corrective lens surface for the custom contact lens . the corrective surface can be anterior of posterior on the lens . the corrective lens &# 39 ; zernike coefficients can be derived by dividing the original zernike coefficients by n − 1 , where n represents the refractive index of the contact lens material . all zenike coefficients can then be multiplied by − 1 to flip the z axis and make it a correcting wavefront . alternatively , ray tracing techniques using a commercially available ray tracing pattern can be used to determine the correcting surface wavefront and hence the zernike coefficients . the correcting surface zernike coefficients are entered into a software program designed to produce lathing instructions for a 3 - axis or similar lathe which will make the correcting surface on the customized contact lens . alternatively instructions may be derived to guide a small beam laser designed to alter a surface of a contact lens . in both cases , the rotation of the lens on the eye is considered and included in the calculations when deriving the correcting surface zernike coefficients . this conversion of measured zernike coefficients and lathing instructions can be performed in a computer attached to the wavefront sensor , or remotely in a computer communicating with the wavefront sensor and transmitted to a custom lens supply platform similar to that described with respect to the foregoing embodiment . the finished lens is transported to the patient and tested . a diagnostic lens having the parameters listed in table i was selected and placed on the patient &# 39 ; s eye . after the lens had settled , a wavefront measurement was made with the lens in place . the measurement was centered on the geometric center of the lens . the wavefront analysis provided the zernike coefficients listed in table ii . analysis of the point spread function ( psf ) excluding the z4 , z5 & amp ; z6 terms ( i . e ., defocus and astigmatism ) revealed a strehl ratio for the 5 . 7 mm pupil over which the data was calculated to be 0 . 03536 , as illustrated in fig8 a . the wavefront data was converted using a commercially available ray tracing program ( e . g ., zemax optical design software from by focus software , inc ., tucson , ariz .) to determine the zenike coefficients for the appropriate correcting lens . they are listed in table iii . ( note that the zernike terms in table ii have been converted to the zemax zernike convention . hence the z term numbers in table iii do not necessarily correspond to those in table ii above or table iv below ). the custom contact lens was manufactured with the same relevant parameters as the diagnostic lens listed in table i . the lens was placed on the patient &# 39 ; s eye and re - measured with the wavefront sensor , producing the set of zenike coefficients listed in table iv . the defocus and astigmatism were not properly corrected by the lens on the eye due to an error in the actual power of the trial lens which was discovered later . however , analysis of the psf excluding the z4 , z5 & amp ; z6 terms ( i . e ., defocus and astigmatism ) revealed a strehl ratio for the 5 . 7 mm pupil over which the data was calculated to be 0 . 09214 , as shown in fig8 b . the strehl ratio and psf provided by the custom contact lens displayed a clear improvement in the optical quality of the patient &# 39 ; s eye . another embodiment of the invention for providing vision correction to a patient is described in conjunction with an exemplary in - situ business model 40 illustrated schematically in fig3 . a patient 12 presents herself in a practitioner &# 39 ; s facility 14 where she is fitted with a non - custom trial lens ( not shown ) including an inlay , an onlay , or a contact lens . a wavefront aberration measurement 16 is obtained and that information is transmitted to an apparatus 42 , preferably a laser , suitable for custom shaping of the anterior surface of the trial lens . in an aspect of this embodiment , the wavefront measuring device may be integrated with the laser , but in any event , the laser is located in proximity to the patient such that the anterior lens surface can be custom shaped in - situ . in an aspect of this embodiment , the aberration measurement information 16 is also transmitted in suitable form to a custom lens supply platform 20 where a custom lens is made for the patient . in another aspect of this embodiment , fitting the patient with the trial lens further involves identifying , by a mark or non - contact means , the geometric center of a surface of the trial lens and obtaining the wavefront aberration measurement along an eye axis passing through the geometric center of the lens as described above . in some individual cases , it may be preferable to dilate the patient &# 39 ; s pupil to cover an appropriate portion of the optical zone of the trial lens . as described above in connection with the foregoing embodiments of the invention , data transmission protocols , process step segregation into business enterprises with associated contractual rights and revenue streams , and related considerations equally apply to the instant embodiments as though fully set forth per se . in a further embodiment according to the invention , a patient may engage herself with a diagnostic platform including a wavefront aberration measuring device , without initial practitioner intervention , that is located as a stand - alone platform . the device would be equipped with telecom or datacom capability to accept input and transmit output regarding patient data , ordering data , billing data , etc . to an appropriate respective platform . in addition , the diagnostic platform would be capable of providing the wavefront aberration and , preferably , correction information in a display format suitable for subjective evaluation by the patient . if so desired , the patient could direct the diagnostic platform to transmit the information to a practitioner and / or to a custom contact lens supply platform where a supply of custom contact lenses could be manufactured and packaged , and shipped to the patient or the patient &# 39 ; s practitioner . although this embodiment of the invention engenders an evolving degree of automation , it is not intended to circumvent the inclusion of a practitioner where participation as such is required by state or federal rules , regulations or laws . notwithstanding the preferred embodiments specifically illustrated and described herein , it will be appreciated that various modifications and variations of the instant invention are possible in light of the description set forth above and the appended claims , without departing from the spirit and scope of the invention .
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an embodiment of the invention is described below while referring to the accompanying drawings . fig1 is a perspective exploded view showing a constitution of a card reader in a first embodiment of the invention . in fig1 a card reader 20 includes a card reader main body 40 , a gasket 50 of elastic material such as rubber for preventing invasion of foreign material , and a head holder 60 for holding a magnetic head 70 . a spring retainer 80 presses the gasket 50 to the main body and has a fulcrum for providing energy by a spring force . a lead wire 90 , an elastic member ( spring ) 100 , mounting screws 120 , and a circuit unit 110 are also provided . fig2 is a perspective view of the card reader . it shows an assembled state of the card reader shown in fig1 . the card reader shown in fig2 is used as assembled in other devices . fig3 shows an example of the card reader installed in an operation panel 10 of an vending machine at a filling station or the like . when a card 30 passes through a card passage 41 , the card reader 20 reads the data recorded on magnetic stripes 32 . in this constitution , the main body 40 is composed of a synthetic resin such as abs , and has a passage 41 formed in the center for allowing the card to pass . at both sides of the card passage 41 , guide walls 46 are provided for stabilizing running of the card , and the guide walls are orthogonal to a mounting surface of the card reader . a first guide wall 46 includes an opening 42 for inserting the magnetic head 70 , a boss 43 for holding the mounting screws of the spring retainer 80 , and a guide 430 of spring 100 . a second guide wall 46 includes a boss ( not shown ) for holding the mounting screws of the circuit unit 110 . fig4 a , fig4 b and fig4 c are explanatory drawings showing the gasket 50 used for preventing invasion of foreign material . fig4 a is a front view , fig4 b is a side view , and fig4 c is a side sectional view . referring to fig4 a , fig4 b and fig4 c , the gasket 50 is made of an elastic member such as rubber , and the magnetic head 70 is inserted therein . the gasket 50 includes an opening 52 for allowing the leading end having the core of the magnetic head 70 to be exposed to the outside of the gasket 50 , a magnetic head inserting portion ( inner circumferential portion ) 53 , and a folding portion 54 for allowing smooth motion of the magnetic head when inserting or passing the card in the shape of the junction from the magnetic head periphery to the outer circumference . the wall thickness of the folding portion 54 is thinner than the thickness of the magnetic head inserting portion 53 or the outer circumferential portion 56 . further , as shown in fig4 a and fig5 a , the dimension of the opening 52 of the gasket 50 and the overall dimension of the magnetic head 70 are set in the following relation : the head holder 60 is composed of synthetic resin such as abs , and has a portion for press - fitting and fixing the magnetic head 70 , and a structure for nearly fixing the spring 100 . the spring retainer 80 is composed of synthetic resin such as abs , and protects the head holder 60 , magnetic head 70 , gasket 50 , etc . the gasket 50 is placed between the spring retainer 80 and the peripheral edge portion 420 ( see fig1 ) of the opening 42 of the main body 40 . the spring retainer 80 is inserted into four screw fixing bosses 43 of the card reader main body 40 , and is fixed to the card reader main body 40 with screws 120 . a lead wire 90 is connected to a head terminal 72 in the upper part of the magnetic head 70 press - fitted into the head holder 60 . this lead wire 90 is connected to the circuit unit 110 provided on the confronting side of the magnetic head 70 of the card reader main body 40 . fig5 a is a perspective exploded view of gasket 50 , magnetic head 70 , and head holder 60 . as shown in fig5 a , the spring 100 , head holder 60 , magnetic head 70 , and gasket 50 are assembled sequentially . fig5 b shows the assembled magnetic head unit 74 . fig6 shows the magnetic head unit 74 mounted on the card reader main body . in this unit 74 , the magnetic head 70 is inserted into the head holder 60 . the head holder 60 has a spring 100 for pressing the magnetic head 70 in a direction shown by the arrow a , and the magnetic head 70 is pressed by the spring 100 at the fulcrum of the spring retainer 80 . referring to fig6 the motion of the head unit 74 is explained . when the card 30 is passed in the card passage 41 of the card reader 20 in the direction of arrow c , the magnetic head 70 installed in the center of gasket 50 reads the card data . the magnetic head 70 inserted in the head holder 60 is pressed in the direction of arrow a by the spring 100 . when the card is inserted , the magnetic head 70 moves in the direction of arrow b due to the thickness of the card . until the card is taken out after being inserted , the magnetic head 70 and card 30 are always pressed by the spring 100 in the direction of arrow a and hence slide in close contact with each other . in the gasket 50 , as shown in fig4 c , a folding portion 54 is provided between the periphery of the magnetic head inserting ( inner circumferential ) portion 53 and the outer circumferential portion 56 , and the folding portion 54 is thinly formed . therefore , the gasket 50 moves and shrinks easily by following the motion of the magnetic head 70 . when the card is not passing through the passage 41 , the magnetic head inserting portion ( inner circumferential portion ) 53 of the gasket 50 is pressed against the peripheral edge portion 420 of the main body by the energizing force of the spring 100 . therefore , when the card does not pass through the passage 41 , invasion of foreign material can be prevented by close contact between the gasket 50 and the periphery of the magnetic head 70 , and close contact between the magnetic head inserting ( inner circumferential ) portion 53 of the gasket 50 and the peripheral edge portion 420 of the main body opening . further , by fastening the spring retainer 80 to the boss 43 of the main body 40 with screws , the outer circumferential portion 56 of the gasket 50 closely contacts the main body peripheral edge portion 420 of the opening . when the card passes through the passage 41 , invasion of foreign material can be prevented by close contact between the gasket 50 and the periphery of the magnetic head 70 , and close contact between the outer circumferential portion 56 of the gasket 50 and the main body peripheral edge portion 420 of the opening . fig7 a and fig7 b are sectional views showing the close contact between the main body and the invasion preventive member ( i . e ., gasket 50 ) having a slope . the opening edge 420 of the main body 40 , and the magnetic head inserting portion 53 of the gasket 50 are shaped so that the gasket 50 may contact the opening edge 420 of the main body 40 in a linear manner by spring force . a slope 58 is formed in gasket 50 as shown in fig7 a , or a rib protrusion 59 is formed around the magnetic head inserting portion of gasket 50 as shown in fig7 b . fig8 a and fig8 b are sectional views showing the close contact between the slope of the main body and the invasion preventive member ( i . e ., gasket 50 ). in order that the gasket 50 may closely contact the main body opening edge 420 due to the spring force , a slope 44 is formed in the opening edge 420 as shown in fig8 a , or a rib protrusion 45 is formed in the opening edge 420 as shown in fig8 b . fig9 a and fig9 b are sectional views showing close contact between the main body and the invasion preventing member . as shown in fig9 a , a slope 44 ( slope angle a ) is provided in the main body opening edge 420 , and a slope 58 ( slope angle β ) is provided around the magnetic head inserting portion 53 of the gasket . these angles are set so that the slope angle α and slope angle β may differ by more than several degrees from each other . as shown in fig9 a , the slope angle α of the main body opening peripheral edge portion 420 is set smaller than the slope angle β of the magnetic head inserting portion 53 . the dimension of the slope 44 of the main body opening peripheral edge portion 420 is set smaller than the dimension of the slope 58 of the magnetic head inserting portion 53 . in this case , the main body slope 44 contacts the gasket 50 in a linear manner . alternatively , as shown in fig9 b , the slope angle α of the main body opening peripheral edge portion 420 is set smaller than the slope angle β around the magnetic head inserting ( inner circumferential ) portion 53 . the dimension of the slope 44 of the main body opening peripheral edge portion 420 is set larger than the dimension of the slope 58 of the magnetic head inserting portion 53 . in this case , the slope 58 of the magnetic head inserting portion 53 contacts the main body slope 44 in a linear manner by the energizing force of the spring 100 . both constitutions in fig9 a and fig9 b are nearly the same in the effect of preventing invasion of foreign material . fig1 shows the shape of the card reader main body of the invention . in fig1 , flanges 49 are provided above the guide walls 46 at both sides of the card passage 41 , and are linked to both end portions 47 , and a slope is provided in at least one end portion 47 . fig1 is a side view of the main body of the card reader of the invention mounted on the unit panel 120 of the operation panel 10 of an automatic vending machine shown in fig3 . waterproof sheet members 130 are adhered to both end portions 47 and flanges 49 of the card reader main body , and the mode of inserting into the unit panel 120 is shown . in fig1 , both end portions 47 of the card reader main body and the unit panel 120 are sloped . when mounting the card reader main body 40 on the unit panel 120 , the waterproof sheet 130 adhered to the card reader main body 40 can be placed in close contact with the unit panel 120 . therefore , invasion of foreign material from this area can be prevented . as clear from the description herein , the card reader of the invention can prevent invasion of water or dust into the magnetic head through the card passage of the main body by the invasion preventive member provided on the circumference of the magnetic head . in the card reader of the invention , by lightly pressing the magnetic head into the invasion preventive member , the magnetic head is allowed to swing freely while preventing invasion of foreign material , so that the card can be read securely . the card reader of the invention has a folding portion provided in the invasion preventive member so that the invasion preventive member can follow the motion of the magnetic head easily , and thereby the card can be read securely . in the card reader of the invention , at least part of the invasion preventive member is formed thinly , and the elasticity is improved , so that the invasion preventive member can follow up the motion of the magnetic head easily , and thereby the card can be read securely . in the card reader of the invention , when the card is not passing through the card passage of the main body , the invasion preventive member is always coming in contact with the main body with a specific pressure ( because the spring is always pushing against the magnetic head ), thereby consistently preventing invasion of foreign material . in the card reader of the invention , the slope of the magnetic head inserting portion of the invasion preventing member contacts the main body in a linear manner , and the surface pressure is increased as compared with the case of surface contact . therefore , invasion of foreign material can be prevented securely . in the card reader of the invention , the slope in the contacting portion of the opening edge linearly contacts the invasion preventing means at its rib leading end , and it is likely to be crushed . therefore , invasion of foreign material can be prevented securely . in the card reader of the invention , the slope of the opening edge linearly contacts the slope of the invasion preventing member , so that invasion of foreign material can be prevented securely . in the card reader of the invention , moreover , since flanges are provided in the upper part of the card passage of the main body , it is easier to adhere the waterproof sheets closely to the unit panel at the flange side . the adhering area of the waterproof sheet is wide , and the adhesion is increased , so that invasion of foreign material can be prevented securely . moreover , since the flanges are wide , the creeping distance from the card passage to the circuit unit is increased , and the resistance to static electricity from the card is increased . in the card reader of the invention , when adhering waterproof sheets to an area other than the card passage of the main body , it can be easily adhered to the unit side cover . therefore , working problems such as peeling and tearing of the waterproof sheet can be avoided .
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referring more particularly now to the drawings , the extender 10 is illustrated and includes an elongated base member 12 , a platform member 14 , a toe strap 16 and a heel strap 18 . the base member is flexible so that it may be flexed upwards to a substantial degree along the length of the extender as shown , for example , in fig7 . however , the base member is sufficiently self - supporting so that when suspended horizontally , the free end 20 thereof may sag but the extender is supported substantially horizontally . a preferred , flexible but self - supporting material for the base member is plexiglass . it is contemplated that other flexible , self - supporting materials may also be used for the base member , for example , fiberglass , plastic or rubber ( particularly a foam ) and other flexible , self - supporting materials . the platform 14 is adapted to receive the shoe of the wearer and is accordingly of a length greater than a large shoe size . elongated space slits 22 - 25 ( fig2 and 3 ) are provided through the platform member for the heel and toe straps . the toe strap is made of a single strap ( fig3 ) which extends into slit 24 of the platform member , and then extends out of slit 25 . strap 16 has two free ends 16a and 16b extending from the platform . ends 16a , b include mating parts of a pile lock , for example , mating velcro material . on end 16a , velcro material 28a is secured to side 30 of the strap end which faces outwardly and on end 16b , mating velcro material 28b is secured to side 32 of the strap end which faces inwardly . the heel strap 18 includes a heel strap member 34 extending through slits 22 , 23 as described for strap 16 and slits 24 , 25 and a cross - strap 36 secured to the free ends 34a , 34b of strap 34 . side 38 of strap 36 is secured to the sides 40 , 42 of strap ends 34a , 34b , respectively , which face outwardly . the ends 36a , 36b of the cross - strap have velcro material secured thereto , velcro material 28a being secured to the outer side 44 of end 36a velcro material 28b being secured to the inner side 38 of end 36b . the platform 14 with the straps extending therefrom is secured to the top of the base member 12 by an adhesive , for example . the platform member is a minor fraction of the length of the base member and accordingly has little or no effect upon the flexibility of the base member as a whole . the platform member is resilient and provides cushioning to the foot of the wearer and is preferably made of rubber . however , the platform member may be made from other resilient materials . preferably , cement or adhesive is used to secure a rubber platform member to the base member . alternatively , the platform portion could be part of the base member , i . e ., forming one piece with the base member . when the platform member is secured to the base member , strap portions 16c and 34c are sandwiched between the platform and base members and secured to the extender thereby . slits 22 and 23 , and slits 24 and 25 are respectively parallel to each other , and are spaced by a distance which is less than the width of a large shoe size , i . e ., less than about two inches . thus , when a shoe is placed on the platform member , part of straps 16a , b will be between the toe of the wearer &# 39 ; s shoe and the platform , and part of straps 34a , b will be between the heel and the platform . this arrangement ensures that the extender is securely strapped to the shoe and reduces substantially side movement of the shoe on the platform member . as shown in fig1 a shoe is strapped onto the platform member by a crossing arrangement in which velcro material 28a on toe end 16a is locked with velcro material 28b on heel cross - strap end 36b , and velcro material 28b on toe end 16b is locked with velcro material 28a on heel cross - strap end 36a . in this crossing arrangement , the straps rum from under the shoe and from the toe to heel , crossing the instep , and the extender is snugly secured to the shoe and ankle of the wearer . in fig4 strap ends 16a , 16b are locked across the toe of the shoe and cross - strap ends 36a , 36b are locked about the ankle of the wearer . this arrangement also snugly secures the extender to the shoe . the platform portion , in addition to providing a resilient platform for a shoe , can also perform a safety function . the platform portions of the extenders serve to offset the shoe of the wearer from the base portion so that when a wearer &# 39 ; s extenders cross , the base of one extender will not strike the wearer &# 39 ; s foot on the other extender , but instead will strike the offset platform . alternatively , the base portions themselves can be made of a resilient material . in accordance with a preferred embodiment the base member can be about 60 inches long , about 5 inches wide and about 1 / 8 inch thick , and the platform member about 12 inches long , about 5 inches wide and about 1 / 2 inch thick . additionally , the heel slits can be located 13 / 4 inches from the end of the platform and extend for about 2 inches ; the toe slits can be located about 61 / 4 inches from the end of the platform and extend for about 2 inches , and opposed slits can be spaced by about 11 / 2 inches . the extenders may be utilized in many ways . for example , as a medium for creative encounter , individuals wearing the extenders interact with one another to form three - dimensional configurations ( fig6 ) or planar configurations . to obtain the configuration shown in fig6 the wearers must maneuver the extenders so that the extender ends come into contact bottom - to - bottom while they are flexed . when the wearer &# 39 ; s toes are lifted and dropped simultaneously , the extender tips of facing wearers are caused to move back and forth alternately towards one wearer and then the other to create a kinetic sculptural happening . additionally , a degree of dexterity is required of each wearer as well as the cooperation of the wearers . in the configuration of the extender shown in fig7 a wearer has grasped the end of each extender so that the ends are flexed substantially vertically . to obtain this configuration , the wearer must lift each foot individually and flap the extender to flex it sufficiently for him to grasp its end . this also requires a degree of dexterity on the part of the wearer . to obtain the illustrated configurations , the extenders must be flexible and exhibit a degree of strength to withstand the forces generated while attempting to obtain the flexed configurations or when unflexing or striking the floor or each other . the ends 20 of the extenders are preferably planar , as planar ends enhance the geometric configurations formed by the extenders . additionally , planar ends with rounded corners 46 reduce risk of injury , particularly when the extenders are used by children . for this reason also , the edges 48 of the extenders are also rounded . while two configurations of use of the extenders have been illustrated in fig6 and 7 , many more configurations are possible . for example , wearers may face each other , as in fig6 but in a sitting position with their extenders in a contracting , flexed configuration as in fig6 . while sitting , each wearer may also move his extenders from side to side . other configurations and uses for the extenders are limited only by the imagination of the users . in accordance with the invention , the extenders may be utilized for many purposes as pointed out hereinbefore . the advantages of the present invention , as well as certain changes and modifications of the disclosed embodiment thereof , will be readily apparent to those skilled in the art . it is the applicant &# 39 ; s invention to cover by his claims all those changes and modifications which could be made to the embodiment of the invention wherein chosen for the purposes of the disclosure without departing from the spirit and scope of the invention .
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the following detailed description will present a preferred embodiment of the invention in reference to the accompanying drawings . fig1 is a longitudinal sectional view illustrating a variable length pencil of the invention before it is used , and fig2 is an exploded sectional view of the variable length pencil of the invention . the variable length pencil of the invention is constituted of a rectangular inner housing 20 , the first and second outer housings 30 and 40 respectively arranged around the upper and lower portions of the inner housing 20 , a power transmission unit 70 fixedly installed inside the inner housing 20 , a head unit 10 fixedly installed in the upper portion of the inner housing 20 and a movable unit 50 moving inside the second outer housing 40 . the first housing 30 is so mounted vertically slidable in respect to the inner housing 20 while contacting with the outside of the inner housing 20 . further , within the inner housing 20 is mounted the power transmission unit 70 . fig7 is a perspective view of the power transmission unit 70 , and fig3 and 4 are sectional views illustrating the installed position thereof . the power transmission unit 70 is constituted of a box - shaped body 72 and a pinion 60 rotatably mounted by fixing means such as a pin 62 within the body 72 . describing this in more detail , inside the body 72 is formed a gear - receiving section 74 with a predetermined width in which the pinion 60 is rotatably mounted by the fixing means such as the pin 62 . further , the gear - receiving section 74 has opened portions at both sides thereof so that both sides of the received pinion 60 are outwardly exposed through the opened portions . in the meantime , the body 72 is provided at both sides with guides 72 a and 72 b opposing each other along the entire length thereof . the both opened sides of the gear - receiving section 74 respectively correspond to the guides 72 a and 72 b so that those portions of the pinion 60 exposed through the opened portions are projected from the bottoms of the guides 72 a and 72 b as shown in fig3 . in the meantime , as specifically shown in fig7 the power transmission unit 70 is composed of an elastic material and has slits 76 at opposite upper portions . as the remaining portions at both sides of the incisions 76 have flexibility , the power transmission unit 70 is elastically supported to the inner wall of the inner housing 20 . further , in the upper portion of the power transmission unit 70 are provided projections 78 so that the power transmission unit 70 can be fixed to the inner housing 20 without any separate fixing means after the power transmission unit 70 is inserted into the inner housing 20 . further , at one end of the first outer housing 30 is preferably provided a fixing protrusion so that the projections 78 are caught to the first outer housing 30 to prevent the first outer housing 30 from being separated or detached from the inner housing 20 . in the upper end of the first outer housing 30 is fixedly installed the head unit 10 . the head unit 10 has a head 12 and the first rack shaft 14 integrally extending downward from the head 12 for a predetermined length . the first rack shaft 14 extends through the first outer housing 30 to mesh with a portion of the pinion 60 of the power transmission unit 70 installed within the inner housing 20 so as to provide vertical transport movement . that is to say , when the first outer housing 30 is coupled with the inner housing 20 , the first rack shaft 14 is placed within the guide 72 a formed at one side of the body 72 constituting the power transmission unit 70 while a portion of the first rack shaft 14 is meshed with an exposed portion of the pinion 60 mounted within the gear - receiving unit 74 of the power transmission unit 70 . the second outer housing 40 and the inner housing 20 are fixedly attached to each other at their ends , and the movable unit 50 is received within the second outer housing 40 . the brush 54 is fixed to the lower end of the movable unit 50 , and the second rack shaft 52 is extended from the upper end of the movable unit 50 . when the second outer housing 40 receiving the movable unit 50 is fixedly coupled with the inner housing 20 , the second rack shaft 52 of the movable unit 50 is placed within the guide 72 b in the body 72 of the power transmission unit 70 to mesh with an exposed portion of the pinion 60 mounted within the gear - receiving section 74 of the power transmission unit 70 . as shown in fig1 the first rack shaft 14 fixed to the head unit 10 and the second rack shaft 52 fixed to the movable unit 50 are opposed to each other in respect to the pinion 60 of the power transmission unit while mesh with each other in respect to the pinion 60 so that the rack shafts 14 and 52 carry out their transport movements in the opposite direction to each other . the rack shafts 14 and 52 are respectively received within the guides 72 a and 72 b of the body 72 constituting the power transmission unit 70 so that each of the rack shafts 14 and 52 can be transported within the guides 72 a and 72 b to carry out correct linear transport . as shown in fig1 and 2 , in the leading end of the first rack shaft 14 of the head unit 10 is installed a flexible piece 18 . the flexible piece 18 is made of a flexible material to naturally curve when the leading end thereof contacts with a blind end having a through hole 42 of the second housing 40 . further , as shown in fig5 the first rack shaft 14 is provided with a projection 14 a at a portion of the leading end thereof to which the flexible piece 18 is attached so that the elastic piece 18 closely contacts with the inner wall of the second outer housing 40 as well as the transport movement of the first rack shaft 14 imparts smooth sliding and inflection to the flexible piece 18 . the projection 14 a permits the flexible piece 18 to further closely contact with the inner wall of the second outer housing 40 to enable smooth sliding . further , when the movable unit 50 is drawn out as the first outer housing 30 slidingly contacts with the outside of the inner housing 20 , the projection 14 a is caught by the end of the inner housing 20 to prevent separation or detachment between the first outer housing 30 and the inner housing 20 due to excessive transport . in the meantime , as shown in fig6 lower edges of the second outer housing 40 are rounded so that the flexible piece 18 moves toward the through hole 42 of the second outer housing 40 . although the flexible piece 18 opens / closes the through hole 42 like this , it is preferred to add a guide member 80 for the purpose of a smooth opening / closing operation of the through hole 42 . such a guide member 80 is specifically shown in fig1 and 8 . as can be seen from fig1 and 2 , the guide member 80 is mounted inside the second outer housing 40 by coupling with the inner periphery thereof . further , fig8 is a perspective view illustrating the guide member 80 . as can be seen from fig8 the guide member 80 is provided with a guide 82 in the longitudinal direction at one side , and rounded at the end of the guide 82 . therefore , the flexible piece 18 is guided along the guide 82 of the guide member 80 without lateral transformation and its leading end is rounded to readily curve toward the closed end having the through hole 42 of the second outer housing 40 . in the meantime , fig9 is a perspective view illustrating the external appearance of the pencil before it is used , in which the first outer housing and the second outer housing 40 closely contact with each other , and the through hole 42 of the second outer housing 40 is closed by the flexible piece 18 . further , fig1 is a perspective view illustrating the external appearance of the pencil in use , in which the first outer housing 30 is separated from the second outer housing 40 to increase the entire length of the pencil while projecting the brush 54 via the through hole 42 of the second outer housing 40 . a process of operating the invention constructed as above will be described in reference to the drawings as follows . fig1 is the longitudinal sectional view illustrating the variable length pencil of the invention before it is used , and fig1 is the longitudinal view illustrating the variable length pencil of the invention in use . as can be seen in the drawings , when the head 12 of the head unit 10 is drawn upward , the first outer housing 30 is transported by sliding for a predetermined length in the same direction along the inner housing 20 . therefore , the first rack shaft 14 fixed to the end of the head 12 is moved upward , and the pinion 60 of the power transmission unit 70 is rotated with its one side being meshed with the first rack shaft 14 . like this , as the pinion is rotated , the second rack shaft 52 of the movable unit 50 meshed with the other side of the pinion 60 is transported downward in a direction opposite to the transport direction of the first rack shaft 14 of the head unit 10 . therefore , the movable unit 50 is transported downward within the second outer housing 40 , and as a result , the brush 54 of the movable unit 50 is transported downward for a predetermined distance to outwardly expose itself . at the same time , the flexible piece 18 installed in the first rack shaft 14 of the head unit 10 retreats along the guide 82 of the guide member 80 to reside within the guide 82 . the above operation is carried out just before the pinion 60 is released from each of the rack shafts 14 and 52 with which the pinion 60 is meshed or the projection 14 a is caught by the inner housing 20 . as shown in fig1 , upon completion of drawing out the movable unit 50 , the entire length of the pencil is increased as much as the transport distances of the rack shafts 14 and 52 added thereto . after the pencil is used , an operation of placing the exposed brush 54 into the second outer housing 40 is carried out in a reverse manner as above . that is , if the head 12 of the head unit 10 is pushed downward , the first outer housing 30 is transported downward as sliding on the inner housing 20 . this causes the first rack shaft 14 to move downward , and through this operation , the pinion 60 of the power transmission unit 70 is rotated reversely in respect to the rotating direction thereof when the first rack shaft 14 moves upward . further , as the pinion 60 is rotated , the second rack shaft 52 of the movable unit 50 meshed with the other side of the pinion 60 is transported upward in a direction opposite to the first rack shaft 14 of the head unit 10 . therefore , the movable unit 50 is transported upward inside the second outer housing 40 , and as a result , the brush 54 which was exposed outside the second outer housing 40 is received into the second outer housing 40 . at the same time , the flexible piece 18 attached to the leading end of the rack shaft 14 of the head unit 10 is moved along the guide 82 of the guide member 80 to close the through hole 42 in the lower end of the second outer housing 40 . in this case , the flexible piece 18 is readily curved since the inner lower end of the second outer housing 40 is rounded . according to the variable length pencil of the invention as set forth above , the brush is outwardly exposed as the entire length of the pencil is increased , but as the entire length of the pencil is decreased , the brush is received into the pencil making the same compact and the flexible piece closes the through hole of the second outer housing to prevent any penetration of dust in the air into the pencil . therefore , there is an effect of advantageously further enhancing the convenience of the pencil in use . also , the invention can prolong the life time of the pencil by preventing the brush within the pencil from being exposed to dust and the like . further , the invention prevents the pencil from directly contacting with the external air so that the brush may not be dried . therefore , the brush can be maintained in a suitable degree of wetness so that a user can have smooth feeling to the brush in use .
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the generalized physical embodiment 10 of the information environment generally referred to as cyberspace is shown if fig1 . an internet 12 provides the logical interconnection for a variety of client computer systems , such as a computer system 14 , to connect through the transmission and reception of electronic mail , among other forms of information , with other client computer systems 18 , 20 . the computer system 14 typically connects through any of a variety of different telephony technologies to a server computer system 16 operated by an internet service provider ( isp ) that connects directly or through higher level isps , as needed , to reach the backbone computer systems that make up the internet 12 . other computer systems such as systems 18 , 20 typically connect through the same or other isps ( not shown ) in order to logically connect with the internet 12 . unsolicited commercial e - mail ( uce ), commonly referred to as spam , may be generated through bulk e - mail deliveries from a computer system , such as the computer system 18 , to the internet 12 . conventionally , uce routes through the internet 12 as ordinary e - mail , spooled by isps 16 ultimately for delivery to identified destination computer systems 14 . the return e - mail address is intentionally obscured to avoid self - identification . the bulk e - mailer operating the system 18 can easily control the removal of the from : line of the e - mail messages , substitute a non - existent return e - mail address , or substitute a valid e - mail address corresponding to an unrelated computer system , such as the system 20 . thus , while the user of a computer system 14 can attempt to identify and complain to the postmaster of an isp providing service to a bulk e - mailer , there is both difficultly and uncertainty by the user of the computer system 14 to properly identify the relevant isp . further , the user of the computer system 14 has little or no authoritative or commercial position to have an isp , other than perhaps their own isp 16 , limit the activities of a bulk e - mailer . as shown in fig2 an e - mail system 22 that implements the present invention can actively identify and filter uce . through the implementation of the system 22 , the user of a computer system 14 is able to efficiently block uce originated from a computer system 18 independent or in collaboration with uce filtering actions , if any , taken by the isps interconnecting the system 18 with the internet 12 . this is achieved while preserving the ability of the system 14 to exchange e - mail with other computer systems , such as the computer system 20 . the e - mail filter system 22 generally includes or inter - operates with a conventional e - mail client system 22 ′. inbound e - mail messages are conventionally received in an inbox 30 for subsequent review by the user of the local computer system executing the client system 22 ′. these e - mail messages may be transferred , upon review , directly to a discard or trash box 32 or transferred elsewhere within the e - mail client computer system . similarly , e - mail messages originated by the e - mail client system 22 ′ are queued to an outbox 34 to pend delivery to an isp . in general , the active e - mail filtering system 22 operates as an interface between the e - mail client system 22 ′ and , typically , a point - of - presence ( pop ) system conventionally hosted by an isp 16 . this interface function can be implemented in a variety of forms dependant largely on the available operative features of the e - mail client 22 ′. for example , where supported , the active e - mail filtering system 22 is preferably implemented as a “ plug - in ” component that integrates into the operative function of the client 22 ′. alternately , the e - mail filtering system 22 can be implemented as a software layer over the pop communications port defined for use by the e - mail client 22 ′. in this alternate embodiment , the e - mail filtering system 22 software layer can be provided on any computer system logically in the communications path used by the e - mail client 22 ′ to access the pop system hosted by the isp . specifically , the software layer embodiment of the e - mail filtering system 22 can be implemented on either the isp 16 or client computer systems 14 . implementation on the isp or a third party computer system 20 allows the e - mail filtering system 22 to be operated as a service for the benefit of a subscribing e - mail client 22 ′. the function of the e - mail filter system 22 , in accord with a preferred embodiment of the present invention , is to actively select to accept or reject e - mail messages received by the system 22 . accept 24 and reject lists 26 are kept for this purpose . additionally , the system 22 operates to identify and challenge e - mail messages from correspondents that are not known to the system 22 . the challenge is presented as an automated reply to an e - mail message from an unknown e - mail address , which is generally defined as an address not found on either the accept 24 or reject 26 e - mail address lists other well - known and conventionally existing e - mail addresses including those , for example , of the host domain of the e - mail client 22 ′ may be inferred to be a known address , though not explicitly listed . in accordance with the preferred embodiment of the present invention , the challenge message is generated automatically by the active challenge system 22 directly in response to the unknown e - mail message received . the challenge request message preferably includes a text statement and a digital signature . the statement preferably identifies the challenge e - mail message as an identification verification message and presents a request for a specific response to the challenge message be returned to the e - mail client system 22 . although the specific response could be as simple as merely replying to the challenge message , in order to discriminate against auto - responders the specific response requested preferably includes directions to , for example , reply to the challenge message with a blank subject line . other individual and additional trivial modifications to the message — such as placing an x between two brackets , deleting a portion of the challenge text , or entering a random four digit number — or the addition of some specific information — such as the name of a state capital or lead character of a movie — could be requested in order to distinguish from and defeat auto - responders being statically programmed to make any single requested modification . also , the specific modification requested may be cycled among a number of such modifications by the active e - mail filtering system 22 in order to effectively randomize the modification request received by any particular auto response system . since preferably , all of the specific modifications requested are cognitive , yet trivial , little burden is placed upon the actual e - mail correspondents in order to establish a lasting level of trust between the correspondent and the active e - mail filtering system 22 . the signature provided in the challenge message may be formed utilizing a conventional encoding or encrypting technology . for example , a simple check - summing algorithm may be utilized to generate the signature value based on the whole of the challenge message , or some predefined portion . other encoding and encrypting algorithms usable with the present invention include md5 , rot13 and public key encryption . in a preferred embodiment of the present invention , the signature value is generated based on a check - sum generated utilizing the challenge request statement as the source text . an embodiment of the present invention , which may ultimately be preferred , alternately or additively generates the signature as an encrypted text block containing a variety of specific information . this information preferably includes the origination date and time of the challenge message , the e - mail address used as the destination for the challenge message , and an identifier of the message for which this challenge message was generated . by including such specific information in the encrypted text block , analysis and evaluation of any responding message received back by the e - mail client 22 can be performed . specifically , utilization of the encrypted signature on e - mail messages originated after some threshold period of time beyond the signature origination date can be readily identified . the disposition of such late responses can then be intelligently handled by the active e - mail filtering system 22 . of course , the window of time within which an encrypted signature is automatically accepted is definable entirely within the operation of the active e - mail filtering system 22 . the challenge e - mail message is sent to the unknown e - mail address with the intent of obtaining a validating response . if the unknown e - mail address is not valid , only auto - responds , or simply does not answer , whatever response received by the e - mail system 22 can be discriminated as a non - validating response . conversely , a validating response will minimally require a cognitive modification be made to an otherwise conventional reply to the challenge message , which will include the digital signature by default . the signature must be included in the reply for the response to be recognized potentially as a challenge reply independent of any evaluation against the accept and reject lists . messages recognized based on the included signature are then evaluated for cognitive compliance as validating responses . when determined to be non - validating , the response and the original message that was challenged are preferably discarded . as an option , the unknown e - mail address can also be placed on the reject list . conversely , a validating response results in the discard of only the validating response itself . the previously unknown e - mail address is added to the accept list and the original message challenged is then passed to the e - mail client system 22 ′ as a non - uce e - mail message . in greater detail , a preferred embodiment of the present invention adds to the conventional e - mail client system 22 ′ an accept list 24 , reject list 26 , and a challenge list 28 . this challenge list 28 may be alternatively provided as separate challenge list 28 data structure or a data store extension 28 of a temporary or pending in - box 36 structure . the pending box 36 may also be implemented logically within the inbox with suitable modification to the otherwise conventional e - mail client system 22 ′ to accommodate the identification of e - mail messages logically residing with in the pending box 36 . this may be accomplished by augmenting the status value associated with each e - mail message with an additional state recognizable as identifying a corresponding e - mail message as pending filtering evaluation by the present invention . the accept and reject lists 24 , 26 provide storage for respective lists of e - mail addresses preferably on the local e - mail client computer system 14 . the form of the addresses as stored may include simple domain names , specific user e - mail addresses , and internet protocol ( ip ) numbers . inclusion and exclusion operators , wildcards and ip range lists may also be utilized in the parsing or other evaluation of the accept and reject lists address . the use of such operators , wild cards and lists in considering whether a specific e - mail address matches an entry in a list of e - mail addresses is known . thus , conventional evaluation of whether a particular e - mail address matches an entry on either the accept list 24 or the reject list 26 is utilized by the present invention . the challenge list 28 may provide storage for destination e - mail addresses of challenge messages sent ( not required ), identifiers of the temporarily stored messages that are being challenged ( can be input from the construction of the challenge list 28 ′ as part of the pending box 36 ), and certain additional information pertaining to the individual challenge messages , such as the signature encoding key and cognitive response expected for each challenge message ( may alternately be determined algorithmically upon evaluation of the challenge reply message ). the use of operators , wildcards , or lists are preferably not necessary in specifying e - mail address entries on the challenge list 28 . since the list 28 operates as a temporary store of information concerning the currently outstanding challenges issued by the system 22 , the matching of e - mail addresses by the e - mail client system 22 against the entries in the challenge list 28 will preferably be on an exact basis . in this preferred embodiment of the present invention , inbound e - mail messages are placed in the pending box 36 while the received e - mail message is evaluated . selected e - mail messages , determined according to the present invention , are ultimately transferred from the pending box 36 to the inbox 30 , where subsequent handling and evaluation of the e - mail message is performed in a conventional manner . when an inbound e - mail message has been stored in the pending box 36 , the content of the e - mail message is optimally evaluated algorithmically in a process step 42 to determine whether the e - mail message may be an a response to a challenge message originated by or on behalf of the client e - mail system 22 ′. this determination is made at least in part by scanning the content of the response message for text that appears to be a digital signature consistent with the present invention and text corresponding to the cognitive request . thus , auto - responses and administrative responses that contain copies of the challenge messages they answer will be detected as potential challenge response messages . messages identified as potential challenge response messages are passed to a process step 48 that operates to determine whether the digital signature is valid and whether the cognitive request presented by the particular challenge message has been appropriately answered . in performing this function , the challenge list 28 may be referenced to obtain the information necessary to decode the digital signature and to qualify the cognitive response . if the digital signature is invalid or if the cognitive response is incorrect , the challenge response message and the received e - mail message that was challenged are both discarded . conversely , if the digital signature and cognitive response are validated , only the challenge response message is discarded and the challenged e - mail message is placed in the inbox 30 for conventional processing . the e - mail address of the challenged message is also placed on the accept list 24 . e - mail messages not recognized as challenge reply messages at step 42 , and all messages if the step 42 is not used , are then considered at step 44 to determine whether the from or reply - to address is present on the accept list 24 . where a match is identified , the e - mail message present in the pending box 36 is passed on to the inbox 30 for subsequent conventional processing . if the accept list match fails at step 44 , a reject step 46 is invoked to determine whether an address match can be found against the reject list 26 . if a reject list match is found , the corresponding e - mail message in the pending box 36 is discarded or , in a preferred embodiment of the present invention , passed to the discard box 32 for subsequent conventional processing . if a reject list match is not found , the message content is preferably evaluated partially through the step 48 to determine whether , for example , a known correspondent is replying to an e - mail message originated from the system 22 ′, but replied to from an e - mail account not previously seen by the system 22 ′. since out - bound messages from the e - mail user of the system 22 are preferably provided with digital signatures , responses to such messages are validated and thus are shown to the user when they are received . as before , the digital signature preferably encodes the date that the message was sent . thus , the step 48 can be set to invalidate messages received beyond a nominal reply period determinable by the e - mail user of the system 22 . preferably , messages containing expired digital signatures are discarded or put in the trash box 32 ; validated messages are passed to the inbox 30 . in a preferred embodiment of the present invention , the address of e - mail messages validated only by virtue of a valid digital signature are not placed on the accept list . rather , no present action is taken regarding messages from this address , thereby permitting the active challenge system 22 ′ to re - evaluate messages received subsequently from that address . the accept list will be updated with this address if , however , the e - mail user chooses to update the list 24 or the e - mail user simply replies directly to this address . finally , messages received but not matched to the accept or reject lists and not containing a digital signature are , in a step 50 , responded to by the preparation and issuance of a challenge message . this message , once generated to include a cognitive request and a current corresponding digital signature , is placed in the out box 34 . referring first to fig3 a variety of preferred embodiments and operational variations of the present invention will be described in connection with an active e - mail filtering system 60 . these options and variations primarily concern the receipt processing of e - mail and the preparation and transmission of the challenge messages and permit location of the active e - mail challenge system 22 , or an autonomous “ robot ” portion thereof , separate from the conventional e - mail client 22 ′ on an isp system 16 or other service provider accessible directly or indirectly through the internet 12 . for such embodiments of the present invention , the remote location of the active filtering system 22 ′ or robot relative to a client computer system 14 serves to off - load a possibly substantial level of processing as well as affording a centralized point for management of changes to the accept and reject lists 24 , 26 . in particular , the centralized management may make the augmentation of the reject list with e - mail addresses obtained from internet sources of known uce sources much easier . while centralized maintenance of the lists 24 , 26 may , for alternate embodiments of the present invention , prove useful as well as convenient for end users of client computer systems , the present invention in all of its embodiments provides for and correctly handles the accumulation of e - mail addresses , formally from unknown sources , onto the accept and reject lists 24 , 26 . for this embodiment 60 , e - mail messages directed to the user are received and handled separately from challenge responses , which are directed to and processed by a separate robot . preferably , the user and robot are set - up in separate e - mail accounts if not also on separate computer systems . thus , inbound e - mail 62 directed to a user &# 39 ; s e - mail account is initially stored in a temporary queue 64 . the received e - mail is evaluated 66 to determine the nominal sender of the received e - mail message . once the sender is identified , the message is further evaluated 68 against the accept list 24 . if the sender is on the accept list 24 , the received e - mail message is transferred to an input queue 70 , which may be a conventional inbox , from the temporary queue . e - mail messages not validated against the accept list 24 may then be evaluated for potential immediate inclusion of the sender e - mail address on the accept list 24 managed by the system 60 . this evaluation is optionally performed to initialize an accept list 24 managed by the system 60 . in a preferably limited time frame where such initialization is enabled , sender e - mail addresses are unilaterally added 82 to the accept list 24 . subsequently , the e - mail user may select to move the sender e - mail address to the reject list 26 or merely delete the address . the corresponding e - mail message stored in the temporary queue is also transferred 70 to the input queue . consequently , the end user of the system 60 is involved in the initial review and categorization of sender e - mail addresses . the end user is also provided the programmable option to terminate the initialization . e - mail messages not validated from the accept list 24 are then evaluated against the reject list 26 . where the sender e - mail address is present on the reject list 26 , the corresponding received e - mail message is discarded 76 from the temporary queue and the challenge list 28 ′ is correspondingly updated specifically , the evaluation of e - mail messages not yet accepted or rejected , are then evaluated 77 to determine whether the message contains a signature recognizable by the system 60 . the signature , where found , is decoded or decrypted 80 depending on the nature of the signature identified . in accordance with alternate preferred embodiments of the present invention , the identification of the signature may depend entirely on an algorithmic evaluation of the signature block itself or upon data included in the challenge list 28 ′. in the latter circumstance , the challenge list 28 ′, may be used to record information identifying different possible types of signatures and , thereby , the corresponding decoding and decrypting algorithms , the scope of pre - existing content utilized in the generation of the signature , and other information usable in identifying whether the particular received e - mail message and its signature were originated by the system 60 . the challenge list 28 ′ preferably also stores a challenge issue date and , implicitly or explicitly , a challenge close date . the issue date is useful for detecting the occurrence of unanswered challenges and removal of any corresponding e - mail message still pending in the temporary queue . the challenge close date can be used to permit the system 60 to establish potentially variable challenge periods , perhaps dependent on the general content of the received e - mail message . in the preferred embodiments , the decoding and decrypting 80 of the signature . where the signature is valid and the origin date is sufficiently recent , or within a challenge acceptance threshold established directly or indirectly by the end user of the system 60 , the e - mail message is considered valid 82 and is transferred to the input queue 70 . received e - mail messages that bear a signature but fail in the validation of the signature or are received late relative to the time threshold established directly or indirectly by the end user is identified as invalid signed message 82 . the invalid received e - mail message is then discarded 76 from the temporary queue 36 . optionally , such invalid signed messages may be further evaluated to identify the sender e - mail address , which may then be added to the reject list 26 . preferably , this option is established directly or indirectly by the end user of the system 60 . conversely , where a reject list match is not found , the corresponding received e - mail message are further processed at a step 80 . e - mail messages received by the system 60 and not yet dispensed with , by virtue of having digital signature to validate , are presumptively from new e - mail correspondents . in accordance with a preferred embodiment of the present invention , these e - mail messages are those to be challenged to confirm that the correspondents are real , as opposed to likely originating from a bulk e - mailer . [ in accordance with at least an alternate embodiment of the present invention , the initial processing of a received e - mail message from an unknown correspondent is handled by preparing a challenge message 84 , by switching , logging or modifying the current account information , sometimes referred to as an e - mail profile , 86 in order to establish the preferred content of the header lines that are to be associated with the challenge message and the sending the challenge message 88 .] the challenge message itself is prepared 84 with content that presents a cognitive response request , and includes a signature . at this point , the challenge list 28 ′ may be updated 78 . the update to the challenge list preferably includes the necessary information to identify the appearance of a signature and enable the decoding or decrypting of the signature as necessary to subsequently validate the signature . in the preferred embodiment , however , the regular form of the signature and an examination of the signature text itself are sufficient to enable the system 60 to algorithmically recognize and then decode or decrypt the signature . by sending challenge e - mail messages from an alternate or “ robot ” e - mail account , challenge response messages are readily segregated from the e - mail stream directed to the user of the e - mail client 22 ′. as shown in fig4 inbound e - mail 62 directed to the robot account are received and inserted 102 into the robot account &# 39 ; s pending box 30 ′. in the manner described above , the received e - mail is scanned for a digital signature that is , in turn , decoded or decrypted 104 . if the signature found is invalid or if no signature is found 106 , the received e - mail message is removed 108 from the pending box 30 ′. the challenge list 110 is correspondingly updated . for received e - mail messages with valid digital signatures , the message is next examined for a correct response 112 to the cognitive request . if the response is either absent or incorrect , the received e - mail message is again removed 108 from the pending box 30 ′. when a valid cognitive response is found , the response e - mail is again discarded 108 ′ and the challenge list is again updated 110 . processing continues , however , with the robot effectively switching e - mail accounts 114 . this account switch is made to the client e - mail 22 user &# 39 ; s account at least to the extent necessary or appropriate to enable the robot to access the pending box 30 of the user account for the purpose of transferring 116 the corresponding challenged e - mail message from the user &# 39 ; s pending box 30 to the user &# 39 ; s inbox 32 . the robot may also automatically update the accept list 24 with the from : e - mail address of the message moved . in a preferred embodiment of the present invention , however , the robot instead provides for the active e - mail filtering client 22 to prompt the user to update either the accept 24 or reject 26 list when the e - mail message is accessed 114 . a preferred process of handling original outbound messages in accordance with the preferred embodiments of the present invention is shown in fig5 . the process 120 is initiated when a message is prepared 122 by the e - mail client 22 ′. when the message is prepared to be sent 124 by transfer 134 to the output queue 34 of the e - mail client 22 , the message headers are first examined to determine whether the message qualifies as an original message . messages identified as challenge messages are not considered original messages . rather , new messages prepared by the e - mail user of the system 14 , and ordinary reply and forward massages are considered original . the destination e - mail address specified in an original message is then matched 126 against the accept list 24 to determine whether the address has already been recorded . if not , the recipient e - mail address is added 128 to the accept list 24 . this ensures that e - mail destinations implicitly recognized and validated by the user of the e - mail client system 22 ′ are subsequently recognized as valid senders of e - mail messages to the system 22 . in either event , a new digital signature is prepared 130 and appended 132 to the outbound message . transfer of the resulting message to the out - box 134 is then complete . the outbound message , along with any other pending outbound messages are subsequently picked up or transferred 136 to the isp servicing the e - mail client 22 . by selectively delaying the deliver of e - mail messages to the client e - mail system 22 ′, the need for managing the contents of the pending box 30 arises . preferably , as generally shown in fig6 a maintenance procedure is provided to periodically 142 examine the pending box for e - mail messages corresponding to outstanding challenge messages sent by the system 14 . the pending box 30 or challenge list 28 may be examined to identify such held e - mail messages 144 . preferably , as each is identified , a check is made for the date the corresponding challenge e - mail message was sent . messages pending for more than some user defined period of time are determined 146 to be expired . the length of this user defined period may be any reasonable number of days or other measure of elapsed time , and preferably is approximately two weeks . expired e - mail messages are removed from the pending box 30 and discarded 148 . the challenge list 28 ′ is correspondingly updated 150 . finally , a determination is made 152 of whether the entire set of pending e - mail messages has been examined , with the result that the maintenance routine 140 either exits or continues processing challenge list entries 144 . referring again to fig3 in the ongoing operation of the system 60 the majority of received e - mail messages will likely be transferred 70 to the input queue 30 based on e - mail address matches against the accept list 24 . in accordance with a preferred embodiment of the present invention , a quick initial development of the accept list 24 can be obtained by effective assimilation of any e - mail archives kept by the user of the system 60 . presumptively , archived e - mail messages are from or are replies to valid and acceptable e - mail correspondents . as illustrated in fig7 a process 154 is preferably provided for the user to select 156 to prepare entries for the accept list 24 . a user identified e - mail archive is then parsed 158 to progressively identify the e - mail address of the correspondent or correspondents identified as the source or destination of the message , including optionally the copied correspondents . as each e - mail address is identified and determined to be unique relative to the accept list 24 , the address is added 160 to the list 24 . the parsing of e - mail messages continues 126 until complete or terminated by the user 162 . thus , a method and system for providing for the effective identification and active filtering of uce has been described . the method and system includes provisions for initialization of filtering lists and the continuing , largely automatic identification of acceptable e - mail addresses through a challenge system that utilizes signed challenges as a basis for the automation . while the present invention has been described particularly with reference to the active filtering of uce from public e - mail transferred through internet based message streams , the present invention is equally applicable to intranets , virtual private networks , and other communication networks not easily controlled by a master addressing authority . in view of the above description of the preferred embodiments of the present invention , many modifications and variations of the disclosed embodiments will be readily appreciated by those of skill in the art . it is therefore to be understood that , within the scope of the appended claims , the invention may be practiced otherwise than as specifically described above .
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referring to fig1 a general illustration of one capacitor according to this invention is shown , in sectional view . it is customary to construct integrated circuit capacitors on substrates , and the illustrated and described embodiments are along these lines . it will be understood , though , that the multiple layer invention can find applicability in other capacitor orientations . thus , for illustrative purposes , a multilayer capacitor , shown generally at 10 , is built on a substrate 12 of an integrated circuit device . capacitor 10 generally comprises a first or bottom electrode 14 , a dielectric 16 and a second or top electrode 18 as is known in the art . both the bottom electrode 14 and the top electrode 18 are constructed of multiple layers according to this invention . in general , as illustrated in fig1 bottom electrode 14 is constructed , for example , of four distinct layers of materials , each layer serving a different function . it is to be understood , however , that this embodiment is merely an example of one capacitor according to this invention , and a greater or lesser number of layers in each electrode will be in keeping with this invention . a first layer 20 of bottom electrode 14 preferably comprises an adhesion layer . layer 20 promotes adhesion of bottom electrode 14 , and hence entire capacitor 10 , to substrate 12 . on top of adhesion layer 20 , a second layer 22 is formed . second layer 22 preferably comprises a diffusion barrier . the diffusion barrier layer 22 , as is known in the art , prevents an upper or further layer of material from diffusing or migrating into the lower layers , by hillocks for example , thus causing unintended electrical paths and impurities in the lower layers . a third layer 24 may be an electrical contact layer , which electrically connects capacitor 10 to other devices and components on the integrated circuit . a fourth layer 26 may be formed over the other layers in bottom electrode 14 . layer 26 may be a plate layer which provides the electrode or plate function as usually found in a capacitor . in this embodiment , layer 26 may also provide a nucleation layer , as will be explained infra , for dielectric growth . continuing in the upward direction through the fig1 capacitor , dielectric 16 is grown , deposited or otherwise established on first or bottom electrode 14 , as is known in the art . a second or top electrode 18 may be constructed of multiple layers on top of dielectric layer 16 , and the structure of the second electrode 18 can be similar to the layering structure of the first electrode 14 , but in mirror image . that is to say , bottom layer 30 of electrode 18 may be a plate layer formed over dielectric 16 . a second layer 32 of second electrode 18 may be formed over the plate layer 30 . this second layer 32 of the second electrode may be a diffusion barrier , as is known in the art and discussed supra in connection with layer 22 of the bottom electrode . a third layer 34 of the second or top electrode 18 may be formed over layer 32 . layer 34 may be , for example , a second electrical contact forming a circuit or connection with other components or devices situated nearby ( or elsewhere ) on the integrated circuit . further layers of the integrated circuit may then be formed on capacitor 10 , as is known in the art . fig2 shows a sectional view of a more specific embodiment of the current invention , showing the various layers and the materials that may be used to fabricate a multilayer capacitor . the capacitor of the fig2 embodiment is shown generally at 110 . capacitor 110 , like capacitor 10 of fig1 is constructed on a substrate 112 of an integrated circuit , and includes a first or bottom electrode 114 , a dielectric 116 thereover , and a second or top electrode 118 spaced from bottom electrode 114 by dielectric 116 . both electrodes 114 and 118 are constructed in a multilayer fashion , according to this invention . the embodiment of fig2 is constructed in an evacuated chamber , as is known in the art , preferably in two separate evacuations or &# 34 ; pump downs &# 34 ; of the chamber . the first or bottom electrode and the dielectric layer is constructed during the first pump down , and the second or upper electrode is constructed during the second pump down . in the following description , all thicknesses may vary approximately + 100 % to - 50 %. in the embodiment illustrated in fig2 bottom electrode 114 comprises three layers over the substrate 112 . substrate 112 may comprise an insulator material on a semiconductor substrate , for example sio 2 deposited on si or gaas . substrate 112 may alternatively comprise a semiconductor material , such as the drain of a mos transistor or the emitter of a bipolar transistor . the first layer 120 may comprise titanium , which serves as an adhesion layer between the substrate 112 and the capacitor 110 . titanium layer 120 is established as discussed below to a preferred thickness of approximately 0 . 05 microns . a second layer 124 of electrode 114 may comprise , for example , titanium nitride . this serves as an electrical contact between the bottom electrode 114 of the embodiment of fig2 and other devices on the integrated circuit , and as a diffusion barrier . the titanium nitride second layer 124 is deposited to a preferred thickness of approximately 0 . 1 microns . a third layer 126 of electrode 114 may comprise platinum , which serves several functions . platinum layer 126 can act as an electrode plate ; platinum is a good material for nucleation of a dielectric layer 116 ; and platinum is a chemically inert interface between dielectric layer 116 and electrically conductive layer 124 . the platinum third layer is deposited via known means , to a preferred thickness of approximately 0 . 05 microns . the first electrode 114 is substantially complete at this point . the next layer in the capacitor is dielectric layer 116 . this layer may be deposited by means known in the art , or may be grown as is known in the art . the dielectric may be a ferroelectric material or a high dielectric constant material . the thickness of the dielectric layer depends on the material chosen . the thickness of a high dielectric constant material would vary inversely according to the desired capacitance of the capacitor . the thickness of a ferroelectric layer depends on the operating voltage of the underlying circuit . for a typical operating voltage of approximately 5 volts , the ferroelectric layer is approximately 0 . 4 microns . on the dielectric 116 may be deposited a first layer 130 of the second or top electrode 118 . layer 130 may be constructed of platinum , for example . the platinum layer 130 serves as the top electrode plate and acts as a chemically inert interface between the dielectric 116 and a conductor layer . platinum layer 130 of the second electrode 118 is deposited by means known in the art to a preferred thickness of approximately 0 . 05 microns . next , a second layer 132 is deposited or otherwise established over first layer 130 , and preferably comprises titanium . the titanium layer 132 serves as a diffusion barrier and adhesion layer in the top electrode 118 . the titanium layer 132 is deposited by known means to a preferred thickness of approximately 0 . 1 microns . the third layer in the top electrode 118 of the embodiment of fig2 is constructed preferably of aluminum . the third layer 134 of aluminum serves as the top electrode &# 39 ; s electrical contact to other devices on the integrated circuit . the aluminum third layer is deposited to a preferred thickness of approximately 0 . 1 microns . as mentioned supra , each layer in both the top and bottom electrodes can be deposited or established a number of known techniques . the technique needs only to be appropriate to the material selected for the layer and the surrounding components . appropriate methods include , but are not limited to , sputtering , evaporation , chemical vapor deposition , molecular beam epitaxy and spin coating . in addition , the final form of a multilayer electrode structure can be achieved by a controlled chemical reaction of the deposited or grown layers . turning now to fig3 and 4 , a further embodiment of this invention is shown , whereby a multilayer structure is created by a controlled chemical reaction of the deposited layers . a partially completed capacitor according to this embodiment of the invention is shown in section in fig3 generally at 210 . the capacitor 210 of this embodiment is built on a substrate 212 , and includes a first or bottom electrode 214 , a dielectric 216 thereover and an upper electrode , not shown in this figure . the deposition of material in this embodiment is preferably performed in one pump down . in this embodiment , a first layer of titanium 220 may be deposited by a means known in the art , as discussed above , onto the substrate 212 . the first layer of titanium 220 is preferably 0 . 15 microns ( all thicknesses of this embodiment may also vary approximately + 100 % to - 50 %). a second layer 226 of platinum is deposited over the first layer 220 to a preferred thickness of 0 . 05 microns . a dielectric layer 216 is next deposited on the platinum second layer 226 , as in the preferred embodiment , above . turning now to fig4 the structure thus formed in fig3 is heated in an oxygen ambient to approximately 750 degrees centigrade . as a result , the titanium first layer 220 in fig3 becomes titanium dioxide 220a in fig4 . the substrate 212a , the platinum second layer 226a and the dielectric layer 216 remain relatively unaffected by this step , as illustrated in fig4 . a top or second electrode is then formed in an identical or similar manner . the oxidation of the titanium layer 220 of fig3 results in an improvement in adhesion of the platinum and lowered film stress . other layers may be added to the multilayer electrode of this embodiment , depending on the circuit , connections required , etc . thus , it will be appreciated that in the preferred embodiments , both layers of a capacitor on an integrated circuit are formed of two or more distinct layers , each layer performing one or more functions . of course , it is not required that both electrodes be so formed , as a given application may call for only one electrode to be multiply - layered according to this invention . those skilled in the art will find other modifications of these embodiments which are within the scope and spirit of the present invention . the foregoing descriptions of two embodiments are illustrative .
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hereinafter , preferred embodiments of the present disclosure will be described in detail with reference to the drawings . although shown in different drawings , the same reference numbers represent the same or similar components . for clarity and conciseness , descriptions on well - known functions and structures will be omitted here to avoid obscuring the subject matter of the present disclosure . embodiments below are used for explaining the present disclosure , but do not limit the scope of the present disclosure . fig1 shows a schematic view of an inspection system according to an embodiment of the present disclosure . as shown in fig1 , the inspection system according to the present embodiment includes a ct device for quarantine . the system includes an x - ray source 11 , a detection and collection apparatus 12 , a conveying apparatus 13 , a controller 14 , a computing unit 15 such as cpu or gpu , and a display unit 16 . the x - ray source 11 and the detection and collection apparatus 12 are installed on a rotation apparatus such as a gantry , and are rotated in a high speed controlled by the controller 14 . the controller 14 controls the conveying apparatus 13 such as a belt to convey one or more objects 17 being scanned from one side of the rotation apparatus to the other side at a constant speed . x - rays emitted from the x - ray source 11 are received by a detector of the detection and collection apparatus 12 after they are transmitted through the object being scanned , and are converted by an analog - to - digital a / d conversion circuit to form a digital signal as projection data . the computing unit 15 , e . g ., an image processing unit , reconstructs the digital signal to be a 3d image which reflects the internal structure and / or material features of the object 17 being scanned , and enhances display of an organic part and / or a contraband part , in of the 3d image , by highlighting the part ( s ). in some embodiments , the x - ray source 11 may be a dual - energy x - ray source , and the detector may also receive x - rays with different energies , so that a dual - energy x - ray inspection may be performed on the object 17 being scanned . the ct scan performed here may be a circular scan or the like . the detection and collection apparatus 12 may be e . g . detectors and data collectors in an integrated module structure , e . g ., a flat - panel detector , which may be used for detecting the rays passing through the object being scanned so as to obtain an analog signal , and for converting the analog signal to a digital signal , thereby outputting projection data of the object 17 being scanned for the x - rays . the controller 14 is connected to the x - ray source 11 , the detection and collection apparatus 12 and the conveying apparatus 13 , and controls each part of the whole system to work synchronously . the computing unit 15 processes and reconstructs data collected by the data collector , and outputs the result . for example , after the one or more objects 17 are scanned by the dual - energy ct device , the obtained dual - energy 3d image data are input to the computing unit 15 ; an installed substance identification system is used for performing substance identification on the object being scanned according to the image data , so as to obtain information of different substances , such as effective atomic numbers , densities , etc ., and for tinting the 3d image so as to be displayed on a screen of the display unit 16 . also , the article which is judged as the object focused in quarantine ( plant , animal , meat , etc .) may be further automatically labeled . as shown in fig1 , the x - ray source 11 is arranged at one side of the object 17 being scanned ; and the detection and collection apparatus 12 , including the detector and the data collector , is arranged at another side of the object 17 being scanned and is used for obtaining transmission data and / or multi - angle projection data of the object 17 being scanned . a data amplifying circuit is included in the data collector , which may work in a ( current ) integrated manner or a pulse ( counting ) manner . a data output cable of the detection and collection apparatus 12 is connected to the controller 14 and the computing unit 15 , and the collected data are stored in the storage according to a trigger command . as will be understood by the skilled in the art , the x - ray source and the detector may utilize a structure without a gantry , i . e ., a statically distributed multi - light source , in other embodiments . in addition , the system according to the above embodiment may also integrate a conventional single - view or multi - view x - ray machine for displaying a 3d image and a single - view or multi - view 2d image synchronously and associating them with each other , which facilitates a human operator for quarantine to merge image reading experiences on the 2d image with a great amount of new information contained in the 3d image , so as to upgrade to a new generation inspection technology stably . fig2 shows an illustrative flowchart of an inspection method according to an embodiment of the present disclosure . as shown in fig2 , in step s 21 , a ct scan is performed on the object being scanned to obtain projection data . for example , the ct scan is performed on the object being scanned by a single - energy or dual - energy ct scan device , so as to obtain multi - angle projection data . in step s 22 , reconstruction is performed based on the projection data to obtain image data reflecting internal features of the object being scanned . for example , the reconstruction of the image may be performed by the computing unit 15 running a program , so as to obtain the 3d image of the object being scanned . in a case of dual - energy ct , the reconstruction is performed to obtain effective - atomic - number images and / or density images . in a case of single - energy ct , the reconstruction is performed to obtain attenuation - coefficient images or ct - number images . in step s 23 , one or more organic and / or contraband parts of the object being scanned are determined . then in step s 24 , display of the determined one or more organic and / or contraband parts are enhanced or highlighted relative to one or more other parts . for example , the computing unit 15 distinguishes the organic part of the object being scanned from a non - organic part of the object being scanned , based on a physical attribute of the object being scanned , such as the attenuation coefficient , basis - material coefficient ( which is obtained by decomposing basis - material in a dual - energy or multi - energy condition ), ct number , density , effective atomic number , etc . in addition , the display unit 16 enhances contrast of the organic part of the object being scanned . for example , most contraband in quarantine has one or more physical attributes different from those of other organics , such as the attenuation coefficient , basis - material coefficient , ct number , density , effective atomic number , etc . identification of contraband in quarantine may be implemented by building a feature database of different substances for comparison in advance . additionally , the ct system can also automatically identify primary contrabands in quarantine , such as fruits , vegetables , meat products , etc . by merging information about physical attributes , shape features , texture features , etc . and , the display unit 16 enhances the contrast of the contraband part of the object being scanned . for example , the computing unit 15 may extend a display grayscale range of an organic and / or contraband part , and use all or a majority of the grayscale range for display of the organic and / or contraband part , improving display fineness of the organic and / or contraband part and contrast between organic and / or contraband parts ; and may use a dedicated color scheme for assigning different types of organic substances with different colors , improving difference between visual effects of different organic substances including contrabands in quarantine . in addition , the computing unit 15 may also filter mixtures and metal substances out so as to avoid influencing an observation line of sight of the human operator , or may maintain the mixtures and the metal substances but enable them not to be rendered so obviously so as to avoid attracting attention of the human operator excessively . for another example , the system may automatically identify primary contrabands in quarantine , such as fruits , vegetables , meat products , etc ., and emphasize them by adding one or more boxes , one or more arrows , by a flashing display , by special coloring , by a sound alarm , by a light alarm , etc . in particular , compared to metal articles , organics , due to their weaker attenuation capability for x - rays , only occupy a upper small part of the grayscale range of the existing ct system , and thus are assigned with orange colors having different saturation degrees as usual , which causes non - obvious display of the organics in the 3d image of the object being scanned , and lower contrast between different types of organics . if there is no definite shape or texture information , the substance type of the organics cannot be particularly identified . due to this , the ct system according to embodiments of the present disclosure may use all or a majority ( e . g . no less than 80 %) of the grayscale range for display of the organics including contrabands in quarantine , e . g ., implementing a mapping of the physical attributes of organics and contrabands in quarantine to a larger grayscale range by a linear or segmentally linear way , or various non - linear ways , and may implement contrast enhancement of organics and contrabands in quarantine by performing global statistics or local statistics on the physical attributes or grayscales , so as to obtain the finest display effect which can present variations of surfaces or internal structures of the organics and / or contrabands . in addition , the ct system according to embodiments of the present disclosure may use a dedicated color palette , which can contain violet , red , and / or yellow with different saturation degrees and various intermediate colors , besides orange with different saturation degrees , enabling organics and contrabands in quarantine with different physical properties to have different hues , thereby further improving the difference in visual effects of different organic substances including contrabands in quarantine . since a human operator is not concern with the mixture and the metal , green and blue which are usually assigned to these two types of substances may also appear in the dedicated color palette . in addition , the 3d image may be pre - segmented , so that the same color is assigned to all of voxels in the same object , in order to improve uniform coloring of the object . in addition , the display unit 15 may hide the one or more non - organic and / or non - contraband parts , of the object being scanned . for example , the computing unit 15 may determine a foreground part of the image data ; and remove pixels in the foreground part whose effective atomic number is larger than a predetermined value , so as to eliminate a shield of the foreground part of the organic part and / or contraband part . for the single - energy ct system , the image processing unit can restore the attenuation coefficient of an arbitrary position within the object , wherein the attenuation coefficient can partly reflect a material attribute of the object . for the dual - energy ct system , the computing unit 15 may also reconstruct the density and the effective atomic number of an arbitrary position within the object , wherein the effective atomic number can accurately reflect the material attribute of the object . the attenuation coefficient or the effective atomic number may be used for removing the mixture and the metal substances , e . g ., rods of a suitcase , in the object being scanned , so as to avoid influencing the observation of the human operator . this is implemented by e . g . comparing the attenuation coefficient or the atomic number value with a predetermined threshold , in which pixels whose attenuation coefficient or atomic number value is higher than the threshold are weakened or not displayed . the attenuation coefficient or the effective atomic number may also be used for selecting the mixture and the metal substance in the object being scanned . by compressing the grayscale range , same color display , gray display or setting a higher transparency or a lower saturation degree , the mixture and the metal substance are not obvious in the 3d image , so that the human operator may focus on observing an organic and / or contraband . the metal rods of the suitcase in the conventional system as shown in fig3 shield the organic and / or contraband part , which adversely affects the judgment of the human operator . however , as shown in fig4 , in the image obtained by the system according to embodiments of the present disclosure , the effect of the metal rods is eliminated , and the display of the contraband in quarantine is enhanced and highlighted , which facilitates the judgment of the human operator . most contraband in quarantine has physical attributes different from those of other organics , such as attenuation coefficient , density , effective atomic number , etc . by building a feature database of different substances for comparison in advance and improving the feature database continuously , the ct system can merge information about physical attributes , shape features , texture features , etc . to automatically identify primary contrabands in quarantine , such as fruits , vegetables , meat products , etc . for an identified contraband in quarantine , it can be emphasized by adding a box , an arrow , by a flashing display , by a special coloring ( e . g . a bright red color ) along with a sound and light alarm of the ct system , etc ., so as to prompt the human operator to focus to have confirmation and manual inspection , which significantly improves the working effect and efficiency of quarantine supervision . fig5 shows a schematic view of an inspection system according to another embodiment of the present disclosure . in the embodiment as shown in fig5 , an object 510 being scanned is placed on a conveying apparatus 540 ( e . g ., a belt ) for inspection , which sequentially passes through a dr system 520 and a dual - energy ct system 530 . in the embodiment as shown in fig5 , the dual - energy ct system 530 and the dr system 520 may be operated synchronously . fig6 shows a schematic structure diagram of the inspection system as shown in fig5 in detail . the inspection device as shown in fig6 includes a dr system on the left and a dual - energy ct system on the right , both of which share a conveying apparatus 630 bearing an object 613 being scanned to move ahead . an x - ray source 611 for dr emits x - rays 612 , which passes through the object 613 being scanned on the bearing mechanism 630 ; a transmission signal is received by a detector module 614 ; an analog signal is converted by a collection circuit 615 into a digital signal , which is transmitted to a controller 617 and a computer 618 , etc . a transmission image of the object 613 being scanned is obtained in the computer 618 , which is stored in a memory or is displayed . in some embodiments , the ray source 611 may include a plurality of x - ray generators , e . g ., distributed x - ray sources including a plurality of x - ray source points . as shown in fig6 , the bearing mechanism 630 bears the object 613 being scanned to go through a scan area between the ray source 611 and the detector 614 . in some embodiments , the detector 614 and the collection circuit 615 are e . g . detectors and data collectors in an integrated module structure , e . g ., a plurality of detectors , for detecting the x - rays passing through an article being scanned so as to obtain the analog signal , and for converting the analog signal to the digital signal , thereby outputting projection data of the object being scanned for the x - rays . the controller 617 controls each part of the whole system to work synchronously . the computer 618 processes and reconstructs data collected by the data collector , and outputs the result . according to the embodiment , the detector 614 and the collection circuit 615 are used for obtaining transmission data of the object 613 being scanned . a data amplifying circuit is included in the collection circuit 615 , which may work in a ( current ) integrated manner or a pulse ( counting ) manner . the collection circuit 615 is connected to the controller 617 and the computer 618 , and the collected data are stored in the computer 618 according to a trigger command . in some embodiments , the detector module 614 includes a plurality of detection units for receiving the x - rays which pass through the object being scanned . the data collection circuit 615 is coupled to the detector module 614 for converting a signal generated by the detector module 614 to detection data . the controller 617 is connected via a control line ctrl 11 to the x - ray source 611 and is connected via a control line ctrl 12 to the detector module 514 which is in turn connected to the data collection circuit 615 , so as to control at least one x - ray generator of the ray source to generate the x - rays which are emitted for passing through the object being scanned as the object moves . in addition , the controller 617 controls the detector module 614 and the data collection circuit 615 to obtain the detection data . the computing unit , such as a processor , in the computer 618 reconstructs the image of the object being scanned based on the detection data . as the object being scanned keeps going ahead , the dual - energy ct system performs the ct scan on the object . an x - ray source 621 for ct emits x - rays 622 , which pass through the object 613 being scanned on the bearing mechanism 630 . as the object moves on , the x - ray source and a detector are rotated for the ct scan , a projection signal is received by the detector module 624 , an analog signal is converted by a data collection circuit 625 into a digital signal , which is sent to the controller 617 and the computer 618 , etc . slice images of the object 613 being scanned are obtained in the computer 618 , which are stored in the memory or are displayed . in some embodiments , the detector module 624 includes a plurality of detection units for receiving the x - rays which pass through the object being scanned . the data collection circuit 625 is coupled to the detector module 624 for converting a signal generated by the detector module 624 to detection data . the controller 617 is connected via a control line ctrl 21 to the x - ray source 621 and is connected via a control line ctrl 22 to the detector module 624 which is in turn connected to the data collection circuit 625 , so as to control two high and low energy x - ray generators of the x - ray source to alternately generate high and low energy x - rays which are emitted for passing through the object being scanned as the object being scanned moves , achieving the dual - energy ct scan . in addition , the controller 617 controls the detector module 624 and the data collection circuit 625 to obtain the projection data . the computing unit in the computer 618 reconstructs the image of the object being scanned based on the projection data , and performs substance identification . as such , the dr system and the ct system operate synchronously . for example , before the ct scan , the dr scan is performed on the object being scanned to obtain the transmitted image ; then the computer determines a position of a suspect contraband based on the transmission image ; and the ct scan device performs the ct scan on at least a part of the object being scanned according to the position determined by the computing unit . in doing so , the ct scan may be performed on only the position of the possible suspect article , which improves the efficiency and accuracy of the inspection . for example , in the embodiments as shown in fig5 and 6 , the object being scanned goes through the dr system and the dual - energy ct system sequentially , and the obtained 2d and dual - energy 3d image data are input to the computer for substance identification . the substance identification system installed in the computer performs substance identification on the object being scanned according to the image data so as to obtain information of different substances , such as the effective atomic numbers , densities , etc ., and tints the 2d image and the 3d image , automatically labeling the article which is judged as the object focused in quarantine ( plant , animal , meat , etc .). in an embodiment of the present disclosure , the substance identification system may hide a part of the object being scanned which is identified to be inorganic , so as to highlight one or more organic components of the object being scanned . in an embodiment of the present disclosure , the substance identification system may further identify and distinguish the organics including contrabands in quarantine more accurately , respectively labeling plants , animals , meat , meat products , etc . with different colors . in addition , the image which has been labeled by substance identification is input to the image processing system in the computer 618 , which in turn highlights the suspect object in quarantine and alarms automatically . in addition , it may be understood by the skilled in the art that the dr scan does not need to be performed before the ct scan , and the ct scan is not necessarily performed according to the position of the suspect contraband determined from the dr image . for example , the dr system may be used as a supplement of the ct system to enable the human operator to continuously use the experiences of reading the 2d image . in addition , the computer may automatically segment the image of the object being scanned which is mixed by multiple kinds of articles into separate articles according to their outline edges , facilitating a human operator to judge the image . alternatively , the computer compares appearances of 3d images of the objects being scanned with templates in the suspect image database ; and highlights suspect objects in connection with results of substance identification . alternatively , the computer automatically identifies shape features of contrabands which are frequently labeled by a user and records the shape features in a database . in an embodiment of the present disclosure , the image processing system in the computer 618 may be configured with a cloud data collection function , e . g ., be connected to a cloud server for uploading the inspection data to the cloud server . the user may authorize different image inspection rights of the cloud server to different inspectors , or enable the image inspection rights of the cloud server to access to another management system . although the inspection devices for quarantine according to the present disclosure is described in connection with particular embodiments , the skilled in the art may apply the inspection devices to other fields for solving the inspection problem in other industries . therefore , various modifications , improvements , expansions and applications which can be made by those skilled in the art based on the embodiments of the present disclosure are to be encompassed by the scope of the present disclosure as defined by the claims and their equivalents .
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the ordered sequence of elements which form the data is represented in an array derived from an analogue waveform . although the data may be a function of more than ne variable , in this invention the data is “ viewed ” or ordered in dependence on one variable . thus , the data can be stored as an array . the array is a one dimensional array , a 1 × n matrix . data in a one dimensional array is also referred hereinbelow as one dimensional data . the values of the data contained in the array may be a sequence of binary values , such as an array of digital samples of an audio signal . one example of the anomaly recognition procedure is described below in connection with fig1 - 8 , where the neighbouring elements of x 0 are selected to be within some one - dimensional , distance of x 0 . ( distance between two elements or sample points in this example may be the number of elements between these points ). detection of anomalies in data represented in a one - dimensional array ( eg : time resolved data or audio data or data from an acoustic source ) concerns instructing a computer to identify and detect irregularities in the array in which the set of data is arranged . there are various reasons why a particular region can be considered as ‘ irregular ’ or ‘ odd ’. it could be due to its odd shape or values when compared with the population data ( the remainder of the data ); it could be due to misplacement of a certain pattern in a set of ordered pattern . put more simply , an anomaly or irregularity , is any region which is considered different to the rest of the data due to its low occurrence within the data : that is , anomalous data will have one or more characteristics which are not the same as those of the majority of the data . in the specific examples given in the description of the invention , the algorithm is tested mainly on audio data with the discrete samples as the one - dimensional data . however , the invention is limited in no way to audio data and may include other data that can be represented in a one dimensional array derived from a waveform having a plurality of cycles . the software which , when run on a computer implements the present invention , “ one dimensional anomaly detector ”, is written in curl language using curl surge lab ide beta 5 — build : 1 . 6 . 0 release / englewood / 0 - 1237 : copyright © 1998 - 2001 and may not be compatible with future releases of curl . the results shown in this description were produced by the software mentioned above . again , however , the invention is not limited to software written using this particular language and may be implemented using other computer languages . this algorithm of the present invention works on the basis of analysing samples . a further algorithm described later as the “ cycle comparison algorithm ” compares cycles defined by certain zero crossings . the method for the sample analysis algorithm will now be described with reference to fig1 to 8 . the components shown in fig4 include a data source 20 and a signal processor 21 for processing the data . the data is either generated or pre - processed using cool edit pro — version 1 . 2 : cool edit pro is copyrighted © 1997 - 1998 by syntrillium software corporation . portions of cool edit pro are copyrighted © 1997 , massachusetts institute of technology . the invention is not limited in this respect , however , and is suitable for data generated or preprocessed using other techniques . fig4 also shows a normaliser 22 . the data is normalised by dividing all values by the maximum modulus value of the data so that the possible values of the data range from − 1 to 1 . a central processing unit ( cpu ) 24 , an output unit 27 such as a visual display unit ( vdu ) or printer , a memory 25 and a calculation processor 26 . the memory 25 includes stores 250 , 254 - 256 , registers 251 , 257 - 259 and a mismatch counter 253 and a comparison counter 252 . the data and the programs for controlling the computer are stored in the memory 25 . the cpu 24 controls the functioning of the computer using this information . with further reference to fig1 - 5 , a data stream to be analysed is received at the input means 23 and stored in a digital form in a data store 250 , as a one dimensional array , where each datum or data element has a value attributed to it . an original sample of data , x 0 , ( a reference test element ) is selected ( step 1 ) from the one dimensional array , and its value is stored in an original sample register 251 . a mismatch count , cx , stored in a mismatch counter 253 , and a count of the number of data comparisons , ix , stored in a comparison counter 252 , are both set to zero ( step 2 ). then a random neighbourhood , x 1 , x 2 , x 3 , ( test elements ) which comprises a number of data in the vicinity of the original sample ( reference test element ), x 0 , of a certain size ( parameter : neighbourhood size ) is selected from neighbouring samples ( step 5 ). the neighbourhood is chosen to lie within a particular range ( or “ neighbourhood range ”) ( parameter : radius ) from the original sample , x 0 . then , a second reference sample , y 0 , is randomly chosen anywhere within a certain domain or range ( parameter : comparison domain ) in the set of data ( step 6 ). the neighbourhood , ( i . e . test elements ) x 1 , x 2 , x 3 selected around the original sample , x 0 together with the original sample , x 0 , have a certain configuration which makes a ‘ pattern ’. the neighbourhood , y 1 , y 2 , y 3 , ( comparison elements ) selected around the random reference sample , ( the reference comparison element ) y 0 , together with the reference sample , y 0 , are chosen to have the same configuration , or pattern , as the neighbourhood around the original sample . in the embodiments shown in fig1 and 3a and 3 b , the values of the data in the original sample ‘ pattern ’ ( test group ), x 0 , x 1 , x 2 , x 3 are then compared by calculation processor 26 , with the values of the data in the reference sample ‘ pattern ’ ( comparison group ), y 0 , y 1 , y 2 , y 3 , defined by the reference sample together with its neighbouring samples ( step 8 ). if the absolute value of the difference , | x 0 − y 0 |, | x 1 − y 1 |, etc , between two respective samples or elements is more than a certain threshold ( parameter : threshold ), then it is considered as being ‘ different ’. if one or more samples in the original sample pattern are different from the reference sample pattern , then it is said that a mismatch occurred . the choice of the threshold can optionally be varied , and may depend on the range of values within the set of data . in the embodiment shown in fig2 , this part of the algorithm is carried out according to similar principles but different values are compared . this is described below in more detail with reference to fig2 and 6 . in all other respects , however , the algorithm shown in fig2 is the same as those shown in fig1 and 3a and 3 b . further , with reference to fig1 - 5 , when a mismatch occurs , the mismatch counter , cx , for the original sample , x 0 , is incremented ( step 10 ). in this case the neighbourhood ( test group ) around the original sample ( reference test element ) is kept , i . e ., the original sample pattern is kept , and the program returns to step 6 to choose another random 2 nd reference sample , y 0 , for the same comparison process . when a match occurs the mismatch counter , cx , is not increased . the program returns to step 5 which creates a new neighbourhood around the original sample , whose configuration has a new pattern , before moving on to choose another random 2 nd reference sample ( step 7 ) for the comparison step ( step 8 ). for each original sample , x 0 , a certain number of comparisons , l , are made which result in a certain number of mismatches and matches . the total number of mismatches plus matches is equal to the number of comparisons ( step 11 and step 14 ). the number of comparisons can be varied and will depend on the data to be analysed and the processing power available . also , the greater the number of comparisons , the greater the accuracy of the anomaly detection . once the comparison step ( step 8 ) has been done the certain number of times , l , the program returns to step 1 to select a different original sample , x 0 and the mismatch counter value , cx , and the number of comparisons , l , is output for original sample , x 0 ( step 15 ). whether the original sample or reference test element , x 0 , is judged to be an anomaly will depend on the number of mismatches in comparison to the number of comparisons , l . the normalised anomaly scores for each original sample , x 0 , are obtained by dividing the mismatch counter , cx , for each sample , x 0 , by the number of comparisons , l , which is also equal to the maximum mismatch count , so that the anomaly score ranges from zero to one , with zero being 0 % mismatch and one being maximum mismatch . fig5 shows an example of a one - dimensional data with each box representing a sample . sample marked ‘ x ’ is the original sample and sample marked ‘ y ’ is the randomly chosen reference sample . the samples , x 1 , x 2 , x 3 , are the neighbourhood samples whose configuration make up the original sample pattern . in the example shown in fig5 , the radius ( or neighbourhood range ) is equal to 3 , the neighbourhood size is equal to 3 and the comparison domain is equal to the region where y is chosen . a mismatch occurs if | xn − yn |& gt ; threshold , where , n , the neighbourhood size takes a value from 1 to 3 . as shown in fig5 , the first sample which could be scored is the sample with a distance ‘ radius ’ away from the start and the last sample to be scored is the sample with a distance ‘ radius ’ away from the end . by way of further explanation of the above example of comparison , a numerical example is set out in table 1 . in the examples given , two of the samples mismatch . as long as one or more samples in the neighbourhood mismatches , the mismatch counter for the original , in this example , x 0 , will be incremented by one . with reference to fig2 and 6 , the inventor has noticed that when the waveform becomes complex or the sampling rate is increased the number of mismatches increases relative to the number of matches . this causes the scores to become saturated . as the complexity of the waveform increases the probability of picking a random reference y sample that matches the original sample x decreases . similarly , as the sampling rate is increased , the probability of finding a match decreases . the increased probability of having a mismatch causes saturation of the scores . to alleviate the problem of score saturation , a ‘ hill climbing ’ strategy has been developed to improve the likelihood of a match . the strategy is called “ hill climbing ” because when a mismatch is found , the waveform is “ climbed ” in both directions along the ordered set of data elements until a match is found . fig2 is a flow diagram showing the steps an algorithm including the “ hill climbing ” process and how they fit in with the steps of the sample analysis algorithm described above . the hill climbing process is shown within the dotted line 20 . it is seen in fig2 that the ‘ hill climbing ’ process includes some additional steps to the sample analysis algorithm shown in fig1 . the “ hill climbing ” process is explained with reference to fig2 and 6 . first the original sample , marked x , is chosen ( step 1 ). the neighbourhood samples , coloured medium dark grey in fig8 and shown in the neighbourhood of the original sample x , are then selected either randomly ( step 5 ) or reused from the previous comparison if a mismatch occurred previously ( refer to step 6 ). in the example shown in fig8 , the neighbourhood size ( parameter : neighbourhood size ) is three , hence three neighbouring samples are selected . and the furthest distance from which a neighbouring sample can be selected is the radius ( parameter : radius ), which is equal to four in the example in fig8 . these samples make up the original “ pattern ” ( step 5 ). next , a reference sample , marked y , is randomly chosen from anywhere in the data within a certain domain ( step 6 ) ( parameter : comparison domain , not shown in fig8 , but shown for example , in fig5 ). then the reference sample , y , is compared with the original sample , x ( step 22 ). it is determined whether the is a mismatch between the reference sample and original sample ( step 24 ). in the example shown in fig8 , the reference sample y lies outside the threshold ( parameter : threshold ) region of the original sample x , hence it does not match the original sample x . therefore , in the case of this mismatch the next step ( steps 26 , 28 , 30 and 32 ) is to ‘ hill climb ’ the reference sample by searching the samples within a search radius around y for a sample that matches with the original sample x . this searching is done one sample at a time in both directions along the one dimensional array ( step 30 ). in fig8 the sample marked a is the first sample near sample y that matches the original sample x as it falls within the threshold region . next , the neighbourhood samples of x ( coloured medium dark grey ) are compared with the corresponding neighbourhood samples of a ( step 28 ). if they match ( step 32 ), then the mismatch counter is not increased and the process is continued with the next comparison by selecting another random reference sample ( step 6 ). in the example shown in fig8 , the corresponding neighbourhood samples x and a do not match ( step 32 ), but in spite of this and in contrast to the steps shown in fig1 , the mismatch counter for sample x is not increased . instead of increasing the mismatch counter , the ‘ hill climbing ’ process is continued as described above . eventually , sample marked b is selected and found to match the original sample x . then the neighbourhood samples of x ( coloured medium dark grey ) are compared with the corresponding neighbourhood samples of b ( step 28 ). if they match one another , then the next comparison is continued with by selecting another random reference sample ( step 6 ). in the example shown in fig8 they do match , so the mismatch counter is not increased , and the process is continued with the next comparison by selecting another random reference sample . it can be seen by reference to fig8 and the explanation above , the ‘ hill climbing ’ process stops when one of two things happen . the process stops when the algorithm finds a matching “ pattern ”. alternatively , the other way the ‘ hill climbing ’ process stops is when the algorithm fails to find any matching “ pattern ” within a certain search radius for the ‘ hill climbing ’ ( illustrated in fig8 ). the radius being set to be equal to the radius of the original sample x &# 39 ; s neighbourhood ( parameter : radius ). the algorithm searches all samples within the search radius ( step 26 ). when the algorithm fails to find any matching “ pattern ” in the neighbourhood , then the mismatch counter for original sample x is increased ( step 10 ). therefore , the mismatch counter for the original sample only increases when there is no matching pattern within the ‘ hill climbing ’ search radius from the randomly selected reference sample . by only increasing the mismatch counter when there are no matching “ patterns ” in the neighbourhood of the reference sample , the constraints imposed on the search for a match are relaxed . thus , the probability of finding a match are increased . this process is successful in eliminating the problem of saturation of the scores observed by the inventors . reference is made to fig1 to 15 which show the results achieved . with reference to fig6 , the inventor has found , that in addition to the problem of saturation another problem exists . due to the effects of constant sampling rate , samples which lie on a larger gradient are more distant apart compared to samples which lie on a small gradient . this is because a constant sampling rate means samples are taken at equal intervals of time . when the waveform changes rapidly , i . e . has a large magnitude of gradient , the difference between two subsequent sample values is therefore large . when the waveform has a small gradient , there is only a slight difference between two subsequent sample values . see fig6 for illustration . the effect of a static threshold or mismatch criterion while comparing samples is as follows : samples which lie on the larger gradient will be discriminated and have high mismatch scores as they are less likely to match with their neighbours . this will result in an artificially high mismatch score for data lying on a steep gradient . similarly , data lying on a shallow gradient will score too low . the inventor has found that this detrimental effect can be removed by using a dynamic threshold , which takes into account the local gradient of the samples . the dynamic threshold is an adaptive variable threshold that is dependent on the sample &# 39 ; s local gradient . in sampling an analogue waveform ( see fig2 ) discrete samples are taken over equal time intervals . each sample acts as a representative for the particular interval . in this interval the waveform however assumes different values . the local gradient can be defined as the difference between the boundary values of the interval and is a measure of the variation in the interval ( the intervals will be chosen smaller than any periodicity of the waveform ). in this way , the sample interval is set to have a non - dimensional value of 1 . by defining a dynamic threshold which increases with increasing local gradient , for example by adding a term proportional to the gradient as above to a static threshold value , the mismatch criterion is increased for steeper gradients and sampled values may thus differ more before they mismatch . for small gradients , samples are mismatched if they differ by a smaller threshold amount . the mismatch criterion or threshold is thus adaptive to the particular environment of a sample . ( parameter : threshold ). the static threshold can be determined to suit the particular data and sensitivity required . similarly , the particular form of the gradient responsive term may vary according to the sampled data and could be determined empirically . ( obtaining a dynamic threshold is optional , and a static threshold is possible instead ). in fig7 , the upper spectrum shows the result with striations due to discrimination on large slopes using the static threshold while the spectrum below shows a more uniform attention score as a result of dynamic thresholding . in the above example , the data comprises an analogue waveform which is sampled at regular intervals , although it will be appreciated that the intervals need not be regular . fig2 shows the steps taken in the case where an analogue waveform is sampled , and includes the step 3 of determining the gradient at the original sample , x 0 , and step 4 of determining the dynamic threshold . in step 8 , the corresponding neighbourhood samples are compared with the dynamic threshold . fig3 shows the steps taken in the case of an array of digital data , and includes step 16 of determining the values of samples neighbouring the original sample , and step 17 determining , the dynamic threshold . in step 8 , as for the case of an analogue waveform , the corresponding neighbourhood samples are compared with the dynamic threshold . the gradient determination step and the step of determining the values of samples neighbouring the original sample are carried out by the calculation processor 26 , and the values determined are stored in the register 259 , where they are accessible as the dynamic threshold value for use in the comparison step ( step 8 ). both the “ hill climbing ” process and the dynamic threshold process may be implemented independently to one another as shown in fig2 , 3 a and 3 b . alternatively , they may be implemented in combination with each other . in particular , the “ hill climbing ” process described above with reference to fig2 and 6 is suitable for combination with either of the dynamic threshold embodiments shown in fig3 a and 38 . fig9 to 15 show results 1 to 7 , respectively . the results shown in these figures are produced after the implementation to the sample analysis algorithm described with reference to fig1 and 5 of a combination of the “ hill climbing ” shown in fig2 and 6 and the dynamic threshold processes shown in fig3 a and 3b described above . the comparison domain for these results is the entire data length . the results show in the lower part of the diagram the input data for analysis . the upper portion of the diagram shows the mismatch scores achieved for each sample using the sample analysis algorithm plus the “ hill climbing ” and dynamic threshold modifications . in the upper portion , an anomaly is identified as being those portions having the highest mismatch scores . the results shown are for audio signals . however , the present invention may also be applied to any ordered set of data elements . the values of the data may be single values or may be multi - element values . result 1 shown in fig9 shows a data stream of 500 elements having a binary sequence of zeros and ones . the anomaly to be detected is a one bit error at both ends of the data . in this example , the number of comparisons was 500 , the radius was equal to 5 , the neighbourhood size was equal to 4 and the threshold was equal to zero . the peaks in the upper portion of the graph show a perfect discrimination of the one bit errors at either end of the datane array . result 2 shown in fig1 shows data stream having the form of a sine wave with a change in amplitude . in this example , the number of comparisons was 500 . the radius was equal to 5 , the neighbourhood size was equal to 4 and the threshold was equal to 0 . 01 . the peaks in the upper portion of the graph show a perfect discrimination of the anomaly . the highest mismatch scores being for those portions of the data stream where the rate of change of amplitude is the greatest . result 3 shown in fig1 shows a data stream having the form of a sine wave with background noise and burst and delay error . in this example , the number of comparisons was 500 , the neighbourhood size was equal to 4 and the threshold was equal to 0 . 15 . the peaks in the upper portion of the graph show a good discrimination of the anomalies present . result 4 shown in fig1 shows a data stream having the form of a 440 khz sine wave that has been clipped . the data has been sampled at a rate of 22 khz . in this example , the number of comparisons was 1000 , the radius was equal to 75 , the neighbourhood size was equal to 4 and the threshold was equal to 0 . 15 . the peaks show a good discrimination of the anomalies . further , it is commented that the gaps in between the peaks can be eliminated by selecting a larger neighbourhood size . result 5 shown in fig1 shows a data stream having the form of a 440 khz sine wave that has been clipped . the data has been sampled at a rate of 11 khz . in this example , the number of comparisons was 1000 , the radius was equal to 10 , the neighbourhood size was equal to 5 and the threshold was equal to 0 . 15 . the peaks show a good discrimination of the anomalies . result 6 shown in fig1 shows a data stream having the form of a 440 khz sine wave including phase shifts . the data has been sampled at a rate of 44 khz . in this example , the number of comparisons was 1000 , the radius was equal to 50 , the neighbourhood size was equal to 4 and the threshold was equal to 0 . 1 . the peaks show good discrimination of the anomalies . result 7 shown in fig1 shows a data stream having the form of a 440 khz sine wave including phase shifts . the data has been sampled at a rate of 44 khz . in this example , the number of comparisons was 1000 , the radius was equal to 50 , the neighbourhood size was equal to 4 and the threshold was equal to 0 . 1 . the peaks show near perfect discrimination of the anomalies . an error correction system is now described with reference to fig1 - 20 , which has application to the present invention . having used the anomaly detection system previously described to identify regions of anomaly in a waveform , error correction is provided to remove the detected errors . from the attention map produced as described above , a suitable filter coefficient is set ( parameter : filter coefficient ) so that only the anomalous region remains in the map before passing the data to an error correction algorithm . the error correction algorithm used depends on the algorithm used to detect the anomaly . for example , a cycle comparison detection algorithm is described further below which is for use together with a cutting and replacing correction algorithm . it has been found that a shape learning error correction algorithm yields better results with the anomaly detection algorithm described above in this application . the shape learning algorithm is described below . the shape learning error correction described below may be implemented directly . the success of the error correction however , is dependent primarily on being able to pinpoint the anomaly with confidence , which is the function of the detection algorithm . the error correction method described below deals with the error by taking a closer look at what is happening when the detection algorithm does the comparison described above . fig1 shows that due to the nature of the detection algorithm , the first and last samples in a high score region are not amongst the erroneous samples . the first sample and last sample that have high score are a distance of ‘ radius ’ ( parameter : radius ) away from the first and last erroneous sample . this is because the first neighbourhood that may select the erroneous sample as one of the neighbourhood samples normally lies a distance ‘ radius ’ away . to explain the details of how the algorithm works the example given in fig1 is referred to . a region of anomaly is indicated with high scores but the actual samples that are erroneous have lower scores than the indicated samples . the algorithm does the error correction routine starting from the left - hand side towards the right - hand side . first , as shown in fig1 , it takes the first sample from the left with a high score and creates two counters for each sample within the radius of the first sample . all samples , x 0 to x 6 , are then compared with other parts of the data . this comparison method is similar to the detection algorithm and uses the two parameters from the detection algorithm , which are the number of comparisons ( parameter : number of comparisons ) and the static threshold value ( parameter : threshold ). x is considered as the original sample . this comparison method uses the dynamic thresholding that is used in the detection algorithm described above . for each comparison of the neighbourhood , x 0 to x 6 , with other parts of the data , if the number of samples in the neighbourhood that mismatches is less than or equal to a value called ‘ range ’ then certain information will be logged in the counters for those samples that mismatch , refer to fig1 . the value ‘ range ’ is given by the parameter “ proportion to fix at one go ” ( parameter : proportion to fix at one go ) multiplied by the ‘ radius ’ ( parameter : radius ) rounded to the nearest integer . the parameter proportion to fix at one go can take a value between 0 and 1 . hence the value ‘ range ’ takes a minimum value of 1 and maximum value of ‘ radius ’. two examples are given in fig1 . when x and y is compared , only one sample mismatches , which is less than the value of ‘ range ’. so , the ‘ mismatch frequency ’ counter is increased for the sample ( s ) that mismatch and the ‘ total mismatch value ’ counter is also updated by adding it with the value of the difference between x and y ( the mismatch value ). however , when x and z is compared , four samples mismatch , which is more than the value of ‘ range ’. if this happens , no information is logged . the counter values are not altered . at the end of the comparison process , the ‘ mismatch frequency ’ counter holds the value indicating how often each of the samples x 0 to x 6 mismatches , and the ‘ total mismatch value ’ counter holds the sum of all the mismatch difference values that have occurred for each of the samples x 0 to x 6 . from these two pieces of information , we can now decide which sample ( s ) are always causing a mismatch and how much to adjust them so that they will match more often . this can be done by first getting a mean value for the mismatch frequencies of all the samples . then any sample ( s ) that have a larger mismatch frequency than the mean value will be considered needing adjustment . the amount to adjust each sample is given by the average value of the mismatch values . this average value is obtained by dividing the value in the ‘ total mismatch value ’ counter by the value in the ‘ mismatch frequency ’ counter of the sample ( s ) that need to be adjusted . the sample ( s ) are then adjusted and the new attention score for the sample x 0 is obtained using the standard detection algorithm . if the new attention score is less than the previous score , the adjustments are kept , otherwise the adjustments are discarded . the algorithm repeats the process again for neighbourhood xn and does the adjustments again as long as the attention score for x 0 decreases . if the attention score for x 0 does not decrease after a certain number of times ( parameter : number of tries to improve score ) consecutively , the algorithm moves on the next sample to be chosen as the original sample . the next sample to be chosen lies ‘ range ’ number of samples to the right of the previous original sample . fig1 illustrates how the algorithm uses the ‘ range ’ value as described above . as shown in fig1 , for each new step the algorithm takes , the new original sample x 0 lies ‘ range ’ samples in front of the previous original sample . this also means that the new neighbourhood will contain ‘ range ’ number of erroneous samples , assuming that all the errors in the previous neighbourhood are corrected perfectly . because of this , when the neighbourhood is compared to an identical reference neighbourhood elsewhere in the data , it is expected that only ‘ range ’ samples to mismatch while the rest of the samples should match . if more than ‘ range ’ samples mismatch , this means that the good samples are also mismatching , hence the reference neighbourhood that it compared with is unlikely to be identical to the original neighbourhood and therefore no information at all is logged . the algorithm is called shape learning because it tries to make adjustments to the erroneous samples so that the overall shape or recurring pattern of the waveform is preserved . as the total number of samples is the same before and after the error correction , the algorithm works fine if the error is not best fixed by inserting or removing samples . if this is the case , then the algorithm will propagate the error along the waveform . this is due to the error correction routine which starts from the left of the ‘ high score ’ region and adjusts the samples towards the right . fig2 , result 8 shows a good example of the phase shift error described above . in fig2 , the lower part of the diagram shows the input data for analysis . the upper portion of the diagram shows the results of the analysis where the y axis in the upper portion shows the mismatch value . in the upper portion , an anomaly is identified as being those ( lighter ) portions having the greatest mismatch values . it is noted that result 8 is shown to illustrate the phase shift . the error recognition has been achieved not using the algorithm described in this application , but using the cycle comparison algorithm described further below . fig2 shows a flow chart outlining the steps of the shape learning error correction described above . firstly , the first “ high score ” original sample , x , and its neighbourhood are obtained , step 100 . next , counters are created for each of the samples in the neighbourhood , step 102 . a random reference sample and its neighbourhood are also selected , step 104 . having done this , the entire neighbourhood is compared , step 106 , and it is determined whether more than the “ range ” of samples mismatch . if the answer is “ yes ”, the comparison counter is increased , step 114 , and the algorithm returns to step 104 to select a random reference sample and its neighbourhood . if the answer is “ no ”, the next step is to obtain the difference , the mismatch value , dn , for the sample or samples that mismatch , step 108 . then the mismatch frequency counter is increased and the mismatch value , dn is added to the mismatch value counter for the sample or samples that mismatch , step 110 . next , it is determined whether the comparison counter is equal to the number of comparisons , step 112 . if the answer is “ no ” the algorithm returns to step 114 , and the comparison counter is increased before the algorithm returns to step 104 to select a random reference sample and its neighbourhood . if the answer is “ yes ”, the mean of the mismatch frequency counters is obtained , step 116 . subsequently , the sample or samples whose mismatch frequency counter is more than the calculated mean in step 116 , are identified , step 118 . the identified sample or samples are adjusted by their average mismatch value , step 120 . having done this , a new attention ( mismatch ) score is obtained for the original sample using the sample analysis detection algorithm described above , step 122 . the new attention ( mismatch ) score is compared with the old ( first ) attention score , step 124 . if it is lower than the old score , the adjustments made are kept and the failed counter is reset . if the new score is not lower , the adjustments made are discarded and the failed counter is increase , step 126 . next , it is determined whether the failed counter is equal to the number of tries to fix the error , step 130 . if the answer is “ no ”, the algorithm returns to step 104 to select a random reference sample and its neighbourhood . if the answer is “ yes ”, the next original sample , x , and it neighbourhood is obtained , step 132 , before the algorithm returns to step 102 , to create counters for each of the samples in the neighbourhood . depending on the type of error and the original waveform , certain methods could prove to be more efficient in removing the error . the shape learning algorithm described above , requires large amounts of processing time due to its looping construct . but nevertheless it is the preferred way of removing the error as it possesses the ability to predict the shape of the waveform . however , on occasion it propagates certain errors as it does not alter the total number of samples . cutting or replacing as described in our copending unpublished application ( ipd reference a30176 ) proves to be the best method in such cases . further , it is noted that in any case the performance of the error correction is dependent on the performance of the anomaly detection algorithm . a detection algorithm of the present invention has been demonstrated to be very tolerant to the type of input data as well as being very flexible in spotting anomalies in one - dimensional data . therefore there are many applications where such detection method may be useful . in the audio field , such a detection algorithm may be used as a line monitor to monitor recordings and playback for unwanted noise as well as being able to remove it . it may also be useful in the medical field as an automatic monitor for signals from a cardiogram or encephalogram of a patient . apart from monitoring human signals , it may also be used to monitor engine noise . like monitoring in humans , the output from machines , be it acoustic signals or electrical signals , deviate from its normal operating pattern as the machine &# 39 ; s operating conditions vary , and in particular , as the machine approaches failure . the algorithm may also be applied to seismological or other geological data and data related to the operation of telecommunications systems , such as a log of accesses or attempted accesses to a firewall . as the detection algorithm is able to give a much earlier warning in the case of systems that are in the process of failing , in addition to monitoring and removing errors , it may also be used as a predictor . this aspect has application for example , in monitoring and predicting traffic patterns . a further embodiment , the referred to as the “ cycle comparison ” is now described . detection of anomalies in an ordered set of data concerns instructing a computer to identify and detect irregularities in the set . there are various reasons why a particular region can be considered as ‘ irregular ’ or ‘ odd ’. it could be due to its odd shape or values when compared with the population data ; it could be due to misplacement of a certain pattern in a set of ordered pattern . put more simply , an anomaly or irregularity , is any region which is considered different due to its low occurrence within the data . in the specific examples given in the description of the invention , the algorithms are tested mainly on sampled audio data with the discrete samples as the one - dimensional data . however , the invention is limited in no way to audio data and may include , as mentioned above other data , or generally data obtained from an acoustic source , such as engine noise or cardiogram data . this algorithm of the present invention works on the basis of identifying and comparing cycles delimited by positive zero crossings that occur in the set of data . the inventors have found however , that the sample analysis algorithm as described above may start to fail when the input waveform becomes too complex . although the ‘ hill climbing ’ method described above has been implemented , saturation is still occurs for more complex waveforms . saturation is an effect observed by the inventors when waveforms become complex or the sampling rate is increased . in these circumstances , the number of mismatches increases relative to the number of matches without necessarily indicating an anomaly . as the complexity of the waveform increases the probability of picking a random reference y sample that matches the original sample x decreases . similarly , as the sampling rate is increased , the probability of finding a match decreases . the increased probability of having a mismatch causes saturation of the scores . also , using the “ hill climbing ” method the processing time required to analyse a 1 s length of audio data sampled at 44 khz sampling rate uses a lot of processing time , requiring up to 220 s of processing time on a pii266 mhz machine . the method for the cycle comparison algorithm will now be described with reference to fig2 to 28 . the components shown in fig2 include a data source 20 and a signal processor 21 for processing the data , a normaliser 22 and an input 23 . the data is either generated or pre - processed using cool edit pro — version 1 . 2 : cool edit pro is copyrighted © 1997 - 1998 by syntrillium software corporation . portions of cool edit pro are copyrighted © 1997 , massachusetts institute of technology . the invention is not limited in this respect , however , and is suitable for data generated or preprocessed using other techniques . also shown in fig2 is a central processing unit ( cpu ) 24 , an output unit 27 such as a visual display unit ( vdu ) or printer , a memory 25 and a calculation processor 26 . the memory 25 includes stores 250 , 254 - 256 , registers 251 , 257 - 259 and a mismatch counter 253 and a comparison counter 252 . the data and the programs for controlling the computer are stored in the memory 25 . the cpu 24 controls the functioning of the computer using this information . with reference to fig2 - 28 where indicated , a data stream to be analysed is received at the input means 23 . firstly , the data is normalised by normaliser 22 by dividing all values by the maximum value of the data so that the possible values of the data range from − 1 to 1 . the normalised data is stored in a digital form in a data store 250 , as a one dimensional array , where each datum has a value attributed to it . then the algorithm identifies all the positive zero crossings in the waveform ( step 0 ). a mean dc level adjustment ( not shown ) may also be made before the positive zero crossings are identified , to accommodate any unwanted dc biasing . the positive zero crossings are those samples whose values are closest to zero and if a line were drawn between whose neighbours , the gradient of the line would be positive . for example , of the sequence of elements having the following values : − 1 , − 0 . 5 , 0 . 2 , 0 . 8 , 1 , 0 . 7 , 0 . 3 , − 0 . 2 , − 0 . 9 , − 0 . 5 , − 0 . 1 , 0 . 4 , the positive zero crossings would be 0 . 2 and − 0 . 1 . fig2 shows a waveform with the positive zero crossings highlighted . they may not always lie on the zero line due to their sampling position . the samples which is closest to the zero line , in other words have the smallest absolute value , are always chosen . a full cycle , as shown for example in fig2 , is made up of the samples lying between two consecutive positive zero crossings . in the example shown the cycles are delimited with respect to the positive zero crossing . however , the cycles are not limited in this respect and may be delimited with respect to other criteria , such as negative zero crossings , peak values , etc . the only limitation is that preferably , both the test cycle and the reference cycle are selected according to the same criteria . with reference to fig2 , the next step ( step 1 ) is to choose a cycle beginning from the start of the data , to be the original cycle , x 0 . the values of the data of the samples in the original cycle , x 0 , are stored in the original cycle register 251 . a mismatch count , cx , stored in a mismatch counter 253 , and a count of the number of data comparisons , ix , stored in a comparison counter 252 , are both set to zero ( step 2 ). the next step ( step 3 ) is to randomly pick another cycle , y 0 , elsewhere in the waveform , within a certain domain ( parameter : comparison domain ), to be the comparing reference cycle . usually , the original cycle and the reference cycle would come from data having the same origin . however , the invention is not limited in this respect . for the cases where the waveform has a form where the comparison domain may be large , for example , waveforms , for example derived from a running engine , which do not vary dramatically over time , the algorithm may be used to compare a test cycle from data from one source with a reference cycle from a second source . for cases , where the comparison domain may not be too large , for example , musical data which varies greatly over a short period of time , comparing a test source with a second reference source of data may not be so satisfactory . reference is made to result 10a shown in fig3 . returning to fig2 , the test cycle and the comparison cycle are then compared ( steps 4 , 5 , 6 , 7 , 8 ) in order to obtain a mismatch score for the reference cycle , y 0 , with respect to the original cycle , x 0 . as seen in fig2 and 25 , each cycle , x 0 , y 0 includes a plurality of data samples or elements each having a value , sj , sj ′, respectively . each value having also a respective magnitude . the comparison of the cycles includes a series of steps and involves determining various quantities derived from the data in the cycles . the calculation processor 26 carries out a series of calculations . the derived quantities are stored in registers 257 , 258 and 259 . firstly , an integration value is obtained for the original cycle and the reference cycle . this , may for example , be the area of the original cycle , sigma | sj |, and the area of the reference cycle , sigma | sj ′| ( step 4 ). with reference to fig2 , the area of a cycle is defined by the sum of the magnitudes of the individual samples in the cycle . due to the definition of the area , which is the sum of the samples in the cycle , the area of identical cycles may vary to a great extent if the sampling rate is low and the waveform frequency is large . hence , while using the cycle comparison algorithm , it is preferable to use at least 11 khz sampling frequency for acceptable accuracy and sensitivity . with reference to fig2 , which shows an example , the next step ( step 5 ) is to derive a quantity which gives an indication of the extent of the difference between the area and the shape of the reference cycle , y 0 , with respect to the original cycle , x 0 . this is defined by the sum of the magnitudes of the difference between each of the corresponding samples in the original cycle and the reference cycle , sigma (¦ sj - sj ′¦). fig4 shows three graphs . the first graph 40 shows the original cycle , x 0 , having samples , sj , having values s 1 to s 14 . the area of the original cycle is equal the sum of the magnitudes of the values , s 1 to s 14 : that being sigma | sj |. the second graph 42 shows the reference cycle , y 0 , having samples , sj ′, having values s 1 ′ to s 14 ′. the area of the reference cycle is equal to the sum of the magnitudes of the values , s 1 ′ to s 14 ′: that being sigma | sj ′|. the third graph 44 shows the difference the cycles as defined by sigma (| sj − sj ′|). the next step ( step 6 ) is to establish whether both cycles have the same number of samples , sj , sj ′. if the number of samples in the cycles are not equal , the shorter cycle is padded with samples of value zero until both the original and reference cycles contain the same amount of samples . fig5 shows an example of the padding described above with respect to step 6 shown in fig1 . in fig2 , cycle 1 has nine samples while cycle 2 only has 6 samples . in order to do a comparison , both cycles are made equal in sample size . this is achieved by padding the cycle having the fewer number of samples . in the example shown in fig2 , cycle 2 is padded with additional samples of value zero until it becomes the same size as the larger cycle , cycle 1 in this case . the quantities derived in the steps described above are used to determine for each comparison of an original cycle with a reference cycle a “ measure of difference ” ( step 8 ), which is a quantity that shows how different one cycle is from the other . maxarea is the largest area of a cycle in the entire comparison domain and miniarea is the smallest area of a cycle in the entire comparison domain . largerareaoftwocycles is the bigger area of the original cycle and the reference cycle . the inventors have derived the definition of the “ measure of difference ” as shown above for the following reasons . with reference to fig2 , the first denominator , largerareaoftwocycles , is neutral to logarithmic increments of the cycle amplitude . this means that every time a cycle is compared against another geometrically similar cycle which is double its amplitude , the measure of difference is the same . for example when a sine cycle of amplitude ‘ x ’ is compared with another sine cycle of amplitude ‘ 2 ×’, the measure of difference is ‘ d ’. hence when a sine cycle of amplitude ‘ x ’ is compared with another sine cycle of amplitude ‘ ½x ’, the measure of difference would still be ‘ d ’. further , with reference to fig2 , the second denominator , | maxarea − minarea |, is a normalizing term for the quantity areadifference which is neutral to linear increments of the cycle amplitude . this means that if the amplitude of a geometrically similar cycle increases linearly , when a cycle is compared to the cycle next to itself , either left or right , both comparisons should give the same magnitude in the ‘ measure of difference ’. either of these denominators may be chosen . it is not necessary to use both . however , if either of these denominations are used , it has been found that some desirable results as well as some undesirable ones occur . one of the denominators tends to be more effective on certain waveforms than the other . therefore , preferably , a hybrid denominator made by adding them together is chosen , as this results in a much more general and unbiased ‘ measure of difference ’ which is effective independent of the waveform . the derived ‘ measure of difference ’ is next compared with a threshold value ( step 9 ) to determine whether there is a mismatch . if the calculated “ measure of differences ” for the original sample , x 0 , and the reference sample , y 0 , more than a certain threshold ( parameter : threshold ), then it is considered as being ‘ different ’. the choice of the threshold can be varied , and will depend on the range of values within the set of data . further , with reference to fig2 , when a mismatch occurs , the mismatch counter , cx , for the original sample , x 0 , is incremented ( step 10 ). when a match occurs the mismatch counter , cx , is not increased . the program returns to step 3 which creates a new random reference cycle , y 1 , before moving on to calculate the quantities described above in steps 4 and 5 , and carrying out any necessary padding in step 6 , before calculating the “ measure of difference ” in step 8 . for each original sample , x 0 , a certain number of comparisons , l , are made which result in a certain number of mismatches and matches . the total number of mismatches plus matches is equal to the number of comparisons ( step 11 and step 14 ). the number of comparisons can be varied and will depend on the data to be analysed and the processing power available . also , the greater the number of comparisons , the greater the accuracy of the anomaly detection . each original cycle , x 0 , is compared with a certain number of reference samples , y 0 . the comparison steps from selecting a reference sample ( step 3 ) to calculating the “ measure of difference ” ( step 8 ) is carried out over a certain number of times ( parameter : comparisons ) once the “ measure of difference ” ( step 8 ) has been calculated for the certain number of reference samples , yl , and the comparison done the certain number of times , l , the program returns to step 1 to select a different original sample , x 1 and the mismatch counter value , cx , and the number of comparisons , l , is output for original sample , x 0 ( step 15 ). whether original sample , x 0 , is judged to be an anomaly will depend on the number of mismatches in comparison to the number of comparisons , l . the normalised anomaly scores for each original sample , x 0 , are obtained by dividing the mismatch counter , cx , for each sample , x 0 , by the number of comparisons , l , which is also equal to the maximum mismatch count , so that the anomaly score ranges from zero to one , with zero being 0 % mismatch and one being maximum mismatch . fig2 to 39 show results obtained using the cycle comparison algorithm . with reference to our copending unpublished patent applications ipd ref a30114 , a30174 and a30175 , it is noted that the cycle comparison algorithm does not require parameter radius and parameter neighbourhood size . if the comparison domain is unspecified , it is assumed to be the entire data length . the results show in the lower part of the diagram the input data for analysis . the upper portion of the diagram shows the mismatch scores achieved for each sample using the cycle analysis algorithm described above with reference to fig2 to 28 . in the upper portion , an anomaly is identified as being those portions having the highest mismatch scores . the results shown are for audio signals . however , the present invention may also be applied to any ordered set of data elements . the values of the data may be single values or may be multi - element values . result 1a shown in fig2 shows a data stream of 500 elements having a binary sequence of zeros and ones . the anomaly to be detected is a one bit error at both ends of the data . in this example , the number of comparisons was 500 , and the threshold was equal to 0 . 1 . however , the choice of the threshold value in this case was not critical . the peaks in the upper portion of the graph show a perfect discrimination of the one bit errors at either end of the data sequence . result 2a shown in fig3 shows data stream having the form of a sine wave with a change in amplitude . in this example , the number of comparisons was 250 and the threshold was equal to 0 . 01 . however , the choice of the threshold value in this case was not critical . the peaks in the upper portion of the graph show a perfect discrimination of the anomaly . the highest mismatch scores being for those portions of the data stream where the rate of change of amplitude is the greatest . result 3a shown in fig3 shows a data stream having the form of a sine wave with background noise and burst and delay error . in this example , the number of comparisons was 250 , and the threshold was equal to 0 . 15 . the peaks in the upper portion of the graph show a perfect discrimination of the anomalous cycles . result 4a shown in fig3 shows a data stream having the form of a 440 khz sine wave that has been clipped . the data has been sampled at a rate of 22 khz . in this example , the number of comparisons was 250 , and the threshold was equal to 0 . 15 . the peaks show a perfect discrimination of the anomalous cycles . result 5a shown in fig3 shows a data stream having the form of a 440 khz sine wave including phase shifts . the data has been sampled at a rate of 44 khz . in this example , the number of comparisons was 250 and the threshold was equal to 0 . 15 . the peaks show a perfect discrimination of the anomalies . result 6a shown in fig3 shows a data stream having the form of a 440 khz sine wave that has been clipped . the data has been sampled at a rate of 44 khz . in this example , the number of comparisons was 250 , and the threshold was equal to 0 . 15 . the peaks show a near perfect discrimination of the anomalous cycles . result 7a shown in fig3 shows a data stream having the form of a 440 khz sine wave that has been clipped . the data has been sampled at a rate of 11 khz . in this example , the number of comparisons was 250 and the threshold was equal to 0 . 05 . in this example , the threshold value is critical as due to the low sampling rate . as discussed above , for signals that lie in the audio range , at a frequency of around 440 khz , the sampling rate is preferably greater than 11 khz . this is shown in the result 6a . the results are less satisfactory due to the low sampling rate . however , the algorithm would have performed much better at a higher sampling rate . result 8a shown in fig3 shows a 440 khz waveform modulated at 220 khz with a sampling rate of 6 khz . in this example , the number of comparisons was 500 and the threshold was 0 . 15 . the results show that although the average score has increased , score saturation has not occurred . the algorithm has still identified the anomalous region . result 9a shown in fig3 shows data having a 440 khz amplitude modulated sine wave . in this example , the sampling rate was 6 khz , the number of comparisons was 250 and the threshold was 0 . 15 . the results show good discrimination of the anomalous cycles . it is noted that some striation effects are evident . result 10a shown in fig3 shows real audio data comprising a guitar chord with a burst of noise . in this example , the sampling rate was 11 khz , the number of comparisons was 250 and the threshold was 0 . 015 . unlike the previous results , the comparison domain was not the entire data length but was 175 cycles . this was critical due to the morphing of cycles in this complex waveform . the results show that the noise has been very well identified . it is further notices that the attack and decay region , where the chord is struck and when it dies away , also score high attention ( mismatch ) scores , as would be expected . the above examples show very good results . for many types of waveform the cycle comparison algorithm described here is favoured over the sample analysis algorithm described with reference to fig1 to 21 . however , it is to be noted that there are some waveforms that may be more suitable for analysis by the sample analysis algorithm , for example where in a waveform it is not considered anomalous for a small amplitude cycle to be adjacent a large amplitude cycle . it has been noticed that the cycle comparison algorithm has problems identifying a misplaced cycle in a set of ordered cycles . this is because as long as the cycle is common in other parts of the waveform , it will not be considered as an anomaly regardless of its position . thus , preferably , it is advantageous to take more than one cycle into account while doing the comparison . thus , the original cycle , x 0 , may be a plurality of cycles . n subsequent cycles , xn , together to do the comparison or to implement a random neighbourhood of cycles for comparison in the same way the algorithms described with reference to fig1 to 21 take a random neighbourhood of samples . an error correction system is now described with reference to fig4 and 20 , which has application to the present invention . having used the anomaly detection system previously described to identify regions of anomaly in a waveform , error correction is provided to remove the detected errors . from the attention map produced as described above , a suitable filter coefficient is set ( parameter : filter coefficient ) so that only the anomalous region remains in the map before passing the data to an error correction algorithm . the data in the attention map is stored in registers . the error correction algorithm used depends on the algorithm used to detect the anomaly . for the cycle comparison algorithm described above is for use together with a cutting and replacing correction algorithm . however , the sample analysis algorithm described above with reference to fig1 to 21 , it has been found that a shape learning error correction algorithm yields better results . the cutting and replacement correction algorithm described below may be implemented directly . the success of the error correction however , is dependent primarily on being able to pinpoint the anomaly with confidence , which is the function of the detection algorithm . fig3 shows the steps taken to perform the cutting cycles routine . this method cuts the erroneous regions away and joins the ends together . this reduces the chances of second order noise . fig4 shows the steps taken to perform the replacing cycles routing . after the erroneous cycle is identified , the algorithm searches a certain number of cycles ( parameter : search radius for replacement cycle ) around the erroneous cycle for a cycle with the lowest score available . it then uses this cycle to replace the erroneous cycle . as with cutting cycles method , this method is best implemented if the cycle comparison algorithm is used for the detection . a detection algorithm of the present invention has been demonstrated to be very tolerant to the type of input data as well as being very flexible in spotting anomalies in one - dimensional data . therefore there are many applications where such detection method may be useful . in the audio field , such a detection algorithm may be used as a line monitor to monitor recordings and playback for unwanted noise as well as being able to remove it . it may also be useful in the medical field as an automatic monitor for signals from a cardiogram or encephalogram of a patient . apart from monitoring human signals , it may also be used to monitor engine noise . like monitoring in humans , the output from machines , be it acoustic signals or electrical signals , deviate from its normal operating pattern as the machine &# 39 ; s operating conditions vary , and in particular , as the machine approaches failure . the algorithm may also be applied to seismological or other geological data and data related to the operation of telecommunications systems , such as a log of accesses or attempted accesses to a firewall . as the detection algorithm is able to give a much earlier warning in the case of systems that are in the process of failing , in addition to monitoring and removing errors , it may also be used as a predictor . this aspect has application for example , in monitoring and predicting traffic patterns . the invention can be described in generally terms as set out in the set of numbered clauses below : 1 . a method of recognising anomalies contained within a set of data derived from an analogue waveform , the data represented by an ordered sequence of data elements each having a value , in respect of at least some of said data elements , including the steps of : selecting a group of test elements comprising at least two elements of the sequence ; selecting a group of comparison elements comprising at least two elements of the sequence , wherein the comparison group has the same number of elements as the test group and wherein the elements of the comparison group have relative to one another the same positions in the sequence as have the elements of the test group ; comparing the value of each element of the test group with the value of the correspondingly positioned element of the comparison group in accordance with a predetermined threshold to produce a decision that the test group matches or does not match the comparison group ; selecting further said comparison groups and comparing them with the test group ; generating a distinctiveness measure as a function of the number of comparisons for which the comparison indicates a mismatch . 2 . a method according to clause 1 including the further step of : identifying ones of said positional relationships which give rise to a number of consecutive mismatches which exceeds said threshold . 3 . a method according to clause 2 including the further steps of : storing a definition of each such identified relationship ; and utilising the stored definitions for the processing of further data . 4 . a method according to clause 2 or clause 3 including the further step of : replacing said identified ones with data which falls within the threshold . 5 . a method according to any preceding clause , wherein the time resolved data is an audio signal . 6 . a method of removing noise from a sequence of data represented by an ordered sequence of data elements each having a value comprising , in respect of at least some of said data elements , including the steps of : selecting a group of comparison elements comprising at least two elements of the sequence , wherein the comparison group has the same number of elements as the test group and wherein the elements of the comparison group have relative to one another the same positions in the sequence as have the elements of the test group ; comparing the value of each element of the test group with the value of the correspondingly positioned element of the comparison group in accordance with a predetermined match criterion to produce a decision that the test group matches or does not match the comparison group ; selecting further said comparison groups and comparing them with the test group ; generating a distinctiveness measure as a function of the number of comparisons for which the comparison indicates a mismatch , identifying ones of said positional relationships which give rise to a number of consecutive mismatches which exceeds a threshold , and replacing said identified ones with data which falls within the threshold . 7 . a computer programmed to perform the method of any of clauses 1 - 6 . 8 . a computer program product directly loadable into the internal memory of a digital computer , comprising software code portions for performing the steps of any of clauses 1 - 6 , when said product is run on a computer . 9 . an apparatus for recognising anomalies contained within a set of data derived from an analogue waveform , the data represented by an ordered sequence of data elements each having a value comprising , in respect of at least some of said data elements , including : means for storing an ordered sequence of data , each datum having a value , means for selecting a group of test elements comprising at least two elements of the sequence ; means for selecting a group of comparison elements comprising at least two elements of the sequence , wherein the comparison group has the same number of elements as the test group and wherein the elements of the comparison group have relative to one another the same positions in the sequence as have the elements of the test group ; means for comparing the value of each element of the test group with the value of the correspondingly positioned element of the comparison group in accordance with a predetermined match criterion to produce a decision that the test group matches or does not match the comparison group ; means for selecting further said comparison groups and comparing them with the test group ; means for generating a distinctiveness measure as a function of the number of comparisons for which the comparison indicates a mismatch . 10 . a computer program product stored on a computer usable medium , comprising : computer readable program means for causing a computer to store an ordered sequence of data derived from an analogue waveform , each datum having a value , computer readable program means for causing a computer to select a group of test elements comprising at least two elements of the sequence ; computer readable program means for causing a computer to select a group of comparison elements comprising at least two elements of the sequence , wherein the comparison group has the same number of elements as the test group and wherein the elements of the comparison group have relative to one another the same positions in the sequence as have the elements of the test group ; computer readable program means for causing a computer to compare the value of each element of the test group with the value of the correspondingly positioned element of the comparison group in accordance with a predetermined match criterion to produce a decision that the test group matches or does not match the comparison group ; computer readable program means for causing a computer to select further said comparison groups and comparing them with the test group ; computer readable program means for causing a computer to generate a distinctiveness measure as a function of the number of comparisons for which the comparison indicates a mismatch . 11 . a method of recognising anomalies in data represented by an ordered array of data elements each having a value , in respect of at least some of said data elements , including the steps of : selecting a group of test elements comprising at least two elements of the array ; selecting a group of comparison elements comprising at least two elements of the array , wherein the comparison group has the same number of elements as the test group and wherein the elements of the comparison group have relative to one another the same positions in the array as have the elements of the test group ; comparing the value of each element of the test group with the value of the correspondingly positioned element of the comparison group in accordance with a dynamic threshold , whose value varies in accordance with the values of the elements around at least one of said test elements , to produce a decision that the test group matches or does not match the comparison group ; selecting further said comparison groups and comparing them with the test group ; generating a distinctiveness measure as a function of the number of comparisons for which the comparison indicates a mismatch . 12 . a method according to clause 1 , including the further step of : determining the local gradient at one of said test elements . 13 . a method according to clause 2 , including the further step of : using said local gradient to determine the dynamic threshold . 14 . a method according to any of the preceding clauses wherein the dynamic threshold is determined in accordance with the local gradient and a predetermined threshold . 15 . a method according to clause 1 , including the further step of : determining the value of the elements neighbouring one of said test elements . 16 . a method according to clause 6 , wherein the dynamic threshold is determined in accordance with said value of the elements neighbouring one of said test elements . 17 . a method according to clause 1 including the further step of : identifying ones of said positional relationships which give rise to a number of consecutive mismatches which exceeds said threshold . 18 . a method according to clause 7 including the further steps of : storing a definition of each such identified relationship ; and utilising the stored definitions for the processing of further data . 19 . a method according to clause 7 or clause 8 including the further step of : replacing said identified ones with data which falls within the threshold . 20 . a computer programmed to perform the method of any of clauses 11 - 19 . 21 . a computer program product directly loadable into the internal memory of a digital computer , comprising software code portions for performing the steps of any of clauses 11 - 19 , when said product is run on a computer . 22 . an apparatus for recognising anomalies in data represented by an ordered array of data elements each having a value , in respect of at least some of said data elements , including : means for storing an ordered array of data , each datum having a value , means for selecting a group of test elements comprising at least two elements of the array ; means for selecting a group of comparison elements comprising at least two elements of the array , wherein the comparison group has the same number of elements as the test group and wherein the elements of the comparison group have relative to one another the same positions in the array as have the elements of the test group ; means for comparing the value of each element of the test group with the value of the correspondingly positioned element of the comparison group in accordance with a dynamic threshold to produce a decision that the test group matches or does not match the comparison group ; means for selecting further said comparison groups and comparing them with the test group ; means for generating a distinctiveness measure as a function of the number of comparisons for which the comparison indicates a mismatch . 23 . an apparatus according to clause 22 , including means for determining the local gradient at one of said test elements . 24 . an apparatus according to clause 23 , including means for determining the dynamic threshold using said local gradient . 25 . an apparatus according to any of clauses 22 - 24 , wherein dynamic threshold is determined in accordance with the local gradient and a predetermined threshold . 26 . an apparatus according to clause 22 including means for determining the value of the elements neighbouring one of said test elements . 27 . an apparatus according to clause 26 , wherein the dynamic threshold is determined in accordance with said value of the elements neighbouring one of said test elements . 28 . an apparatus according to clause 22 including means for identifying ones of said positional relationships which give rise to a number of consecutive mismatches which exceeds said threshold . 29 . an apparatus according to clause 28 including means for storing a definition of each such identified relationship ; and utilising the stored definitions for the processing of further data . 30 . an apparatus according to clause 28 or 29 including means for replacing said identified ones with data which falls within the threshold . 31 . a computer program product stored on a computer usable medium , comprising : computer readable program means for causing a computer to store an ordered array of data , each datum having a value , computer readable program means for causing a array ; computer readable program means for causing a computer to select a group of comparison elements comprising at least two elements of the array , wherein the comparison group has the same number of elements as the test group and wherein the elements of the comparison group have relative to one another the same positions in the array as have the elements of the test group ; computer readable program means for causing a computer to compare the value of each element of the test group with the value of the correspondingly positioned element of the comparison group in accordance with a dynamic threshold to produce a decision that the test group matches or does not match the comparison group ; computer readable program means for causing a computer to select further said comparison groups and comparing them with the test group ; computer readable program means for causing a computer to generate a distinctiveness measure as a function of the number of comparisons for which the comparison indicates a mismatch . 32 . a method of recognising anomalies in data represented by an ordered array of data elements each having a value , in respect of at least some of said data elements , including the steps of : i ) selecting a first test element from said array , ii ) selecting a random reference element from said array , iii ) comparing the value of the test element with the value of the random reference element , iv ) if the value of said test element does not match the value of said random reference element searching for a matching element within the neighbourhood of said random reference element , v ) changing a mismatch parameter as a measure of anomalies in said data array if no matching element within said neighbourhood of said random reference element is found and selecting a new random reference element , vi ) repeating steps iii ) to v ) a number of times . 33 . a method according to clause 32 including the steps of : vii ) if in step iv ) a matching element is found within said neighbourhood of said random reference element performing a comparison of the values of elements of a group of elements about said first test element with the values of a corresponding group of elements about said matching element , viii ) if said groups are found to match increasing a comparison value . 34 . a method according to clause 33 wherein said elements of said group of elements about said first test element and said elements of said group of elements about said matching element are arranged in the same manner about said test element and said matching element respectively and corresponding elements of said groups are compared in accordance with a threshold value . 35 . a method according to clause 33 in which step vi ) is repeated until said comparison value is equal to a set value and when said comparison value is equal to said set value selecting a second test element and repeating steps i ) to vi ) for said second test element . 36 . a method according to clause 34 , wherein the values are compared in accordance with a dynamic threshold , the value of which varies in accordance with the values of the elements around at least one of the test elements . 37 . a method according to clause 36 , including the further step of : determining the local gradient at one of said test elements . 38 . a method according to clause 39 , including the further step of : using said local gradient to determine the dynamic threshold . 39 . a method according to any of preceding clauses 36 to 38 wherein the dynamic threshold is determined in accordance with the local gradient and a predetermined threshold . 40 . a method according to clause 34 including the further step of : identifying the particular arrangements of elements which give rise to a number of consecutive mismatches which exceeds said threshold and storing data representing such particular arrangements of elements . 41 . a method according to clause 40 including the further step of : replacing said stored data with corresponding data of arrangements giving rise to matches falling within the threshold . 42 . a computer programmed to perform the method of any of clauses 31 - 41 . 43 . a computer program product directly loadable into the internal memory of a digital computer , comprising software code portions for performing the steps of any of clauses 31 - 41 , when said product is run on a computer . 44 . an apparatus for recognising anomalies in data represented by an ordered array of data elements each having a value , in respect of at least some of said data elements , means for selecting a first test element from said array , means for selecting a random reference element from said array , means for comparing the value of the test element with the value of the random reference element , means for searching for a matching element within the neighbourhood of said random reference element if the value of said test element does not match the value of said random reference element , means for changing a mismatch parameter as a measure of anomalies in said data array if no matching element is found within said neighbourhood of said random reference element and for selecting a new random reference element . 45 . an apparatus according to clause 44 , wherein if a matching element is found within said neighbourhood of said random reference element means are provided to perform a comparison of the values of elements of a group of elements about said first test element with the values of a corresponding group of elements about said matching element , and if said groups are found to match means are provided to increase a comparison value . 46 . an apparatus according to clause 45 wherein said elements of said group of elements about said first test element and said elements of said group of elements about said matching element are arranged in the same manner about said test element and said matching element respectively and corresponding elements of said groups are compared in accordance with a threshold value . 47 . an apparatus according to clause 45 , including means for repeating step vi ) until said comparison value is equal to a set value and when said comparison value is equal to said set value selecting a second test element and including means for repeating steps i ) to vi ) for said second test element . 48 . an apparatus according to clause 46 , wherein the values are compared in accordance with a dynamic threshold , the value of which varies in accordance with the values of the elements around at least one of the test elements . 49 . an apparatus according to clause 48 , including means for determining the local gradient at one of said test elements . 50 . an apparatus according to clause 49 including means for using said local gradient to determine the dynamic threshold . 51 . an apparatus according to any one of clauses 48 - 50 , wherein the dynamic threshold is determined in accordance with the local gradient and a predetermined threshold . 52 . an apparatus according to clause 46 , including means for identifying the particular arrangements of elements which give rise to a number of consecutive mismatches which exceeds said threshold and storing data representing such particular arrangements of elements . 53 . an apparatus according to clause 52 , including means for replacing said stored data with corresponding data of arrangements giving rise to matches falling within the threshold . 54 . an apparatus according to clause 44 including means for identifying ones of said test elements which give rise to a number of consecutive mismatches which exceed said threshold . 55 . an apparatus according to clause 54 including means for storing a definition of each such test elements ; and utilising the stored test elements for the processing of further data . 56 . an apparatus according to clause 54 or 55 including means for replacing said identified ones with data which falls within the threshold . 57 . a computer program product stored on a computer usable medium , comprising : computer readable program means for causing a computer to store an ordered array of data elements each having a value , in respect of at least some of said data elements , computer readable program means for causing a computer to select a first test element from said array , computer readable program means for causing a computer to select a random reference element from said array , computer readable program means for causing a computer to compare the value of the test element with the value of the random reference element , computer readable program means for causing a computer to search for a matching element within the neighbourhood of said random reference element if the value of said test element does not match the value of said random reference element , computer readable program means for causing a computer to change a mismatch parameter as a measure of anomalies in said data array if no matching element is found within said neighbourhood of said random reference element and for selecting a new random reference element . 58 . a method of recognising anomalies contained within an array of data elements , each element having a value , including the steps of , in respect of at least some of said data elements , i ) identifying cycles in the set of data in accordance with predetermined criteria , ii ) selecting a test cycle of elements from said set of data , iii ) randomly selecting a comparison cycle from said set of data , iv ) determining an integration value for said test cycle and said reference cycle respectively , v ) comparing said integration values and deriving therefrom a measure of the difference of said test and said reference cycles , vi ) using said measure to determine a mismatch of said test and said reference cycles . 59 . a method according to clause 58 , including the further step of : vii ) randomly selecting further reference cycles and comparing them with the test cycle according to steps v ) and vi ) and counting the number of mismatches . 60 . a method according to clause 58 in which a mismatch is determined by comparing said measure to a threshold value . 61 . a method according to clause 59 , including the further step of : viii ) generating a distinctiveness measure as a function of the number of mismatches between test and reference cycles . 62 . a method according to any preceding clause , including the further step of : ix ) establishing whether the test and reference cycles include the same number of elements , and if the number of elements are not equal , padding the cycle with fewer elements with elements of set value , so that both cycles contain the same number of elements . 63 . a method according to any preceding clause , in which step iv ) comprises determining the difference of the sums of values of the element of the test cycle and the comparison cycle respectively . 64 . a method according to clause 59 in which step vii ) is repeated a set number of times , after which a fresh test cycle is selected . 65 . a computer programmed to perform the method of any of clauses 58 to 64 . 66 . a computer program product directly loadable into the internal memory of a digital computer , comprising software code portions for performing the steps of any of clauses 58 to 64 , when said product is run on a computer . 67 . an apparatus for recognising anomalies contained within an array of data elements , each element having a value , the apparatus including : means for identifying cycles in the set of data in accordance with predetermined criteria , means for selecting a test cycle of elements from said set of data , means for randomly selecting a comparison cycle from said set of data , means for determining an integration value for said test cycle and said reference cycle respectively , means for comparing said integration values and deriving therefrom a measure of the difference of said test and said reference cycles , means for using said measure to determine a mismatch of said test and said reference cycles . 68 . an apparatus according to clause 67 , further including : means for randomly selecting further reference cycles and comparing them with the test cycle , and means for counting the number of mismatches . 69 . an apparatus according to clause 67 , in which a mismatch is determined by comparing said measure to a threshold value . 70 . an apparatus according to clause 68 or clause 69 , further including : means for generating a distinctiveness measure as a function of the number of mismatches between test and reference cycles . 71 . an apparatus according to any of clauses 67 to 70 , further including : means for establishing whether the test and reference cycles include the same number of elements , and if the number of elements are not equal , padding the cycle with fewer elements with elements of set value , so that both cycles contain the same number of elements . 72 . an apparatus according to any of clauses 68 to 71 , wherein said determining means determines the difference of the sums of values of the element of the test cycle and the comparison cycle respectively . 73 . an apparatus according to clause 68 , including means for selecting a fresh test cycle after the comparison means is repeated a predetermined number of times . 74 . a computer program product stored on a computer usable medium , comprising : computer readable program means for causing a computer to identify cycles in the set of data in accordance with predetermined criteria , computer readable program means for causing a computer to select a test cycle of elements from said set of data , computer readable program means for causing a computer to randomly select a comparison cycle from said set of data , computer readable program means for causing a computer to determine an integration value for said test cycle and said reference cycle respectively , computer readable program means for causing a computer to compare said integration values and deriving therefrom a measure of the difference of said test and said reference cycles , computer readable program means for causing a computer to use said measure to determine a mismatch of said test and said reference cycles . 75 . a computer program product stored on a computer usable medium according to clause 74 , further comprising : computer readable program means for causing a computer to select further said comparison cycles and comparing them with the test cycle . 76 . a computer program product stored on a computer usable medium according to either clause 74 or 75 , further comprising : computer readable program means for causing a computer to generate a distinctiveness measure as a function of the number of comparisons for which the comparison indicates a mismatch .
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in the following contents , the embodiments of the present invention will be described in detail with reference to the examples ; however , a person skilled in the art would understand that the following examples are merely used to explain the present invention , rather than being deemed as limiting the scope of the present invention . examples , for which no concrete situations are specified , are performed according to conventional situations or situations recommended by the manufactures . reagents or instruments , for which no manufacturers are specified , are conventional products available commercially . in order to explain the use of the stats and erk signal pathway inhibitor in the preparation of drugs for treating tumors , the targeted cancer inhibition effect of mogrosides by way of signal pathway is explained by taking mogrol i e1 and mogrol ii a2 as examples , and the targeted cancer inhibition effect of an analog of mogrosides is explained by taking mogrol as an example . 1 ) grinding momordica grosvenori , adding water in accordance with a weight - ratio of 1 : 6 between momordica grosvenori and water , performing extraction at a temperature of 80 ° c . for twice , 1 hour each time , and combining extracted solutions ; 2 ) adding chitosan to the combined extracted solutions for flocculation , and removing tannins and soluble proteins from the extracted solutions to provide a clear aqueous solution ; 3 ) utilizing xad - 16 resin for adsorbing the aqueous solution and using 30 % ethanol for elution to provide a mixed solution of enriched mogrosides in water and ethanol ; 4 ) concentrating the mixed solution under reduced pressure till an extractum status , and recycling the ethanol , and diluting the extractum by adding deionized water of a mass of 4 times that of the extracturn to the extractum , to provide an aqueous solution of crude mogrosides ; 5 ) performing a decolorization treatment to the aqueous solution of crude mogrosides utilizing diaion pa resin , and collecting the solution flowing down from the resin column to provide an enriched solution ; and 6 ) concentrating the enriched solution at 50 ° c . under reduced pressure till dry , and adding ethanol for dissolution to obtain a mixture , and then separating the obtained mixture by c 18 reversed - phase high - performance liquid chromatography with acetonitrile - water as a mobile phase , performing elution in a linear gradient of 20 %- 75 %, collecting target substance , and evaporating solvents to provide mogroside i e1 as a white crystal . the molecular formula of the obtained mogroside i e1 is c 36 h 62 o 9 , with a molecular weight of 638 . 9 and a cas registry number : 88901 - 39 - 7 , and the structural formula of mogroside i e1 is 1 ) grinding mornordica grosvenori , adding water in accordance with a weight - ratio of 1 : 8 between mornordica grosvenori and water , performing extraction at 95 ° c . for 4 times , 2 hours each time , and combining extracted solutions ; 2 ) adding chitosan to the combined extracted solutions for flocculation , and removing tannins and soluble proteins from the extracted solutions to provide a clear aqueous solution ; 3 ) utilizing xad - 16 resin for adsorbing the aqueous solution and using 50 % ethanol for elution to provide a mixed solution of enriched mogrosides in water and ethanol ; 4 ) concentrating the mixed solution under reduced pressure till an extractum status , and recycling the ethanol , and diluting the extractum by adding deionized water of a mass of 5 times that of the extractum to the extractum , to provide an aqueous solution of crude mogrosides ; 5 ) performing a decolorization treatment to the aqueous solution of crude mogrosides utilizing diaion pa resin , and collecting the solution flowing down from the resin column to provide an enriched solution ; and concentrating the enriched solution at 50 ° c . under reduced pressure till dry , and adding ethanol for dissolution to obtain a mixture , and then separating the obtained mixture by c 18 reversed - phase high - performance liquid chromatography with acetonitrile - water as a mobile phase , performing elution in a linear gradient of 20 %- 75 %, collecting target substance , and evaporating solvents to provide mogroside ii a2 as a white crystal . the obtained mogroside ii a2 has a cas registry number : 88901 - 45 - 5 , with a molecular formula of c 42 h 72 o 14 and a molecular weight of 801 . 01 , and the structural formula of mogroside ii a2 is performing the hplc analysis on the obtained mogroside i e1 and mogroside ii a2 , and the obtained chromatograms are shown in fig1 and 2 . it can be seen from fig1 and 2 that mogroside i e1 and mogroside ii a2 prepared through the method for preparing the mogrosides and analogs thereof according to the present invention both have a purity of higher than 96 %. ( 1 ) a method for preparing mogrol i included the steps of : 1 ) grinding momordica grosvenori , adding water in accordance with the weight - ratio of 1 : 6 between mornordica grosvenori and water , performing extraction at a temperature of 80 ° c . for twice , 1 hour each time , and combining extracted solutions ; 2 ) adding chitosan to the combined extracted solutions for flocculation , and removing tannins and soluble proteins from the extracted solutions to provide a clear aqueous solution ; 3 ) utilizing xad - 16 resin for adsorbing the aqueous solution and using 30 % ethanol for elution to provide a mixed solution of enriched mogrosides in water and ethanol ; 4 ) concentrating the mixed solution under reduced pressure till an extractum status , and recycling the ethanol , and diluting the extractum by adding deionized water of a mass of 4 times that of the extractum to the extractum to provide an aqueous solution of crude mogrosides ; 5 ) performing a decolorization treatment to the aqueous solution of crude glycoside utilizing diaion pa resin , and collecting the solution flowing down from the resin column to provide an enriched solution ; 6 ) adding a glycosidase to the enriched solution for reaction at a temperature of 45 ° c . for 6 hours , wherein the weight of the glycosidase is 4 % of the weight of the enriched solution ; and 7 ) performing centrifugation to give a precipitate , wherein the obtained precipitate is a crude product of mogrol , washing the crude product of mogrol with water for 3 times to remove water - soluble impurities , and performing freeze drying to provide mogrol i . the obtained mogrol i has a molecular weight of 476 . 7 and a cas registry number : 88930 - 15 - 8 , the molecular formula thereof is c 30 h 52 o 4 , and the structural formula thereof is performing the hplc analysis to the obtained mogrol i , and the obtained chromatogram is shown in fig3 . it can be seen from fig3 that mogrol i prepared through the method for preparing mogrol provided in the present invention has a purity of higher than 98 %. ( 2 ) a method for preparing mogrol ii included the steps of : 1 ) grinding momordica grosvenori , adding water in accordance with the weight - ratio of 1 : 8 between momordica grosvenori and water , performing extraction at a temperature of 95 ° c . for 4 times , 2 hours each time , and combining extracted solutions ; 2 ) adding chitosan to the combined extracted solutions for flocculation , and removing tannins and soluble proteins from the extracted solutions to provide a clear aqueous solution ; 3 ) utilizing xad - 16 resin for adsorbing the aqueous solution and using 50 % ethanol for elution to provide a mixed solution of enriched mogrosides in water and ethanol ; 4 ) concentrating the mixed solution under reduced pressure till an extractum status , and recycling the ethanol , and diluting the extractum by adding deionized water of a mass of 4 - 5 times that of the extractum to the extractum to provide an aqueous solution of crude mogrosides ; 5 ) performing a decolorization treatment to the aqueous solution of crude glycoside utilizing diaion pa resin , and collecting the solution flowing down from the resin column to provide an enriched solution ; 6 ) adding a glycosidase to the enriched solution for reaction at a temperature of 55 ° c . for 8 hours , wherein the weight of the glycosidase is 6 % of the weight of the enriched solution ; and 7 ) performing centrifugation to give a precipitate , wherein the obtained precipitate is a crude product of mogrol , washing the crude product of mogrol with water for 5 times to remove water - soluble impurities , and performing freeze drying to provide mogrol ii . the obtained mogrol ii has a molecular weight of 476 . 7 and a cas registry number : 88930 - 15 - 8 , the molecular formula thereof is c 30 h 52 o 4 , and the structural formula thereof is performing the hplc analysis on the obtained mogrol ii , and an identical result to that of the above - mentioned mogrol i was obtained , namely , the purity of the obtained mogrol ii was also higher than 98 %. as the structures of the above - mentioned mogrol i and mogrol ii are identical , mogrol i and mogrol ii can be both referred to in the present application as mogrol . the inhibition of the stat3 and erk signal pathways achieved by mogroside i e1 , mogroside ii a2 and mogrol was detected by western blotting , specifically : group 1 : histiocytic lymphoma u937 cells ( 1 × 10 6 cells / well ) were inoculated into a 6 - well culture plate for staying overnight , and 0 and 10 μmol / l of mogroside i e1 , mogroside ii a2 and mogrol were added respectively , and the culture was continued for 24 hours ; group 2 : human melanoma a875 cells ( 1 × 10 6 cells / well ) were inoculated into a 6 - well culture plate for staying overnight , and 0 and 10 μmol / l of mogroside i e1 , mogroside ii a2 and mogrol were added respectively , and the culture was continued for 24 hours ; group 3 : leukemia cells k562 ( 1 × 10 6 cells / well ) were inoculated into a 6 - well culture plate for staying overnight , and 0 and 10 μmol / l of mogroside i e1 mogroside ii a2 and mogrol were added respectively , and the culture was continued for 24 hours ; after the termination of the cell culture , the culture solution was removed , and the residue was washed with pbs ( 0 . 01 mol / l , ph 7 . 4 ), and then a cell lysis solution containing protease inhibitors was added at an amount of 50 μl / well , and the mixture was placed in an ice bath for lysis at 4 ° c . for 30 min and then centrifuged at 14000 r / min for 10 min , and then total proteins were obtained from the supernatant ; the protein concentrations were measured with bovine serum albumin ( bsa ) as the standard . 50 μg of the total proteins was separated by polyacrylamide gel electrophoresis with 12 % sos , electrophoretically transferred to a pvof membrane ( polyvinylidene fluoride membrane ), and blocked for 1 h by 5 % of skim milk ( containing 0 . 1 % of tween 20 ), and then antibodies p - stat3 ( tyr705 ) and p - erk1 / 2 as well as β - actin were added , and the primary antibody was incubated at 4 ° c . overnight ( β - actin was used as reference in loading amount ); the membrane was washed for 3 times with tbs - t , 5 min each time ; secondary antibody marked by horseradish peroxidase ( hrp ) was added for incubation at room temperature for 1 h , the membrane was washed for 3 times with a wash solution ( tbs - t ), 10 min each time , and then ecl was added for incubation in dark for 5 min , and subsequently , a fluorescence imaging analyzer was used for image development and scanning analysis , and the results of western blotting detection are shown in fig4 to 6 . results obtained after u937 cell treatment by mogrol i e1 , mogrol ii a2 and mogrol were identical to each other . taking the effect of mogrol i e1 on u937 cells as an example , details are shown in fig4 . it can be seen that the expression levels of phosphorylated erk1 / 2 ( p - erk1 / 2 ) and phosphorylated stat3 ( p - stat3 ) were significantly decreased after the mogrosides and analogs thereof acted on the u937 cells for 24 hours . in addition , 0 , 10 , 150 and 250 μmol / l of the mogrosides and analogs thereof were used for treating the u937 cells for 24 hours , and the results showed that the decreasing degree of the expression levels of phosphorylated erk1 / 2 ( p - erk1 / 2 ) and phosphorylated stat3 ( p - stat3 ) was enhanced with the increase of the treatment concentration of the mogrosides and analogs thereof . it indicates that mogrosides and analogs thereof have effects of inhibiting the activation of stat3 and erk proteins and blocking the stat3 and erk signal pathways . results obtained after melanoma a875 cell treatment by mogrol i e1 mogrol ii a2 and the mogrol were identical to each other . the effect of mogrol ii a2 on melanoma a875 cells is shown in fig5 ; in addition , the effect of the mogrol on melanoma a875 cells is shown in fig7 and 8 . it can be seen that the expression levels of phosphorylated erk1 / 2 ( p - erk1 / 2 ) and phosphorylated stat3 ( p - stat3 ) were significantly decreased after the mogrosides and analogs thereof acted on the melanoma a875 cells for 24 hours . in addition , it has been verified by experiments that the decreasing degree of the expression levels of phosphorylated erk1 / 2 ( p - erk1 / 2 ) and phosphorylated stat3 ( p - stat3 ) was enhanced with the increase of the treatment concentration of the mogrosides and analogs thereof , which was identical to the results of u937 cells . it indicates that mogrosides and analogs thereof have the effects of inhibiting the activation of stat3 and erk proteins and blocking the stat3 and erk signal pathways . results obtained after leukemia cell k562 treatment by mogrol i e1 , mogrol ii a2 and mogrol were identical to each other . taking the effect of mogrol ii a2 on leukemia cells k562 as an example , details are shown in fig6 . it can be seen that the expression levels of phosphorylated erk1 / 2 ( p - erk1 / 2 ) and phosphorylated stat3 ( p - stat3 ) were significantly decreased after the mogrosides and analogs thereof acted on the leukemia cells k562 for 24 hours . moreover , it has been verified by experiments that the decreasing degree of the expression levels of phosphorylated erk1 / 2 ( p - erk1 / 2 ) and phosphorylated stat3 ( p - stat3 ) was enhanced with the increase of the treatment concentration of the mogrosides and analogs thereof , which was identical to the results of u937 cells . it indicates that mogrosides and analogs thereof have the effects of inhibiting the activation of stat3 and erk proteins and blocking the stat3 and erk signal pathways . the stat3 and erk signal pathways can regulate cyclins and apoptosis genes , and in order to verify the effects of mogrol i e1 mogrol ii a2 and mogrol , the expression status of downstream genes of stat3 and erk was detected , wherein the influences of the three mogrosides and analogs thereof , i . e . mogrol i e1 , mogrol ii a2 and mogrol , on bcl - 2 and p21 proteins in the histiocytic lymphoma u937 cells , human melanoma a875 cells and leukemia cells k562 were determined , respectively . the regulation of bcl - 2 and p21 proteins by mogrosides and analog thereof to the was detected by western blotting , specifically : histiocytic lymphoma u937 cells , human melanoma a875 cells and leukemia cells k562 ( 1 × 10 6 cells / well ) were inoculated into a 6 - well culture plate overnight , and 0 and 10 μmol / l of the mogrosides and analogs thereof were added respectively , and kept cultured for 24 h . after the termination of the cell culture , the culture solution was removed , and the residue was washed with pbs ( 0 . 01 mol / l , ph 7 . 4 ), then a cell lysis solution containing protease inhibitors was added at an amount of 50 μl / well , and the mixture was placed in an ice bath for lysis at 4 ° c . for 30 min and then centrifuged at a speed of 14000 r / min for 10 min , and then total proteins were obtained from the supernatant . the protein concentration was measured with bovine serum albumin ( bsa ) as the standard . 50 μg of the total proteins were separated by polyacrylamide gel electrophoresis with 12 % sds , and electrophoretically transferred to a pvdf membrane ( polyvinylidene fluoride membrane ), and blocked for 1 h by 5 % of skim milk ( containing 0 . 1 % of tween 20 ), and then antibodies p21 , bcl - 2 and β - actin were added , wherein the primary antibody was incubated at 4 ° c . overnight ( β - actin was used as reference loading amount ); the membrane was washed for 3 times with tbs - t , 5 min each time ; secondary antibody marked by horseradish peroxidase ( hrp ) was added for incubation at room temperature for 1 h , the membrane was washed with rinse solution ( tbs - t ) for 3 times , 10 min each time , and then ecl was added for incubation in dark for 5 min , and subsequently , a fluorescence imaging analyzer was used for image development and scanning analysis . the results of western blotting detection are shown in fig9 to 11 . results obtained after u937 cell treatment by mogroside i e1 , mogroside ii a2 and mogrol were identical to each other . taking the effect of mogroside i e1 on the u937 cells as an example , details are shown in fig9 . it can be seen that the downstream cycle regulatory protein p21 associated with the stat3 signal was significantly up - regulated , while the anti - apoptotic protein bcl - 2 was significantly down - regulated after the mogrosides and analogs thereof acted on the u937 cells for 24 h . in addition , 0 , 10 , 150 and 250 μmol / l of different mogrosides and analogs thereof were used for treating u937 cells for 24 h . after different concentrations of mogrosides and analogs thereof acted on u937 cells for 24 h , the mogrosides and analogs thereof can all inhibit the activation of stat3 in a dose - dependent way , and simultaneously up - regulate the cycle regulatory protein p21 and inhibit the expression of the anti - apoptotic protein bcl - 2 . the expression levels of p21 and bcl - 2 proteins exhibit a drug - concentration dependence , and it indicates that mogrosides and analogs thereof regulate the expression of the downstream cyclins and apoptosis genes of the signal pathway by blocking the stat3 and erk sites , so as to achieve the effects of inhibiting the growth of cancer cells and promoting the apoptosis of cancer cells . results obtained after melanoma a875 cell treatment by mogroside i e1 mogroside ii a2 and mogrol were identical to each other . taking the effect of mogroside ii a2 on the melanoma a875 cells as an example , details are shown in fig1 . it can be seen that the downstream cycle regulatory protein p21 associated with the stat3 signal was significantly up - regulated , while the anti - apoptotic protein bcl - 2 was significantly down - regulated , after the mogrosides and analogs thereof acted on the human melanoma a875 cells for 24 h . in addition , it is proved by experiments that after different concentrations of mogrosides and analogs thereof acted on the human melanoma a875 cells for 24 h , the mogrosides and analogs thereof can inhibit the activation of stat3 in a dose - dependent way , and simultaneously up - regulate the cycle regulatory protein p21 and inhibit the expression of the anti - apoptotic protein bcl - 2 , and the results are identical to those of the u937 cells . the expression levels of p21 and bcl - 2 proteins exhibit a drug - concentration dependence , and it indicates that the mogrosides and analogs thereof regulate the expression of the downstream cyclins and apoptosis genes of the signal pathway by blocking the stat3 and erk sites , so as to achieve the effects of inhibiting the growth of cancer cells and promoting the apoptosis of cancer cells . results obtained after leukemia cell k562 treatment by mogroside i e1 mogroside ii a2 and mogrol were identical to each other . taking the effect of the mogrol on the leukemia cells k562 as an example , details are shown in fig1 . it can be seen that the downstream cycle regulatory protein p21 associated with the stat3 signal was significantly up - regulated , while the anti - apoptotic protein bcl - 2 was significantly down - regulated , after the mogrosides and analogs thereof acted on the leukemia cells k562 for 24 h ; moreover , it is proved by tests that after that different concentrations of mogrosides and analogs thereof acted on the leukemia cells k562 for 24 h , the mogrosides and analogs thereof can inhibit the activation of stat3 in a dose - dependent way , and simultaneously up - regulate the cycle regulatory protein p21 and inhibit the expression of the anti - apoptotic protein bcl - 2 , and the results were identical to those of the u937 cells . the expression levels of the p21 and bcl - 2 proteins exhibit a drug - concentration dependence , and it indicates that mogrosides and analogs thereof regulate the expression of the downstream cyclins and apoptosis genes of the signal pathway by blocking the stat3 and erk sites , so as to achieve the effects of inhibiting the growth of cancer cells and promoting the apoptosis of cancer cells . bcl - 2 is an anti - apoptotic protein and can inhibit programed cell death , and the overexpression of bcl - 2 is an important cause of malignant cell proliferation , while bcl - 2 is a downstream protein regulated by stat3 . when the phosphorylation of stat3 proteins in u937 cells , human melanoma a875 cells and leukemia cells k562 treated by the mogrosides and analogs thereof ( mogroside i e1 , mogroside ii a2 and mogrol ) was inhibited , the expression of bcl - 2 protein was significantly decreased , and the expression level of bcl - 2 protein was positively correlated with the inhibition suffered by stat3 , which is also an important reason for the promotion of apoptosis of cancer cells . the influences of mogroside i e1 , mogroside ii a2 and mogrol on the cell cycle distribution of the histiocytic lymphoma u937 cells , the human melanoma a875 cells and the leukemia cells k562 . the cell cycle arrest achieved by drugs is an important approach to the inhibition of cancer cell proliferation . histiocytic lymphoma u937 cells , human melanoma a875 cells and leukemia cells k562 in logarithmic growth phase were selected , and after the respective culture with 0 and 10 μmol / l of the mogrosides and analogs thereof ( mogroside i e1 , mogroside ii a2 and the mogrol ) for 24 h , 0 . 25 % pancreatin was added for digestion , the cells of the drug groups and the control groups were collected and washed with pbs and then centrifuged at 2500 rpm for 5 min , and then the cells were collected , fixed with 70 % cold ethanol , and stayed overnight at 4 ° c ., which was then subjected to centrifugation to remove ethanol , and pbs containing rnase a was added , and propidium iodide ( pi ) was added for staining , and the resulting mixture was mixed evenly ( rnase a had a final concentration of 50 mg / l ., and the final concentration of pi was 25 mg / l ), incubated in dark at 37 ° c . for 30 min , anddetected by flow cytometer . the stat3 signal pathway relates to the expression of cell cycle genes , and accordingly influences the cell cycle progression . the results obtained after u937 cell treatment by mogroside i e1 , mogroside ii a2 and mogrol were identical to each other . it can be concluded from the detection results of the flow cytometer that cells of g0 / g1 phase of the lymphoma u937 cells have a gradually increasing proportion after the treatment by the mogrosides and analogs thereof , which indicates that mogrosides and analogs thereof can lead to the g0 / g1 arrest of the u937 cells . in addition , 0 , 1 , 10 , 150 and 250 μmol / l of the three mogrosides and analogs thereof were used for treating the u937 cells for 24 h , and the results obtained after u937 cell treatment by mogroside i e1 , mogroside ii a2 and mogrol were identical to each other . it is concluded that with the rise of the concentration of the mogrosides and analogs thereof , the proportion of cells in g0 / g1 phase is gradually increased , and the cell cycle distribution is significantly changed , which indicates that mogrosides and analogs thereof can lead to the g0 / g1 arrest of the u937 cells , and the cycle arrest effect of the mogrosides and analogs thereof on cancer cells exhibits a dose - dependence . it indicates that mogrosides and analogs thereof can induce the cell cycle arrest of tumor cells by inhibiting the stat3 signal pathway and regulating cyclins , so as to inhibit the growth of tumors . the results obtained after melanoma a875 cell treatment by mogroside i e1 , mogroside ii a2 and mogrol were identical to each other . it can be concluded from the detection results of the flow cytometer that the cells in the g0 / g1 phase of human melanoma a875 cells have a gradually increasing proportion after the treatment by mogrosides and analogs thereof , which indicates that mogrosides and analogs thereof can lead to the g0 / g1 arrest of the human melanoma a875 cells . in addition , taking the effect exerted by the mogrol on the melanoma a875 cells as an example , details are shown in fig1 . it can be seen that with the rise of the concentration of the mogrosides and analogs thereof , the proportion of cells in the g0 / g1 phase is gradually increased , and the cell cycle distribution is significantly changed , which indicates that mogrosides and analogs thereof can lead to the g0 / g1 arrest of the human melanoma a875 cells , and the cycle arrest effect of the mogrosides and analogs thereof on cancer cells exhibits a dose - dependence , and the results are identical to those of the u937 cells . it indicates that mogrosides and analogs thereof can induce the cell cycle arrest of tumor cells by inhibiting the stat3 signal pathway and regulating cyclins , so as to inhibit the growth of tumors . the results obtained after leukemia cell k562 treatment by mogroside i e1 , mogroside ii a2 and mogrol were identical to each other . the cell cycle of the leukemia cells k562 was arrested after the treatment by the mogrosides and analogs thereof . in addition , with the rise of the concentration of the mogrosides and analogs thereof , the proportion of cell arrest is gradually increased , and the cell cycle distribution is significantly changed , which indicates that the mogrosides and analogs thereof can lead to the cell cycle arrest of the leukemia cells k562 , and the cycle arrest effect of the mogrosides and analogs thereof on cancer cells exhibits a dose - dependence . it indicates that mogrosides and analogs thereof can induce the cell cycle arrest of tumor cells by inhibiting the stats signal pathway and regulating cyclins , so as to inhibit the growth of tumors . lymphoma u937 cells , human melanoma a875 cells and leukemia cells k562 in logarithmic growth phase were selected , and after the respective culture with 0 and 10 μmol / l of the mogrosides and analogs thereof ( i . e . mogroside i e1 , mogroside ii a2 and mogrol ) for 24 h , cells were collected and washed twice with 200 μl of cold pbs , and then the cells were collected again ; 100 μl of binding buffer was added for re - suspending the cells , and after the addition of 2 μl of annexin v - fitc and well mixing , the resulting mixture was placed in dark at room temperature for 10 min , and then 5 μl of propidium iodide ( pi ) was added and then well mixed ; the mixture was placed in dark at room temperature for 10 min , and detected by flow cytometer , and the results are shown in fig1 - 15 . the results obtained after u937 cell treatment by mogroside i e1 , mogroside ii a2 and mogrol were identical to each other . taking the mogrol as an example , the results are shown in fig1 . it can be seen that the mogrosides and analogs thereof act on the histiocytic lymphoma u937 cells for 24 h , and mogrol can induce the apoptosis of the histiocytic lymphoma u937 cells . in addition , 0 , 10 , 150 and 250 μmol / l of the mogrosides and analogs thereof were used for treating the u937 cells for 24 h , and it is concluded that with the rise of the concentration of the mogrosides and analogs thereof , the level of cell apoptosis increases , namely , the effect of the mogrosides and analogs thereof on the lymphoma u937 cells exhibits a dose - dependence . the results obtained after human melanoma a875 cell treatment by mogroside i e1 mogroside ii a2 and the mogrol were identical to each other . taking mogroside i e1 as an example , the results are shown in fig1 . it can be seen that the mogrosides and analogs thereof act on the human melanoma a875 cells for 24 h , and the mogrosides and analogs thereof can induce the apoptosis of the human melanoma a875 cells . moreover , different concentrations of the mogrosides and analogs thereof were utilized to act on the human melanoma a875 cells . taking mogroside ii a2 as an example , the results are shown in fig1 . it can be seen that with the rise of the concentration of the mogrosides and analogs thereof , the amount for cell apoptosis increases , namely , the effect of the mogrosides and analogs thereof on the human melanoma a875 cells exhibits a dose - dependence . the results are identical to those of the lymphoma u937 cells . the results obtained after leukemia cell k562 treatment by mogroside i e1 , mogroside ii a2 and the mogrol were identical to each other . taking mogroside ii a2 as an example , the results are shown in fig1 . it can be seen that the mogrosides and analogs thereof act on the leukemia cells k562 for 24 h , and the mogrosides and analogs thereof can induce the apoptosis of the leukemia cells k562 . moreover , different concentrations of the mogrosides and analogs thereof are utilized to act on the leukemia cells k562 , and with the rise of the concentration of the mogrosides and analogs thereof , the amount for cell apoptosis increases , namely , the effect of the mogrosides and analogs thereof on the leukemia cells k562 exhibits a dose - dependence . the results are identical to those of the lymphoma u937 cells . lymphoma u937 cells , human melanoma a875 cells and leukemia cells k562 in logarithmic growth phase were selected , and the concentrations of the cells were adjusted to 1 × 10 4 cells / ml , and the cells were transferred to a 6 - well plate for culture , and after the 24 - hour culture , drugs were added to achieve final concentrations of 0 , 10 , 100 and 250 μmol / l , wherein only whole medium was added to the negative control groups , while mogroside ii a2 was added to the positive control groups , after 24 - hour culture , waste solution was removed , and fixing solution was added to each well for fixing for 25 min , and then the resulting mixture was washed twice , 3 min each time , and then hoechst 33258 staining solution was added for staining in dark at room temperature for 30 min , and the cell morphology variation was observed using a fluorescence microscope . the view of the a875 melanoma cells under the effect of mogroside ii a2 observed by fluorescence microscope is shown in fig1 . in fig1 , fig . a shows a group treated with the culture solution , wherein the cell nucleus under the fluorescence microscope is intact and evenly colored , and the fluorescence is dispersive and relatively dim ; and figs . b , c , and d show cells of groups treated with 10 , 100 and 250 μmol / l respectively , wherein with the increase of the drug concentration , the chromatin thereof exhibits hyperchromatic massive or granular fluorescence , and the cell nucleus chromatin is coagulated , and the cell nucleus undergoes lysis , and the coloring is irregular and exhibits a typical variation of cell apoptosis . in addition , the action effects of mogroside ii a2 on the lymphoma u937 cells and the leukemia cells k562 are identical to the results of the human melanoma a875 cells . moreover , the same method was also utilized to respectively treat the human melanoma a875 cells , the lymphoma u937 cells and the leukemia cells k562 with mogroside i e1 and the mogrol , and the results obtained were identical to the results of mogroside ii a2 . it can be concluded that the mogrosides and analogs thereof can induce the apoptosis of various cancer cells , after that the mogrosides and analogs thereof act on the human melanoma a875 cells , the lymphoma u937 cells and the leukemia cells k562 for 24 h , and the amount for cell apoptosis increased with the rise of the concentration of the mogrosides and analogs thereof , namely , the effect of the mogrosides and analogs thereof on cancer cells exhibits a dose - dependence . lymphoma u937 cells , human melanoma a875 cells and leukemia cells k562 in logarithmic growth phase were taken , and the cell concentrations were adjusted to 2 × 10 7 cells / ml , and then the cells were inoculated to a 96 - well culture plate ( 100 μl each well ); and after the pre - culture for 24 h , 100 μl of culture solution prepared in different concentrations were added , such that each group of the mogrosides and analogs thereof had a final concentration of 0 . 1 , 1 , 10 , 100 , 200 and 250 μmol / l ( 6 doses ), respectively , and cells cultured with dmso were set as control groups . mtt colorimetric experiments were performed after 24 h , respectively : prior to the finish of each experiment , 15 μl of mtt solution in a concentration of 5 mg / ml was added to each well , and the culture was continued in dark at 37 ° c . for 4 h , then 150 μl of dmso was added to each well and oscillating in a shaker for 10 min , and then the residue was placed in a microplate reader to detect the optical density od ) at 490 nm , and the inhibition rate was calculated according to the following formula : cell growth inhibition rate ( control group od 490 — test group od 490 )/ control group od 490 × 100 %. the results obtained after u937 cell treatment by mogrol i e1 , mogrol ii a2 and mogrol were identical to each other . taking mogrol i e1 as an example , the results are shown in fig1 . it can be seen : the mtt experiment results show that the mogrosides and analogs thereof have an inhibitory effect on the proliferation of the histiocytic lymphoma u937 cells , and the inhibition rate thereof increases with the rise of the drug concentration or the prolongation of the action time , and it indicates that the inhibitory effect of the mogrosides and analogs thereof on the proliferation of the histiocytic lymphoma u937 cells has a significant dose - dependence and time - dependence . the anova variance analysis shows that the differences between different dose groups , between different time groups and their differences from the control groups all have a statistical significance . the results obtained after melanoma a875 cell treatment by mogrol i e1 , mogrol ii a2 and the mogrol were identical to each other . taking the mogrol as an example , the results are shown in fig1 . it can be seen : the mtt experiment results show that mogrosides and analogs thereof have an inhibitory effect on the proliferation of the melanoma a875 cells , and the inhibition rate thereof increases with the rise of the drug concentration or the prolongation of the action time , and it indicates that the inhibitory effect of the rnogrosides and analogs thereof on the proliferation of the melanoma a875 cells has a significant dose - dependence and time - dependence . anova variance analysis shows that the differences between different dose groups , between different time groups and their differences from the control groups all have a statistical significance . the results obtained after leukemia cell k562 treatment by mogrol i e1 , mogrol ii a2 and the mogrol were identical to each other . taking mogrol ii a2 as an example , the results are shown in fig2 . it can be seen : the mtt experiment results show that mogrosides and analogs thereof have an inhibitory effect on the proliferation of the leukemia cells k562 , and the inhibition rate thereof increases with the rise of the drug concentration or the prolongation of the action time , and it indicates that the inhibitory effect of the mogrosides and analogs thereof on the proliferation of the leukemia cells k562 has a significant dose - dependence and time - dependence . after analysis of variance , the differences between different dose groups , between different time groups and their differences from the control groups all have a significant meaning . in addition , tests of examples 3 to 8 were also performed regarding prostate cancer cells , renal carcinoma cells , head and neck squamous cell carcinoma cells , lung cancer cells , ovarian cancer cells , breast cancer cells , pancreatic cancer cells , liver cancer cells and colon cancer cells , and the results thereof were all identical to the results of the lymphoma u937 cells . moreover , tests of examples 3 to 8 were also performed on mogrol iii , mogrol iv , mogroside v and mogroside vi , and the results thereof were all identical to those of mogrol i e1 and mogrol ii a2 ; in addition , tests of examples 3 - 8 were also performed regarding prostate cancer cells , renal carcinoma cells , head and neck squamous cell carcinoma cells , lung cancer cells , ovarian cancer cells , breast cancer cells , pancreatic cancer cells , liver cancer cells and colon cancer cells , and the results thereof were all identical to the results of the lymphoma u937 cells . the mogrosides and analogs thereof provided in the present application are prepared into health care products and foodstuffs , e . g . biscuits , chewing gum , beverages , tea , cream candy and dairy products ; and they also have a very good inhibitory effect on malignant melanoma , prostate cancer , renal carcinoma , head and neck squamous cell carcinoma , lung cancer , ovarian cancer , breast cancer , pancreatic cancer , liver cancer , colon cancer , lymphoma and leukemia . the above - mentioned examples explain the stat3 and erk signal pathway inhibitor provided in the present invention , which main components , i . e . the mogrosides and analogs thereof , have efficacies of selectively inhibiting the signal pathways of nuclear transcription factors stat3 and erk , and of inhibiting tumor cell growth and inducing its apoptosis and inhibiting tumor proliferation . tumors relating to the stat3 signal pathway include solid tumors , such as malignant melanoma , prostate cancer , renal carcinoma , head and neck squamous cell carcinoma , lung cancer , ovarian cancer , breast cancer , pancreatic cancer , liver cancer and colon cancer ; and non - solid tumors such as lymphoma and leukemia , e . g . large granular lymphocytic leukemia , chronic lymphoblastic leukemia and acute lymphoblastic leukemia . as the mogrosides and analogs thereof have a pharmaceutical value of inhibiting stat3 and erk signal pathways , it can be deduced that they also have an inhibitory effect on other cancers relating to stat3 and erk signals . although the present invention has already been explained and described through specific examples , it shall be aware that many further modifications and variations may also be made without departing from the spirit and scope of the present invention . thus , it means that all these modifications and variations falling in the scope of the present invention are included in the appended claims .
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turning now to the drawings and , more particularly , fig1 shows an example of a method 100 of forming semiconductor devices , replacement metal gate ( rmg ) gate field effect transistors ( fets ), and integrated circuit ( ic ) chips with preferred rmgfets , according to a preferred embodiment of the present invention . although described with reference to cmos , the present invention has application to any suitable replacement metal gate technology . the preferred method 100 has application to forming rmgfets on bulk or silicon on insulator ( soi ) wafers with soi planar , mesa , fin or nanowire channels . bulk wafers may be silicon , germanium ( ge ), a iii - v semiconductor or compound thereof . fin or nanowire channels may include more than one fin or nanowire . fabrication begins in step 102 defining dummy devices ( fets ). dummy sidewall spacers are formed step 104 on the dummy dielectric layer . patterning 106 the dummy dielectric , which partially undercuts the dummy spacers . next , 108 source / drain regions and interlayer dielectric are formed on the wafer . the dummy gates are removed in step 110 to re - expose the remaining dummy dielectric . the dummy dielectric is removed in 112 . then , source / drain extensions are formed in 114 under the dummy spacers . in step 116 metal gates are formed to complete the rmgfets . thereafter , in step 118 chip processing continues to complete integrated circuit ( ic ) chip definition . so , in step 102 dummy devices ( fets ) are defined on a typical semiconductor wafer . preferably , dummy fets include dummy gates on a dummy dielectric layer . the dummy gates locate fet channels in / on a semiconductor surface of the wafer . previously , at this point in typical prior art rmgfet formation , the dummy dielectric layer was patterned with the dummy gates ( as dummy gate dielectric ) and source / drain extension regions were defined adjacent to the dummy gates . fig2 a - b show an example of defining a chip device on a semiconductor wafer 120 ( definition step 102 in fig1 ). the semiconductor wafer may be an soi wafer or a bulk doped or undoped wafer of silicon ( si ), silicon germanium ( sige ) or any suitable semiconductor . device channels , formed in / on the semiconductor wafer 120 , may be bulk surface channels or soi channels , planar , fins or nanowires . channels may be defined using an active isolation step such as , for example , shallow trench isolation ( sti ) or mesa formation . a dummy dielectric layer 122 is , preferably , a 3 to 6 nanometer ( 3 - 6 nm ) thick oxide formed on the wafer surface 124 , with excellent etch selectivity to subsequently formed dummy gate 126 material . suitable such oxides include , for example , sio 2 , geo 2 , and aluminum oxide ( al 2 o 3 ). dummy gates 126 are formed by first forming a layer of a suitable material , e . g . polysilicon ( poly ), on the dummy dielectric layer 122 . a hard mask 128 patterned on the dummy gate material layer defines and protects gates 126 . the hard mask 128 may be any suitable material , including for example , silicon nitride ( si 3 n 4 ) layer , patterned photolithographically using a suitable well know photolithographic mask and etch . after forming the hard mask 128 pattern , exposed dummy gate material is removed , e . g ., etched with an etchant selective to poly . as noted hereinabove , source / drain extension regions are not defined adjacent to the dummy gates 126 at this point . instead , as shown in the example of fig3 , dummy sidewall spacers 130 are formed ( step 104 in fig1 ) along the dummy gates 126 and on the dummy dielectric 122 . the dummy sidewall spacers 130 may be formed , for example , by forming a conformal layer of sidewall dielectric and removing horizontal portions with a directional etch , e . g ., a reactive ion etch ( rie ). the dummy sidewall spacer 130 dielectric may be any suitable dielectric , preferably a nitride such as , si 3 n 4 , sibcn , sinh or bn . fig4 shows an example of patterned ( 106 in fig1 ) dummy dielectric 140 undercutting the dummy spacers 130 . the dummy gates 126 and sidewall spacers 130 serve as a mask for patterning 106 the dummy dielectric layer . patterning 106 partially undercuts 142 the dummy spacers 130 . the patterned dummy dielectric 140 remains under the dummy gates 126 , and at least partially under dummy sidewalls spacers 130 to undercuts 142 , where source / drain extension regions are subsequently formed . patterning the dummy dielectric 140 completes placeholder 144 formation for source / drain region and interlayer dielectric formation . so , as shown in the example of fig5 a - b , fet source / drains 150 ( formed 108 in fig1 ) form outboard of the dummy spacers 130 and extend into the placeholder undercuts 142 , followed by ild 152 formation . the fet source / drains 150 may be formed , for example , by epitaxially growing doped semiconductor on the semiconductor surface ( e . g ., on fins ) at source / drain regions and / or by a deep source / drain ion - implant . preferably for finfets , doped epitaxially grown semiconductor is phosphorous or arsenic - doped silicon ( si ) grown on nfet fins , and boron - doped silicon germanium ( sige ) grown on pfet fins . interlayer dielectric 152 covers the source / drain regions 150 and fills between the placehholders 144 . fig6 a - b show an example of removing ( step 110 in fig1 ) the dummy gates 126 to re - expose the patterned dummy dielectric 140 between the dummy spacers 130 . an interlayer dialectic ( ild ) 160 formed on the wafer fills between the dummy spacers 130 . preferably , the ild 160 is an oxide such as sio 2 , or a lower k oxide . the patterned hard mask 128 is removed , e . g ., using an oxide cmp , to re - expose the tops of dummy gates 126 . in this example , the cmp removes upper portions of the dummy spacers 130 and ild 160 . the exposed dummy gates 126 may be removed , for example , with a suitable etch selective to silicon . fig7 shows an example of the structure after ( 112 in fig1 ) removing all of the patterned dummy dielectric to re - expose the wafer surface between and beneath the dummy spacers 130 , i . e ., at the channel and extensions . the patterned dummy dielectric may be removed using any suitable wet etch , such as a hydrofluoric acid ( hf ) based solution , or a highly selective dry etch . fig8 a - c show an example of forming ( 114 in fig1 ) source / drain extensions under the dummy spacers 130 . preferably , source / drain extensions are formed by depositing and selectively patterning an atomic layer dopant through the open space between the dummy spacers . a dopant diffusion step , e . g ., an extension anneal , forms well controlled source / drain extensions from the patterned atomic layer dopant . in one preferred embodiment , a seven angstrom ( 7 å ) atomic layer dopant ( aldo ) is deposited on the wafer selective to the dummy spacers 130 , forming aldo 180 where previously existing patterned dummy dielectric was removed . suitable atomic layer dopants include atomic boron or germanium - boron for pfets and atomic phosphorous ( p ) for nfets . selectively etching aldo 180 , e . g ., in a timed etch , removes the dopant from the fet channel surface 182 , leaving dopant pockets 184 (& lt ; 3 nm wide ) under the dummy spacers 130 . a junction rapid anneal drives in the dopant in pockets 184 , activating extension 186 . preferably , the junction rapid anneal is at a temperature that does not alter channel material stability . for example , annealing temperature may range from 450 - 900 ° c . depending on the channel material with lower temperatures for iii - v semiconductor and ge , and relatively higher temperatures for si - based channels . because , there is no need for subsequent high temperature processing steps or anneals , the source / drain extension 186 junctions remain where they form , essentially unaffected by subsequent fabrication steps . fig9 a - d show an example of forming ( 116 in fig1 ) metal gates above the channel , between the source / drain extensions to complete the rmgfets . first , a suitable selective wet etch strips the dummy spacers 130 away , and exposes the extensions 186 . final low - k spacers 190 are formed above the extensions 186 , e . g ., by forming a conformal layer of sidewall dielectric and removing horizontal portions with a directional etch , e . g ., a reactive ion etch ( rie ). suitable low - k dielectric may include , for example , sibcn , sinh or bn . a high - k gate dielectric layer 192 is formed , e . g ., deposited , on the wafer . suitable such high - k dielectric may be , for example , hafnium oxide ( hfo 2 ), hfsio , hfsion , alo , al 2 o 3 , titanium oxide ( tio 2 ), lanthanum oxide ( la 2 o 3 ) or a combination or stack thereof . metal gates 194 are formed by forming a metal layer on the high - k gate dielectric layer 192 and removing surface portions of the metal layer and high - k dielectric layer 192 to the ild 160 . the surface metal layer and high - k dielectric layer 192 may be removed using a typical cmp that re - planarizes the wafer surface and leaves metal gates 194 in metal gate dielectric 196 . fig1 shows an example of a wafer 200 with multiple ic chips 202 after ( 118 in fig1 ) middle of the line ( mol ) dielectric and contact formation and through normal back end of the line ( beol ) steps . circuit definition continues normally as wiring is formed 116 on and above the planarized surface . the wiring connects devices ( preferred fets ) together into circuits 202 and circuits 202 together on the chips 204 . beol fabrication continues complete the chips 204 , e . g ., connecting the circuits to pads and terminal metallurgy . thus advantageously , short channel effects are reduced / minimized in ics with preferred rmgfets . source / drain extensions are formed well controlled , because they are formed after forming interlayer dielectric ( ild ) on already completed source / drain regions and just prior to forming metal gates . while the invention has been described in terms of preferred embodiments , those skilled in the art will recognize that the invention can be practiced with modification within the spirit and scope of the appended claims . it is intended that all such variations and modifications fall within the scope of the appended claims . examples and drawings are , accordingly , to be regarded as illustrative rather than restrictive .
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with reference to the drawings , in fig1 , a weight - bearing harness ( 10 ) to be worn by a person ( the “ wearer ”) over at least one shoulder of the wearer is shown in perspective view from the front . in some embodiments , the harness ( 10 ) comprises at least a first strap ( 12 ) which , when worn , is positioned over one shoulder of the wearer , where the strap ( 12 ) descends downwardly from the wearer &# 39 ; s shoulder in the front (“ front strap ” ( 14 )) and in the back (“ back strap ” ( 16 )) of the wearer to a lower second strap which encircles the wearer at about the wearer &# 39 ; s waist or hip region (“ waist strap ” ( 18 )); the front strap ( 14 ) is attached at its front end ( 20 ) and the back strap ( 16 ) is attached at its back end ( 22 ) to the waist strap ( 18 ) in the front region ( 24 ) and back region ( 26 ) of the waist strap ( 18 ), respectively . in particular embodiments , the front strap ( 14 ) and back strap ( 16 ) descend about vertically from the wearer &# 39 ; s shoulder to the waist strap ( 18 ); in other particular embodiments , the front strap ( 14 ) and back strap ( 16 ) descend at an angle from the wearer &# 39 ; s shoulder , such that the strap ( 12 ) is worn over one shoulder , and attached at its front end ( 20 ) and back end ( 22 ) to the waist strap front region ( 24 ) and waist strap back region ( 26 ) at positions somewhere under the wearer &# 39 ; s opposite shoulder . in other embodiments , as shown in fig2 , 3 , and 4 , the weight - bearing harness ( 110 ) comprises two straps , a first strap 112 and a third strap 113 which when worn are positioned one over each of the wearer &# 39 ; s shoulders , where each strap descends downwardly in the front (“ front straps ” 114 , 115 ) and in the back (“ back straps ” 116 , 117 ) of the wearer from each of the wearer &# 39 ; s shoulders to a lower second strap which encircles the wearer at about the wearer &# 39 ; s waist or hip region (“ waist strap ” 118 ); the straps 112 , 113 are attached at their front ends 120 , 121 and at their back ends 122 , 123 to the waist strap 118 in the front region of the waist strap 124 and in the back region of the waist strap 126 , respectively . in particular embodiments , the back straps 116 , 117 may descend straight down the wearer &# 39 ; s back from the wearer &# 39 ; s shoulders to the back region of the waist strap 126 ; in other particular embodiments , the back straps 116 , 117 may cross each other at the back of the wearer before continuing down to the back region of the waist strap 126 ; in another embodiment , the back straps 116 , 117 may be attached to each other at the back of the wearer at least one point , from which they then descend vertically to the back region of the waist strap 126 either jointly , as one strap , or as two separate straps . the two back straps 116 , 117 may be joined to each other by at least a fourth strap ( a “ horizontal back strap ,” not shown ) or by a back brace ( not shown ) or by other means to provide greater comfort and back support . in other particular embodiments , the back straps 116 , 117 comprise one piece from the wearer &# 39 ; s shoulders to the wearer &# 39 ; s waist ( a “ back piece ,” not shown ), and are thus connected to the front straps 114 , 115 at about the wearer &# 39 ; s shoulders and to the back region of the waist strap 126 at the bottom of the back piece of the wearer &# 39 ; s back ; and in yet other particular embodiments , the back straps 116 , 117 may extend downward from the wearer &# 39 ; s shoulders some length before being connected to a single back piece , which is then connected to the back region of the waist strap 126 . the straps 12 , 112 , 113 may be of any suitable width and length , and may further comprise means to adjust their length to more snugly fit the wearer ; such means are well known and include but are not limited to ties , cinches , buckles , velcro , and the like . the harness may further comprise means to adjust the position of the straps 12 , 112 , 113 relative to the wearer , to improve fit and comfort ; such means are well known and include but are not limited to ties , cinches , buckles ( 38 , as shown in fig4 ), velcro , and the like . the waist strap 18 , 118 has two ends at the wearer &# 39 ; s front toward the center of the wearer 30 , 32 , 130 , 132 , and when worn are generally fastened together by any well known means , which include but are not limited to ties , cinches , buckles , velcro , and the like . the waist strap 18 , 118 may also be of any suitable width and length , and may further comprise means to adjust their length to more snugly fit the wearer ; such means are well known and include but are not limited to ties , cinches , buckles , velcro , and the like . at least one handle 34 is attached to at least one front strap 14 , 114 , 115 or to a front region of a waist strap 24 , 124 . in some embodiments , two handles 34 are attached one to each front strap 14 , 114 , 115 , and in other embodiments , four handles 34 are attached to the front straps 114 , 115 , two to a strap . in other embodiments at least one handle 34 is attached to a front region of a waist strap 24 , 124 , preferably toward the ends of the waist strap 31 , 32 , 130 , 132 , and in other embodiment two handles 34 are attached to a front region of a waist strap 24 , 124 , preferably toward the ends of the waist strap 31 , 32 , 130 , 132 , one handle 34 on either side of the center line of the wearer and on either side of the two ends of the waist strap 31 , 32 , 130 , 132 at the front of the wearer . and in other embodiments at least one handle 34 is attached to a front strap 14 , 114 , 115 and at least one handle 34 is attached to a front region of a waist strap 24 , 124 in any of the configurations as described above . the handles 34 are positioned on a front strap 14 , 114 , 115 or on a front region of a waist strap 24 , 124 so that when the harness 10 , 110 is worn and a handle 34 is grasped by the hand of the wearer either on the same side as or opposite to location of the handle 34 on a front strap 14 , 114 , 115 or on a front region of a waist strap 24 , 124 , the arm is either perpendicular to the ground , or slightly angled up away from perpendicular or angled slightly downward from perpendicular . the handles 34 may be attached to a front strap 14 , 114 , 115 , or a front region of a waist strap 24 , 124 at one or more points . a handle 34 may be any configuration which is comfortably grasped by the wearer &# 39 ; s hand and which when grasped provide support for the wearer &# 39 ; s arm . exemplary handles include but are not limited to : a strip of material attached at both of its ends to a strap ; a strip of material fashioned into a loop attached at one end to a strap ; a circular or oval shaped handle ; a knob in any shape easily grasped by a hand , where the knob may further comprise a slight flange at its lower end for further supporting the hand grasping it . a handle 34 may be attached to a strap 14 , 114 , 115 , 24 , 124 in a fixed fashion , such that the handle 34 does not generally reorient itself with respect to the strap 14 , 114 , 115 , 24 , 124 , or a handle 34 may be attached to a strap 14 , 114 , 115 , 24 , 124 in such a fashion such that it can rotate to different angles with respect to the strap 14 , 114 , 115 , 24 , 124 , to accommodate different angles of the hand grasping it . a handle 34 may also be attached to a strap 14 , 114 , 115 , 24 , 124 in a retractable fashion , such that the handle 34 can be pulled out to a certain length , and then retracted close to or into a strap 14 , 114 , 115 , 24 , 124 when not in use . alternatively , a handle 34 may be removably attached to a strap 14 , 114 , 115 , 24 , 124 , by means including but not limited to by ties , snaps , buttons , clips , buckles , and the like , such that a handle 34 may be removed from a harness 10 , 110 and later again removably attached . a handle 34 may also be attached to a strap 14 , 114 , 115 , 24 , 124 by means of a knob which fits into a groove or slot , where the groove or slot is located on a strap 14 , 114 , 115 , 24 , 124 and the knob on the handle 34 , or vice versa ; in these embodiments , the handle 34 is attached to a strap 14 , 114 , 115 , 24 , 124 by sliding the knob into the groove or slot . the front straps 14 , 114 , 115 , 24 , 124 may further comprise additional means for removably securing items to the front straps . such means include but are not limited to ties , loops , snaps , buttons , velcro , buckles , hooks , rings ( such as a d ring 36 as shown in fig4 ), clips and the like , attached to the front straps 14 , 114 , 115 , 24 , 124 to which items may be clipped or otherwise secured . exemplary items that may be secured to the harness 10 , 110 via these means include but are not limited to baby items such as pacifiers , toys , bibs , bottles , and in certain embodiments , baby carriers , such as baby carrier pouches . a baby carrier may be securely and removably fastened at several points to the front of the harness 10 , 110 by such means as described above ; alternatively , additional straps may be securely fastened to the front of the harness 10 , 110 , either permanently or removably such as with zippers , buckles , and the like , where these additional straps comprise means by which a baby carrier may be securely and removably fastened to the front of harness 10 , 110 . harness straps 12 , 112 , 18 , 118 may be made of any conventional material suitable for this use , including nylon , webbing , leather , rubberized material and the like . harness straps 12 , 112 , 18 , 118 may further comprise padded sections for increased comfort during wear , such as over the shoulders , and at the back . likewise , handles 34 may also be fashioned of any material suitable to this particular use , including strapping material , rubber , foam , tubing , padded webbing , mixed materials such as plastic and foam , and the like . the harness 10 , 110 may be worn over an outer garment of the wearer , where an outer garment is worn outside of all other garments ; exemplary outer garments include but are not limited to coats , jackets , blazers , vests , shirts , sweatshirts , and the like ; m these embodiments , the ends of the waist strap 30 , 32 , 130 , 132 include a means to securely fasten the harness to the wearer , as described above . the harness 10 , 110 may also be incorporated into an outer garment of the wearer . an exemplary embodiment is shown in fig5 , in which weight - bearing harness 110 is incorporated into the interior of a vest 140 . the harness 110 is incorporated into the interior portion 142 of the garment , such as within a lining 144 . the harness 110 may be attached to the interior 144 of a garment 140 by the straps 112 , such as at the shoulder seams of either the underside of the lining 144 ( that side which faces the interior 142 of the garment 140 , and thus faces away from the wearer ) of the garment 140 , or to the seams or shoulder region of the interior 142 of the garment 140 itself . the waist strap 118 may be attached to the garment 140 , either at the garment interior 142 or to the underside of the lining 144 of the garment 140 , for a portion of the back region of the waist strap 126 ( which would then be attached to the back of the garment 146 or to the back of the garment lining 144 ) up to the entire length of the waist strap 118 from the back region of the waist strap 126 to the front region of the waist strap 124 ( where the front region of the waist strap 124 would be attached to the front of the garment 148 or to the front of the garment lining 144 ). the harness 110 may be even more securely attached to a garment 140 by attaching either the back straps 116 , 117 , the front straps 114 , 115 or both sets of straps 116 , 117 , 114 , 115 and for portions of their length up to their entire length , to the interior 142 of the garment 140 itself or to the underside of the lining 144 . in an embodiment , when weight bearing harness 110 is incorporated into a garment 140 , a portion of the waist strap 118 may remain unattached from the garment 140 , such as is shown in fig5 . in this embodiment , the ends of the waist strap 130 , 132 as shown in fig5 may then be fastened together by any of the means as described above , thus securing the waist strap to the body of the wearer of the garment 140 . in another embodiment shown in fig6 , the ends of the waist straps 130 , 132 are attached to a garment 150 at the front of the garment 152 , such that the each end of the waist strap 130 , 132 ends at and is attached to one side 156 , 158 of a front center closure 154 of the garment 150 . in fig6 , closing the garment 150 ( such as by a zipper or buttons or snaps or the like positioned on the front center closure 154 ) results in closing the waist strap 18 , 118 securely around the body of the wearer of the garment 150 . at least one handle 34 ( and / or additional attachment means , if present , such as d ring 36 ) is accessed by at least one discreet opening 160 in the outer portion of the garment 150 , where the opening extends through the outer portion of the garment 150 , and if necessary the garment lining 144 , to provide access to a handle 34 . the opening is disposed over a handle 34 , such that the handle 34 can be hidden from view when not in use , and may be pulled through the opening 160 to be grasped by the wearer &# 39 ; s hand when in use . at least one opening 160 may also be disposed over any at least one further attachment means ( such as d ring 36 ) attached to a strap 14 , 114 , 115 , 24 , 124 such that the attachment means may be accessed when the garment 150 is worn by a wearer . an opening 160 may simply be a slit in the outer garment 150 , or it may further comprise flaps , zippers , buttons , snaps , hooks , velcro , and the like , or any combination of these , to close the opening 160 and further conceal and / or pad the handles 34 and any other attachment means present . the harness 10 , 110 may also be worn under an outer garment of a wearer . in these embodiments , the outer garment is configured as described above , with at least one opening 160 in the outer portion of the garment 150 disposed over at least one handle 34 such that a handle 34 can be hidden from view when not in use , and may be pulled through the opening 160 to be grasped by the wearer &# 39 ; s hand when in use . when necessary , an opening 160 extends through an outer garment and into the interior , and through a garment lining 144 if present , so that a handle 34 of a harness 10 , 100 may be accessed when the garment is worn over the harness 10 , 110 . at least one opening 160 may also be disposed over any at least one further attachment means ( such as d ring 36 ) attached to a strap 14 , 114 , 115 , 24 , 124 such that the attachment means may be accessed when the garment 150 is worn by a wearer . to carry a child 162 or other item with a harness 110 in place , as shown in fig6 , the wearer simply places the child 162 or other item on a forearm and then reaches across the chest with the hand attached to the forearm to a handle 34 on a front strap 114 on the side opposite the carrying arm , as shown in fig6 . as described previously , the wearer may grasp a handle 34 on the opposite side or the same side as the arm carrying a weight ; the wearer &# 39 ; s arm may be perpendicular to the ground , or angled slightly up or down . the harness 110 is designed to fit the wearer snugly , transfer some of the weight of the child 162 or other item carried in the wearer &# 39 ; s arms to the wearer &# 39 ; s shoulders and back , and to properly distribute the weight of a carried child 162 or other item over the wearer &# 39 ; s shoulders and back . the back support provided by a harness 10 , 110 further assists the wearer in maintaining good posture when carrying a child 162 or other item . a harness 10 , 110 is particularly useful in carrying infants and young children , such as toddlers and older , by the arms of the wearer of the harness 10 , 110 . many other items can also be carried in the arms of the wearer of the harness , including but not limited to books , bags ( containing other items such as groceries ), boxes , and the like , which are carried on the arm , as well as items with handles which can be carried suspended from the wearer &# 39 ; s arms . additional items may be carried by attaching them to the handles or to any additional attachment means which may be part of the harness . if a harness 10 , 110 is incorporated into an outer garment 150 , the wearer accesses a handle 34 by reaching through an opening 160 ( after first opening it , if necessary ). a harness incorporated into an outer garment allows the wearer to maintain a fashionable look when the harness is not in use , and to still appear quite fashionable when the garment is in use for carrying at least one item in at least one arm of the wearer . the harness is easy to use , easily accessible , and always available . it allows the wearer to carry items such as babies , books , bags , tools and the like closer to the wearer &# 39 ; s center of gravity . and it avoids or decreases arm muscle fatigue when carrying such items “ by hand ” for any other than short periods of time . it is understood that this invention is not confined to the particular structures herein illustrated and described , but embraces such modified forms hereof as come within the scope of the following claims .
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reference is made now in detail to a specific embodiment of the present invention , which illustrates the best mode presently contemplated by the inventor for practicing the invention . alternative embodiments are also briefly described as applicable . referring to fig1 a programmable array logic ( pal ) device 10 includes a programmable logic array 12 , a register pair 14 , a multiplexer 16 , input logic 18 , an observability buffer 20 , and a dual clock buffer 22 . associated with logic array 12 are a number of input buffers such as buffers 24 and 26 , a number of output buffers such as buffers 28 and 30 , and a number of data sense amplifiers such as those shown at 32 and 34 . external inputs and outputs to logic device 10 include pins 1 , 2 , 5 , and 11 as well as input pin 36 and i / 0 pins 38 and 40 . logic array 12 is preferably a fuse programmable and array and a fixed or array having a plurality of array inputs such as inputs 42a / b and 44a / b , a plurality of control inputs such as control input 46 , and a plurality of array outputs such as outputs 48 , 50 , 52 , 54 , and 56 . alternatively or additionally , logic array 12 can include a fuse programmable or array . the manufacture and use of a logic array 12 is well known to those skilled in the art , and will not be discussed here in detail . a good reference describing pal architecture is the programmable array logic handbook published by advanced micro devices , inc . of sunnyvale , calif . input buffer 24 couples input pin 36 to array input lines 42a and 42b . more specifically , input pin 36 is coupled to the input of a first inverter 58 , the output of which is coupled to array input 42b and to the input of a second inverter 60 which has an output coupled to array input 42a . thus , a signal applied to pin 36 is developed on input 42a , and its inverse is developed on input 42b . in an analogous manner , a signal applied to pin 38 develops a signal on input 44a , and an inverse signal on input 44b . array outputs 48 and 50 are inverted by inverters 28 and 30 , respectively , to produce a synchronous preset ( sp ) signal on a line 62 , and an asynchronous reset ( ar ) signal on a line 64 . data sense amplifier 32 includes a first inverter 66 and a second inverter 68 which produce a data ( d ) signal on a line 70 and an inverse data signal ( id ) on a line 72 . similarly , data sense amplifier 34 produces a data signal ( d ) on a line 74 and an inverse data signal ( id ) on a line 76 . the register pair 14 includes a buried register 78 and an output register 80 . both buried register 78 and output register 80 include a preload enable ( p ) input , an inverse data input ( id ), a data input ( d ), an asynchronous reset input ( ar ), a synchronous preset input ( sp ), a preload data input ( pd ), and a clock input ( ci ). buried register 78 has a data output qb , and output register 80 has a data output q . buried register 78 has its id and d inputs coupled to lines 76 and 74 , respectively , and its ar and sp inputs coupled to lines 64 and 62 , respectively . output register 80 has its id and d inputs coupled to lines 72 and 70 , respectively , and its ar and sp inputs coupled to lines 64 and 62 , respectively . the p inputs of buried register 78 and output register 80 are both coupled to a line 82 , and their pd inputs are coupled to i / 0 pin 40 by a line 84 . multiplexer 16 has a q input which is coupled to the q output of output register 80 , and a qb input which is coupled to the qb output of buried registers 78 . multiplexer 16 also has an iobs select input coupled to a line 86 , and an obs select input coupled to a line 88 . the iobs and obs select inputs determine which of data inputs q and qb is multiplexed to line 84 and thus to i / 0 in 40 . input logic 18 includes a zenered buffer 90 , a zenered inverter 92 , a zenered nor gate 94 , a zenered or gate 96 , a zenered inverter 98 , and a pair of nand gates 100 and 102 . zenered gates 90 - 98 are tri - level logic devices having input logic levels lo , hi , and zhi . in ttl implementations of the present device , a lo input is no more than 0 . 8 volts , a hi input is no less than 2 . 0 volts , and a zhi input is nominally 11 volts . while the - outputs of zenered gates 90 - 98 have internal logic levels that are either lo or hi , only zhi is recognized as a logical high input to the zenered gates . thus , applying zhi to the input of zenered buffer 90 produces an internal logic level hi on line 82 , and applying a lo or hi to the input of zenered buffer 90 produces an internal logic level lo on line 82 . the rest of the gates of logic device 10 are not zenered , and thus are responsive to and generate only lo and hi logic signals . pin 2 is coupled to a line 104 which is connected to inputs of zenered buffer 90 , zenered inverter 92 , and zenered nor gate 94 . zenered buffer 90 develops a preload enable signal ( preload ) on line 82 , zenered invertor 92 develops an inverted preload enable signal ( ipreen ) on a line 105 , and zenered nor gate 94 develops an observability disable ( obsd ) signal on a line 106 . pin 1 is connected to a line 108 which is coupled to dual clock buffer 22 , zenered nor gate 94 , and zenered or gate 96 . except during the program mode of the present device , pin 1 is used as an external clock input pin , and develops a clock signal on line 108 . the clock signal on line 108 can generally be considered to be the master clock for the device 10 . pin 11 is coupled by a line 110 to an input of zenered nor gate 94 and to an input of zenered or gate 96 . zenered or gate 96 develops a programming and verification ( pvcc ) signal on line 46 which is input to logic array 12 and to nand gates 100 and 102 . pin 5 is coupled to a line 112 which is input into zenered inverter 98 and to nand gate 100 . the output of nand gate 100 on a line 114 is input to nand gate 102 as the signal i5 . zenered inverter 98 develops an observe during preload signal ( iobspre ) on a line 116 , and nand gate 102 develops an observe during verify ( iobsver ) signal on a line 118 . the observability buffer 20 includes an and gate 120 and an or gate 122 . and gate 120 is coupled to line 56 of logic array 12 and to line 106 of input logic 18 . the output of and gate 120 is developed on a line 124 which is a non - inverted input to or gate 122 . or gate 122 has a pair of inverted inputs which are coupled to lines 116 and 118 of input logic 18 , and an inverted output on line 86 and a non - inverted output on a line 88 . the signal on line 88 is the observation signal ( obs ), and the signal on line 86 is the inverse observation signal ( iobs ). clock buffer 22 includes a pair of and gates 126 and 128 , and a pair of or gates 130 and 132 . inverted inputs of and gates 126 and 128 are coupled to line 105 , and non - inverted inputs to and gates 126 and 128 are coupled to lines 86 and 88 , respectively . the outputs of and gates 126 and 128 on lines 134 and 136 , respectively , are input to or gates 130 and 132 , respectively . inverted inputs to or gates 130 and 132 are coupled to line 108 . or gate 130 develops a buried register clock signal ( cpb ) on a line 138 , and or gate 132 develops a output register clock signal ( cpo ) on a line 140 . line 138 is coupled to the clock input of buried register 78 , and line 140 is coupled to the clock input of output register 80 . as mentioned previously , logic device 10 operates on three input logic levels , namely lo , hi , and zhi . the logic device 10 has four modes of operation , namely the logic mode , the preload mode , the verify mode , and the program mode . of these four modes , the first three are associated with observing the contents of register pair 14 , and the program mode is used to program the logic array 12 . the four modes of operation will be discussed one at a time , commencing with the observability modes , and finishing with the programming mode . the logic mode of operation of logic device 10 will be discussed with reference to fig1 a , and 2b . fig2 a is a truth table for the various input , output , ard internal signals found in logic device 10 , and fig2 b is the legend for fig2 a . the encircled letters a - p in fig1 correspond to the encircled letters a - p of fig2 a . when in the logic mode , data of either output register 80 or of buried state register 78 can be observed under user control by producing an obspt signal on line 56 . to observe the data of output register 80 , the obspt signal on line 56 must be lo , and to observe the data of the buried state register 78 the obspt on line 56 must be hi . the obspt is produced within logic array 12 from the various inputs 36 and 38 . when in the logic mode , none of pins 1 , 2 , 5 , or 11 are zenered . thus , the preload signal on line 82 is lo , the ipreen signal on line 105 is hi , the obsd signal on line 106 is hi , the iobspre signal d on line 116 is hi , and the iobsver signal on line 118 is hi . since the preload enable inputs of buried register 78 and output register 80 are not enabled by the preload signal , register pair 14 operate as standard set / reset ( sr ) or d - type registers . since the ipreen signal on line 105 is hi , the output signals at l and m of and gates 126 and 128 , respectively , are lo . therefore , the clock signal on line 108 is inverted by or gates 130 and 132 and are output on lines 138 and 140 , respectively , as clock signals cpb and cpo . it should be noted that when in the logic mode , clock signals cpb and cpo are synchronized , and are essentially an inverted image of the clock signal . therefore , buried registers 78 and output register 80 are clocked together during the logic mode , and the device 10 operates as if it only had a single clock . every clock cycle the buried register 78 and the output register 80 clock in data from the outputs of data sense amplifier 34 and 32 , respectively . the data being clocked into registers 78 and 80 will , after a short internal delay , show up at outputs qb and q , respectively . multiplexer 16 couples either the q output of output register 80 or the qb output of buried register 78 to line 84 under the control of the iobs and the obs signals on lines 86 and 88 , respectively . since the obsd signal on line 106 , the iobspre signal on line 116 , and the iobsver signal on line 118 are all hi , the obs signal on line 88 is essentially the same as the obspt signal on line 56 . when obs on line 88 is hi and iobs on line 86 is lo , qb is multiplexed to line 84 , and in the inverse case q is multiplexed to line 84 . thus , when in the logic mode , a logical hi signal on line 56 allows the observation of the contents of buried register 78 , while a logical lo signal on line 56 allows the observation of output register 80 . still referring to fig1 a , and 2b to preload the buried register 78 and output register 80 the pin 2 is raised to a zhi logic level , which causes the preload signal on line 82 to go hi , the ipreen signal on line 105 to go lo . and the obsd signal on line 106 to go lo . the hi on line 82 enables the preload inputs of buried register 78 and output register 80 . the hi on line 82 furthermore disables multiplexer 16 , causing its output on line 84 to be tri - stated via an inverted enable input en . the lo logic level ipreen signal on line 105 enables and gates 126 and 128 , and the lo logic level obsd signal on line 106 disables and gate 120 , causing the signal level on line 124 to go lo . if the input signal on pin 5 is lo or hi , the signal iobspre on line 116 will be hi , as will be the iobsver signal on line 118 . since the signal level on line 124 is lo , and the signals on lines 116 and 118 are hi , the obs signal on line 88 will be lo , and the iobs signal on line 86 will be hi . furthermore , since line 86 and 88 are also inputs to the clock buffer 22 , a hi signal for iobs and a lo signal for obs enables and gate 126 and disables and gate 128 . since the ipreen signal on line 105 is lo , the output of and gate 126 is hi and the output of and gate 128 on line 136 is lo . thus , the cpb signal on line 138 must always be hi , while the signal cpo on line 140 will be the inverse of the clock signal on line 108 . in consequence , only output register 80 will be clocked when pin 2 is at a zhi level and pin 5 is at a lo or hi level , and only output register 80 will be preloaded via a line 84 . if pin 5 is raised to zhi while pin 2 is still at a zhi level , iobspre on line 116 is forced lo which , in turn , forces obs on line 88 hi and iobs on line 86 lo . as mentioned previously , multiplexer 16 is disabled and its output on line 84 is tri - stated during the preload cycle . furthermore , the obs and iobs signals on lines 88 and 86 , respectively , disable and gate 126 and enable and gate 128 . thus , when obs is hi and iobs is lo , cpo on line 140 is hi while cpb on line 138 is essentially an inversion of the clock signal on line 108 . in consequence , only buried register 78 is clocked and thus only buried register 78 preloads data from line 84 . it is important to note that clock buffer 22 operates differently in the preload mode than it did in the logic mode . as mentioned previously , in the logic mode cpb and cpo were essentially the same clock signals . however , in the preload mode only one of the clock signals cpb and cpo is activated at a time under the control of the input signal applied to pin 5 . the preload waveforms will be discussed with reference to fig3 . time delays or periods are indicated by td , and are not necessarily to scale . during a first period 300 , pin 5 is raised to zhi if the buried state registers are to be preloaded , and is hi or lo if the output registers are to be loaded . during period 302 , pin 2 is raised to zhi to preload enable the buried register 78 and the output register 80 . after a time delay in period 304 , the preload data is clocked into the selected register during a period 306 . after time delay periods 308 and 310 the zhi logic level on pin 2 is removed and the preload cycle is completed . the verification mode can be used to verify product terms stored within logic array 12 . since all of the product terms are associated either with a buried register 78 or an output register 80 , it is necessary to clock the desired product term into a register and then observe the contents of that register . to enter the verification mode , pin 11 is forced to a zhi level which , in turn , forces obsd on line 106 to a lo , and pvcc on line 46 to a hi . the hi logic level pvcc signal on line 46 is input to logic array 12 to enable appropriate gates within the logic array so that individually selected product terms are developed on the array outputs 52 and 54 . the hi logic level pvcc signal is also input into nand gates 100 and 102 . as before , the lo logic level obsd signal on line 106 forces and gate 120 to output a lo logic level signal on line 124 . pin 5 is used to select either the output qb of buried register 78 or the output q of register 80 for observation . when pin 5 is lo , signal i5 on line 114 is hi and signal iobsver on line 118 is lo . this , in turn , forces obs on line 88 to go hi and iobs on line 86 to go lo . since ipreen on line 105 is hi , cpb on line 138 and cpo on line 140 are essentially inversions of the clock signal on line 108 . thus , individually selected product terms from logic array 12 are being loaded into buried register 78 and output register 80 on a clock pulse . with obs on line 88 hi , multiplexer 16 selects input qb for output on line 84 . when pin 5 is hi , signal i5 on line 114 is forced l0 and iobsver on line 118 is forced hi . since the signal on line 124 is lo , iobspre on line 116 is hi , and iobsver on line 118 is hi , the or gate 122 forces the obs signal on line 88 to a lo level and iobs on line 86 to a hi level . again , individually selected product terms from logic array are clocked into buried register 78 and output register 80 on a clock pulse . however , multiplexer 16 is caused to select input q for output on line 84 when pin 5 is forced hi . referring now to fig4 the verification waveforms will be discussed . as before , td represents a time delay or period , and is not necessarily to scale in the drawings . starting in period 410 , pin 11 is at the zhi level to force device 10 into its verification mode . after a time delay in period 410 , a clock signal is applied to pin 1 to permit individually selected product terms from logic array 12 to be clocked into buried register 78 and output register 80 . the data output at pin 40 is stable after the end of period 412 . referring now to fig1 and 4 , to enter the programming mode the clock signal , if present , is removed from pin 1 and a zhi signal is applied to pin 1 . the zhi level signal on line 108 forces obsd on line 106 to go lo , causing signal on line 124 to also go lo and the pvcc signal on line 46 to go hi . control logic within logic array 12 is activated by the hi level pvcc signal on line 46 to permit individually selected product terms within logic array 12 to be programmed . referring more particularly to the waveforms of fig4 after a settling period 400 , pin 1 is raised to zhi during period 402 . column addresses are applied to various input pins , and a programming voltage vop is applied to the device 10 during a period 404 . during period 406 , pin 11 is raised to zhi to blow the appropriate fuse of the individually selected product term . in the present implementation of device 10 , a blown fuse is a logical lo as verified on an appropriate output pin . with reference to fig5 an observability buffer 20 &# 39 ; includes a number of bipolar npn transistors 510 , 512 , 514 , 516 , 518 , 520 , and 522 ; a number of diodes ( rectifiers ) 524 , 526 , 528 , 530 , and 532 ; and a number of resistors 534 , 536 , 538 , 540 , 542 , 544 , 546 , and 548 . a fuse 550 is provided to balance a fuse within logic array 12 ( not shown ). when in the logic mode , obsd , iobspre , and iobsver are all hi , and the obspt signal on line 56 controls the outputs of observability buffer 20 &# 39 ;. when obspt is lo , the base of transistor 510 will be lo , causing the transistor to turn off . this will force the base of transistor 512 hi , causing it to conduct and thereby turning off transistor 514 and turning on transistor 516 . this , in turn , causes the obs signal on line 88 to go lo , turns off transistor 518 , turns on transistor 520 , and turns off transistor 522 to raise the iobs signal on line 86 to hi . when in the logic mode and when obspt is hi , transistor 510 is turned on , forcing the base of transistor 512 to a lo signal level . this causes transistor 512 to turn off , transistor 514 to turn on , and transistor 516 to turn off , causing the obs signal on line 88 to go hi . the base of transistor 518 is coupled to line 88 by diode 530 and will therefore also be at a hi logic level , turning on transistor 518 and 522 , with the result that the iobs signal on line 86 will go lo . in the preload mode , the obsd signal on line 106 is lo , which pulls the base of transistor 510 down to a lo logic level , shutting it off . in consequence , the obspt signal on line 56 is disabled . since , in the preload mode , the iobsver signal on line 118 is always hi , the iobspre signal on 116 will control the outputs of observability buffer 20 &# 39 ;. when the iobspre signal on line 116 is hi , transistor 512 is turned on , shutting off transistor 514 and turning on transistor 516 . the obs signal on line 88 will therefore be lo when the iobspre signal 116 is hi . the iobs signal on line 86 will be the inversion of the obs signal on line 88 ( i . e . hi ) because transistors 518 and 522 will be off , and transistor 520 will be on . when the iobspre signal on line 116 is lo , the base of transistor 512 is pulled lo , shutting off transistor 512 . this , in turn , turns on transistor 514 and turns off transistor 516 , causing the obs signal on line 88 to go hi and the iobs signal on line 86 to go lo . in the verify mode , the obsd signal on line 106 is lo which ensures that transistor 510 is off and that the cbspt signal on line 56 is disabled . since the iobspre signal on line 116 is always hi , the iobsver signal on line 118 controls the outputs of the observability buffer 20 &# 39 ;. the iobsver signal on line 118 controls the observability buffer 20 &# 39 ; during the verify mode in the same manner that the iobspre signal on line 116 controls the observability buffer 20 &# 39 ; during the preload mode . the observability buffer 20 &# 39 ; can be thought of as being comprised of three stages , namely an input stage 552 , a first inversion stage 554 , and a second inversion stage 556 . the input stage 552 is responsive to a first input signal obspt , a second input signal obsd , a third input signal iobspre , and a fourth input signal iobsver , and is operative to develop an intermediate signal on a line 558 . in effect , transistor 510 and diodes 524 and 526 cooperate to perform the logical nand operation on the obspt and obsd signals , and line 558 serves as a hard - wired and for the signal on the collector of transistor 510 and for the iobspre and iobsver signals . the first inversion stage 554 and the second inversion stage 556 are substantially identical , and are coupled together by diode 530 . it should be noted that the logic gates of observability buffer 20 of fig1 are slightly different than the logic embodied in the three stages of observability buffer 20 &# 39 ; of fig5 . this serves as an example that there are many possible logic gate combinations for the observability buffer which can produce the results shown in the truth table of fig2 a . the foregoing description of the preferred embodiment of the present 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 . obviously , many modifications and variations will be apparent to practitioners skilled in this art . it is possible that the invention may be practiced in many fabrication technologies in mos or bipolar processes . similarly , any process steps described might be interchangeable with other steps in order to achieve the same result . the embodiment was chosen and described in order to best explain the principles of the invention and its practical application , thereby enabling others skilled in the art to understand the invention for various embodiments and with various modifications as are suited to the particular use contemplated . it is intended that the scope of the invention be defined by the claims appended hereto and their equivalents .
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with reference to fig1 there is shown a preferred embodiment of the present invention , a duplex electrical connector 20 that is an assembly of a two - piece die cast connector body 22 including a front connector body 24 and a rear connector body 26 . the front connector body 24 and rear connector body 26 are slideably connectable to one another along lines 27 as shown in fig1 . the front connector body 24 includes a nose portion 28 and a leading end 30 and a trailing end 32 . a fastening arrangement 34 is included on the leading end of the front connector body 22 for fastening the duplex electrical connector 20 to an electrical panel or junction box ( not shown ). the fastening arrangement 34 includes a seat 36 on the nose portion 28 and a snap ring 38 that is shown exploded away from the leading end 30 of the front connector body 24 . the rear connector body 26 includes a leading end 40 , a trailing end 42 with two bores 44 therein , and a cable retaining ring 46 inserted in each trailing bore 44 . a throat insert 48 is inserted the nose portion 28 of the front connector body 26 and a fastener 50 secures the front connector body 24 and rear connector body 26 together . referring to fig2 - 4 , the front connector body 24 includes a top side 52 , a bottom side 54 , and a lip 56 extending from the top side 52 of the front connector body 24 at the trailing end 32 . a tab 58 extends from the lip 56 at the top side 52 of the front connector body 24 as shown in fig3 and includes an aperture 60 therein . the front connector body 24 further includes a leading flange 62 and an intermediate flange 64 surrounding the seat 36 . a trailing flange 65 extends along the bottom periphery of the trailing end 32 . the front connector body further includes rounded shoulders 66 . two viewports 68 are included on both the top side 52 and bottom side 54 of the front connector body 24 . with reference to fig5 - 7 , the front connector body 24 includes a wide bore 70 at the trailing end 32 narrowing to a narrower leading bore 72 . the interior walls 74 that form the transition from the wide bore 70 to the leading bore 72 are smooth , gradually arcuate , and devoid of sharp edges to enable easy passage of wire conductors from the wide bore 70 to the leading bore 72 . each viewport 68 on the top side 52 is axially aligned with a viewport on the bottom side 54 of the front connector body 24 as shown by axis 76 in fig7 . referring to fig8 - 10 , the rear connector body 26 includes a top side 78 , a bottom side 80 , and a front extension 82 extending from the leading end 40 . the front extension 82 extends from the lower half of the rear connector body and includes an open channel 84 therein . a boss 86 is included on the top side 78 of the rear connector body 26 and includes an aperture 88 therein . two semi - circular notches 90 are included in the front extension 82 . openings 92 a and 92 b are included in the rear connector body 26 , with each opening in communication with one of the trailing bores 44 . as shown in fig1 , the front extension 82 may include outer portions 82 a and an inner portion 82 b separated by the semi - circular notches 90 . as shown in fig1 and 15 , a rim 91 extends from the outer periphery 93 of the rear connector body 26 at the leading end 40 . with reference to fig1 and 17 , the duplex electrical connector 20 is assembled by securing front connector body 24 and rear connector body 26 together with fastener 50 to form a two - piece die cast connector body 22 . snap ring 38 , which is preferably a split ring formed of a resilient metal and in its unbiased state includes a diameter smaller than the diameter of the seat 36 , is slightly expanded to slip over the leading flange 62 and is then secured onto the seat 36 on the nose portion 28 of front connector body 24 . the snap ring 38 includes locking tangs 94 thereon . the locking tangs 94 will function to secure the leading end 30 of the duplex electrical connector 20 to an electrical box or panel . leading flange 62 and intermediate flange 64 surround the seat 36 and hold snap ring 38 in place on the connector . a cable retaining ring 46 , which is preferably a split ring formed of a resilient metal and in its unbiased state includes a diameter larger than the diameter of each of the trailing bores 44 , is slightly compressed and then slipped into each of the trailing bores 44 . locking tangs 96 on the cable retaining rings 46 snap into openings 92 a and 92 b in rear connector body 26 and hold the cable retaining rings securely within the trailing bores 44 . throat insert 48 , preferably constructed of plastic , is pressed into the leading bore 72 ( see fig6 ) of front connector body 24 and held therein by a friction fit . throat insert 48 , optional for use on the duplex electrical connector 20 , acts to shield wire conductors from the interior of the leading bore in order to minimize fraying or abrasion of the outer sheath of the conductors ( not shown ). with reference to fig1 and 19 , each cable retaining ring 46 includes three cable retaining tangs 98 extending inward of the cable retaining ring , including a center tang 98 a and two outer tangs 98 b . center tang 98 a includes a flat end 101 that is perpendicular to the sides 103 of the center tang . outer tangs 98 b include ends 105 that are angled with respect to the sides 107 of the outer tangs . the orientation of the tangs 98 a and 98 b with respect to the duplex connector are set by the arrangement of the openings 92 a and 92 b ( see fig1 ) in the rear connector body 26 . outer tangs 92 b are positioned such that the short sides 107 are oriented toward the center 109 of the duplex connector and toward opposing quadrants . as shown in fig1 , when an electrical cable is inserted within the left trailing bore 44 a , the tangs 98 a and 98 b in the left trailing bore push the cable toward the center of the connector and toward the right lower quadrant of the bore 44 a , or in the direction of arrow 111 in fig1 . when an electrical cable is inserted within the right trailing bore 44 b , the tangs 98 a and 98 b in the right trailing bore push the cable toward the center of the connector and toward left upper quadrant of the bore 44 b , or in the direction of arrow 113 in fig1 . the orientation of the tangs 98 a and 98 b therefore advantageously maintain separation of the electrical cables and direct them toward the center of the leading bore ( see fig6 ). referring to fig2 - 22 , to secure the two connector body portions 24 and 26 together , front connector body 24 is slid sideways with respect to rear connector body 26 in the direction of arrow 115 until trailing flange 65 of front connector body latches into open channel 84 on front extension 82 of rear connector body 26 . fastener 50 is then secured through aperture 60 in tab 58 of front connector body 24 into aperture 88 in rear connector body 26 . with reference to fig2 and 24 , the duplex electrical connector 20 includes a leading end 117 and a trailing end 119 . the connector is used to secure one or two electrical cables ( not shown ) to a panel or an electrical box . to operate the invention , leading end 117 is simply pressed into the knockout of an electrical box . locking tangs 94 on snap ring 38 , being constructed of resilient metal such as spring steel , deflect inward when in contact with the walls of the knockout and then spring outward to their unbiased position after clearing the wall . the leading end is then securely locked into the knockout in the electrical box . one or two electrical cables ( not shown ) are then inserted into the bores 44 on the trailing end 119 of the duplex connector 20 . the three cable retaining tangs 98 a and 98 b ( see fig1 ), then direct each electrical cable to the center of the connector and the proper quadrant , after which the electrical cables are locked securely to the duplex connector 20 . the types of electrical cables and conduits that can be connector to an electrical box with the duplex electrical connector 20 include mc / hcf steel or aluminum cable , ac / hcf steel or aluminum cable , flexible metal conduit steel and aluminum , including both regular and reduced wall thickness , and mc cable continuous corrugated aluminum . with reference to fig1 , the present invention provides a method for securing an electrical cable to an electrical box , the method including : a . providing a duplex fitting 20 including a front connector body 24 having a leading end 30 , a trailing end 32 including a lip 56 and a trailing flange 65 , and a tab 58 with an aperture 68 therein ; b . providing a rear connector body 26 having a leading end 40 including a front extension 82 , an open channel 84 , and a rim 91 , and a boss 86 with a bore 88 therein ; c . pressing the trailing end 32 of the front connector body 24 against the leading end 40 of the rear connector body 26 ; d . sliding the trailing end 32 of the front connector body 24 along the leading end 40 of the rear connector body 26 until the trailing flange 65 of the front connector body 24 engages the open channel 84 in the rear connector body 26 and the lip 56 of the front connector body 24 engages the rim of the rear connector body 26 ; and e . threading a screw 50 through the aperture 68 in the tab 58 of said front connector body 24 and into the bore 88 of the boss 86 of the rear connector body 26 . preferably , the front connector body 24 and rear connector body 26 are each die - cast in one - piece of zinc alloy . the snap ring 38 and cable retaining rings 46 are preferably constructed of spring steel . the throat insert 48 is preferably constructed of plastic . although the description above contains many specific descriptions , materials , and dimensions , these should not be construed as limiting the scope of the invention but as merely providing illustrations of some of the presently preferred embodiments of this invention . thus the scope of the invention should be determined by the appended claims and their legal equivalents , rather than by the examples given .
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reference will now be made in detail to the subject matter disclosed , which is illustrated in the accompanying drawings . the scope of the invention is limited only by the claims ; numerous alternatives , modifications and equivalents are encompassed . for the purpose of clarity , technical material that is known in the technical fields related to the embodiments has not been described in detail to avoid unnecessarily obscuring the description . referring to fig1 , a block diagram of a system for displaying data having multiple security levels is shown . the system may include a processor 100 . the processor may be connected to a mls display 102 . the mls display 102 may render one or more entities 112 , 114 , 116 ; and each of the one or more entities 112 , 114 , 116 may be associated with a different security level . for example , a first entity 112 may be associated with a security level such as “ unclassified ” while a second entity 114 and a third entity 116 may be associated with a security level such as “ secret .” entities 112 , 114 , 116 may include data received via communication channels , representations of physical objects identified by radar , or any other data subject to graphical representation . the processor 100 may also be connected to one or more input devices 118 and a memory 120 . an input device 118 may include any device capable of receiving a user input to select a security level , or an entity having a security level , such as a touch screen , keyboard or voice input . the memory 120 may comprise a data structure to associate entities 112 , 114 , 116 with a security level . the system may also include one or more data communication devices 106 , 108 , 110 . data communication devices 106 , 108 , 110 may include navigation equipment , identification equipment , communication equipment , or any other device capable of sending , receiving or producing data for representation on a display such as the mls display 102 . each of the one or more data communication devices 106 , 108 , 110 may produce or communicate data at varying levels of security . the processor 100 may receive data , and an associated indicator of a security level for such data , from each of the one or more data communication devices 106 , 108 , 110 . alternatively , a security level for particular data may be inferred based on the nature of the data communication device 106 , 108 , 110 from which the data was received . the processor 100 and the mls display 102 may render data from each of the one or more communication device 106 , 108 , 110 as one or more entities 112 , 114 , 116 . the security level associated with each entity 112 , 114 , 116 may correspond to the security level associated with the data used to render the entity 112 , 114 , 116 . referring to fig2 , a block diagram of a system displaying de - emphasized entities is shown . in a system such as the system shown in fig1 , having a processor 100 connected to a mls display 102 , the processor 100 and mls display 102 may render entities 212 , 214 , 216 having more than one associated security levels . the entities 212 , 214 , 216 may be rendered based on data and a security level associated with the data . such data and associated security level may be stored in a data structure in a memory 120 connected to the processor 100 . a user may select a particular security level associated with one or more entities 212 , 214 , 216 through an input device 118 . the processor 100 and mls display 102 may render entities 212 , 214 , 216 in such a way as to emphasize entities 212 , 214 , 216 associated with the selected security level and de - emphasize entities 212 , 214 , 216 associated with a different security level . for example , a first entity 212 may be associated with a security level such as “ unclassified ” while a second entity 214 and a third entity 216 may be associated with a security level such as “ secret .” a user may select “ unclassified ” using the input device 118 . the processor may reference a data structure in the memory 120 to determine which entities 212 , 214 , 216 are associated with an “ unclassified ” security level . the processor 100 and mls display 102 may then render the second entity 214 and third entity 216 in such a way as to de - emphasize those entities 214 , 216 . de - emphasizing may include dimming , removing or otherwise visually distinguishing the de - emphasized entities 214 , 216 so as to make the entities 212 associated with the selected security level relatively more pronounced . additionally or alternatively , the processor 100 may emphasize entities 212 associated with the selected security level . alternatively , a user may select an entity 212 , 214 , 216 via an input device capable of allowing direct selection of entities 212 , 214 , 216 . the processor 100 may reference one or more data structures associating the selected entity 212 , 214 , 216 with a security level . the processor 100 and mls display 102 may then render entities 212 , 214 , 216 in such a way as to emphasize entities 212 , 214 , 216 associated with the security level corresponding to the elected entity 212 , 214 , 216 and de - emphasize entities 212 , 214 , 216 associated with a different security level . de - emphasized entities 214 , 216 may continue to be selectable via the input device 118 . the processor 100 may designate de - emphasized entities 214 , 216 as non - selectable to further enhance de - cluttering and segregation of entities 212 , 214 , 216 on the mls display 102 . a system according to this embodiment may allow a user to easily distinguish entities 212 , 214 , 216 based on the security level of each entity 212 , 214 , 216 and thereby help the user limit disclosure of information to data and entities 212 , 214 , 216 within a particular security classification . the processor 100 and mls display 102 may also render a visual indication of the security level associated any emphasized entities 212 . security levels may be hierarchical such that an authorization to receive data at a particular security level may include an authorization to receive data at all inferior security levels . where security levels are hierarchical , the processor 100 may de - emphasize entities 212 , 214 , 216 having superior security levels as compared to a security level selected via an input device 118 , but not de - emphasize entities 212 , 214 , 216 having inferior security levels . a user may also select , via the input device 118 , to return to a default rendering on the mls display 102 . the processor 100 may then re - render all entities 212 , 214 , 216 normally . referring to fig3 , a flowchart for a method of de - cluttering an mls display is shown . a user may select a desired security level through an input device connected to a processor . the processor may receive 300 the security level selection from the user and identify 302 one or more entities associated with the selected security level . entities may be associated with a selected security level in a data structure , or data used to render entities may be associated with a security level . entities associated with a selected security level may include entities associated with an inferior security level in a system where security levels are hierarchical . the processor may then de - emphasize 304 entities having a security level other than the selected security level such that the entities may be rendered in a visually distinct way . de - emphasis may include dimming the de - emphasized entities or prohibiting the de - emphasized entities from being drawn . the processor may also designate 306 one or more of the de - emphasized entities as non - selectable . “ security levels ” according to the present invention may be relative or absolute . while the foregoing discussion has specifically referenced “ unclassified ” and “ secret ” as examples of security levels , security levels may include any appropriate designation . furthermore , definitions of security levels may not be consistent between systems or networks . a system according to the present invention may interpret security levels as necessary to conform to entities and associated security levels already rendered in the system . it is believed that the present invention and many of its attendant advantages will be understood by the foregoing description , and it will be apparent that various changes may be made in the form , construction , and arrangement of the components thereof without departing from the scope and spirit of the invention or without sacrificing all of its material advantages . the form herein before described being merely an explanatory embodiment thereof , it is the intention of the following claims to encompass and include such changes .
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in the following detailed description , reference is made to the accompanying drawings which form a part hereof wherein like numerals designate like parts throughout , and in which are shown , by way of illustration , specific embodiments in which the disclosure may be practiced . it is to be understood that other embodiments may be utilized and structural or logical changes may be made without departing from the scope of the present disclosure . therefore , the following detailed description is not to be taken in a limiting sense , and the scope of a portion of the present disclosure is defined by the appended drawings and their equivalents . throughout the specification and drawings , the following terms take at least the meanings explicitly associated herein , unless the context clearly dictates otherwise . the meanings identified below are not intended to limit the terms , but merely provide illustrative examples for use of the terms . the meaning of “ a ,” “ an ,” and “ the ” may include reference to both the singular and the plural . reference in the specification to “ one embodiment ” or “ an embodiment ” means that a particular feature , structure , or characteristic described in connection with the embodiment is included in at least one embodiment of the disclosure . the meaning of “ in ” may include “ in ” and “ on .” the appearances of the phrases “ in one embodiment ” or “ in an embodiment ” in various places in the specification do not necessarily all refer to the same embodiment , but it may . the term “ connected ” or “ coupled ” can mean a direct connection between items , an indirect connection through one or more intermediaries , or communication between items in a manner that may not constitute a direct mechanical , systematic , physical , or other connection between the items connected . for example , in various embodiments component devices may be connected via a wireless connection that may allow for the exchange of data and / or information between the participating devices . the terms “ consumer ”, “ customer ” and “ user ” may or may not be used interchangeably . the various embodiments of performance evaluation systems in this disclosure are designed to collect multiple types of logs from a wireless device to determine the performance of the device or an application on the device . in one embodiment , the system performance evaluation uses a data collection tool to collect logs in multiple ways . for example , radio logs for voice & amp ; data may be collected . these are wireless protocol layer logs that relate to the radio interface . os / application layer logs may also be collected . these are logs related to various services . these logs are generally captured by the client on the mobile device . context aware connectivity logs may also be collected from the device or an external tool , which currently include logs for bt , nfc , wi - fi and may also include any new connectivity technology as needed . device information logs may also be collected and include battery , memory , processor , process , and other component device logs . once the contextual and device logs are collected at the device , in one embodiment , each individual set of collected logs may be uploaded , collectively or individually , to the database module via a parser using a wireless network , lan connectivity or wi - fi . the parser processes all logs and combines related events . the business logic modules may be custom designed per the customer requirements and processes the parsed data . an embodiment of custom logic for business module may include data for understanding the data throughput of a device or network in comparison with other networks . another embodiment of a custom logic may include data processing logic to determine the performance of a device under test and provide a comparative report including results from other devices . alternatively in a third embodiment of custom business logic the data and logs are parsed to understand the performance characteristics of a particular family of devices using a common component such as a specific chipset . in a fourth example of embodiment the business logic may be developed with the logs collected to calculate the relationship of connectivity logs with performance to determine the area of performance for a particular network . for example if at a range of − 65 dbm to − 95 dbm the throughput is better than 12 mbps then from the network design information it is possible to calculate the total area which has a throughput performance of above 12 mbps . other embodiments can manipulate the test data to analyze device , network or application performance and are considered within the scope of this disclosure . analysis of processed data may be available to create reports . report generation may be accomplished locally or remotely . in one embodiment , the web service may include report presentation , necessary data performance ratings and custom recommendations as needed for the specific customer . in another embodiment the results of the tests may be represented in an active geographical map with logs and data displayed on the maps in different ways . a third embodiment may report the analysis and the results in a combination of maps , graphs and other forms of data representation . other embodiments can manipulate the test data to analyze device , network or application performance and are considered within the scope of this disclosure . referring now to fig1 , various components of a performance evaluation system of services and applications on devices in live wireless environments are shown in a suitable operating environment in accordance with various embodiments of the present disclosure . fig1 is a high level system diagram , which shows components of the performance evaluation system including a device under test ( 100 ), test client ( 200 ), an external computing device ( 300 ), and a backend system ( 400 ) that includes a database server and a web service . the wireless test client 200 may be installed and runs on multiple platforms including on device ( 100 ), laptop ( 300 ), back end system server 400 , etc . so that it may be used by the tester . in one embodiment , the mobile test client 200 includes operational control logic on a receiving client . the back end system 400 includes , among other components , a database module and tools including : business logic modules that include reporting tools and a web service module that includes endpoints . other configurations may include other components or a subset of the above described components to enable a collaborative environment for wireless product or a group of products testing . referring now to fig4 , a flow diagram view of a performance evaluation system of services and applications on devices in live wireless environments is shown in accordance with at least one embodiment . more particularly , fig4 is a system flow chart of a sample scenario . in the illustrated scenario the test application and the custom configuration file is downloaded on the device under test ( 100 ) via an over the air methodology or via the external computing device . the test is run and the associated logs and device information are either sent to the back end server ( 400 ) directly over the air or through the external computing device ( 300 ). if it is connected to the device under test . the back end system completes the parsing and analysis of the data using the custom business logic and creates the reports . the customer may see these reports via a web service . in one embodiment , the test client 200 or client application on an external computing device , such as a laptop or another wireless device , interfaces or connects with the device under test . this client is capable of configuring the test allowing for user input . this variable configuration file can be made available to a user at the site of testing or a remote user . the collected device logs are then transmitted to a remote database via a wired or wireless interface . the client application may also have a user interface that may convey the status of the test to the user and may also allow for certain remedial action ( such as restarting the test ). the back end system database server 400 receives the combined logs from the client application or directly from the device under test . the parser formats the received logs and deposits the data into the relational database . business logic server / application , in one embodiment , has the logic to generate reports and ratings . this node in the system may have a predetermined logic as well as a customized logic that the user can generate via the web service . the web service may provide the interface to the licensed user . in one embodiment , the web service may have an interface that allows the user to provide certain customizations to the test and may also allow the user to generate custom reports . in another embodiment the web service has the logic to manage permissions and authentication for the user and / or a group of users . the performance evaluation system may also include user experience modules that include user authentication , certificate based transactions and user interface presentation . other embodiments can manipulate the test data to analyze or troubleshoot device , network or application performance and are considered within the scope of this disclosure . referring now to fig2 , various test clients and components of the test client are shown configured in accordance with at least one embodiment . fig2 shows a test client ( s ) ( 200 ). the full client / application may reside on the external computing device ( 300 ) which when connected to the device under test ( 100 ) controls , manages and monitors the test . the external computing client receives the logs and device information related to the test and transmits this to the backend . the device under test may have a light client that can be downloaded over the air . this client will be capable of running the test and transmitting the logs and device information back to the server over the air or at a later time to the external computing device when it is connected . in one embodiment , the front end of this test client tool is a software client application on the mobile operating system ( e . g ., android ; apple ios or windows phone ) that may include the ability to : 1 . load a test configuration file , where a user customizable test scripts can be run . the user customizable test scripts are run sequentially or in parallel and can target various applications or services that are already available on the mobile device . 2 . run a debugger / logger of the events and protocol messages related to each service / application that are run from the above and store the results in separate log files . this would include also capturing radio level protocol logs . in one embodiment , the test client may use laptop usb connectivity to a mobile device to run a configuration app and to upload log files to an external storage location . as previously shown , the test client 200 can be installed on the device under test [ 100 ] and on an external computing device . the test client 200 can also be updated by the back end system server . at least two variations of the test client 200 may exist . in one embodiment , the light client may be present on the device [ 300 ] and this may communicate with the full client on the external computing device [ 200 ]. the configuration files and the test scripts related to a specific routine as identified by the customer and uploaded on to the device under test [ 300 ] via the external computing device [ 200 ]. the tests are then run and logs collected . these logs are then packaged and sent to the back end system [ 400 ] via a communication channel from the external computing device [ 200 ]. in another embodiment , the device under test [ 100 ] may act independently and run the test as directed by the user . the collected logs may be packaged and sent directly via a communication channel to the back end system server [ 400 ] thus not requiring an external computing device [ 200 ]. in one embodiment , the test client on the device consists of at least two applications that are mutually exclusive . the first application is a test configuration client . one sample process block diagram of the test configuration client is shown and described in fig2 . the test configuration client collects device information from the device as follows [ 201 ]: device name , device software version , device hardware version , device firmware version , and test date / time . in one embodiment , the collected information is put in a folder “ device info ” for later access . the test configuration client may also load user customizable ui script that loads a test script ui that the user can use to select the tests that needs to be run . the selected tests can be run in sequence or simultaneously . the running of the selected test scripts enable the event logging trace [ 202 ] on the debugger tool ( internal os tool ) to log information . for example , the following table provides some available tests that may be selected . the logging and filtering of the event logs [ 203 ] by the test configuration client is also shown . the event logging captures designated events that are running on the mobile device under test . these include not only the events related to the test being run but also other useful information like radio signal information ( signal strength , signal quality ), data state , phone manager state , location info etc . next the system is shown parsing and saving of logs into folders [ 204 ]. in one embodiment , different captured logs may be collected in combined logs . to run the correct metrics from the captured logs , the combined logs must be parsed . in one embodiment of the client , the initial parsing of the combined logs can be done in the device under test ( dut ). this initial parsing of the combined logs is to separate the combined logs pertaining to an event into separate folders that can be easily uploaded to the back end system server where the business analysis can be done . in another embodiment , the combined logs are captured by the external computing device attached to the mobile device under test and parsed into their separate folders . next , the system uploads log folders to the back end system , which may include a database server [ 205 ]. in one embodiment of the process , the log folders can be uploaded using wi - fi to the back end system server . in another embodiment the cellular communication channel itself can be used to upload the combined logs . referring now to fig6 , radio logs collected during a voice call test are shown in accordance with at least one embodiment . the chart depicts activities and events associated with a particular call . these may vary depending on the network and device technology and hence will be unique to the test . the logs may also include other information , for example location etc . as per the design of the test and the custom test configuration . in this particular example , the different protocol states of the radio call control ( cc ) may be observed . as seen from the combined logs , the time to connect the call is the time difference between the connection request [ 14 : 10 : 13 : 318 ] and the cc / connect [ 14 : 10 : 24 : 518 ] which is approximately 11 seconds . referring now to fig7 , operating system ( os )/ application logs collected during a voice call test are represented . more specifically , fig5 depicts activities and events associated with a particular call . these may vary depending on the network and device technology and hence will be unique to the test . these logs may also include other information , for example location , etc . as per the design of the test and the custom test configuration . in the example shown in fig7 , we can see the different event states related to a voice call . various performance information can be gleaned from the logs . for example , as seen from the combined logs , the duration of the call is the time difference between the connection [ 14 : 10 : 24 : 613 ] and the disconnection [ 14 : 10 : 38 . 758 ] which is approximately 14 secs . referring now to fig5 , a flowchart of a test client process 200 is shown in accordance with at least one embodiment . the user can use the default test configuration or customize the configuration ( 201 ) that is used in the test . logging is enabled ( 202 ) and the captured logs ( 203 ) are parsed , packaged and saved ( 204 ). the test client then sends these logs and device information to the back end system ( 205 ) that stores this information in the database , analyses and creates reports . these reports are then made available to the licensed user . device testing : application ( s ) may be on the wireless device that runs the test process . this app can be an independent on device application or a larger application that is controlled by an external device . the test application can be used to test and determine the performance of multiple software and hardware components ( e . g . chipset ) of the device . in addition certain pre - determined consumer and enterprise applications can also be tested . collecting logs : the test client applications 200 collect data and logs from the operating system as well as the lower layers of the device ( such as chipsets and other hardware ) from the device and store it in a predetermined file on the device . when the device is connected to an external computing device ( via usb for example ) the combined logs can be downloaded or streamed to that device . this may be accomplished by collecting device logs that pertain to the entire stack ( operating system as well as the silicon and radio ) and combining the combined logs of various layers of the device and network communication protocol for devices in which the various logs need to be collected separately . in one embodiment , controlling the test process including methods for initiating , controlling , managing and termination of the tests or operation on the device from a local or remote location . also installation of the configurable device client software may originate from a local or remote location . controlling the test process may also include methods for transferring the combined logs either in real time or at a delayed time to a computing device ( memory card , laptop or server ). in one embodiment , the test process may also include methods to auto - detect the device based on custom set of variables . in one embodiment , the test process includes methods for auto configuration of the test / operation and device based on a custom set of variables , which may or may not have been provided by the test requestor . the test process may allow configuring of the test from a local and / or remote location . in one embodiment , encryption may be used to secure the combined logs : encryption may occur during collection of the logs and / or during the process of combining the logs so that the resulting combined logs would be encrypted . for example , one may use custom logic to encrypt the device logs and data prior to transmitting them . decryption of the encrypted combined logs may start with an authentication process on the backend system . this process may safeguard the data to improve veracity of the results . the performance evaluation system may monitor a variety of locations and devices within the target test system . in particular , the system may be monitored at various points including wireless device , computing nodes , and reports . the monitoring allows for local or remote control of the system . referring now to fig3 , the architecture of a device loaded with a test client application in accordance with at least one embodiment . more particularly , a view of the various architecture , abstract , and sw layers of a typical wireless device is shown . the actual implementation may vary by device . the test client will be loaded on to the application layer as an application . in one embodiment , the device under test can be any wireless device . a wireless device can be a mobile device or a fixed wireless device . the system described in this invention consists of test applications that can be run independently on the device under test or can be controlled by a client application on an external computing system . the communication method between the device under test and the external computing device can utilize any standard technology such as a usb connection or a bluetooth ( bt ) connection . this system can auto - detect the identification of the device under test by collecting device specific and software specific information . in one embodiment , the device under test and the client on the external computing device can collect device logs ( including os , baseband and hardware ) and package this before transmitting . fig2 and fig2 , illustrates a screen shot of an external tool for specific voice and data tests being integrated into the performance system in accordance with one embodiment the system can consider a variety of metrics including voice and audio services / apps , such as cs voice - mo and / or cs voice - mt . a . normal conditions b . voice and data ( background ) conditions c . lte packet data conditions d . supporting radio logs other system services / apps that can be evaluated include conference calls - lync , voip ( wi - fi calling / volte ) using metrics as outlined above , music streaming ( pandora ) performance , voicemail performance , combinations of the above , and location based services and voice / music . referring now to fig9 and fig2 , various components of a backend system are shown in accordance with at least one embodiment . the backend system ( 400 ) at a minimum includes a web service server ( 401 ), relational database ( 402 ), business logic unit ( 403 ) and a web service ui module ( 404 ). the web service server ( 401 ) receives the logs and device information from the device under test ( 100 ) or the external computing device ( 300 ). these logs are decrypted , parsed and stored in the relational database ( 402 ) as per the database schema . the business logic server ( 403 ) custom logic associated with the particular test or user is applied to the data to create reports and analysis that this made available to the user ( may be licensed ) via the web service ui ( 404 ). the back end system processing portion of the system includes a relational database ( 402 ), a business logic unit ( 403 ) and a web service ( 401 ). the web service ( 401 ) includes a user interface ( 404 ) that enables the licensed user to generate the reports and provide customization . this back end system may receive the combined logs via the client application or directly from the device via a wireless network . in one embodiment , the backend system 400 may use one or more of the following methods and processes : encryption / decryption : the data and logs may be encrypted and decrypted data storage : the data is eventually sent ( via tethered means or the cloud ) and stored on a relational database . data parsing : data is parsed using accustom logic that allows for various reports to be generated that are pivoted on custom requirements generating reports : the reports are generated using custom logic and are made available to licensed users . the data from testing may be crowd sourced and utilized to provide a performance rating to the device or application under test . providing web service : an interactive web service may be provided to licensed users that may allow these users to customize their reports and test process based on their license agreement . in various embodiments , the network may include at least one of a wireless network , the internet or an intranet . accordingly , a participating telephony device may be any wireless device . referring now to fig1 , a flow diagram view of a test routine analysis and process is shown in accordance with at least one embodiment . the flow diagram depicts one embodiment of a test routine analysis and process as per the description in fig1 . in one embodiment , collecting the performance of an application utilizing a wireless device may include one or more of the following methods and processes . collecting device logs that pertain to the entire stack ( operating system as well as the silicon ). combining the logs of various layers of the device . originating , initiating , controlling , managing and terminating of the tests / operation on the wireless device . transferring the combined logs either in real time or at a delayed time to a computing device ( memory card , laptop or server ). auto detection of the application / device based on custom set of variables . auto configuration of the test / operation and application based on a custom set of variables . configuring the test / operation from a local or remote location . scheduling the test / process from a local or remote location . monitoring the operation on wireless device may include at least one of the methods of log analysis or custom test probes to gain an understanding of the status of the tests including the status of normal progression , abnormal progression or an unexpected state . this information may be utilized along with human understanding of the environment to determine the next steps . for example one step might include taking remedial action to ensure that the tests are completed . another step is to validate that the complete logs have been collected . in one embodiment the status of the tests is transmitted to a local or remote location . initiating remedial action to be done from the local or remote location . the log files and metadata of the test procedure may be packaged , encrypted and transmitted in a secure environment . decryption of the packages may utilize custom authentication methods including but not limited to use of certificates , parity checks and other authentication methodology . the test results and the combined logs may be analyzed using a procedure and logic that includes information from the device under test , network and any associated back end system servers . the analysis procedure may have a custom logic to meet the customer requirements . for example in one embodiment the call performance may be analyzed from the combined logs of the device and from network traces provided by the mobile operator to highlight dropped calls due to inter radio technology handovers . in another embodiment the device oem might want to use logic to determine if the device fails to set up a data call in a particular application and radio technology . in this scenario logs are taken from the device and can be analyzed with additional information from the application server that might be provided . thus the analysis logic can be customized as per the customer needs , request or other criteria . other examples of reports are shown in fig the test results , logs and reports may be made available to the customer via a web service . referring now to fig1 , a communication flow diagram associated with a user request for a default ( pre - defined ) test and report coupled with a request for a new test report using the same logs and data is shown in accordance with at least one embodiment . in this example the business logic associated with the new report is applied to the same logs and data to create this new report . sample communications flow for a pre - determined report combined with new user report using the same set of data and logs is referred to fig1 . for example the user might have asked for a report of dropped calls and on seeing this report now wants a new report indicating the number of background data calls that happened during the same test . this supplemental report request can be analyzed using custom logic . referring now to fig1 , a communication flow diagram associated with a user request for a new test and report is shown in accordance with at least one embodiment . the sample communication flow associated with the user request for a new test and report . the user might now design a new test request for the next test run and the sample communication flow is shown in fig1 . this requires a new configuration file that is sent to the device under test ( 100 ) or to the external computing device ( 300 ) so that the test client ( 200 ) can manage and run the customized test . this also shows the user requesting new test report using the same logs and data . in this example the business logic associated with the new report is applied to the same logs and data to create this new report . turning now to the web service user interface , in one embodiment , the web service may include : 1 . allow the customer to get custom reports that can be pivoted on various pieces of data utilizing data from a single test or multiple tests . 2 . present ratings based on predetermined or custom logic 3 . provide a custom user interface based on the rights and privileges accorded to the end customer the method may be enhanced with data or tools external to the test procedure including but not limited to network logs , network design information and application information . this system can by utilized by various entities to determine the performance of a device or application and develop an understanding of the cause of this performance this system can by utilized by wireless operators this system can by utilized by wireless device application creators this system can by utilized by enterprise entities this system can by utilized by device manufacturers this system can by utilized by end consumers g . login to move onto custom screen based on user permission referring now to fig1 , a test request page including possibilities for customization of a test and a report as per user requests is shown in accordance with at least one embodiment . this shows one embodiment of a web service ui test request page : while this is a functional depiction of a possible test request page made available to the licensed user , it is understood that other components may be added or removed from the request page . the sample set of features shown here indicate the possibilities for customization of the test as per the user . referring now to fig1 , a report page for a voice call made available to the licensed user is shown in accordance with at least one embodiment . the shown web service ui provides a sample report page : this is also a functional depiction of a possible test report page for a voice call made available to the licensed user , but other configurations may be made that add or remove illustrated components . the illustrated sample page includes information on the device ( 100 ), report information , observations , and a map of the area that was tested . in this sample the details of the logs associated with a particular location are shows . another way to pivot the report may be based on time ( vs . location ). referring now to fig1 , a report page for a data call made available to the licensed user is shown in accordance with at least one embodiment . the illustrated web service ui shows a sample report page . this report is a functional depiction of a possible test report page for a data call made available to the licensed user . other reports may include additional information and / or remove portions of the illustrated report . the sample page includes information on the device ( 100 ), report information , performance comparisons , observations , performance graphs and a map of the area that was tested . in this sample the details of the logs associated with a particular location are shows . another way to pivot the report may be based on time ( vs . location ). referring now to fig8 , a flow diagram view of a client application on an external computing device ( such as a laptop or another wireless device ) that interfaces with the device under test is shown in accordance with various embodiments . in one embodiment , the client application is resident on an external computing device ( such as a laptop or another wireless device ) and interfaces with the device under test . this client is capable of configuring the test allowing for user input . this variable configuration file can be made available to a user at the site of testing or a remote user . the collected device logs are then transmitted to a remote database via a wired or wireless interface . the client application may also have a user interface that may convey the status of the test to the user and may also allow for certain remedial action ( such as restarting the test ). referring now to fig2 illustrates the various key performance indicators rating indexes otherwise also referred to as the health index and sample formulae that is used to develop the indexes in accordance with various embodiments referring now to fig1 , 20 , and 21 , screenshots illustrate features and functionality for the on device client interface is shown in accordance with various embodiments . more specifically fig1 shows a screenshot of a mobile device client landing page in accordance with various embodiments . fig2 depicts a screen shot of a mobile device client for manual test configuration in accordance with various embodiments . fig2 shows a screen shot of a mobile device client for specific test configuration in accordance with various embodiments . additionally , although specific embodiments have been illustrated and described herein , it will be appreciated by those of ordinary skill in the art and others , that a wide variety of alternate and / or equivalent implementations may be substituted for the specific embodiments shown and described without departing from the scope of the embodiments described herein . this application is intended to cover any adaptations or variations of the embodiments discussed herein . while various embodiments have been illustrated and described , as noted above , many changes can be made without departing from the spirit and scope of the embodiments described herein .
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fig1 illustrates a board 10 illustrated as squares having a series of playing squares 11 located close to the edge , along each side of the board 10 . many of playing squares 11 are feature squares 11a which indicate a trait or interest associated with a particular personality type . feature squares are colour coded so that , for example , the feature squares coded with the colour purple will indicate interests appropriate for the same personality trait . ______________________________________jigsaw puzzle bluecrossword puzzle greensales clerk brownrace horse silverteddy bear redromantic evening redlaw vegas silverresearch study yellowtheatre tickets yellowhouse pet orangepension plan purplelogical argument blueincome taxes greensports fan brownlong walk orangepleasure trip silverlove letters redcomputer technology yellowsingle apartment orangeold coins purplepublic figure brownstock market greenlegal ppers bluesavings bond purplequiet spot orangescience fiction yellowdozen roses redlottery ticket silverreal estate purpleactual proof bluemoney order greenstand - up comic brown______________________________________ the playing squares also include direction squares 11b which in fig1 are labelled &# 34 ; what &# 39 ; s my type ?&# 34 ;. a player landing on a direction square will draw a card from the stack 12 marked &# 34 ; what &# 39 ; s my type ?&# 34 ;. fig2 illustrates typical directions found on turning over card 12 . the playing squares also include at the corners a start square 13 , a visit the analyst square 14 , a free draw square 15 and a return to the analyst square 16 . the significance of these can most conveniently be explained in connection with the rules . board markers 17 and 17a shown in fig1 and fig3 a are typical board markers colour coded and bearing insignia 18 and 18a to indicate a category of interests or traits associated with personality types . the colour codes match those on the feature squares . when board markers such as 17 and 17a are turned over , they reveal one of several notations that correspond to the feature squares which they represent , as well as indicating an appropriate interest or trait as illustrated by fig3 a . board markers are turned down and distributed at random on squares 19 which are preferably located interiorly of the playing squares . the board markers act as tokens and correspond to each feature square . as illustrated in fig4 playing piece 20 may be of conventional design including base 21 and upper portion 21a that can easily be grasped . preferably , as illustrated by fig5 and 5a there are feature square cards 22 which act as tokens and provide written information about the feature squares . the game could be played using board markers 17 or feature square square cards 22 as tokens , but it is best to use both . the backs of the feature square cards correspond to the feature squares as exemplified by fig5 a . fig1 also indicates four stacks of choice cards 23 , 24 , 25 , 26 . choice cards 23 each include a question as to personality having two possible answers , with one of the answers showing an aspect of personality opposite to that shown by the other answer . choice cards such as those in stack 23 indicate a choice between &# 34 ; lucky strikes &# 34 ; coded silver and indicating a gambling nature ; and &# 34 ; clear cuts &# 34 ; coded purple suggesting a more cautious aspect of personality . similarly , choice cards 24 contrast &# 34 ; sweet dreams &# 34 ; coded yellow and &# 34 ; sure things &# 34 ; coded green . choice cards 25 contrast &# 34 ; social charms &# 34 ; coded brown and &# 34 ; private lives &# 34 ; coded orange , and choice cards 26 contrast &# 34 ; hard truths &# 34 ; coded blue and &# 34 ; warm fuzzies &# 34 ; coded red . fig6 , 8 and 9 illustrate typical questions from choice cards 25 , 24 , 26 and 23 respectively , each answer is colour coded by means of a coloured stripe and appropriate insignia such as brown stripe 27 and orange stripe 28 . the game could be played using cards with coloured designations or insignia only , but it is better if both methods of identification are used . fig1 illustrates a personality type tabulator 30 which includes aligned rows 31 , 32 , 33 and 34 each indicating an opposite pair of feature styles that correspond to the colour coding which matches the colour stripes and insignia such as 27 and 28 on the choice cards . in the centre of each row there is a neutral position 35 . each row including the neutral position has holes 36 to receive pegs such as 37 . if the choice card in fig6 is , for example , answered &# 34 ; outgoing and energetic &# 34 ;, peg 37 will be advanced from the neutral position to the first hole 38 in the brown &# 34 ; social charms &# 34 ; section . depending on the player &# 39 ; s next answer to a question from stack 25 , the peg will either be returned to the neutral position or advanced to the second hole in the brown &# 34 ; social charms &# 34 ; category . as will be explained in connection with the rules , it is necessary to qualify under each feature style by advancing the appropriate peg from the neutral position at least one and preferably two holes to qualify to obtain tokens , namely , board markers 17 and feature cards 22 . in other words , such tokens are obtained only if the player has qualified to obtain them both by having landed on the appropriate playing square , and also by having advanced the corresponding peg at least two holes in the direction matching the insignia and description on the token . the player must correctly locate the appropriate board marker , which will involve memory if it has been previously turned over and turned back . once a board marker has been claimed it is then located and conveniently stored in recesses 40 on the personality type tabulator . as colours cannot be illustrated on fig1 a colour key is included at the bottom to identify the various colours used to designate the letters . as will be explained in the rules , the game ends when a player has a token , such as a board marker in each of the four categories illustrated by the rows in fig1 . there are 16 possible combinations e . g . social charms , plus sure things , plus hard truths , plus lucky strikes is one combination . the method of declaring a winner is most conveniently explained in connection with the rules . a personality type profile card 38 as illustrated in fig1 may then be provided from a selection of 16 to indicate the personality of the declared winner as indicated by the colour coded feature style combination on the personality type tabulator , being the same as at 41 on fig1 . we will now present the preferred playing directions and rules from which variations may be made within the scope of the appended claims . how to play what &# 39 ; s my type ? ( what &# 39 ; s my type ? is a proposed trademark ). the aim of what &# 39 ; s my type ? is to answer questions which enable you to learn more about your personality type . the game is played by 2 to 6 people throwing dice and moving playing pieces around the board in a clockwise direction . when a playing piece lands on a feature square , the player answers a corresponding choice card . two answers are provided on the choice card and the player picks whichever one is closer to his or her usual way of doing things . the answers to these questions correspond to various features styles which typify how people ordinarily look at things and make decisions . the personality type tabulators are used to keep track of each player &# 39 ; s responses to the choice cards . there are four pairs of opposite feature styles portrayed along the game board . a player &# 39 ; s personality type consists of the feature styles that are indicated by the personality type tabulator . a player who lands on a feature square which matches any one of the preferred feature styles in his or her personality type has a chance to claim the feature square . the object of what &# 39 ; s my type ? is to be the first player who claims one feature square for each of the four feature styles in his or her personality type . what &# 39 ; s my type ? cards add some rather interesting moments to the game and there is always the unexpected opportunity to visit the analyst . there are no right or wrong answers to any of the questions on the choice cards . none of the players are ever eliminated from the game and no personality type has any particular advantage over the rest . the equipment consists of the game board , a pair of dice , six playing pieces , six personality type tabulators ; twenty - four feature style point pegs , thirty - two feature square cards , 32 board markers ; four sets of choice cards , sixteen what &# 39 ; s my type ? profile cards , and a deck of what &# 39 ; s my type ? cards . shuffle each deck of cards separately and place them face down on the game board in their marked spots . randomly place the thirty - two board markers face down along the inner squares on the game board . no player should know the position of any board marker before the start of the game . each of the players selects a playing piece to represent his or her position on the game board and receives a personality type tabulator along with four feature style point pegs . the remaining equipment is looked after by a player who is selected to be the analyst . the personality type tabulators are used to keep a running total of each player &# 39 ; s responses to the questions from the choice cards . each of the four horizontal columns on the personality type tabulator contains a pair of opposite feature styles ( example : private lives and social charms ). when a player answers a question , the corresponding feature style point peg is moved one hole ( along the horizontal column ) in the direction of the feature style identified on the choice card . the feature style point pegs may be moved in either direction and from one feature style to the other . the positions of the four feature style point pegs identify the preferred feature styles in a player &# 39 ; s personality type . the middle holes are the starting positions for the feature style point pegs and are referred to as neutral positions . when a player correctly draws a matching board marker and claims a feature square -- the board marker is then positioned in the correct holder on the personality type tabulator . every player selects a playing piece and positions it on the start square . the players roll the dice to determine who will start first . the player with the highest roll begins the game . he or she rolls the dice and moves his or her playing piece according to the number shown on both dice . playing pieces always move in a clockwise direction around the outer squares on the game board . upon completion , the turn passes to the player on the left . playing pieces remain in their location until the player &# 39 ; s next turn -- unless another player lands on the same square . only one playing piece may occupy the same square on the board at one time ( except visit the analyst ). when a player lands on a square already occupied , the first playing piece to land there goes to visit the analyst . each time a playing piece lands on a game board square there are several possible options ; a player may be eligible to draw , answer a choice card , take a what &# 39 ; s my type ? card , earn a free draw , receive an extra turn , or return to visit the analyst . when a player rolls doubles three times in a row , the playing piece goes immediately to visit the analyst -- unless the player happens to land on start . a player receives an extra turn for landing on start . landing on start also cancels the number of doubles that a player may have rolled to reach the square . the feature squares portray the various feature styles which combine to identify a player &# 39 ; s personality type . descriptions for each feature style are printed on the feature square cards . whenever a player lands on a feature square , he or she must first answer a choice card question . the players may decide who will ask each question . a player is not entitled to ask himself or herself a choice card question . feature squares remain unclaimed until a player who is eligible to draw lands there and correctly draws the matching board marker . a draw consists of turning a board marker completely face up for all to see . to be eligible for a draw , a player must have a minimum of two feature style points ( as shown by the coloured portion on the personality type tabulator ) for the style portrayed on the feature square . for example : a player with two or more feature style points for lucky strikes who lands on race horse , las vegas , pleasure trip , or lottery ticket is eligible to draw . after a player draws a board marker it is either returned face down to its original position or placed in the personality type tabulator -- if it matches the feature square . a player may claim only one feature square at a time from any feature style pairing . at all times , the board markers in the personality type tabulator must correspond to the feature styles indicated by the positions of the feature style point pegs . if one of the player &# 39 ; s feature style preferences becomes neutral , he or she must remove the board marker from the personality type tabulator and return it along with the feature square card to the analyst . there is no penalty for landing on another player &# 39 ; s feature square . however , in place of the draw , a player ( who is eligible to draw ) may challenge the owner for the right to claim the square . when this happens , the two players must throw the dice to see who will keep the feature square and board marker . if the owner rolls doubles he or she wins , otherwise , the player who rolls the higher number keeps the square . a tie goes to the owner . the one who loses the challenge must return to visit the analyst . when a playing piece lands on what &# 39 ; s my type ? the player takes the top card from the deck and upon completing the directions , returns the card face down to the bottom of the deck . the card marked &# 34 ; excused from visiting the analyst &# 34 ; may be kept by the player until needed . after it is used it must be returned to the bottom of the deck . cards which require the player to answer a choice card entitle the player to select the category of the card . &# 34 ; return to visit the analyst &# 34 ; is the only card which causes a player to lose his or her next turn . a player who lands on free draw must draw from any available board marker and proceed directly to the feature square , position the board marker in his or her personality type tabulator , and then receive a choice card question . if the player is not eligible to draw a board marker , when he or she lands on free draw , then his or her playing piece remains on the square and his or her turn ends . if a playing piece lands on or is sent to visit the analyst , the player is required to remain on the square until he or she rolls an even number with the dice . there is no other means of leaving the square except by using a what &# 39 ; s my type ? &# 34 ; exemption &# 34 ; card before rolling the dice . if a player throws doubles and lands on visit the analyst , he or she is not entitled to roll again and the turn passes to the next player . at the start of play , a player is selected to be the analyst for the entire game . the analyst acts as the controller for the feature square cards , board markers , and what &# 39 ; s my type ? profile cards . when a feature card is claimed , the analyst issues the player with the feature square card . when a player forfeits a feature square , he or she returns the feature square card and board marker to the analyst . next , the analyst takes all of the corresponding board markers that are unclaimed ( including the one being returned ) and randomly repositions them so that no player knows their new locations . the game is over when the first player has claimed one feature square for each feature style in his or her personality type . at this point the player immediately returns his or her playing piece to visit the analyst . the player is then asked one question from each of the four choice card decks to confirm the player &# 39 ; s personality type . the player is not entitled to learn either the category of the choice card being answered or the feature style represented by his or her response -- until all four answers have been given . the player must forfeit to the analyst any feature square which did not match the response given to the corresponding choice card and play continues . the player who successfully defends his or her personality type in this manner receives the appropriate what &# 39 ; s my type ? profile card from the analyst , after it has been read aloud to all of the players . the corresponding what &# 39 ; s my type ? profile card is easily identified by matching the colours on the card with those on the board markers in the personality type tabulator .
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fig3 shows a rough construction of the saturable reactor in accordance with the present invention . a pair of dual drum cores 14 , 15 are arranged in parallel with a certain specified clearance and common permanent magnets 21 , 22 are arranged closely to each other with the same polarities , for example , n polarities opposed at both ends of these dual drum cores . the dual drum core herein used is a core which is made of a material with high magnetic permeability such as , for example , ferrite and provided with disk - shaped flanges 141 , 142 , 143 , 151 , 152 and 153 at both ends and the center of the bar type magnetic core and with winding portions 14a , 14b , 15a , and 15b around the coils are to be wound between these flanges . common impedance coil 17 is wound around the winding portions 14a , 15a of the drum cores 14 , 15 and another common impedance coil 16 is wound around the winding portions 14b , 15b . the control coil 18 wound around the coil bobbin not shown is arranged around a pair of dual drum cores 14 , 15 . said impedance coils 16 , 17 and the control coil 18 are connected to the horizontal deflection coil and the vertical deflection coil of the deflection yoke . fig4 shows the electrical circuit of the deflection yoke and the saturable reactor is shown inside the one - dotted broken line 10 . one - side ends of impedance coils 16 , 17 are directly connected to the terminals 20a of the horizontal deflection circuit 20 and the other ends are respectively connected to one - side ends of the horizontal deflection coils 11 , 12 and the other end of the horizontal deflection coil is connected to the terminal 20b of the horizontal deflection coil 20 . in other words , the series circuit of the horizontal deflection coil and the impedance coil is connected in parallel to the horizontal deflection circuit 20 . on the other hand , the control coil 18 is connected to the terminal 19a of the vertical deflection circuit 19 through the vertical deflection coils 13 , 13 &# 39 ;, which are connected in series , and the other end of the coil 18 is connected to the terminal 19b of the circuit 19 . the following describes the operation of the saturable reactor . when the vertical deflection current i v from the vertical deflection circuit 19 is supplied to the control coil 18 and the horizontal deflection current i h supplied from the horizontal deflection circuit 20 flows through the the impedance coils 16 , 17 , a magnetic flux is generated in the direction as shown with the arrowhead in fig3 . in other words , a control flux φ v in the arrowhead direction shown with a one - dotted broken line is generated by the control coil 18 in the winding portions 14a , 14b , 15a and 15b of the drum cores 14 , 15 and the magnetic fluxes φh1 , φh2 from the impedance coils 16 , 17 are generated as shown with the solid arrowhead so that the directions of magnetic flux φh2 passing through the winding portions 14a , 15a and magnetic flux φh1 passing through the winding portions 14b , 15b are reversed . these magnetic fluxes φh1 , φh2 pass through the closed magnetic path formed by the flanges 141 - 143 , 151 - 153 and the winding portions 14a , 15a , 14b and 15b of the drum core . magnets 21 , 22 add the biased magnetic fluxes φm1 , φm2 shown with reversed arrowheads to the winding portions 14a , 14b , 15a , 15b as shown with a broken line and return to the magnets from the flanges 143 , 153 through the space magnetic path . the directions of magnetic fluxes φv , φh1 , φh2 shown in fig3 only indicate the timing when deflection currents i v , i h exist . in fact , these directions vary at every half cycle of deflection currents i v , i h supplied to impedance coils 16 , 17 and the control coil 18 . as known from fig3 since the magnetism of the winding portions 14a , 15b of the drum cores are biased to φv + φm2 , it becomes equivalent to the reduction of magnetic permeabilities of the drum cores whereby the inductance of the impedance coil 17 also reduces . in other words , the impedance of the impedance coil 17 reduces and the amount of current of the horizontal deflection current i h flowing through the horizontal deflection coil 12 slightly increases or does not nearly increase . this is because the cores are magnetically biased up to a point near the saturation point of the b - h curve which depends on the material of the drum cores . on the other hand , since the winding portions 14b , 15b are magnetically biased to φv - φm1 , such bias becomes equivalent to an increase of the magnetic permeability , the impedance of the impedance coil 16 increases and the horizontal deflection current flowing through the horizontal deflection coil 11 reduces . the above - mentioned operation is carried out in a cycle of the vertical deflection current and the horizontal deflection current flowing through the horizontal deflection coils 11 , 12 is differentially varied in a cycle of the vertical deflection current . if such deflection current is supplied to the deflection yoke , the cross misconvergence as shown in fig2 is corrected and the amount of misconvergence is within the tolerance . the magnetitude of misconvergence can be adjusted by varying the magnetic flux density of magnetic fluxes φm1 , φm2 supplied from magnets 21 , 22 . for example , the balance of magnetic bias against the drum cores 14 , 15 can be changed by biasing one or both of magnets 21 , 22 to the right or left on the figure . the densities of magnetic fluxes can be varied by reducing the sizes or thickness of the magnets . fig5 to 8 respectively show the structures of embodiments of the saturable reactor in accordance with the present invention . the coil bobbin 23 which is made of a plastic material and formed in an oval profile has the cylindrical part 231 and the enlarged cylindrical parts 232 , 233 which are formed at both ends of said cylindrical part 231 around which the control coil 18 is wound . inside the cylindrical part 231 of the coil bobbin 23 , two tubular tunnels 24 , 25 are provided which communicate each other through the space 26 as expressly shown by the cross sectional view in fig7 . in two tunnels 24 , 25 are inserted the dual drum cores 14 , 15 around which impedance coils 16 , 17 are wound as shown in fig5 and 6 . in other words , cores 14 , 15 are supported by the disk - shaped flanges 141 - 143 , 151 - 153 from the inside wall of the coil bobbin 23 . in this case , the closest parts of flanges 141 - 143 and 151 - 153 are separated as much as the width of the partition s so that the fluctuation of the reluctance of the closed magnetic circuit formed by two drum cores 14 , 15 is reduced . projection members 232a , 233a , 233b which control the positions of magnets 21 , 22 are provided in the enlarged cylindrical parts 232 , 233 formed at both ends of the coil bobbin 23 , as shown in fig5 and fig6 and oval - shaped plate magnets 21 , 22 are inserted into the section surrounded by these projection members as shown with the one - dotted broken line . the magnets are magnetized in the direction of thickness . in addition , the enlarged cylindrical parts 232 , 233 are protected with the covers 27 , 28 made of a plastic material as shown in fig5 . covers 27 , 28 are composed of the oval cylindrical member 271 and the plate member 272 as shown in fig8 . the engaging hole 29 is provided at the shorter diameter part of the oval cylindrical member 271 and the stepped stopper 30 is provided at both ends of the plate member 272 in the longer diameter direction . the engaging hole 29 engages with the engaging claws ( not shown ) provided on the outside of the enlarged cylindrical parts 232 , 233 and the stopper 30 hits against the projection members 232a , 233a inside the enlarged cylindrical parts in order to fix the covers 27 , 28 to the enlarged cylindrical parts 232 , 233 . lugs 31 are provided on the plate number 272 of the covers 27 , 28 in the direction of the longer diameter . these lugs 31 are formed by providing the u - shaped holes 31a in the plate member 272 . the lugs 31 are provided with projections 32 , which are projected inside the covers 27 , 28 , at their tip ends to depress the magnets 21 , 22 against the flanges 141 , 142 , 151 , 152 of the drum cores as shown in fig5 . various variations of the embodiment can be made within the range of the objects of the present invention . for example , the permanent magnets can be small - sized to be slidable inside the enlarged cylindrical member and can also be formed in a rectangular or circular shape . the shape of the coil bobbin and the cover can also be changed in the stage of design .
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an exemplary embodiment of the invention is illustrated in fig1 to 3 , and various possible solutions are illustrated in fig4 and 5 in terms of two driving situations . in fig1 the front wheels of a motor vehicle are designated by 1 and 2 , and its rear wheels by 3 and 4 . an engine 5 is normally connected through a drive shaft 10 with a differential 6 through which the rear wheels 3 and 4 are driven . in the vehicle shown in fig1 provision is made for shifting to four - wheel drive , to which end a longitudinal differential 7 can be switched so that in addition to the shaft 10 for the rear - wheel drive a shaft 8 is driven , through which and through a further differential 9 the front wheels are driven . the shafts 8 and 10 can be rigidly coupled to the engine through a central lock contained in the differential 7 . the differentials 6 and 9 may also have differential locks that can be engaged . the assumption is here made that the shifting to four - wheel drive and the engagement of the locks are brought about automatically by means of a control circuit 11 to which signals corresponding to the speeds of the wheels 1 to 4 are fed . ( this is indicated in fig1 only by the wheel speed sensors 2a and 4a for the wheels 2 and 4 , respectively . corresponding wheel speed sensors 1a and 3a are also connected to the control circuit 11 .) on the basis of the wheel - speed differences ascertained , a shifting to four - wheel drive and / or an engaging of the differential locks occurs , triggered by means of lines 13 . a brake light switch signal is fed to the terminal 12 for releasing the locks and disengaging the four - wheel drive . shown in fig2 is the associated anti - lock braking system , consisting of the four wheel - speed sensors 1a to 4a , an evaluation circuit 20 , brake - pressure control units 21 and 22 for the two front wheels 1 and 2 , and a single brake - pressure control unit 23 for the rear wheels 3 and 4 . also shown in fig2 is the control circuit 11 from fig1 to which the signals of the sensors 1a to 4a are fed , and which delivers the switching signals for the four - wheel drive and the differential locks by way of the terminals 24 to 27 . the switching signals at the terminals 26 ( for four - wheel drive shifting ) and 27 ( for the central lock ) are also fed to the evaluation circuit to enter into the formation of the reference value . fig3 is a basic diagram showing the formation of slip in the evaluation circuit 20 of fig2 . the wheel - speed signal of one of the sensors 1a to 4a is fed to a terminal 30 and then to a reference - value former 31 and a comparator 32 . switching signals for the four - wheel drive ( terminal 34 ) and for engagement of the central lock ( terminal 35 ) are further fed to the reference - value former 31 . the reference value produced by the latter is compared in the comparator 32 with the wheel - signal , and a broke pressure - reduction signal is generated at a terminal 33 when the wheel - speed signal falls below the reference - speed signal . the diagram of fig4 illustrates the mode of operation of the reference - value former 31 of fig3 for the driving situation in which the vehicle starts to climb a hill with the wheels spinning . curve 40 shows the wheel speed , curve 41 the vehicle speed , and curves 42a , 42b and 42c different ( alternative ) reference values . the driving situation starts at t o . at t 1 , shifting to four - wheel drive occurs automatically since the wheels are spinning ( the vehicle speed 41 remains practically zero ). this illustrates the case where the gradient of the reference speed 42 is limited and of the same magnitude ( e . g ., 0 . 2 grade ) whether the four - wheel drive is engaged or not . since the wheels continue to spin , the central lock is engaged at t 2 . now the reference value is either held constant ( curve 42a ) or then increased just slightly and continuously ( not illustrated ), reduced with a constant gradient ( curve 42b ), or set at a minimal speed ( curve 42c ; here approximately equal to the vehicle speed ). this state persists until the brakes are applied at t 3 ( see brake light switch signal bls ) and the wheel speed is consequently reduced . at t 3 the central lock is released and the four - wheel drive is also disengaged . the reference value now can rise with a given gradient of about 0 . 2 to 0 . 4 gr ( course 42 &# 39 ; in curve 42a ; course 42 &# 34 ; in curves 42 b and 42c ). at t 4 , the wheel - speed signal ( 40 ) drops below the reference value ( 42 &# 39 ;), and a brake pressure - reduction signal ( av ) is now generated at the terminal 33 . at the same time the reference value is reduced with a given negative gradient of about 0 . 3 to 0 . 4 gr . the brake pressure reduction here brought about actually occurs only rarely or , when it does , only momentarily . this would not be the case if the reference value were allowed to rise further , as in the range from t o to t 2 , which would result in a temporarily depressurized brake . in the case of the reduction proposed according to curve 42b and 42 &# 34 ;, the advantage described in enhanced , and in the case of curve 42c and 42 &# 34 ; it is even less likely that the brake pressure will be reduced . in the case of the last - mentioned curve , but also in the case of curve 42b with an appropriate negative gradient , the reference speed cannot exceed the vehicle speed even when the vehicle decelerates , with the central lock engaged . the vehicle speed will not be appreciably exceeded by the reference speed even with the central lock momentarily released ( for example , to check whether engaging the lock is still appropriate ). in the case of curve 42b and 42 &# 34 ;, even spurious signals indicating an engaged central lock will not appreciably distort the reference . in fig4 the assumption is made that the gradient is the same with and without four - wheel drive . actually , the reference value could be allowed to rise with a steeper gradient during the period from t o to t 1 ( as is usually the case with abs ). however , there is then the risk that if the shifting to four - wheel drive is not recognized , the reference signal will increase too much and a long - lasting pressure - reduction phase will also result . fig5 is based on the assumption that the vehicle is about to climb a hill , with the wheels at first spinning but then reaching ground with a higher coefficient of friction ( μ ). the wheel - speed curve is denoted by 50 , and the reference - speed curve ( or the corresponding signal curve ) by 52 ( with the different characteristics 52a to 52c and 52 &# 39 ; and 52 &# 34 ;, respectively ). the vehicle is to start moving at t o , but since the wheels are spinning the vehicle speed 51 remains practically zero . at t 1 , shifting to four - wheel drive occurs ; however , in this example also , the gradient of the reference speed is not changed . only at time t 2 , when the central lock is engaged , does one of the optional reference curves 52a or 42c of fig4 provided as alternatives , become effective . at time t 3 , the wheel reaches high - μ ground and is at first decelerated until the slip ceases ( at t 4 ). here the vehicle speed has caught up with the wheel speed , and both speeds increase in unison until the brake is applied at t 5 ( bls signal ). between t 2 and t 5 , the reference speed has taken a selected course according to the curves 52a to 52c . from t 5 onward , the reference speed increases according to curves 52 &# 39 ;,/ 52 &# 34 ; with a given positive gradient ( about 0 . 2 to 0 . 4 gr ). at the same time , the four - wheel drive and the locks were here disengaged . from t 5 onward , pressure - reduction signals av are generated by the wheel - speed oscillations due to the deceleration until ( at t 6 ) pressure - reduction signals are generated also by the slip . in the case of fig5 the curve 52a and 52 &# 34 ;, or the case of the slight increase in the reference , not shown here , is preferred since the reference catches up with the wheel speed sooner . the increase in the reference after the application of the brakes is advantageous in the case of fig5 but a drawback in the case of fig4 . as a compromise , a small gradient ( e . g ., 0 . 3 to 0 . 4 gr ) is preferably selected . there has thus been shown a novel anti - lock braking system which fulfills all the objects and advantages sought therefor . many changes , modifications , variations and other uses and applications of the subject invention will , however , become apparent to those skilled in the art after considering this specification and the accompanying drawings which disclose the preferred embodiments thereof . all such changes , modifications , variations and other uses and applications which do not depart from the spirit and scope of the invention are deemed to be covered by the invention which is limited only by the claims which follow .
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hereinafter , the present invention will be further illustrated with reference to the following examples . however , these examples are only provided for illustration purposes , and are not to limit the scope of the present invention . all of the modifications made based on the above disclosures will fall into the scope of the present invention . r 1 represents — h , — c m h ( 2m + 1 ) , c 3 - c 2 cycloalkyl , — c m h ( 2m + 1 ) substituted by c 3 - c 2 cycloalkyl , c 3 - c 2 cycloalkyl substituted by — c m h ( 2m + 1 ) , heterocyclyl containing 3 - 8 carbon atoms , amino substituted by heterocyclyl containing 3 - 8 carbon atoms , aryl containing 6 - 8 carbon atoms , or heteroaryl containing 6 - 8 carbon atoms ; said heterocyclyl contains 1 - 3 heteroatoms selected from n , o and s ; said heteroaryl contains 1 - 3 heteroatoms selected from n , o and s ; r 2 represents — h , — nh 2 , — oh , — f , — cl , — br , — cf 3 , — c m h ( 2m + 1 ) , — oc m h ( 2m + 1 ) , — nhc m h ( 2m + 1 ) , aryloxy containing 6 - 12 carbon atoms , or arylamino containing 6 - 12 carbon atoms ; r 3 represents c 3 - c 2 cycloalkyl , c 3 - c 2 cycloalkyl substituted by — c m h ( 2m + 1 ) , aryl containing 6 - 80 carbon atoms , or heteroaryl containing 6 - 80 carbon atoms ; said heteroaryl contains 1 - 15 heteroatoms selected from n , o and s ; r 4 - r 8 respectively represent — h , — f , — cl , — br , — cf 3 , — ocf 3 , — oc m h ( 2m + 1 ) , aqueous ammonia ( 8 . 0 ml ) and n , n - diisopropylethylamine ( 13 . 2 ml ) were dissolved into 150 ml dichloromethane . the mixture was added dropwise to a solution of 2 , 4 - dichloro - 5 - nitropyrimidine ( 10 . 0 g ) in dichloromethane ( 30 ml ) at 0 ° c . after the completion of the dropwise addition , the mixture was kept at the same temperature to react for 1 hour . the precipitate was filtered off . the filter cake was recrystallized to obtain a yellow solid ( 8 . 1 g ) in a yield of 90 . 1 %. 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 20 ( s , 1h ), 9 . 02 ( s , 1h ), 8 . 60 ( s , 1h ) ppm . a solution of methyl amine - ethanol ( 7 . 6 ml ) and n , n - diisopropylethylamine ( 13 . 2 ml ) were dissolved into 150 ml dichloromethane . the mixture was added dropwise to a solution of 2 , 4 - dichloro - 5 - nitropyrimidine ( 10 . 0 g ) in dichloromethane ( 30 ml ) at 0 ° c . after the completion of the dropwise addition , the mixture was kept at the same temperature to react for half an hour . purification was conducted by a column chromatography to obtain a yellow solid ( 8 . 3 g ) in a yield of 85 . 4 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 9 . 05 ( s , 1h ), 8 . 41 ( s , 1h ), 3 . 22 ( s , 3h ) ppm . isopropylamine ( 4 . 5 ml ) and n , n - diisopropylethylamine ( 13 . 2 ml ) were dissolved into 150 ml dichloromethane . the mixture was added dropwise to a solution of 2 , 4 - dichloro - 5 - nitropyrimidine ( 10 . 0 g ) in dichloromethane ( 30 ml ) at 0 ° c . after the completion of the dropwise addition , the mixture was kept at the same temperature to react for half an hour . purification was conducted by a column chromatography to obtain a bright - yellow solid ( 10 . 1 g ) in a yield of 90 . 4 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 9 . 03 ( s , 1h ), 8 . 24 ( s , 1h ), 4 . 53 ( m , 1h ), 1 . 34 ( d , j = 6 . 8 hz , 6h ) ppm . cyclopropylamine ( 1 . 8 ml ) and n , n - diisopropylethylamine ( 6 . 6 ml ) were dissolved into 75 ml dichloromethane . the mixture was added dropwise to a solution of 2 , 4 - dichloro - 5 - nitropyrimidine ( 5 . 0 g ) in dichloromethane ( 15 ml ) at 0 ° c . after the completion of the dropwise addition , the mixture was kept at the same temperature to react for 40 min . purification was conducted by a column chromatography to obtain a bright - yellow solid ( 2 . 6 g ) in a yield of 47 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 8 . 84 ( s , 1h ), 7 . 35 ( s , 1h ), 3 . 84 ( m , 1h ), 1 . 36 ( m , 4h ) ppm . cyclopentylamine ( 5 . 17 ml ) and n , n - diisopropylethylamine ( 12 . 4 ml ) were dissolved into 125 ml dichloromethane . the mixture was added dropwise to a solution of 2 , 4 - dichloro - 5 - nitropyrimidine ( 9 . 7 g ) in dichloromethane ( 30 ml ) at 0 ° c . after the completion of the dropwise addition , the mixture was kept at the same temperature to react for 80 min . purification was conducted by a column chromatography to obtain a bright - yellow solid ( 7 . 9 g ) in a yield of 65 . 13 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 9 . 03 ( s , 1h ), 8 . 38 ( s , 1h ), 4 . 59 ( m , 1h ), 2 . 13 - 2 . 21 ( m , 2h ), 1 . 72 - 1 . 85 ( m , 4h ), 1 . 53 - 1 . 71 ( m , 2h ) ppm . cyclopentylamine ( 5 . 2 ml ) and n , n - diisopropylethylamine ( 13 . 2 ml ) were dissolved into 150 ml dichloromethane . the mixture was added dropwise to a solution of 2 , 4 - dichloro - 5 - nitro - 6 - methylpyrimidine ( 10 . 7 g ) in dichloromethane ( 30 ml ) at 0 ° c . after the completion of the dropwise addition , the mixture was kept at the same temperature to react for 1 hour . purification was conducted by a column chromatography to obtain a bright - yellow solid ( 11 . 2 g ) in a yield of 84 . 8 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 8 . 44 ( s , 2h ), 4 . 41 ( m , 1h ), 2 . 64 ( s , 3h ), 2 . 01 - 2 . 15 ( m , 2h ), 1 . 61 - 1 . 76 ( m , 4h ), 1 . 45 - 1 . 63 ( m , 2h ) ppm . isopropylamine ( 4 . 5 ml ) and n , n - diisopropylethylamine ( 13 . 2 ml ) were dissolved into 150 ml dichloromethane . the mixture was added dropwise to a solution of 2 , 4 - dichloro - 5 - nitro - 6 - methoxypyrimidine ( 11 . 5 g ) in dichloromethane ( 30 ml ) at 0 ° c . after the completion of the dropwise addition , the mixture was kept at the same temperature to react for 45 min . purification was conducted by a column chromatography to obtain a yellow solid ( 10 . 9 g ) in a yield of 86 . 1 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 8 . 25 ( s , 1h ), 4 . 42 ( m , 1h ), 4 . 01 ( s , 3h ), 1 . 23 ( d , j = 6 . 8 hz , 6h ) ppm . isopropylamine ( 4 . 5 ml ) and n , n - diisopropylethylamine ( 13 . 2 ml ) were dissolved into 150 ml dichloromethane . the mixture was added dropwise to a solution of 2 , 4 - dichloro - 5 - nitro - 6 - methylaminopyrimidine ( 11 . 5 g ) in dichloromethane ( 30 ml ) at 0 ° c . after the completion of the dropwise addition , the mixture was kept at the same temperature to react for half an hour . purification was conducted by a column chromatography to obtain a yellow solid ( 10 . 4 g ) in a yield of 82 . 1 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ8 . 17 ( s , 1h ), 4 . 48 ( m , 1h ), 2 . 78 ( s , 3h ), 1 . 31 ( d , j = 6 . 8 hz , 6h ) ppm . isopropylamine ( 4 . 5 ml ) and n , n - diisopropylethylamine ( 13 . 2 ml ) were dissolved into 150 ml dichloromethane . the mixture was added dropwise to a solution of 2 , 4 - dichloro - 5 - nitro - 6 - methylpyrimidine ( 10 . 7 g ) in dichloromethane ( 30 ml ) at 0 ° c . after the completion of the dropwise addition , the mixture was kept at the same temperature to react for half an hour . purification was conducted by a column chromatography to obtain a bright - yellow solid ( 10 . 2 g ) in a yield of 86 . 8 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 8 . 01 ( s , 1h ), 4 . 48 ( m , j = 4 . 1 , 1h ), 2 . 72 ( s , 3h ), 1 . 32 ( d , j = 6 . 8 hz , 6h ) ppm . cyclohexylamine ( 5 . 72 ml ) and n , n - diisopropylethylamine ( 12 . 4 ml ) were dissolved into 125 ml dichloromethane . the mixture was added dropwise to a solution of 2 , 4 - dichloro - 5 - nitropyrimidine ( 9 . 7 g ) in dichloromethane ( 30 ml ) at 0 ° c . after the completion of the dropwise addition , the mixture was kept at the same temperature to react for 80 min . purification was conducted by a column chromatography to obtain a bright - yellow solid ( 9 . 1 g ) in a yield of 71 . 2 %. esi - ms ( m / z , %) 258 ( m − h ) + ; 1 h nmr ( 400 mhz , cdcl 3 ): δ9 . 04 ( s , 1h ), 8 . 35 ( s , 1h ), 4 . 34 ( m , 1h ), 2 . 03 ( m , 2h ), 1 . 79 ( m , 2h ), 1 . 53 - 1 . 25 ( m , 6h ). cyclohexylmethylamine ( 3 . 11 g ) and n , n - diisopropylethylamine ( 6 . 2 ml ) were dissolved into 45 ml dichloromethane . the mixture was added dropwise to a solution of 2 , 4 - dichloro - 5 - nitropyrimidine ( 4 . 85 g ) in dichloromethane ( 30 ml ) at 0 ° c . after the completion of the dropwise addition , the mixture was kept at the same temperature to react for 20 min . purification was conducted by a column chromatography to obtain a bright - yellow sheet - like solid ( 1 . 73 g ) in a yield of 26 %. esi - ms ( m / z , %) 272 ( m − h ) + . 1 h nmr ( 400 mhz , cdcl 3 ): δ 9 . 03 ( s , 1h ), 8 . 48 ( s , 1h ), 3 . 52 ( m , 2h ), 1 . 78 - 1 . 64 ( m , 7h ), 1 . 33 - 1 . 14 ( m , 4h ), 1 . 08 - 1 . 00 ( m , 2h ). 4 - amino - n -( 4 - methylpiperazin - 1 - yl ) benzamide ( 4 . 7 g ) was added to a solution of compound 2 - 3 ( 4 . 3 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 3 . 5 hours , cooled to room temperature , filtered , washed and dried to obtain a yellow solid ( 5 . 9 g ) in a yield of 71 . 2 %. 1 h nmr ( 400 mhz , dmso - d 6 ): δ 10 . 01 ( s , 1h ), 9 . 32 ( s , 1h ), 8 . 78 ( s , 1h ), 8 . 21 ( m , 2h ), 7 . 84 ( s , 1h ), 7 . 63 ( m , 2h ), 4 . 31 ( m , 1h ), 2 . 75 ( t , j = 4 . 8 hz , 4h ), 2 . 38 ( br , 4h ), 2 . 13 ( s , 3h ), 1 . 19 ( d , j = 6 . 8 hz , 6h ) ppm . 4 - amino - 3 - fluoro - n -( 4 - methylpiperazin - 1 - yl ) benzamide ( 5 . 0 g ) was added to a solution of compound 2 - 3 ( 4 . 3 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 4 hours , cooled to room temperature , filtered , washed and dried to obtain a yellow solid ( 6 . 5 g ) in a yield of 75 . 7 %. 1 h nmr ( 400 mhz , dmso - d 6 ): δ 10 . 11 ( s , 1h ), 9 . 47 ( s , 1h ), 8 . 99 ( s , 1h ), 8 . 38 ( d , j = 7 . 6 hz , 1h ), 7 . 86 ( m , 1h ), 7 . 65 ( m , 2h ), 4 . 27 ( m , 1h ), 2 . 89 ( t , j = 4 . 8 hz , 4h ), 2 . 42 ( br , 4h ), 2 . 19 ( s , 3h ), 1 . 23 ( d , j = 6 . 4 hz , 6h ) ppm . 4 - amino - 3 - methoxy - n -( 4 - methylpiperazin - 1 - yl ) benzamide ( 5 . 3 g ) was added to a solution of compound 2 - 3 ( 4 . 3 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 4 . 5 hours , cooled to room temperature , filtered , washed and dried to obtain a yellow solid ( 6 . 8 g ) in a yield of 77 . 1 %. 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 13 ( s , 1h ), 8 . 38 ( d , j = 6 . 8 hz , 1h ), 7 . 93 ( m , 1h ), 7 . 63 ( d , j = 8 . 0 hz , 1h ), 7 . 46 ( m , 1h ), 7 . 08 ( m , 1h ), 7 . 01 ( m , 1h ), 4 . 31 ( m , 1h ), 3 . 86 ( s , 3h ), 3 . 55 ( br , 4h ), 2 . 52 ( br , 4h ), 2 . 32 ( s , 3h ), 1 . 24 ( d , j = 6 . 4 hz , 6h ) ppm . 4 - amino - n -( 4 - methylpiperidin - 1 - yl ) benzamide ( 4 . 6 g ) was added to a solution of compound 2 - 3 ( 4 . 3 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 4 . 5 hours , cooled to room temperature , filtered , washed and dried to obtain a yellow solid ( 5 . 7 g ) in a yield of 70 . 0 %. 1 h nmr ( 400 mhz , dmso - d 6 ): δ 10 . 58 ( s , 1h ), 9 . 02 ( s , 1h ), 8 . 48 ( d , j = 5 . 6 hz , 1h ), 8 . 20 ( d , j = 6 . 8 hz , 1h ), 7 . 86 ( m , 4h ), 4 . 45 ( m , 1h ), 3 . 80 ( m , 1h ), 2 . 94 ( br , 4h ), 2 . 32 ( s , 3h ), 1 . 62 - 1 . 83 ( m , 4h ), 1 . 33 ( d , j = 6 . 4 hz , 6h ) ppm . 4 -( 4 - methylpiperazinyl ) phenylamine ( 3 . 8 g ) was added to a solution of compound 2 - 1 ( 3 . 5 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 4 . 5 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid ( 5 . 2 g ) in a yield of 79 . 5 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 9 . 07 ( s , 1h ), 8 . 52 ( s , 2h ), 8 . 40 ( s , 1h ), 7 . 57 ( s , 1h ), 7 . 51 ( s , 1h ), 7 . 10 ( m , 2h ), 3 . 31 ( t , j = 4 . 8 hz , 4h ), 2 . 81 ( t , j = 4 . 8 hz , 4h ), 2 . 30 ( s , 3h ) ppm . 4 -( 4 - methylpiperazinyl ) phenylamine ( 3 . 8 g ) was added to a solution of compound 2 - 2 ( 3 . 8 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 3 . 5 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid ( 5 . 1 g ) in a yield of 74 . 8 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 9 . 11 ( s , 1h ), 8 . 34 ( s , 1h ), 7 . 59 ( s , 1h ), 7 . 51 ( m , 2h ), 7 . 23 ( m , 2h ), 4 . 21 ( s , 3h ), 3 . 15 ( t , j = 4 . 8 hz , 4h ), 2 . 87 ( t , j = 4 . 8 hz , 4h ), 2 . 48 ( s , 3h ) ppm . 4 -( 4 - methylpiperazinyl ) phenylamine ( 3 . 8 g ) was added to a solution of compound 2 - 3 ( 4 . 3 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 3 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid ( 6 . 2 g ) in a yield of 84 . 1 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 9 . 02 ( s , 1h ), 8 . 42 ( s , 1h ), 7 . 63 ( s , 1h ), 7 . 51 ( s , 2h ), 6 . 95 ( m , 2h ), 4 . 41 ( m , 1h ), 3 . 22 ( t , j = 4 . 8 hz , 4h ), 2 . 61 ( t , j = 4 . 8 hz , 4h ), 2 . 37 ( s , 3h ), 1 . 33 ( d , j = 6 . 4 hz , 6h ) ppm . 4 -( 4 - methylpiperazinyl ) phenylamine ( 3 . 8 g ) was added to a solution of compound 2 - 4 ( 4 . 3 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 3 . 5 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid ( 6 . 4 g ) in a yield of 87 . 2 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 9 . 08 ( s , 1h ), 8 . 39 ( s , 1h ), 7 . 90 ( s , 1h ), 7 . 58 ( m , 2h ), 6 . 94 ( m , 2h ), 4 . 32 ( m , 1h ), 3 . 05 ( t , j = 4 . 8 hz , 4h ), 2 . 90 ( t , j = 4 . 8 hz , 4h ), 2 . 67 ( s , 3h ), 1 . 39 ( m , 4h ) ppm . 4 -( 4 - methylpiperazinyl ) phenylamine ( 3 . 8 g ) was added to a solution of compound 2 - 5 ( 4 . 8 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 3 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid ( 6 . 0 g ) in a yield of 76 . 0 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 9 . 03 ( s , 1h ), 8 . 47 ( s , 1h ), 7 . 69 ( s , 1h ), 7 . 51 ( m , 2h ), 7 . 11 ( m , 2h ), 4 . 43 ( m , 1h ), 3 . 28 ( t , j = 4 . 8 hz , 4h ), 2 . 67 ( t , j = 4 . 8 hz , 4h ), 2 . 45 ( s , 3h ), 2 . 15 - 2 . 23 ( m , 2h ), 1 . 74 - 1 . 86 ( m , 4h ), 1 . 50 - 1 . 72 ( m , 2h ) ppm . 4 -( 4 - methylpiperazinyl ) phenylamine ( 3 . 8 g ) was added to a solution of compound 2 - 6 ( 5 . 1 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 5 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid ( 6 . 4 g ) in a yield of 78 . 3 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 8 . 42 ( s , 1h ), 7 . 62 ( s , 1h ), 7 . 41 ( s , 2h ), 6 . 98 ( m , 2h ), 4 . 21 ( m , 1h ), 3 . 14 ( t , j = 4 . 8 hz , 4h ), 2 . 56 ( t , j = 4 . 8 hz , 4h ), 2 . 51 ( s , 3h ), 2 . 34 ( s , 3h ), 1 . 47 - 1 . 85 ( m , 8h ) ppm . 4 -( 4 - methylpiperazinyl ) phenylamine ( 3 . 8 g ) was added to a solution of compound 2 - 7 ( 4 . 9 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 5 . 5 hours , cooled to room temperature , filtered , washed and dried to obtain a reddish - brown solid ( 6 . 5 g ) in a yield of 81 . 5 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 8 . 51 ( s , 1h ), 7 . 86 ( s , 1h ), 7 . 43 ( s , 2h ), 7 . 01 ( m , 2h ), 4 . 32 ( m , 1h ), 3 . 94 ( s , 3h ), 3 . 08 ( t , j = 4 . 8 hz , 4h ), 2 . 64 ( t , j = 4 . 8 hz , 4h ), 2 . 53 ( s , 3h ), 1 . 43 ( d , j = 6 . 4 hz , 6h ) ppm . 4 -( 4 - methylpiperazinyl ) phenylamine ( 3 . 8 g ) was added to a solution of compound 2 - 8 ( 4 . 9 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 6 hours , cooled to room temperature , filtered , washed and dried to obtain a reddish - brown solid ( 6 . 0 g ) in a yield of 75 . 4 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 8 . 58 ( s , 1h ), 7 . 81 ( s , 1h ), 7 . 47 ( s , 2h ), 7 . 08 ( m , 2h ), 4 . 45 ( m , 1h ), 3 . 14 ( t , j = 4 . 8 hz , 4h ), 2 . 79 ( s , 3h ), 2 . 54 ( t , j = 4 . 8 hz , 4h ), 2 . 42 ( s , 3h ), 1 . 45 ( d , j = 6 . 4 hz , 6h ) ppm . 4 -( 4 - methylpiperazinyl ) phenylamine ( 3 . 8 g ) was added to a solution of compound 2 - 9 ( 4 . 6 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 3 . 5 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid ( 6 . 3 g ) in a yield of 82 . 3 %. 1 h nmr ( 400 mhz , dmso - d 6 ): δ 11 . 01 ( s , 1h ), 10 . 15 ( s , 1h ), 7 . 66 ( d , j = 8 . 4 , 2h ), 6 . 99 ( d , j = 9 . 2 , 2h ), 4 . 35 ( s , 1h ), 3 . 76 ( d , j = 11 . 2 , 2h ), 3 . 46 ( d , j = 10 . 8 , 2h ), 3 . 11 ( m , j = 13 . 6 , 4h ), 2 . 79 ( s , 3h ), 2 . 60 ( s , 3h ), 1 . 27 ( d , j = 6 . 4 , 6h ) ppm . 4 - amino - n -( 4 - methylpiperazin - 1 - yl ) benzamide ( 4 . 85 g ) was added to a solution of compound 2 - 5 ( 4 . 7 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 4 . 5 hours , cooled to room temperature , filtered , washed and dried to obtain a yellow solid ( 6 . 4 g ) in a yield of 72 . 6 %. ms m / z ( esi ): 441 [ m + h ] + . 4 - amino - 3 - fluoro - n -( 4 - methylpiperidin - 1 - yl ) benzamide ( 5 . 0 g ) was added to a solution of compound 2 - 3 ( 4 . 3 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 4 . 0 hours , cooled to room temperature , filtered , washed and dried to obtain a yellow solid ( 6 . 3 g ) in a yield of 72 . 8 %. ms m / z ( esi ): 432 [ m + h ] + . n -( 3 - aminophenyl ) acrylamide ( 3 . 2 g ) was added to a solution of compound 2 - 3 ( 4 . 3 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 3 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid ( 6 . 0 g ) in a yield of 88 . 3 %. ms m / z ( esi ): 344 [ m + h ] + . 4 -( 2 - morpholinoethoxy ) phenylamine ( 4 . 4 g ) was added to a solution of compound 2 - 3 ( 4 . 3 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 3 . 5 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid ( 6 . 4 g ) in a yield of 80 . 0 %. ms m / z ( esi ): 403 [ m + h ] + . 4 -( 3 -( 4 - methylpiperazin - 1 - yl ) propylamino ) phenylamine ( 4 . 9 g ) was added to a solution of compound 2 - 3 ( 4 . 3 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 4 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid ( 6 . 8 g ) in a yield of 79 . 9 %. ms m / z ( esi ): 429 [ m + h ] + . 4 - morpholinophenylamine ( 3 . 6 g ) was added to a solution of compound 2 - 3 ( 4 . 3 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 4 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid ( 5 . 3 g ) in a yield of 74 . 7 %. ms m / z ( esi ): 359 [ m + h ] + . 4 - morpholinomethylphenylamine ( 3 . 8 g ) was added to a solution of compound 2 - 5 ( 4 . 8 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 4 . 0 hours , cooled to room temperature , filtered , washed and dried to obtain a yellow solid ( 6 . 3 g ) in a yield of 80 . 6 %. ms m / z ( esi ): 399 [ m + h ] + . 4 -( 4 - methylpiperazinyl ) phenylamine ( 3 . 1 g ) was added to a solution of compound 2 - 10 ( 2 . 3 g ) in n - butanol ( 40 ml ). the mixture was reacted at 90 ° c . for 4 . 0 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid ( 4 . 13 g ) in a yield of 83 . 8 %. ms m / z ( esi ): 412 [ m + h ] + . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 10 . 71 ( s , 1h ), 10 . 35 ( s , 1h ), 8 . 96 ( s , 1h ), 8 . 48 ( d , j = 6 . 8 hz , 1h ), 7 . 71 ( d , j = 8 . 8 hz , 1h ), 6 . 99 ( d , j = 9 . 2 hz , 2h ), 4 . 04 ( m , 1h ), 3 . 78 ( m , 2h ), 3 . 46 ( m , 2h ), 3 . 15 ( m , 2h ), 3 . 04 ( m , 2h ), 2 . 83 ( s , 1h ), 1 . 98 ( m , 2h ), 1 . 65 ( m , 1h ), 1 . 43 ( m , 4h ), 1 . 26 ( m , 1h ) ppm . 4 -( 2 - methoxyethoxy ) phenylamine ( 2 . 7 g ) was added to a solution of compound 2 - 5 ( 3 . 7 g ) in n - butanol ( 80 ml ). the mixture was reacted at 90 ° c . for 4 . 0 hours , cooled to room temperature , filtered , washed and dried to obtain a yellow floc - like solid ( 4 . 53 g ) in a yield of 80 . 9 %. ms m / z ( esi ): 374 [ m + h ] + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ10 . 34 ( s , 1h ), 8 . 95 ( s , 1h ), 8 . 50 ( s , 1h ), 7 . 70 ( d , j = 6 . 0 hz , 2h ), 6 . 93 ( d , j = 8 . 8 hz , 2h ), 4 . 43 ( m , 1h ), 4 . 07 ( m , 2h ), 3 . 64 ( m , 2h ), 3 . 30 ( s , 3h ), 2 . 03 ( m , 2h ), 1 . 72 ( m , 2h ), 1 . 61 ( m , 4h ) ppm . 4 -(( 4 - ethylpiperazin - 1 - yl ) methyl ) phenylamine ( 3 . 6 g ) was added to a solution of compound 2 - 5 ( 6 . 0 g ) in n - butanol ( 130 ml ). the mixture was reacted at 90 ° c . for 4 . 0 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid in a yield of 81 . 8 %. ms m / z ( esi ): 426 [ m + h ] + . 4 -(( 4 - methylpiperazin - 1 - yl ) methyl ) phenylamine ( 4 . 7 g ) was added to a solution of compound 2 - 5 ( 5 . 28 g ) in n - butanol ( 130 ml ). the mixture was reacted at 90 ° c . for 4 . 0 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid in a yield of 85 . 7 %. ms m / z ( esi ): 412 [ m + h ] + . 4 -( 4 - methylpiperazinyl ) phenylamine ( 1 . 13 g ) was added to a solution of compound 2 - 11 ( 1 . 6 g ) in n - butanol ( 25 ml ). the mixture was reacted at 90 ° c . for 4 . 0 hours , cooled to room temperature , filtered , washed and dried to obtain an orange - red solid ( 4 . 13 g ) in a yield of 87 . 6 %. ms m / z ( esi ): 426 [ m + h ] + . a solution of rongalite ( sodium dithionite ) ( 9 . 6 g ) in water ( 30 ml ) was added to a solution of 4 - 1 ( 2 . 1 g ) in tetrahydrofuran ( 25 ml ). the mixture was stirred at room temperature for 6 - 12 hours , adjusted to a ph of 7 - 8 by adding a saturated potassium carbonate solution , and then extracted with dichloromethane ( 5 × 20 ml ). the organic phase was dried over anhydrous sodium sulfate , and rotary evaporated to dryness to obtain a jade - green solid ( 1 . 2 g ) in a yield of 63 . 2 %. 1 h nmr ( 400 mhz , dmso - d 6 ): δ 10 . 01 ( s , 1h ), 9 . 32 ( s , 1h ), 8 . 78 ( s , 1h ), 8 . 01 ( m , 2h ), 7 . 83 ( s , 1h ), 7 . 72 ( m , 2h ), 4 . 29 ( m , 1h ), 4 . 08 ( s , 2h ), 2 . 87 ( t , j = 4 . 8 hz , 4h ), 2 . 47 ( br , 4h ), 2 . 24 ( s , 3h ), 1 . 22 ( d , j = 6 . 8 hz , 6h ) ppm . a solution of rongalite ( 9 . 6 g ) in water ( 30 ml ) was added to a solution of 4 - 2 ( 2 . 2 g ) in tetrahydrofuran ( 25 ml ). the mixture was stirred at room temperature for 6 - 12 hours , adjusted to a ph of 7 - 8 by adding a saturated potassium carbonate solution , and then extracted with dichloromethane ( 5 × 20 ml ). the organic phase was dried over anhydrous sodium sulfate , and rotary evaporated to dryness to obtain a jade - green solid ( 1 . 4 g ) in a yield of 68 . 4 %. 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 26 ( s , 1h ), 8 . 44 ( m , 1h ), 7 . 81 ( s , 1h ), 7 . 56 ( d , j = 10 . 8 hz , 2h ), 7 . 40 ( s , 1h ), 6 . 24 ( d , j = 7 . 2 hz , 1h ), 4 . 31 ( s , 2h ), 4 . 22 ( m , 1h ), 2 . 86 ( t , j = 4 . 8 hz , 4h ), 2 . 41 ( br , 4h ), 2 . 18 ( s , 3h ), 1 . 22 ( d , j = 6 . 4 hz , 6h ) ppm . in a 500 ml round - bottom flask , compound 4 - 3 ( 4 . 0 g ) was dissolved into 150 ml ethanol , and then 40 ml water and 5 . 0 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 2 . 7 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 3 . 5 hours . the mixture was filtered while hot , rotary evaporated to dryness , and subjected to a column chromatography to obtain a bluish - black solid ( 2 . 8 g ) in a yield of 75 . 0 %. ms m / z ( esi ): 415 [ m + h ] + . in a 500 ml round - bottom flask , compound 4 - 4 ( 4 . 0 g ) was dissolved into 150 ml ethanol , and then 40 ml water and 5 . 0 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 2 . 7 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 4 . 2 hours . the mixture was filtered while hot , rotary evaporated to dryness , and subjected to a column chromatography to obtain a bluish - black solid ( 2 . 6 g ) in a yield of 70 . 8 %. ms m / z ( esi ): 384 [ m + h ] + . in a 500 ml round - bottom flask , compound 4 - 5 ( 6 . 6 g ) was dissolved into 160 ml ethanol , and then 40 ml water and 5 . 35 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 6 . 6 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 4 . 5 hours . the mixture was filtered while hot , rotary evaporated to dryness , and recrystallized to obtain a bluish - black solid in a yield of 71 . 0 %. 1 h nmr ( 400 mhz , dmso - d 6 ): δ 8 . 18 ( s , 1h ), 7 . 56 ( d , j = 9 . 2 hz , 2h ), 6 . 79 ( d , j = 8 . 8 hz , 2h ), 6 . 00 ( d , j = 7 . 6 hz , 1h ), 4 . 24 ( m , 1h ), 4 . 01 ( s , 2h ), 2 . 99 ( t , j = 4 . 4 hz , 4h ), 2 . 43 ( t , j = 4 . 8 hz , 4h ), 2 . 21 ( s , 3h ), 1 . 21 ( d , j = 6 . 4 hz , 6h ) ppm . in a 100 ml round - bottom flask , compound 4 - 6 ( 1 . 0 g ) was dissolved into 60 ml ethanol , and then 15 ml water and 0 . 8 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 0 . 84 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 1 . 5 hours . the mixture was filtered while hot , rotary evaporated to dryness , and subjected to a column chromatography to obtain a bluish - black solid ( 0 . 7 g ) in a yield of 70 . 2 %. ms m / z ( esi ): 314 [ m + h ] + . in a 500 ml round - bottom flask , compound 4 - 7 ( 3 . 7 g ) was dissolved into 200 ml ethanol , and then 50 ml water and 2 . 7 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 2 . 8 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 3 hours . the mixture was filtered while hot , rotary evaporated to dryness , and subjected to a column chromatography to obtain a bluish - black solid ( 2 . 4 g ) in a yield of 70 . 6 %. 1 h nmr ( 400 mhz , dmso - d 6 ): δ 8 . 18 ( s , 1h ), 7 . 56 ( d , j = 9 . 2 hz , 2h ), 6 . 79 ( d , j = 8 . 8 hz , 2h ), 6 . 00 ( d , j = 7 . 6 hz , 1h ), 4 . 24 ( m , 1h ), 4 . 01 ( s , 2h ), 2 . 99 ( t , j = 4 . 4 hz , 4h ), 2 . 43 ( t , j = 4 . 8 hz , 4h ), 2 . 21 ( s , 3h ), 1 . 21 ( d , j = 6 . 4 hz , 6h ) ppm . in a 100 ml round - bottom flask , compound 4 - 8 ( 1 . 1 g ) was dissolved into 60 ml ethanol , and then 15 ml water and 0 . 8 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 0 . 84 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 1 . 5 hours . the mixture was filtered while hot , rotary evaporated to dryness , and subjected to a column chromatography to obtain a column chromatography to obtain bluish - black solid ( 0 . 8 g ) in a yield of 79 . 2 %. ms m / z ( esi ): 340 [ m + h ] + . in a 250 ml round - bottom flask , compound 4 - 9 ( 2 . 0 g ) was dissolved into 100 ml ethanol , and then 25 ml water and 1 . 4 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 1 . 4 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 2 . 5 hours . the mixture was filtered while hot , rotary evaporated to dryness , and recrystallized to obtain a bluish - black solid ( 1 . 1 g ) in a yield of 59 . 3 %. ms m / z ( esi ): 368 [ m + h ] + . in a 500 ml round - bottom flask , compound 4 - 10 ( 3 . 7 g ) was dissolved into 200 ml ethanol , and then 50 ml water and 2 . 7 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 2 . 8 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 3 hours . the mixture was filtered while hot , rotary evaporated to dryness , and subjected to a column chromatography to obtain a bluish - black solid ( 2 . 6 g ) in a yield of 75 . 7 %. ms m / z ( esi ): 382 [ m + h ] + . in a 500 ml round - bottom flask , compound 4 - 11 ( 3 . 9 g ) was dissolved into 200 ml ethanol , and then 50 ml water and 2 . 7 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 2 . 8 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 3 hours . the mixture was filtered while hot , rotary evaporated to dryness , and subjected to a column chromatography to obtain a bluish - black solid ( 2 . 5 g ) in a yield of 70 . 0 %. ms m / z ( esi ): 372 [ m + h ] + . in a 500 ml round - bottom flask , compound 4 - 12 ( 3 . 8 g ) was dissolved into 200 ml ethanol , and then 50 ml water and 2 . 7 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 2 . 8 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 3 hours . the mixture was filtered while hot , rotary evaporated to dryness , and subjected to a column chromatography to obtain a bluish - black solid ( 2 . 4 g ) in a yield of 67 . 3 %. ms m / z ( esi ): 371 [ m + h ] + . in a 500 ml round - bottom flask , compound 4 - 13 ( 3 . 7 g ) was dissolved into 200 ml ethanol , and then 50 ml water and 2 . 7 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 2 . 8 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 3 hours . the mixture was filtered while hot , rotary evaporated to dryness , and subjected to a column chromatography to obtain a bluish - black solid ( 2 . 5 g ) in a yield of 73 . 3 %. 1 h nmr ( 400 mhz , cdcl 3 ): δ 7 . 51 ( d , j = 8 . 8 , 2h ), 6 . 89 ( d , j = 8 . 8 , 2h ), 6 . 59 ( s , 1h ), 5 . 17 ( d , j = 7 . 2 , 1h ), 4 . 63 ( s , 2h ), 4 . 22 ( m , j = 6 . 72 , 1h ), 3 . 14 ( t , j = 5 . 0 , 4h ), 2 . 59 ( t , j = 4 . 8 , 4h ), 2 . 35 ( s , 3h ), 2 . 25 ( s , 3h ), 1 . 26 ( d , j = 6 . 4 , 6h ) ppm . in a 500 ml round - bottom flask , compound 4 - 14 ( 4 . 4 g ) was dissolved into 150 ml ethanol , and then 40 ml water and 5 . 0 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 2 . 7 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 3 . 5 hours . the mixture was filtered while hot , rotary evaporated to dryness , and recrystallized to obtain a bluish - black solid ( 3 . 2 g ) in a yield of 77 . 9 %. ms m / z ( esi ): 411 [ m + h ] + . a solution of rongalite ( 9 . 6 g ) in water ( 30 ml ) was added to a solution of 4 - 15 ( 2 . 2 g ) in tetrahydrofuran ( 25 ml ). the mixture was stirred at room temperature for 6 - 12 hours , adjusted to a ph of 7 - 8 by adding a saturated potassium carbonate solution , and then extracted with dichloromethane ( 5 × 20 ml ). the organic phase was dried over anhydrous sodium sulfate , and rotary evaporated to dryness to obtain a jade - green solid ( 1 . 5 g ) in a yield of 69 . 6 %. ms m / z ( esi ): 402 [ m + h ] + . n -( 3 - aminophenyl ) acrylamide ( 3 . 2 g ) was added to a solution of compound 2 - 3 ( 4 . 3 g ) in n - butanol ( 150 ml ). the mixture was reacted at 90 ° c . for 3 hours , cooled to room temperature , filtered , washed and dried to obtain a red solid ( 6 . 0 g ) in a yield of 88 . 3 %. ms m / z ( esi ): 344 [ m + h ] + . in a 100 ml round - bottom flask , compound 4 - 17 ( 1 . 21 g ) was dissolved into 60 ml ethanol , and then 15 ml water and 0 . 8 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 0 . 84 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 1 . 5 hours . the mixture was filtered while hot , rotary evaporated to dryness , and subjected to a column chromatography to obtain a bluish - black solid in a yield of 75 . 2 %. ms m / z ( esi ): 373 [ m + h ] + . in a 100 ml round - bottom flask , compound 4 - 18 ( 1 . 3 g ) was dissolved into 60 ml ethanol , and then 15 ml water and 0 . 8 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 0 . 84 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 1 . 5 hours . the mixture was filtered while hot , rotary evaporated to dryness , and subjected to a column chromatography to obtain a bluish - black solid in a yield of 78 . 9 %. ms m / z ( esi ): 399 [ m + h ] + . in a 100 ml round - bottom flask , compound 4 - 19 ( 1 . 1 g ) was dissolved into 60 ml ethanol , and then 15 ml water and 0 . 8 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 0 . 84 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 2 . 5 hours . the mixture was filtered while hot , rotary evaporated to dryness , and subjected to a column chromatography to obtain a bluish - black solid in a yield of 74 . 1 %. ms m / z ( esi ): 329 [ m + h ] + . in a 500 ml round - bottom flask , compound 4 - 20 ( 3 . 85 g ) was dissolved into 150 ml ethanol , and then 40 ml water and 5 . 0 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 2 . 7 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 3 . 5 hours . the mixture was filtered while hot , rotary evaporated to dryness , and subjected to a column chromatography to obtain a bluish - black solid in a yield of 74 . 5 %. ms m / z ( esi ): 369 [ m + h ] + . in a 100 ml round - bottom flask , compound 4 - 21 ( 1 . 03 g ) was dissolved into 40 ml ethanol , and then 10 ml water and 0 . 67 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 0 . 7 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 3 . 7 hours . the mixture was filtered while hot , and rotary - evaporated to dryness to obtain a crude product in a yield of 78 . 9 %. ms m / z ( esi ): 382 [ m + h ] + . in a 250 ml round - bottom flask , compound 4 - 22 ( 3 . 73 g ) was dissolved into 120 ml ethanol , and then 30 ml water and 2 . 67 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 2 . 8 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 4 hours . the mixture was filtered while hot , and rotary - evaporated to dryness to obtain a crude product in a yield of 84 . 6 %. ms m / z ( esi ): 344 [ m + h ] + . in a 500 ml round - bottom flask , compound 4 - 23 ( 10 g ) was dissolved into 240 ml ethanol , and then 60 ml water and 2 . 67 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 6 . 6 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 4 hours . the mixture was filtered while hot , and rotary - evaporated to dryness to obtain a crude product in a yield of 82 . 7 %. ms m / z ( esi ): 396 [ m + h ] + . in a 500 ml round - bottom flask , compound 4 - 24 ( 9 . 42 g ) was dissolved into 240 ml ethanol , and then 60 ml water and 1 . 92 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 6 . 85 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the reaction time was 4 hours . the mixture was filtered while hot , and rotary - evaporated to dryness to obtain a crude product in a yield of 80 . 6 %. ms m / z ( esi ): 382 [ m + h ] + . in a 100 ml round - bottom flask , compound 4 - 23 ( 2 . 0 g ) was dissolved into 30 ml ethanol , and then 10 ml water and 0 . 62 g nh 4 cl were added thereto . the mixture was stirred at room temperature for 10 minutes , and warmed to 90 ° c . 1 . 29 g fe powder was added to the mixture in three portions . tlc detection indicated the completion of the reaction of the starting material . the mixture was filtered while hot , and rotary - evaporated to dryness to obtain a crude product in a yield of 81 . 4 %. ms m / z ( esi ): 396 [ m + h ] + . compound 5 - 1 ( 2 . 3 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 1 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 64 . 3 %. esi - ms ( m / z , %) 484 . 29 ( m − h ) − ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 63 ( s , 1h ), 9 . 21 ( s , 1h ), 9 . 11 ( s , 1h ), 7 . 85 ( m , 4h ), 7 . 73 ( d , j = 8 . 4 hz , 2h ), 7 . 34 ( m , 2h ), 7 . 00 ( m , 1h ), 4 . 94 ( m , 1h ), 2 . 88 ( t , j = 4 . 4 hz , 4h ), 2 . 42 ( br , 4h ), 2 . 19 ( s , 3h ), 1 . 70 ( d , j = 6 . 8 hz , 6h ) ppm . compound 5 - 1 ( 2 . 3 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 3 - chloro - 4 - fluorophenyl isothiocyanate ( 1 . 35 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 1 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 62 . 9 %. esi - ms ( m / z , %) 536 . 27 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 65 ( s , 1h ), 9 . 31 ( s , 1h ), 9 . 20 ( s , 1h ), 8 . 51 ( s , 1h ), 8 . 23 ( m , 1h ), 7 . 86 ( d , j = 8 . 8 hz , 2h ), 7 . 78 ( m , 1h ), 7 . 75 ( t , j = 6 . 6 hz , 2h ), 7 . 41 ( t , j = 9 . 2 hz , 1h ), 4 . 90 ( s , 1h ), 2 . 88 ( d , j = 4 hz , 4h ), 2 . 43 ( m , 4h ), 2 . 20 ( s , 3h ), 1 . 70 ( d , j = 6 . 8 hz , 6h ) ppm . compound 5 - 2 ( 2 . 4 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and meta - acetamidophenyl isothiocyanate ( 1 . 4 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 2 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69 . 1 %. esi - ms ( m / z , %) 561 . 18 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 10 . 00 ( s , 1h ), 9 . 52 ( s , 1h ), 9 . 20 ( s , 1h ), 8 . 88 ( s , 1h ), 8 . 42 ( s , 1h ), 8 . 26 ( m , 1h ), 8 . 08 ( s , 1h ), 7 . 66 ( d , j = 10 . 0 hz , 2h ), 7 . 57 ( d , j = 7 . 2 hz , 1h ), 7 . 21 ( m , 2h ), 4 . 94 ( m , 1h ), 2 . 90 ( s , 4h ), 2 . 68 ( br , 4h ), 2 . 06 ( s , 3h ), 1 . 64 ( d , j = 6 . 0 hz , 6h ) ppm . compound 5 - 2 ( 2 . 4 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 2 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 64 . 8 %. esi - ms ( m / z , %) 502 . 17 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 37 ( s , 1h ), 9 . 10 ( s , 1h ), 8 . 88 ( s , 1h ), 8 . 43 ( s , 1h ), 8 . 25 ( m , 1h ), 7 . 84 ( d , j = 8 . 4 hz , 2h ), 7 . 64 ( d , j = 10 . 4 hz , 2h ), 7 . 00 ( m , 2h ), 4 . 90 ( m , 1h ), 2 . 89 ( s , 4h ), 2 . 42 ( br , 4h ), 2 . 19 ( s , 3h ), 1 . 65 ( d , j = 6 . 4 hz , 6h ) ppm . compound 5 - 2 ( 2 . 4 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 3 - chloro - 4 - fluorophenyl isothiocyanate ( 1 . 35 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 2 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 68 . 8 %. esi - ms ( m / z , %) 554 . 30 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d6 ): δ9 . 21 ( s , 1h ), 9 . 04 ( s , 1h ), 8 . 41 ( s , 1h ), 8 . 22 ( d , j = 5 . 2 hz , 1h ), 7 . 74 ( m , 1h ), 7 . 62 ( d , j = 8 . 8 hz , 1h ), 7 . 57 ( d , j = 8 . 8 hz , 1h ), 7 . 39 ( m , 1h ), 6 . 87 ( d , j = 8 . 4 hz , 2h ), 4 . 84 ( m , 1h ), 3 . 05 ( s , 4h ), 2 . 45 ( br , 4h ), 2 . 22 ( s , 3h ), 1 . 66 ( d , j = 6 . 4 hz , 6h ) ppm . compound 5 - 15 ( 2 . 4 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 15 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 67 . 6 %. esi - ms ( m / z , %) 502 . 22 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 22 ( s , 1h ), 8 . 87 ( s , 1h ), 8 . 49 ( s , 1h ), 8 . 44 ( s , 1h ), 8 . 29 ( t , j = 8 . 4 , 1h ), 7 . 86 ( d , j = 8 . 0 , 2h ), 7 . 78 ( d , j = 8 . 8 , 2h ), 7 . 34 ( t , j = 7 . 6 , 2h ), 7 . 01 ( t , j = 7 . 2 , 1h ), 4 . 97 ( m , 1h ), 4 . 04 ( m , 1h ), 3 . 38 ( m , 2h ), 3 . 09 ( m , 2h ), 2 . 72 ( s , 3h ), 1 . 99 ( m , 4h ), 1 . 65 ( d , j = 6 . 8 , 6h ) ppm . compound 5 - 3 ( 2 . 5 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 3 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 66 . 5 %. esi - ms ( m / z , %) 514 . 21 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 10 . 98 ( s , 1h ), 9 . 65 ( s , 1h ), 8 . 90 ( s , 1h ), 8 . 50 ( s , 1h ), 8 . 27 ( d , j = 7 . 6 hz , 1h ), 7 . 83 ( d , j = 7 . 6 hz , 2h ), 7 . 39 ( t , j = 8 hz , 2h ), 7 . 18 - 7 . 08 ( m , 3h ), 5 . 026 ( m , 1h ), 3 . 94 ( s , 4h ), 3 . 42 ( d , j = 7 . 6 hz , 2h ), 3 . 09 ( d , j = 12 hz , 2h ), 2 . 79 ( d , j = 7 . 2 hz , 3h ), 1 . 66 ( d , j = 6 . 4 hz , 6h ) ppm . to a solution of compound 5 - 4 ( 2 . 0 g ) and methyl 3 - ethynylphenylcarbamodithioate ( 1 . 3 g ) in n , n - dimethylformamide ( 30 ml ) were added copper oxide ( 0 . 08 g ) and potassium carbonate ( 1 . 4 g ). the mixture was heated to 60 ° c . and reacted for 2 - 6 hours . the reaction solution was cooled to room temperature and filtered . the filtrate was washed with ethyl acetate , a saturated saline solution and water . the organic layer was dried over anhydrous sodium sulfate and concentrated . purification was conducted by a column chromatography to obtain an off - white solid in a yield of 64 . 1 %. esi - ms ( m / z , %) 507 . 22 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d6 ): δ 9 . 51 ( s , 1h ), 9 . 04 ( s , 1h ), 8 . 91 ( s , 1h ), 7 . 88 ( m , 4h ), 7 . 65 ( d , 2h ), 7 . 41 ( m , 2h ), 7 . 12 ( m , 1h ), 4 . 80 ( m , 1h ), 4 . 14 ( s , 1h ), 3 . 71 ( m , 1h ), 2 . 80 ( m , 4h ), 2 . 39 ( br , 4h ), 2 . 21 ( s , 3h ), 1 . 62 ( d , 6h ) ppm . compound 5 - 4 ( 2 . 3 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 4 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 67 . 9 %. esi - ms ( m / z , %) 483 . 25 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 72 ( s , 1h ), 9 . 63 ( s , 1h ), 9 . 11 ( s , 1h ), 8 . 45 ( s , 1h ), 8 . 28 ( s , 1h ), 7 . 89 - 7 . 81 ( m , 5h ), 7 . 34 ( t , j = 7 . 8 hz , 2h ), 7 . 00 ( t , j = 7 . 2 hz , 1h ), 4 . 95 ( m , 1h ), 4 . 02 ( s , 1h ), 3 . 44 ( d , j = 10 . 8 hz , 2h ), 3 . 08 ( s , 2h ), 2 . 75 ( s , 3h ), 1 . 99 ( s , 2h ), 1 . 82 ( d , j = 11 . 2 hz , 2h ), 1 . 70 ( d , j = 6 . 8 hz , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 67 . 5 %. esi - ms ( m / z , %) 441 . 29 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d6 ): δ 9 . 09 ( d , j = 6 . 8 hz , 2h ), 8 . 36 ( s , 1h ), 7 . 83 ( d , j = 8 . 0 hz , 2h ), 7 . 69 ( d , j = 9 . 2 hz , 2h ), 7 . 33 ( m , 2h ), 6 . 97 ( m , 3h ), 4 . 92 ( m , 1h ), 3 . 44 ( br , 4h ), 3 . 17 ( br , 4h ), 2 . 81 ( s , 3h ), 1 . 67 ( d , j = 6 . 8 hz , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and meta - bromophenyl isothiocyanate ( 1 . 5 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 57 . 4 %. esi - ms ( m / z , %) 519 . 19 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 47 ( s , 1h ), 9 . 09 ( s , 1h ), 8 . 42 ( s , 1h ), 8 . 25 ( s , 1h ), 7 . 85 ( d , j = 8 . 0 hz , 1h ), 7 . 67 ( d , j = 8 . 8 hz , 2h ), 7 . 28 ( t , j = 8 . 4 hz , 1h ), 7 . 14 ( d , j = 8 . 0 hz , 1h ), 6 . 93 ( d , j = 8 . 8 hz , 2h ), 4 . 99 ( m , 1h ), 3 . 51 - 3 . 40 ( m , 2h ), 3 . 25 ( s , 2h ), 3 . 07 ( s , 4h ), 2 . 64 ( s , 3h ), 1 . 66 ( d , j = 6 . 8 ; h , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and meta - ethynylphenyl isothiocyanate ( 1 . 1 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 53 . 9 %. esi - ms ( m / z , %) 465 . 23 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 10 ( s , 1h ), 9 . 02 ( s , 1h ), 8 . 41 ( s , 1h ), 8 . 07 ( s , 1h ), 7 . 81 ( d , j = 8 . 4 hz , 1h ), 7 . 64 ( d , j = 9 . 2 hz , 2h ), 7 . 34 ( t , j = 8 . 0 , 1h ), 7 . 08 ( d , j = 7 . 2 hz , 1h ), 6 . 88 ( d , j = 9 . 2 hz , 2h ), 4 . 85 ( m , 1h ), 4 . 18 ( s , 1h ), 3 . 05 ( s , 4h ), 2 . 47 ( t , j = 9 . 0 , 4h ), 2 . 22 ( s , 3h ), 1 . 67 ( d , j = 6 . 8 hz , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 3 - chloro - 4 - fluorophenyl isothiocyanate ( 1 . 35 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 60 . 8 %. esi - ms ( m / z , %) 493 . 16 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d6 ): δ 9 . 21 ( s , 1h ), 9 . 04 ( s , 1h ), 8 . 41 ( s , 1h ), 8 . 22 ( d , j = 5 . 2 hz , 1h ), 7 . 74 ( m , 1h ), 7 . 62 ( d , j = 8 . 8 hz , 1h ), 7 . 57 ( d , j = 8 . 8 hz , 1h ), 7 . 39 ( m , 1h ), 6 . 87 ( d , j = 8 . 4 hz , 2h ), 4 . 84 ( m , 1h ), 3 . 05 ( br , 4h ), 2 . 45 ( br , 4h ), 2 . 22 ( s , 3h ), 1 . 66 ( d , j = 6 . 4 hz , 6h ) ppm . compound 5 - 8 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and meta - bromophenyl isothiocyanate ( 1 . 5 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 8 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 58 . 2 %. esi - ms ( m / z , %) 517 . 21 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d6 ): δ 9 . 78 ( s , 1h ), 9 . 32 ( s , 1h ), 8 . 45 ( s , 1h ), 7 . 79 ( m , 2h ), 7 . 61 ( m , 2h ), 7 . 49 ( m , 2h ), 7 . 36 ( m , 1h ), 4 . 15 ( m , 1h ), 2 . 94 ( tr , 4h ), 2 . 63 ( br , 4h ), 2 . 19 ( s , 3h ), 1 . 26 ( m , 4h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and para - bromophenyl isothiocyanate ( 1 . 5 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 53 . 4 %. esi - ms ( m / z , %) 519 . 22 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 25 ( s , 1h ), 9 . 11 ( s , 1h ), 8 . 39 ( s , 1h ), 7 . 85 ( d , j = 8 . 8 hz , 2h ), 7 . 69 ( d , j = 9 . 2 hz , 2h ), 7 . 50 ( d , j = 8 . 8 hz , 2h ), 6 . 95 ( d , j = 9 . 2 hz , 2h ), 4 . 91 ( m , 1h ), 3 . 69 ( s , 1h ), 3 . 45 ( s , 1h ), 3 . 17 ( s , 1h ), 3 . 00 ( s , 1h ), 2 . 82 ( s , 3h ), 1 . 66 ( d , j = 6 . 8 hz , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and meta - trifluoromethylphenyl isothiocyanate ( 1 . 4 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 55 . 8 %. esi - ms ( m / z , %) 509 . 24 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 10 . 80 ( s , 1h ), 10 . 03 ( s , 1h ), 8 . 50 ( s , 1h ), 8 . 32 ( s , 1h ), 8 . 19 ( d , j = 8 . 0 , 1h ), 7 . 62 ( t , j = 7 . 8 , 1h ), 7 . 55 ( d , j = 8 . 8 , 2h ), 7 . 40 ( d , j = 7 . 6 , 1h ), 7 . 04 ( d , j = 9 . 2 , 2h ), 5 . 05 ( m , 1h ), 3 . 78 ( d , j = 12 . 4 , 4h ), 3 . 04 - 3 . 20 ( m , 4h ), 2 . 82 ( d , j = 4 . 0 , 3h ), 1 . 64 ( d , j = 6 . 4 , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and meta - methoxyphenyl isothiocyanate ( 1 . 2 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 58 . 8 %. esi - ms ( m / z , %) 471 . 28 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 06 ( d , j = 16 . 8 , 2h ), 8 . 37 ( s , 1h ), 7 . 69 ( d , j = 8 . 8 , 2h ), 7 . 52 ( s , 1h ), 7 . 42 ( d , j = 4 . 0 , 1h ), 7 . 22 ( t , j = 8 . 2 , 1h ), 6 . 95 ( d , j = 9 . 2 , 2h ), 6 . 56 ( m , 1h ), 4 . 91 ( m , 1h ), 3 . 76 ( s , 1h ), 2 . 81 ( s , 1h ), 1 . 66 ( d , j = 6 . 8 , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and para - methoxyphenyl isothiocyanate ( 1 . 2 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 59 . 8 %. esi - ms ( m / z , %) 471 . 28 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 04 ( s , 1h ), 8 . 93 ( s , 1h ), 8 . 30 ( s , 1h ), 7 . 71 ( m , j = 8 . 9 , 4h ), 6 . 94 ( t , j = 9 . 4 , 4h ), 4 . 90 ( m , 1h ), 3 . 75 ( s , 3h ), 3 . 46 - 3 . 43 ( m , 4h ), 3 . 17 - 3 . 06 ( m , 4h ), 2 . 81 ( s , 3h ), 1 . 67 ( d , j = 6 . 8 , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 3 - chloro - 4 -( 3 - fluorobenzyloxy ) phenyl isothiocyanate ( 2 . 1 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65 . 7 %. esi - ms ( m / z , %) 599 . 22 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 02 ( d , j = 4 . 8 hz , 2h ), 8 . 36 ( s , 1h ), 8 . 08 ( d , j = 2 . 4 hz , 1h ), 7 . 67 ( m , 3h ), 7 . 46 ( m , 1h ), 7 . 31 ( t , j = 7 . 6 hz , 2h ), 7 . 20 ( m , 2h ), 6 . 91 ( d , j = 8 . 8 hz , 2h ), 5 . 21 ( s , 2h ), 4 . 83 ( m , 1h ), 3 . 15 ( s , 4h ), 2 . 81 ( s , 3h ), 2 . 48 ( s , 2h ), 2 . 30 ( s , 2h ), 1 . 66 ( d , j = 6 . 8 hz , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and ( 3 - chloro - 4 -( pyridin - 2 - yl ) methoxy ) phenyl isothiocyanate ( 2 . 0 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65 . 9 %. esi - ms ( m / z , %) 582 . 31 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d6 ): δ 9 . 13 ( s , 1h ), 8 . 60 ( d , 1h ), 8 . 30 ( s , 1h ), 7 . 85 ( m , 3h ), 7 . 69 ( m , 1h ), 7 . 60 ( d , 2h ), 7 . 30 - 7 . 15 ( m , 4h ), 7 . 05 ( d , 1h ), 4 . 88 ( m , 1h ), 3 . 48 ( br , 4h ), 2 . 97 ( br , 4h ), 2 . 78 ( s , 3h ), 1 . 59 ( d , j = 6 . 8 hz , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 3 -( 3 -( 3 - chloro - 4 - fluorophenyl ) ureido ) phenyl isothiocyanate ( 2 . 3 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 62 . 5 %. esi - ms ( m / z , %) 627 . 21 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 8 . 99 ( d , j = 9 . 6 hz , 2h ), 8 . 88 ( s , 1h ), 8 . 80 ( s , 1h ), 8 . 34 ( s , 1h ), 7 . 94 ( s , 1h ), 7 . 84 ( m , 1h ), 7 . 63 ( d , j = 9 . 2 hz , 2h ), 7 . 47 ( d , j = 8 hz , 1h ), 7 . 37 - 7 . 28 ( m , 2h ), 7 . 22 ( t , j = 8 hz , 1h ), 7 . 11 ( d , j = 8 hz , 1h ), 6 . 88 ( d , j = 9 . 2 hz , 2h ), 4 . 90 ( m , 1h ), 3 . 06 ( t , j = 4 . 8 hz , 3h ), 2 . 51 ( m , 4h ), 2 . 48 ( d , j = 4 . 4 hz , 2h ), 2 . 26 ( d , j = 19 . 6 hz , 2h ), 1 . 67 ( d , j = 6 . 8 hz , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 4 -( 3 - fluorophenylcarbamoyl ) phenyl isothiocyanate ( 2 . 0 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 54 . 6 %. esi - ms ( m / z , %) 578 . 22 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 10 . 30 ( s , 1h ), 9 . 44 ( s , 1h ), 9 . 12 ( s , 1h ), 8 . 44 ( s , 1h ), 7 . 98 ( s , 3h ), 7 . 78 ( d , j = 11 . 6 hz , 1h ), 7 . 68 ( d , j = 8 . 8 hz , 2h ), 7 . 59 ( d , j = 7 . 2 hz , 2h ), 7 . 38 ( m , 1h ), 6 . 91 ( m , 3h ), 4 . 94 ( m , 1h ), 3 . 27 ( s , 4h ), 2 . 96 ( d , j = 8 hz , 2h ), 2 . 73 ( s , 3h ), 2 . 55 ( s , 2h ), 1 . 69 ( d , j = 6 . 4 hz , 6h ) ppm ; compound 5 - 8 ( 2 . 0 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 86 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 8 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 58 . 3 %. esi - ms ( m / z , %) 439 . 23 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 10 . 14 ( s , 1h ), 9 . 64 ( s , 1h ), 8 . 39 ( s , 1h ), 7 . 851 ( d , j = 8 hz , 2h ), 7 . 60 ( d , j = 8 . 8 hz , 2h ), 7 . 41 ( t , j = 8 hz , 2h ), 7 . 13 ( t , j = 7 . 2 hz , 1h ), 7 . 05 ( d , j = 9 . 2 hz , 2h ), 3 . 43 - 3 . 50 ( m , 4h ), 3 . 20 - 3 . 24 ( m , 4h ), 2 . 82 ( d , j = 3 . 2 hz , 3h ), 1 . 19 - 1 . 30 ( m , 4h ) ppm . compound 5 - 6 ( 1 . 9 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 86 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 6 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 51 . 1 %. esi - ms ( m / z , %) 413 . 24 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 57 ( s , 1h ), 9 . 52 ( s , 1h ), 8 . 37 ( s , 1h ), 7 . 88 ( d , j = 7 . 6 hz , 2h ), 7 . 656 ( d , j = 8 . 4 hz , 2h ), 7 . 37 ( t , j = 8 hz , 2h ), 7 . 05 ( t , j = 7 . 2 hz , 1h ), 6 . 99 ( d , j = 8 . 8 hz , 2h ), 3 . 69 ( s , 3h ), 3 . 381 ( s , 4h ), 3 . 16 ( d , j = 8 . 8 hz , 2h ), 3 . 03 ( d , j = 12 hz , 2h ), 2 . 82 ( s , 3h ) ppm . compound 5 - 5 ( 2 . 4 g ) was dissolved into dichloromethane ( 120 ml ). to the mixture were successively added edci ( 3 . 1 g ), n , n - diisopropylethylamine ( 6 . 6 ml ), and para - trifluoromethylphenyl isothiocyanate ( 1 . 1 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 5 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 57 . 3 %. esi - ms ( m / z , %) 399 . 27 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 10 . 89 ( s , 1h ), 9 . 93 ( s , 1h ), 8 . 77 ( s , 1h ), 8 . 20 ( s , 1h ), 7 . 30 ( d , j = 7 . 2 hz , 2h ), 7 . 63 ( d , j = 8 . 4 hz , 2h ), 7 . 34 ( t , j = 6 . 8 hz , 2h ), 7 . 00 ( s , 1h ), 6 . 87 ( d , j = 8 . 8 hz , 2h ), 3 . 04 ( t , j = 4 . 4 hz , 4h ), 2 . 46 ( t , j = 4 . 4 hz , 4h ), 2 . 23 ( s , 3h ) ppm . compound 5 - 9 ( 1 . 6 g ) was dissolved into dichloromethane ( 65 ml ). to the mixture were successively added edci ( 1 . 7 g ), n , n - diisopropylethylamine ( 3 . 7 ml ), and phenyl isothiocyanate ( 0 . 6 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 52 . 1 %. esi - ms ( m / z , %) 467 . 26 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 18 ( s , 1h ), 9 . 08 ( s , 1h ), 8 . 36 ( s , 1h ), 7 . 85 ( d , j = 7 . 6 hz , 2h ), 7 . 67 ( d , j = 8 . 4 hz , 2h ), 7 . 32 ( t , j = 3 . 6 hz , 2h ), 6 . 93 - 7 . 00 ( m , 3h ), 5 . 04 ( t , j = 8 hz , 1h ), 3 . 36 ( s , 8h ), 2 . 79 ( s , 3h ), 2 . 46 ( s , 2h ), 2 . 05 ( s , 4h ), 1 . 70 ( s , 2h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and para - trifluoromethylphenyl isothiocyanate ( 1 . 4 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 55 . 4 %. esi - ms ( m / z , %) 509 . 25 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 46 ( s , 1h ), 9 . 09 ( s , 1h ), 8 . 44 ( s , 1h ), 8 . 03 ( d , j = 8 . 4 hz , 2h ), 7 . 67 ( m , j = 8 . 8 hz , 4h ), 6 . 90 ( d , j = 8 . 8 hz , 2h ), 4 . 90 ( m , 1h ), 3 . 10 ( s , 4h ), 2 . 59 ( s , 4h ), 2 . 32 ( s , 3h ), 1 . 68 ( d , j = 6 . 4 hz , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 3 - acrylylaminophenyl isothiocyanate ( 1 . 5 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 58 . 9 %. esi - ms ( m / z , %) 510 . 25 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 51 ( s , 1h ), 9 . 07 ( s , 1h ), 8 . 52 ( s , 1h ), 8 . 09 ( d , j = 8 . 4 hz , 2h ), 7 . 61 ( m , 4h ), 6 . 92 ( d , j = 8 . 8 hz , 2h ), 6 . 54 ( s , 1h ), 6 . 05 ( s , 1h ), 5 . 59 ( s , 1h ), 4 . 79 ( m , 1h ), 2 . 93 ( s , 4h ), 2 . 62 ( br , 4h ), 2 . 38 ( s , 3h ), 1 . 61 ( d , j = 6 . 4 hz , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 3 - pyridinyl isothiocyanate ( 1 . 0 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65 . 7 %. esi - ms ( m / z , %) 442 . 26 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 38 ( s , 1h ), 9 . 13 ( s , 1h ), 8 . 99 ( s , 1h ), 8 . 40 ( s , 1h ), 8 . 36 ( d , j = 8 . 4 hz , 1h ), 8 . 20 ( d , j = 4 . 4 hz , 1h ), 7 . 70 ( d , j = 8 . 8 hz , 2h ), 7 . 37 ( m , 1h ), 6 . 96 ( d , j = 8 . 8 hz , 2h ), 4 . 97 - 4 . 92 ( m , 1h ), 3 . 35 ( s , 6h ), 2 . 80 ( s , 3h ), 2 . 53 ( s , 2h ), 1 . 69 ( s , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and cyclohexyl isothiocyanate ( 1 . 0 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 67 . 8 %. esi - ms ( m / z , %) 447 . 28 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 10 . 89 ( s , 1h ), 9 . 26 ( s , 1h ), 8 . 23 ( s , 1h ), 7 . 62 ( d , j = 9 . 2 , 2h ), 6 . 95 ( d , j = 8 . 8 , 2h ), 4 . 72 ( m , 1h ), 4 . 03 ( m , j = 7 . 1 , 1h ), 3 . 69 ( s , 4h ), 3 . 13 - 3 . 09 ( m , 4h ), 2 . 80 ( s , 3h ), 1 . 98 ( d , j = 5 . 6 , 2h ), 1 . 76 ( d , j = 9 . 6 , 2h ), 1 . 57 ( d , j = 6 . 8 , 6h ), 1 . 37 - 1 . 26 ( m , 6h ) ppm . compound 5 - 10 ( 2 . 3 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 mlg ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 10 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 61 . 1 %. esi - ms ( m / z , %) 481 . 27 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 12 ( s , 1h ), 8 . 39 ( s , 1h ), 7 . 75 ( m , 2h ), 7 . 59 ( m , 2h ), 7 . 46 ( m , 2h ), 7 . 10 m , 3h ), 4 . 62 ( m , 1h ), 3 . 38 ( s , 6h ), 2 . 75 ( s , 3h ), 2 . 68 ( s , 3h ), 2 . 42 ( br , 2h ), 2 . 15 ( s , 4h ), 1 . 76 ( m , 4h ) ppm . compound 5 - 11 ( 2 . 2 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 mlg ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 11 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 63 . 5 %. esi - ms ( m / z , %) 471 . 28 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d6 ): δ 8 . 56 ( s , 1h ), 7 . 82 ( d , j = 8 . 0 hz , 2h ), 7 . 61 ( d , j = 8 . 4 hz , 2h ), 7 . 39 ( m , 2h ), 7 . 26 ( m , 2h ), 7 . 02 ( m , 2h ), 4 . 92 ( m , 1h ), 4 . 06 ( s , 3h ), 3 . 49 ( br , 4h ), 3 . 27 ( br , 4h ), 2 . 83 ( s , 3h ), 1 . 61 ( d , j = 6 . 8 hz , 6h ) ppm . compound 5 - 12 ( 2 . 2 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 mlg ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 12 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65 . 4 %. esi - ms ( m / z , %) 470 . 25 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d6 ): δ 8 . 61 ( s , 1h ), 7 . 83 ( d , j = 8 . 0 hz , 2h ), 7 . 69 ( m , 2h ), 7 . 37 ( m , 2h ), 7 . 25 ( m , 1h ), 7 . 04 ( m , 3h ), 4 . 71 ( m , 1h ), 3 . 49 ( br , 4h ), 3 . 27 ( br , 4h ), 2 . 86 ( s , 3h ), 1 . 65 ( d , j = 6 . 8 hz , 6h ) ppm . compound 5 - 13 ( 2 . 2 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 13 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 66 . 7 %. esi - ms ( m / z , %) 455 . 28 ( m − h ) − ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 08 ( s , 1h ), 9 . 01 ( s , 1h ), 7 . 84 ( d , j = 8 . 0 , 2h ), 7 . 71 ( d , j = 8 . 8 , 2h ), 7 . 32 ( t , j = 7 . 8 , 2h ), 6 . 96 ( t , j = 8 . 4 , 3h ), 4 . 91 ( m , j = 6 . 6 , 1h ), 3 . 67 ( s , 4h ), 3 . 27 ( s , 4h ), 2 . 80 ( s , 3h ), 2 . 49 ( s , 3h ), 1 . 66 ( d , j = 6 . 8 , 6h ) ppm . compound 5 - 9 ( 2 . 2 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 3 - chloro - 4 - fluorophenyl isothiocyanate ( 1 . 35 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 67 . 6 %. esi - ms ( m / z , %) 519 . 20 ( m − h ) − ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 41 ( s , 1h ), 9 . 10 ( s , 1h ), 8 . 42 ( s , 1h ), 8 . 23 ( m , j = 3 . 07 , 1h ), 7 . 80 ( m , 1h ), 7 . 66 ( d , j = 8 . 8 , 2h ), 7 . 39 ( t , j = 9 . 2 , 1h ), 6 . 94 ( d , j = 9 . 2 , 2h ), 5 . 01 ( m , 1h ), 3 . 41 ( s , 4h ), 2 . 81 ( s , 3h ), 2 . 54 ( s , 4h ), 2 . 46 ( s , 2h ), 2 . 05 ( s , 4h ), 1 . 70 ( d , j = 4 . 4 , 2h ) ppm . compound 5 - 9 ( 2 . 2 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 3 - pyridinyl isothiocyanate ( 1 . 0 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 64 . 3 %. esi - ms ( m / z ,%) 468 . 23 ( m − h ) − ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 40 ( s , 1h ), 9 . 11 ( s , 1h ), 8 . 97 ( d , j = 2 . 0 , 1h ), 8 . 40 ( s , 1h ), 8 . 35 ( d , j = 8 . 4 , 1h ), 8 . 20 ( d , j = 4 . 4 , 1h ), 7 . 66 ( d , j = 8 . 8 , 2h ), 7 . 36 ( m , j = 6 . 6 , 1h ), 6 . 93 ( d , j = 8 . 8 , 2h ), 5 . 02 ( m , 1h ), 3 . 20 ( s , 4h ), 2 . 73 ( s , 3h ), 2 . 47 ( s , 4h ), 2 . 06 ( s , 4h ), 1 . 71 ( s , 2h ), 1 . 23 ( s , 2h ) ppm . compound 5 - 14 ( 2 . 46 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 3 - pyridinyl isothiocyanate ( 1 . 0 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 14 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 70 . 3 %. esi - ms ( m / z , %) 511 . 23 ( m − h ) − ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 66 ( d , j = 11 . 2 , 2h ), 9 . 48 ( s , 1h ), 8 . 99 ( d , j = 2 . 0 , 1h ), 8 . 49 ( s , 1h ), 8 . 36 ( d , j = 7 . 6 , 1h ), 8 . 22 ( d , j = 4 . 0 , 1h ), 7 . 86 ( d , j = 8 . 8 , 2h ), 7 . 75 ( d , j = 8 . 4 , 2h ), 7 . 39 ( m , j = 4 . 3 , 1h ), 5 . 06 ( m , 1h ), 3 . 21 ( s , 4h ), 2 . 78 ( s , 3h ), 2 . 51 ( s , 4h ), 2 . 10 ( s , 4h ), 1 . 76 ( s , 2h ), 1 . 24 ( s , 2h ) ppm . compound 5 - 16 ( 1 . 87 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 16 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65 . 5 %. esi - ms ( m / z , %) 414 . 23 ( m − h ) + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ 10 . 05 ( s , 1h ), 9 . 29 ( s , 1h ), 9 . 02 ( s , 1h ), 8 . 40 ( s , 1h ), 8 . 02 ( s , 1h ), 7 . 84 ( d , j = 8 . 0 , 2h ), 7 . 57 ( d , j = 6 . 8 , 1h ), 7 . 34 ( t , j = 7 . 2 , 2h ), 7 . 20 ( t , j = 7 . 4 , 2h ), 7 . 00 ( t , j = 7 . 2 , 1h ), 6 . 49 ( m , j = 9 . 1 , 1h ), 6 . 26 ( d , j = 16 . 8 , 1h ), 5 . 74 ( d , j = 10 . 0 , 1h ), 4 . 90 ( m , 1h ), 1 . 68 ( d , j = 6 . 8 , 6h ) ppm . compound 5 - 17 ( 2 . 23 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 17 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 70 . 5 %. esi - ms ( m / z , %) 474 . 26 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 08 ( s , 1h ), 8 . 30 ( s , 1h ), 8 . 01 ( s , 1h ), 7 . 88 ( d , j = 8 . 0 hz , 2h ), 7 . 71 ( d , j = 9 . 2 hz , 2h ), 7 . 30 ( m , 2h ), 7 . 17 ( m , 3h ), 4 . 84 ( m , 1h ), 4 . 04 ( m , 2h ), 3 . 84 ( m , 4h ), 3 . 24 ( br , 4h ), 2 . 81 ( m , 2h ), 1 . 63 ( d , j = 6 . 8 hz , 6h ) ppm . compound 5 - 18 ( 2 . 39 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 18 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69 . 1 %. esi - ms ( m / z , %) 500 . 29 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 09 ( s , 1h ), 8 . 56 ( s , 1h ), 7 . 83 ( s , 1h ), 7 . 69 ( s , 1h ), 7 . 53 ( m , 2h ), 7 . 36 ( m , 4h ), 6 . 96 ( m , 3h ), 4 . 95 ( m , 1h ), 3 . 44 ( m , 2h ), 3 . 11 ( m , 2h ), 2 . 95 ( m , 8h ), 2 . 41 ( s , 3h ), 1 . 68 ( m , 2h ), 1 . 62 ( d , j = 6 . 8 hz , 6h ) ppm . compound 5 - 7 ( 2 . 05 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 2 - chloro - 5 - pyridinyl isothiocyanate ( 1 . 3 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 7 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69 . 8 %. esi - ms ( m / z , %) 476 . 29 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 65 ( s , 1h ), 9 . 21 ( s , 1h ), 8 . 85 ( s , 1h ), 8 . 44 ( d , j = 6 . 8 hz , 2h ), 7 . 68 ( d , j = 8 . 0 hz , 2h ), 7 . 49 ( d , j = 8 . 8 hz , 1h ), 6 . 96 ( d , j = 8 . 0 hz , 2h ), 4 . 96 ( m , 1h ), 3 . 71 ( m , 2h ), 3 . 47 ( m , 2h ), 3 . 15 ( br , 2h ), 3 . 03 ( m , 2h ), 2 . 82 ( s , 2h ), 1 . 67 ( d , j = 6 . 4 hz , 6h ) ppm . compound 5 - 19 ( 1 . 97 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 0 . 9 ml ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 19 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale yellow solid in a yield of 70 . 6 %. esi - ms ( m / z , %) 586 . 27 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ 9 . 01 ( d , j = 7 . 2 hz , 2h ), 8 . 37 ( s , 1h ), 8 . 08 ( d , j = 2 . 4 hz , 1h ), 7 . 67 ( m , 3h ), 7 . 46 ( m , 1h ), 7 . 31 ( m , 2h ), 7 . 20 ( m , 2h ), 6 . 91 ( d , j = 9 . 2 hz , 2h ), 5 . 21 ( s , 2h ), 4 . 83 ( m , 1h ), 3 . 74 ( m , 4h ), 3 . 03 ( m , 4h ), 1 . 67 ( d , j = 6 . 4 hz , 6h ) ppm . compound 5 - 9 ( 2 . 2 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 4 - bromophenyl isothiocyanate ( 1 . 65 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 66 . 7 %. esi - ms ( m / z , %) 548 . 18 ( m − h ) + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 22 ( s , 1h ), 9 . 09 ( s , 1h ), 8 . 39 ( s , 1h ), 7 . 83 ( d , j = 9 . 2 hz , 2h ), 7 . 65 ( d , j = 7 . 0 hz , 2h ), 7 . 50 ( d , j = 9 . 2 hz , 2h ), 6 . 93 ( d , j = 8 . 8 hz , 2h ), 4 . 95 ( m , 1h ), 3 . 27 - 3 . 02 ( m , 4h ), 2 . 75 ( m , 4h ), 2 . 45 ( s , 3h ), 2 . 05 ( m , 4h ), 1 . 68 ( m , 2h ), 1 . 23 ( m , 2h ). compound 5 - 9 ( 2 . 2 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 3 - nitrophenyl isothiocyanate ( 1 . 50 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65 . 4 %. esi - ms ( m / z , %) 514 . 23 ( m − h ) + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 75 ( s , 1h ), 9 . 23 ( s , 1h ), 8 . 87 ( s , 1h ), 8 . 45 ( s , 1h ), 8 . 32 ( d , j = 7 . 6 hz , 1h ), 7 . 84 ( d , j = 7 . 2 hz , 1h ), 7 . 65 ( m , 3h ), 6 . 95 ( d , j = 8 . 8 hz , 2h ), 5 . 04 ( m , 1h ), 3 . 72 ( m , 2h ), 3 . 49 ( m , 2h ), 3 . 16 ( m , 2h ), 2 . 99 ( m , 2h ), 2 . 83 ( s , 3h ), 2 . 45 ( m , 2h ), 2 . 06 ( m , 4h ), 1 . 71 ( m , 2h ). compound 5 - 9 ( 2 . 2 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and benzyl isothiocyanate ( 1 . 45 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 63 . 9 %. esi - ms ( m / z , %) 483 . 26 ( m − h ) + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ8 . 97 ( s , 1h ), 8 . 15 ( s , 1h ), 7 . 63 ( m , 3h ), 7 . 35 ( m , 4h ), 7 . 25 ( m , 1h ), 6 . 91 ( d , j = 9 . 2 hz , 2h ), 4 . 75 ( m , 1h ), 4 . 56 ( d , j = 8 . 0 hz , 2h ), 3 . 67 ( m , 2h ), 3 . 44 ( m , 2h ), 3 . 16 ( m , 2h ), 2 . 97 ( m , 2h ), 2 . 82 ( s , 3h ), 2 . 38 ( m , 2h ), 1 . 99 ( m , 4h ), 1 . 65 ( m , 2h ). compound 5 - 9 ( 2 . 2 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 3 - ethynylphenyl isothiocyanate ( 1 . 34 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69 . 5 %. esi - ms ( m / z , %) 493 . 28 ( m − h ) + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 26 ( s , 1h ), 9 . 13 ( s , 1h ), 8 . 43 ( s , 1h ), 8 . 09 ( s , 1h ), 7 . 84 ( d , j = 8 . 0 hz , 1h ), 7 . 67 ( d , j = 8 . 4 hz , 2h ), 7 . 34 ( m , 1h ), 7 . 09 ( d , j = 7 . 2 hz , 1h ), 6 . 94 ( d , j = 10 . 8 hz , 2h ), 5 . 00 ( m , 1h ), 4 . 20 ( s , 1h ), 3 . 67 ( m , 2h ), 3 . 47 ( m , 2h ), 3 . 17 ( m , 2h ), 3 . 00 ( m , 2h ), 2 . 78 ( s , 3h ), 2 . 46 ( m , 2h ), 2 . 05 ( m , 4h ), 1 . 71 ( m , 2h ). compound 5 - 9 ( 2 . 2 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 2 - fluoro - 4 - bromophenyl isothiocyanate ( 1 . 60 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69 . 7 %. esi - ms ( m / z , %) 565 . 20 ( m − h ) + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 06 ( s , 1h ), 8 . 93 ( s , 1h ), 8 . 35 ( s , 1h ), 7 . 85 ( m , 1h ), 7 . 61 ( m , 3h ), 7 . 40 ( d , j = 8 . 4 hz , 1h ), 8 . 67 ( d , j = 9 . 2 hz , 2h ), 4 . 88 ( m , 1h ), 3 . 10 ( m , 4h ), 2 . 62 ( m , 4h ), 2 . 43 ( m , 2h ), 2 . 34 ( s , 3h ), 2 . 03 ( m , 4h ), 1 . 68 ( m , 2h ). compound 5 - 20 ( 2 . 2 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and phenyl isothiocyanate ( 1 . 0 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69 . 9 %. esi - ms ( m / z , %) 470 . 27 ( m − h ) + . 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 57 ( s , 1h ), 9 . 16 ( s , 1h ), 8 . 45 ( s , 1h ), 7 . 91 ( s , 1h ), 7 . 86 ( d , j = 8 . 0 hz , 2h ), 7 . 76 ( s , 1h ), 7 . 47 ( s , 1h ), 7 . 38 ( m , 2h ), 7 . 22 ( s , 1h ), 7 . 03 ( m , 1h ), 5 . 04 ( m , 1h ), 4 . 10 ( m , 2h ), 3 . 70 ( m , 4h ), 3 . 15 ( m , 2h ), 2 . 37 ( m , 2h ), 2 . 05 ( m , 4h ), 1 . 75 ( m , 2h ), 1 . 29 ( m , 2h ). compound 5 - 9 ( 2 . 2 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 4 . 9 ml ), and 3 - fluorophenyl isothiocyanate ( 1 . 0 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 67 . 4 %. esi - ms ( m / z , %) 487 . 25 ( m − h ) + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 42 ( s , 1h ), 9 . 13 ( s , 1h ), 8 . 42 ( s , 1h ), 7 . 92 ( d , j = 12 . 0 hz , 1h ), 7 . 67 ( d , j = 9 . 2 hz , 2h ), 7 . 59 ( d , j = 8 . 0 hz , 1h ), 7 . 35 ( m , 1h ), 6 . 94 ( d , j = 8 . 8 hz , 2h ), 6 . 79 ( m , 1h ), 5 . 02 ( m , 1h ), 3 . 68 ( m , 2h ), 3 . 44 ( m , 2h ), 3 . 18 ( m , 2h ), 3 . 01 ( m , 2h ), 2 . 81 ( s , 3h ), 2 . 44 ( m , 2h ), 2 . 05 ( m , 4h ), 1 . 70 ( m , 2h ). compound 5 - 21 ( 1 . 53 g ) was dissolved into dichloromethane ( 35 ml ). to the mixture were successively added edci ( 1 . 54 g ), n , n - diisopropylethylamine ( 3 . 31 ml ), and phenyl isothiocyanate ( 0 . 56 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 21 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 69 . 4 %. esi - ms ( m / z , %) 483 . 25 ( m − h ) + . 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 04 ( s , 1h ), 8 . 99 ( s , 1h ), 8 . 34 ( s , 1h ), 7 . 80 ( d , j = 8 . 4 hz , 2h ), 7 . 67 ( d , j = 8 . 8 hz , 2h ), 7 . 33 ( m , 2h ), 6 . 98 ( m , 1h ), 6 . 87 ( d , j = 8 . 4 hz , 2h ), 4 . 74 ( m , 1h ), 3 . 05 ( m , 4h ), 2 . 61 ( m , 2h ), 5 . 47 ( m , 4h ), 2 . 23 ( s , 3h ), 1 . 91 ( m , 2h ), 1 . 81 ( m , 3h ), 1 . 44 ( m , 2h ), 1 . 34 ( m , 1h ). compound 5 - 9 ( 2 . 1 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine - 2 . 1 ml ), and 3 - hydroxyphenyl isothiocyanate ( 1 . 05 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 70 . 4 %. esi - ms ( m / z , %) 485 . 25 ( m − h ) + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 36 ( s , 1h ), 9 . 07 ( s , 1h ), 8 . 93 ( s , 1h ), 8 . 35 ( s , 1h ), 7 . 67 ( d , j = 9 . 2 hz , 2h ), 7 . 38 ( s , 1h ), 7 . 16 ( d , j = 9 . 2 hz , 1h ), 7 . 08 ( m , 1h ), 6 . 93 ( d , j = 9 . 2 hz , 2h ), 6 . 39 ( s , 1h ), 4 . 96 ( m , 1h ), 3 . 43 ( m , 2h ), 3 . 34 ( m , 2h ), 3 . 16 ( m , 4h ), 2 . 75 ( s , 1h ), 2 . 46 ( m , 2h ), 2 . 04 ( m , 4h ), 1 . 69 ( m , 2h ). compound 5 - 9 ( 2 . 2 g ) was dissolved into dichloromethane ( 70 ml ). to the mixture were successively added edci ( 2 . 7 g ), n , n - diisopropylethylamine ( 2 . 5 ml ), and 3 - chlorophenyl isothiocyanate ( 1 . 42 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 71 . 7 %. esi - ms ( m / z , %) 503 . 25 ( m − h ) + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 38 ( s , 1h ), 9 . 13 ( s , 1h ), 8 . 44 ( s , 1h ), 8 . 11 ( s , 1h ), 7 . 75 ( d , j = 8 . 0 hz , 1h ), 7 . 65 ( d , j = 8 . 4 hz , 2h ), 7 . 35 ( m , 1h ), 7 . 02 ( m , 1h ), 6 . 94 ( d , j = 8 . 8 hz , 2h ), 5 . 01 ( m , 1h ), 3 . 43 ( m , 4h ), 3 . 10 ( m , 4h ), 2 . 82 ( s , 3h ), 2 . 45 ( m , 2h ), 2 . 05 ( m , 4h ), 1 . 70 ( m , 2h ) ppm . compound 5 - 9 ( 2 . 1 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine 2 . 1 ml ), and 3 - methylphenyl isothiocyanate ( 1 . 0 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 72 . 7 %. esi - ms ( m / z , %) 483 . 25 ( m − h ) + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 08 ( s , 1h ), 9 . 02 ( s , 1h ), 8 . 37 ( s , 1h ), 7 . 68 - 7 . 62 ( m , 4h ), 7 . 22 ( m , 1h ), 6 . 93 ( d , j = 8 . 8 hz , 2h ), 6 . 80 ( d , j = 7 . 6 hz , 1h ), 4 . 99 ( m , 1h ), 3 . 67 ( m , 2h ), 3 . 44 ( m , 2h ), 3 . 03 ( m , 4h ), 2 . 81 ( s , 3h ), 2 . 45 ( m , 2h ), 2 . 31 ( s , 3h ), 2 . 04 ( m , 4h ), 1 . 69 ( m , 2h ) ppm . compound 5 - 9 ( 2 . 55 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 2 . 67 g ), n , n - diisopropylethylamine 2 . 7 ml ), and 3 , 5 - dichlorophenyl isothiocyanate ( 1 . 7 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 73 . 7 %. esi - ms ( m / z , %) 537 . 25 ( m − h ) + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 40 ( s , 1h ), 9 . 08 ( s , 1h ), 8 . 48 ( s , 1h ), 7 . 97 ( s , 1h ), 7 . 60 ( d , j = 8 . 8 hz , 2h ), 7 . 21 ( m , 2h ), 6 . 99 ( m , 2h ), 4 . 90 ( m , 1h ), 3 . 12 ( m , 2h ), 3 . 04 ( m , 2h ), 2 . 54 ( m , 4h ), 2 . 21 ( m , 4h ), 2 . 04 ( s , 3h ), 1 . 67 ( m , 2h ), 1 . 19 ( m , 2h ) ppm . compound 5 - 9 ( 2 . 7 g ) was dissolved into dichloromethane ( 100 ml ). to the mixture were successively added edci ( 2 . 8 g ), n , n - diisopropylethylamine ( 3 ml ), and 2 , 5 - difluorophenyl isothiocyanate ( 1 . 5 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 70 . 6 %. esi - ms ( m / z , %) 505 . 25 ( m − h ) + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 16 ( s , 1h ), 9 . 06 ( s , 1h ), 8 . 43 ( s , 1h ), 7 . 91 ( m , 1h ), 7 . 56 ( m , 2h ), 7 . 32 ( m , 1h ), 6 . 91 ( m , 3h ), 4 . 92 ( m , 1h ), 3 . 45 ( m , 4h ), 3 . 23 - 3 . 03 ( m , 4h ), 2 . 80 ( s , 3h ), 2 . 42 ( m , 2h ), 2 . 03 ( m , 4h ), 1 . 68 ( m , 2h ) ppm . compound 5 - 22 ( 3 . 2 g ) was dissolved into dichloromethane ( 90 ml ). to the mixture were successively added edci ( 3 . 6 g ), n , n - diisopropylethylamine 3 . 3 ml ), and phenyl isothiocyanate ( 1 . 52 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 75 . 3 %. esi - ms ( m / z , %) 443 . 25 ( m − h ) − . 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 20 ( s , 1h ), 9 . 06 ( s , 1h ), 8 . 36 ( s , 1h ), 7 . 86 ( d , j = 9 . 6 hz , 2h ), 7 . 65 ( d , j = 8 . 0 hz , 2h ), 7 . 34 ( m , 2h ), 6 . 97 ( m , 1h ), 6 . 85 ( d , j = 8 . 0 hz , 2h ), 5 . 05 ( m , 1h ), 4 . 04 ( m , 2h ), 3 . 64 ( m , 2h ), 3 . 31 ( s , 3h ), 2 . 43 ( m , 2h ), 2 . 03 ( m , 4h ), 1 . 68 ( m , 2h ) ppm . compound 5 - 9 ( 2 . 1 g ) was dissolved into dichloromethane ( 60 ml ). to the mixture were successively added edci ( 2 . 15 g ), n , n - diisopropylethylamine ( 2 ml ), and 2 , 4 , 5 - trichlorophenyl isothiocyanate ( 1 . 6 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . after cooling the mixture , a solid was separated out and purified by recrystallization to obtain a pale yellow solid in a yield of 74 . 3 %. esi - ms ( m / z , %) 571 . 25 ( m − h ) + ; 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 09 ( s , 1h ), 9 . 01 ( s , 1h ), 8 . 27 ( s , 1h ), 7 . 64 ( m , 2h ), 7 . 12 ( m , 1h ), 6 . 89 ( d , j = 8 . 4 hz , 2h ), 6 . 78 ( d , j = 7 . 2 hz , 1h ), 4 . 93 ( m , 1h ), 3 . 64 ( m , 2h ), 3 . 41 ( m , 2h ), 3 . 13 ( m , 4h ), 2 . 75 ( s , 3h ), 2 . 43 ( m , 2h ), 2 . 14 ( m , 4h ), 1 . 65 ( m , 2h ) ppm . compound 5 - 23 ( 4 . 6 g ) was dissolved into dichloromethane ( 100 ml ). to the mixture were successively added edci ( 1 . 67 g ), n , n - diisopropylethylamine 1 . 2 ml ), and phenyl isothiocyanate ( 0 . 79 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 25 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 65 . 1 %. esi - ms ( m / z , %) 497 . 25 ( m − h ) + . 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 25 ( s , 1h ), 9 . 06 ( s , 1h ), 8 . 40 ( s , 1h ), 7 . 82 ( d , j = 8 . 0 hz , 2h ), 7 . 71 ( d , j = 8 . 4 hz , 2h ), 7 . 34 ( m , 2h ), 7 . 15 ( d , j = 8 . 4 hz , 2h ), 6 . 99 ( m , 1h ), 4 . 97 ( m , 1h ), 3 . 38 ( s , 2h ), 2 . 47 - 2 . 29 ( m , 12h ), 2 . 05 ( m , 2h ), 1 . 71 ( m , 2h ), 0 . 97 ( m , 3h ) ppm . compound 5 - 25 ( 4 . 6 g ) was dissolved into dichloromethane ( 100 ml ). to the mixture were successively added edci ( 1 . 74 g ), n , n - diisopropylethylamine 1 . 2 ml ), and phenyl isothiocyanate ( 0 . 82 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 25 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 71 . 8 %. esi - ms ( m / z , %) 483 . 25 ( m − h ) + . 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 25 ( s , 1h ), 9 . 05 ( s , 1h ), 8 . 39 ( s , 1h ), 7 . 82 ( d , j = 8 . 0 hz , 2h ), 7 . 70 ( d , j = 8 . 0 hz , 2h ), 7 . 33 ( m , 2h ), 7 . 15 ( d , j = 8 . 0 hz , 2h ), 6 . 99 ( m , 1h ), 4 . 97 ( m , 2h ), 3 . 38 ( m , 4h ), 2 . 50 ( m , 4h ), 2 . 33 ( m , 4h ), 2 . 14 ( s , 3h ), 2 . 05 ( m , 4h ), 1 . 71 ( m , 2h ) ppm . compound 5 - 9 ( 1 . 3 g ) was dissolved into dichloromethane ( 60 ml ). to the mixture were successively added edci ( 0 . 8 g ), n , n - diisopropylethylamine ( 2 ml ), and 2 , 5 - dichlorophenyl isothiocyanate ( 0 . 72 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 16 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . purification was conducted by a column chromatography to obtain a pale yellow solid in a yield of 64 . 3 %. esi - ms ( m / z , %) 537 . 23 ( m − h ) + . 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 02 ( s , 1h ), 8 . 62 ( s , 1h ), 8 . 37 ( s , 1h ), 7 . 91 ( s , 1h ), 7 . 59 ( d , j = 8 . 4 hz , 2h ), 7 . 49 ( d , j = 7 . 6 hz , 1h ), 7 . 10 ( m , 1h ), 6 . 86 ( d , j = 9 . 2 hz , 2h ), 4 . 91 ( m , 1h ), 3 . 04 ( m , 4h ), 2 . 45 ( m , 4h ), 2 . 22 ( s , 3h ), 2 . 00 ( m , 4h ), 1 . 67 ( m , 2h ) ppm . compound 5 - 9 ( 2 . 2 g ) was dissolved into dichloromethane ( 40 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 5 ml ), and 2 , 4 - dichlorophenyl isothiocyanate ( 1 . 5 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 12 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . purification was conducted by a column chromatography to obtain a pale yellow solid in a yield of 67 . 4 %. esi - ms ( m / z , %) 537 . 22 ( m − h ) + . 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 01 ( s , 1h ), 8 . 70 ( s , 1h ), 8 . 26 ( s , 1h ), 7 . 59 ( d , j = 8 . 4 hz , 4h ), 7 . 39 ( s , 1h ), 6 . 86 ( d , j = 8 . 8 hz , 2h ), 4 . 90 ( m , 1h ), 3 . 04 ( m , 4h ), 2 . 45 ( m , 6h ), 2 . 22 ( s , 3h ), 2 . 00 ( m , 4h ), 1 . 67 ( m , 2h ) ppm . compound 5 - 9 ( 2 . 2 g ) was dissolved into dichloromethane ( 40 ml ). to the mixture were successively added edci ( 2 . 3 g ), n , n - diisopropylethylamine ( 5 ml ), and 3 - bromophenyl isothiocyanate ( 1 . 54 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 12 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 9 . purification was conducted by a column chromatography to obtain a pale yellow solid in a yield of 69 . 5 %. esi - ms ( m / z , %) 547 . 12 ( m − h ) + . 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 34 ( s , 1h ), 9 . 13 ( s , 1h ), 8 . 44 ( s , 1h ), 8 . 22 ( s , 1h ), 7 . 83 ( d , j = 8 . 4 hz , 1h ), 7 . 67 ( d , j = 8 . 8 hz , 2h ), 7 . 29 ( m , 1h ), 7 . 15 ( d , j = 8 . 0 hz , 1h ), 6 . 94 ( d , j = 9 . 2 hz , 2h ), 5 . 01 ( m , 1h ), 3 . 65 ( m , 4h ), 3 . 28 ( m , 4h ), 2 . 81 ( s , 3h ), 2 . 45 ( m , 2h ), 2 . 05 ( m , 4h ), 1 . 70 ( m , 2h ) ppm . compound 5 - 23 ( 2 . 0 g ) was dissolved into dichloromethane ( 25 ml ). to the mixture were successively added edci ( 1 . 92 g ), n , n - diisopropylethylamine ( 2 . 25 ml ), and phenyl isothiocyanate ( 0 . 82 g ). the mixture was stirred at room temperature for half an hour , and refluxed for 10 hours . tlc detection indicated the completion of the reaction of the starting material 5 - 23 . after cooling the mixture , purification was conducted by a column chromatography to obtain a pale red solid in a yield of 66 . 2 %. esi - ms ( m / z , %) 497 . 26 ( m − h ) + . 1 h nmr ( 400 mhz , dmso - d 6 ): δ9 . 04 ( s , 1h ), 8 . 59 ( s , 1h ), 8 . 30 ( s , 1h ), 7 . 81 ( d , j = 8 . 4 hz , 2h ), 7 . 65 ( d , j = 8 . 8 hz , 2h ), 7 . 31 ( m , 2h ), 6 . 88 ( m , 1h ), 6 . 75 ( d , j = 8 . 4 hz , 2h ), 3 . 78 ( m , 2h ), 3 . 05 ( m , 4h ), 1 . 82 - 1 . 54 ( m , 7h ), 1 . 36 - 1 . 18 ( m , 4h ), 1 . 12 - 1 . 00 ( m , 2h ). assay 1 : the test of the arylamino purine derivatives for the kinase inhibitory activity the object of this assay was to test the inventive compounds for the kinase inhibitory activity in vitro . in this assay , an isotopic labeling method was used to label the γ phosphate group on atp . egfr ( including wild type , l858r mutant type and l858r / t790m double mutant type ), vegfr2 , alk , btk , c - kit , c - src , met , pdgfrα and flt3 kinases were tested in vitro for the activity inhibition . staurosporine was used as a reference molecule ( or referred to as a positive control ). the kinase inhibitory activities of the tested compounds were expressed in the ic 50 value ( half inhibition concentration ) or the kinase activity inhibitory rate by the tested compounds at 10 μm . the ic 50 value can be obtained by the calculation of the inhibitory rates at a series of different concentrations of the tested compounds . 0 . 1 mg / ml glutamic acid / tyrosine ( 4 : 1 ) polymerized polypeptide ( poly ( glu , tyr ) 4 : 1 ) ( the substrate for wild type and l858r mono mutant type egfrs , c - kit and pdgfrα ); 250 μm polypeptide ggmediyfefmggkkk ( the substrate for l858r / t790m double mutant type egfr ); 250 μm polypeptide kvekigegty gvvyk ( the substrate for btk and c - src ); 10 mm a solution of magnesium acetate and γ - 33 p - atp ; egfrs ( including wild type , l858r mono mutant type and l858r / t790m double mutant type egfrs ), vegfr2 , alk , btk , c - kit , c - src , met , pdgfrα , flt3 kinase , and the tested compounds . to a reaction tube were successively added the buffer solution ( 8 mm mops , ph 7 . 0 , 0 . 2 mm edta , 10 mm mncl 2 ), the kinase to be tested ( 5 - 10 mu ) ( egfr / alk / btk / c - kit / c - src / met / pdgfrα / vegfr2 ), the substrate for the kinase to be tested ( a reference material ), 10 mm of the solution of magnesium acetate and γ - 33 p - atp , and different concentrations of the tested compounds . the reaction was started by adding mgatp ( the final concentration of atp is the km value of the corresponding kinase , i . e ., 10 μm for egfrwild type , 200 μm for egfr l858r , 45 μm for egfr l858r / t790m , 200 μm for alk , 200 μm for btk , 200 μm for c - kit , 90 μm for vegfr2 , 200 μm for c - src , 45 μm for met , 120 μm for pdgfrα , and 200 μm for flt3 ), and incubated at room temperature for 40 minutes . the reaction was terminated with 54 of the 3 % phosphate buffer solution . 10 μl of the reaction liquid was titrated on the filtermat a membrane . the membrane was washed with 75 mm of the phosphate solution thrice ( 5 minutes each time ), and then with methanol once , and finally dried . the membrane was subjected to a scintillation counting . the value of the scintillation counting reflected the phosphorylation level of the substrate and therefore could characterize the inhibition of the kinase activity . through the above procedures , the inhibitory activities of the present compounds were tested for the kinases egfrs ( comprising wild type , l858r mutant type and l858r / t790m double mutant type ), vegfr2 , alk , btk , c - kit , c - src , met , pdgfrα , and flt3 . the kinase inhibitory activities ( ic 50 values ) of the tested compounds for egfrs ( comprising wild type , l858r mutant type and l858r / t790m double mutant type ) and vegfr2 are shown in table 1 . the activity inhibition ratio (%) of the tested compounds at 10 μm for the kinases alk , btk , c - kit , c - src , met , pdgfrα , and flt3 are shown in table 2 . the results indicated that the tested compounds had strong inhibitory activities on the wild type , l858r mutant type and l858r / t790m double mutant type egfrs , and some of the tested compounds also had good inhibitory activities on vegfr2 , alk , btk , c - kit , c - src , met , pdgfrα , flt3 kinases . the object of this assay was to test the inventive compounds for the inhibitory activity of in - vitro tumor cell proliferation . the mtt ( tetreamethyl - azo - zole - salt ) colorimetric method was used in this assay . rpmi - 1640 , fetal bovine serum , pancreatin and the like were purchased from gibco brl company ( invitrogen corporation , usa ). the imdm culture medium was purchased from atcc ( american type culture collection ). tetreamethyl - azo - zole - salt ( mtt ) and dimethylsulfoxide ( dmso ) were the products available from sigma company ( usa ). the arylamino purine derivatives were synthesized by the present inventors . in this in - vitro assay , 100 % dmso was formulated into a 10 mm stocking solution and preserved in a freezer at − 20 ° c . and in dark place for use . the stocking solution was diluted with a complete culture solution to a desired concentration immediately before use . human non - small cell lung carcinoma cell strains hcc827 , pc - 9 , h1975 ( egfr l858r / t790m mutation ) and h292 ( egfr wt ), and other tumor type cell strains , including human acute myelogenous leukemia cell strain mv4 - 11 , human chronic granulocytic leukemia cell strain k562 , human squamous cell carcinoma cell strain a431 , human breast carcinoma cell strains mda - mb - 468 and bt 474 , human colon cancer cell strains sw480 , hct116 and sw620 , human liver cancer cell strain hep g2 , human gastric cancer cell strain mk - 45 , and human malignant melanoma cell strain a375 used in this assay were all purchased from atcc company , usa and kept in the laboratory . all of the above - mentioned non - small cell lung carcinoma cell strains and the breast carcinoma cell strain bt 474 were cultured with a rpmi - 1640 complete culture medium containing 10 % fetal bovine serum , 100 u / ml penicillin and 100 μg / ml streptomycin under 5 % co2 and at 37 ° c . the other cell strains were cultured with a dmem complete culture medium containing 10 % fetal bovine serum ( having a mv4 - 11 cell content of 20 %), 100 u / ml penicillin and 100 μg / ml streptomycin under 5 % co2 and 37 ° c . a cell suspension having a cell concentration of 1 - 2 × 10 4 cells / ml was treated with a complete cell culture solution to adjust the cell concentration , wherein the cell concentrations for hcc827 and mv4 - 11 were adjusted to 6 × 10 4 cells / ml and 1 × 10 5 cells / ml respectively . the cell suspension was inoculated in a 96 - well plate with 200 μl cell suspension / well and cultured overnight . next day , the supernatant was drawn off and discarded . then , the cells were treated with the tested compounds in a gradient concentration respectively . in the meanwhile , a negative control group free of the drug substance and an isovolumetric solvent control group ( having a dmso concentration of 1 %) were used . the triplicate wells were used for each of dose groups . the culturing was conducted at 37 ° c . under 5 % co2 . after 72 hours , 200 mtt agent having a concentration of 5 mg / ml was added to each of wells . the culturing was further conducted for 2 - 4 hours . the supernatant was discarded . then 1504 dmso was added to each of wells . the contents in the well were mixed homogenously by oscillation for 15 minutes . the absorbance ( a ) value was measured with a microplate reader at λ = 570 nm ( the a value is in the direct proportion to the number of living cells ) and averaged . the relative cell proliferation inhibitory rate is ( a 570 control - group − a 570 dose - group )/ a 570 control - group × 100 %. the assay was repeated for at least three times . the data was expressed as number average . the statistical data were analyzed using t - test . p & lt ; 0 . 05 was considered significant . the cell proliferation inhibition of the following compounds was expressed as ic50 or inhibitory rate . according to the above - mentioned procedure , human non - small cell lung carcinoma cell strains hcc827 , pc - 9 ( egfr dele746 - a750 deletion mutation ), h1975 ( egfr l858r / t790m mutation ) and h292 ( egfr wt ), and other tumor type cell strains , including human acute myelogenous leukemia cell strain mv4 - 11 , human chronic granulocytic leukemia cell strain k562 , human squamous cell carcinoma cell strain a431 , human breast carcinoma cell strains mda - mb - 468 and bt 474 , human colon cancer cell strains sw480 , hct116 and sw620 , human liver cancer cell strain hep g2 , human gastric cancer cell strain mk - 45 , and human malignant melanoma cell strain a375 were subjected to the proliferation inhibition activity test . the proliferation inhibitory activities ( ic 50 ) of the tested compounds for human non - small cell lung carcinoma cell strains hcc827 , pc - 9 and h1975 are shown in the table 3 . the proliferation inhibitory activities ( ic 50 ) of the tested compounds for human tumor cell strains mv4 - 11 , k562 , a431 , mda - mb - 468 , bt474 , sw480 , hct116 , hepg2 , sw620 , mk - 45 , h292 and a375 are shown in the tables 4 and 5 . the results indicated that the tested compounds had strong inhibitory activities on the cell strains hcc827 and pc - 9 which were sensitive to gefitinib ; some of the tested compounds also had a good inhibitory activity on the cell strain h1975 which was resistant to gefitinib ; and in addition , some of the tested compounds also had good inhibitory activities on the other tumor cell strains including human mv4 - 11 , k562 , a431 , mda - mb - 468 , bt474 , sw480 , hct116 , hepg2 , sw620 , mk - 45 , h292 , a375 and the like . the object of this assay was to determine the in - vivo anti - tumor effect of the present compound . in this assay , a nude mouse subcutaneously transplanted non - small cell lung carcinoma model was used to test the present compound 8 - 10 for the in - vivo anti - tumor activity . the used cell strain was human non - small cell lung carcinoma cell strain hcc827 . rpmi - 1640 , fetal bovine serum , pancreatin and the like were purchased from gibco brl company ( invitrogen corporation , usa ); rpmi 1640 culture medium was purchased from atcc ( american type culture collection ); human non - small cell lung carcinoma cell strain hcc827 was purchased from atcc company , usa ; and balb / c nude mice were purchased from institute of zoology , chinese academy of sciences . balb / c nude mice , aged 6 - 8 weeks , were inoculated with hcc827 cell subcutaneously at the posterior segment of rib in a concentration of about 5 × 10 6 cells / 0 . 1 ml per mouse . upon the growth of the tumor up to 200 - 300 mm 3 ( about 20 days ), mice were grouped ( n = 6 ) and administrated intragastrically . ( each of drug groups was dissolved in 5 % dmso + 1 % tween80 + 94 % water ). observation indices : the mice were measured every three days for the weight , and the length and width of tumor , and the tumor volume was calculated as length × width 2 × 0 . 52 . the mice were observed for the reactions such as diarrhea , convulsion , exanthema , and substantial weight reduction . the measured tumor growth curves for each of the groups are shown in fig1 . the photograph of tumors obtained by dissection after the assay is shown in fig2 . the results indicated that the tested compound 8 - 10 had a substantial in - vivo growth inhibition for the egfr dele746 - a750 mutated human non - small cell lung carcinoma cell strain hcc827 . upon administrating in 2 mg / kg q . d . or higher , the tumor growth could be substantially inhibited , or even the tumor could be eliminated . in the course of administration , the nude mice did not show the untoward reactions such as weight reduction , exanthema , and diarrhea , which indicated that under the test doses , the tested compound 8 - 10 had a low toxicity in the dose range of administration . the object of this assay was to determine the in - vivo anti - tumor effect of the present compound . in this assay , a nod - scid mouse subcutaneously transplanted human leukemic solid tumor model was used to test the present compound 8 - 29 for the in - vivo anti - tumor activity . the used cell strain was human acute myelogenous leukemia cell strain mv4 - 11 . imdm , fetal bovine serum , pancreatin and the like were purchased from gibco brl company ( invitrogen corporation , usa ); imdm culture medium was purchased from atcc ( american type culture collection ), human leukemia cell strain mv4 - 11 was purchased from atcc company , usa ; and the nod - scid mice were purchased from laboratory animal center , peking union medical college , china . nod - scid mice , aged 6 - 8 weeks , were inoculated with mv4 - 11 cell subcutaneously at the posterior segment of rib in a concentration of about 1 × 10 7 cells / 0 . 1 ml per mouse . upon the growth of the tumor up to 400 - 500 mm 3 ( about 20 days ), mice were grouped ( n = 6 ) and administrated intragastrically . ( each of drug groups was dissolved in 5 % dmso + 25 % peg400 + 70 % water ) observation indices : the mice were measured every three days for the weight , and the length and width of tumor , and the tumor volume was calculated as length × width 2 × 0 . 52 . the mice were observed for the reactions such as diarrhea , convulsion , exanthema , and substantial weight reduction . the measured tumor growth curves for each of the groups are shown in fig3 . the results indicated that the tested compound 8 - 29 had a substantial in - vivo growth inhibition for the flt3 - itd mutated human acute myelogenous leukemia cell strain mv4 - 11 . upon administrating in 5 mg / kg q . d . or higher , the tumor growth could be substantially inhibited , or even the tumor could be eliminated . in the course of administration , the mice did not show the untoward reactions such as weight reduction , exanthema , and diarrhea , which indicated that under the test doses , the tested compound 8 - 29 had a low toxicity in the dose range of administration .
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the following detailed description is presented to enable any person skilled in the art to make and use the invention . for purposes of explanation , specific details are set forth to provide a thorough understanding of the present invention . however , it will be apparent to one skilled in the art that these specific details are not required to practice the invention . descriptions of specific applications are provided only as representative examples . various modifications to the preferred embodiments will be readily apparent to one skilled in the art , and the general principles defined herein may be applied to other embodiments and applications without departing from the scope of the invention . the present invention is not intended to be limited to the embodiments shown , but is to be accorded the widest possible scope consistent with the principles and features disclosed herein . the electric roof access hatch unlocking and opening system consists of a locking mechanism , an opening mechanism , and a control panel , each more fully described below . through its electronic circuitry , the control panel controls the actions of the locking mechanism and the opening mechanism . the locking mechanism is a device , as depicted in fig4 , fig9 , and fig1 , which engages a lock on the roof access hatch . it is controlled by the control panel 1 ( as depicted in fig1 and fig2 ) and may either lock or unlock upon application of a current . in the present embodiment , when current is applied , solenoid 4 retracts , pulling latch 19 into a recessed state . the locking system is preferably solenoid driven , as depicted in fig9 . however , other electrically - operated locking mechanisms may be used , including , but not limited to , magnetic locks , motor - operated locks , and electric strikes . the locking mechanism optionally includes a manual key override 3 , as depicted in fig9 a , that allows the locking system to be unlocked in the event of emergency if the control panel circuitry or opening mechanism cannot function properly due to extended power outages or damage to any component . lever 24 is operatively coupled to the manual key override . inserting and turning a key in the manual key override 3 causes lever 24 to push against a protrusion 25 on the latch 19 , forcing the latch 19 into a recessed state , allowing access hatch 8 to be opened . opening mechanism 5 is depicted in fig3 and in fig5 . in the preferred embodiment , the opening mechanism is driven by a linear thrust actuator 6 . linear thrust actuator 6 is coupled to access hatch 8 at a pivot point 7 on angled access hatch mounting bracket 27 . angled access hatch mounting bracket 27 is configured such that pivot point 7 is located at a distance from the hinge side of the roof access hatch . when the control panel circuitry applies power to opening mechanism 5 , the thrust rod of linear thrust actuator 6 extends . as the linear thrust actuator 6 extends , it applies a force to pivot point 7 . the force of the linear thrust actuator 6 at pivot point 7 causes access hatch 8 to rotate about the axis of the roof access hatch hinge , causing the hatch to lift open from the side opposite the hinges . other mechanisms for opening the roof access hatch may be used and include electric motors or pneumatic cylinders . the opening mechanism 5 may be adjustable to accommodate different angles and mounting positions and varying thicknesses of insulation . as can be seen from fig1 , the roof - mounted mounting bracket 12 may be coupled to linear thrust actuator 6 by use of adjustable bracket 14 . in the preferred embodiment , the bracket consists of a bar with equally spaced holes along its length . the linear thrust actuator 6 is affixed to the upper end of the adjustable bracket using bracket pin 13 . the lower end of adjustable bracket 14 is connected to the roof - mounted mounting bracket 12 . the roof - mounted mounting bracket 12 is further securely attached to the underside of the roof decking 16 . to accommodate for varying thicknesses of installations or lowered mounting positions , bracket pin 13 can be inserted into any of the equally spaced holes situated along the length of the bar on the adjustable bracket . bracket pin 13 can also be removed to disengage the roof access hatch 8 from the opening mechanism 5 . circuitry in the control panel 1 activates the locking mechanism 2 and the opening mechanism 5 . although various methods of providing power to the locking and opening mechanisms are known and may be used , a simple circuit is disclosed herein . an example of such a circuit can be seen in fig6 , fig7 , and fig8 . control panel 1 can be placed into different modes of operation as the operator desires . in the open mode , the control panel circuitry directs the roof access hatch to open . in the closed mode , the control panel circuitry directs the roof access hatch to close . the off position is the default position to be used when the roof access hatch is not being utilized . in the preferred embodiment , the various modes are selected by use of a key switch 26 . as seen in fig1 , status lights 10 on the front of the control panel 1 , may indicate the current mode of operation of the roof access hatch 8 . when control panel 1 is placed in open mode , power is applied to open relay 28 that sends power to the opening mechanism 5 and to a lock relay 29 for limited duration sufficient to unlock the locking mechanism 2 . the lock relay 29 transmits power to the locking mechanism 2 , causing it to unlock . in the current embodiment , this is a delay - on - break relay . this lock relay 29 keeps the latch 19 recessed until the hatch access 8 begins to open . open relay 28 is set to output power to the linear thrust actuator 6 at a time after the lock relay 29 has unlocked the roof access hatch 8 , but before the flow of current to the locking mechanism 2 is terminated . in the preferred embodiment , the open relay 28 is a delay - on - make relay . when the open relay 28 permits current to flow , power is transmitted to the linear thrust actuator 6 in the opening mechanism 5 , causing the opening mechanism to lift open the roof access hatch 8 . the open relay 28 stops transmitting power after a duration sufficient for the linear thrust actuator 6 to fully open the roof access hatch 8 . the duration will vary based on the size and weight of the roof access hatch . limit switches may be used on the roof access hatch to prevent the opening mechanism from forcing the roof access hatch beyond the fully open position . when control panel 1 is placed in close mode , power is applied to the close relay 34 . the close relay 34 transmits current to the linear thrust actuator 6 with the polarity reversed such that the linear thrust actuator 6 returns to a retracted state , pulling the roof access hatch 8 closed . the close relay 34 transmits power only for a duration sufficient to close the roof access hatch . the spring loaded latch 19 on the locking mechanism 2 secures the roof access hatch 8 in a locked position when the roof access hatch 8 is in a fully closed position . the control panel 1 is placed into either the open mode , close mode , or off mode by use of a switch . in the preferred embodiment , a key switch 26 is used to place the control panel into one of the three modes , allowing the operator to remove the key for security purposes . other known access control devices may be used to place the control panel into its various modes , including , but not limited to , pushbutton operation , biometric means , or computer - based access control . indicator lights 10 on the front of the control panel 1 may be used to indicate the status of the electrically - operated access hatch 8 , such as whether the roof access hatch 8 is opening or closing and whether the lock is engaged . current is supplied to control panel 1 from an exterior source , such as a standard power outlet . the control panel 1 may optionally house a surge protector 30 , as seem in fig2 , to protect the circuitry of the control panel 1 from electrical spikes . the current is transmitted to a dc transformer 31 that converts incoming power to a dc current . in the preferred embodiment , the transformer outputs 12v dc . however , any voltage may be adapted for use in the system . the control panel optionally includes a battery charger 32 and battery 33 . the battery 33 provides emergency back - up power if the external power source fails . this allows the operator to use the roof access hatch 8 as an emergency egress if there is a power failure . backup power relay 36 switches the source of power from the dc transformer 31 to the battery 33 in the event of a power outage . the opening mechanism 5 optionally has an emergency release that allows the roof access hatch 8 to be separated from the opening mechanism 5 in the event that manual operation is required in an emergency . in the preferred embodiment , the emergency release is bracket pin 13 that may be removed from adjustable bracket 14 causing the linear thrust actuator 6 to disconnect from roof - mounted mounting bracket 12 . in the event of an emergency , such as a malfunction or damage to the claimed device , or when the emergency battery 33 is depleted of reserve power during extended power outages , the roof access hatch can be manually opened . to open the roof access hatch 8 , the manual override key 3 is turned to unlock locking mechanism 2 , and bracket pin 13 is removed from adjustable bracket 14 . the roof access hatch 8 can then freely open . to close the roof access hatch 8 in the event of an emergency , the roof access hatch 8 can be pulled closed manually . to do so , linear thrust actuator 6 must be disengaged from adjustable bracket 14 by removal of bracket pin 13 . the roof access hatch 8 can then be pulled shut using handle 17 which is preferably affixed to the outside of locking mechanism 2 . however , the handle 17 can be located anywhere on the roof access hatch 8 . as the roof access hatch 8 is pulled closed , the latch 19 on the locking mechanism is pushed inward toward the roof access hatch hinge . the latch 19 is springloaded by means of spring 18 so that latch 19 returns to its fully extended state once access hatch 8 is in the fully closed position . under normal operating conditions , the linear thrust actuator 6 maintains access hatch 8 in the open position while the operator is on the roof . the roof access hatch will not blow closed in gusty winds while the linear thrust actuator is in the open position . however , when the roof access hatch is opened manually by removal of bracket pin 13 , a prop bar similar to that used to keep the hood of a vehicle open can be used to keep the roof access hatch open . this prop bar will prevent the operator from being trapped on the roof by preventing the closure of the roof access hatch . the electrically - operated access hatch 8 may also optionally include safety features to prevent accidental closure of the roof access hatch while a person is accessing the hatch . sensors may be mounted to detect the presence of a person near the opening mechanism of the roof access hatch . in the preferred embodiment , a retro reflective photoelectric beam sensor is employed to ensure that a person is not injured by a closing roof access hatch . the retro reflective photoelectric beam sensor is mounted on the wall near the hinge side of the roof access hatch 8 . a reflector placed on the wall near the ladder 22 reflects emitted light back to the light sensor of the retro reflective photoelectric beam sensor . a person or object near the roof access hatch would prevent emitted light from reflecting back to the retro reflective photoelectric beam sensor . the retro reflective photoelectric beam sensor is configured to cause the control panel 1 to interrupt power to the linear thrust actuator 6 whenever light is not reflected back , indicating the presence of a person or object near the roof access hatch 8 . this is handled by the safety relay 35 in control panel 1 that directs power to the open relay 28 if the light is not reflected back to the retro reflective photoelectric beam sensor . the roof access hatch will cease closing and will enter open mode . the circuitry disclosed in this application is one possible embodiment of the invention . however , it is evident to a person of ordinary skill in the art that the circuitry can be designed in many variations to operate the opening and locking mechanisms of the roof access hatch . specifically , a computer board or digital circuitry may be used that performs the same functions as the circuitry disclosed . the electric roof access hatch unlocking and opening system can be mounted to a roof access hatch 8 that is already installed in a building . alternatively , the electric roof access hatch unlocking and opening system may be part of a kit that includes the roof access hatch 8 and any accessories such as a ladder 22 . it should be understood that features of any of these embodiments may be used with another in a way that will now be understood in view of the foregoing disclosure . although the present invention has been described and illustrated with respect to at least one preferred embodiment and use therefor , it is not to be so limited since modifications and changes can be made therein which are within the fully intended scope of the invention .
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in accordance with some embodiments , circuits and methods for wireless transmitters are provided . turning to fig1 , an example 100 of a digital polar phased array transmitter in accordance with some embodiments is shown . in some embodiments , any suitable number of transmitters 100 can be used in a transmitter application . for example , in some embodiments , one transmitter ( having four ( for example ) elements ( described below )) can be used . in another embodiment , four transmitters ( each having four ( for example ) elements ( described below )) can be used , for example . in some embodiments , any suitable modulation technique can be used with transmitter ( s ) 100 . for example , in some embodiments , qam64 modulation can be used . as illustrated , transmitter 100 includes a local oscillator reference input 102 , a frequency multiplier 104 , a quadrature hybrid 106 , a resistor 108 , a phase modulator 110 , a digital interface 112 , an array driver 114 , digital polar transmitter elements 116 , 118 , 120 , and 122 , transmitter outputs 124 , 126 , 128 , and 130 , serial digital inputs 132 , a global biasing circuit 170 , and an esd circuit 172 . a local oscillator reference signal is received by transmitter 100 at input 102 . any suitable local oscillator reference signal having any suitable frequency can be used . for example , in some embodiments , local oscillator reference signal can have a frequency of 30 ghz . the local oscillator reference signal is received by frequency multiplier 104 and multiplied to a higher frequency . any suitable frequency multiplier can be used ( e . g ., a frequency multiplier as described below in connection with fig2 can be used ), and the local oscillator reference signal can be multiplied by any suitable amount . for example , in some embodiments , the frequency multiplier can multiply the local oscillator reference signal by two . the output of frequency multiplier 104 can be received by quadrature hybrid 106 . the quadrature hybrid can be any suitable quadrature hybrid in accordance with some embodiments . as illustrated , resistor 108 can be connected from one of the inputs of the quadrature hybrid to ground to provide a reference impedance . any suitable resistor can be used in some embodiments . for example , a 50 ohm resistor can be used . in - phase and quadrature components of the multiplied local oscillator reference signal can be output by hybrid 106 to phase modulator 110 . the phase modulator can be any suitable phase modulator , such as the phase modulator / shifter described below in connection with fig3 and 4 . the phase modulator can be controlled by phase control outputs [ p 0 , i - p 7 , i ] and [ p 0 , q - p 7 , q ] of digital interface 112 . array driver 114 can receive the output of phase modulator 110 and provide a drive signal to digital polar transmitter elements 116 , 118 , 120 , and 122 that is split evenly among the digital polar transmitter elements . any suitable array driver can be used in some embodiments . for example , in some embodiments , the array driver described below in connection with fig5 can be used . digital polar transmitter elements 116 , 118 , 120 , and 122 can drive transmitter outputs 124 , 126 , 128 , and 130 in response to the drive signal from array driver 114 and amplitude control outputs [ a 0 - a 7 ] of digital interface 112 . each of transmitter outputs 124 , 126 , 128 , and 130 can be connected to a suitable antenna . for example , in some embodiments , the antenna ( s ) can be phased array antennas , on - printed - circuit - board antennas , and / or any other suitable type of antenna . any suitable number of digital polar transmitter elements can be used in some embodiments . for example , in some embodiments , four digital polar transmitter elements can be used to drive a 2 × 2 array of four antennas . as further shown in fig1 , digital polar transmitter elements 116 , 118 , 120 , and 122 can each include a resistor 140 , a quadrature hybrid 142 , a phase shifter 144 , a limiting amplifier 146 , and a hybrid power digital amplitude converter ( dac ) 148 . the drive signal from array driver 114 can be provided to quadrature hybrid 142 . the quadrature hybrid can be any suitable quadrature hybrid in accordance with some embodiments . as illustrated , resistor 140 can be connected from one of the inputs of the quadrature hybrid to ground to provide a reference impedance . any suitable resistor can be used in some embodiments . for example , a 50 ohm resistor can be used . in - phase and quadrature components of the drive signal from array driver 114 can be output by hybrid 142 to phase shifter 144 . the phase shifter can be any suitable phase shifter , such as the phase modulator / shifter described below in connection with fig3 and 4 . the phase shifter can be controlled by control signals φ 1 , φ 2 , φ 3 , and φ 4 from a controller 174 . these control signals can be used to control the phase of the signal to be transmitted by the digital polar transmitter element for any suitable purpose , such as for beamforming . controller can include any suitable hardware processor ( e . g ., a microprocessor , microcontroller , dedicated control logic , a digital signal processor , etc . ), a scan chain , registers , memory , interfaces , inputs , outputs , etc . and can perform any suitable functions , such as controlling phase shifters 144 , controlling bias functions , performing specialized processing for phased arrays , compensating for various implementation non - idealities that result in beam pointing error , etc . the outputs of phase shifter 144 can be provided to limiting amplifier 146 . the limiting amplifier can be any suitable limiting amplifier , such as the limiting amplifier described below in connection with fig6 . the output of limiting amplifier 146 can be provided to hybrid power dac 148 . hybrid power dac 148 can be any suitable hybrid power dac in some embodiments . for example , hybrid power dac 148 can be implemented using the hybrid power dac described below in connection with fig7 . as shown in fig1 , digital interface 112 can include variable gain amplifiers ( vgas ) 158 , continuous time linear equalizers ( ctles ) 160 , and demultiplexers 162 , 164 , and 166 . digital interface can receive digital serial inputs 132 . more particularly , inputs 132 can include i phase control inputs , q phase control inputs , amplitude control inputs , and a clock at inputs 150 , 154 , 152 , and 156 , respectively . based on the inputs received at 132 , the digital interface can generate phase control outputs [ p 0 , i - p 7 , i ] and [ p 0 , q - p 7 , q ] and amplitude control outputs [ a 0 - a 7 ] from demultiplexers 162 , 166 , and 164 , respectively . global biasing circuitry 170 can be provided , as known in the art , to generate biasing voltages in circuit 100 in accordance with some embodiments . esd circuitry 172 can be provided , as known in the art , to protect circuit 100 from electrostatic discharge and over - voltage conditions in accordance with some embodiments . fig2 shows an example 200 of a frequency multiplier that can be used to implement frequency multiplier 104 of fig1 in some embodiments . as shown , a local oscillator reference signal can be received at node 202 , the signal multiplied by two , and then the resulting signal output at node 204 . in some embodiments , match blocks 206 and 208 can include any suitable components for matching the impedance of the points on the left and right of each match block . for example , in some embodiments , match blocks 206 and 208 can include inductors , spirals , transmission lines , and / or capacitors . turning to fig3 , an example 300 of a phase modulator / shifter that can be used as phase modulator 110 and / or phase shifter 144 of fig1 in some embodiments . as shown , phase modulator / shifter 300 includes mixers 302 and 304 . any suitable mixers can be used as mixers 302 and 304 . for example , in some embodiments , example mixer 400 described below in connection with fig4 can be used as mixers 302 and / or 304 . as shown in fig4 , mixer 400 includes eight switching transistors represented in this figure by transistors 402 , 404 , 406 , and 408 . the transistors other than transistor 408 ( the most significant bit ( msb ) transistor ) are binary weighted with weights of w , 2w , . . . , 2 6 w , where w represents a given combination of finger width and number of fingers in a transistor . any suitable combination of finger width and number of fingers can be used in the transistors for w , such as a finger width of 0 . 152 micron and one finger , in some embodiments . the gates of these transistors are connected to inputs b 0 , b 1 , b 2 , . . . , b 7 . these bits can be provided by phase control bits [ p 0 , i - p 7 , i ], [ p 0 , q - p 7 , q ], φ 1 , φ 2 , φ 3 , or φ 4 shown in fig1 in some embodiments . the binary value that is provided to the inputs , determines the amount of modulation or shift of the input signal such that a higher value turns on a higher total weighting of switches , resulting in a higher current flow through the switches . although eight transistors and inputs are shown , any suitable number of inputs and transistors can be used in some embodiments . a bias voltage , v b , can also be provided to calibrate the shifter to account for variations in process , voltage , and temperature . turning to fig5 , an example 500 of an array driver that can be used to implement array driver 114 of fig1 is shown in accordance with some embodiments . as shown , an input signal can be presented at inputs 502 of driver 500 , the signal will be amplified , and the resulting signal will be provided at node 504 . turning to fig6 , an example 600 of a limiting amplifier that can be used to implement limiting amplifier 146 of fig1 is shown in accordance with some embodiments . as shown , an input signal can be presented at node 602 of limiting amplifier 600 , the signal will be amplified , and the resulting signal will be provided at node 504 . fig7 shows an example 700 of a hybrid power dac that can be used to implement hybrid power dac 148 of fig1 in accordance with some embodiments . as shown , in some embodiments , hybrid power dac 700 can be implemented as a differential class - e power amplifier with four stacked transistors that is augmented with trail transistors ( at the common source node ) and a supply inverter ( connected to the differential dc - feed spiral of the four - stack class e power amplifier ) to incorporate amplitude modulation capability . in some embodiments , hybrid power dac 700 includes inputs 702 and 704 , outputs 706 and 708 , inverters 710 , switching transistors 712 , 714 , and 716 , stacked transistors 717 , 718 , 720 , and 722 , dc feed inductors ( implemented as transmission lines ) 724 , gate bias inputs 726 , 728 , 730 , and 732 , two - stack drivers 734 , and match blocks 736 . as shown in fig7 , hybrid power dac 700 includes two inverters 710 and n − 1 switching transistors , represented in this figure by transistors 712 , 714 , and 716 . the n − 1 switching transistors ( represented by transistors 712 , 714 , and 716 ) are binary weighted with weights of w 1 , 2w 1 , . . . , 2 n - 1 w 1 , where w 1 represents a given combination of finger width and number of fingers in a transistor . any suitable combination of finger width and number of fingers can be used in the transistors for w 1 , such as a finger width of 2 . 793 micron and two fingers , in some embodiments . the gates of the transistors are connected to inputs b 0 , b 1 , b 2 , . . . , b n - 1 and the input to the inverter is connected to input b n ( the most significant bit ( msb )). as suggested by the use of n in fig7 , any suitable number of switching transistors , and hence inputs b 0 . . . b n - 1 can be used in some embodiments . the binary value that is provided to inputs b 0 , b 1 , b 2 , . . . , b n determines the amount of amplification provided by the hybrid power dac . these bits can be provided by amplitude control bits [ a 0 - a 7 ] shown in fig1 in some embodiments . more particularly , a higher value at inputs b 0 , b 1 , b 2 , . . . , b n - 1 turns on a higher total weighting of the switching transistors , resulting in a higher current flow through the switching transistors , and the value of input b n at the input to inverter 710 determines the supply voltage v dd , pa supplied to the stack of transistors including stacked transistors 717 , 718 , 720 , and 722 and the switching transistors . the manner in which this amplification is achieved is further illustrated in connection with fig1 . as shown , for a given input at the gate of transistor m 1 1002 , a voltage between ground and 2v dd ( represented by voltage 1010 ) ( where , v dd here represents the nominal voltage supply in the technology used , for example , 1 . 2v nominally in 45 nm soi cmos ) is produced at the source of transistor m 2 1004 . this results in a voltage between v on and 2v dd being present at the gate of transistor m 2 1004 through capacitance cgs between the source and the gate of transistor m 2 1004 ( which capacitance is inherently present in transistor m 2 1004 ), resulting in a voltage between ground and 4v dd ( represented by voltage 1012 ) being produced at the source of transistor m 3 1006 . this results in a voltage between v on and 4v dd being present at the gate of transistor m 3 1006 through capacitance cgs between the source and the gate of transistor m 3 1006 , resulting in a voltage between ground and 6v dd ( represented by voltage 1014 ) being produced at the source of the transistor above transistor m 3 1006 . this process is repeated for the transistors going upward along the stack represented by transistors 1002 , 1004 , 1006 , and 1008 until a voltage of between v on and 2 ( n − 1 ) v dd ( represented by voltage 1016 ) is produced at the gate of transistor m n 1008 , which results in a voltage between ground and 2nv dd being produced at the drain of transistor m n 1008 and the output of the stack . as stated above , whether the output of the stack is at ground or 2nv dd depends on the input at the gate of transistor m 1 1002 . referring back to fig7 , the corresponding inputs in the hybrid power dac are at the gates of transistors m 1 717 . as shown , these input are controlled by the outputs of two - stack drivers 734 , which are driven by inputs 702 and 704 . an example 800 of a two - stack driver that can be used for two - stack driver 734 in accordance with some embodiments is shown in fig8 . as shown , the input to the two - stack driver is provided at node 802 and the output is produced at node 804 . as shown in fig7 , the outputs of two - stack drivers 734 are connected to the gates of transistors m 1 717 by match blocks 736 . in some embodiments , match blocks 736 can include any suitable components for matching the impedance of the points on the left and right of each match block . for example , in some embodiments , match blocks 736 can include inductors , spirals , transmission lines , and / or capacitors . as also shown in fig7 , the gates of transistors m 1 717 , m 2 718 , m 3 720 , and m 4 722 are biased by bias voltages v g1 , v g2 , v g3 , and v g4 . these bias voltages can be produced in any suitable manner . for example , in some embodiments , for each hybrid power dac 700 , an adaptive bias circuit , such as adaptive bias circuit 900 shown in fig9 , can be provided . as illustrated in fig9 , circuit 900 includes a voltage divider 902 formed from four resistors r 1 . these resistors can have any suitable value . the voltage divider is powered by v dd , pa , which as described in fig7 is variable and controlled by the output of inverters 710 . voltages v 1 , v 2 , and v 3 shown in fig9 are provided to transistors 904 , 906 , and 908 , respectively . the bias voltages are then produced at the nodes labelled v g1 , v g2 , v g3 , and v g4 . resistors r big can have any suitable values sufficiently large compared to the gate impedance ( of the gates connected to the corresponding bias voltage ) to have suitable performance but not too large so as to affect modulation speed . in some embodiments , r big can be a 1 kω resistor . in some embodiments , transistor 910 can be implemented as a bank of parallel binary weighted transistors ( e . g ., like the binary weighted transistors described above in connection with fig4 and 7 ) so that the bias voltages produced by circuit 900 can be controlled by controller 174 of fig1 . in some of these embodiments , any suitable number of parallel binary weighted transistors can be provided , and each of the transistors can have any suitable weighting ( s ). when such control is not needed , transistor 910 can be a single transistor . although specific components having specific properties ( e . g ., resistances , capacitance , sizes , relative sizes , voltages , etc .) are shown in fig1 - 10 , one or more of the components in any one or more of these figures can be omitted or substituted with one or more alternate components having one or more different properties , in some embodiments . the provision of the examples described herein ( as well as clauses phrased as “ such as ,” “ e . g .,” “ including ,” and the like ) should not be interpreted as limiting the claimed subject matter to the specific examples ; rather , the examples are intended to illustrate only some of many possible aspects . although the invention has been described and illustrated in the foregoing illustrative embodiments , it is understood that the present disclosure has been made only by way of example , and the numerous changes in the details of implementation of the invention can be made without departing from the spirit and scope of the invention , which is only limited by the claims which follow . features of the disclosed embodiments can be combined and rearranged in various ways .
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the novel features of the invention are set forth with particularity in the appended claims . a better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments , in which the principles of the invention are utilized . while preferred embodiments of the present invention have been shown and described herein such embodiments are provided by way of example only . it should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention . those ordinary skilled in the art will appreciate that numerous variations , changes , and substitutions are possible without departing from the invention . it is intended that the following claims define the scope of aspects of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby . the section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described . all documents , or portions of documents , cited in the application including , without limitation , patents , patent applications , articles , books , manuals , and treatises are hereby expressly incorporated by reference in their entirety for any purpose . unless defined otherwise , all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the claimed subject matter belongs . all patents , patent applications , published materials referred to throughout the entire disclosure herein , unless noted otherwise , are incorporated by reference in their entirety . in the event that there is a plurality of definitions for terms herein , those in this section prevail . where reference is made to a url or other such identifier or address , it is understood that such identifiers can change and particular information on the internet can come and go , but equivalent information can be found by searching the internet or other appropriate reference source . reference thereto evidences the availability and public dissemination of such information . it is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of any subject matter claimed . in this application , the use of the singular includes the plural unless specifically stated otherwise . it must be noted that , as used in the specification and the appended claims , the singular forms “ a ”, “ an ” and “ the ” include plural referents unless the context clearly dictates otherwise . it should also be noted that use of “ or ” means “ and / or ” unless stated otherwise . furthermore , use of the term “ including ” as well as other forms , such as “ include ”, “ includes ”, and “ included ” is not limiting . likewise , use of the term “ comprising ” as well as other forms , such as “ comprise ”, “ comprises ”, and “ comprised ” is not limiting . definition of standard chemistry terms may be found in reference works , including carey and sundberg “ advanced organic chemistry 4 ed .” vols . a ( 2000 ) and b ( 2001 ), plenum press , new york . unless otherwise indicated , conventional methods of mass spectroscopy , nmr , hplc , ir and uv / vis spectroscopy and pharmacology , within the skill of the art are employed . unless specific definitions are provided , the nomenclature employed in connection with , and the laboratory procedures and techniques of , analytical chemistry , synthetic organic chemistry , and medicinal and pharmaceutical chemistry described herein are those known in the art . standard techniques can be used for chemical syntheses , chemical analyses , pharmaceutical preparation , formulation , and delivery , and treatment of patients . reactions and purification techniques can be performed e . g ., using kits of manufacturer &# 39 ; s specifications or as commonly accomplished in the art or as described herein . the foregoing techniques and procedures can be generally performed of conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification . throughout the specification , groups and substituents thereof can be chosen by one skilled in the field to provide stable moieties and compounds . where substituent groups are specified by their conventional chemical formulas , written from left to right , they equally encompass the chemically identical substituents that would result from writing the structure from right to left . as a non - limiting example , ch 2 o is equivalent to och 2 . unless otherwise noted , the use of general chemical terms , such as though not limited to “ alkyl ,” “ amine ,” “ aryl ,” are equivalent to their optionally substituted forms . for example , “ alkyl ,” as used herein , includes optionally substituted alkyl . the compounds presented herein may possess one or more stereocenters and each center may exist in the r or s configuration , or combinations thereof . likewise , the compounds presented herein may possess one or more double bonds and each may exist in the e ( trans ) or z ( cis ) configuration , or combinations thereof . presentation of one particular stereoisomer , regioisomer , diastereomer , enantiomer or epimer should be understood to include all possible stereoisomers , regioisomers , diastereomers , enantiomers or epimers and mixtures thereof . thus , the compounds presented herein include all separate configurational stereoisomeric , regioisomeric , diastereomeric , enantiomeric , and epimeric forms as well as the corresponding mixtures thereof . techniques for inverting or leaving unchanged a particular stereocenter , and those for resolving mixtures of stereoisomers are well known in the art and it is well within the ability of one of skill in the art to choose an appropriate method for a particular situation . see , for example , fumiss et al . ( eds . ), vogel &# 39 ; s encyclopedia of practical organic chemistry 5 . sup . th ed ., longman scientific and technical ltd ., essex , 1991 , 809 - 816 ; and heller , acc . chem . res . 1990 , 23 , 128 . the term “ bond ” or “ single bond ” refers to a chemical bond between two atoms , or two moieties when the atoms joined by the bond are considered to be part of larger substructure . the term “ optional ” or “ optionally ” means that the subsequently described event or circumstance may or may not occur , and that the description includes instances where said event or circumstance occurs and instances in which it does not . for example , “ optionally substituted alkyl ” means either “ alkyl ” or “ substituted alkyl ” as defined below . further , an optionally substituted group may be un - substituted ( e . g ., ch 2 ch 3 ), fully substituted ( e . g ., cf 2 cf 3 ), mono - substituted ( e . g ., ch 2 ch 2 f ) or substituted at a level anywhere in - between fully substituted and mono - substituted ( e . g ., ch 2 chf 2 , cf 2 ch 3 , cfhchf 2 , etc ). it will be understood by those skilled in the art with respect to any group containing one or more substituents that such groups are not intended to introduce any substitution or substitution patterns ( e . g ., substituted alkyl includes optionally substituted cycloalkyl groups , which in turn are defined as including optionally substituted alkyl groups , potentially ad infinitum ) that are sterically impractical and / or synthetically non - feasible . thus , any substituents described should generally be understood as having a maximum molecular weight of about 1 , 000 daltons , and more typically , up to about 500 daltons ( except in those instances where macromolecular substituents are clearly intended , e . g ., polypeptides , polysaccharides , polyethylene glycols , dna , rna and the like ). as used herein , c 1 - cn , includes c 1 - c 2 , c 1 - c 3 , . . . c 1 - cn . by way of example only , a group designated as “ c 1 - c 4 ” indicates that there are one to four carbon atoms in the moiety , i . e . groups containing 1 carbon atom , 2 carbon atoms , 3 carbon atoms or 4 carbon atoms , as well as the ranges c 1 - c 2 and c 1 - c 3 . thus , by way of example only , “ c 1 - c 4 alkyl ” indicates that there are one to four carbon atoms in the alkyl group , i . e ., the alkyl group is selected from among methyl , ethyl , propyl , iso - propyl , n - butyl , isobutyl , sec - butyl , and t - butyl . whenever it appears herein , a numerical range such as “ 1 to 10 ” refers to each integer in the given range ; e . g ., “ 1 to 10 carbon atoms ” means that the group may have 1 carbon atom , 2 carbon atoms , 3 carbon atoms , 4 carbon atoms , 5 carbon atoms , 6 carbon atoms , 7 carbon atoms , 8 carbon atoms , 9 carbon atoms , or 10 carbon atoms . the terms “ heteroatom ” or “ hetero ” as used herein , alone or in combination , refer to an atom other than carbon and hydrogen . heteroatoms are independently selected from among oxygen , nitrogen , sulfur , phosphorous , silicon , selenium and tin but are not limited to these atoms . in embodiments in which two or more heteroatoms are present , the two or more heteroatoms can be the same as each another , or some or all of the two or more heteroatoms can each be different from the others . the term “ alkyl ” as used herein , alone or in combination , refers to an optionally substituted straight - chain , or optionally substituted branched - chain saturated hydrocarbon monoradical having from one to about ten carbon atoms , more preferably one to six carbon atoms . examples include , but are not limited to methyl , ethyl , n - propyl , isopropyl , 2 - methyl - 1 - propyl , 2 - methyl - 2 - propyl , 2 - methyl - 1 - butyl , 3 - methyl - 1 - butyl , 2 - methyl - 3 - butyl , 2 , 2 - dimethyl - 1 - propyl , 2 - methyl - 1 - pentyl , 3 - methyl - 1 - pentyl , 4 - methyl - 1 - pentyl , 2 - methyl - 2 - pentyl , 3 - methyl - 2 - pentyl , 4 - methyl - 2 - pentyl , 2 , 2 - dimethyl - 1 - butyl , 3 , 3 - dimethyl - 1 - butyl , 2 - ethyl - 1 - butyl , n - butyl , isobutyl , sec - butyl , t - butyl , n - pentyl , isopentyl , neopentyl , tert - amyl and hexyl , and longer alkyl groups , such as heptyl , octyl and the like . whenever it appears herein , a numerical range such as “ c 1 - c 6 alkyl ” or “ c 1 — 6 alkyl ”, means that the alkyl group may consist of 1 carbon atom , 2 carbon atoms , 3 carbon atoms , 4 carbon atoms , 5 carbon atoms or 6 carbon atoms , although the present definition also covers the occurrence of the term “ alkyl ” where no numerical range is designated . the term “ alkylene ” as used herein , alone or in combination , refers to a diradical derived from the above - defined monoradical , alkyl . examples include , but are not limited to methylene (— ch 2 ), ethylene (— ch 2 ch 2 ), propylene (— ch 2 ch 2 ch 2 ), isopropylene (— ch ( ch 3 ) ch 2 ) and the like . the term “ alkenyl ” as used herein , alone or in combination , refers to an optionally substituted straight - chain , or optionally substituted branched - chain hydrocarbon monoradical having one or more carbon - carbon double - bonds and having from two to about ten carbon atoms , more preferably two to about six carbon atoms . the group may be in either the cis or trans conformation about the double bond ( s ), and should be understood to include both isomers . examples include , but are not limited to ethenyl ( ch ═ ch 2 ), 1 - propenyl ( ch 2 ch ═ ch 2 ), isopropenyl [ c ( ch 3 )═ ch 2 ], butenyl , 1 , 3 - butadienyl and the like . whenever it appears herein , a numerical range such as “ c 2 - c 6 alkenyl ” or “ c 2 — 6 alkenyl ”, means that the alkenyl group may consist of 2 carbon atoms , 3 carbon atoms , 4 carbon atoms , 5 carbon atoms or 6 carbon atoms , although the present definition also covers the occurrence of the term “ alkenyl ” where no numerical range is designated . the term “ alkynyl ” as used herein , alone or in combination , refers to an optionally substituted straight - chain or optionally substituted branched - chain hydrocarbon monoradical having one or more carbon - carbon triple - bonds and having from two to about ten carbon atoms , more preferably from two to about six carbon atoms . examples include , but are not limited to ethynyl , 2 - propynyl , 2 - butynyl , 1 , 3 - butadiynyl and the like . whenever it appears herein , a numerical range such as “ c 2 - c 6 alkynyl ” or “ c 2 — 6 alkynyl ”, means that the alkynyl group may consist of 2 carbon atoms , 3 carbon atoms , 4 carbon atoms , 5 carbon atoms or 6 carbon atoms , although the present definition also covers the occurrence of the term “ alkynyl ” where no numerical range is designated . the term “ aliphatic ” as used herein , alone or in combination , refers to an optionally substituted , straight - chain or branched - chain , non - cyclic , saturated , partially unsaturated , or fully unsaturated nonaromatic hydrocarbon . thus , the term collectively includes alkyl , alkenyl and alkynyl groups . the terms “ heteroalkyl ”, “ heteroalkenyl ” and “ heteroalkynyl ” as used herein , alone or in combination , refer to optionally substituted alkyl , alkenyl and alkynyl structures respectively , as described above , in which one or more of the skeletal chain carbon atoms ( and any associated hydrogen atoms , as appropriate ) are each independently replaced with a heteroatom ( i . e . an atom other than carbon , such as though not limited to oxygen , nitrogen , sulfur , silicon , phosphorous , tin or combinations thereof . the terms “ halo alkyl ”, “ halo alkenyl ” and “ haloalkynyl ” as used herein , alone or in combination , refer to optionally substituted alkyl , alkenyl and alkynyl groups respectively , as defined above , in which one or more hydrogen atoms is replaced by fluorine , chlorine , bromine or iodine atoms , or combinations thereof . in some embodiments two or more hydrogen atoms may be replaced with halogen atoms that are the same as each another ( e . g . difluoromethyl ); in other embodiments two or more hydrogen atoms may be replaced with halogen atoms that are not all the same as each other ( e . g . 1 - chloro - 1 - fluoro - 1 - iodoethyl ). non - limiting examples of haloalkyl groups are fluoromethyl and bromoethyl . a non - limiting example of a haloalkenyl group is bromoethenyl . a non - limiting example of a haloalkynyl group is chloroethynyl . the terms “ cycle ”, “ cyclic ”, “ ring ” and “ membered ring ” as used herein , alone or in combination , refer to any covalently closed structure , including alicyclic , heterocyclic , aromatic , heteroaromatic and polycyclic fused or non - fused ring systems as described herein . rings can be optionally substituted . rings can form part of a fused ring system . the term “ membered ” is meant to denote the number of skeletal atoms that constitute the ring . thus , by way of example only , cyclohexane , pyridine , pyran and pyrimidine are six - membered rings and cyclopentane , pyrrole , tetrahydrofuran and thiophene are five - membered rings . the term “ fused ” as used herein , alone or in combination , refers to cyclic structures in which two or more rings share one or more bonds . the term “ cycloalkyl ” as used herein , alone or in combination , refers to an optionally substituted , saturated , hydrocarbon monoradical ring , containing from three to about fifteen ring carbon atoms or from three to about ten ring carbon atoms , though may include additional , non - ring carbon atoms as substituents ( e . g . methylcyclopropyl ). a non - limiting example of “ cycloalkyl ” includes azinyl , azetidinyl , oxetanyl , thietanyl , homopiperidinyl , oxepanyl , thiepanyl , oxazepinyl , diazepinyl , thiazepinyl , 1 , 2 , 3 , 6 - tetrahydropyridinyl , 2 - pyrrolinyl , 3 - pyrrolinyl , indolinyl , 2h - pyranyl , 4h - pyranyl , dioxanyl , 1 , 3 - dioxolanyl , pyrazolinyl , dithianyl , dithiolanyl , dihydropyranyl , dihydrothienyl , dihydrofuranyl , pyrazolidinyl , imidazolinyl , imidazolidinyl , 3 - azabicyclo [ 3 . 1 . 0 ] hexyl , 3 - azabicyclo [ 4 . 1 . 0 ] heptyl , 3h - indolyl and quinolizinyl and the like . the terms also include all ring forms of the carbohydrates , including but not limited to the monosaccharides , the disaccharides and the oligosaccharides . the term “ aromatic ” as used herein , refers to a planar , cyclic or polycyclic , ring moiety having a delocalized at - electron system containing 4n + 2 n electrons , where n is an integer . aromatic rings can be formed by five , six , seven , eight , nine , or more than nine atoms . aromatics can be optionally substituted and can be monocyclic or fused - ring polycyclic . the term aromatic encompasses both all carbon containing rings ( e . g ., phenyl ) and those rings containing one or more heteroatoms ( e . g ., pyridine ). the term “ aryl ” as used herein , alone or in combination , refers to an optionally substituted aromatic hydrocarbon radical of six to about twenty ring carbon atoms , and includes fused and non - fused aryl rings . a fused aryl ring radical contains from two to four fused rings where the ring of attachment is an aryl ring , and the other individual rings may be alicyclic , heterocyclic , aromatic , heteroaromatic or any combination thereof . further , the term aryl includes fused and non - fused rings containing from six to about twelve ring carbon atoms , as well as those containing from six to about ten ring carbon atoms . a non - limiting example of a single ring aryl group includes phenyl ; a fused ring aryl group includes naphthyl , phenanthrenyl , anthracenyl , azulenyl ; and a non - fused bi - aryl group includes biphenyl . the term “ heteroaryl ” as used herein , alone or in combination , refers to optionally substituted aromatic mono - radicals containing from about five to about twenty skeletal ring atoms , where one or more of the ring atoms is a heteroatom independently selected from among oxygen , nitrogen , sulfur , phosphorous , silicon , selenium and tin but not limited to these atoms and with the proviso that the ring of said group does not contain two adjacent o or s atoms . in embodiments in which two or more heteroatoms are present in the ring , the two or more heteroatoms can be the same as each another , or some or all of the two or more heteroatoms can each be different from the others . the term heteroaryl includes optionally substituted fused and non - fused heteroaryl radicals having at least one heteroatom . the term heteroaryl also includes fused and non - fused heteroaryls having from five to about twelve skeletal ring atoms , as well as those having from five to about ten skeletal ring atoms . bonding to a heteroaryl group can be via a carbon atom or a heteroatom . thus , as a non - limiting example , an imidazole group may be attached to a parent molecule via any of its carbon atoms ( imidazol - 2 - yl , imidazol - 4 - yl or imidazol - 5 - yl ), or its nitrogen atoms ( imidazol - 1 - yl or imidazol - 3 - yl ). likewise , a heteroaryl group may be further substituted via any or all of its carbon atoms , and / or any or all of its heteroatoms . a fused heteroaryl radical may contain from two to four fused rings where the ring of attachment is a heteroaromatic ring and the other individual rings may be alicyclic , heterocyclic , aromatic , heteroaromatic or any combination thereof . a non - limiting example of a single ring heteroaryl group includes pyridyl ; fused ring heteroaryl groups include benzimidazolyl , quinolinyl , acridinyl ; and a non - fused bi - heteroaryl group includes bipyridinyl . further examples of heteroaryls include , without limitation , furanyl , thienyl , oxazolyl , acridinyl , phenazinyl , benzimidazolyl , benzofuranyl , benzoxazolyl , benzothiazolyl , benzothiadiazolyl , benzothiophenyl , benzoxadiazolyl , benzotriazolyl , imidazolyl , indolyl , isoxazolyl , isoquinolinyl , indolizinyl , isothiazolyl , isoindolyloxadiazolyl , indazolyl , pyridyl , pyridazyl , pyrimidyl , pyrazinyl , pyrrolyl , pyrazolyl , purinyl , phthalazinyl , pteridinyl , quinolinyl , quinazolinyl , quinoxalinyl , triazolyl , tetrazolyl , thiazolyl , triazinyl , thiadiazolyl and the like , and their oxides , such as for example pyridyl - n - oxide and the like . the term “ heterocyclyl ” as used herein , alone or in combination , refers collectively to heteroalicyclyl and heteroaryl groups . herein , whenever the number of carbon atoms in a heterocycle is indicated ( e . g ., c 1 - c 6 heterocycle ), at least one non - carbon atom ( the heteroatom ) must be present in the ring . designations such as “ c 1 - c 6 heterocycle ” refer only to the number of carbon atoms in the ring and do not refer to the total number of atoms in the ring . designations such as “ 4 - 6 membered heterocycle ” refer to the total number of atoms that are contained in the ring ( i . e ., a four , five , or six membered ring , in which at least one atom is a carbon atom , at least one atom is a heteroatom and the remaining two to four atoms are either carbon atoms or heteroatoms ). for heterocycles having two or more heteroatoms , those two or more heteroatoms can be the same or different from one another . heterocycles can be optionally substituted . non - aromatic heterocyclic groups include groups having only three atoms in the ring , while aromatic heterocyclic groups must have at least five atoms in the ring . bonding ( i . e . attachment to a parent molecule or further substitution ) to a heterocycle can be via a heteroatom or a carbon atom . the term “ alkoxy ” as used herein , alone or in combination , refers to an alkyl ether radical , o - alkyl , including the groups o - aliphatic and o - carbocycle , wherein the alkyl , aliphatic and carbocycle groups may be optionally substituted , and wherein the terms alkyl , aliphatic and carbocycle are as defined herein . non - limiting examples of alkoxy radicals include methoxy , ethoxy , n - propoxy , isopropoxy , n - butoxy , iso - butoxy , sec - butoxy , tertbutoxy and the like . the term “ mek inhibitor ” as used herein refers to a compound that exhibits an ic 50 , with respect to mek activity , of no more than about 100 μm or not more than about 50 μm , as measured in the mek1 kinase assay described generally herein . “ ic 50 ” is that concentration of inhibitor which reduces the activity of an enzyme ( e . g ., mek ) to half - maximal level . compounds described herein have been discovered to exhibit inhibition against mek . compounds of the present invention preferably exhibit an ic 50 with respect to mek of no more than about 10 μm , more preferably , no more than about 5 μm , even more preferably not more than about 1 μm , and most preferably , not more than about 200 nm , as measured in the mek1 kinase assay described herein . the term “ selective ,” “ selectivity ,” or “ selectivity ” as used herein refers to a compound of this invention having a lower ic 50 value for a mek enzyme as compared to any other enzymes ( e . g ., at least 2 , 5 , 10 or more - fold lower ). the term may also refer to a compound of this invention having a lower ic 50 value for a mek1 enzyme as compared to a mek2 enzyme ( e . g ., at least 2 , 5 , 10 or more - fold ) or alternatively having a lower ic 50 value for a mek2 enzyme as compared to a mek1 enzyme ( e . g ., at least 2 , 5 , 10 or more - fold lower ). the term “ subject ”, “ patient ” or “ individual ” as used herein in reference to individuals suffering from a disorder , a disorder , a condition , and the like , encompasses mammals and non - mammals . examples of mammals include , but are not limited to , any member of the mammalian class : humans , non - human primates such as chimpanzees , and other apes and monkey species ; farm animals such as cattle , horses , sheep , goats , swine ; domestic animals such as rabbits , dogs , and cats ; laboratory animals including rodents , such as rats , mice and guinea pigs , and the like . examples of non - mammals include , but are not limited to , birds , fish and the like . in one embodiment of the methods and compositions provided herein , the mammal is a human . the terms “ treat ,” “ treating ” or “ treatment ,” and other grammatical equivalents as used herein , include alleviating , abating or ameliorating a disease or condition symptoms , preventing additional symptoms , ameliorating or preventing the underlying metabolic causes of symptoms , inhibiting the disease or condition , e . g ., arresting the development of the disease or condition , relieving the disease or condition , causing regression of the disease or condition , relieving a condition caused by the disease or condition , or stopping the symptoms of the disease or condition , and are intended to include prophylaxis . the terms further include achieving a therapeutic benefit and / or a prophylactic benefit . by therapeutic benefit is meant eradication or amelioration of the underlying disorder being treated . also , a therapeutic benefit is achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the patient , notwithstanding that the patient may still be afflicted with the underlying disorder . for prophylactic benefit , the compositions may be administered to a patient at risk of developing a particular disease , or to a patient reporting one or more of the physiological symptoms of a disease , even though a diagnosis of this disease may not have been made . the terms “ effective amount ”, “ therapeutically effective amount ” or “ pharmaceutically effective amount ” as used herein , refer to a sufficient amount of at least one agent or compound being administered which will relieve to some extent one or more of the symptoms of the disease or condition being treated . the result can be reduction and / or alleviation of the signs , symptoms , or causes of a disease , or any other desired alteration of a biological system . for example , an “ effective amount ” for therapeutic uses is the amount of the composition comprising a compound as disclosed herein required to provide a clinically significant decrease in a disease . an appropriate “ effective ” amount in any individual case may be determined using techniques , such as a dose escalation study . the terms “ administer ,” “ administering ”, “ administration ,” and the like , as used herein , refer to the methods that may be used to enable delivery of compounds or compositions to the desired site of biological action . these methods include , but are not limited to oral routes , intraduodenal routes , parenteral injection ( including intravenous , subcutaneous , intraperitoneal , intramuscular , intravascular or infusion ), topical and rectal administration . those of skill in the art are familiar with administration techniques that can be employed with the compounds and methods described herein , e . g ., as discussed in goodman and gilman , the pharmacological basis of therapeutics , current ed . ; pergamon ; and remington &# 39 ; s , pharmaceutical sciences ( current edition ), mack publishing co ., easton , pa . in preferred embodiments , the compounds and compositions described herein are administered orally . the term “ acceptable ” as used herein , with respect to a formulation , composition or ingredient , means having no persistent detrimental effect on the general health of the subject being treated . the term “ pharmaceutically acceptable ” as used herein , refers to a material , such as a carrier or diluent , which does not abrogate the biological activity or properties of the compounds described herein , and is relatively nontoxic , i . e ., the material may be administered to an individual without causing undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained . the term “ pharmaceutical composition ,” as used herein , refers to a biologically active compound , optionally mixed with at least one pharmaceutically acceptable chemical component , such as , though not limited to carriers , stabilizers , diluents , dispersing agents , suspending agents , thickening agents , and / or excipients . the term “ carrier ” as used herein , refers to relatively nontoxic chemical compounds or agents that facilitate the incorporation of a compound into cells or tissues . the term “ agonist ,” as used herein , refers to a molecule such as a compound , a drug , an enzyme activator or a hormone modulator which enhances the activity of another molecule or the activity of a receptor site . the term “ antagonist ,” as used herein , refers to a molecule such as a compound , a drug , an enzyme inhibitor , or a hormone modulator , which diminishes , or prevents the action of another molecule or the activity of a receptor site . the term “ modulate ,” as used herein , means to interact with a target either directly or indirectly so as to alter the activity of the target , including , by way of example only , to enhance the activity of the target , to inhibit the activity of the target , to limit the activity of the target , or to extend the activity of the target . the term “ modulator ,” as used herein , refers to a molecule that interacts with a target either directly or indirectly . the interactions include , but are not limited to , the interactions of an agonist and an antagonist . the term “ pharmaceutically acceptable salt ” as used herein , refers to salts that retain the biological effectiveness of the free acids and bases of the specified compound and that are not biologically or otherwise undesirable . compounds described herein may possess acidic or basic groups and therefore may react with any of a number of inorganic or organic bases , and inorganic and organic acids , to form a pharmaceutically acceptable salt . these salts can be prepared in situ during the final isolation and purification of the compounds of the invention , or by separately reacting a purified compound in its free base form with a suitable organic or inorganic acid , and isolating the salt thus formed . examples of pharmaceutically acceptable salts include those salts prepared by reaction of the compounds described herein with a mineral or organic acid or an inorganic base , such salts including , acetate , acrylate , adipate , alginate , aspartate , benzoate , benzenesulfonate , bisulfate , bisulfite , bromide , butyrate , butyn - 1 , 4 - dioate , camphorate , camphorsulfonate , caprylate , chlorobenzoate , chloride , citrate , cyclopentanepropionate , decanoate , digluconate , dihydrogenphosphate , dinitrobenzoate , dodecylsulfate , ethanesulfonate , formate , fumarate , glucoheptanoate , glycerophosphate , glycolate , hemisulfate , heptanoate , hexanoate , hexyne - 1 , 6 - dioate , hydroxybenzoate , hydroxybutyrate , hydrochloride , hydrobromide , hydro iodide , 2 - hydroxyethanesulfonate , iodide , isobutyrate , lactate , maleate , malonate , methanesulfonate , mandelate . metaphosphate , methoxybenzoate , methylbenzoate , monohydrogenphosphate , 1 - napthalenesulfonate , 2 - napthalenesulfonate , nicotinate , nitrate , palmoate , pectinate , persulfate , 3 - phenylpropionate , phosphate , picrate , pivalate , propionate , pyrosulfate , pyrophosphate , propiolate , phthalate , phenylacetate , phenylbutyrate , propanesulfonate , salicylate , succinate , sulfate , sulfite , suberate , sebacate , sulfonate , tartrate , thiocyanate , tosylate undeconate and xylenesulfonate . other acids , such as oxalic , while not in themselves pharmaceutically acceptable , may be employed in the preparation of salts useful as intermediates in obtaining the compounds of the invention and their pharmaceutically acceptable acid addition salts ( see examples at berge et al ., j . plum . sci . 1977 , 66 , 1 - 19 .). further , those compounds described herein which may comprise a free acid group may react with a suitable base , such as the hydroxide , carbonate or bicarbonate of a pharmaceutically acceptable metal cation , with ammonia , or with a pharmaceutically acceptable organic primary , secondary or tertiary amine . representative alkali or alkaline earth salts include the lithium , sodium , potassium , calcium , magnesium , and aluminum salts and the like . illustrative examples of bases include sodium hydroxide , potassium hydroxide , choline hydroxide , sodium carbonate , iv ′ ( c 1 — 4 alkyl ) 4 , and the like . representative organic amines useful for the formation of base addition salts include ethylamine , diethylamine , ethylenediamine , ethanolamine , diethanolamine , piperazine and the like . it should be understood that the compounds described herein also include the quaternization of any basic nitrogen - containing groups they may contain . water or oil - soluble or dispersible products may be obtained by such quaternization . see , for example , berge et al ., supra . the term “ solvate ” as used herein refers to a combination of a compound of this invention with a solvent molecule formed by solvation . in some situations , the solvate refers to a hydrate , i . e ., the solvent molecule is a water molecule , the combination of a compound of this invention and water forms a hydrate . the term “ polymorph ” or “ polymorphism ” as used herein refers to a compound of this invention present in different crystal lattice forms . the term “ ester ” as used herein refers to a derivative of a compound of this invention derived from an oxoacid group and a hydroxyl group , either one of which can be present at the compound of this invention . the term “ tautomer ” as used herein refers to an isomer readily interconverted from a compound of this invention by e . g ., migration of a hydrogen atom or proton . the term “ pharmaceutically acceptable derivative or prodrug ” as used herein , refers to any pharmaceutically acceptable salt , ester , salt of an ester or other derivative of a compound of this invention , which , upon administration to a recipient , is capable of providing , either directly or indirectly , a compound of this invention or a pharmaceutically active metabolite or residue thereof . particularly favored derivatives or prodrugs are those that increase the bioavailability of the compounds of this invention when such compounds are administered to a patient ( e . g ., by allowing orally administered compound to be more readily absorbed into blood ) or which enhance delivery of the parent compound to a biological compartment ( e . g ., the brain or lymphatic system ). pharmaceutically acceptable prodrugs of the compounds described herein include , but are not limited to , esters , carbonates , thiocarbonates , n - acyl derivatives , n - acyloxyalkyl derivatives , quaternary derivatives of tertiary amines , n - mannich bases , schiff bases , amino acid conjugates , phosphate esters , metal salts and sulfonate esters . various forms of prodrugs are well known in the art . see for example design of prodrugs , bundgaard , a . ed ., elseview , 1985 and method in enzymology , widder , k . et al ., ed . ; academic , 1985 , vol . 42 , p . 309 - 396 ; bundgaard , h . “ design and application of prodrugs ” in a textbook of drug design and development , krosgaard - larsen and h . bundgaard , ed ., 1991 , chapter 5 , p . 113 - 191 ; and bundgaard , h ., advanced drug delivery review , 1992 , 8 , 1 - 38 , each of which is incorporated herein by reference . the prodrugs described herein include , but are not limited to , the following groups and combinations of these groups ; amine derived prodrugs : hydroxy prodrugs include , but are not limited to acyloxyalkyl esters , alkoxycarbonyloxyalkyl esters , alkyl esters , aryl esters and disulfide containing esters . the terms “ enhance ” or “ enhancing ,” as used herein , means to increase or prolong either in potency or duration of a desired effect . thus , in regard to enhancing the effect of therapeutic agents , the term “ enhancing ” refers to the ability to increase or prolong , either in potency or duration , the effect of other therapeutic agents on a system . an “ enhancing - effective amount ,” as used herein , refers to an amount adequate to enhance the effect of another therapeutic agent in a desired system . the terms “ pharmaceutical combination ”, “ administering an additional therapy ”, “ administering an additional therapeutic agent ” and the like , as used herein , refer to a pharmaceutical therapy resulting from mixing or combining more than one active ingredient and includes both fixed and non - fixed combinations of the active ingredients . the term “ fixed combination ” means that at least one of the compounds described herein , and at least one co - agent , are both administered to a patient simultaneously in the form of a single entity or dosage . the term “ non - fixed combination ” means that at least one of the compounds described herein , and at least one co - agent , are administered to a patient as separate entities either simultaneously , concurrently or sequentially with variable intervening time limits , wherein such administration provides effective levels of the two or more compounds in the body of the patient . these also apply to cocktail therapies , e . g . the administration of three or more active ingredients . the terms “ co - administration ”, “ administered in combination with ” and their grammatical equivalents or the like , as used herein , are meant to encompass administration of the selected therapeutic agents to a single patient , and are intended to include treatment regimens in which the agents are administered by the same or different route of administration or at the same or different times . in some embodiments the compounds described herein will be co - administered with other agents . these terms encompass administration of two or more agents to an animal so that both agents and / or their metabolites are present in the animal at the same time . they include simultaneous administration in separate compositions , administration at different times in separate compositions , and / or administration in a composition in which both agents are present . thus , in some embodiments , the compounds of the invention and the other agent ( s ) are administered in a single composition . the term “ metabolite ,” as used herein , refers to a derivative of a compound which is formed when the compound is metabolized . the term “ active metabolite ,” as used herein , refers to a biologically active derivative of a compound that is formed when the compound is metabolized . the term “ metabolized ,” as used herein , refers to the sum of the processes ( including , but not limited to , hydrolysis reactions and reactions catalyzed by enzymes ) by which a particular substance is changed by an organism . thus , enzymes may produce specific structural alterations to a compound . for example , cytochrome p450 catalyzes a variety of oxidative and reductive reactions while uridine diphosphate glucuronyltransferases catalyze the transfer of an activated glucuronic - acid molecule to aromatic alcohols , aliphatic alcohols , carboxylic acids , amines and free sulfhydryl groups . further information on metabolism may be obtained from the pharmacological basis of therapeutics , 9th edition , mcgraw - hill ( 1996 ). scheme 1 above illustrates the preparation of pyridone hydroxamate derivatives of ( 7 ). alkylation of diethylacetone 1 , 3dicarboxylate afford intermediate ( 2 ). condensation with iminoaniline derivatives ( 3 ) affords the pyridone ( 4 ). the iminoaniline derivatives ( 3 ) can be prepared in two steps from anilines by coupling to form the urea followed by reaction with carbon tetrabromide and triphenylphosphine to afford intermediates ( 3 ) [ scheme 2 ]. o - alkylation of ( 4 ) affords compound ( 5 ) which upon treatment with an amine affords the desired compounds ( 7 ). scheme 3 illustrates the preparation of the dihydrofuro pyridinone derivatives represented by ( 13 ). alkylation of dimethylacetone 1 , 3dicarboxylate ( 8 ) with 2 - halo carboxaldehydes ( 9 ) affords intermediate ( 10 ). subsequent condensation with iminoaniline derivatives ( 3 ) generates the bicyclic dihydro pyridinone ( 11 ). hydrolysis of the ester yields ( 12 ) which upon coupling with an amine affords the requisite analogs ( 13 ). to n , n ′- carbonyldiimidazole ( 51 . 3 g , 316 mmol ) in dry dmf ( 52 ml ) was added tea ( 3 . 55 ml , 25 . 5 mmol ) after addition of a solution of 2 - fluoro - 4 - iodoaniline ( 50 . 0 g , 211 mmol ) in dry dmf ( 52 ml ) at 0 ° c . under a n 2 atmosphere . the reaction mixture was stirred at room temperature for 16 h followed by the addition of a solution of 40 % methylamine ( 24 . 5 g , 316 mmol ) at 0 ° c . after stirring for 1 h at room temperature , the reaction mixture was added to water / toluene ( v / v = 2 / 1 ) while stirring . the resulting solid was collected by filtration , rinsed with water and dried in vacuo to give 1 -( 2 - fluoro - 4 - iodophenyl )- 3 - methylurea ( 57 . 6 g , 93 %) as a white solid , which was used for the next reaction without further purification . 1 h nmr ( dmso - d 6 , varian 400 mhz ) δ 2 . 64 ( 3h , d , j = 2 . 4 hz ), 6 . 45 - 6 . 49 ( 1h , m ), 7 . 40 - 7 . 42 ( 1h , m ), 7 . 55 ( 1h , dd , j = 5 . 4 , 2 . 0 hz ), 7 . 95 ( 1h , t , j = 8 . 8 hz ), 8 . 36 ( 1h , brs ). to a solution of 1 -( 2 - fluoro - 4 - iodophenyl )- 3 - methylurea ( 15 . 0 g , 51 . 0 mmol ) and tea ( 28 . 3 ml , 204 mmol ) in dcm ( 250 ml ) was added cbr 4 ( 33 . 8 g , 102 mmol ) and pph 3 ( 26 . 8 g , 102 mmol ) at room temperature . the reaction mixture was stirred at room temperature for 4 h . the solvent was removed by reduce pressure and the residue purified by flash column chromatography on sio 2 ( hex : etoac = 20 : 1 to 5 : 1 ) to give 2 - fluoro - 4 - iodo - n -(( methylimino ) methylene ) aniline ( 9 . 00 g , 64 %) as a red oil . 1 h nmr ( cdcl 3 , varian 400 mhz ) δ 3 . 17 ( 3h , s ), 6 . 78 ( 1h , t , j = 8 . 4 hz ), 7 . 33 - 7 . 36 ( 1h , m ), 7 . 38 - 7 . 41 ( 1h , m ). to a solution of 2 -( vinyloxy ) ethanol ( 20 . 4 ml , 227 mmol ), triphenylphosphine ( 59 . 5 g , 227 mmol ), and n - hydroxyphthalimide ( 37 . 0 g , 227 mmol ) in thf ( 450 ml ) was added dead ( 35 . 9 ml , 227 mmol ) at 0 ° c . under a n 2 atmosphere . after stirring for 16 h at room temperature , the reaction mixture was concentrated in vacuo . the residue was filtered , washed with chloroform and the filtrate was concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 2 : 1 ) to give 2 -( 2 -( vinyloxy ) ethoxy ) isoindoline - 1 , 3 - dione ( 32 . 5 g , 61 . 4 %) as a yellow solid . 1 h nmr ( cdcl 3 , varian 400 mhz ) δ 4 . 04 - 4 . 08 ( 3h , m ), 4 . 19 ( 1h , dd , j = 14 . 4 , 2 . 2 hz ), 4 . 45 - 4 . 48 ( 2h , m ), 6 . 47 ( 1h , dd , j = 14 . 0 , 6 . 8 hz ), 7 . 53 - 7 . 78 ( 2h , m ), 7 . 80 - 7 . 87 ( 2 m , m ). to a solution of 2 -( 2 -( vinyloxy ) ethoxy ) isoindoline - 1 , 3 - dione ( 32 . 0 g , 137 mmol ) in dcm ( 96 . 0 ml ) was added dropwise an aqueous solution of methylhydrazine ( 15 . 8 ml , 137 mmol ) at room temperature . after being stirred for 1 h at room temperature , the resultant suspension was diluted with diethyl ether and filtered . the filtrate was concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 3 : 2 to 1 : 1 ) to give o -( 2 -( vinyloxy ) ethyl )- hydroxylamine ( 10 . 7 g , 76 %) as a yellow oil . 1 h nmr ( cdcl 3 , varian 400 mhz ) δ 3 . 85 - 3 . 93 ( 4h , m ), 4 . 03 ( 1h , dd , j = 6 . 8 , 2 . 0 hz ), 4 . 22 ( 1h , dd , j = 14 . 2 , 2 . 0 hz ), 5 . 51 ( 2h , brs ), 6 . 50 ( 1h , dd , j = 14 . 2 , 6 . 8 hz ). to a solution of dimethyl 3 - oxopentanedioate ( 55 . 0 g , 316 mmol ) in pyridine ( 113 ml ) was added 2 - chloropropanal ( 91 . 0 g , 524 mmol ) dropwise at 0 ° c . the reaction mixture was stirred at 50 ° c . for 24 h . the residue was diluted with etoac and washed with water and brine , dried over mgso 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 to give methyl 2 -( 2 - methoxy - 2 - oxoethyl ) furan - 3 - carboxylate ( 45 . 0 g , 72 %) as a yellow oil . 1 h - nmr ( cdcl 3 , varian , 400 mhz ) δ 3 . 73 ( 3h , s ), 3 . 83 ( 3h , s ), 4 . 09 ( 2h , s ), 6 . 70 ( 1h , d , j = 2 . 0 hz ), 7 . 34 ( 1h , d , j = 2 . 0 hz ). to a solution of methyl 2 -( 2 - methoxy - 2 - oxoethyl ) furan - 3 - carboxylate ( 9 . 94 g , 50 . 1 mmol ) in dry thf ( 200 ml ) was added nah ( 55 wt % dispersion in mineral oil , 2 . 29 g , 52 . 6 mmol ) at 0 ° c . the reaction mixture was stirred at room temperature for 30 min , and then 2 - fluoro - 4 - iodo - n -(( methylimino ) methylene ) aniline ( intermediate 1 , 13 . 8 g , 50 . 1 mmol ) was added slowly with a dropping funnel . the reaction mixture was stirred at room temperature for 3 h . the reaction mixture was quenched with water and extracted with etoac and brine ( 50 ml ), dried over na 2 so 4 , filtered and concentrated in vacuo . the residual solid was suspended in water , collected by filtration , rinsed with water and dried in vacuo to give methyl 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylate ( 11 . 8 g , 53 %) as a yellow solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 3 . 35 ( 3h , s ), 3 . 96 ( 3h , s ), 6 . 45 ( 1h , t , j = 8 . 4 hz ), 6 . 96 ( 2h , d , j = 1 . 2 hz ), 7 . 36 - 7 . 38 ( 1h , d , j = 4 . 2 hz ), 7 . 48 - 7 . 51 ( 1h , m ), 7 . 53 ( 1h , d , j = 1 . 0 hz ), 9 . 85 ( 1h , s ). a solution of the 3 - chlorobut - 1 - ene ( 1 . 11 ml , 11 . 0 mmol ) in dcm ( 12 . 0 ml ) was cooled to − 60 ° c . a mixture of o 3 / o 2 was then bubbled through the solution for 20 min . the solution was purged with nitrogen , warmed to room temperature , treated with triphenylphosphine ( 3 . 48 g , 13 . 2 mmol ) and stirred vigorously for 30 min . the mixture was used for the next reaction without further purification . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 1 . 61 ( 3h , d , j = 7 . 2 hz ), 4 . 28 ( 1h , qd , j = 1 . 0 , 0 . 8 , 0 . 8 , 0 . 8 hz ), 9 . 53 ( 1h , m ). to a cooled ( 0 ° c .) and stirred solution of prop - 2 - yn - 1 - ol ( 5 . 19 ml , 89 . 0 mmol ) and pyridine ( 14 . 4 ml , 178 mmol ) in diethyl ether ( 90 . 0 ml ) was added methyl chloroformate ( 6 . 91 ml , 89 . 0 mmol ) dropwise over 10 min . the mixture was stirred at room temperature for 15 hours and then dilute hydrochloric acid was added . after extraction with ether , the organic layer was washed with brine and dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 3 : 1 ) to give methyl prop - 2 - ynyl carbonate ( 5 . 27 g , 52 %) as a colorless liquid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 2 . 53 ( 1h , t , j = 2 . 2 hz ), 3 . 82 ( 3h , s ), 4 . 74 ( 2h , d , j = 2 . 8 hz ). to n , n ′- carbonyldiimidazole ( 480 mg , 2 . 96 mmol ) in dry dmf ( 0 . 7 ml ) was added tea ( 0 . 33 ml , 2 . 38 mmol ) after addition of a solution of 2 - chloro - 4 - iodoaniline ( 500 mg , 1 . 97 mmol ) in dry dmf ( 0 . 7 ml ) at 0 ° c . under a n 2 atmosphere . the reaction mixture was stirred at room temperature for 16 hour followed by the addition of a solution of 40 % methylamine ( 230 mg , 2 . 96 mmol ) at 0 ° c . after stiffing for 1 hour at room temperature , the reaction mixture was added to water / toluene ( v / v = 2 / 1 ) while stiffing . the resulting solid was collected by filtration , rinsed with water and dried in vacuo to give 1 -( 2 - chloro - 4 - iodophenyl )- 3 - methylurea ( 530 mg , 87 %) as a yellow solid , which was used for the next reaction without further purification . 1 h nmr ( dmso - d 6 , varian 400 mhz ) δ 2 . 64 ( 3h , d , j = 4 . 8 hz ), 6 . 90 - 6 . 93 ( 1h , m ), 7 . 54 - 7 . 57 ( 1h , m ), 7 . 73 ( 1h , d , j = 1 . 6 hz ), 7 . 97 ( 1h , d , j = 8 . 8 hz ), 8 . 07 ( 1h , s ). to a solution of 1 -( 2 - chloro - 4 - iodophenyl )- 3 - methylurea ( 530 mg , 51 . 0 mmol ) and tea ( 0 . 95 ml , 6 . 83 mmol ) in dcm ( 9 ml ) was added cbr 4 ( 1 . 13 g , 3 . 41 mmol ) and pph 3 ( 0 . 89 g , 3 . 41 mmol ) at room temperature . the reaction mixture was stirred at room temperature for 4 hours . the solvent was removed by reduce pressure and the residue purified by flash column chromatography on sio 2 ( hex : etoac = 20 : 1 to 5 : 1 ) to give 2 - fluoro - 4 - iodo - n -(( methylimino ) methylene ) aniline ( 340 mg , 68 %) as a red oil . 1 h nmr ( cdcl 3 , varian 400 mhz ) δ 3 . 15 ( 3h , s ), 6 . 80 ( 1h , d , j = 8 . 4 hz ), 7 . 41 - 7 . 43 ( 1h , dd , j = 8 . 2 , 2 . 2 hz ), 7 . 63 - 7 . 68 ( 1h , m ). to a solution of dimethyl 3 - oxopentanedioate ( 55 . 0 g , 316 mmol ) in pyridine ( 113 ml ) was added 2 - chloropropanal ( 91 . 0 g , 524 mmol ) dropwise at 0 ° c . the reaction mixture was stirred at 50 ° c . for 24 hours . the residue was diluted with etoac and washed with water and brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 to give methyl 2 -( 2 - methoxy - 2 - oxoethyl ) furan - 3 - carboxylate ( 45 . 0 g , 72 %) as a yellow oil . 1 h - nmr ( cdcl 3 , varian , 400 mhz ) δ 3 . 73 ( 3h , s ), 3 . 83 ( 3h , s ), 4 . 09 ( 2h , s ), 6 . 70 ( 1h , d , j = 2 . 0 hz ), 7 . 34 ( 1h , d , j = 2 . 0 hz ). to a solution of methyl 2 -( 2 - methoxy - 2 - oxoethyl ) furan - 3 - carboxylate ( 305 mg , 1 . 53 mmol ) in dry thf ( 8 . 0 ml ) was added nah ( 55 wt % dispersion in mineral oil , 67 . 1 mg , 1 . 53 mmol ) at 0 ° c . the reaction mixture was stirred at room temperature for 30 min , and then 2 - chloro - 4 - iodo - n -(( methylimino ) methylene ) aniline ( intermediate 6 , 450 mg , 1 . 53 mmol ) was added slowly . the reaction mixture was stirred at room temperature for 2 hours . the reaction mixture was quenched with water and extracted with etoac and brine ( 50 ml ), dried over na 2 so 4 , filtered and concentrated in vacuo . the residual solid was suspended in water , collected by filtration , rinsed with water and dried in vacuo to give methyl 6 -( 2 - chloro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylate ( 320 mg , 45 %) as a yellow solid . 1 h - nmr ( dmso - d 6 , varian , 400 mhz ): δ 3 . 24 ( 3h , s ), 3 . 76 ( 3h , s ), 6 . 60 ( 1h , d , j = 8 . 4 hz ), 7 . 01 - 7 . 02 ( 1h , m ), 7 . 50 - 7 . 52 ( 1h , dd , j = 8 . 4 , 2 . 0 hz ), 7 . 87 ( 1h , m ), 7 . 94 ( 1h , m ), 9 . 25 ( 1h , s ). to 2 - hydroxyisoindoline - 1 , 3 - dione ( 300 mg , 1 . 84 mmol ) and ( bromomethyl ) cyclopropane ( 0 . 180 ml , 1 . 84 mmol ) in dmf ( 1 . 00 ml ) was added et 3 n ( 0 . 306 ml , 2 . 21 mmol ) dropwise at room temperature . the mixture was stirred at 65 ° c . for 15 hours . and then the reaction mixture was cooled and precipitate was filtered and washed with water . the solid obtained was dried in vacuo to give 2 -( cyclopropylmethoxy ) isoindoline - 1 , 3 - dione ( 193 mg , 48 %) as a light brown solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 0 . 38 ( 2h , m ), 0 . 63 ( 2h , m ), 1 . 29 ( 1h , m ), 4 . 05 ( 2h , d , j = 7 . 2 hz ), 7 . 75 ( 2h , m ), 7 . 85 ( 2h , m ). to a solution of 2 -( cyclopropylmethoxy ) isoindoline - 1 , 3 - dione ( 1 . 07 g , 4 . 93 mmol ) in dcm ( 6 . 00 ml ) at room temperature was added n - methylhydrazine sulfate ( 0 . 710 g , 4 . 93 mmol ). and the mixture was stirred at room temperature for 1 hour . the reaction mixture was diluted with diethyl ether and filtered . the filtrate was concentrated in vacuo . the residue was suspended in etoac and filtered again . 4m hcl in 1 , 4 - dioxane ( 1 . 35 ml , 5 . 42 mmol ) was added to the filtrate and the resulting precipitate was collected by filtration and dried under vacuum to give o -( cyclopropylmethyl ) hydroxylamine hydrochloride ( 55 . 9 mg , 9 . 2 %) as a yellow solid . 1 h - nmr ( dmso - d 6 , varian , 400 mhz ): δ 0 . 29 ( 2h , m ), 0 . 57 ( 2h , m ), 1 . 06 ( 1h , m ), 3 . 79 ( 2h , d , j = 7 . 2 hz ), 10 . 69 ( 2h , br ). to a solution of tert - butyl hydroxycarbamate ( 300 mg , 2 . 25 mmol ) in etoh ( 17 . 0 ml ) was added koh ( 152 mg , 2 . 70 mmol ) and stirred at room temperature till the koh dissolved into solution . to this was added 2 - bromoisobutyricacid ethyl ester ( 0 . 397 ml , 2 . 70 mmol ) and refluxed 15 hours . the white solid was discarded and the filterate was concentrated . the residue was partitioned between water and etoac . the combined etoac layer was dried with na 2 so 4 , filtered and filtrate was concentrated to give ethyl 2 -( tert - butoxycarbonylaminooxy )- 2 - methylpropanoate ( 410 mg , 74 %) as a colorless oil . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 1 . 29 ( 3h , t , j = 1 . 3 hz ), 1 . 47 ( 9h , s ), 1 . 49 ( 6h , s ), 4 . 20 ( 2h , q , j = 7 . 1 hz ), 7 . 37 ( 1h , s ). to a solution of ethyl 2 -( tert - butoxycarbonylaminooxy )- 2 - methylpropanoate ( 410 mg , 1 . 66 mmol ) in anhydrous thf ( 4 . 20 ml ) at 0 ° c . under n 2 was added lialh 4 ( 83 . 0 mg , 2 . 19 mmol ) slowly and stirred for 1 hour . to this was added h 2 o ( 1 . 00 ml ), after aq . naoh ( 1 . 00 ml ), h 2 o ( 3 . 00 ml ) and the mixture was stirred for 30 min at room temperature . then filtered washed with etoac , the filtrate was extracted with etoac for 3 times , the combined organic extracts were dried , filtered and concentrated in vacuo to give tert - butyl 1 - hydroxy - 2 - methylpropan - 2 - yloxycarbamate ( 310 mg , 91 %) as a white solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 1 . 14 ( 6h , s ), 1 . 42 ( 9h , s ), 3 . 33 ( 2h , d , j = 7 . 2 hz ), 4 . 41 ( 1h , br ). * nh peak was not observed . to a solution of tert - butyl 1 - hydroxy - 2 - methylpropan - 2 - yloxycarbamate ( 310 mg , 1 . 51 mmol ) in dcm ( 1 . 60 ml ) was added 4 m hcl in 1 , 4 - dioxane ( 2 . 79 ml , 11 . 2 mmol ) at room temperature and stirred for 1 h . the reaction was concentrated under reduced pressure and the residue was filtered with diethyl ether , and solid was concentrated in vacuum to give 2 -( aminooxy )- 2 - methylpropan - 1 - ol hydrochloride ( 236 mg , 110 %) as a colorless oil . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 1 . 24 ( 6h , s ), 3 . 48 ( 2h , s ), 10 . 66 ( 3h , s ). * oh peak was not observed . to a solution of ( r )-( 2 , 2 - dimethyl - 1 , 3 - dioxolan - 4 - yl ) methanol ( 1 . 00 g , 7 . 57 mmol ), triphenylphosphine ( 1 . 99 g , 7 . 57 mmol ), and n - hydroxyphthalimide ( 1 . 23 g , 7 . 57 mmol ) in thf ( 5 . 2 ml ) was added dead ( 2 . 64 ml , 15 . 1 mmol ) at 0 ° c . under a n 2 atmosphere . after stiffing for 16 h at room temperature , the reaction mixture was concentrated in vacuo . the residue was filtered , washed with chloroform and the filtrate was concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 9 : 1 ˜ 1 : 1 ) to give ( r )- 2 -(( 2 , 2 - dimethyl - 1 , 3 - dioxolan - 4 - yl ) methoxy ) isoindoline - 1 , 3 - dione ( 1 . 44 g , 68 . 6 %) as a white solid . 1 h nmr ( cdcl 3 , varian 400 mhz ) δ 1 . 35 ( 3h , s ), 1 . 41 ( 3h , s ), 3 . 98 ( 1h , dd , j = 8 . 8 , 5 . 2 hz ), 4 . 12 - 4 . 20 ( 2h , m ), 4 . 32 ( 1h , dd , j = 10 . 2 , 5 . 8 hz ), 4 . 47 - 4 . 53 ( 1h , m ), 7 . 74 - 7 . 79 ( 2h , m ), 7 . 83 - 7 . 86 ( 2h , m ). to a solution of ( r )- 2 -(( 2 , 2 - dimethyl - 1 , 3 - dioxolan - 4 - yl ) methoxy ) isoindoline - 1 , 3 - dione ( 1 . 44 g , 5 . 19 mmol ) in dcm ( 10 . 4 ml ) was added hydrazine hydrate ( 0 . 26 g , 5 . 19 mmol ) at room temperature . the reaction mixture was stirred at room temperature for 30 min . the solvent was removed by reduce pressure . the resultant suspension was diluted with diethyl ether and filtered to remove insoluble solid . the filtrate was concentrated in vacuo to give ( r )— o -(( 2 , 2 - dimethyl - 1 , 3 - dioxolan - 4 - yl ) methyl ) hydroxylamine ( 700 mg , 92 %) as a yellow oil . 1 h nmr ( cdcl 3 , varian 400 mhz ) δ 1 . 37 ( 3h , s ), 1 . 44 ( 3h , s ), 3 . 68 - 3 . 79 ( 3h , m ), 4 . 05 - 4 . 09 ( 1h , m ), 4 . 32 - 4 . 38 ( 1h , m ), 5 . 56 ( 2h , brs ). to a solution of methyl 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylate ( intermediate 3 , 7 . 00 g , 15 . 8 mmol ) in meoh ( 500 ml ) was added k 2 co 3 ( 8 . 75 g , 63 . 3 mmol ) at room temperature followed by the addition of water ( 500 ml ) via dropping funnel . the reaction mixture was stirred at 70 ° c . for 3 h . the reaction mixture was quenched with water and then acidified with 10 % aq . hcl until ph 1 ˜ 2 . the resulting solid was collected by filtration , rinsed with water and dried in vacuo to give 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylic acid ( 5 . 48 g , 81 %) as a yellow solid , which was used for the next reaction without further purification . 1 h - nmr ( dmso - d 6 , varian , 400 mhz ) δ 3 . 25 ( 3h , s ), 6 . 69 ( 1h , t , j = 8 . 8 hz ), 6 . 98 ( 1h , d , j = 1 . 2 hz ), 7 . 41 ( 1h , d , j = 4 . 2 hz ), 7 . 69 ( 1h , dd , j = 10 . 6 , 1 . 0 hz ), 7 . 90 ( 1h , d , j = 1 . 0 hz ), 9 . 66 ( 1h , s ), 13 . 2 ( 1h , s ). to a solution of 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylic acid ( 4 . 00 g , 9 . 34 mmol ) in dmf ( 110 ml ) was added o -( 2 -( vinyloxy ) ethyl ) hydroxylamine ( intermediate 2 , 1 . 15 g , 11 . 2 mmol ) at room temperature and then was cooled to 0 ° c . to the reaction mixture was added edc ( 2 . 14 g , 11 . 2 mmol ), hobt ( 1 . 71 g , 11 . 2 mmol ), and tea ( 1 . 56 ml , 11 . 2 mmol ). the mixture was stirred at room temperature for 3 h . the reaction was extracted with etoac , washed with water and brine , dried over na 2 so 4 , filtered and concentrated in vacuo to give 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 2 . 43 g , 50 %) as a white solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 3 . 32 ( 3h , s ), 3 . 99 - 4 . 01 ( 2h , m ), 4 . 07 - 4 . 27 ( 2h , m ), 4 . 29 - 4 . 31 ( 2h , m ), 6 . 48 - 6 . 55 ( 2h , m ), 7 . 01 ( 1h , d , j = 1 . 2 hz ), 7 . 37 ( 1h , d , j = 4 . 2 hz ), 7 . 47 ( 1h , dd , j = 5 . 0 , 1 . 0 hz ), 7 . 50 ( 1h , d , j = 1 . 2 hz ), 10 . 0 ( 1h , s ), 10 . 9 ( 1h , s ). to a solution of 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 1 . 57 g , 3 . 06 mmol ) in meoh ( 15 ml ) was added 2n aq . hcl at room temperature . the mixture was stirred at room temperature for 30 min . the residue was diluted with dcm and washed with water and brine , dried over na 2 so 4 , filtered and concentrated in vacuo to give 6 -( 2 - fluoro - 4 - iodophenylamino )- n -( 2 - hydroxyethoxy )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 1 . 35 g , 91 %) as a white solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ) δ 3 . 30 ( 3h , s ), 3 . 75 - 3 . 78 ( 2h , m ), 4 . 05 ( 1h , t , j = 6 . 4 hz ), 4 . 09 - 4 . 11 ( 2h , m ), 6 . 55 ( 1h , t , j = 8 . 4 hz ), 7 . 01 ( 1h , d , j = 0 . 8 hz ), 7 . 38 - 7 . 40 ( 1h , m ), 7 . 49 ( 1h , dd , j = 4 . 8 , 1 . 0 hz ), 7 . 52 ( 1h , d , j = 1 . 0 hz ), 9 . 86 ( 1h , s ), 10 . 8 ( 1h , s ). m / z = 487 . 8 [ m + h ] + to a solution of diethyl 3 - oxopentanedioate ( 20 . 0 g , 99 . 0 mmol ) in dry thf ( 198 ml ) was added nah ( 55 %, 4 . 53 g , 104 mmol ) at 0 ° c . the mixture was stirred for 30 minutes at 0 ° c . after dropwise addition of mei ( 14 . 0 g , 99 . 0 mmol ) at 0 ° c ., the reaction mixture was stirred at room temperature for 2 days , and then quenched saturated aq . nh 4 cl ( 200 ml ). the mixture was extracted with etoac ( 3 × 50 ml ). the combined organic layers were washed water ( 300 ml ) and brine ( 300 ml ), dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 9 : 1 ) to afford diethyl 2 - methyl - 3 - oxopentanedioate ( 11 . 1 g , 52 %) as a colorless oil . 1 h nmr ( cdcl 3 , varian 400 mhz ) δ 1 . 28 ( 6h , t , j = 7 . 2 hz ), 1 . 38 ( 3h , d , j = 7 . 2 hz ), 3 . 57 ( 1h , d , j = 16 . 0 hz ), 3 . 66 ( 1h , d , j = 16 . 0 hz ), 3 . 72 ( 1h , q , j = 7 . 2 hz ), 4 . 16 - 4 . 24 ( 4h , m ). to a solution of diethyl 2 - methyl - 3 - oxopentanedioate ( 9 . 56 g , 44 . 2 mmol ) in dry thf ( 88 ml ) was added nah ( 55 %, 2 . 02 g , 46 . 4 mmol ) at 0 ° c . the mixture was stirred for 30 minutes at 0 ° c . after dropwise addition of 2 - fluoro - 4 - iodo - n -(( methylimino ) methylene ) aniline ( intermediate 1 , 12 . 2 g , 44 . 2 mmol ) at 0 ° c ., the reaction mixture was stirred at room temperature overnight , and then quenched with saturated 1n aq . hcl ( 60 ml ). the mixture was extracted with etoac ( 3 × 30 ml ). the combined organic layers were washed water ( 100 ml ) and brine ( 100 ml ), dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 7 : 3 to 1 : 1 ) to afford ethyl 2 -( 2 - fluoro - 4 - iodophenylamino )- 4 - hydroxy - 1 , 5 - dimethyl - 6 - oxo - 1 , 6 - dihydropyridine - 3 - carboxylate ( 2 . 98 g , 15 %) as a yellow oil . 1 h nmr ( cdcl 3 , varian 400 mhz ) δ 1 . 36 ( 3h , t , j = 7 . 2 hz ), 2 . 05 ( 3h , s ), 3 . 35 ( 3h , s ), 4 . 40 ( 2h , q , j = 7 . 2 hz ), 6 . 33 ( 1h , t , j = 8 . 4 hz ), 7 . 36 ( 1h , d , j = 8 . 4 hz ), 7 . 50 ( 1h , dd , j = 10 . 0 , 2 . 0 hz ), 8 . 28 ( 1h , brs ), 11 . 20 ( 1 m , brs ). a mixture of ethyl 2 -( 2 - fluoro - 4 - iodophenylamino )- 4 - hydroxy - 1 , 5 - dimethyl - 6 - oxo - 1 , 6 - dihydropyridine - 3 - carboxylate ( 2 . 78 g , 6 . 23 mmol ), dimethyl sulfate ( 0 . 60 ml , 6 . 23 mmol ) and k 2 co 3 ( 1 . 72 , 12 . 5 mmol ) in acetone ( 31 ml ) was refluxed for 1 hour , cooled to room temperature , and then partitioned between etoac and water . the separated aqueous layer was extracted with etoac . the combined organic layers were washed with brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 3 : 2 ) to afford ethyl 2 -( 2 - fluoro - 4 - iodophenylamino )- 4 - methoxy - 1 , 5 - dimethyl - 6 - oxo - 1 , 6 - dihydropyridine - 3 - carboxylate ( 1 . 04 g , 36 %) as a yellow oil . 1 h nmr ( cdcl 3 , varian 400 mhz ) δ 1 . 35 ( 3h , t , j = 7 . 2 hz ), 2 . 09 ( 3h , s ), 3 . 32 ( 3h , s ), 3 . 78 ( 3h , s ), 4 . 31 ( 2h , q , j = 7 . 2 hz ), 6 . 35 ( 1h , t , j = 8 . 4 hz ), 7 . 34 ( 1h , d , j = 8 . 4 hz ), 7 . 46 ( 1h , dd , j = 10 . 0 , 2 . 0 hz ), 8 . 88 ( 1h , brs ). to a mixture of ethyl 2 -( 2 - fluoro - 4 - iodophenylamino )- 4 - methoxy - 1 , 5 - dimethyl - 6 - oxo - 1 , 6 - dihydropyridine - 3 - carboxylate ( 1 . 29 g , 2 . 80 mmol ) and o -( 2 -( vinyloxy ) ethyl ) hydroxylamine ( intermediate 2 , 433 mg , 4 . 20 mmol ) in dry thf ( 14 ml ) was added lihmds ( 16 . 8 ml , 16 . 8 mmol , 1 . 0 m solution in hexane ) at 0 ° c . the reaction mixture was stirred for 2 hours at room temperature , and then quenched with saturated 1n aq . hcl ( 50 ml ). the mixture was extracted with etoac ( 3 × 20 ml ). the combined organic layers were washed with water ( 50 ml ) and brine ( 50 ml ), dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 1 : 1 to 1 : 2 ) to afford 2 -( 2 - fluoro - 4 - iodophenylamino )- 4 - methoxy - 1 , 5 - dimethyl - 6 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 1 , 6 - dihydropyridine - 3 - carboxamide ( 850 mg , 54 %) as a yellow solid . 1 h nmr ( cdcl 3 , varian 400 mhz ) δ 2 . 08 ( 3h , s ), 3 . 27 ( 3h , s ), 3 . 79 ( 3h , s ), 3 . 94 - 3 . 96 ( 2h , m ), 4 . 06 ( 1h , dd , j = 6 . 8 , 2 . 4 hz ), 4 . 19 - 4 . 26 ( 3h , m ), 6 . 41 ( 1h , t , j = 8 . 4 hz ), 6 . 50 ( 1h , dd , j = 14 . 6 , 6 . 8 hz ), 7 . 34 ( 1h , d , j = 8 . 4 hz ), 7 . 45 ( 1h , dd , j = 10 . 0 , 2 . 0 hz ), 10 . 18 ( 1h , brs ), 10 . 52 ( 1h , brs ). m / z = 517 . 9 [ m + h ] + to a solution of 2 -( 2 - fluoro - 4 - iodophenylamino )- 4 - methoxy - 1 , 5 - dimethyl - 6 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 1 , 6 - dihydropyridine - 3 - carboxamide ( 400 mg , 0 . 773 mmol ) in meoh ( 8 . 0 ml ) was added 2m aq . hcl ( 2 . 3 ml , 4 . 64 mmol ) at room temperature . the reaction mixture was stirred for 15 minutes at room temperature , and then concentrated in vacuo . the residue was dissolved in dcm , neutralized with saturated aq . nahco 3 at 0 ° c . the separated aqueous layer was extracted with dcm . the combined organic layers were washed with brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residual solid was suspended in et 2 o , collected by filtration , and washed with et 2 o to afford 2 -( 2 - fluoro - 4 - iodophenylamino )- n -( 2 - hydroxyethoxy )- 4 - methoxy - 1 , 5 - dimethyl - 6 - oxo - 1 , 6 - dihydropyridine - 3 - carboxamide ( 357 mg , 94 %) as a yellow solid . 1 h nmr ( dmso - d 6 , varian 400 mhz ) δ 1 . 95 ( 3h , s ), 3 . 25 ( 3h , s ), 3 . 40 - 3 . 46 ( 2h , m ), 3 . 59 - 3 . 61 ( 2h , m ), 3 . 73 ( 3h , s ), 4 . 64 ( 1h , brs ), 6 . 40 ( 1h , t , j = 8 . 8 hz ), 7 . 31 ( 1h , dd , j = 8 . 4 , 1 . 2 hz ), 7 . 45 ( 1h , dd , j = 10 . 0 , 2 . 0 hz ), 8 . 25 ( 1h , brs ), 11 . 13 ( 1h , brs ). m / z = 491 . 9 [ m + h ] + to a solution of dimethyl 3 - oxopentanedioate ( 1 . 30 ml , 8 . 83 mmol ) in pyridine ( 2 . 28 ml ) was added crude 2 - chloropropanal ( intermediate 4 , 817 mg , 8 . 83 mmol ) dropwise at 0 ° c . the reaction mixture was stirred at 40 ° c . for 15 hours . the residue was diluted with dcm and washed with water and brine , dried over mgso 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 5 : 1 ) to give methyl 5 - ethyl - 2 -( 2 - methoxy - 2 - oxoethyl ) furan - 3 - carboxylate ( 420 mg , 22 %) as a colorless liquid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 2 . 28 ( 3h , s ), 3 . 72 ( 3h , s ), 3 . 80 ( 3h , s ), 4 . 02 ( 2h , s ), 6 . 27 ( 1h , s ). to a solution of 2 - fluoro - 4 - iodo - n -(( methylimino ) methylene ) aniline ( intermediate 1 , 1 . 22 g , 5 . 75 mmol ) in dry thf ( 25 . 0 ml ) was added nah ( 55 wt % dispersion in mineral oil , 0 . 263 g , 6 . 04 mmol ) at 0 ° c . the reaction mixture was stirred at room temperature for 30 min , and then methyl 5 - ethyl - 2 -( 2 - methoxy - 2 - oxoethyl ) furan - 3 - carboxylate ( 1 . 59 g , 5 . 75 mmol ) was added slowly with dropping funnel . the reaction mixture was stirred at room temperature for 15 hours . the reaction mixture was quenched with water , extracted with etoac . the resulting solid was collected by filtration , rinsed with water and dried in vacuo to give methyl 6 -( 2 - fluoro - 4 - iodophenylamino )- 2 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylate ( 833 mg , 32 %) as a yellow solid , which was used for the next reaction without further purification . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 2 . 45 ( 3h , d , j = 1 . 2 hz ), 3 . 36 ( 3h , s ), 3 . 95 ( 3h , s ), 6 . 40 ( 1h , t , j = 8 . 4 hz ), 6 . 54 ( 1h , m ), 7 . 34 ( 1h , d , j = 8 . 4 hz ), 7 . 57 ( 1h , m ), 9 . 72 ( 1h , s ). to a solution of methyl 6 -( 2 - fluoro - 4 - iodophenylamino )- 2 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylate ( 273 mg , 0 . 599 mmol ) in meoh ( 18 . 0 ml ) was added k 2 co 3 ( 331 mg , 2 . 40 mmol ) at room temperature . and then water ( 18 . 0 ml ) was added slowly with dropping funnel . the reaction mixture was stirred at 70 ° c . for 1 hour . the reaction mixture was quenched with water and then concentrated in vacuo to give potassium 6 -( 2 - fluoro - 4 - iodophenylamino )- 2 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylate ( 554 mg , 192 %) as a white solid . lc - ms : calcd . 441 . 98 . found 442 . 72 [ m + h ] + . to a solution of potassium 6 -( 2 - fluoro - 4 - iodophenylamino )- 2 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylate ( 280 mg , 0 . 583 mmol ) in dmf ( 6 . 50 ml ) was added o -( 2 -( vinyloxy ) ethyl ) hydroxylamine ( intermediate 2 , 66 . 1 mg , 0 . 641 mmol ) at room temperature and then was cooled to 0 ° c . to a reaction mixture was added edci ( 168 mg , 0 . 875 mmol ), hobt ( 134 mg , 0 . 875 mmol ) and tea ( 0 . 143 ml , 1 . 02 mmol ). the mixture was stirred at 40 ° c . for 15 h . the residue was extracted with etoac and washed with water and brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 2 : 1 ) to give 6 -( 2 - fluoro - 4 - iodophenylamino )- 2 , 5 - dimethyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 42 . 3 mg , 14 %) as a brown solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 2 . 46 ( 3h , s ), 3 . 32 ( 3h , s ), 4 . 00 ( 2h , m ), 4 . 07 - 4 . 27 ( 2h , m ), 4 . 29 - 4 . 31 ( 2h , m ), 6 . 48 - 6 . 55 ( 2h , m ), 7 . 36 ( 1h , d , j = 12 . 8 hz ), 7 . 46 ( 1h , dd , j = 10 . 0 , 2 . 0 hz ), 7 . 70 ( 1h , d , j = 8 . 0 hz ), 10 . 0 ( 1h , s ), 10 . 8 ( 1h , s ). to a solution of 6 -( 2 - fluoro - 4 - iodophenylamino )- 2 , 5 - dimethyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 42 . 3 mg , 0 . 0800 mmol ) in meoh ( 0 . 400 ml ) was added 1 n aq . hcl ( 0 . 52 ml , 0 . 515 mmol ) at room temperature . the reaction mixture was stirred at room temperature for 10 min . the solvent was evaporated , diluted with dcm , and aq . nahco 3 was added until ph 7 at 0 ° c . dcm was evaporated and solidify with ether / hexane to give 6 -( 2 - fluoro - 4 - iodophenylamino )- n -( 2 - hydroxyethoxy )- 2 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 15 . 2 mg , 37 . 8 %) as a light brown solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 2 . 49 ( 3h , s ), 3 . 30 ( 3h , s ), 3 . 77 ( 2h , m ), 4 . 06 ( 1h , t , j = 6 . 4 hz ), 4 . 11 ( 2h , t , j = 4 . 4 hz ), 6 . 50 ( 1h , t , j = 8 . 6 hz ), 7 . 58 ( 1h , m ), 7 . 39 ( 1h , d , j = 4 . 0 hz ), 7 . 48 ( 1h , d , j = 9 . 8 , 1 . 8 hz ), 9 . 84 ( 1h , s ), 10 . 7 ( 1h , s ). m / z = 501 . 8 [ m + h ] + . a mixture of pd 2 ( dba ) 3 ( 0 . 239 g , 0 . 261 mmol ) and 1 , 2 - bis ( diphenylphosphino ) ethane ( 0 . 208 g , 0 . 521 mmol ) in thf ( 226 ml ) was added methyl prop - 2 - ynyl carbonate ( intermediate 5 , 5 . 94 g , 52 . 1 mmol ) and diethyl 3 - oxopentanedioate ( 10 . 5 g , 52 . 1 mmol ) at room temperature . the reaction mixture was heated to reflux overnight under nitrogen atmosphere . after being cooled to room temperature , the reaction mixture was filtered through a celite pad and washed with etoac . the filtrate was concentrated in vacuo , and the residue was purified by column chromatography on sio 2 ( hex : etoac = 4 : 1 ) to give ethyl 2 -( 2 - ethoxy - 2 - oxoethyl )- 4 - methylfuran - 3 - carboxylate ( 4 . 67 g , 37 %) as a yellow oil . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 1 . 26 ( 3h , t , j = 9 . 0 hz ), 1 . 34 ( 3h , t , j = 6 . 0 hz ), 2 . 16 ( 3h , s ), 4 . 01 ( 2h , s ), 4 . 18 ( 2h , q ), 4 . 28 ( 2h , q ), 7 . 12 ( 1h , s ). to a solution of ethyl 2 -( 2 - ethoxy - 2 - oxoethyl )- 4 - methylfuran - 3 - carboxylate ( 4 . 67 g , 19 . 4 mmol ) in dry thf ( 100 ml ) was added nah ( 55 wt % dispersion in mineral oil , 0 . 891 g , 20 . 4 mmol ) at 0 ° c . the reaction mixture was stirred at room temperature for 30 min , and then 2 - fluoro - 4 - iodo - n -(( methylimino ) methylene ) aniline ( intermediate 1 , 6 . 98 g , 25 . 3 mmol ) was added slowly . the reaction mixture was stirred at room temperature for 15 hours . the reaction mixture was quenched with water , extracted with etoac . the resulting solid was collected by filtration , rinsed with water and dried in vacuo to give ethyl 6 -( 2 - fluoro - 4 - iodophenylamino )- 3 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylate ( 1 . 22 g , 13 %) as a yellow solid , which was used for the next reaction without further purification . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 1 . 41 ( 3h , t , j = 7 . 2 hz ), 2 . 36 ( 3h , s ), 3 . 33 ( 3h , s ), 4 . 39 ( 2h , q ), 6 . 43 ( 1h , t , j = 8 . 4 hz ), 7 . 27 ( 1h , m ), 7 . 35 ( 1h , m ), 7 . 48 ( 1h , m ), 9 . 78 ( 1h , s ). to a solution of ethyl 6 -( 2 - fluoro - 4 - iodophenylamino )- 3 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylate ( 1 . 22 g , 2 . 59 mmol ) in thf ( 12 . 0 ml ) and meoh ( 12 . 0 ml ) was added k 2 co 3 ( 1 . 43 g , 10 . 4 mmol ) at room temperature . and then water ( 12 . 0 ml ) was added slowly with dropping funnel . the reaction mixture was stirred at 65 ° c . for 9 hours . the reaction mixture was quenched with water and then acidified with 1n aq . hcl until ph 1 ˜ 2 . the resulting solid was collected by filtration , rinsed with water and dried in vacuo to give 6 -( 2 - fluoro - 4 - iodophenylamino )- 3 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylic acid ( 860 mg , 75 %) as a white solid , which was used for the next reaction without further purification . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 2 . 21 ( 3h , s ), 3 . 19 ( 3h , s ), 6 . 64 ( 1h , t , j = 8 . 2 hz ), 7 . 37 ( 1h , m ), 7 . 60 ( 1h , m ), 7 . 65 ( 1h , m ), 9 . 59 ( 1h , s ). to a solution of 6 -( 2 - fluoro - 4 - iodophenylamino )- 3 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylic acid ( 680 mg , 1 . 54 mmol ) in dmf ( 35 . 0 ml ) was added o -( 2 -( vinyloxy ) ethyl ) hydroxylamine ( intermediate 2 , 190 mg , 1 . 85 mmol ) at room temperature and then was cooled to 0 ° c . to a reaction mixture was added edci ( 442 mg , 2 . 31 mmol ), hobt ( 353 mg , 2 . 31 mmol ) and tea ( 0 . 322 ml , 2 . 31 mmol ). the mixture was stirred at room temperature for 15 hours . the residue was extracted with etoac and washed with water and brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 2 : 1 ) to give 6 -( 2 - fluoro - 4 - iodophenylamino )- 3 , 5 - dimethyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 382 mg , 47 %) as a brown solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 2 . 37 ( 3h , s ), 3 . 30 ( 3h , s ), 4 . 00 ( 2h , m ), 4 . 09 ( 1h , m ), 4 . 22 ( 1h , m ), 4 . 29 ( 2h , m ), 6 . 49 ( 2h , m ), 7 . 27 ( 1h , m ), 7 . 37 ( 1h , m ), 7 . 47 ( 1h , m ), 10 . 0 ( 1h , s ), 10 . 9 ( 1h , s ). to a solution of 6 -( 2 - fluoro - 4 - iodophenylamino )- 3 , 5 - dimethyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 200 mg , 0 . 379 mmol ) in meoh ( 11 . 1 ml ) and thf ( 11 . 1 ml ) was added 1n aq . hcl ( 2 . 20 ml , 2 . 20 mmol ) at room temperature . the reaction mixture was stirred at room temperature for 10 min . the reaction mixture was added aq . nahco 3 until ph 7 at 0 ° c . the residue was extracted with etoac and washed with water and brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 1 : 1 ) to give 6 -( 2 - fluoro - 4 - iodophenylamino )- n -( 2 - hydroxyethoxy )- 3 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 84 . 1 mg , 44 %) as a light brown solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 2 . 26 ( 3h , s ), 3 . 34 ( 3h , s ), 3 . 48 ( 2h , t , j = 4 . 6 hz ), 3 . 65 ( 2h , t , j = 4 . 8 hz ), 6 . 53 ( 1h , t , j = 8 . 8 hz ), 7 . 33 ( 1h , m ), 7 . 58 ( 1h , dd , j = 10 . 8 , 1 . 6 hz ), 7 . 64 ( 1h , m ). * oh alcohol , nh amide , nh peak were not observed . m / z = 501 . 8 [ m + h ] + . a mixture of dimethyl 3 - oxopentanedioate ( 13 . 7 g , 79 . 0 mmol ), 1 , 4 - dithiane - 2 , 5 - diol ( 4 . 00 g , 26 . 3 mmol ), libr ( 685 mg , 7 . 88 mmol ) in 1 , 4 - dioxane ( 132 ml ) was refluxed overnight , cooled to room temperature . the insoluble solid was filtered and washed with et 2 o , and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 85 : 15 ) to give the methyl 2 -( 2 - methoxy - 2 - oxoethyl ) thiophene - 3 - carboxylate ( 5 . 07 g , 90 %) as a yellow oil . 1 h nmr ( cdcl 3 , varian 400 mhz ): δ 3 . 74 ( 3h , s ), 3 . 84 ( 3h , s ), 4 . 22 ( 2h , s ), 7 . 15 ( 1h , d , j = 5 . 2 hz ), 7 . 44 ( 1h , d , j = 5 . 2 hz ). to a solution of methyl 2 -( 2 - methoxy - 2 - oxoethyl ) thiophene - 3 - carboxylate ( 1 . 00 g , 4 . 67 mmol ) in dry thf ( 23 . 0 ml ) was added nah ( 55 %, 224 mg , 5 . 13 mmol ) at 0 ° c . the mixture was stirred for 30 minutes at 0 ° c . after dropwise addition of 2 - fluoro - 4 - iodo - n -(( methylimino ) methylene ) aniline ( intermediate 1 , 1 . 29 g , 4 . 67 mmol ) at 0 ° c ., the reaction mixture was stirred at room temperature for 30 min , and then quenched saturated aq . nh 4 cl ( 30 ml ). the mixture was extracted with etoac ( 2 × 20 ml ). the combined organic layers were washed water ( 50 ml ) and brine ( 50 ml ), dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 4 : 1 ) to give the methyl 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrothieno [ 3 , 2 - c ] pyridine - 7 - carboxylate ( 654 mg , 31 %) as a yellow solid . 1 h nmr ( cdcl 3 , varian 400 mhz ): δ 3 . 38 ( 3h , s ), 3 . 97 ( 3h , s ), 6 . 45 ( 1h , t , j = 8 . 4 hz ), 7 . 19 ( 1h , d , j = 5 . 2 hz ), 7 . 36 ( 1h , d , j = 8 . 4 hz ), 7 . 49 ( 1h , dd , j = 10 . 0 , 2 . 0 hz ), 7 . 61 ( 1h , d , j = 8 . 4 hz ), 9 . 70 ( 1h , brs ). a mixture of methyl 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrothieno [ 3 , 2 - c ] pyridine - 7 - carboxylate ( 1 . 36 g , 2 . 96 mmol ) and o -( 2 -( vinyloxy ) ethyl ) hydroxylamine ( intermediate 2 , 458 mg , 4 . 44 mmol ) in dry thf ( 20 ml ) was added lihmds ( 17 . 8 ml , 17 . 8 mmol , 1 . 0 m solution in hexane ) at 0 ° c . the reaction mixture was stirred for 1 hour at room temperature , and then quenched saturated 1n aq . hcl ( 50 ml ). the mixture was extracted with etoac ( 2 × 20 ml ). the combined organic layers were washed water ( 50 ml ) and brine ( 50 ml ), dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 3 : 7 ) to give the 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrothieno [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 575 mg , 37 %) as a yellow solid . 1 h nmr ( cdcl 3 , varian 400 mhz ): δ 3 . 41 ( 3h , s ), 3 . 94 - 3 . 97 ( 2h , m ), 4 . 07 ( 1h , dd , j = 6 . 8 , 2 . 4 hz ), 4 . 18 - 4 . 25 ( 3h , m ), 6 . 37 ( 1h , t , j = 8 . 4 hz ), 6 . 46 ( 1h , dd , j = 14 . 6 , 6 . 8 hz ), 7 . 28 ( 1h , d , j = 5 . 2 hz ), 7 . 32 ( 1h , d , j = 8 . 4 hz ), 7 . 47 ( 1h , dd , j = 10 . 0 , 2 . 0 hz ), 7 . 62 ( 1h , d , j = 5 . 2 hz ), 8 . 71 ( 1h , brs ), 9 . 21 ( 1h , brs ). to a solution of 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrothieno [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 300 mg , 0 . 567 mmol ) in meoh ( 6 . 0 ml ) was added 2n aq . hcl ( 1 . 7 ml , 3 . 40 mmol ) at room temperature , the reaction mixture was stirred for 30 minutes at room temperature , then concentrated in vacuo . the residue was dissolved in dcm , neutralized with saturated aq . nahco 3 at 0 ° c . the separated aqueous layer was extracted with dcm . the combined organic layers were washed with brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residual solid was suspended in meoh , collected by filtration , and washed with meoh to give the 6 -( 2 - fluoro - 4 - iodophenylamino )- n -( 2 - hydroxyethoxy )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrothieno [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 217 mg , 76 %) as a white solid . 1 h nmr ( dmso - d 6 , varian 400 mhz ): δ 3 . 43 ( 3h , s ), 3 . 40 - 3 . 47 ( 2h , m ), 3 . 57 - 3 . 64 ( 2h , m ), 4 . 67 ( 1h , brs ), 6 . 51 ( 1h , t , j = 8 . 8 hz ), 7 . 31 ( 1h , dd , j = 8 . 4 , 1 . 2 hz ), 7 . 49 ( 1h , d , j = 5 . 2 hz ), 7 . 57 ( 1h , dd , j = 10 . 8 , 2 . 0 hz ), 7 . 62 ( 1h , d , j = 5 . 2 hz ), 8 . 30 ( 1h , brs ), 11 . 30 ( 1h , brs ). m / z = 503 . 7 [ m + h ] + . to a solution of dimethyl 3 - oxopentanedioate ( 25 . 0 g , 144 mmol ) in acetic acid ( 50 ml ) was added a solution of nano 2 ( 10 . 4 g , 151 mmol ) in water ( 25 ml ) at 0 ° c . the reaction mixture was stirred overnight at room temperature . after evaporation of volatile solvents , the residue was partitioned between etoac ( 50 ml ) and water ( 50 ml ). the separated aqueous layer was extracted ( 2 × 30 ml ). the combined organic layers were washed water ( 100 ml ) and brine ( 100 ml ), dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 3 : 2 ) to give the dimethyl 2 -( hydroxyimino )- 3 - oxopentanedioate ( 15 . 3 g , 52 %) as a yellow oil . 1 h nmr ( cdcl 3 , varian 400 mhz ): δ 3 . 76 ( 3h , s ), 3 . 84 ( 2h , s ), 3 . 93 ( 3h , s ), 9 . 74 ( 1h , brs ). a mixture of dimethyl 2 -( hydroxyimino )- 3 - oxopentanedioate ( 15 . 3 g , 75 . 0 mmol ) and 10 % pd / c ( 1 . 50 g ) in acetic anhydride ( 377 ml ) was stirred at room temperature for 3 hours under hydrogen atmosphere ( balloon ). the reaction mixture was filtered through a celite pad , washed with etoac ( 200 ml ), and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 1 : 9 ) to give the dimethyl 2 - acetamido - 3 - oxopentanedioate ( 9 . 28 g , 53 %) as a yellow oil . 1 h nmr ( cdcl 3 , varian 400 mhz ): δ 2 . 09 ( 1h , s ), 3 . 75 ( 3h , s ), 3 . 76 ( 2h , s ), 3 . 83 ( 3h , s ), 5 . 42 ( 1h , d , j = 6 . 4 hz ), 6 . 64 ( 1h , brs ). to a solution of dimethyl 2 - acetamido - 3 - oxopentanedioate ( 9 . 28 g , 40 . 2 mmol ) in chloroform ( 200 ml ) was added socl 2 ( 8 . 79 ml , 120 mmol ) at 0 ° c . the mixture was refluxed for 6 hours , cooled to room temperature . after evaporation of volatile solvents , the residue was diluted with dcm ( 50 ml ), neutralized with saturated aq . nahco 3 at 0 ° c ., and extracted with dcm ( 2 × 30 ml ). the combined organic layers were washed water ( 100 ml ) and brine ( 100 ml ), dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 1 : 2 ) to give the methyl 5 -( 2 - methoxy - 2 - oxoethyl )- 2 - methyloxazole - 4 - carboxylate ( 4 . 06 g , 47 %) as a yellow solid . 1 h nmr ( cdcl 3 , varian 400 mhz ): δ 2 . 49 ( 3h , s ), 3 . 75 ( 3h , s ), 3 . 90 ( 3h , s ), 4 . 10 ( 2h , s ). to a solution of methyl 5 -( 2 - methoxy - 2 - oxoethyl )- 2 - methyloxazole - 4 - carboxylate ( 2 . 00 g , 4 . 67 mmol ) in dry thf ( 47 ml ) was added nah ( 55 %, 450 mg , 10 . 3 mmol ) at 0 ° c . the mixture was stirred for 30 minutes at 0 ° c . after dropwise addition of 2 - fluoro - 4 - iodo - n -(( methylimino ) methylene ) aniline ( intermediate 1 , 3 . 11 g , 11 . 3 mmol ) at 0 ° c ., the reaction mixture was stirred at 0 ° c . for 30 min , and then quenched saturated aq . nh 4 cl ( 50 ml ). the mixture was extracted with etoac ( 2 × 30 ml ). the combined organic layers were washed water ( 70 ml ) and brine ( 70 ml ), dried over na 2 so 4 , filtered and concentrated in vacuo . the residual was suspended in et 2 o , collected by filtration , and washed with et 2 o to give the methyl 6 -( 2 - fluoro - 4 - iodophenylamino )- 2 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrooxazolo [ 4 , 5 - c ] pyridine - 7 - carboxylate ( 1 . 85 g , 43 %) as a brown solid . 1 h nmr ( cdcl 3 , varian 400 mhz ): δ 2 . 64 ( 3h , s ), 3 . 36 ( 3h , s ), 3 . 96 ( 3h , s ), 6 . 50 ( 1h , t , j = 8 . 4 hz ), 7 . 40 ( 1h , d , j = 8 . 4 hz ), 7 . 50 ( 1h , dd , j = 10 . 0 , 2 . 0 hz ), 9 . 92 ( 1h , brs ). to a solution of methyl 6 -( 2 - fluoro - 4 - iodophenylamino )- 2 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrooxazolo [ 4 , 5 - c ] pyridine - 7 - carboxylate ( 1 . 60 g , 3 . 50 mmol ) in a mixture of thf ( 40 ml ), meoh ( 40 ml ) and h 2 o ( 40 ml ) was added 2 m aq . k 2 co 3 ( 2 . 62 ml , 5 . 25 mmol ) at room temperature . the reaction mixture was stirred at 70 ° c . for 3 hours . the mixture was extracted with etoac ( 2 × 40 ml ). the aqueous layer was acidified with 3 n aq . hcl until ph 3 . the resulting solid was collected by filtration , washed with water and et 2 o to give the 6 -( 2 - fluoro - 4 - iodophenylamino )- 2 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrooxazolo [ 4 , 5 - c ] pyridine - 7 - carboxylic acid ( 1 . 21 g , 78 %) as a yellow solid . 1 h - nmr ( dmso - d 6 , varian , 400 mhz ): δ 2 . 56 ( 3h , s ), 3 . 25 ( 3h , s ), 6 . 75 ( 1h , t , j = 8 . 8 hz ), 7 . 44 ( 1h , d , j = 8 . 8 hz ), 7 . 69 ( 1h , dd , j = 10 . 8 , 2 . 0 hz ), 9 . 70 ( 1h , s ), 13 . 33 ( 1h , brs ). a mixture of 6 -( 2 - fluoro - 4 - iodophenylamino )- 2 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrooxazolo [ 4 , 5 - c ] pyridine - 7 - carboxylic acid ( 1 . 21 g , 2 . 74 mmol ), o -( 2 -( vinyloxy ) ethyl ) hydroxylamine ( intermediate 2 , 424 mg , 4 . 11 mmol ), hobt ( 630 mg , 4 . 11 mmol ), and edc ( 788 mg , 4 . 11 mmol ) in dmf ( 14 ml ) was added tea ( 0 . 764 ml , 5 . 48 mmol ) at room temperature . the mixture was stirred at room temperature for 1 h , and quenched with saturated aq . nh 4 cl ( 20 ml ). the mixture was extracted with etoac ( 3 × 10 ml ), and the combined organic layers were washed with water ( 3 × 30 ml ) and brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residual was suspended in etoac , collected by filtration , and washed with etoac to give the 6 -( 2 - fluoro - 4 - iodophenylamino )- 2 , 5 - dimethyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrooxazolo [ 4 , 5 - c ] pyridine - 7 - carboxamide ( 826 g , 57 %) as a yellow solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 2 . 66 ( 3h , s ), 3 . 33 ( 3h , s ), 4 . 00 - 4 . 02 ( 2h , m ), 4 . 09 - 4 . 12 ( 1h , m ), 4 . 26 ( 1h , dd , j = 14 . 4 , 2 . 4 hz ), 4 . 30 - 4 . 33 ( 2h , m ), 6 . 50 - 6 . 57 ( 2h , m ), 7 . 40 ( 1h , d , j = 8 . 4 hz ), 7 . 48 ( 1h , dd , j = 10 . 0 , 2 . 0 hz ), 9 . 70 ( 1h , s ), 10 . 96 ( 1h , s ). to a solution of 6 -( 2 - fluoro - 4 - iodophenylamino )- 2 , 5 - dimethyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrooxazolo [ 4 , 5 - c ] pyridine - 7 - carboxamide ( 300 mg , 0 . 568 mmol ) in meoh ( 6 . 0 ml ) was added 2n aq . hcl ( 1 . 7 ml , 3 . 40 mmol ) at room temperature , the reaction mixture was stirred for 30 minutes at room temperature , then concentrated in vacuo . the residue was dissolved in dcm , neutralized with saturated aq . nahco 3 at 0 ° c . the separated aqueous layer was extracted with dcm . the combined organic layers were washed with brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( dcm : meoh = 95 : 5 ) to give the 6 -( 2 - fluoro - 4 - iodophenylamino )- n -( 2 - hydroxyethoxy )- 2 , 5 - dimethyl - 4 - oxo - 4 , 5 - dihydrooxazolo [ 4 , 5 - c ] pyridine - 7 - carboxamide ( 186 mg , 65 %) as a white solid . 1 h nmr ( dmso - d 6 , varian 400 mhz ): δ 2 . 56 ( 3h , s ), 3 . 39 ( 3h , s ), 3 . 47 - 3 . 50 ( 2h , m ), 3 . 59 - 3 . 62 ( 2h , m ), 4 . 68 ( 1h , t , j = 5 . 6 hz ), 6 . 63 ( 1h , t , j = 8 . 8 hz ), 7 . 35 ( 1h , d , j = 8 . 4 hz ), 7 . 60 ( 1h , dd , j = 10 . 8 , 2 . 0 hz ), 9 . 00 ( 1h , brs ), 11 . 34 ( 1h , brs ). m / z = 502 . 9 [ m + h ] + . to a solution of compound cubr 2 ( 11 . 5 g , 51 . 7 mmol ) in etoac ( 160 ml ) was added a solution of dimethyl 2 - oxopentanedioate ( 3 . 00 g , 17 . 2 mmol ) in chcl 3 ( 80 ml ) at room temperature . the reaction mixture was refluxed overnight , cooled to room temperature . after evaporation of volatile solvents , the residue was purified by column chromatography on sio 2 ( hex : etoac = 3 : 2 ) to give the dimethyl 3 - bromo - 2 - oxopentanedioate ( 4 . 36 g , quant .) as a yellow oil . 1 h nmr ( cdcl 3 , varian 400 mhz ): δ 3 . 06 ( 1h , a bx , j ab = 17 . 3 hz , j ax = 9 . 3 hz ), 3 . 34 ( 1h , a b x , j ab = 17 . 3 hz , j bx = 5 . 9 hz ), 3 . 71 ( 3h , s ), 3 . 95 ( 3h , s ), 5 . 40 ( 1h , ab x , j ax = 9 . 3 hz , j bx = 5 . 9 hz ). a mixture of dimethyl 3 - bromo - 2 - oxopentanedioate ( 4 . 36 g , 17 . 2 mmol ) and methanethioamide ( 1 . 6 m in dioxane , 53 . 8 ml , 86 . 0 mmol ) in etoh ( 86 ml ) was refluxed overnight , cooled to room temperature . after evaporation of volatile solvents , the residue was purified by column chromatography on sio 2 ( hex : etoac = 2 : 3 ) to give the methyl 5 -( 2 - methoxy - 2 - oxoethyl ) thiazole - 4 - carboxylate ( 2 . 02 g , 54 %) as a yellow oil . 1 h nmr ( cdcl 3 , varian 400 mhz ): δ 3 . 77 ( 3h , s ), 3 . 96 ( 3h , s ), 4 . 37 ( 2h , s ), 8 . 73 ( 1h , s ). to a solution of methyl 5 -( 2 - methoxy - 2 - oxoethyl ) thiazole - 4 - carboxylate ( 2 . 02 g , 9 . 40 mmol ) in dry thf ( 47 ml ) was added nah ( 55 %, 490 mg , 11 . 3 mmol ) at 0 ° c . the mixture was stirred for 30 minutes at 0 ° c . after dropwise addition of 2 - fluoro - 4 - iodo - n -(( methylimino ) methylene ) aniline ( intermediate 1 , 2 . 59 g , 9 . 40 mmol ) at 0 ° c ., the reaction mixture was stirred at room temperature for 1 hour , and then quenched saturated aq . nh 4 cl ( 50 ml ). the mixture was extracted with etoac ( 2 × 30 ml ). the combined organic layers were washed water ( 70 ml ) and brine ( 70 ml ), dried over na 2 so 4 , filtered and concentrated in vacuo . the residual was purified by column chromatography on sio 2 ( hex : etoac = 2 : 3 to 1 : 2 ) to give the methyl 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrothiazolo [ 4 , 5 - c ] pyridine - 7 - carboxylate ( 434 mg , 10 %) as an orange solid . 1 h nmr ( cdcl 3 , varian 400 mhz ): δ 3 . 41 ( 3h , s ), 3 . 97 ( 3h , s ), 6 . 54 ( 1h , t , j = 8 . 8 hz ), 7 . 41 ( 1h , d , j = 8 . 4 hz ), 7 . 52 ( 1h , dd , j = 10 . 0 , 2 . 0 hz ), 9 . 94 ( 1h , brs ). to a solution of methyl 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrothiazolo [ 4 , 5 - c ] pyridine - 7 - carboxylate ( 100 mg , 0 . 218 mmol ) in a mixture of thf ( 2 ml ), meoh ( 2 ml ) and h 2 o ( 2 ml ) was added 2 m aq . k 2 co 3 ( 0 . 163 ml , 0 . 327 mmol ) at room temperature . the reaction mixture was stirred at 70 ° c . for 3 hours . the mixture was extracted with etoac ( 2 × 10 ml ). the aqueous layer was acidified with 3 n aq . hcl until ph 3 . the resulting solid was collected by filtration , washed with water and et 2 o to give the 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrothiazolo [ 4 , 5 - c ] pyridine - 7 - carboxylic acid ( 66 . 9 mg , 69 %) as a yellow solid . 1 h - nmr ( dmso - d 6 , varian , 400 mhz ): δ 3 . 28 ( 3h , s ), 6 . 75 ( 1h , t , j = 8 . 8 hz ), 7 . 40 ( 1h , d , j = 8 . 4 hz ), 7 . 69 ( 1h , dd , j = 10 . 6 , 2 . 0 hz ), 9 . 07 ( 1h , s ), 9 . 62 ( 1h , brs ). a mixture of 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrothiazolo [ 4 , 5 - c ] pyridine - 7 - carboxylic acid ( 66 . 9 mg , 0 . 150 mmol ), o -( 2 -( vinyloxy ) ethyl ) hydroxylamine ( intermediate 2 , 23 . 0 mg , 0 . 225 mmol ) in dmf ( 1 ml ) was added hatu ( 171 mg , 0 . 450 mmol ) at room temperature . the mixture was stirred at room temperature for 4 hours , and quenched with saturated aq . nh 4 cl ( 10 ml ). the mixture was extracted with etoac ( 2 × 10 ml ), and the combined organic layers were washed with water ( 3 × 10 ml ) and brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residual was purified by column chromatography on sio 2 ( dcm : meoh = 95 : 5 ) to give the 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrothiazolo [ 4 , 5 - c ] pyridine - 7 - carboxamide ( 14 mg , 17 %) as a brown solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 3 . 69 ( 3h , s ), 3 . 90 - 3 . 93 ( 2h , m ), 3 . 98 - 4 . 02 ( 3h , m ), 4 . 13 ( 1h , dd , j = 14 . 4 , 2 . 4 hz ), 6 . 47 - 6 . 52 ( 2h , m ), 7 . 31 ( 1h , d , j = 8 . 8 hz ), 7 . 43 ( 1h , dd , j = 10 . 0 , 2 . 0 hz ), 8 . 90 ( 1h , s ). to a solution of 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrothiazolo [ 4 , 5 - c ] pyridine - 7 - carboxamide ( 14 . 0 mg , 0 . 026 mmol ) in meoh ( 0 . 5 ml ) was added 2n aq . hcl ( 0 . 079 ml , 0 . 158 mmol ) at room temperature , the reaction mixture was stirred for 1 hour at room temperature , then concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( dcm : meoh = 93 : 7 to 9 : 1 ) to give the 6 -( 2 - fluoro - 4 - iodophenylamino )- n -( 2 - hydroxyethoxy )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrothiazolo [ 4 , 5 - c ] pyridine - 7 - carboxamide ( 5 . 2 mg , 39 %) as a yellow solid . 1 h nmr ( cdcl 3 , varian 400 mhz ): δ 3 . 40 - 3 . 47 ( 2h , m ), 3 . 74 ( 3h , s ), 3 . 76 - 3 . 81 ( 2h , m ), 6 . 52 ( 1h , t , j = 8 . 8 hz ), 7 . 34 ( 1h , d , j = 8 . 4 hz ), 7 . 44 ( 1h , dd , j = 10 . 0 , 1 . 6 hz ), 8 . 94 ( 1h , s ), 9 . 20 ( 1h , brs ), 11 . 06 ( 1h , brs ). m / z = 504 . 6 [ m + h ] + . to a solution of methyl 6 -( 2 - chloro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylate ( intermediate 7 , 320 mg , 0 . 69 mmol ) in dry thf ( 17 . 0 ml ) was added o -( 2 -( vinyloxy ) ethyl ) hydroxylamine ( intermediate 2 , 108 mg , 1 . 04 mmol ) at room temperature and then was cooled to 0 ° c . to the reaction mixture was added lihmds ( 3 . 50 g , 4 . 19 mmol ) at 0 ° c . under a n 2 atmosphere . the mixture was stirred at room temperature for 1 hour . the reaction mixture was quenched with water and extracted with etoac , washed with water and brine , dried over na 2 so 4 , filtered and concentrated in vacuo to give 6 -( 2 - chloro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 310 mg , 84 %) as a white solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 3 . 99 - 4 . 01 ( 2h , m ), 4 . 07 - 4 . 09 ( 1h , dd , j = 6 . 8 , 2 . 4 hz ), 4 . 25 - 4 . 26 ( 1h , dd , j = 14 . 4 , 2 . 4 hz ), 6 . 36 ( 1h , d , j = 8 . 4 hz ), 6 . 49 - 6 . 54 ( 1h , m ), 7 . 01 ( 1h , m ), 7 . 43 - 7 . 45 ( 1h , dd , j = 8 . 6 , 1 . 8 hz ), 7 . 51 ( 1h , m ), 7 . 77 ( 1h , m ), 10 . 0 ( 1h , s ), 10 . 8 ( 1h , s ). to a solution of 6 -( 2 - chloro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - n -( 2 -( vinyloxy ) ethoxy )- 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 200 mg , 0 . 37 mmol ) in meoh ( 4 ml ) was added 2n aq . hcl ( 1 . 21 ml ) at room temperature . the mixture was stirred at room temperature for 30 min . the residue was neutralized with aq . nahco 3 at 0 ° c . the separated aqueous layer was extracted with dcm . the combined organic layers were washed with brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residual solid was suspended in et 2 o , collected by filtration , and washed with et 2 o to give 6 -( 2 - chloro - 4 - iodophenylamino )- n -( 2 - hydroxyethoxy )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 170 mg , 89 %) as a white solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ) δ 3 . 29 ( 3h , s ), 3 . 50 - 3 . 51 ( 2h , m ), 3 . 70 - 3 . 72 ( 2h , m ), 4 . 66 - 4 . 681 ( 1h , m ), 6 . 46 ( 1h , t , j = 8 . 4 hz ), 7 . 03 ( 1h , m ), 7 . 45 - 7 . 48 ( 1h , dd , j = 8 . 4 , 2 . 0 hz ), 7 . 78 ( 1h , m ), 7 . 96 ( 1h , m ), 8 . 91 ( 1h , s ), 11 . 3 ( 1h , s ). m / z = 503 . 6 [ m + h ] + . to a solution of 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylic acid ( example 1 , step a ; 150 mg , 0 . 350 mmol ) in dmf ( 1 . 00 ml ) was added o -( cyclopropylmethyl ) hydroxylamine hydrochloride ( intermediate 8 , 47 . 6 mg , 0 . 385 mmol ) at room temperature and then was cooled to 0 ° c . to a reaction mixture was added edci ( 101 mg , 0 . 526 mmol ), hobt ( 80 . 0 mg , 0 . 526 mmol ) and tea ( 0 . 146 ml , 1 . 05 mmol ). the mixture was stirred at room temperature for 15 hours . the residue was extracted with etoac and washed with water and brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 2 : 1 ) to give n -( cyclopropylmethoxy )- 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 30 . 3 mg , 16 %) as a purple solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ); δ 0 . 35 ( 2h , m ), 0 . 63 ( 2h , m ), 3 . 32 ( 3h , s ), 3 . 87 ( 2h , d , j = 7 . 2 hz ), 6 . 50 ( 1h , t , j = 8 . 4 hz ), 7 . 01 ( 1h , m ), 7 . 36 ( 1h , m ), 7 . 47 ( 1h , m ), 7 . 53 ( 1h , m ), 9 . 86 ( 1h , s ), 10 . 9 ( 1h , s ). * nh peak was not observed . m / z = 497 . 90 [ m + h ] + . to a solution of 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylic acid ( example 1 , step a ; 150 mg , 0 . 350 mmol ) in dmf ( 3 . 50 ml ) was added o -( 1 - hydroxy - 2 - methylpropan - 2 - yl ) hydroxylammonium chloride ( intermediate 9 , 74 . 4 mg , 0 . 526 mmol ) at room temperature and then was cooled to 0 ° c . to a reaction mixture was added edci ( 101 mg , 0 . 526 mmol ), hobt ( 80 . 0 mg , 0 . 526 mmol ) and tea ( 0 . 0730 ml , 0 . 526 mmol ). the mixture was stirred at room temperature for 15 hours . the residue was extracted with etoac and washed with water and brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 1 : 1 ) to give 6 -( 2 - fluoro - 4 - iodophenylamino )- n -( 1 - hydroxy - 2 - methylpropan - 2 - yloxy )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 30 . 1 mg , 17 %) as a white solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 1 . 34 ( 6h , s ), 3 . 31 ( 3h , s ), 3 . 39 ( 2h , d , j = 6 . 8 hz ), 6 . 55 ( 1h , t , j = 8 . 4 hz ), 7 . 02 ( 1h , d , j = 2 . 0 hz ), 7 . 39 ( 1h , d , j = 8 . 4 hz ), 7 . 48 ( 1h , m ), 7 . 52 ( 1h , m ), 9 . 46 ( 1h , s ), 10 . 80 ( 1h , s ). m / z = 515 . 9 . 0 [ m + h ] + . to a solution of 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylic acid ( example 1 , step a ; 150 mg , 0 . 350 mmol ) in dmf ( 3 . 50 ml ) was added methoxymethanamine hydrochloride ( 51 . 3 mg , 0 . 526 mmol ) at room temperature and then was cooled to 0 ° c . to a reaction mixture was added edci ( 101 mg , 0 . 526 mmol ), hobt ( 80 . 0 mg , 0 . 526 mmol ) and tea ( 0 . 0730 ml , 0 . 526 mmol ). the mixture was stirred at room temperature for 15 hours . the residue was extracted with etoac and washed with water and brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 1 : 1 ) to give 6 -( 2 - fluoro - 4 - iodophenylamino )- n - methoxy - 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 66 . 2 mg , 41 %) as a purple solid . 1 h - nmr ( cdcl 3 , varian , 400 mhz ): δ 3 . 34 ( 3h , s ), 3 . 90 ( 3h , s ), 6 . 51 ( 1h , t , j = 8 . 4 hz ), 7 . 01 ( 1h , s ), 7 . 38 ( 1h , d , j = 14 hz ), 7 . 49 ( 2h , m ), 9 . 88 ( 1h , s ), 10 . 98 ( 1h , s ). m / z = 458 . 0 [ m + h ] + . to a mixture of methyl 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carb ( example 1 , step a ; 1 . 30 g , 2 . 94 mmol ) and ( r )— o -(( 2 , 2 - dimethyl - 1 , 3 - dioxolan - 4 - yl ) methyl ) hydroxylamine ( intermediate 10 , 0 . 65 g , 4 . 41 mmol in dry thf ( 7 . 35 ml ) was added lihmds ( 17 . 6 ml , 16 . 6 mmol , 1 . 06 m solution in hexane ) at 0 ° c . the reaction mixture was stirred for 20 min at 0 ° c ., and then quenched with saturated 1n aq . hcl ( 50 ml ). the mixture was extracted with etoac ( 3 × 20 ml ). the combined organic layers were washed with water ( 50 ml ) and brine ( 50 ml ), dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 1 : 1 to 1 : 2 ) to give ( r )— n -(( 2 , 2 - dimethyl - 1 , 3 - dioxolan - 4 - yl ) methoxy )- 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 1 . 07 g , 65 . 3 %) as a yellow solid . 1 h nmr ( cdcl 3 , varian 400 mhz ) δ 1 . 40 ( 3h , s ), 1 . 47 ( 3h , s ), 3 . 32 ( 3h , s ), 3 . 85 ( 1h , dd , j = 8 . 4 , 6 . 4 hz ), 4 . 05 - 4 . 18 ( 3h , m ), 4 . 43 - 4 . 48 ( 1h , m ), 6 . 51 ( 1h , t , j = 8 . 4 hz ), 7 . 01 ( 1h , d , j = 2 . 0 hz ), 7 . 37 ( 1h , d , j = 8 . 4 hz ), 7 . 46 - 7 . 50 ( 2h , m ), 10 . 14 ( 1h , s ), 10 . 96 ( 1h , brs ). to a solution of ( r )— n -(( 2 , 2 - dimethyl - 1 , 3 - dioxolan - 4 - yl ) methoxy )- 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 1 . 07 g , 1 . 92 mmol ) in meoh ( 28 ml ) was added 1 n aq . hcl ( 9 . 31 ml , 9 . 31 mmol ) at room temperature . the mixture was stirred at room temperature for 14 hours . the residue was diluted with dcm and washed with water and brine , dried over na 2 so 4 , filtered and concentrated in vacuo to give ( r )— n -( 2 , 3 - dihydroxypropoxy )- 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 580 mg , 58 . 4 %) as a white solid . 1 h - nmr ( dmso - d 6 , varian , 400 mhz ) δ 2 . 42 ( 1h , t , j = 5 . 8 hz ), 3 . 30 ( 3h , s ), 3 . 62 - 3 . 67 ( 1h , m ), 3 . 73 - 3 . 79 ( 1h , m ), 3 . 97 - 4 . 02 ( 1h , m ), 4 . 03 - 4 . 14 ( 2h , m ), 4 . 44 ( 1h , d , t , j = 2 . 0 hz ), 6 . 56 ( 1h , t , t , j = 8 . 4 hz ), 7 . 01 ( 1h , d , t , j = 2 . 0 hz ), 7 . 40 ( 1h , d , t , j = 8 . 4 hz ), 7 . 49 ( 1h , dd , j = 9 . 8 , 1 . 8 hz ), 7 . 52 ( 1h , d , t , j = 2 . 0 hz ), 10 . 00 ( 1h , s ), 10 . 79 ( 1h , brs ). m / z = 517 . 8 [ m + h ] + . to a solution of 6 -( 2 - fluoro - 4 - iodophenylamino )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxylic acid ( example 1 , step a ; 1 . 18 g , 2 . 76 mmol ) in dmf ( 21 . 5 ml ) was added 3 - aminopropan - 1 - ol ( 228 mg , 3 . 03 mmol ) at room temperature and then was cooled to 0 ° c . to the reaction mixture was added edc ( 792 mg , 4 . 13 mmol ), hobt ( 633 g , 4 . 13 mmol ), and tea ( 0 . 77 ml , 5 . 51 mmol ). the mixture was stirred at room temperature for 2 hours . the reaction was extracted with etoac , washed with water and brine , dried over na 2 so 4 , filtered and concentrated in vacuo . the residue was purified by column chromatography on sio 2 ( hex : etoac = 1 : 1 ˜ 1 : 2 ) to give to give 6 -( 2 - fluoro - 4 - iodophenylamino )- n -( 3 - hydroxypropyl )- 5 - methyl - 4 - oxo - 4 , 5 - dihydrofuro [ 3 , 2 - c ] pyridine - 7 - carboxamide ( 130 mg , 9 . 7 %) as a violet solid . 1 h - nmr ( dmso - d 6 , varian , 400 mhz ) δ 1 . 53 - 1 . 60 ( 2h , m ), 3 . 24 ( q , 2h , j = 6 . 4 hz ), 3 . 34 ( 3h , s ), 3 . 42 - 3 . 46 ( 2h , m ), 4 . 50 ( 1h , t ), 6 . 60 ( 1h , t , j = 8 . 8 hz ), 7 . 02 ( 1h , d , j = 2 . 4 hz ), 7 . 36 ( 1h , dd , j = 1 . 0 hz ), 7 . 63 ( 1h , dd , j = 1 . 8 hz ), 7 . 92 ( 1h , d , j = 2 . 0 hz ), 8 . 22 ( 1h , t , j = 5 . 6 hz ), 9 . 93 ( 1h , s ). m / z = 486 . 0 [ m + h ] + . the kinase glo plus assay kit was purchased from promega . the substrate , apt , dtt , and dimethylsulfoxide were purchased from sigma - aldrich . the map2k1 ( mek1 ) kinase , europium labeled antibody , tracer 236 and binding buffer a were purchased from invitrogen . the recombinant human epithelial growth factor ( egf ) was purchased from r & amp ; d system . the surefire phospho - erk1 / 2 assay kit and the alphascreen general igg ( protein a ) detection kit were both purchased from perkinelmer . a mek1 kinase assay ( lance , perkinelmer ) was developed for supporting compound profiling and lead optimization . in this assay , un - phosphorylated / inactive erk1 ( millipore ) was used as the substrate for mek1 ( millipore ). then the phosphorylated erk1 was able to phosphorylate ulight ™- mbp peptide ( perkinelmer ). the phosphorylated peptide was detected by europium - anti - phospho - mbp ( perkinelmer ). in a reaction , the activity of mek1 ( 0 . 25 nm ) was measured in a buffer containing 50 μm atp , 2 nm inactive erk1 , 50 nm ulight ™- mbp peptide , and a compound for 90 min at 23 ° c . after quenching the reaction , 2 nm europium - anti - phospho - mbp was added to the reaction mixture and incubated for 60 min , followed by a detection using envision . the ic 50 values were derived through a curve fitting using grafit . to investigate whether a compound is able to inhibit the activity of mek in cells , a mechanism - based assay using a375 cell line ( melanoma ) was developed . in this assay ( alphascreen , perkinelmer ), inhibition of mek was detected by reduced erk phosphorylation . a375 cells were cultured in a tissue culture flask to 80 % confluence in dmem plus 10 % fetal bovine serum . cells were collected and plated onto 96 well culture plates at 3 × 10 4 cells / well . plates were incubated overnight at 37 ° c . with 5 % co 2 to allow cells to adhere . compounds were added to the plates and incubated at 37 ° c . for 1 hour . after removing the medium , 100 μl of cell lysis buffer were added to each well and 4 μl of cell lysate were transferred into a 384 well white proxiplate ( perkinelmer ). the phospho - erk levels were determined by following the standard protocol supplied with the perkinelmer surefire phospho - erk 1 / 2 assay kit ®. plates were read out by envision ( perkinelmer ). the data were analyzed using graphpad prism . select compounds prepared as described above were assayed according to the biological procedures described herein . the results are given in the table below :
| 2 |
referring to fig1 there is shown a schematic layout of a floor plan for an integrated memory circuit device 10 of the present invention . as is well known , the device 10 is fabricated from silicon and is an integrated circuit device or a chip 10 . in the preferred embodiment , the device or chip 10 is an 8m × 8 - bit flash eeprom , using non - volatile memory cells of the split gate type arranged in a nor array 12 as disclosed in u . s . pat . no . 5 , 668 , 757 , which disclosure is incorporated by reference . as disclosed in u . s . pat . no . 5 , 668 , 757 programming of the memory cell occurs by hot channel electron tunneling . further , in the preferred embodiment , although the device 10 has its non - volatile memory cells arranged in a nor array 12 , the device 10 emulates the operation of a nand type page mode device . however , it should be noted that the present invention is not limited to this specific density or configuration or mode of operation . the memory cell array 12 is located in the center of the device 10 . on the left side of the array 12 , a control gate decoder 14 is located . on the right side of the array 12 , a word - line decoder 16 is located . a plurality of page buffers 18 are placed on the upper side of the array 12 . in the preferred embodiment , there are 512 × 8 page buffers that correspond to a page of 1024 × 8 memory cells . peripheral circuits 24 are located on the upper side of the device 10 . on the left side of the device 10 , charge pumps 22 are placed . on the right side of the device 10 , the current pumps 20 are placed . in the vicinity of corners of the device 10 , pads ( such as i / o , power and control ) are placed . since the memory cell array is configured as 8m × 8 - bit , the entire memory cell array 12 is divided into 8 identical sub - arrays ( sub - array 12 - 0 sub - array 12 - 1 , . . . sub - array 12 - 7 ). each sub - array has a corresponding i / o . thus , sub - array 12 - 0 corresponds to i / o - 0 , . . . sub - array 12 - 7 corresponds to i / o - 7 . although the memory cell array 12 is divided into 8 identical sub - arrays 12 - n , each word line from the word line decoder 16 , and each control gate line from the control gate decoder 14 runs “ horizontally ” across all eight identical sub - arrays 12 - n . in the preferred embodiment , a word line and a control line crosses 1024 × 8 cells , with each cell each having an associated bit line . thus , there are 1024 cells in each sub - array 12 - n . within each sub - array 12 - n , there are 512 page buffers 18 . thus , there are two memory cells associated with each page buffer 18 . to simplify the illustration , only one of the 8 sub - arrays 12 - n and its corresponding page buffers 18 - n is described and shown in the following drawings . referring to fig2 a , a plurality of adjacent signal lines pdb 0 to pdb 511 are connected to page buffers 18 l . each signal line pdb is connected to one page buffer 18 l . therefore , there are 512 page buffers 18 l . each signal line pdb is further eventually connected to a pair of immediately adjacent bit lines blj and bl ( j + 1 ) through bit line switches 46 l , sense amplifiers 36 u , and bit line switches 46 u and 44 to the memory array 12 ( see fig3 ). thus , the 512 pdb lines connected the 512 page buffers to 1024 bit lines bl . each bit line ( blx ) is in turn connected to a column of non - volatile memory cells . when a particular row of memory cells is selected there are 1024 memory cells associated with the 512 pdb lines . all the 512 ( from # 0 to # 511 ) page buffers 18 l that are connected to the signal lines pdb 0 - pdb 511 are further grouped into 16 interleaved sub - pages 18 l - n . thus , each sub - page 18 l - n comprises 32 page buffers 18 l . the grouping of each sub - page 18 l - n and its members are as follows : thus , sub - page 18 l - 0 comprises page buffers 18 l connected to pdb [ 0 ], [ 16 ], [ 32 ], [ 48 ], . . . [ 496 ] sub - page 18 l - 1 comprises page buffers 18 l connected to pdb [ 1 ], [ 17 ], [ 33 ], [ 49 ], . . . ,[ 497 ] sub - page 18 l - 2 comprises page buffers 18 l connected to pdb [ 2 ], [ 18 ], [ 34 ], [ 50 ], . . . ,[ 498 ] finally , sub - page 18 l - 15 comprises page buffers 18 l connected to pdb [ 15 ], [ 31 ], [ 47 ], [ 63 ], . . . , [ 511 ] as can be seen from the foregoing , each sub - page 18 l - n comprises page buffers 18 l that are not located immediately adjacent to one another . instead , page buffers 18 l of the same sub - page 18 l - n are connected to signal lines pdb that are spaced equal distance apart ( namely by the size of 15 page buffers 18 l ) from one another and are grouped together to form a sub - page . thus , the 16 sub - pages 18 l - 0 - 18 l - 15 are interleaved with one another . with this arrangement , the current drawn by selected memory cells during a sub - page pre - fetch can be spread out evenly across the whole memory cell sub - array 12 - n rather than being crowded over an area as narrow as the pitch of 32 adjacent pdb signal lines . the distance between two adjacent pdbs is carefully selected based on the sheet resistance of source diffusion area of memory cells . referring to fig2 a , the source line of each memory cell is connected together by a local diffusion path . a metal strapping runs through the cell array horizontally . periodic vss taps are made to connect the local diffusion path to vss . if the sub - page distance l is long enough to accommodate 1 vss tap for each selected bit line as depicted in the figure , the vss bounce ( or ground bounce ) will be minimized down to icell × rdiff . where icell is the cell current and rdiff is the diffusion resistance . if the sub - page distance is reduced to l / 4 , 1 vss tap is shared among 4 selected bit lines , the vss bounce increases differently for those 4 bit lines as depicted in fig2 b . therefore , an optimal value of l could be resulted from the trade off between the layout area penalty of vss taps and the vss bounce . referring to fig3 there is shown a schematic diagram of the interconnection of the bit lines bl 0 . . . bl 1023 from the memory array 12 ( shown in fig1 ) to the output of the device 10 . the 1024 bit lines from the memory array 12 are first supplied to bit line switches 44 . the 1024 bit lines supplied to the bit line switches 44 are reduced to 512 signal lines mblx ( x = 0 , 511 ). thus , each pair of adjacent bit lines blj and bl ( j + 1 ) are connected to a signal line mblx . the 512 signal lines mblx are supplied to a first column decoder 46 u . the first column decoder 46 u also receives the column signals yls ( 0 . . . 15 ). each 16 adjacent mbl signal lines is assigned to 1 xdl line . thus , the 512 mbl signal lines are decoded to 32 xdl lines . the first column decoder 46 u functions as a multiplexer / de - multiplexer in selecting one of 16 mbl lines to be connected to a single xdl line . each of the 32 xdl lines is supplied to a respective sensing circuit 36 u . thus , there are 32 sensing circuits 36 u in the first section 18 u of the page buffer 18 u / 18 l . since each sensing circuit 36 u is associated with 32 bit lines bl , the size ( width ) of each sensing circuit 36 u can be 32 times the pitch or size ( width ) of each memory cell . therefore , the sensing circuit 36 u can be very large compared to each memory cell . fig3 a is a schematic circuit diagram showing the bit - line pre - charge circuits 36 u - 8 / 36 u - 9 / 36 u - 10 . these pre - charge transistors are used to pre - charge the selected bit - lines to the predetermined voltage level biasp before starting the page - mode read operation . the pre - charge transistor is activated by the signal xdlpb . each sensing circuit 36 u has an output sdlbx ( 0 . . . 31 ). the 32 sdlb lines are supplied to a second column decoder 46 l which is also decoded by the column signals yls ( 0 . . . 15 ), and connect the 32 sdlb lines to 512 pdbx ( 0 . . . 511 ) lines . the second column decoder also functions s a multiplexer / de - multiplexer in connecting a single output of a qclt 36 u to one of selected 16 pdb lines . the 512 pdb lines are supplied to a plurality of latches 34 in the second section 18 l of the page buffer 18 u / 18 l , with one latch 34 associated with each of the 512 pdb lines . the 512 latches 34 are grouped into 32 sub - pages 36 l . each sub - page 36 l comprises 32 latches 34 with each latch 34 associated with a pdb line spaced apart from one another , all as discussed with reference to fig2 a . the output of the each latch 34 is connected to an output line pdx ( in reality the output line pdx is a pair of output lines , comprising pdx and pdx ( bar )). since there are 512 latches , there are 512 output lines pdx . 16 adjacent latches 34 and their associated output lines pd ( x , x + 15 ) are grouped together to form a group . in total there are 32 groups of output lines pdx . the 32 groups of output lines pdx are supplied to a third column decoder 38 , which also functions as a multiplexer / de - multiplexer . the third column decoder 38 selects one of the output lines pdx from each group 36 l , based upon the select signals yl 0 . . . yl 15 . thus , the third column decoder 38 selects 32 outputs , one from each group 36 lx , representing all of the outputs of the latches 34 from the same selected sub - page 18 - n . the 32 outputs of the third column decoder 38 are supplied to a pre - charge circuit 38 p , which outputs the 32 signals at nodes dlu 0 . . . dlu 15 , dlu 0 . . . dlu 15 . ( shown in fig3 b ) ( again , each line represents a pair of output lines .) the pre - charge transistors of the pre - charge circuit 38 p are used to pre - charge the intermediate nodes dlux before switching the third column decoders 38 . fig3 b is a schematic circuit diagram showing the dlux pre - charge circuits 38 p / 40 p . from the output of the pre - charge circuit 38 p , the signals dlu 0 . . . dlu 15 , dlu 0 . . . dlu 15 are supplied to the fourth column decoder 40 . the fourth column decoder 40 selects one of the output lines from the first group of 16 dlu signals , and one of the output lines from the second group of 16 dlu signals , based upon the select signals yu 0 . . . yu 15 . thus , the fourth column decoder 40 selects 2 outputs , with each being a pair of lines . the two outputs from the fourth column decoder 40 are supplied to a pre - charge circuit 40 p , which outputs the 2 signals at nodes dll 0 and dll 1 . the pre - charge transistors of the pre - charge circuit 40 p are used to pre - charge the intermediate nodes dllx before switching the fourth column decoders 40 . from the pre - charge circuit 40 p , the signals dll 0 and dll 1 are supplied to the fifth column decoder 42 , which selects one of the signals as the output dl ( a pair output lines : dl and dlb ), based upon the select signals z 0 and z 1 . the selected signal dl ( dl and dlb ) from the fifth column decoder 42 is supplied to the output buffer 48 . thus , through the action of the third , fourth and fifth column decoders 38 / 40 / 42 one signal ( both the signal and its complement ) stored in a latch 34 from a selected sub page 18 l - n is outputted from the device 10 . the pre - charge circuits 38 p / 40 p serve only to pre - charge certain nodes before the column decoders 38 / 40 / 42 are activated . since all these intermediate nodes dlux / dllx are loaded with large parasitic capacitance , any switching on the column decoders 38 / 40 / 42 will cause disturbance to the data latches 34 . to prevent this disturbance , all dlux / dllx nodes must be pre - charged to vcc − vtn before switching . fig3 c is a schematic circuit diagram showing in detail the output buffer 48 . the pair of output signals dl and dlb , representing the data and data inverse signals from the output of a latch from the selected page buffer 18 l , are supplied to a differential amplifier 48 sa . the output , dout , of the differential amplifier 48 sa , is supplied to a series of latches and is then supplied to a multiplexer / de - multiplexer 48 m . in the page mode of operation , this would be the path of the signal . however , the device 10 can also operate in a non - page mode , wherein the signal from a non - volatile memory cell is read out directly and not stored in the page buffer 18 l . in that event , the signal from the non - volatile memory cell along with the signal from a reference cell are supplied to a sense amplifier 48 na . the output of the sense amplifier 48 na is supplied to a series of latches and to another input to the multiplexer / de - multiplexer 48 m . the output of the multiplexer / de - multiplexer 48 m is supplied as the output of the device 10 . the latched signal , csaout , from the sense amplifier 48 na , is also supplied in a feedback manner to a feedback circuit 48 r , which is connected to the output lines dl and dlb , and is used in a read - modify - write mode during programming operation , which will be discussed greater detail hereinafter . referring to fig4 there is shown a detailed circuit diagram of the sensing circuit 36 u shown in fig3 . the sensing circuit or quick current level translators ( qclt ) 36 u receives data on the input line xdl and supplies its output to sdlb . each xdl is connected to a plurality of bit lines through the first column decoder 46 u . each sdlb is connected to a plurality of page latches 36 l through the second column decoder 46 l . page latches are connected to corresponding output buffers through the column decoders 38 / 40 / 42 . the qclt 36 u is a current - mode analog - to - digital converter that converts the input current signal at local data line xdl to binary codes and stores the codes in the q - latches 36 u - 2 shown in fig4 . the data stored in q - latches 36 u - 2 will be transferred to page latches 34 for clocking out . in the prior arts of page - mode non - volatile memory , current sensing devices are usually combined with data storage devices to form a complicated page buffer . this complicated page buffer is often found difficult to layout within the tight bit line pitch . at the same time , the tight pitch also limits the delicacy of the page buffer design . furthermore , in order to fit in the pitch , the current sensing devices are often made primitive . unlike the prior arts , in the present invention , the sensing devices ( qclt ) 36 u are completely separated from the data storage devices ( page latches 34 ). every 32 bit - lines share 1 qclt . the pitch for qclt is greater . with this design , the sensing device qclt can perform high precision current sensing while the page latch design can be made as simple as possible to fit in the tight pitch . fig4 is a schematic circuit diagram of the qclt 36 u . each qclt comprises a q latch 36 u - 2 , a current - mode comparator 36 u - 1 , a program driving circuit 36 u - 12 , a program verifying circuit 36 u - 13 , a pre - charging transistor 36 u - 10 , a pmos transistor in diode connection 36 u - 7 , a tri - state inverter 36 u - 3 , pass - gate transistors 36 u - 8 / 36 u - 9 / 36 u - 11 / 36 u - 4 / 36 u - 17 , a latch reset circuit 36 u - 6 , two latch preset circuits 36 u - 5 / 36 u - 14 , all as connected and as shown in fig4 . the operation of the qclt 36 u will be discussed hereinafter . fig4 a is a schematic circuit diagram of a page latch 34 . this page latch 34 is simply an sram cell . the program / read operation of the qclt 36 u is as follows : referring to fig4 b there is shown a detailed timing diagram of the read operation for the present invention . to perform the read operation , data node qd of the q latch 36 u - 2 is first reset to 0v by reset circuit 36 u - 6 . the selected bit line blx ( connected by xdl ) is pre - charged to biasl − vtn by pre - charge circuit 36 u - 10 . pmos transistor 36 u - 7 mirrors the cell current into the comparator 36 u - 1 . if the selected cell conducts no current , output vo of the comparator 36 u - 1 stays at 0v . if the selected cell conducts current higher than a pre - determined value , vo becomes vcc . the data at node vo is supplied to the preset circuit 36 u - 5 and when signal latrd is high , the data at node qd will be supplied to vcc . while latrd is high , inverter 36 u - 3 is tri - stated to avoid noise feeding back to the comparator 36 u - 1 . data node qd will be transferred to node pd of page latch 34 ( shown in fig4 a ) through data line sdlb by switching signal xtlat and pglat both to high . once data node qd becomes high after sensing , the pass gate transistor 36 u - 8 will be cut off and the comparator 36 u - 1 will be disconnected from the selected bit line xdl , and from the selected memory cell . by doing this , the selected memory cell will conduct no more current after sensing and the power consumption is greatly reduced . referring to fig4 c there is shown a detailed timing diagram for the programming operation for the present invention . before starting the program operation , all the page latches 34 are reset by signal rstpgb . then data to be programmed are loaded from io pads to the selected page latches 34 through the third column decoder 38 / 40 / 42 . since node sdlb of each qclt 36 u is connected to a plurality of page latches 34 , only one data from a page latch 34 can be uploaded to q latch 36 u - 2 for programming during one program iteration . to upload the selected page latch data , pglat and xtlat are switched to high and q latch 36 u - 2 is tri - stated by switching ph 2 to low ( ph 2 b to high ). next , signal pgmd turns on the pass gate transistor 36 u - 11 that connects the program driver circuit 36 u - 12 to local data line xdl . xdl is connected to the selected bit line through the first column decoder 46 u . depending the data stored in q latch 36 u - 2 , the selected bit line will be driven to either vcc − vtn or 0v . if the selected cell is to be programmed to higher threshold voltage than its original value , its bit line will be pulled down to 0v ( this is the program state ). if the threshold voltage of the selected cell is not to be modified , its bit line will be pulled up to vcc − vtn ( this is the program inhibit state ). referring to fig4 d there is shown a detailed timing diagram for the program verification operation for the present invention . the program verification operation is similar to the current sensing operation depicted in fig4 b except that data node qd of q latch 36 u - 2 is modified in a different way . in fig4 b , node qd will be flipped to 0v if the selected cell conducts current higher than a pre - determined value . in fig4 d , node qd will be flipped to vcc if the selected cell conducts no current . if the selected cell is successfully programmed , its threshold voltage will be higher than a pre - determined value and will conduct no more current under verification condition . once this no - current state is reached , node qd will be flipped to vcc and its corresponding bit line will be pulled up to vcc − vtn (“ program inhibit ” state ). each qdb is wired - nor to pvdt , as shown in fig4 e . if all qdb are high , pvdt will also become high . by checking pvdt , program iterations can be determined to be “ pass ” or “ fail ”. referring to fig4 f there is shown a detailed circuit diagram of the current - mode comparator 36 u - 1 . the comparator 36 u - 1 receives the input voltage line ( shown as vin in fig4 ) and the reference voltage vref ( shown as biasr in fig4 ), converting to current signals lin and iref respectively , and based upon the comparison generates an output voltage vout ( shown as vo in fig4 ). fig5 is a circuit block diagram showing various circuits for performing program and read operations according a preferred embodiment of the present invention . the device of the present invention is also capable of performing what is termed “ gapless read ” fig6 is a timing chart for performing a page - mode gapless read operation . fig7 is a flow chart for performing the page - mode read operation shown in fig6 . in a “ gapless read ” operation , the pre - charge transistors of 36 u - 10 ( shown in fig3 a ) are used to pre - charge the selected bit - lines to the pre - determined voltage level biasl − vtn before starting the page - mode read operation . the pre - charge transistor is activated by the signal xdlpb . the signal ylsx is a decoded signal which represents the selection of the particular sub - page 18 l - x . when the particular ylsx is activated , it pre - charges those 32 bit lines associated with sub - page 18 l - x . for example , if yls 0 is activated , then bit lines bl 0 , bl 16 , bl 32 , bl 48 , . . . , bl 496 are all pre - charged to biasl − vtn . to perform the page - mode read operation , the q latch 36 u - 2 is first reset by the latch reset circuit 36 u - 6 and the selected bit - line is pre - charged to the voltage level of biasl − vtn by bit - line pre - charge circuits 36 u - 10 . depending on the data stored in the selected memory cell , mbl ( or the bit line or column line ) will be driven to either one of the two binary voltage levels : high or low after bit - line pre - charging . the data stored in memory cells can be in one of two states : on or off . each state represents one of the binary data : 1 or 0 . if the selected memory cell is in an on condition , this cell will draw current to discharge mbl from pre - charged level of biasl − vtn down to 0v ( low level ). if the selected memory is in an off condition , this cell draws no current and mbl stays at the pre - charged level of biasl − vtn ( high level ). after the pre - charged bit - line reach electrical steady state , the data stored in the selected memory cell is translated into the corresponding voltage level on xdl . in the period shown as “ sense out sub - page ( 0 ) yls & lt ; 0 & gt ;” a particular sub - page x is selected . when the signal xdlpb goes low , the selected bit line is pre - charged . when yls & lt ; 0 & gt ; first goes high , reset of latch 36 u - 2 occurs by rstqclt being high , and the transistors in the first column decoder 46 u are turned on . the memory cells from the selected sub - page x are then read and stored in the associated latches 34 . in the next period shown as “ sense out sub - page ( 1 ) yls & lt ; 1 & gt ;” a second particular sub - page x + 1 is selected . the memory cells from the selected sub - page x + 1 are then read and stored in the associated latches 34 . in the next time period shown as “ clock out sub - page yl & lt ; 0 & gt ;” the data stored in the latches 34 associated with sub - page x is clocked out . in the next time period shown as “ clock out sub - page yl & lt ; 1 & gt ;” the data stored in the latches 34 associated with sub - page x + 1 is clocked out . at the same time , however , the data in the memory cells from a third particular sub - page x + 2 is selected . the memory cells from the selected sub - page x + 2 are then read and stored in the associated latches 34 . thereafter , in each time period , a read of the data from the latches 34 occurs while at the same time data from memory cells associated with another sub - page group is read and is stored in their associated latches . fig8 is a flow chart for performing the page - mode program operation related to fig4 c ˜ 4 d . this flow chart comprises 2 main loops . before starting the program operation , all the page latches must be reset to “ program inhibit ” state and a starting address must be input to the on - chip address counter . the starting address for programming will be latched by a first set of on - chip address registers . in loop 1 , bytes of data will be loaded into page latches sequentially . as the address counter increments , a second set of address registers store the latest address as the end address for programming . in loop 2 , consecutive sub - pages will be programmed successively . as stated above , 2 sets of address registers are used to store both the starting and end address for programming . therefore , in this loop , only those sub - pages that are previously loaded with data in loop 1 will be programmed . program verification is also embedded for each sub - page program in loop 2 . the circuits described heretofore can also be used to store multi - levels in a memory cell . in the following description , embodiments capable of performing multi - level page - mode read and program operation will be detailed . fig9 shows typical threshold voltage distribution of a multi - level cells in a flash memory array . the cell threshold voltage falls into one of 4 groups . two bits of binary codes are assigned to each group . in this figure , the group of lowest threshold voltage value is assigned state ‘ 11 ’ while the group of highest threshold voltage value is assigned state ‘ 00 ’. with this state assignment , two bits of binary data are mapped to 4 threshold voltage levels . hence , 2 - bit binary data could be stored in the form of four different threshold voltage levels . to manipulate the threshold voltage level , cells are first erased to their lowest threshold level ‘ 11 ’. then multi - step program iterations are used to boost up the threshold voltage incrementally until it reaches the desired level . to read a multi - level cell , a multi - step sensing operation is adopted to detect and convert the threshold voltage level into a two - bit binary code . during the multi - step sensing , a multi - level voltage source is applied to cong terminal . the variable voltage level applied to cong is used as reference to detect the threshold voltage . the detecting algorithm is commonly known as “ successive approach ”. at the beginning , cong is set to vcr 1 and sensing circuitry is turned on to detect whether the selected cell conducts current or not . if the cell conducts current , the threshold voltage belongs to group ‘ 11 ’. if the cell conducts no current , cong will be set to vcr 2 to sense a higher level . step by step , cong level is raised higher each time to sense higher threshold voltage level . once the threshold voltage level of the selected cell is found , the corresponding binary codes will be assigned and stored fig1 is a schematic view of a qclt 36 u modified from fig4 for multi - level read / program operation . the basic structure is mostly identical to the embodiment shown in fig4 except that the q latch related circuitry 36 u - 2 is duplicated , shown as 36 u - 2 h and 36 u - 2 l , and pattern - recognition circuitry ptr 36 u - 15 / 36 u - 16 h / 36 u - 16 l is added . fig1 a shows the page latches 34 for multi - level operation . fig1 b is a schematic circuit diagram of the pattern - recognition device ptr . the ptr circuit is used to selectively accept or reject some specific data paterns . the ptr circuit accepts only specific patterns of data loaded into q latches 36 u - 2 h / 36 u - 2 l before program iteration starts . if the data loaded into q latches 36 u - 2 h / 36 u - 2 l is not accepted by ptr , q latches 36 u - 2 h / 36 u - 2 l will be reset to “ program inhibit ” state . this pattern selection device could eliminate over - programming to those cells that need not to be programmed . the program / read operation of this multi - level qclt 36 is detailed below . refer to fig1 c ˜ 10 f for detail timing diagram of cell current sensing . the multi - level read operation is divided into 3 serial sections . in the first section , the inputs { qdh , qdl } of q latches 36 u are first reset to { 0 , 0 } state , respectively , by 36 u - 6 h / 36 u - 6 l . cong is connected to vcr 1 output of the multi - level voltage source and the selected bit line is pre - charged to biasl − vtn by 36 u - 10 . pmos transistor 36 u - 7 mirrors the cell current into the comparator 36 u - 1 . if the threshold voltage of the selected cell is higher than vcr 1 , vo of the comparator 36 u - 1 stays at 0v . otherwise , as shown in fig1 c , vo becomes vcc and the inputs { qdh , qdl } to q latches 36 u - 2 h / 36 u - 2 l will be flipped to { 1 , 1 } state when signal lat 11 ( supplied to 36 u - 5 h / 36 u - 5 l ) is high . while lat 11 is high , inverter 36 u - 3 h / 36 u - l is tri - stated to avoid noise feeding back to the comparator 36 u - 1 . once the inputs { qdh , qdl } to q latches 36 u - 2 h / 36 u - 2 l become { 1 , 1 } after sensing , pass gate transistor 36 u - 8 h / 36 u - 8 l will be cut off and the comparator 36 u - 1 will be disconnected from the selected memory cell . by doing this , the selected cell will conduct no more current after sensing and the data { qdh , qdl } is frozen during the rest of the sensing operation . in the second section , cong is raised to vcr 2 and the selected bit line is pre - charged . if threshold voltage of the selected cell is higher than vcr 2 , vo of the comparator 36 u - 1 stays at 0v . otherwise , as depicted in fig1 d , vo becomes vcc and inputs { qdh , qdl } to q latches 36 u - 2 h / 36 u - 2 l will be flipped to { 1 , 0 } state , respectively , when signal lat 10 is high . once inputs { qdh , qdl } become { 1 , 0 } after sensing , pass gate transistor 36 u - 8 h will be cut off . the data { qdh , qdl } is frozen during the rest of sensing operation . in the third section , cong is raised to vcr 3 and the selected bit line is pre - charged . if threshold voltage of the selected cell is higher than vcr 3 , vo of the comparator 36 u - 1 stays at 0v . otherwise , as depicted in fig1 e , vo becomes vcc and { qdh , qdl } will be flipped to { 0 , 1 } state when signal lat 01 is high . once { qdh , qdl } becomes { 0 , 1 } after sensing , pass gate transistor 36 u - 8 l will be cut off . the data { qdh , qdl } is frozen during the rest of sensing operation . if the threshold voltage of the selected cell is higher than vcr 3 , { qdh , qdl } stays at { 0 , 0 } state as depicted in fig1 f . data { qdh , qdl } will be transferred to node { pdh , pdl } of page latches 34 h / 34 l through local data line sdlb while signal xtlath / xlatl and pglath / pglatl become high . for programming a cell to multi - levels , refer to fig1 g ˜ 10 i for detail program timing diagram . before starting the program operation , all the page latches 34 are reset by signal rstpgb . then data to be programmed are loaded from io pads to the selected page latches 34 through the third column decoder 38 / 40 / 42 . since node sdlb of each qclt 36 u is connected to a plurality of page latches , only one { pdh , pdl } pair of those page latch data can be uploaded to { qdh , qdl } for programming during one program iteration . to upload the selected { pdh , pdl }, pglath / pglatl and xtlath / xlatl are switched to high and q latches 36 u - 2 h / 36 u - 2 l are tri - stated by switching ph 2 / ph 3 to low ( ph 2 b / ph 3 b to high ). after { qdh , qdl } is loaded , ptr 36 u - 15 is activated to check the data pattern of { qdh , qdl } by properly switching signal loadpatl , loadpatm , loadpath and patrec . different { qdh , qdl } patterns represent different threshold voltage levels to which the cells are about to be programmed . the multi - level program algorithm of the present invention will selectively accept specific { qdh , qdl } patterns according the target threshold voltage level . if the { qdh , qdl } pattern is not accepted by ptr , { qdh , qdl } will be set to “ program inhibit ” state (“ 11 ” state ) by 36 u - 16 h / 36 u - 16 l . for instance , as depicted in fig1 g , the target threshold voltage level is “ 10 ”. data pattern “ 10 ”, “ 01 ”, “ 00 ” will be accepted and data pattern “ 11 ” is “ program inhibit ” state . in fig1 h , the target level is “ 01 ”. data pattern “ 01 ” and “ 00 ” are accepted . pattern “ 10 ” is rejected because level 10 is lower than the target level and should not be over - programmed to level “ 01 ”. in fig1 i , the target level is “ 00 ”, data pattern “ 01 ”, “ 10 ” will be rejected to prevent over - programming to level “ 00 ”. next , signal pgmd turns on the pass gate transistor 36 u - 11 that connects the programming circuit 36 u - 12 to local data line xdl . xdl is connected to the selected bit line through the first column decoder 46 u . depending the { qdh , qdl } data stored in q latches , the selected bit line will be driven to either vcc − vtn or 0v . if the selected cell is about to be programmed to higher threshold voltage than its original value , its bit line will be pulled down to 0v . if the threshold voltage of the selected cell is not to be modified , its bit line will be pulled up to vcc − vtn . fig1 j is a timing diagram of multi - level program verification . the program verification operation is similar to the current sensing operation depicted in fig1 c except that data { qdh , qdl } is modified in a different way . cong is set to one of vcr 1 , vcr 2 or vcr 3 according the target threshold voltage level . { qdh , qdl } will be flipped to “ program inhibit ” state (“ 11 ” state ) if the selected cell conducts no current . if the selected cell is successfully programmed , its threshold voltage will be higher than the target level and will conduct no more current under verification condition . once this no - current state is reached , { qdh , qdl } will be flipped to “ 11 ” and its corresponding bit line will be pulled up to vcc − vtn (“ program inhibit ” state ). each qdhb / qdlb is wired - nor to pvdt . if all qdh / qdl become high , pvdt will also become high . by checking pvdt , program iterations can be determined to be “ pass ” or “ fail ”. fig1 k shows how the qdhb / qdlb nodes are wired to form a nor logic . fig1 is a flow chart for performing the multi - level page - mode program operation . this flow chart is mostly identical to fig8 except that an extra section of data pattern recognition algorithm is added to eliminate over - programming ( refer to ptr fig1 b ). fig1 a is another flow chart modified from fig1 . in this chart , the data pattern recognition algorithm is changed and new ptr depicted in fig1 b is used to replace ptr of fig1 b . in this new algorithm , only one specific pattern is accepted for each target threshold voltage level . for instance , if the target level is “ 10 ”, only pattern “ 10 ” will be accepted and all the other patterns will be rejected ( flipped to “ program inhibit ” state ). referring to fig1 b there is shown one embodiment of the ptr 36 u - 15 . the signal loadpatall is supplied to the gate of transistor 80 . transistor 80 connects the output signal hitb to node 98 . at node 98 there are 6 parallel branch paths : designated as a , b , c , d , e and f . the signal loadpatl is supplied to the gate of transistors 82 a , 82 b , and 82 c . the signal loadpatm is supplied to the gate of transistors 84 d and 84 e . the signal loadpath is supplied to the gate of transistor 86 f . the data signal qdh is supplied to the gate of transistor 88 c . the inverse of the signal qdh , qdhb is supplied to the gate of transistors 90 a , 90 b , 90 d , 90 e and 90 f . the signal qdl is supplied to the gate of transistor 92 b and 92 e . the inverse of the signal qdl , qdlb is supplied to the gate of transistors 94 a , 94 c , 94 d , and 94 f . as can be seen from fig1 b , all the transistors in the same current path ( a , b , c , d , e , or f ) are connected in series . thus , transistors 82 a , 90 a and 94 a are connected in series . similarly , transistors 82 b , 90 b , and 92 b are connected in series . although there is shown in fig1 b the designations “ 00 ”,“ 01 ”, and “ 10 ”. it should be noted that these are not inputs . rather they are comments showing when the states of { qdh , qdl } connect hitb to ground , as explained hereinbelow . in fig1 b , when loadpatall = 1 , then transistor 80 connects hitb to node 98 . further if loadpatl = 1 , and if qdhb =“ 1 ” and qdlb =“ 1 ”, then hitb will be connected to vss through transistors 82 a , 90 a , and 94 a . when qdhb =“ 1 ” and qdlb =“ 1 ”, then this means that the inverse of the signals or qdh and qdl are both “ 0 ”. thus hitb is connected to ground when { qdh , qdl } are in the state of { 0 , 0 }. similarly , if loadpatl = 1 , and { qdh , qdl } are in the state of { 0 , 1 }, then hitb is connected to ground through transistors 82 b , 90 b , and 92 b . if loadpatl = 1 , and { qdh , qdl } are in the state of { 1 , 0 }, then hitb is connected to ground through transistors 82 c , 88 c , and 94 c . the other three conditions when hitb is connected to ground occurs when loadpatm = 1 , and { qdh , qdl } are in the states of { 0 , 0 }; or when loadpatm = 1 , and { qdh , qdl } are in the states of { 0 , 1 }; or when loadpath = 1 , and { qdh , qdl } are in the states of { 0 , 0 }. once hitb = 0 , the data of { qdh , qdl } is accepted and will be programmed into memory cells . in contrast in fig1 b , when loadpatall = 1 , and loadpatl = 1 , if the states of { qdh , qdl } are “ 10 ”, hitb will become 0 . when loadpatall = 1 , loadpatm = 1 , if the states of { qdh , qdl } are “ 01 ”, hitb will become 0 . finally , when loadpatall = 1 , and loadpath = 1 , if the states of { qdh , qdl } are “ 00 ”, hitb will become 0 . once hitb = 0 , the data of { qdh , qdl } is accepted and will be programmed into memory cells . with reference to the algorithm of programming shown in fig1 , the ptr of fig1 b is adopted . when program level =“ 10 ”, loadpatall = 1 and loadpatl = 1 , hitb will be 0 if { qdh , qdl } equal to any one of “ 00 ”,“ 01 ”, or “ 10 ”. cells which are going to be programmed to three different levels “ 00 ”,“ 01 ”,“ 10 ” are first programmed to level “ 01 ” as shown in fig1 g . when program level =“ 01 ”, loadpatall = 1 , and loadpatm = 1 , hitb will be 0 if { qdh , qdl } equal to either one of “ 00 ” or “ 01 ”. if { qdh , qdl }=“ 10 ”, hitb will be 1 and { qdh , qdl } will be flipped to “ 11 ”. cells which are going to be programmed to two different level “ 00 ” or “ 01 ” are then programmed to level “ 01 ” as shown in fig1 h . when program level =“ 00 ”, loadpatall = 1 and loadpath = 1 , hitb will be 0 if { qdh , qdl } equal to “ 00 ”. if { qdh , qdl }=“ 01 ” or “ 10 ”, hitb will be 1 and { qdh , qdl } will be flipped to “ 11 ”. cells which are going to be programmed to level “ 00 ” are then programmed to level “ 00 ” as shown in fig1 i . in this algorithm , cells which are to be programmed to different levels (“ 00 ”,“ 01 ”,“ 10 ”) are programmed in such a manner that all those cells are first programmed to the lowest level ( in this case “ 10 ”) regardless of their individual target level . then , in the following program interval , cells are programmed to the middle level (“ 01 ”). during this program interval , cells targeted for level “ 10 ” will be selectively rejected by ptr device ( when hitb = 1 ). only cells with target level “ 00 ” and “ 01 ” will be programmed to level “ 01 ”. similarly , in the final program interval , only cells targeted for level “ 00 ” will be programmed to level “ 00 ”, while cells targeted for level “ 10 ” and “ 01 ” will be selectively rejected . the programming algorithm of fig1 a differs from that shown in fig1 only in the ptr device portion and the method of operation based upon this difference . in the programming algorithm shown in fig1 a , the ptr of fig1 b is adopted . when program level =“ 10 ”, loadpatall = 1 and loadpatl = 1 , hitb will be 0 only if { qdh , qdl } equal to “ 10 ”. cells which are going to be programmed to level “ 10 ” are programmed to level “ 01 ”. when program level =“ 01 ”, loadpatall = 1 , and loadpatm = 1 , hitb will be 0 only if { qdh , qdl } equal to “ 01 ”. cells which are going to be programmed to level “ 01 ” are then programmed to level “ 01 ”. when program level =“ 00 ”, loadpatall = 1 and loadpath = 1 , hitb will be 0 only if { qdh , qdl } equal to “ 00 ”. cells which are going to be programmed to level “ 00 ” are then programmed to level “ 00 ”. in this algorithm , cells which are to be programmed to different levels (“ 00 ”,“ 01 ”,“ 10 ”) are programmed in such a manner that cells of the same target level are programmed to their individual target level in one program interval . during program interval for level “ 10 ”, level “ 00 ” and “ 01 ” will be rejected ( hitb = 1 ). during program interval for level “ 01 ”, level “ 00 ” and “ 10 ” will be rejected . during program interval for level “ 00 ”, level “ 01 ” and “ 10 ” will be rejected .
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next , an embodiment of a surrounding environment recognition device of the invention will be described below with reference to the drawings . further , in the embodiment below , an example will be described in which the surrounding environment recognition device of the invention is applied to an in - vehicle environment recognition device mounted on a vehicle such as an automobile , but the invention is not limited to the in - vehicle environment recognition device . for example , the surrounding environment recognition device can be also applied to a construction machine , a robot , a monitoring camera , an agricultural machine , and the like . fig1 is a block diagram showing an internal function of the surrounding environment recognition device . an in - vehicle surrounding environment recognition device 10 of the embodiment is used to recognize a surrounding environment of a vehicle on the basis of an image obtained by capturing an external environment by an in - vehicle camera . the surrounding environment recognition device 10 includes an in - vehicle camera which captures an outside image of the vehicle and a recognition device which recognizes a surrounding environment on the basis of an image captured by the in - vehicle camera . however , the in - vehicle camera is not essentially necessary for the surrounding environment recognition device as long as only an outside image captured by the in - vehicle camera or the like can be acquired . the surrounding environment recognition device 10 includes , as illustrated in fig1 , an image capturing unit 100 , a lens state diagnosis unit 200 , a sensing range determination unit 300 , an application execution unit 400 , and a notification control unit 500 . the image capturing unit 100 captures a vehicle surrounding image acquired by , for example , in - vehicle cameras 101 ( see fig6 ) attached to front , rear , left , and right sides of a vehicle body ( an image acquisition unit ). the application execution unit 400 recognizes an object from the image acquired by the image capturing unit 100 and executes various applications for detecting a pedestrian or a vehicle ( hereinafter , referred to as an application ). the lens state diagnosis unit 200 diagnoses a lens state of each in - vehicle camera 101 on the basis of the image acquired by the image capturing unit 100 . the in - vehicle camera 101 includes an imaging element such as a cmos and a lens of an optical system disposed at the front side of the imaging element . further , the lens of the embodiment is not limited to a focus adjusting lens and generally also includes a glass of an optical system ( for example , a stain preventing filter lens or a polarizing lens ) disposed at the front side of the imaging element . the lens state diagnosis unit 200 diagnoses a stain caused by a particulate deposit , cloudness , or a water droplet of the lens . when the in - vehicle camera 101 is disposed , for example , outside the vehicle , there is concern that a particulate deposit of mud , trash , or bugs may adhere to the lens or the lens may become cloudy like obscure glass due to dust or a water stain . further , there is concern that the water droplet adheres to the lens so that the lens becomes dirty . when the lens of the in - vehicle camera 101 becomes dirty , a part or the entirety of a background captured in an image is hidden or a background image becomes dim due to low sharpness or becomes distorted . as a result , there is concern that the object may not be easily recognized . the sensing range determination unit 300 determines a sensing enabled range capable of recognizing a recognition object on the basis of the lens state diagnosed by the lens state diagnosis unit 200 . the sensing enabled range changes in response to a stain degree including a particulate deposit adhering position and a particulate deposit size with respect to the lens . also , the sensing enabled range also changes in response to the application executed by application execution unit 400 . for example , even when the lens stain degree and the distance from the lens to the object are the same , the sensing enabled range becomes wider when the recognition object of the application is a large object such as a vehicle compared to a small object such as a pedestrian . the notification control unit 500 executes a control that notifies at least one of the sensing enabled range and the sensing disabled range to a user on the basis of information from the sensing range determination unit 300 . the notification control unit 500 notifies a change in sensing enabled range to the user , for example , in such a manner that the sensing enabled range is displayed or a warning sound or a message is generated for the user by the use of an in - vehicle monitor or a warning device . in this way , the information can be provided for the vehicle control device in response to the sensing enabled range so that the vehicle control device can use the information for a vehicle control . fig6 is a schematic diagram showing an example of a system configuration of the vehicle and an entire configuration of the in - vehicle camera system . the surrounding environment recognition device 10 has an internal configuration of the image processing device 2 that executes an image process of the in - vehicle camera 101 and an internal function of the vehicle control device 3 that executes a vehicle control or a notification to a driver on the basis of a process result transmitted from the image processing device . the image processing device 2 includes , for example , the lens state diagnosis unit 200 , the sensing range determination unit 300 , and the application execution unit 400 and the vehicle control device 3 includes the notification control unit 500 . the vehicle 1 includes a plurality of in - vehicle cameras 101 , for example , four in - vehicle cameras 101 including a front camera 101 a capturing a front image of the vehicle 1 , a rear camera 101 b capturing a rear image thereof , a left camera 101 c capturing a left image thereof , and a right camera 101 d capturing a right image thereof . accordingly , the peripheral image of the vehicle 1 can be continuously captured . in addition , the in - vehicle camera 101 may not be provided at a plurality of positions , but may be provided at one position . further , only the front or rear image maybe captured instead of the peripheral image . the left and right in - vehicle cameras 101 may be configured as cameras attached to side mirrors or cameras installed instead of the side mirrors . the notification control unit 500 is a user interface and is mounted on hardware different from the image processing device 2 . the notification control unit 500 executes a control that realizes a preventive safety function or a convenience function by the use of a result obtained by the application execution unit 400 . fig7 is a diagram showing an example of a screen displayed on the in - vehicle monitor . from the past , there is known an overview display method of suggesting a sensing enabled range of an application obtained when a predetermined application is executed during a normal operation of the system while a distance space is viewed from the upside of an own vehicle ( the vehicle 1 ) to the in - vehicle monitor 700 . a minimum sensing line 701 in which an object closest to the vehicle 1 can be sensed ( recognized ) by a predetermined application is indicated by a small oval surrounding the periphery of the vehicle 1 and a maximum sensing line 702 in which an object farthest from the vehicle 1 can be sensed ( recognized ) by the same application is indicated by a large oval . when a space between the minimum sensing line 701 and the maximum sensing line 702 becomes a sensing range 704 and the lens is in a normal state without a stain , the entire sensing range 704 becomes the sensing enabled range . in addition , a reference numeral 703 indicated by the dashed line in the drawing indicates a part in which the image capturing ranges of the adjacent in - vehicle cameras overlap each other . the sensing range 704 is set in response to the application in execution . for example , when the object of the application is relatively large like the vehicle 1 , the maximum sensing line 702 and the minimum sensing line 701 respectively increase in size . further , when the object is relatively small like a pedestrian or the like , the maximum sensing line 702 and the minimum sensing line 701 respectively decrease in size . when a stain or the like exists on the lens of the in - vehicle camera 101 , it is difficult to detect a recognition object in a background part hidden by the stain or the like even within the sensing range 704 . as a result , there is concern for a performance deterioration state in which the application cannot exhibit predetermined performance . in the surrounding environment recognition device of the invention , a control of notifying the performance deterioration state of the application to the user is executed . as a notification method , for example , a method can be employed in which the sensing enabled range and the sensing disabled range of the sensing range 704 are visually displayed on the in - vehicle monitor or the like so that the performance deterioration state is accurately notified to the user . in this display method , a detectable distance from the vehicle 1 can be easily checked and a sensing ability deterioration degree caused by deterioration in performance can be easily suggested to the user . further , the performance deterioration state of the application may be notified to the user in such a manner that an led provided on a meter panel or the like inside a vehicle interior is turned on or a warning sound or a vibration is generated . fig8 is a diagram showing an example of a screen displayed on the in - vehicle monitor . an in - vehicle monitor 801 displays an image 802 captured by the in - vehicle camera 101 installed at the front part of the vehicle and also displays a sensing enabled region 803 and a sensing disabled region 804 to be displayed to overlap the image 802 . the image 802 includes a road r at the front side of the vehicle 1 and left and right white lines wl indicating a travel vehicle lane . by such a display , the sensing enabled region 803 set in response to the lens state can be notified to the driver while the lens state of the in - vehicle camera 101 ( see fig6 ) is viewed . then , since the sensing enabled region 803 and the lens state indicating , for example , a message that “ wiping is necessary since a far place is not visible in such a stain degree ” are viewed simultaneously , the sensing ability of the in - vehicle camera 101 can be easily notified to the driver . fig9 is a diagram showing an example of an image displayed on a front glass of the vehicle . here , a scene which is viewed from the vehicle interior through a front glass 901 by the use of a head up display ( hud ) overlaps a real world . since the sensing enabled region 803 or the sensing disabled region 804 are viewed while overlapping a road of the real world , the sensing enabled region or the sensing distance of the actual in - vehicle camera 101 can be easily and visually checked . here , since a projection type head up display for the front glass 901 shields a driver &# 39 ; s view , a display on the entire face of the front glass 901 is difficult . for this reason , as illustrated in fig9 the overlap display with the road using the lower side of the front glass 901 may be performed in such a manner that the sensing enabled region 803 is suggested to overlap the real world by the use of the overlap display at the upper side of the front glass 901 . next , the execution content of the lens state diagnosis unit 200 , the sensing range determination unit 300 , the application execution unit 400 , and the notification control unit 500 illustrated in fig1 will be described sequentially . fig2 is a block diagram showing an internal function of the lens state diagnosis unit 200 . the lens state diagnosis unit 200 includes a particulate deposit detector 210 , a sharpness detector 220 , and a water droplet detector 230 and diagnoses a stain state in accordance with the type of stain adhering to the lens of the in - vehicle camera 101 on the basis of the image acquired by the image capturing unit 100 . fig1 ( a ) to 10 ( c ) are diagrams showing a method of detecting a particulate deposit adhering to the lens . here , fig1 ( a ) shows an image 1001 at the front side of the in - vehicle camera 101 and fig1 ( b ) and 10 ( c ) show a method of detecting the particulate deposit . as illustrated in fig1 ( a ) , the image 1001 is dirty since a plurality of particulate deposits 1002 adhere to the lens . the particulate deposit detector 210 detects the particulate deposit adhering to the lens , for example , the particulate deposit 1002 such as mud shielding the appearance of the background . when the particulate deposit 1002 such as mud adheres to the lens , the background is not easily visible and the brightness is continuously low compared to the periphery . thus , it is possible to detect the particulate deposit 1002 by detecting a region having a small brightness change amount . first , the particulate deposit detector 210 divides an image region of the image 1001 into a plurality of blocks a ( x , y ) as illustrated in fig1 ( b ) . next , the brightness values of the pixels of the image 1001 are detected and a total sum i t ( x , y ) of the brightness values of the pixels included in the block a ( x , y ) is calculated for each block a ( x , y ). then , a difference δi ( x , y ) between the total sum i t ( x , y ) calculated for a captured image of a current frame and a total sum i t - 1 ( x , y ) calculated for a captured image of a previous frame is calculated for each block a ( x , y ). then , the block a ( x , y ) in which the difference δi ( x , v ) is smaller than those of the peripheral blocks is detected and a score sa ( x , y ) corresponding to the block a ( x , y ) is increased by a predetermined value , for example , “ 1 ”. the particulate deposit detector 210 calculates an elapse time ta from the initialization of the score sa ( x , y ) of each block a ( x , y ) after the above - described determination for all pixels of the image 1001 . then , a time average sa ( x , y )/ ta of the score sa ( x , y ) is calculated in such a manner that the score sa ( x , y ) of each block a ( x , y ) is divided by the elapse time ta . the particulate deposit detector 210 calculates a total sum of the time average sa ( x , y )/ ta of all blocks a ( x , y ) and divides the total sum by the number of all blocks of the captured image to calculate a score average sa_ave . when a stain 1002 such as mud continuously adheres to the lens of the in - vehicle camera 101 , the score average sa_ave increases in each of the sequentially captured frames . in other words , when the score average sa_ave is large , there is a high possibility that mud or the like adheres to the lens for a long period of time . it is determined whether the time average sa ( x , y )/ ta exceeds a predetermined threshold value . here , a region in which the time average exceeds the threshold value is determined as a region ( a particulate deposit region ) in which a background is not visible due to mud . this region is used to calculate the sensing enabled range of each application in response to the size of the region in which the time average exceeds the threshold value . further , a final determination is made for the operation of each application by the use of the score average sa_ave . fig1 ( c ) shows a score example in which all blocks are depicted as color gradation depending on the score . then , when the score is equal to or larger than a predetermined threshold value , a region 1012 is determined in which the background is not visible due to the particulate deposit . next , an operation of the sharpness detector 220 will be described with reference to fig1 ( a ) and 11 ( b ) . fig1 ( a ) and 11 ( b ) are diagrams showing a method of detecting the sharpness of the lens . the sharpness detector 220 detects the lens state on the basis of a sharpness index representing whether the lens is clear or unclear . a state where the lens is not clear indicates , for example , a state where a lens surface becomes cloudy due to the stain and a contrast becomes low . accordingly , an outline of an object is dimmed and the degree is indicated by the sharpness . as illustrated in fig1 ( a ) , the sharpness detector 220 sets a left upper detection region bg_l ( background left ), an upper detection region bg_t ( background top ), and a right upper detection region bg_r ( background right ) at a position where a horizontal line is reflected on the image 1001 . the upper detection region bg_t is set to a position including a horizontal line and a vanishing point where two lane marks wl are provided in parallel on the road intersect each other at a far position . the left upper detection region bg_l is set to the left side of the upper detection region bg_t and the right upper detection region bg_r is set to the right side of the upper detection region bg_t . the regions including the horizontal line are set so that edges are essentially included on the image . further , the sharpness detector sets a left lower detection region rd_l ( road left ) and a right lower detection region rd_r ( road right ) at a position where the lane mark wl is reflected on the image 1001 . the sharpness detector 220 executes an edge detection process on pixels within each region of the left upper detection region bg_l , the upper detection region bg_t , the right upper detection region bg_r , the left lower detection region rd_l , and the right lower detection region rd_r . in the edge detection for the left upper detection region bg_l , the upper detection region bg_t , and the right upper detection region bg_r , an edge such as a horizontal line is essentially detected . further , in the edge detection for the left lower detection region rd_l and the right lower detection region rd_r , the edge of the lane mark wl or the like is detected . the sharpness detector 220 calculates an edge strength value for each pixel included in the detection regions bg_l , bg_t , bg_r , rd_l , and rd_r . then , the sharpness detector 220 calculates an average value blave of the edge strength values of each of the detection regions bg_l , bg_t , bg_r , rd_l , and rd_r and determines a sharpness degree on the basis of the average value blave . as illustrated in fig1 ( b ) , the sharpness is set so that the lens is clear as the edge strength becomes strong and the lens nclear as the edge strength becomes weak . it is determined that the application recognition performance is influenced when the calculated average value blave is lower than standard sharpness . then , the application performance deterioration degree is determined for each application by the use of the sharpness average value for each region . when the sharpness is lower than minimal sharpness α2 , it is determined that the recognition in each application is difficult . fig1 ( a ) to 12 ( c ) are diagrams showing a method of detecting a water droplet adhering to the lens . the water droplet detector 230 of fig2 extracts a water droplet feature amount by comparing the brightness of the peripheral pixels on an imaging screen illustrated in fig1 ( a ) . the water droplet detector 230 sets pixels which are separated from an interest point by a predetermined distance ( for example , three pixels ) in the up direction , the right up direction , the right down direction , the left up direction , and the left down direction as inner reference points pi and sets pixels which are further separated therefrom by a predetermined distance ( for example , pixels more than three pixels ) in the five directions as outer reference points po . next , the water droplet detector 230 compares the brightness for each inner reference point pi and each outer reference point po . there is a high possibility that the vicinity of the inside of the edge of the water droplet 1202 is brighter than the outside due to a lens effect . here , the water droplet detector 230 determines whether the brightness of the inner reference point pi at the inside of the edge of the water droplet 1202 is higher than the brightness of the outer reference point po in each of five directions . in other words , the water droplet detector 230 determines whether the interest point is at the center of the water droplet 1202 . when the brightness of the inner reference point pi in each direction is higher than the brightness of the outer reference point po in the same direction , the water droplet detector 230 increases a score sb ( x , y ) of a region b ( x , y ) included in the interest point in fig1 ( b ) by a predetermined value , for example , “ 1 ”. as for the score of b ( x , y ), an instantaneous value at a predetermined time tb is stored and a past score stored for the time tb or more is discarded . the water droplet detector 230 executes the above - described determination for all pixels in a captured image . then , the water droplet detector obtains a total sum of the score sb ( x , y ) of each block b ( x , y ) for an elapse time tb , calculates a time average score sb ( x , y ) by dividing the total sum by the time tb , and calculates a score average sb_ave by dividing the time average score by the number of all blocks in the captured image . a degree in which the score sb ( x , y ) of each divided region exceeds a specific threshold value thrb is determined as a score . then , the divided region exceeding the threshold value and the score are depicted on a map as illustrated in fig1 ( c ) and a sum sb 2 of the scores on the map is calculated . when the water droplet continuously adheres to the lens of the in - vehicle camera 101 , the score average sb_ave for each frame increases . in other words , when the score average sb_ave is large , there is a high possibility that the water droplet adheres to the lens position . the water droplet detector 230 determines whether many water droplets adhere to the lens by the use of the score average sb_ave . the sum sb 2 is appropriate when the water droplet adhering amount on the lens is large and a failure determination on the entire system is made by the use of this value . in the determination of each logic , a separate water droplet occupying ratio is used to determine a maximal detection distance . both the water droplet adhering amount and the score average sb_ave are used in the determination for deterioration in performance of the recognition application due to the stain of the lens . the a method of calculating the sensing enabled range is considered . fig1 ( c ) shows a score example in which all blocks are depicted as color gradation depending on the score . then , when the score is equal to or larger than a predetermined threshold value , a region in which a background is not visible due to the water droplet is determined . fig3 is a diagram showing an internal function of the sensing range determination unit . the sensing range determination unit 300 includes a particulate deposit distance calculation unit 310 , a sharpness distance calculation unit 320 , and a water droplet distance calculation unit 330 and executes a process of determining the sensing enabled range by the use of a diagnosis result of the lens state diagnosis unit 200 . in the particulate deposit distance calculation unit 310 , a sensing enabled range capable of guaranteeing the detection of each application by the use of the detection result of the particulate deposit detector 210 is converted . in the sharpness distance calculation unit 320 , a sensing enabled range capable of guaranteeing the detection of each application by the use of the detection result of the sharpness detector 220 is converted . in the water droplet distance calculation unit 330 , a sensing enabled range capable of guaranteeing the detection of each application by the use of the detection result of the water droplet detector 230 is converted . the particulate deposit distance calculation unit 310 calculates the sensing enabled range in response to the detection result of the particulate deposit detector 210 . it is determined whether the time average sa ( x , y )/ ta exceeds a predetermined threshold value by the use of the result of the particulate deposit detector 210 . then , a region exceeding the threshold value is determined as a region in which a background is not visible due to mud . for example , as illustrated in fig1 - 1 ( a ), when a particulate deposit 1302 such as mud adheres to a left upper side of an image 1301 , it is determined that the time average sa ( x , y )/ ta corresponding to the region of the particulate deposit 1302 exceeds a predetermined threshold value . accordingly , as indicated by a dark region 1303 in fig1 - 1 ( b ), a region in which a background is not visible due to the particulate deposit 1302 is selected on the image . next , the sensing enabled range in this case is defined for each application . an important point herein is that the size of the recognition object in each application is different . first , an example for a pedestrian detection application will be described . as illustrated in fig1 - 2 ( a ) and 13 - 2 ( b ), a pedestrian p overlaps a region in which a background is not visible due to the particulate deposit 1302 . on the image , the size of the pedestrian p becomes different in response to a distance in the depth direction . since a percentage ( a ratio ) in which the particulate deposit 1302 shields the pedestrian p increases as the pedestrian p is located at a far position , it is difficult to guarantee a detection at a far position and a detection in the left direction of the front fish - eye camera . in the example illustrated in fig1 - 2 ( a ), a pedestrian is separated from an own vehicle by 6 . 0 m and most part of the pedestrian is hidden by the shade of the particulate deposit 1302 so that only a shape smaller than 40 % of the size of the pedestrian is visible . for this reason , the pedestrian detector 430 of the application execution unit 400 cannot recognize the pedestrian ( an unrecognizable state ). meanwhile , as illustrated in fig1 - 2 ( b ) when the pedestrian is separated from the own vehicle by 1 . 0 m , a shape equal to or larger than 40 % of the size of the pedestrian is visible . for this reason , the pedestrian detector 430 can recognize the pedestrian ( a recognizable state ). this process is executed for each depth distance z . as the pedestrian , a pedestrian having a body shape ( a standard size ) with a height of 1 . 8 m is supposed . then , the size of the pedestrian p on the image 1301 in appearance is calculated for each depth distance z from 1 m to 5 m . here , a maximal percentage of the pedestrian p hidden by the particulate deposit 1302 ( a ratio in which a recognition object having a standard size is hidden by a particulate deposit region ) is calculated by the comparison of the shape of the pedestrian p in each depth and a region part ( a particulate deposit region ) in which a background ot visible due to the particulate deposit 1302 such as mud . for example , a depth in which 30 % or more of the pedestrian p is not visible to maximal and a viewing angle θ from the camera 101 are calculated . fig1 - 3 ( a ) and 13 - 3 ( b ) illustrated examples in which a sensing disabled range 1331 incapable of recongnizing ( sensing ) the pedestrian and a sensing enabled range 1332 capable of recognizing ( sensing ) the pedestrian are displayed on a display unit 1330 such as an in - vehicle monitor . the sensing range determination unit 300 determines the sensing enabled range capable of sensing the pedestrian and the sensing disabled range incapable of sensing the pedestrian by the lens state diagnosed by the lens state diagnosis unit 200 when the application is executed . in the example illustrated in fig1 - 3 ( a ), the sensing disabled range 1331 is set such that the pedestrian farther than a predetermined distance 705 is not visible in response to the shape or the size of the particulate deposit . the predetermined distance 705 is set such that a position moves close to the vehicle 1 as the size of the particulate deposit becomes large and a position moves away from the vehicle 1 as the size of the particulate deposit becomes small . an angle θ determining the horizontal width of the sensing disabled range 1331 is set in response to the size of the particulate deposit . then , in the example of fig1 - 3 ( b ), particulate deposit adheres to the in - vehicle camera 101 a attached to the front part of the vehicle 1 . here , since there is a high possibility that a far position is not visible due to the influence of the particulate deposit , a position farther than the predetermined distance 705 of the image captured by the in - vehicle camera 101 installed at the front part of the vehicle cannot be used . a concept of a vehicle detection is similar to that of the pedestrian detection and a vehicle m corresponding to a recognition object has a width of 1 . 8 m and a depth of 4 . 7 m . then , a difference from the pedestrian p is that a direction of the vehicle m corresponding to the detection object is the same as a direction in which a lane is recognized or an own vehicle travels . a calculation is made on the assumption that the vehicle is a preceding vehicle or a preceding vehicle traveling on an adjacent vehicle lane in the same direction . for example , as illustrated in fig1 - 1 ( a ), a case in which a preceding vehicle m traveling on a lane wl overlaps the left upper particulate deposit 1302 will be examined in each depth . since the vehicle n is larger than the pedestrian p , it is possible to detect a position farther than the pedestrian p . here , when 40 % or more of the vehicle body is hidden , it is determined that the detection is not easily guaranteed . since the vehicle m is a rigid body compared to the pedestrian p and an artificial object , it is possible to guarantee the detection even when the hidden percentage ( ratio ) increases compared to the pedestrian p . for example , as illustrated in fig1 - 2 ( a ) and 14 - 2 ( b ), since the percentage in which the particulate deposit 1302 shields the vehicle m increases as the vehicle m is located at a far position , it is difficult to guarantee a detection at a far position and a detection in the front direction of the front fish - eye camera . in the example illustrated in fig1 - 2 ( a ), since the preceding vehicle is separated from the own vehicle by 7 . 0 m , a vehicle detector 420 cannot recognize the vehicle ( an unrecognizable state ). further , in the example illustrated in fig1 - 2 ( b ), since the preceding vehicle is separated from the own vehicle by 3 . 0 m , the vehicle detector 420 can recognize the vehicle ( a recognizable state ). a basic concept of a lane recognition is similar to that of the pedestrian detection or the vehicle detection . a difference is that a size of the recognition object is not set . however , it is important that , since the lane wl is recognized from a far position of 10 m to the vicinity of 50 cm , an invisible range from a certain meter position to a certain meter position is detected . then , it is determined whether a stain region on a screen is hidden in a certain range on the road by the use of the geometry of the camera . in the case of a white line ( the lane wl ), the right recognition performance using parallelism is influenced when a far left side is not visible . for this reason , when it is determined that a left position farther than 5 m is not visible , it is determined that a far right side of the white line cannot be recognized due to the same performance . even in an actual image process , an erroneous detection may be reduced by an image process excluding a position farther than 5 m . alternatively , only the stain region maybe excluded from the sensing region . while a detection guarantee range is suggested , it is determined whether the detection guarantee range can be used for a control , can be used for a warning instead of a control , or cannot be used for any purpose in consideration of the accuracy of the horizontal position , the yaw angle , and the curvature of the lane recognition deteriorating as a detection guarantee region becomes narrow . a parking frame exists on the road as in the white line , but an approximate size of an object can be regarded as a given size differently from the white line . of course , there is a slight difference in the size of the parking frame depending on a place . however , for example , a parking frame having a width of 2 . 2 m and a depth of 5 m is defined and the possibility of the hidden percentage inside the frame of the region is calculated . in fact , since only a frame line is important , the parking frame can be detected even when only the inside of the frame becomes dirty due to mud . however , when the parking frame is not visible due to the movement of the vehicle , the performance of the application cannot be guaranteed . thus , the possibility of the hidden percentage inside the frame due to mud is calculated . when the percentage exceeds 30 %, an operation cannot be guaranteed . this calculation is also executed for each depth . further , the application using the parking frame is used for a parking assist in many cases while the vehicle is turned . for this reason , even when 30 % or more of mud adheres to a position farther than 7 m at the left side of the front camera in the depth direction , a range capable of guaranteeing the application is defined as the vicinity within 7 m in the front camera . in a barrier detection , all three - dimensional objects existing around the vehicle are defined as detection objects and thus the size of the detection object cannot be defined . for this reason , in the barrier detection , a case in which a foot of a three - dimensional object existing on the road cannot be specified is defined as a case in which the barrier detection performance cannot be guaranteed . for this reason , a basic concept is supposed on the assumption that a road region having a certain size is reflected on a mud detection region . then , an invisible distance due to a shielding ratio increasing at a certain range from the own vehicle is obtained by conversion and thus the barrier detection performance guarantee range is determined . for example , as illustrated in fig1 ( a ) , when the particulate deposit 1302 adheres to the lens so that a region in which an arrow in the up direction is not visible exist , this region can be determined as a region in which a background is not visible due to the particulate deposit , that is , a sensing disabled range 1303 can be determined as illustrated in fig1 ( b ) . in this way , in the vehicle detection or the pedestrian detection capable of assuming the approximate three - dimensional size of the detection object corresponding to the three - dimensional object , the three - dimensional object having a certain size and corresponding to the detection object is assumed and a percentage in which the three - dimensional object is shielded by a certain degree of a stain on the image is calculated when the three - dimensional position is changed in the depth direction on the road and the horizontal direction perpendicular thereto . here , an unrecognizable three - dimensional position is determined when the percentage shielded by the particulate deposit exceeds a threshold value and a recognizable three - dimensional position is determined when the percentage does not exceed the threshold value . in this way , when the durable shielding ratio of the object in each application illustrated in fig1 is calculated in the particulate deposit state , a position where a detection object detection rate decreases is estimated as a three - dimensional region based on the own vehicle . here , when the object size is not defined as in the barrier detection , a certain size at a foot position is assumed and the visible state of the region may be determined instead . fig1 is a table showing a durable shielding ratio and a standard size of the recognition object of the application . here , the durable shielding ratio indicates a state where the recognition object can be recognized when the size of the particulate deposit on the image is smaller than the size of the recognition object by a certain percentage . for example , when the particulate deposit is 50 % or less of the size of the vehicle in the vehicle detection , the vehicle can be recognized . further , when the particulate deposit is 40 % or less of the size of the pedestrian in the pedestrian detection , the vehicle can be recognized . in this way , when the sensing enabled range of the camera is estimated in the three - dimensional region on the image , the sensing enabled range changing in response to the lens state of the camera can be easily notified to the user . in the sharpness distance calculation unit 320 illustrated in fig3 , a guaranteed detection distance is calculated on the basis of the average value blave of the sharpness obtained by the sharpness detector 220 . first , standard sharpness α1 of the lens sharpness necessary for obtaining the edge strength used to recognize the recognition object to the maximal detection distance in each application is set . fig1 ( a ) is a diagram showing a relation between the maximal detection distance and the edge strength of each application . then , when the sharpness is equal to or larger than the standard sharpness α1 , each application can guarantee a sensing operation to the maximal detection distance . however , the guaranteed detection distance from the maximal detection distance becomes shorter as the sharpness becomes lower than the standard sharpness α1 . the sharpness distance calculation unit 320 shortens the guaranteed detection distance as the sharpness decreases from the standard sharpness α1 . fig1 ( b ) is a graph showing a relation between a detection distance and sharpness . here , when the sharpness blave exists between the standard sharpness al and the minimal sharpness α2 , the guaranteed detection distance of the application changes . regarding the setting of each application , as illustrated in the table of fig1 ( a ) , when the maximal detection distance of each application exists and a range of the maximal detection distance is guaranteed , the standard sharpness α1 or more set for each application needs to be indicated by the average value blave of the sharpness . as the average value blave of the sharpness decreases from the standard sharpness α1 , the guaranteed detection distance decreases . when the sharpness reaches the minimal sharpness α2 of the target application , the detection is not available . for example , when the application is for the vehicle detection , the maximal detection distance becomes 10 m when the standard sharpness is 0 . 4 and the minimal detection distance becomes 0 m when the minimal sharpness is 0 . 15 . then , when the application is for the pedestrian detection , the maximal detection distance becomes 5 m when the standard sharpness is 0 . 5 and the minimal detection distance becomes 0 m when the minimal sharpness is 0 . 2 . fig1 ( a ) and 17 ( b ) are diagrams showing a method of determining the sensing enabled range by the sensing range determination unit 300 in response to the sharpness . fig1 ( a ) shows an example in which the low sharpness state is displayed on the in - vehicle monitor and fig1 ( b ) shows an example in which the sensing disabled range 1331 incapable of recognizing ( sensing ) the pedestrian and the sensing enabled range 1332 capable of recognizing ( sensing ) the pedestrian are displayed on the display unit 1330 such as an in - vehicle monitor . for example , when the sharpness is low due to cloudness as illustrated in fig1 ( a ) , there is a high possibility that a far position is not visible . for this reason , as illustrated in fig1 ( b ) it is defined that a position farther than the predetermined distance 705 in the image captured by the in - vehicle camera 101 installed at the front part of the vehicle cannot used . the predetermined distance 705 is set such that a position moves close to the vehicle 1 as the sharpness becomes closer to the minimal sharpness and a position moves away from the vehicle 1 as the sharpness becomes closer to the standard sharpness . in the water droplet distance calculation unit 330 illustrated in fig3 , the sensing enabled range for each application is calculated on the basis of the result of the water droplet detector 230 . a region within a process region of each application and having a score sb ( x , y ) exceeding the threshold value thrb is calculated on the basis of the threshold value thrb and the score sb ( x , y ) obtained as a result of the water droplet detection . since this is obtained as a numerical value indicating the amount of the water droplet within the process region of each application , the water droplet occupying ratio is obtained for each application ( each recognition application ) in such a manner that an area of a water droplet adhering region ( an area of a water droplet region corresponding to a region in which the water droplet adheres ) within the process region of the application is divided by an area of the process region . by using the water droplet occupying ratio , the maximal detection distance is determined . as illustrated in fig1 ( a ) , there is a high possibility that the lens state promptly changes in the case of a water droplet 1902 . for example , the lens state may change due to the water droplet of falling rain or from the road or the water droplet amount may be reduced due to the opposite traveling wind or the heat generated during the activation of the camera . likewise , there is a high possibility that the lens state may change at all times . for this reason , it is possible to prevent a determination that the position 1903 is in a region which is out of a viewing angle or cannot be detected due to the position of the current water droplet . in the lens state involving with the current water droplet adhering amount , a far position or a small object position cannot be correctly determined . accordingly , an operation depending on the lens state is guaranteed in such a manner that the detection distance is set to be short . since the process region is different for each application , the water droplet distance calculation unit 330 calculates the guaranteed detection distance from the water droplet occupying ratio obtained in consideration of the process region . further , the water droplet occupying ratio capable of guaranteeing the maximal detection distance of the application from the value of the water droplet occupying ratio is set as the durable water droplet occupying ratio illustrated in fig2 ( a ) . further , the water droplet occupying ratio incapable of guaranteeing the detection and the operation of the application is set as the limited water droplet occupying ratio . the limited water droplet occupying ratio state indicates a state where the guaranteed detection distance is 0 m . here , the guaranteed detection distance from the durable water droplet occupying ratio to the limited water droplet occupying ratio decreases linearly as illustrated in fig2 ( b ) . the image of the background is not easily visible when the water droplet adheres to the lens . thus , the image may be erroneously detected or may not be detected for an image recognition logic as the water droplet adhering amount on the lens increases . for this reason , since the water droplet adhering amount within the range of the image process for recognizing the recognition object among the water droplets adhering to the lens is obtained , the water droplet adhering amount is used while being converted to a degree causing an erroneous detection or a non - detection in each application ( water droplet durability ). for example , when the water droplet occupying ratio within the process region of the lane recognition is high , a large water droplet amount exists in the region where a lane exists on the image . accordingly , there is a possibility that the lane cannot be appropriately recognized . here , as for the detection of a far position which can be easily influenced by the distortion of the water droplet , the guaranteed target is not ensured at a level in which the water droplet occupying ratio is slightly raised and the guaranteed target is not ensured even in a near distance in response to an increase in water droplet occupying ratio . for example , even when the application in execution is the vehicle detection , the maximal detection distance of 10 m can be guaranteed until the water droplet occupying ratio becomes 35 % or less of the durable water droplet occupying ratio 35 %. here , when the water droplet occupying ratio becomes larger than 60 % of the limited water droplet occupying ratio , the minimal detection distance becomes 0 m . then , when the application is the pedestrian detection , the maximal detection distance of 5 m can be guaranteed when the water droplet occupying ratio becomes 30 % of the durable water droplet occupying ratio . then , the minimal detection distance becomes 0 m when the water droplet occupying ratio becomes larger than 50 % of the limited water droplet occupying ratio . fig4 is a block diagram showing an internal function of the application execution unit 400 . the application execution unit 400 includes , for example , a lane recognition unit 410 , a vehicle detector 420 , a pedestrian detector 430 , a parking frame detector 440 , and a barrier detector 450 to be executed on the basis of a predetermined condition . the application execution unit 400 executes various applications used for recognizing the image in order to improve the preventive safety or the convenience by using the image captured by the in - vehicle camera 101 as an input . the lane recognition unit 410 executes , for example , the lane recognition used to warn or prevent a vehicle lane departure , to conduct a vehicle lane keep assist , and to conduct a deceleration before a curve . in the lane recognition unit 410 , a feature amount of the white line wl is extracted from the image and the linear property or the curved property of the feature amount is evaluated in order to determine whether the own vehicle exists at a certain horizontal position within the vehicle lane or to estimate a yaw angle representing an inclination with respect to the vehicle lane and a curvature of a travel vehicle lane . then , when there is a possibility that the own vehicle may depart from the vehicle lane in response to the vehicle horizontal position , the yaw angle , or the curvature , an alarm for warning the risk to the driver is generated . alternatively , when there is a possibility that the vehicle lane departure may occur , a control of returning the own vehicle to the own vehicle lane in order to prevent the departure is executed . here , when the vehicle is controlled , there is a need to stabilize the vehicle lane recognition performance and to highly accurately obtain the horizontal position and the yaw angle . further , when the vehicle lane to a far position can be extracted with high accuracy , an assist may be executed which has high curvature estimation accuracy , can be used for a control on a curve , and can support a smooth curve travel operation . the vehicle detector 420 extracts a square shape on the image of the rear face of the preceding vehicle as a feature amount in order to extract a vehicle candidate . it is determined that the candidate is not a stationary object by checking whether the candidate moves on the screen at the own vehicle speed differently from the background . further , the candidate may be narrowed by the pattern matching for a candidate region . in this way , when the vehicle candidate is narrowed to estimate the relative position with respect to the own vehicle , it is determined whether the own vehicle may contact or collide with the vehicle candidate . accordingly , it is determined whether the vehicle candidate becomes a warning target or a control target . in the application used to follow the preceding vehicle , an automatic following operation with respect to the preceding vehicle is executed by the control of the own vehicle speed in response to the relative distance of the preceding vehicle . the pedestrian detector 430 narrows a pedestrian candidate by extracting a feature amount based on a head shape or a leg shape of a pedestrian . further , a moving pedestrian is detected on the basis of a determination reference indicating a state whether the pedestrian candidate moves in a collision direction by the use of a comparison of a movement of a background of a stationary object moving along with the movement of the own vehicle . by the pattern matching , the stationary pedestrian may be also used as a target . in this way , when the pedestrian is detected , it is possible to execute a warning or control process depending on whether the pedestrian jumps into the own vehicle lane . further , it is possible to obtain an application which is very helpful for a low - speed region such as a parking place or an intersection instead of a road travel state . the parking frame detector 440 extracts a white line feature amount similarly to the white line recognition when the vehicle travels at a low speed , for example , 20 km or less . next , all lines having different inclination degrees and existing on the screen are extracted by hough transformation . further , a parking frame is checked to assist the driver &# 39 ; s parking operation instead of searching for a simple white line . it is checked whether the horizontal width of the parking frame is a width in which the vehicle 1 needs to be stopped or the vehicle 1 can be parked in a parking region by detecting a bumper block or a white line at the front or rear side of the vehicle 1 . when the parking frame is visible to a far position in a wide parking lot , the user can select a suitable parking frame from a plurality of parking frame candidates . however , only when a near parking frame is visible , the user needs to approach a near parking space in order to recognize the parking frame . further , since the recognition is basically used for the parking control of the vehicle 1 , the user is informed of the non - control state when the recognition is not stable . the barrier detector 450 extracts a feature point on an image . the feature point having an original feature on an image including an angle for an object may be considered as a feature point having the same feature when a change on the image is small even at the next frame . by the use of the feature points between two frames or multiple frames , a three - dimensional restoration is executed . at this time , a barrier which may collide with the own vehicle is detected . fig5 is a block diagram showing an internal function of the notification control unit 500 . the notification control unit 500 includes , for example , a warning unit 510 , a control unit 520 , a display unit 530 , a stain removing unit 540 , an led display unit 550 , and the like . the notification control unit 500 is an interface unit that receives the determination result of the sensing range determination unit 300 and transmits the information to the user . for example , in a normal state where a sensing disabled range does not exist in a sensing range necessary for the application and the entire sensing range becomes a sensing enabled range , a green led is turned on . then , a green led is turned on and off in a suppression mode . then , in a system give - up state having a temporary possibility of an early return due to a rain or the like , an orange led is turned on . meanwhile , in a system give - up state having a low possibility of a return unless the lens is wiped by the user due to a durable stain such as mud or cloudness on the lens , a red led is turned on . in this way , a system configuration is obtained in order to warn a current preventive safety application operation state and an abnormal state caused by the stain of the lens of a current system to the user . in addition , the system give - up state indicates a state where an application for recognizing a recognition object is stopped for the preventive safety when it is determined that an image suitable for an image recognition cannot be captured due to the particulate deposit on the lens surface . further , the system give - up state indicates a state where a can output is stopped even when the recognition is not stopped or a warning corresponding to a final output or a recognition object recognition result is not transmitted to the user during a vehicle control or a display on a screen or even when a can output is generated . in the system give - up state , the give - up state of the recognition system may be notified to the user through a display or a voice while the recognition object recognition result is not notified to the user . in addition , when the preventive safety application is temporarily changed to the system give - up state , this transition state may be notified to the user through a display for warning the stop of the preventive safety application or a voice for warning the stop of the preventive safety application while not disturbing the driving operation of the driver . in this way , a function of notifying the transition of the application of the lane recognition or the vehicle detection to the stop state to the user may be provided . further , a return state may be notified to the user through a display or a voice . further , in a situation in which visibility is not improved by a road structure tracking unit although the lens state is improved when it is determined that a durable stain adheres to the lens , the lens may be improved after an orange display is selected as a failure display in a durable give - up state . in fact , there is also a possibility influenced by the light source or the background . further , when it is determined that a durable stain other than a water droplet adheres to the lens so that a particularly red led is turned on , an instruction may be given to the user so that the lens is wiped by the user when the vehicle is stopped or before the vehicle starts to travel . since the user is informed of the application operation state based on the lens state diagnosed by the lens state diagnosis unit 200 and the sensing enabled range determined by the sensing range determination unit 300 , it is possible to prevent a problem in which a preventive safety function is stopped without a notice to the user . when the user is informed of the current system state so that the user does not doubt the failure of the system and the vehicle lane departure is warned to the user during the operation of the vehicle lane recognition , an improvement treatment method using a lens wiping and clearing hardware is notified to the user . when a situation is not easily improved unless the user removes the stain of the lens surface in the system give - up state caused by the stain of the lens , this state is notified to the user . accordingly , a further improvement request is notified to the user and a non - operation state of a current application is notified to the user . fig2 is a diagram comparing the sensing enabled range in response to the recognition object . when the particulate deposit adhering to the front in - vehicle camera 101 has the same size and position and the recognition object of the application corresponds to three kinds of recognition objects , that is , a vehicle , a pedestrian , and a barrier , the size of the recognition object is different in each application and thus the sensing range is also different . for example , when the recognition object is the vehicle , a forward vehicle length la 2 of a minimum sensing range 2101 and a forward vehicle length la 1 of a maximum sensing range 2102 are longer than a forward vehicle length lp 2 of a minimum sensing range 2111 and a forward vehicle length lp 1 of a maximum sensing range 2112 of the pedestrian and a forward vehicle length lm 2 of a minimum sensing range 2121 and a forward vehicle length lm 1 of a maximum sensing range 2122 of the barrier are smaller than the forward vehicle length lp 2 of the minimum sensing range 2111 and the forward vehicle length lp 1 of the maximum sensing range 2112 of the pedestrian . meanwhile , an angle θ in which a background is hidden by the particulate deposit is substantially the same among the applications , but is corrected in response to the size of the recognition object . according to the surrounding environment recognition device 10 of the invention , it is possible to notify the sensing enabled range set in response to the stain of the lens of the in - vehicle camera 101 to the user and to allow the user to check a range capable of recognizing the recognition object of the application . thus , it is possible to allow the user to drive the vehicle while further keeping an eye on the surrounding environment by preventing a careless attention on the surrounding environment due to the overestimation of the application . while the embodiment of the invention has been described , the invention is not limited to the above - described embodiment and various modifications in design can be made without departing from the spirit of the invention of claims . for example , the above - described embodiment has been carefully explained for the easy comprehension of the invention and all configurations may not be essentially provided . further , a part of a configuration of a certain embodiment may be replaced as a configuration of the other embodiment and a configuration of the other embodiment may be added to a configuration of a certain embodiment . furthermore , the other configurations may be added to , deleted from , or replaced by a part of a configuration of each embodiment .
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the b lymphocyte donor is selected from anti - rh ( d ) donors undergoing plasmapheresis , based on the activity of his or her anti - rh ( d ) serum antibodies in the adcc activity assay described in § 33 . after a whole blood donation , in 1998 , the “ buffy coat ” fraction ( leukocyte concentrate ) was recovered . the peripheral blood mononuclear cells are separated from the other elements by centrifugation on ficoll plus ( pharmacia ). they are then diluted to 10 6 cell / ml in imdm containing 20 % ( v / v ) of fetal calf serum ( fcs ), to which 20 % of culture supernatant of the b95 - 8 line ( atcc - crl1612 ), 0 . 1 μg / ml of cyclosporin a ( sandoz ), 50 μg / ml of gentamycin sulfate ( life technologies ) are added , and distributed into round - bottomed 96 - well plates or 24 - well plates ( p24 greiner ). they are then placed in an incubator at 37 ° c ., 7 % co 2 . after 3 weeks , the presence of anti - rh ( d ) antibodies is sought by adcc . each one of the 16 microwells of a positive p24 plate well is transferred into a new p24 well . this enrichment is repeated after 10 to 15 days of culturing and each microwell is amplified in a p96 and then in a p24 . the positive p96 wells are taken up and amplified in a flat - bottomed p24 ( nunc ). after a few days of culturing , the presence of anti - rh ( d ) antibodies is sought by adcc . the cells derived from one or more p24 wells are enriched in specific cells by the formation and separation of rosettes with papain - treated rh ( d )- positive red blood cells : one volume of red blood cells washed in 0 . 9 % nacl is incubated for 10 minutes at 37 ° c . with 1 volume of papain ( merck ) solution at 1 / 1 000th ( m / v ), and then washed 3 times in 0 . 9 % nacl . the cells were then washed once in hanks solution , suspended in fcs and mixed with the papain - treated red blood cells in a ratio of 1 cell to 33 red blood cells . the mixture is placed in a cone - bottomed centrifuged tube , centrifuged for 5 minutes at 80 g and incubated for one hour in melting ice . the mixture is then carefully agitated and ficoll is deposited at the bottom of the tube for separation at 900 g for 20 minutes . the pellet containing the rosettes is hemolyzed in a solution of nh 4 cl for 5 minutes and the cells are placed in culture again in a p24 containing irradiated human mononuclear cells . after approximately 1 week , the supernatants are evaluated in cela ( paragraph 3 . 2 ) and adcc assays for the presence of anti - rh ( d ) antibodies having good activity . a further cycle of enrichment is carried out if the percentage of cells forming rosettes significantly increases compared to the preceding cycle . the ir - enriched cells are distributed at 5 and 0 . 5 cells per well in round - bottomed 96 - well plates containing irradiated human mononuclear cells . after approximately 4 weeks of culturing , the supernatants from the wells containing cell aggregates are evaluated by adcc assay . the wells from cloning the ebv - transformed cells exhibiting an advantageous adcc activity are amplified in culture and then fused with the heteromyeloma k6h6 - b5 ( atcc crl - 1823 ) according to the standard peg technique . after fusion , the cells are distributed , in a proportion of 2 × 10 4 cells / well , into flat - bottomed p96s containing murine intraperitoneal macrophages and in a selective medium containing aminopterin and ouabain ( sigma ). after 3 to 4 weeks of culturing , the supernatants of the wells containing cell aggregates are evaluated by adcc assay . cloning by limiting dilution is carried out at 4 , 2 and 1 cell / well in flat - bottomed p96s . after 2 weeks , the microscopic appearance of the wells is examined in order to identify the single clones , and the medium is then renewed . after approximately 2 weeks , the supernatants of the wells containing cell aggregates are evaluated by adcc assay . ebv transformation of the cells of donor d13 made it possible to select a well , designated t125 2a2 , on which the following were successively carried out : 2 enrichments , 3 cycles of ir , and cloning at 5 cells / well to give 2 clones : 1 ) t125 2a2 ( 5 / 1 ) a2 from which the dna was extracted in order to prepare the recombinant vector ; 2 ) t125 ( 5 / 1 ) a2 which was fused with k6h6 - b5 to give f60 2f6 and then , after 5 rounds of cloning , f60 2f6 ( 5 ) 4c4 , a clone selected for constituting a cell stock prior to preparing libraries . a line producing an igg3 was prepared according to the same method as that used to prepare the antibody of igg1 isotype . the cells of origin originate from a donation of whole blood , from a designated donor , from which the “ buffy coat ” fraction ( leukocyte concentrate ) was recovered . after purification by affinity chromatography on protein a sepharose ( pharmacia ) and dialysis in 25 mm tris buffer , 150 mm nacl , ph 7 . 4 , the concentration of the antibody t125 is determined by the elisa technique . the biological activity in vitro is then measured by the adcc technique . coating : anti - igg ( calbiochem ) at 2 μg / ml in 0 . 05m carbonate buffer , ph 9 . 5 , overnight at 4 ° c . saturation : dilution buffer ( pbs + 1 % bsa + 0 . 05 % tween 20 , ph 7 . 2 ), 1 h at ambient temperature . washing ( to be renewed at each step ): h 2 o + 150 mm nacl + 0 . 05 % tween 20 . dilution of the samples , in dilution buffer to approximately 100 ng / ml and of the control range made up of lfb polyvalent human iggs prediluted to 100 ng / ml . incubation for 2 h at ambient temperature . conjugate : anti - igg ( diagnostic pasteur ) diluted to 1 / 5 000 , 2 hours at ambient temperature . substrate : opd at 0 . 5 mg / ml ( sigma ) in phosphate - citrate buffer containing sodium perborate ( sigma ), 10 minutes in the dark . reaction stopped with 1n hcl , and read at 492 nm . coating : anti - kappa ( caltag lab ) at 5 μg / ml in 0 . 05m carbonate buffer , ph 9 . 5 , overnight at 4 ° c . saturation : dilution buffer ( pbs + 1 % bsa + 0 . 05 % tween 20 , ph 7 . 2 ), 1 h at ambient temperature . the washing ( to be renewed at each step ): h 2 o + 150 mm nacl + 0 . 05 % tween 20 . dilution of the samples , in dilution buffer , to approximately 100 ng / ml and of the control range made up of the lfb monoclonal antibody ad3t1 ( kappa / gamma 3 ) prediluted to 100 ng / ml . incubation for 2 h at ambient temperature . conjugate : biotinylated anti - kappa ( pierce ) diluted to 1 / 1 000 in the presence of streptavidin - peroxidase ( pierce ) diluted to 1 / 1 500 , 2 hours at ambient temperature . substrate : opd at 0 . 5 mg / ml ( sigma ) in phosphate - citrate buffer containing sodium perborate ( sigma ), 10 minutes in the dark . the reaction is stopped with 1n hcl , and read at 492 nm . 3 . 2 — specific assaying of anti - d by the cela ( cellular enzyme linked assay ) technique : this method is used for specifically assaying the anti - d antibodies in particular when this involves a culture supernatant at culturing stages at which other non - anti - d immunoglobulins are present in the solution ( early stages after ebv transformation ). principle : the anti - d antibody is incubated with rhesus - positive red blood cells and then revealed with an alkaline phosphatase - labeled anti - human ig . 100 μl of rh + red blood cells at 10 % diluted in liss - 1 % bsa dilution buffer . dilution of the samples , in dilution buffer , to approximately 500 ng / ml and of the control range made up of a purified monoclonal human anti - d igg ( df5 , lfb ) prediluted to 500 ng / ml . incubation for 45 min at ambient temperature . washing ( to be renewed at each step ): h 2 o + 150 mm nacl . conjugate : anti - igg alkaline phosphatase ( jackson ) diluted to 1 / 4 000 in pbs + 1 % bsa , 1 h 30 at ambient temperature . substrate : pnpp at 1 mg / ml ( sigma ) in 1m diethanolamine , 0 . 5 mm mgcl 2 , ph 9 . 8 . the reaction is stopped with 1n naoh , and read at 405 nm . the adcc ( antibody - dependent cellular cytotoxicity ) technique makes it possible to evaluate the ability of the ( anti - d ) antibodies to induce lysis of rh - positive red blood cells , in the presence of effector cells ( mononuclear cells or lymphocytes ). briefly , the red blood cells of an rh - positive cell concentrate are treated with papain ( 1 mg / ml , 10 min at 37 ° c .) and then washed in 0 . 9 % nacl . the effector cells are isolated from a pool of at least 3 buffy - coats , by centrifugation on ficoll ( pharmacia ), followed by a step of adhesion in the presence of 25 % fcs , so as to obtain a lymphocyte / monocyte ratio of the order of 9 . the following are deposited , per well , into a microtitration plate ( 96 well ): 100 μl of purified anti - d antibody at 200 ng / ml , 25 μl of rh + papain - treated red blood cells ( i . e . 1 × 10 6 ), 25 μl of effector cells ( i . e . 2 × 10 6 ) and 50 μl of polyvalent igg ( tegeline , lfb , for example ) at the usual concentrations of 10 and 2 mg / ml . the dilutions are made in imdm containing 0 . 25 % fcs . after overnight incubation at 37 ° c ., the plates are centrifuged , and the hemoglobin released into the supernatant is then measured in the presence of a substrate specific for peroxidase activity ( 2 , 7 - diaminofluorene , daf ). the results are expressed as percentage lysis , 100 % corresponding to total red blood cell lysis in nh 4 cl ( 100 % control ), and 0 % to the reaction mixture without antibody ( 0 % control ). the specific lysis is calculated as a percentage according to the following formula : the results given in fig1 show the activity of the antibody produced by the heterohybrid f60 compared to those of the reference antibodies : the anti - rh ( d ) polyclonal antibodies poly - d lfb 51 and winrho w03 ( cangene )= positive controls the monoclonal antibody df5 ( inactive in vivo on clearance of rh ( d )- positive red blood cells ( brossard / fnts , 1990 , not published ))= negative control the igg1s purified ( separated from the igg3s ) from the polyclonal winrho w03 . two concentrations of human iggs ( tegeline lfb ) are used to show that inhibition of activity of the negative control is linked to the binding of competing iggs to the fcγ type i receptors . this assay makes it possible to assess the binding of the anti - rh ( d ) antibodies of igg1 isotype to fcγriii , and in particular to differentiate igg3 antibodies . given the low affinity of this receptor for monomeric iggs , prior binding of the antibodies to the d antigen is necessary . principle : the antibody to be tested ( anti - d ) is added to membranes of rh + red blood cells coated with a microtitration plate , followed by transfected jurkat cells expressing the fcγriii receptor at their surface . after centrifugation , the “ rh + membrane / anti - d / cd16 jurkat ” interaction is visualized by a homogeneous plating of the cd16 jurkats in the well . in the absence of interaction , the cells are , on the contrary , grouped at the center of the well . the intensity of the reaction is expressed as numbers of +. method : 1 ) incubation for 1 h at 37 ° c . of the anti - d antibody ( 50 μl at 1 μg / ml in imdm ) on a capture r plate ( immunochim ), and then washes in water + 0 . 9 % nacl . addition of cd16 jurkat ( 2 × 10 6 cells / ml ) in imdm + 10 % fcs . incubation for 20 min at 37 ° c . and then centrifugation and evaluation of cell adhesion ( against a control range ). 2 ) revelation of the anti - d bound to the capture r plates by an elisa - type technique using anti - human igg - peroxidase at 1 / 5 000 ( sanofi diagnostics pasteur ) after having lysed the cd16 jurkat cells with 0 . 2m tris - hcl , 6m urea , ph 5 . 3 - 5 . 5 . opd revelation and then reading of optical density ( o . d .) at 492 nm . expression of results : an arbitrary value of 0 to 3 is allotted as a function of the binding and of the plating of the cd16 jurkat cells . these values are allotted at each od interval defined ( increments of 0 . 1 ). the following are plotted : either a curve : adhesion of the jurkat cells ( y ) as a function of the amount of anti - d bound to the red blood cell membranes ( x ). or a histogram of the “ binding indices ” corresponding , for each antibody , to the sum of each jurkat cell binding value ( 0 to 3 ) allotted per od interval ( over a portion common to all the antibodies tested ). an example of a histogram is given in fig2 . the anti - rh ( d ) antibodies of igg1 isotype ( f60 and t125 yb2 / 0 ) show a binding index close to that of the polyclonal igg1s ( winrho ), whereas the negative control antibodies df5 and ad1 do not bind . similarly , the antibody of igg3 isotype ( f41 ) exhibits a good binding index , slightly less than that of the igg3s purified from the polyclonal winrho and greater than that of the antibody ad3 ( other igg3 tested and ineffective in clinical trial , in a mixture with ad1 ( biotest / lfb , 1997 , not published ). 1 — isolation and amplification of the cdnas encoding the heavy and light chains of the ab the total rnas were extracted from an anti - d ab - producing clone ( igg g1 / kappa ) obtained by ebv transformation : t125 a2 ( 5 / 1 ) a2 ( see paragraph 2 , example 1 ). the corresponding cdnas were synthesized by reverse transcription of the total rnas using oligo dt primers . the vh / t125 - a2 sequence is obtained by amplification of the t125 - a2 cdnas using the following primers : primer a2vh5 , located 5 ′ of the leader region of the vh gene of t125 - a2 , introduces a consensus leader sequence ( in bold ) deduced from leader sequences already published and associated with vh genes belonging to the same vh3 - 30 family as the vh gene of t125 - a2 ; this sequence also comprises an eco ri restriction site ( in italics ) and a kozak sequence ( underlined ): antisense primer gsp2anp , located 5 ′ of the constant region ( ch ) of t125 - a2 : the ch / t125 - a2 sequence is obtained by amplification of the t125 - a2 cdnas using the following primers : the first g base of the ch sequence is here replaced with a c ( underlined ) in order to recreate , after cloning , an eco ri site ( see paragraph 2 . 1 . 1 ). antisense primer h3 ′ xba , located 3 ′ of the ch of t125 - a2 , introduces an xba i site ( underlined ) 3 ′ of the amplified sequence : the entire kappa chain of t125 - a2 ( k / t125 - a2 sequence ) is amplified from the t125 - a2 cdnas using the following primers : primer a2vk3 , located 5 ′ of the leader region of the vk gene of t125 - a2 , introduces a consensus sequence ( in bold ) deduced from the sequence of several leader regions of vk vh genes belonging to the same vk1 subgroup as the vk gene of t125 - a2 ; this sequence also comprises an eco ri restriction site ( in italics ) and a kozak sequence ( underlined ): anti sense primer kse1 , located 3 ′ of kappa , introduces an eco ri site ( underlined ): fig1 gives a diagrammatic illustration of the strategies for amplifying the heavy and light chains of t125 - a2 . the construction of t125 - h26 is summarized in fig2 . it is carried out in two stages : first of all , construction of the intermediate vector v51 - ch / t125 - a2 by insertion of the constant region of t125 - a2 into the expression vector v51 derived from pci - neo ( fig3 ) and then cloning of the variable region into v51 - ch / t125 - a2 . the amplified ch / t125 - a2 sequence is inserted , after phosphorylation , at the eco ri site of the vector v51 ( fig3 ). the ligation is performed after prior treatment of the eco ri sticky ends of v51 with the klenow polymerase in order to make them “ blunt - ended .” the primer g1 used for amplifying ch / t125 - a2 makes it possible to recreate , after its insertion into v51 , an eco ri site 5 ′ of ch / t125 - a2 . the vh / t125 - a2 sequence obtained by amplification is digested with eco ri and apa i and then inserted at the eco ri and apa i sites of the vector v51 - g1 / t125 - a2 . the construction of t125 - k47 is given in fig4 . the k / t125 - a2 sequence obtained by pcr is digested with eco ri and inserted at the eco ri site of the expression vector v47 derived from pci - neo ( fig5 ). the construction of t125 - ig24 is illustrated diagrammatically in fig6 . this vector , which contains the two transcription units for the heavy and kappa chains of t125 - a2 , is obtained by inserting the sal i - xho i fragment of t125 - k47 , containing the transcription unit for k / t125 - a2 , at the xho i and sal i sites of t125 - h26 . thus , the heavy and light chains of t125 - a2 are expressed under the control of the cmv promoter ; other promoters may be used : rsv , igg heavy chain promoter , mmlv ltr , hiv , β - actin , etc . a second vector for expressing t125 - a2 is also constructed , in which the consensus leader sequence of the kappa chain is replaced with the real sequence of the leader region of t125 - a2 determined beforehand by sequencing products from “ pcr 5 ′- race ” ( rapid amplification of cdna 5 ′ ends ). the construction of this t125 - ls4 vector is described in fig7 . it is carried out in two stages : first of all , construction of a new vector for expressing the t125 - a2 kappa chain , t125 - kls18 , and then assembly of the final expression vector , t125 - ls4 , containing the two heavy chain and modified light chain transcription units . the 5 ′ portion of the kappa consensus leader sequence of the vector t125 - k47 is replaced with the specific leader sequence of t125 ( kls / t125 - a2 ) during a step of amplification of the k / t125 - a2 sequence carried out using the following primers : primer a2vk9 , modifies the 5 ′ portion of the leader region ( in bold ) and introduces an eco ri site ( underlined ) and also a kozak sequence ( in italics ): the vector t125 - kls18 is then obtained by replacing the eco ri fragment of t125 - k47 , containing the k / t125 - a2 sequence of origin , with the new sequence kls / t125 - a2 digested via eco ri . the sal i - xho i fragment of t125 - kls18 , containing the modified kls / t125 - a2 sequence , is inserted into t125 - h26 at the xho i and sal i sites . the two expression vectors t125 - ig24 and t125 - ls4 were used to transfect cells of the yb2 / 0 line ( rat myeloma , atcc line no . 1662 ). after transfection by electroporation and selection of transformants in the presence of g418 ( neo selection ), several clones were isolated . the production of recombinant anti - d abs is approximately 0 . 2 μg / 10 6 cells / 24 h ( value obtained for clone 3b2 of r270 ). the adcc activity of this recombinant ab is greater than or equal to that of the poly - d controls ( fig1 ). the abs produced using the two expression vectors are not significantly different in terms of level of production or of adcc activity . the gene amplification system used is based on the selection of transformants resistant to methotrexate ( mtx ). it requires the prior introduction of a transcription unit encoding the dhfr ( dihydrofolate reductase ) enzyme into the vector for expressing the recombinant ab ( shitari et al ., 1994 ). the scheme shown in fig8 describes the construction of the vector for expressing t125 - a2 , containing the murine dhfr gene . a first vector ( v64 ) was constructed from a vector derived from pci - neo , v43 ( fig9 ), by replacing , 3 ′ of the sv40 promoter and 5 ′ of a synthetic polyadenylation sequence , the neo gene ( hind iii - csp 45 i fragment ) with the cdna of the murine dhfr gene ( obtained by amplification from the plasmid pmt2 ). this vector is then modified so as to create a cla i site 5 ′ of the dhfr transcription unit . the cla i fragment containing the dhfr transcription unit is then inserted at the cla i site of t125 - ls4 . yb2 / 0 cells transfected by electroporation with the vector t125 - dhfr13 are selected in the presence of g418 . the recombinant ab - producing transformants are then subjected to selection in the presence of increasing doses of mtx ( from 25 nm to 25 μm ). the progression of the recombinant ab production , reflecting the gene amplification process , is followed during the mtx selection steps . the mtx - resistant transformants are then cloned by limiting dilution . the level and the stability of the recombinant ab production are evaluated for each clone obtained . the anti - d antibody productivity after gene amplification is approximately 13 (+/− 7 ) μg / 10 6 cells / 24 h . yb2 / 0 cells transfected by electroporation with vector t125 - dhfr13 are selected in the presence of g418 . the best recombinant ab - producing transformants are cloned by limiting dilution before selection in the presence of increasing doses of mtx . the progression of the production by each clone , reflecting the gene amplification process , is followed during the mtx selection steps . the level and the stability of the recombinant ab production are evaluated for each mtx - resistant clone obtained . after purification by affinity chromatography on protein a sepharose ( pharmacia ) and dialysis into 25 mm tris buffer , 150 mm nacl , ph 7 . 4 , the concentration of the t125 antibody is determined by the elisa technique . the biological activity in vitro is then measured by the adcc assay described above . the results are given in fig1 . several studies describe the effect of enzymatic inhibitors on the glycosylation of immunoglobulins and on their biological activity . an increase in adcc activity is reported by rothman et al ., 1989 , this being an increase which cannot be attributed to an enhancement of the affinity of the antibody for its target . the modification of glycosylation caused by adding dmm consists of inhibition of the α - 1 , 2 mannosidase i present in le golgi . it leads to the production of a greater proportion of polymannosylated , nonfucosylated structures . various anti - rh ( d ) antibody - producing lines were brought into contact with dmm and the functional activity of the monoclonal antibodies produced was evaluated in the form of culture supernatants or after purification . the cells ( heterohybrid or lymphoblastoid cells ) are seeded at between 1 and 3 × 10 5 cell / ml , and cultured in imdm culture medium ( life technologies ) with 10 % of fcs and in the presence of 20 μg / ml of dmm ( sigma , boehringer ). after having renewed the medium 3 times , the culture supernatants are assayed by human igg elisa and then by adcc . the addition of dmm may make it possible to restore the adcc activity of an antibody derived from the cloid t125 = t125 ri ( 3 ) ( described in example 1 ) and which has lost this activity through sustained culturing . the strong activity of the antibody produced by the heterohybridoma f60 ( the production of which is described in example 1 ) is not modified by culturing in the presence of dmm . the nucleotide sequence of the antibody df5 , a negative control in the adcc assay , is used to study the transfection of this antibody into some lines , in parallel to transfection of the antibody t125 . the sequences encoding the ab df5 are isolated and amplified according to the same techniques used for the recombinant ab t125 - a2 . the corresponding cdnas are first of all synthesized from total rna extracted from the anti - d ab -( igg g1 / lambda )- producing clone 2mdf5 obtained by ebv transformation . amplification of the heavy and light chains is then carried out from these cdnas using the primers presented below . amplification of the variable region of the heavy chain of df5 ( vh / df5 sequence ): primer df5vh1 , located 5 ′ of the leader region ( in bold ) of the vh gene of df5 ( sequence published : l . chouchane et al . ); this primer also comprises an eco ri restriction site ( in italics ) and a kozak sequence ( underlined ): antisense primer gsp2anp , located 5 ′ of the constant region ( ch ) already described in paragraph 1 . 2 ( example 2 ). amplification of the constant region ch of df5 ( ch / df5 sequence ): primers g1 and h3 ′ xba already described in paragraph 1 . 3 ( example 2 ). primer df5vlbd1 , located 5 ′ of the leader region of the vl gene of df5 , introduces a consensus sequence ( in bold ) deduced from the sequence of several leader regions of vl genes belonging to the same vl1 subgroup as the vl gene of 2mdf5 ; this sequence also comprises an eco ri restriction site ( in italics ) and a kozak sequence ( underlined ): antisense primer lse1 , located 3 ′ of lambda , introduces an eco ri site ( underlined ): the construction of the vectors for expressing the heavy chain ( df5 - h31 ), light chain ( df5 - l10 ) and heavy and light chains ( df5 - ig1 ) of the ab df5 is carried out according to a construction scheme similar to vectors expressing the ab t125 - a2 . all the leader sequences of origin ( introduced in the amplification primers ) are conserved in these various vectors . 2 . 2 — transfection of various cell lines with the antibodies t125 and df5 the three expression vectors t125 - ig24 , t125 - ls4 and df5 - igg1 are used to transfect cells of various lines : stable or transient transfections are performed by electroporation or using a transfection reagent . the modification of effector activity of a humanized monoclonal antibody as a function of the expressing cell has been described by crowe et al . ( 1992 ), with the cho , nso and yb2 / 0 cell lines . the results obtained here confirm the importance of the expressing cell line with respect to the functional characteristics of the antibody to be produced . among the cells tested , only the vero , yb2 / 0 and cho lec - 1 lines make it possible to express recombinant anti - rh ( d ) monoclonal antibodies with strong lytic activity in the adcc assay ( see example 1 and table 4 ). characterization of the glycan structures of the anti - rh - d antibody was carried out on four purified products having an adcc activity ( f60 , and three recombinant proteins derived from t125 ) in comparison with two purified products inactive or very weakly active in the adcc assay according to the invention ( d31 and df5 ). in practice , the oligosaccharides are separated from the protein by specific enzymatic deglycosylation with pngase f at asn 297 . the oligosaccharides thus released are labeled with a fluorophore , separated and identified by various complementary techniques which allow : fine characterization of the glycan structures by matrix - assisted laser desorption ionization ( maldi ) mass spectrometry by comparison of the experimental masses with the theoretical masses . determination of the degree of sialylation by ion exchange hplc ( glycosep c ) separation and quantification of the oligosacharride forms according to hydrophilicity criteria by normal - phase hplc ( glycosep n ) separation and quantification of the oligosaccharides by high performance capillary electrophoresis - laser induced fluorescence ( hpce - lif ). the various active forms studied are f60 and three recombinant antibodies , r 290 , r 297 and r 270 , derived from t125 and produced in yb2 / 0 . fine characterization of the glycan structures by mass spectrometry ( fig7 ) shows that these forms are all of the bi - antennary type . in the case of r 270 , the major form is of the agalactosylated , nonfucosylated type ( g0 , exp . mass 1459 . 37 da , fig1 ). three other structures are identified : agalactosylated , fucosylated ( g0f at 1605 . 41 da ), monogalactosylated , nonfucosylated ( g1 at 1621 . 26 da ) and monogalactosylated , fucosylated ( g1f at 1767 . 43 da ) in minor amount . these same four structures are characteristic of r 290 , f 60 and r 297 ( fig1 ). these four antibodies which are active in adcc are also characterized by the absence of oligosaccharides having a bisecting n - acetylglucosamine residue . quantification of the glycan structures by the various techniques of hplc and hpce - lif ( table 1 ) confirms the presence of the four forms identified by mass : g0 , g0f , g1 and g1f . the degree of sialylation is very low , in particular for the recombinant products , from 1 to 9 . 4 %, which is confirmed by the similarity of the mass spectra obtained before and after enzymatic desialylation . the degree of fucosylation ranges from 34 to 59 %. the various inactive forms studied are d31 and df5 . quantification of the glycan structures by the various chromatographic and capillary electrophoresis techniques ( table 1 ) reveals , for these two antibodies , a degree of sialylation close to 50 %, and a degree of fucosylation of 88 and 100 % for d31 and df5 , respectively . these degrees of sialylation and fucosylation are much higher than those obtained from the active forms . characterization of the glycan structures shows that the major form is , for the two antibodies , of the bi - antennary , monosialylated , digalactosylated , fucosylated type ( g2s1f , table 1 ). the characterization by mass spectrometry of d31 ( fig7 ) reveals that the neutral forms are mainly of the monogalactosylated , fucosylated type ( gif at 1767 . 43 da ) and digalactosylated , fucosylated type ( g2f at 1929 . 66 da ). the inactive antibody df5 is characterized by the presence of oligosaccharides having an intercalated glcnac residue . in particular , the mass analysis ( fig8 ) reveals the presence of a major neutral form of the monogalactosylated , fucosylated , bisecting , intercalated glcnac type ( g1fb at 1851 . 03 da ). on the other hand , these structural forms are undetectable or present in trace amounts on the active antibodies studied . the adcc activity of d31 after the action of dmm increases from 10 % to 60 %. the glycan structures of dmm d31 differ from those of d31 by the presence of oligomannose forms ( man 5 , man 6 and man 7 ) ( see fig9 ). the various active antibodies are modified on asn 297 with n - glycosylations of the bi - antennary and / or oligomannoside type . for the bi - antennary forms , this involves short structures with a very low degree of sialylation , a low degree of fucosylation , a low degree of galactosylation and no intercalated glcnac . boylston , j . m ., gardner , b ., anderson , r . l ., and hughes - jones , n . c . production of human igm anti - d in tissue culture by eb virus - transformed lymphocytes . scand . j . immunol . 12 : 355 - 358 ( 1980 ). bron , d ., feinberg , m . b ., teng , n . n . h . and kaplan , h . s . production of human monoclonal igg antibodies against rhesus ( d ) antigen . proc . nat . acad . sci . usa 81 : 3214 - 3217 ( 1984 ). chouchane , l ., van spronsen , a ., breyer , j ., guglielmi , p ., and strosberg , a d . molecular characterization of a human anti - rh ( d ) antibody with a dii segment encoded by a germ - line sequence . eur . j . biochem . 1 ; 207 ( 3 ): 1115 - 1121 ( 1992 ). crawford , d . h ., barlow , m . j ., harrison , j . f ., winger , l . and huehns , e . r . production of human monoclonal antibody to rhesus d antigen . lancet , i : 386 - 388 ( 1983 ). doyle , a ., jones , t . j ., bidwell , j . l . and bradley , b . a . in vitro development of human monoclonal antibody secreting plasmacytomas . hum . immunol . 13 : 199 - 209 ( 1985 ). edelman , l ., margaritte , c ., chaabihi , h ., monchâtre , e ., blanchard , d ., cardona , a ., morin , f ., dumas , g ., petres , s . and kaczorek , m . obtaining a functional recombinant anti - rhesus ( d ) antibody using the baculovirus - insect cell expression system . immunology , vol . 91 ( 1 ), 13 - 19 ( 1997 ). foung , s . k . h ., blunt , j . a ., wu , p . s ., ahearn , p ., winn , l . c ., engleman , e . g . and grumet , f . c . human monoclonal antibodies to rho ( d ). vox sang . 53 : 44 - 47 ( 1987 ). goossens , d ., champomier , f ., rouger , p ., and salmon , c . human monoclonal antibodies against blood group antigens : preparation of a series of stable ebv immortalized b clones producing high levels of antibody of different isotypes and specificities . j . immunol . methods 101 : 193 - 200 ( 1987 ). issitt , p . d . genetics of the rh blood group system : some current concepts . med . lab . sci . 45 : 395 - 404 ( 1988 ). jefferis , r , lund , j ., mizutani , h ., nakagawa , h ., kawazoe , y ., arata , y . and takahashi , n . a comparative study of the n - linked oligosaccharides structure of human igg subclass proteins . biochem . j ., 268 : 529 - 537 ( 1990 ). koskimies , s . human lymphoblastoid cell line producing specific antibody against rh - antigen d . scand . immunol . 11 : 73 - 77 ( 1980 ). kumpel , b . m ., goodrick , m . j ., pamphilon , d . h ., fraser , i . d ., poole g . d ., morse , c ., standen , g . r ., chapman , g . e ., thomas , d . p . and anstee , d . j . human rh d monoclonal antibodies ( brad - 3 and brad - 5 ) cause accelerated clearance of rh d + red blood cells and suppression of rh d immunization in rh d volunteers . blood , vol . 86 , no . 5 , 1701 - 1709 ( 1995 ). kumpel , b . m ., poole , g . d . and bradley , b . a . human monoclonal anti - d antibodies . i . their production , serology , quantitation and potential use as blood grouping reagents . brit . j . haemat . 71 : 125 - 129 ( 1989a ). kumpel , b . m ., rademacher , t . w ., rook , g . a . w ., williams , p . j ., wilson , i . b . m . galacatosylation of human igg anti - d produced by ebv - transformed b lympho - blastoid cell lines is dependent on culture method and affects fc receptor mediated functional activity . hum . antibodies and hybridomas , 5 : 143 - 151 ( 1994 ). leatherbarrow , r . j ., rademacher , t . w ., dwek , r . a ., woof , j . m ., clark , a ., burton , d . r ., richardson , n . and feinstein , a . effector functions of monoclonal aglycosylated mouse igg2a ; binding and activation of complement component ci and itneraction with human fc receptor . molec . immun . 22 , 407 - 415 ( 1985 ). lomas , c ., tippett , p ., thompson , k . m ., melamed , m . d . and hughes - jones , n . c . demonstration of seven epitopes on the rh antigen d using human monoclonal anti - d antibodies and red cells from d categories . vox sang . 57 : 261 - 264 ( 1989 ). lund , j ., takahaski , n ., nakagawa , h ., goodall , m ., bentley , t ., hindley , s . a ., tyler , r . and jefferis , r . control of igg / fc glycosylation : a comparison of oligosaccharides from chimeric human / mouse and mouse subclass immunoglobulin g5 . molec . immun . 30 , no . 8 , 741 - 748 ( 1993 ). lund , j ., tanaka , t ., takahashi , n ., sarmay , g ., arata , y . and jefferis , r . a protein structural change in aglycosylated igg3 correlates with loss of hu fc □ ri and hu fcγriii binding and / or activation . molec . immun . 27 , 1145 - 1153 ( 1990 ). ma , j . k . and hein , m . b . immunotherapeutic potential of antibodies produced in plants . trends biotechnol . 13 , 522 - 527 ( 1995 ). mc cann - carter , m . c ., bruce , m ., shaw , e . m ., thorpe , s . j ., sweeney , g . m ., armstrong , s . s . and james , k . the production and evaluation of two human monoclonal anti - d antibodies . transf . med . 3 : 187 - 194 ( 1993 ). melamed . m . d ., gordon , j ., ley , s . j ., edgar , d . and hughes - jones , n . c . senescence of a human lymphoblastoid clone producing anti - rhesus ( d ) eur . j . immunol . 115 : 742 - 746 ( 1985 ). parekh , r . b ., dwek , r . a ., sutton , b . j ., femanes , d . l ., leung , a ., stanworth , d ., rademacher , t . w ., mizuochi , t ., taniguchi , t ., matsuta , k ., takeuchi , f ., nagano , y ., miyamoto , t . and kobata , a . association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum igg . nature , 316 : 452 - 457 ( 1985 ). rothman , r . j ., perussia , b ., herlyn , d . and warren , l . antibody - dependent cytotoxicity mediated by natural killer cells is enhanced by castanospermine - induced alterations of igg glycosylation . mol . immunol . 26 ( 12 ): 1113 - 1123 ( 1989 ). shitara k ., nakamura k ., tokutake - tanaka y ., fukushima m ., and hanai n . a new vector for the high level expression of chimeric antibodies to myeloma cells . j . immunol . methods 167 : 271 - 278 ( 1994 ). thompson , k . m ., hough , d . w ., maddison , p . j ., mclamed , m . d . and hughes - jones , n . c . production of human monoclonal igg and igm antibodies with anti - d ( rhesus ) specificity using heterohybridomas . immunology 58 : 157 - 160 ( 1986 ). thomson , a ., contreras , m ., gorick , b ., kumpel , b ., chapman , g . e ., lane , r . s ., teesdale , p . hughes - jones , n . c . and mollison , p . l . clearance of rh d - positive red cells with monoclonal anti - d . lancet 336 : 1147 - 1150 ( 1990 ). tippett , p . sub - divisions of the rh ( d ) antigen . med . lab . sci . 45 : 88 - 93 ( 1988 ). ware , r . e . and zimmerman , s . a . anti - d : mechanisms of action . seminars in hematology , vol . 35 , no . 1 , supp . 1 : 14 - 22 ( 1998 ). yu , i . p . c ., miller , w . j ., silberklang , m ., mark , g . e ., ellis , r . w ., huang , l ., glushka , j ., van halbeek , h ., zhu , j . and alhadeff , j . a . structural characterization of the n - glycans of a humanized anti - cd18 murine immunoglobulin g . arch . biochem . biophys . 308 , 387 - 399 ( 1994 ). zupanska , b ., thompson , e ., brojer , e . and merry , a . h . phagocytosis of erythrocytes sensitized with known amounts of igg1 and igg3 anti - rh antibodies . vox sang . 53 : 96 - 101 ( 1987 ).
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referring to the drawings it will be appreciated that a method and apparatus for detecting the presence or absence of an object at a predetermined location can be implemented in various forms . the following embodiments are described by way of example only . references herein to ‘ light ’ are not intended to be limited to visible light but are to be understood as also including non - visible radiation , including infrared and ultraviolet radiation having wavelengths outside the visible spectrum , for example . references to ‘ reflection ’ include scattering of light or radiation from a surface . fig1 shows a schematic diagram of a first preferred embodiment of an optical arrangement for determining the presence or absence of a die at a predetermined location . in this embodiment the predetermined location is at a die - handling collet of a collet assembly for die placement . the collet assembly is used to pick up individual dice fabricated from a silicon or sapphire wafer , and to place the dice at a bonding position where , for example , the die is attached to a substrate , such as a lead frame . a light source 1 , for example a laser diode , is arranged to illuminate at least a portion of a site in the collet . as shown in fig1 , the site is occupied by a die 2 . the light from the source is preferably collimated or focused , such as by a lens 22 ( see fig3 ) into a narrow incident beam 3 . in a preferred application the collimated or focused beam is between 0 . 02 to 0 . 5 mm wide , and most preferably 0 . 05 mm wide . the incident beam is directed through the collet , whose inner diameter can be as small as 0 . 02 mm , at a small portion of the die 2 . noise caused by reflections of light from the inner surface of the collet other than at the die site in the collet , are minimised by making the diameter of the beam sufficiently small so that very little , other than the die , is illuminated . in the case shown in fig1 , the illuminating light is incident upon the surface 4 of the die substantially normal to the orientation of the surface 4 . however , other angles of incident light that are close to normal incidence may be used , in which case the light will be reflected from the die surface at a corresponding angle , as long as angles of incidence and reflection are sufficiently small to allow the light to be received . the light source illuminates the die surface after passing through a beam splitter 5 . in the case shown in fig1 , where the die 2 is transparent , a major fraction 6 of the light is transmitted through the die 2 . however , a smaller fraction 7 of the incident source light is reflected from the die surface 4 back toward the beam splitter 5 which reflects the light to a light detector , which may be in the form of a photo - sensor 8 . fig1 shows this reflected fraction or beam 7 offset from the incident beam 3 . this offset is only shown for clarity of the explanation provided by fig1 , and in practice the incident and reflected beams coincide , at least at the die surface 4 . an output signal from the photo - sensor 8 is connected to an electronic amplifier 9 which produces an amplified output 10 for further processing to make a determination of the presence or absence of a die at the collet , based on the light received by the photo - sensor 8 . the photo - sensor 8 can be an image sensor or a general light power sensor . in the case of the preferred application , where the optical arrangement monitors the presence or absence of a die fabricated from a wafer made of sapphire , the die is substantially transparent . in general , the reflectivity r of a surface of a transparent body can be expressed as : typically for sapphire , n is between 1 . 55 to 1 . 7 . if n = 1 . 55 , then r = 0 . 047 ( or 4 . 7 %). however reflection occurs at both the top and bottom surfaces of the sapphire die giving a total reflectivity of about 9 . 4 %. thus , even if the die is substantially transparent and as long as its refractive index is not equal to 1 , the die will still reflect a fraction of the incident light beam back for detection by the photo - sensor . this reflectivity by the die allows a determination of the presence or absence of a transparent object such as a sapphire die in the collet to be based upon reflected rather than the traditional transmitted light . determination based upon scattering of light by an object is also possible , as long as an intensity of the scattered light is sufficient to reach the photo - sensor . a second arrangement is shown in fig2 . corresponding features in fig1 and 2 are labelled alike . in this arrangement the positions of the illuminating light source 1 and the photo - sensor 8 are interchanged , so that light from the illuminating source 1 is directed to the beam splitter 5 which reflects the incident beam 3 toward the surface 4 of the die 2 . a major fraction 6 of the incident light is transmitted through the die , while a minor fraction 7 of the incident light is reflected back through the beam splitter 5 to the photo - sensor 8 . fig3 shows a cross - sectional side view of a collet assembly 20 utilising the arrangement of the first preferred embodiment . the light source or laser diode 1 is arranged at the top of the collet assembly 20 to project a beam of light through the collet assembly 20 . the light from the source is collimated or focused by a lens 22 into a narrow incident beam . the incident beam passes through the beam splitter 5 and is directed through the collet 21 such that at least a portion of a site at the opening of the collet 21 is illuminated . a die 2 is located at the said opening . the incident beam is reflected from the surface of the die 2 back toward the beam splitter 5 which reflects the light to the photo - sensor 8 . in fig3 , the light source 1 and photo - sensor 8 are integrated with and located on the collet assembly 20 . fig4 shows a cross - sectional side view of a collet assembly 20 where the light source 1 and light detector 8 are located remotely from the collet assembly 20 . an optical fibre 23 is used to direct incident light from the remotely located laser diode 1 to the surface of the die 2 at the collet 21 . another optical fibre 24 is used to direct light reflected from the surface of the die 2 to the photo - sensor 8 , which is also remotely located . in another alternative arrangement ( not shown ), a single fibre directs both incident light to , and reflected light from , the die . in alternative arrangements ( not shown ), optical systems such as light guides , mirrors , etc , can be used to direct the incident light from the light source 1 , or to direct light reflected by the die surface back to the photo - sensor 8 . an advantage of using optical fibres 23 , 24 is that the light source and / or the sensor need not be mounted on the collet assembly 20 so that heavier and more complicated designs can be used without burdening a bond arm controlling it . it should be appreciated that either or both of the light source 1 and the photo - sensor 8 may be mounted on the collet assembly 20 or may be located remotely . fig5 is a schematic view of the layout of a placement apparatus that uses the missing die detection arrangements described above . a bond arm 11 is mounted to rotate about an axis 12 . a collet assembly 20 is carried at the distal end 13 of the bond arm . the illuminating light source and the photo - sensor are mounted in the collet assembly 20 . the illuminated light is collimated or focused into a beam providing a small spot size which is projected through the collet and onto the position to be occupied by a die . signal - to - noise ratio of the detecting signal is high because background noise is reduced by the use of the collimated or focused beam and small spot size . fig5 shows the bond arm 11 in three positions . in a first bond arm position 11 a , the pick - up head and collet are located over a selected die ( not shown ) on a sapphire wafer 14 on which individual dice have been fabricated and diced . the collet is operated in an attempt to pick up the selected die and the bond arm 11 is rotated to move the collet toward a third bond arm position 11 c . the sapphire wafer has a highly specular surface which can interfere with measurements of light reflected from an individual die above the wafer . therefore , a dark background 15 is arranged under an intermediate second position 11 b through which the bond arm moves when passing from the first position 11 a to a third position 11 c . while the collet is moving over the dark background , the photo - sensor signal processor is triggered , for example by a signal from a host controller or a bond arm controller , to make a measurement of light reflected from the die , if present , in the collet . the measurement is undertaken while the bond arm keeps moving as it is moving over the dark background . the measurement is compared to a reference signal , representing a reference level of detected light intensity in the absence of a die plus a reasonable margin , that can be manually preset or automatically learned by the signal processor . if the reflection measurement is greater than the reference signal this is taken as an indication that a die is present in the collet , otherwise a missing die alarm is raised and the bond arm is returned to the first bond arm position 11 a , to make another attempt to pick up a die . if the indication derived from the reflection measurement is that a die is present in the collet , the bond arm continues moving to the third bond arm position 11 c at which the collet is released to place the die in a bonding position . the bond arm then begins to return back to the first bond arm position 11 a . while the collet is returning over the dark background 15 , the photo - sensor signal processor is again triggered to make a second measurement of light reflected from the die , if present , in the collet . again the measurement is undertaken while the bond arm keeps moving and the measurement compared to the reference signal . if the reflection measurement is less than the reference signal this is taken as an indication that a die is not present in the collet , and that the die was well placed . otherwise , a reflection signal greater than the reference is taken as an indication that the die was not placed and an unplaced die alarm is raised . if the reflection measurement is less than the reference signal , indicating that a die is not present in the collet , then the reference signal may be replaced by this reflection measurement with a reasonable margin added . in this way the reference signal may be continually updated to accommodate variations in ambient conditions , for example background light levels , and to accommodate drift of the apparatus performance parameters , for example in the light source and the photo - sensor . the bond arm returns to the first position 11 a to complete one die placement cycle . although the embodiment refers to a transparent die , it should be appreciated that a presence of a non - transparent die can also be detected by an apparatus and method according to the invention . the foregoing describes the invention including preferred forms thereof . alterations and modifications as will be obvious to those skilled in the art are intended to be incorporated within the scope hereof as defined in the accompanying claims .
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embodiments of the present invention will be described in detail on the basis of the following drawings . first , a configuration of an x - ray ct apparatus 1 will be described with reference to fig1 and fig2 . as illustrated in fig1 , the x - ray ct apparatus 1 includes a scanner 2 on which an x - ray tube 11 and a detector 12 are loaded , a bed 4 on which a test object 10 is placed , an arithmetic device 5 that processes data obtained from the detector 12 , an input device 6 such as a mouse , a trackball , a keyboard , a touch panel and so forth , a display device 7 that displays a reconstructed image and so forth and others . an operator inputs imaging conditions , reconstruction parameters and so forth via the input device 6 . the imaging conditions are , for example , a bed feed rate , a tube current , a tube voltage , a slice position and so forth . in addition , the reconstruction parameters are , for example , a region of interest , a reconstructed image size , a back projection phase width , a reconstruction filter function and so forth . as illustrated in fig2 , the x - ray ct apparatus 1 includes the scanner 2 , an operation unit 3 and the bed 4 when broadly classified . the scanner 2 includes the x - ray tube 11 ( an x - ray source ), the detector 12 ( an x - ray detector ), a collimator 13 , a drive device 4 , a central control device 15 , an x - ray control device 16 , a high - voltage generation device 17 , a scanner control device 18 , a bed control device 19 , a bed movement measuring device 20 , a collimator control device 21 , a preamplifier 22 , an a / d converter 23 and so forth . the x - ray ct apparatus 1 is broadly classified into a multislice ct using the detector 12 that detection elements are arrayed in two - dimensional directions and a single slice ct using the detector 12 that the detection elements are arrayed in line , that is , in one - dimensional direction ( only in a channel direction ). in the multislice ct , x - ray beams which spread in a cone - like form or in a pyramid - like form are irradiated from the x - ray tube 11 which is an x - ray source conforming with the detector 12 . in the single slice ct , the x - ray beams which spread in a fan - like form are irradiated from the x - ray tube 11 . in general , in imaging using the x - ray ct apparatus 1 , x - ray irradiation is performed while a gantry part is going around the test object 10 placed on the bed 4 . the central control device 15 controls to input the imaging conditions and the reconstruction parameters through the input device 6 in the operation unit 3 and to transmit control signals desired for imaging to the collimator control device 21 , the x - ray control device 16 , the scanner control device 18 and the bed control device 19 . the collimator control device 21 controls the position of the collimator 13 on the basis of the control signal . when imaging is started by receiving an imaging start signal , the x - ray control device 16 controls the high - voltage generation device 17 on the basis of the control signal . the high - voltage generation device 17 applies the tube voltage and the tube current to the x - ray tube 11 . in the x - ray tube 11 , electrons of energy according to the applied tube voltage are emitted from a cathode and the emitted electrons strike a target ( an anode ), thereby irradiating the test object 10 with the x - ray of energy according to the energy of the electrons . in addition , the scanner control device 18 controls the drive device 14 on the basis of the control signal . the drive device 14 drives the gantry part on which the x - ray tube 11 , the detector 12 , the preamplifier 22 and so forth are loaded so as to go around the test object 10 . the bed control device 19 controls the bed 4 on the basis of the control signal . the x - ray irradiated from the x - ray tube 11 is controlled by the collimator 13 in irradiation region , is absorbed ( attenuated ) in accordance with an x - ray attenuation coefficient into each tissue in the test object 10 , passes through the test object 10 and is detected by the detector 12 arranged at a position facing the x - ray tube 11 . the detector 12 includes the plurality of detection elements which are arrayed in the two - dimensional directions ( the channel direction and a column direction orthogonal to the channel direction . the x - ray received by each detection element is converted into real projection data . that is , the x - ray detected by the detector 12 is converted into current , is amplified by the preamplifier 22 , is converted into digital data by the a / d converter 23 , is subjected to logarithmic transformation , is calibrated and is input into the arithmetic device 5 as the real projection data . at that time , since the mutually facing x - ray tube 11 and detector 12 rotate around the test object 10 , the real projection data is collected at discrete x - ray tube positions ( and corresponding detector positions ) in a rotation direction . a real projection data acquisition unit at each x - ray tube position is called a “ view ”. the arithmetic device 5 includes a reconstruction arithmetic device 31 , an image processing device 32 and so forth . in addition , an input / output device 9 includes the input device 6 , the display device 7 , a memory device 8 ( a memory unit ) and so forth . the reconstruction arithmetic device 31 performs an image reconstructing process using the real projection data and generates a reconstructed image . the reconstruction arithmetic device 31 generates filtered projection data by superimposing a reconstruction filter on the real projection data of each view and performs back projection processing on the filtered projection data by adding weight in a view direction , thereby non - destructively imaging a tomographic image as a distribution map of an x - ray attenuation coefficient in the test object 10 . the reconstruction arithmetic device 31 stores the generated reconstructed image into the memory device 8 . in addition , the reconstruction arithmetic device 31 displays the reconstructed image as a ct image on the display device 7 . alternatively , the image processing device 32 may perform image processing on the reconstructed image stored in the memory device 8 and displays the image so processed as the ct image on the display device 7 . in the following , an image processing method that adds respective mutually corresponding pixels of an original image generated from original information acquired by the x - ray ct apparatus 1 and so forth and a smoothed image which is generated from the same original information and is reduced at least in streak artifact with weighting by using a weighting coefficient and generate a target image that the edge of the structure is maintained and the streak artifact is removed will be described . in the image processing method according to the embodiment of the present invention , the target image is generated so as to meet the following three constraint conditions . ( constraint condition 1 ) the pixel value of the target image is to be within a range of pixel values of mutually corresponding pixels in the original image and the smoothed image . ( constraint condition 2 ) the target image is to be an image which is smooth spatially ( that is , in one image space ). ( constraint condition 3 ) the target image is to be suppressed in increase in noise such as the streak artifact and so forth in a region (= one of the flat regions ) which is thought to be the same organ in comparison with the smoothed image . the constraint condition 1 is a condition which has been defined in order not to lose the original image ( however , the noise is excluded ) acquired by the x - ray ct apparatus 1 and so forth . the constraint condition 1 may be expressed in such a different form as min ( a minimum pixel value of the original image and a minimum pixel value of the smoothed image ) s a pixel value of the target image 5 max ( a maximum pixel value of the original image and a maximum pixel value of the smoothed image ). incidentally , min ( ) is an operator for outputting a minimum value and max ( ) is an operator for outputting a maximum value . the constraint condition 2 is a condition which has been defined in order to avoid discontinuity which would occur in the target image . the constraint condition 3 is a condition which has been defined in order to remove mainly the granular noise and the streak artifact . the image processing method according to the embodiment of the present invention features to meet the constraint condition 3 in particular . the weighting coefficient used for weighted addition is determined by condition coefficients indicating the conditions of the original image and the smoothed image . the condition coefficient has a value of a nonlinear function that a difference in pixel value between a pixel of interest of the original image or the smoothed image and an adjacent pixel thereof is set as a variable . in the embodiment of the present invention , a generalized gaussian function is used as the nonlinear function . however , any nonlinear function will do as long as it is a smooth continuous function , has a plurality of arbitrary parameters and is arbitrarily adjustable in shape , and there is no particular limit thereon . if the nonlinear function is the smooth continuous function , the aforementioned “( constraint condition 2 ) the target image is to be an image which is smooth spatially ( that is , in one image space )” will be met . as other examples of the nonlinear function , a logistic function and so forth may be given . an image vector is put as x =( x 1 , . . . , x j ), a set of adjacent pixels r relative to a pixel of interest s is put as n s and a condition coefficient g s ( x ) of the pixel of interest s is defined by the following formula using the generalized gaussian function . here , p is an arbitrary parameter for adjusting the gradient of the generalized gaussian function and is set to have the same value for all slices . ν is an arbitrary parameter for adjusting a bending position of the generalized gaussian function . w sr is a weighting coefficient according to a distance between the pixel of interest s and the adjacent pixel r and is defined , for example , as in the following formula . here , l sr is the distance between the pixel of interest s and the adjacent pixel r . l is a ratio of the size of a pixel to the size of an element of the detector . however , w sr may not necessarily be limited to the formula ( 2 ) and may be a function whose value is increased as the adjacent pixel r is closer to the pixel of interest s . in addition , the set n s of pixels adjacent to the pixel of interest s and the gradient p of the generalized gaussian function may be empirically determined . in the formula ( 1 ), if the pixel values of the pixel of interest s and the adjacent pixel r are equal to each other , the condition coefficient will become 1 , and the larger the difference in pixel value between the pixel of interest s and the adjacent pixel r is , the more the condition coefficient will approach 0 . one example of a change in shape of functions when ν has been set to arbitrary constants c , 2c and 4c for the difference in pixel value between the pixel of interest s and the adjacent pixel r is illustrated in fig3 . thinking of the situation by fixing the difference in pixel value , the more ν is increased , the more the condition coefficient is liable to have a value close to 1 . according to the embodiment of the present invention , the parameter ν for adjusting the bending position of the function is determined such that the condition coefficient has a value almost close to 1 relative to the difference in pixel value between the pixel of interest s and the adjacent pixel r which would occur due to the presence of the streak artifact in one tomographic image . in the following , the first embodiment of the present invention will be described following the stream of a processing flow illustrated in fig4 while appropriately referring to other drawings . the arithmetic device 5 of the x - ray ct apparatus 1 ( hereinafter , referred to as the “ arithmetic device 5 ) determines the shape of the nonlinear function on the basis of feature amounts of the original image and the smoothed image . a process of determining the shape of the nonlinear function will be described later with reference to fig5 . the arithmetic device 5 divides regions of the original image and the smoothed image into mutually corresponding small regions . for example , as illustrated in fig6 , the arithmetic device 5 partitions the regions of an original image 41 and a smoothed image 42 in a lattice shape and divides them into small regions . the size of the small region is empirically determined . however , the method of dividing one region into small regions is not limited to this example . in the embodiment of the present invention , the regions of the original image 41 and the smoothed image 42 may be just divided into the small regions by the same dividing method . in addition , the shape of the small region is not limited to a rectangle . in the embodiment of the present invention , the plurality of adjacent pixels may be included in the same small region . in addition , one pixel may be included in the plurality of small regions redundantly . the arithmetic device 5 calculates variation values of the original image 421 and the smoothed image 42 from the pixel values of the pixels included in the small region for each of the respective small regions pertaining to both of the original image 41 and the smoothed image 42 . the variation value is , for example , a standard deviation value , ( the maximum value − the minimum value ) and so forth . the variation value is a value indicating a variation of each small region and may be a statistic calculated from the pixel values of the pixels included in each small region . in the following , description will be made by giving the standard deviation value as an example in order to avoid confusion . here , for the convenience of explanation , serial numbers i = 1 , . . . are allocated to the small regions and attention will be paid to an i - th small region . the standard deviation value of the original image 41 in the i - th small region is put as σ i ( org ) and the standard deviation value of the smoothed image 42 is put as σ i ( smt ) . the arithmetic device 5 calculates a decreasing rate of the variation value of the smoothed image 42 based on the variation value of the original image 41 for every small region . in the present embodiment , the decreasing rate of the standard deviation value is calculated . for the i - th small region , the decreasing rate of the standard deviation value of the smoothed image 42 based on the standard deviation value of the original image 41 is put as ρ i and is calculated by the following formula . the arithmetic device 5 calculates the decreasing rate ρ i of the standard deviation value in all of the small regions on the basis of the formula ( 3 ). the shape of the nonlinear function is determined using a feature amount ( for example , the decreasing rate ρ i ) calculated from the pixel values of the pixels in both of the original image 41 and the smoothed image 42 as in the formula ( 3 ) and the processing illustrated in fig4 is performed , thereby meeting the aforementioned “( constraint condition 3 ) the target image is to be suppressed in increase in noise such as the streak artifact and so forth in a region (= one of the flat regions ) which is thought to be the same organ in comparison with the smoothed image ”. incidentally , in related art ( for example , japanese patent no . 3700798 and japanese patent application laid - open no . hei07 - 93543 ) relating to the technique of mixing together two images which are the same as each other in original information , only the feature amount calculated from the pixel values of the pixels included in only one of the images is used . for example , with the standard deviation value calculated from the pixel values of the pixels included in only one of the images , it is difficult to discriminate between whether the noise has been reduced and whether the structure has blurred as a result of execution of an arbitrary smoothing process . accordingly , it is difficult for related art to generate such a target image that the streak artifact is removed as generated in the embodiment of the present invention . the arithmetic device 5 extracts a feature amount calculation region from the set of small regions on the basis of the decreasing rate ρ i . in the first embodiment , the arithmetic device 5 extracts a small region whose decreasing rate has a maximum value in the small regions included within a predetermined range ( for example , in the same slice ) as the feature amount calculation region . incidentally , the predetermined range may be either in a plurality of slices or in all of the slices . in the following , description will be made assuming that a k - th small region has been extracted as the feature amount calculation region . the arithmetic device 5 determines the shape of the nonlinear function from the feature amount calculated from the pixel values of the pixels included in the feature amount calculation region ( the k - th small region ). in the following , an example that the feature amount is calculated by using a standard deviation value σ k ( org ) of the original image 41 calculated in step s 202 and a standard deviation value σ k ( smt ) of the smoothed image 42 calculated in step s 203 will be described . however , the present invention is not limited to this example and another variation value ( for example , the difference between the maximum value and the minimum value of the pixels in the small region concerned ) may be used in place of the standard deviation value . an arbitrary constant is putt as α ( 0 & lt ; α & lt ; 1 ) and the shape of the nonlinear function is set such that the condition coefficient takes the value of α when the difference in pixel value is σ k ( a general notation of σ k ( org ) and σ k ( smt ) ( see fig3 ). α is an actual value such as , for example , 0 . 99 , 0 . 98 , 0 . 97 or the like . for example , for the generalized gaussian function in the formula ( 1 ), the parameter ν for adjusting the bending position of the function is defined as in the following formula . here , t is a positive coefficient which is not 1 and is empirically determined from statistical information obtained from already photographed images by taking the influence of the noise such as the streak artifact and so forth into account . for example , for an image that only gaussian noise ( the granular noise ) is generated , t = 1 is put and introduction of t into the formula ( 4 ) may be unnecessary . however , the embodiment of the present invention targets on the image that the streak artifact which is the noise stronger than the gaussian noise is generated , t of a value larger than 1 is introduced into the formula ( 4 ). in the formula ( 4 ), the parameters for adjusting the bending positions of the nonlinear functions calculated in the original image 41 and the smoothed image 42 respectively are put as σ k ( org ) and σ k ( smt ) . the arithmetic device 5 dynamically determines the shape of the nonlinear function for every predetermined range ( for example , for every slice ) by executing the processing illustrated in fig5 . one of the features of the first embodiment lies in the point that the region whose decreasing rate ρ i of the standard deviation value of the smoothed image 42 to the standard deviation value of the original image 41 has a maximum value is extracted as the feature amount calculation region and the shape of the nonlinear function is determined using the standard deviation value of the feature amount calculation region . the aforementioned projection data smoothing filter has such a characteristic that it greatly decreases the streak artifact . owing to this characteristic , the decreasing rate ρ i of the standard deviation value is increased in the small region including the streak artifact . in addition , the projection data smoothing filter also has such a characteristic that blurring of the structure is involved . owing to this characteristic , since the standard deviation value of the original image is increased in the small region including the structure and the denominator in the formula ( 3 ) is increased , the decreasing rate ρ i of the standard deviation value is decreased consequently . that is , the possibility that the region whose the decreasing rate ρ i of the standard deviation value has the maximum value may include the streak artifact is high . therefore , extraction of the region whose decreasing rate ρ i of the standard deviation value has the maximum value as the feature amount calculation region leads to extraction of the small region which includes the streak artifact as the feature amount calculation region . then , it is possible to obtain the target image that the streak artifact is removed eventually by substituting the standard deviation value of the small region which includes the streak artifact into the formula ( 4 ) and determining the value of the parameter ν for adjusting the bending position of the nonlinear function . getting back to the description of the flow in fig4 , in the following , processes of calculating the condition coefficients indicating the respective conditions of the original image 41 and the smoothed image 42 using the nonlinear function and calculating the weighting coefficient for weighted addition from the condition coefficients of the original image 41 and the smoothed image 42 will be described . the arithmetic device 5 calculates the condition coefficients of the original image 41 and the smoothed image 42 using the nonlinear function whose shape is determined in step s 101 . the process of calculating the condition coefficients is executed following the formula ( 1 ). the arithmetic device 5 calculates the weighing coefficient of each pixel of the original image 41 and the smoothed image 42 by using the condition coefficients calculated in step s 102 . the image vector of the original image 41 is put as x ( org ) ={ x 1 ( org ) , . . . , x j ( org ) and the image vector of the smoothed image 42 is put as x ( smt ) ={ x 1 ( smt ) , . . . , x j ( smt ) . in weighted addition of the images , the weighting coefficient pertaining to the pixel of interest s is put as λ s . the process of calculating λ s is executed following any one of the following formula ( 5 ), formula ( 6 ) and formula ( 7 ). λ s ≡ g s ( x ( org ) , ν k ( org ) )· g s ( x ( smt ) , ν k ( smt ) ) ( 5 ) λ s ≡{ g s ( x ( org ) , ν k ( org ) + g s ( x ( smt ) , ν k ( smt ) )}/ 2 ( 6 ) λ s ≡{ g s ( x ( org ) , ν k ( org ) )· g s ( x ( smt ) , ν k ( smt ) } 1 / 2 ( 7 ) one of the features of the embodiment of the present invention lies in the point that the values of the weighting coefficients of the mutually corresponding pixels are calculated using the condition coefficients of both of the original image 41 and the smoothed image 42 as expressed in the formula ( 5 ) to the formula ( 7 ). in the formula ( 5 ) and the formula ( 7 ), in a case where the condition coefficient takes a value close to 1 in at least either of the original image 41 and the smoothed image 42 and it is decided that the pixel of interest s corresponds to an edge part of the structure , the weighting coefficient takes a value close to 0 . on the other hand , in a case where the condition coefficients of both of the original image 41 and the smoothed image 42 take values close to 1 and it is decided that the pixel of interest s corresponds to a flat region ( for example , a region which is thought to be the same organ ), the weighting coefficient takes a value close to 1 . in the formula ( 6 ), in a case where the condition coefficients of both of the original image 41 and the smoothed image 42 take values close to 0 , the weighting coefficient takes a value close to 0 . in addition , in the formula ( 6 ), in a case where the condition coefficients of both of the original image 41 and the smoothed image 42 tales values close to 1 , the weighting coefficient takes a value close to 1 . on the other hand , in the formula ( 6 ), in a case where a difference in value of condition coefficient between the original image 41 and the smoothed image 42 is large , a mean value of the both is defined as the weighting coefficient . considering from the above , in a case where it is desired to sharply recover the edge of the structure in the target image , it is desirable to use the formula ( 5 ) or the formula ( 7 ). on the other hand , in a case where it is desired to smoothly recover the edge of the structure in the target image , it is desirable to use the formula ( 6 ). the both ways of recovering the edge may be properly used depending on the application . the arithmetic device 5 generates the target image by performing weighed addition of the original image 41 and the smoothed image 42 by using the weighting coefficient calculated in step s 103 . the image vector of the target image after weighted addition has been performed is set as x ( mrg ) ={ x 1 ( mrg ) , . . . , x j ( mrg ) }. the arithmetic device 5 performs weighted addition for the pixel of interest s of the target image by using the following formula . x s ( mrg ) = λ s ( x s ( smt ) − x s ( org ) )+ x s ( org ) ( 8 ) the aforementioned “( constraint condition 1 ) the pixel value of the target image is to be within a range of pixel values of mutually corresponding pixels in the original image and the smoothed image ” is met by performing weighted addition by using the formula ( 8 ). examples of schematic diagrams of the original image 41 , the smoothed image 42 and a target image 43 are illustrated in fig7 . as illustrated in fig7 , a streak artifact 51 is being generated in the original image 41 . in addition , a blur 52 of the edge of the structure is being generated in the smoothed image 42 . it is possible to generate the target image 43 that the edge of the structure is maintained and the streak artifact 51 is removed from such original image 41 and smoothed image 42 as mentioned above by the image processing method according to the embodiment of the present invention illustrated in fig4 . as illustrated in fig7 , the edge of the structure is maintained and the streak artifact 51 is removed in the target image 43 . in the following , the second embodiment of the present invention will be described . incidentally , description of the contents which are common to the first embodiment is omitted . in the first embodiment , the small region whose decreasing rate of the variation value of the smoothed image 42 to the variation value of the original image 41 has the maximum value is extracted as the feature amount calculation region and the parameter ν for adjusting the bending position of the nonlinear function is determined on the basis of the feature amount of the feature amount calculation region . at that time , the feature amount calculation region is extracted by analyzing in more detail the relation between the decreasing rate of the variation value and the variation value of the original image 41 or the smoothed image 42 . owing to this , the precision that the flat region including the streak artifact 51 is extracted as the feature amount calculation region is improved . in the second embodiment , the arithmetic device 5 extracts m higher - rank small regions which are higher in decreasing rate ρ i of the standard deviation value in the small regions included within the predetermined range ( for example , in the same slice ) in step s 205 in fig5 . that is , the arithmetic device 5 extracts the small regions counted from the small region whose decreasing rate ρ i of the standard deviation value has the maximum value down to an m - th ranked small region . here , m is an arbitrary constant and is empirically determined . next , the arithmetic device 5 extracts the small region whose standard deviation value has a maximum value in m higher - rank small regions as the feature amount calculation region in each of the original image 41 and the smoothed image 42 . the feature amount calculation process , the nonlinear function shape determination process , the condition coefficient calculation process , the weighing coefficient calculation process , the weighted addition process and so forth which are succeeding processes are the same as those in the first embodiment . according to the second embodiment , the precision that the flat region including the streak artifact 51 is extracted as the feature amount calculation region is improved . it is apparent that the object of the present invention is attained from the above - mentioned description relating to the various embodiments of the present invention . although the present invention has been described and illustrated in detail , they simply aim at description and illustration and the present invention is not limited to them . in addition , the gist of the present invention is to be limited only by the scope of the patent claims . 1 : x - ray ct apparatus , 2 : scanner , 3 : operation unit , 4 : bed , 5 : arithmetic device , 6 : input device , 7 : display device , 8 : memory device , 10 : test object , 11 : x - ray tube , 41 : original image , 42 : smoothed image , 43 : target image , 51 : streak artifact , 52 : blur of structure edge
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the general organization of the exemplified year - round air conditioner will become apparent upon consideration of fig1 and 2 . broadly it comprises : 1 . a housing 10 having a filter - screened air inlet 12 and a louvered air outlet 14 . 2 . a water receptacle 16 withdrawably mounted on the bottom 18 of the housing 10 . 3 . a wet band assembly 20 also withdrawably mounted within the housing 10 in partial immersion in the water w contained in the receptacle 16 . 4 . a fan 22 within the housing 10 for producing an airflow a from air inlet 12 to air outlet 14 through the wet band assembly 20 . 5 . a damper 24 pivotally mounted at the air outlet 14 for dividing the same into a cool air outlet 26 and a warm air outlet 28 and for selectively communicating the cool and warm air outlets with the air inlet 12 . 6 . an electric heater 30 mounted on the damper 24 for heating the air as it is expelled through the warm air outlet 28 . the housing 10 is of generally boxlike shape , mounted on casters 32 for portability . the air inlet 12 is defined in the rear wall 34 of the housing midway between its top and bottom ends . a filter screen 36 covers the air inlet 12 for removal of dust from the incoming room air . the air outlet 14 , on the other hand , is defined in the front wall 38 of the housing 10 in the vicinity of its top end . this air outlet is fitted with a dual louver assembly 40 comprising a set of vertical slats 42 and a set of horizontal slats 44 . during cooling or heating operation of the air conditioner the vertical slats 42 are to be jointly and repeatedly oscillated about their vertical pivots by an electric motor drive unit 46 for correspondingly oscillating the conditioning airstream being discharged through the cool air outlet 26 or warm air outlet 28 . the horizontal slats 44 are to be manually turned about their horizontal pivots for varying the angle of the conditioning air - stream either upwardly or downwardly . molded of plastic material , the water receptacle 16 is to be inserted in the housing 10 through an aperture 48 in its rear wall 34 . a lid 50 openably closes the aperture 48 . a pair of guide plates 52 are firmly erected on the bottom 18 of the housing 10 , one on each side of the water receptacle 16 . placed on the bottom 18 of the housing through the aperture 48 , the water receptacle 16 is to be slid along the pair of upstanding guide plates 52 to its preassigned working position best depicted in fig1 . the lid 50 has a pusher 54 projecting interiorly therefrom to butt on the rear wall of the water receptacle 16 . upon closure of the lid 50 , therefore , the pusher 54 pushes the water receptacle 16 to its working position . open at the top , the water receptacle 16 has its top edge bent outwardly into an l - shaped rim 56 ( fig2 ) for ease of handling by the user . the rim 56 is crimped or curled at 58 for reinforcement . closing the open top of the water receptacle 16 is a cover 60 which may also be molded of plastics material and which rests on the ledge 62 formed by part of the l - shaped rim 56 of the water receptacle . the cover 60 has an elongate aperture 64 defined therein for the passage of the wet band assembly 20 with considerable clearance . a plate 66 depending from the cover 60 in the vicinity of the aperture 64 functions to minimize the waving of the water w in the receptacle 16 upon exertion of external forces on the air conditioner . further , the cover 60 is formed to include a depression 68 for the receipt of water from a replenishing vessel 70 removably mounted thereon . this replenishing vessel has a built - in valve mechanism , not shown , whereby the water receptacle 16 is replenished through an opening 72 in the cover depression 68 to keep the water at a constant level . the housing 10 has an aperture 74 defined in its front wall 38 for the insertion and withdrawal of the replenishing vessel 70 to and from its illustrated working position on the water receptacle cover 60 . a hinged or otherwise openable lid 76 normally holds the aperture 74 closed . the wet band assembly 20 is formed as a discrete unit and is readily withdrawable from within the housing 10 for servicing . as shown in both fig1 and 2 and on an enlarged scale in fig3 the wet band assembly 20 comprises : 1 . a pair of elongate , channeled side frames 78 in parallel spaced relation to each other . 2 . a drive roll 80 and an idler roll 82 rotatably mounted at the opposite extremities of the pair of side frames 78 . 3 . a relatively wide , endless band 84 of generally porous , water - absorbent , air - permeable material , such as that normally used for filtration purposes , wrapped around and extending between the drive and idler rolls 80 and 82 . 4 . a small motor drive unit 86 ( hereinafter referred to as the band motor ) mounted on one of the side frames 78 and coupled to the drive roll 80 for imparting rotation thereto and hence for driving the endless porous band 84 in the direction of the arrows in fig1 . on the opposite sides of the wet band assembly 20 there are provided a pair of support plates 88 in fixed relation to the housing 10 . a pair of channeled guides 90 are affixed respectively to the opposed surfaces of the support plates 88 , sloping rearwardly as they extend upwardly . the wet band assembly 20 , or its pair of side frames 78 , is to slide along the guideways 92 defined by the channeled guides 90 to and away from its working position indicated in fig1 and 2 . preferably the side frames 78 of the wet band assembly should have some transverse play with respect to the respective channeled guides 90 . the rear wall 34 of the housing 10 is further apertured at 94 , fig1 for the introduction and withdrawal of the wet band assembly 20 to and away from its working position . the aperture 94 is provided with a hinged lid 96 pivotable about a pin 98 . disposed immediately interiorly of the aperture 94 is a slot 100 in alignment with the pair of guideways 92 defined by the channeled guides 90 . the wet band assembly 20 has its top end portion held engaged in the slot 100 when it is in the working position . preferably the pair of side frames 78 of the wet band assembly 20 should have their top end portions flared in order that the wet band assembly may not drop too far into the slot 100 . either or both of these top ends of the side frames 78 may be provided with a handle or handles 102 to facilitate the manipulation of the wet band assembly 20 into and out of the housing 10 . thus , on being inserted into the slot 100 in the housing 10 through the aperture 94 , the wet band assembly 20 slides along the pair of opposed guideways 92 until the flaring top end portions of its side frames 78 become caught at the entrance of the slot 100 . in this operating position of the wet band assembly 20 , its idler roll 82 lies wholly in the water w in the receptacle 16 , so that the endless porous band 84 is partly submerged in the water through the aperture 64 in the receptacle cover 60 . as the band motor 86 revolves the drive roll 80 , therefore , the porous band 84 travels over the rolls 80 and 82 while being constantly wetted by the water in the receptacle 16 . it will also be observed from fig1 that the wet band assembly 20 intervenes between air inlet 12 and air outlet 14 in the housing 10 . consequently the airflow a , induced by the fan 22 , passes the porous band 84 on its way from air inlet 12 to air outlet 14 . the fan 22 is mounted within a curved , tapering air duct 104 which functions to guide the airflow a from the wet band assembly 20 to the air outlet 14 . the air duct 104 has a larger entrance end 106 open toward the wet band assembly 20 and a smaller exit end or air passage 108 open toward the air outlet 14 . the fan 22 lies at or adjacent the entrance end 106 of the air duct 104 . mounted exteriorly of the air duct 104 , on one side thereof , is a motor drive unit 110 for the fan 22 . this motor drive unit will hereinafter be referred to as the fan motor in contradistinction to the band motor 86 . with reference to fig1 the damper 24 extends horizontally across the air outlet 14 and so partitions the same into the upper , cool air outlet 26 and the lower , warm air outlet 28 . arranged at or adjacent to the exit end or air passage 108 of the air duct 104 , the damper 24 pivots about a horizontal axis at 112 for selectively communicating the cool air outlet 26 and warm air outlet 28 with the air inlet 12 in coaction with the air duct . fig1 indicates the two operating positions of the damper 24 by the solid and phantom lines . in the solid - line slanting position the damper 24 places the warm air outlet 28 in communication with the air inlet 12 . when pivoted clockwise to the phantom horizontal position , on the other hand , the damper 24 establishes communication between the cool air outlet 26 and air inlet 12 . the electric heater 30 is mounted on that surface of the damper 24 which is directed downwardly when the damper is in the horizontal position in this particular embodiment . the heater 30 is to be energized only when the damper 24 is in the slanting position , heating the air - stream a being discharged through the warm air outlet 28 . in the horizontal position of the damper 24 , on the other hand , the heater 30 is held deenergized and retracted away from the path of the airstream flowing through the cool air outlet 26 . such energization and deenergization of the heater 30 take place automatically as the damper 24 is manually activated between its two working positions . the following description will make clear how the heater 30 is automatically set into and out of operation with the pivotal motion of the damper 24 . fig4 illustrates a manual actuating mechanism 114 for the damper 24 . the manual actuating mechanism 114 includes an arm 116 rigidly anchored at one end on the pivot pin 112 of the damper 24 for joint pivotal motion therewith . the other end of the arm 116 is pin jointed at 118 to one end of a link 120 , the other end of which is likewise pin jointed at 122 to one end of a hand lever 124 . medially pivoted at 126 , the hand lever 124 has a knob 128 on the other end which projects out of the conditioner housing 10 for manipulation by the user . a heater switch 130 is positioned adjacent the hand lever 124 of the damper actuating mechanism 114 . the hand lever 124 has an abutment 132 secured thereto for movement into and out of abutting engagement with the actuator arm 134 of the heater switch 130 . it is clear from the foregoing discussion of fig4 that the manual actuation of the hand lever 124 to the solid line position results in the pivotal motion of the damper 24 to the phantom horizontal position of fig1 . the damper 24 , when in this position , places the cool air outlet 26 in communication with the air inlet 12 . also , when turned to the solid line position of fig4 the hand lever 124 causes the heater switch 130 to deenergize the heater 30 . when pivoted counterclockwise to the phantom position of fig4 on the other hand , the hand lever 124 causes the damper 24 to pivot to the solid - line slanting position of fig1 and hence to communicate the warm air outlet 28 with the air inlet 12 . the heater switch 130 becomes closed upon counterclockwise turn of the hand lever 124 , so that the heater 30 becomes energized to heat the airstream being discharged through the warm air outlet 28 . fig5 is a schematic diagram of a plug - in electric circuitry to be incorporated into the year - round air conditioner of the above - described mechanical construction . the circuitry has a plug 136 for insertion in a service outlet or the like . a pair of supply lines 138 and 140 are connected to the plug 136 , with the supply line 138 having a power switch 142 . connected between the pair of supply lines 138 and 140 are : 1 . a line 144 having a timer switch 146 , a lid switch 148 , a relay coil 150 associated with the power switch 142 , and a current limit switch 152 . 3 . a line 158 having the heater switch or warm switch 130 , the heater 30 and , in parallel with the latter , a warm pilot lamp 160 . 4 . lines 162 and 164 having the fan motor 110 capable of operation at a high or low speed , and a capacitor 166 . 6 . a line 170 having a cool switch 172 and a cool pilot lamp 174 . as shown also in fig1 the lid switch 148 on the line 144 is to be activated by the hinged lid 96 normally closing the aperture 94 through which the wet band assembly 20 is inserted in and withdrawn from the conditioner housing 10 . the warm switch 130 and the cool switch 172 are coordinated with each other in such a manner that one is opened when the other is closed , and vice versa . the circuitry of fig5 further includes a rotary multicontact switch 176 for the on - off control of the two - speed fan motor 110 and the band motor 86 . the rotary switch comprises an annular row of fixed contacts designated 1 through 7 , and a dual movable contact 178 capable of simultaneous engagement with any two diametrically opposed fixed contacts . the operational description of the year - round air conditioner follows . for the production of warm , moist air the user may close the power switch 142 , operate the movable contact 178 of the rotary switch 176 into engagement either with the fixed contacts 1 and 5 or with the fixed contacts 2 and 6 , and turn the hand lever 124 of the damper actuating mechanism 114 to the phantom position of fig4 . the power pilot lamp 156 glows upon closure of the power switch 142 . the simultaneous engagement of the movable contact 178 of the rotary switch 176 with the fixed contacts 1 and 5 , or 2 and 6 , results in the operation of both the band motor 86 and the fan motor 110 . driven by the fan motor 110 at high or low speed , the fan 22 draws room air into the conditioner housing 10 through the filter screen 36 at the air inlet 12 . within the housing 10 the filtered airstream a passes the wetted porous band 84 traveling over the pair of rolls 80 and 82 , thereby to be both moistened and refiltered . then the dust - free moist air enters the duct 104 . as the hand lever 124 of the damper actuating mechanism 114 is activated as above , the damper 24 pivots to the solid - line slanting position of fig1 thereby placing the warm air outlet 28 in communication with the air inlet 12 . simultaneously the warm switch 130 becomes closed by the hand lever 124 to cause the heater 30 to be energized and the warm pilot lamp 160 to glow . thus the heater 30 heats the filtered , moistened air as it flows through the warm air outlet 28 out into the room . positioned at the relatively constricted part of the airflow path , the heater 30 can effectively heat the air to a required temperature range in spite of its limited capacity . further , the damper 24 in its slanting position coacts with the air duct 104 to direct the stream of warm , moist air downwardly through the warm air outlet 28 , toward the floor , for most efficiently heating the room . for the production of warm air without humidification the user may operate the rotary switch 176 to move one of the arms of its movable contact 178 into engagement with either the fixed contact 4 or 7 . then only the fan motor 110 will be set into operation , with the band motor 86 held out of operation . for cooling the room , on the other hand , the user may close the power switch 142 , actuate the movable contact 178 of the rotary switch 176 into engagement either with the fixed contacts 1 and 5 or with the fixed contacts 2 and 6 , and manipulate the hand lever 124 of the damper actuating mechanism 114 to the solid line position of fig4 . thus the band motor 86 and the fan motor 110 are both set into operation as in the above described case of warm , moist air supply . drawn by the fan 22 into the conditioner housing 10 through the filter screen 36 at the air inlet 12 , the air passes the wetted porous band 84 thereby to be cooled by the evaporative cooling process , besides being refiltered . the hand lever 124 when turned to the solid line position of fig4 causes the damper 24 to pivot to the phantom horizontal position of fig1 . thereupon the exit end 108 of the air duct 104 opens to the cool air outlet 26 . the hand lever 124 also opens the warm switch 130 . as has been stated , the opening of the warm switch 130 results in the closure of the cool switch 172 , with the consequent glowing of the cool pilot lamp 174 . after passing the air duct 104 , the cool , clean air is directed by the damper 24 into and through the cool air outlet 26 out into the room . it should be appreciated that the cool airstream encounters no obstacle at all on its way from fan 22 to cool air outlet 26 . accordingly the cool air will be produced noiselessly at a sufficiently high flow rate . while one embodiment of the invention has been shown and described herein , it will be understood that it is illustrative only and not to be taken as a definition of the scope of the invention . a variety of modifications will readily occur to one skilled in the art on the basis of this disclosure . an example is the location of the heater 30 . although this heater is shown to be mounted on the pivotal damper 24 in the illustrated embodiment , it may be fixedly positioned anywhere at or adjacent the warm air outlet so as not to run counter to the objectives of the invention . this and other modifications or alterations of the invention may be resorted to within the broad teaching hereof ; hence the invention should be accorded the full scope of the following claims so as to embrace any and all equivalent devices .
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all numbers used herein , including those in the examples and claims , should be understood as being modified by the term “ about ” unless otherwise stated , such as with a specified precision . unless expressly stated to the contrary , all ranges cited herein are inclusive . as used herein , the singular forms “ a ,” “ an ,” and “ the ” include plural reference unless the context dictates otherwise . the terms “ scy - 078 ” and “ compound 1 ” refer to the compound shown below , and refer to the freebase form unless otherwise indicated . another name for scy - 078 is ( 1s , 4ar , 6as , 7r , 8r , 10ar , 10br , 12ar , 14r , 15r )- 15 -[[( 2r )- 2 - amino - 2 , 3 , 3 - trimethylbutyl ] oxy ]- 8 -[( 1r )- 1 , 2 - dimethylpropyl ]- 1445 -( 4 - pyridinyl )- 1h - 1 , 2 , 4 - triazol - 1 - yl ]- 1 , 6 , 6a , 7 , 8 , 9 , 10 , 10a , 10b , 11 , 12 , 12a - dodecahydro - 1 , 6a , 8 , 10a - tetramethyl - 4h - 4a - propano - 2h - phenanthro [ 1 , 2 - c ] pyran - 7 - carboxylic acid . the terms “ pharmaceutically acceptable salt ” and the like should be understood to include , but not limited to , citrate salts , hippurate salts , fumarate salts , glycolate salts , mesylate salts , and calcium salts . as used here , phrases such as “ scy - 078 salt ,” “ scy - 078 salts ,” “ salt of scy - 078 ,” “ salts of scy - 078 ,” “ pharmaceutically acceptable salt of scy - 078 ,” and “ pharmaceutically acceptable salts thereof ” should be understood to be salts in various forms , for example , the polymorphs disclosed herein . in addition , as used here , phrases such as “ scy - 078 phosphate ,” “ scy - 078 citrate ,” “ scy - 078 hippurate ,” “ scy - 078 glycolate ,” “ scy - 078 mesylate ,” “ scy - 078 fumarate ,” and “ scy - 078 calcium ” should be understood to be salts in various forms , for example , the polymorphs disclosed herein . the term “ solvent ” and the like refer to any appropriate aqueous or organic solvent . solvents include , but are not limited to , methanol , acetic acid , tetrahydrofuran , 2 methyl - tetrahydrofuran , 1 , 4 - dioxane , n - methyl - 2 - pyrrolidone , dimethyl sulfoxide , dimethylacetamide , isopropyl alcohol , acetonitrile , acetone , ethyl acetate , water and mixtures thereof . the term “ pharmaceutically acceptable carrier ” and the like refer to an ingredient that is compatible with scy - 078 and is not harmful to a patient &# 39 ; s health . pharmaceutically acceptable carriers include , but are not limited to , one or more of the following : aqueous vehicles and solvents , such as water , saline solutions , and alcohols ; buffers ; surface active agents ; dispersing agents ; inert diluents ; preservatives ; suspending agents ; emulsifying agents ; demulcents ; thickening agents ; emulsifying agents ; antioxidants ; and stabilizing agents . other additional ingredients that may be included in the pharmaceutical compositions of the disclosure are generally known in the art and may be described , for example , in remington &# 39 ; s pharmaceutical sciences , mack publishing co ., easton , pa ., which is incorporated by reference herein . the term “ injection ” and the like refer to the insertion of a composition into the body by syringe , hollow needle , or the like . the term “ injection ” and the like include , but are not limited to , intravenous injections , including those entailing administering using an iv bag containing a diluent . the term “ effective amount ” refers to an amount of the active ingredient that , when administered to a subject , alleviates at least some of the symptoms or stops the progression of the identified disease or condition . the terms “ disease ” or “ condition ” include , but are not limited to , infections such as fungal infections . exemplary dosage amounts can be found , for example , in u . s . pat . no . 8 , 188 , 085 , the relevant portions of which are incorporated herein by reference . the term “ å ” refers to angstroms . terms such as “ 2θ ” or “ 2 th .” refer to degrees 2 theta . the xrpd peaks recited herein should be understood to reflect a precision of ± 0 . 2 for the 2 theta peaks , and the equivalent precision for d - spacings as per bragg &# 39 ; s law . the present disclosure also fully incorporates section 941 of the united states pharmacopeia . the national formulary from 2014 ( usp 37 / nf 32 , volume 1 ) relating to characterization of crystalline and partially crystalline solids by x - ray powder diffraction . the present disclosure relates to , among other things , pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , glycolate , mesylate , fumarate , and calcium . in one embodiment , the salt is selected from citrate , hippurate , mesylate , and fumarate . in a further embodiment , the scy - 078 salt is selected from scy - 078 hippurate type a , scy - 078 hippurate type b , and scy - 078 hippurate type c . in another embodiment , the scy - 078 salt is selected from scy - 078 fumarate type a and scy - 078 fumarate type b . in yet another embodiment , the salt is a scy - 078 citrate salt . in yet a further embodiment , the salt is scy - 078 citrate type a . the present disclosure further relates to pharmaceutically acceptable salts of scy - 078 that have a chemical purity of at least 90 %. in another embodiment , pharmaceutically acceptable salts of scy - 078 have a chemical purity of at least 95 %. in a further embodiment , pharmaceutically acceptable salts of scy - 078 have a chemical purity of at least 98 %. in yet another embodiment , pharmaceutically acceptable salts of scy - 078 have a chemical purity of at least 99 %. in still another embodiment , the present disclosure relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a chemical purity of at least 90 %, at least 95 %, at least 98 %, or at least 99 %. the present disclosure additionally relates to pharmaceutically acceptable salts of scy - 078 that have a kinetic solubility of at least 2 mg / ml at 4 hours in dextrose buffer at ph 5 . 5 . in one embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of at least 4 mg / ml at 4 hours in dextrose buffer at ph 5 . 5 . in another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of from 2 mg / ml to 5 mg / ml at 4 hours in dextrose buffer at ph 5 . 5 . in yet another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of from 4 mg / ml to 5 mg / ml at 4 hours in dextrose buffer at ph 5 . 5 . in still another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility greater than scy - 078 ( as a freebase ) at 4 hours in dextrose buffer at ph 5 . 5 . the present disclosure additionally relates to pharmaceutically acceptable salts of scy - 078 that have a kinetic solubility of at least 2 mg / ml at 24 hours in dextrose buffer at ph 5 . 5 . in one embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of at least 4 mg / ml at 24 hours in dextrose buffer at ph 5 . 5 . in another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of at least 8 mg / ml at 24 hours in dextrose buffer at ph 5 . 5 . in a further embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of from 2 mg / ml to 9 mg / ml at 24 hours in dextrose buffer at ph 5 . 5 . in yet another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of from 4 mg / ml to 9 mg / ml at 24 hours in dextrose buffer at ph 5 . 5 . in still another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of from 8 mg / ml to 9 mg / ml at 24 hours in dextrose buffer at ph 5 . 5 . the present disclosure additionally relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 2 mg / ml to 5 mg / ml at 4 hours in dextrose buffer at ph 5 . 5 . in one embodiment , the disclosure relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 4 mg / ml to 5 mg / ml at 4 hours in dextrose buffer at ph 5 . 5 . in yet another embodiment , the disclosure relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 2 mg / ml to 9 mg / ml at 24 hours in dextrose buffer at ph 5 . 5 . in still another embodiment , the disclosure also relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 4 mg / ml to 9 mg / ml at 24 hours in dextrose buffer at ph 5 . 5 . in another embodiment , the disclosure relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 8 mg / ml to 9 mg / ml at 24 hours in dextrose buffer at ph 5 . 5 . the present disclosure additionally relates to pharmaceutically acceptable salts of scy - 078 that have a kinetic solubility of at least 2 mg / ml at 4 hours in phosphate buffer at ph 6 . 0 . in one embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of at least 4 mg / ml at 4 hours in phosphate buffer at ph 6 . 0 . in another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of from 2 mg / ml to 5 mg / ml at 4 hours in phosphate buffer at ph 6 . 0 . in yet another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of from 4 mg / ml to 5 mg / ml at 4 hours in phosphate buffer at ph 6 . 0 . in still another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of at least 4 . 5 mg / ml at 24 hours in phosphate buffer at ph 6 . 0 . in one embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of at least 7 mg / ml at 24 hours in phosphate buffer at ph 6 . 0 . in another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of from 4 . 5 mg / ml to 8 mg / ml at 24 hours in phosphate buffer at ph 6 . 0 . in yet another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of from 7 mg / ml to 8 mg / ml at 24 hours in phosphate buffer at ph 6 . 0 . the present disclosure additionally relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 1 mg / ml to 5 mg / ml at 4 hours in phosphate buffer at ph 6 . 0 . in one embodiment , the disclosure relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 4 mg / ml to 5 mg / ml at 4 hours in phosphate buffer at ph 6 . 0 . in another embodiment , the disclosure relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 4 mg / ml to 8 mg / ml at 24 hours in phosphate buffer at ph 6 . 0 . in yet another embodiment , the disclosure relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 7 mg / ml to 8 mg / ml at 24 hours in phosphate buffer at ph 6 . 0 . the present disclosure additionally relates to pharmaceutically acceptable salts of scy - 078 that have a kinetic solubility of at least 16 mg / ml at 1 hour in sgf media . in one embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of at least 17 mg / ml at 1 hour in sgf media . in another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of at least 18 mg / ml at 1 hour in sgf media . in yet another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of at least 20 mg / ml at 1 hour in sgf media . the present disclosure additionally relates to pharmaceutically acceptable salts of scy - 078 that have a kinetic solubility of from 17 mg / ml to 21 mg / ml at 1 hour in sgf media . in another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of from 18 mg / ml to 21 mg / ml at 1 hour in sgf media . in yet another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of from 20 mg / ml to 21 mg / ml at 1 hour in sgf media . the present disclosure additionally relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 12 mg / ml to 21 mg / ml at 1 hour in sgf media . in one embodiment , the disclosure relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 13 mg / ml to 21 mg / ml at 1 hour in sgf media . in another embodiment , the disclosure relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 18 mg / ml to 21 mg / ml at 1 hour in sgf media . in yet another embodiment , the disclosure relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 20 mg / ml to 21 mg / ml at 1 hour in sgf media . the present disclosure additionally relates to pharmaceutically acceptable salts of scy - 078 that have a kinetic solubility of at least 17 mg / ml at 24 hours in fassif media . in one embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of at least 22 mg / ml at 24 hours in fassif media . in another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of from 17 mg / ml to 22 mg / ml at 24 hours in fassif media . in yet another embodiment , the pharmaceutically acceptable salts of scy - 078 have a kinetic solubility of from 21 mg / ml to 22 mg / ml at 24 hours in fassif media . the present disclosure additionally relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 17 mg / ml to 22 mg / ml at 24 hours in fassif media . in one embodiment , the disclosure relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a kinetic solubility of from 21 mg / ml to 22 mg / ml at 24 hours in fassif media . the present disclosure additionally relates to pharmaceutically acceptable salts of scy - 078 having any of the disclosed kinetic solubilities and having a water sorption of not greater than 7 % at 25 ° c . and 80 % relative humidity as determined by dvs . in one embodiment , the pharmaceutically acceptable salts of scy - 078 have a water sorption of from 2 % to 7 % at 25 ° c . and 80 % relative humidity as determined by dvs . in another embodiment , the pharmaceutically acceptable salts of scy - 078 have a water sorption of from 3 % to 7 % at 25 ° c . and 80 % relative humidity as determined by dvs . in yet another embodiment , the pharmaceutically acceptable salts of scy - 078 have a water sorption of from 6 % to 7 % at 25 ° c . and 80 % relative humidity as determined by dvs . the present disclosure additionally relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a water sorption of from 2 % to 7 % at 25 ° c . and 80 % relative humidity as determined by dvs . in one embodiment , the disclosure relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a water sorption of from 3 % to 7 % at 25 ° c . and 80 % relative humidity as determined by dvs . in one embodiment , the disclosure relates to pharmaceutically acceptable salts of scy - 078 , wherein the salt is selected from citrate , hippurate , mesylate , and fumarate , and wherein the salt has a water sorption of from 6 % to 7 % at 25 ° c . and 80 % relative humidity as determined by dvs . the present disclosure further relates to hippurate salts of scy - 078 , such as scy - 078 hippurate type a , scy - 078 hippurate type b , and scy - 078 hippurate type c . in one embodiment , the scy - 078 hippurate type a has an xrpd pattern comprising peaks at one or more of the following locations : table a fwhm pos . [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 6 . 276484 353 . 472400 0 . 102336 14 . 08226 12 . 90 7 . 023845 139 . 782300 0 . 307008 12 . 58545 5 . 10 7 . 900725 1475 . 766000 0 . 127920 11 . 19048 53 . 85 8 . 241444 302 . 522300 0 . 102336 10 . 72859 11 . 04 9 . 723080 945 . 921800 0 . 089544 9 . 09681 34 . 52 11 . 283030 414 . 659200 0 . 102336 7 . 84238 15 . 13 11 . 492390 300 . 886600 0 . 076752 7 . 69998 10 . 98 12 . 610210 2740 . 558000 0 . 089544 7 . 01982 100 . 00 12 . 910370 765 . 158500 0 . 063960 6 . 85728 27 . 92 13 . 561180 243 . 791900 0 . 153504 6 . 52963 8 . 90 14 . 149930 371 . 812900 0 . 102336 6 . 25924 13 . 57 15 . 182550 1607 . 490000 0 . 102336 5 . 83577 58 . 66 15 . 806230 690 . 955800 0 . 179088 5 . 60688 25 . 21 16 . 673670 482 . 323700 0 . 179088 5 . 31709 17 . 60 17 . 068480 365 . 833300 0 . 127920 5 . 19498 13 . 35 18 . 200570 206 . 779900 0 . 153504 4 . 87432 7 . 55 18 . 933070 395 . 979900 0 . 153504 4 . 68736 14 . 45 19 . 293830 277 . 037400 0 . 102336 4 . 60052 10 . 11 19 . 924160 251 . 428800 0 . 204672 4 . 45638 9 . 17 20 . 583290 158 . 800000 0 . 204672 4 . 31514 5 . 79 21 . 951230 220 . 614300 0 . 153504 4 . 04923 8 . 05 23 . 477450 72 . 922780 0 . 409344 3 . 78934 2 . 66 24 . 511240 99 . 987140 0 . 255840 3 . 63181 3 . 65 24 . 954920 117 . 325600 0 . 153504 3 . 56824 4 . 28 25 . 993010 108 . 058000 0 . 204672 3 . 42804 3 . 94 28 . 257860 72 . 489400 0 . 409344 3 . 15822 2 . 65 31 . 063590 95 . 037750 0 . 179088 2 . 87907 3 . 47 31 . 653730 62 . 090590 0 . 307008 2 . 82673 2 . 27 for example , the scy - 078 hippurate type a has an xrpd pattern comprising one or more peaks at d - spacings of 11 . 20 , 7 . 02 , and 5 . 84 a . in another example , the scy - 078 hippurate type a has an xrpd pattern comprising one or more peaks at degrees 2 theta of 7 . 90 , 12 . 6 , and 15 . 18 . in one embodiment , the scy - 078 hippurate type b has an xrpd pattern comprising peaks at one or more of the following locations : table b fwhm pos . [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 5 . 887601 118 . 925500 0 . 102336 15 . 01151 9 . 56 6 . 889384 462 . 675400 0 . 063960 12 . 83077 37 . 19 7 . 277837 251 . 176000 0 . 051168 12 . 14678 20 . 19 8 . 767134 927 . 066800 0 . 076752 10 . 08643 74 . 52 9 . 945603 1143 . 995000 0 . 102336 8 . 89377 91 . 96 10 . 843500 681 . 448200 0 . 102336 8 . 15925 54 . 78 11 . 822440 140 . 502200 0 . 127920 7 . 48575 11 . 29 12 . 417990 1244 . 014000 0 . 089544 7 . 12805 100 . 00 13 . 714490 435 . 466500 0 . 089544 6 . 45698 35 . 00 14 . 608760 1242 . 496000 0 . 102336 6 . 06367 99 . 88 15 . 050420 474 . 015800 0 . 102336 5 . 88670 38 . 10 16 . 071560 476 . 890000 0 . 127920 5 . 51491 38 . 33 16 . 476910 708 . 831400 0 . 102336 5 . 38014 56 . 98 16 . 857150 185 . 689200 0 . 102336 5 . 25963 14 . 93 17 . 289970 422 . 781900 0 . 127920 5 . 12893 33 . 99 17 . 612420 996 . 474200 0 . 089544 5 . 03575 80 . 10 18 . 405510 186 . 288500 0 . 153504 4 . 82051 14 . 97 19 . 118560 303 . 851800 0 . 127920 4 . 64230 24 . 43 19 . 623870 158 . 474700 0 . 153504 4 . 52389 12 . 74 20 . 218430 314 . 377200 0 . 153504 4 . 39218 25 . 27 21 . 746130 200 . 050600 0 . 153504 4 . 08695 16 . 08 23 . 075880 129 . 668200 0 . 204672 3 . 85436 10 . 42 23 . 853540 106 . 856400 0 . 204672 3 . 73044 8 . 59 25 . 372290 96 . 670350 0 . 204672 3 . 51048 7 . 77 29 . 216870 66 . 396300 0 . 230256 3 . 05670 5 . 34 32 . 714200 31 . 053470 0 . 614016 2 . 73748 2 . 50 for example , the scy - 078 hippurate type b has an xrpd pattern comprising one or more peaks at d - spacings of 8 . 90 , 7 . 13 , and 6 . 10 a . in another example , the scy - 078 hippurate type b has an xrpd pattern comprising one or more peaks at degrees 2 theta of 9 . 95 , 12 . 42 , and 14 . 61 . in one embodiment , the scy - 078 hippurate type c has an xrpd pattern comprising peaks at one or more of the following locations : table c pos . fwhm [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 3 . 027072 11818 . 150000 0 . 051168 29 . 18766 100 . 00 5 . 916137 351 . 270000 0 . 102336 14 . 93916 2 . 97 6 . 916698 947 . 910600 0 . 102336 12 . 78016 8 . 02 7 . 251646 624 . 847700 0 . 076752 12 . 19059 5 . 29 8 . 761702 1828 . 733000 0 . 076752 10 . 09268 15 . 47 9 . 962105 2404 . 236000 0 . 102336 8 . 87907 20 . 34 10 . 897800 1593 . 408000 0 . 102336 8 . 11872 13 . 48 11 . 868550 552 . 254500 0 . 102336 7 . 45677 4 . 67 12 . 432300 2880 . 441000 0 . 127920 7 . 11988 24 . 37 12 . 857840 525 . 634600 0 . 076752 6 . 88518 4 . 45 13 . 091360 511 . 764400 0 . 115128 6 . 76288 4 . 33 13 . 709840 1112 . 219000 0 . 102336 6 . 45916 9 . 41 14 . 555290 3086 . 294000 0 . 153504 6 . 08582 26 . 11 14 . 984610 1215 . 693000 0 . 102336 5 . 91241 10 . 29 15 . 341160 506 . 870800 0 . 153504 5 . 77579 4 . 29 16 . 136210 1315 . 742000 0 . 089544 5 . 49296 11 . 13 16 . 453540 1710 . 358000 0 . 153504 5 . 38772 14 . 47 16 . 897030 606 . 324900 0 . 102336 5 . 24730 5 . 13 17 . 280760 1171 . 798000 0 . 127920 5 . 13164 9 . 92 17 . 591700 2258 . 867000 0 . 102336 5 . 04163 19 . 11 18 . 190770 538 . 754800 0 . 127920 4 . 87692 4 . 56 18 . 425670 516 . 831300 0 . 179088 4 . 81528 4 . 37 19 . 151570 950 . 084500 0 . 102336 4 . 63437 8 . 04 19 . 602330 487 . 956400 0 . 127920 4 . 52881 4 . 13 20 . 234760 861 . 917600 0 . 153504 4 . 38867 7 . 29 20 . 860030 424 . 598600 0 . 153504 4 . 25851 3 . 59 21 . 725360 459 . 496200 0 . 307008 4 . 09081 3 . 89 22 . 532320 498 . 240700 0 . 102336 3 . 94610 4 . 22 23 . 078810 380 . 947900 0 . 127920 3 . 85388 3 . 22 23 . 551950 208 . 488500 0 . 409344 3 . 77752 1 . 76 23 . 874020 377 . 598600 0 . 102336 3 . 72728 3 . 20 25 . 381750 351 . 553600 0 . 102336 3 . 50919 2 . 97 25 . 844490 207 . 070300 0 . 204672 3 . 44740 1 . 75 27 . 188450 192 . 463400 0 . 153504 3 . 27997 1 . 63 27 . 681830 144 . 369000 0 . 307008 3 . 22262 1 . 22 29 . 319670 172 . 870900 0 . 511680 3 . 04622 1 . 46 30 . 833510 86 . 432220 0 . 307008 2 . 90002 0 . 73 34 . 979000 90 . 330020 0 . 204672 2 . 56525 0 . 76 35 . 588330 69 . 479680 0 . 307008 2 . 52271 0 . 59 37 . 270360 55 . 666410 0 . 307008 2 . 41264 0 . 47 for example , the scy - 078 hippurate type c has an xrpd pattern comprising one or more peaks at d - spacings of 29 . 19 , 8 . 88 , 7 . 12 , and 6 . 09 å . in another example , the scy - 078 hippurate type c has an xrpd pattern comprising one or more peaks at degrees 2 theta of 3 . 03 , 9 . 96 , 12 . 43 , and 14 . 56 . the present disclosure further relates to fumarate salts of scy - 078 , such as scy - 078 fumarate type a and scy - 078 fumarate type b . in one embodiment , the scy - 078 fumarate type a has an xrpd pattern comprising peaks at one or more of the following locations : table d fwhm pos . [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 7 . 747007 167 . 350400 0 . 153504 11 . 41218 2 . 00 8 . 493147 8373 . 572000 0 . 102336 10 . 41119 100 . 00 9 . 346397 181 . 715800 0 . 204672 9 . 46257 2 . 17 9 . 931064 167 . 355100 0 . 153504 8 . 90676 2 . 00 10 . 442940 371 . 960600 0 . 089544 8 . 47130 4 . 44 10 . 706620 463 . 482500 0 . 076752 8 . 26326 5 . 54 11 . 231160 490 . 618200 0 . 153504 7 . 87848 5 . 86 13 . 030860 311 . 426800 0 . 102336 6 . 79415 3 . 72 13 . 700070 569 . 254300 0 . 102336 6 . 46374 6 . 80 14 . 895760 234 . 024600 0 . 153504 5 . 94748 2 . 79 15 . 204970 269 . 752200 0 . 153504 5 . 82722 3 . 22 16 . 350790 434 . 953000 0 . 127920 5 . 42135 5 . 19 16 . 976580 3015 . 489000 0 . 115128 5 . 22289 36 . 01 17 . 726110 1152 . 135000 0 . 230256 5 . 00370 13 . 76 18 . 205910 303 . 920500 0 . 102336 4 . 87290 3 . 63 18 . 863510 267 . 939100 0 . 153504 4 . 70449 3 . 20 20 . 164360 63 . 804870 0 . 409344 4 . 40383 0 . 76 20 . 898390 184 . 877000 0 . 102336 4 . 25078 2 . 21 21 . 419940 168 . 417300 0 . 102336 4 . 14844 2 . 01 22 . 228150 318 . 867400 0 . 127920 3 . 99940 3 . 81 23 . 936960 77 . 330220 0 . 307008 3 . 71763 0 . 92 25 . 533030 318 . 681700 0 . 089544 3 . 48874 3 . 81 26 . 114530 59 . 303240 0 . 204672 3 . 41236 0 . 71 26 . 883130 111 . 136200 0 . 204672 3 . 31652 1 . 33 30 . 876670 38 . 684340 0 . 614016 2 . 89607 0 . 46 for example , the scy - 078 fumarate type a has an xrpd pattern comprising one or more peaks at d - spacings of 10 . 41 , 5 . 22 , and 5 . 00 a . in another example , the scy - 078 fumarate type a has an xrpd pattern comprising one or more peaks at degrees 2 theta of 8 . 49 , 16 . 98 , and 17 . 73 . in one embodiment , the scy - 078 fumarate type b has an xrpd pattern comprising peaks at one or more of the following locations : table e fwhm pos . [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 5 . 449312 94 . 567020 0 . 307008 16 . 21786 19 . 92 6 . 318422 110 . 456500 0 . 409344 13 . 98888 23 . 26 9 . 799620 153 . 670200 0 . 614016 9 . 02593 32 . 36 10 . 577440 403 . 264100 0 . 255840 8 . 36388 84 . 93 10 . 995710 322 . 682700 0 . 089544 8 . 04665 67 . 96 11 . 970210 133 . 555200 0 . 307008 7 . 39367 28 . 13 13 . 136230 472 . 855300 0 . 102336 6 . 73989 99 . 58 13 . 551710 408 . 076200 0 . 102336 6 . 53417 85 . 94 14 . 201760 320 . 510900 0 . 204672 6 . 23651 67 . 50 15 . 712210 472 . 732700 0 . 076752 5 . 64022 99 . 56 16 . 216750 474 . 828900 0 . 076752 5 . 46586 100 . 00 16 . 849640 211 . 687300 0 . 204672 5 . 26195 44 . 58 20 . 391740 103 . 586500 0 . 358176 4 . 35524 21 . 82 21 . 343910 97 . 997770 0 . 409344 4 . 16305 20 . 64 28 . 564840 34 . 739620 0 . 614016 3 . 12498 7 . 32 for example , the scy - 078 fumarate type b has an xrpd pattern comprising one or more peaks at d - spacings of 8 . 36 , 6 . 74 , 6 . 53 , 5 . 64 , and 5 . 47 å . in another example , the scy - 078 fumarate type b has an xrpd pattern comprising one or more peaks at degrees 2 theta of 10 . 58 , 13 . 14 , 13 . 55 , 15 . 71 , and 16 . 22 . the present disclosure further relates to glycolate salts of scy - 078 . in one embodiment , the scy - 078 glycolate has an xrpd pattern comprising peaks at one or more of the following locations : table f fwhm pos . [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 7 . 879599 291 . 814000 0 . 127920 11 . 22044 54 . 74 8 . 983378 233 . 086200 0 . 204672 9 . 84412 43 . 72 9 . 855934 117 . 677600 0 . 153504 8 . 97448 22 . 07 11 . 483230 269 . 580500 0 . 204672 7 . 70610 50 . 56 12 . 311460 163 . 106800 0 . 358176 7 . 18949 30 . 59 14 . 259570 285 . 813400 0 . 179088 6 . 21136 53 . 61 14 . 651000 437 . 366100 0 . 102336 6 . 04628 82 . 04 15 . 433320 533 . 138100 0 . 102336 5 . 74151 100 . 00 16 . 892280 103 . 441500 0 . 614016 5 . 24877 19 . 40 18 . 826490 177 . 863500 0 . 204672 4 . 71365 33 . 36 20 . 401140 101 . 236100 0 . 307008 4 . 35325 18 . 99 21 . 743970 54 . 436950 0 . 614016 4 . 08735 10 . 21 24 . 981860 29 . 298130 0 . 614016 3 . 56445 5 . 50 for example , the scy - 078 glycolate has an xrpd pattern comprising one or more peaks at d - spacings of 11 . 22 , 6 . 21 , 6 . 05 , and 5 . 74 a . in another example , the scy - 078 glycolate has an xrpd pattern comprising one or more peaks at degrees 2 theta of 7 . 88 , 14 . 26 , 14 . 65 , and 15 . 43 . the present disclosure further relates to mesylate salts of scy - 078 . in one embodiment , the scy - 078 mesylate has an xrpd pattern comprising peaks at one or more of the following locations : table g fwhm pos . [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 5 . 321569 44 . 016770 0 . 307008 16 . 60688 3 . 75 6 . 654286 233 . 467600 0 . 076752 13 . 28355 19 . 89 8 . 041747 243 . 835400 0 . 204672 10 . 99455 20 . 77 9 . 224843 236 . 712900 0 . 153504 9 . 58698 20 . 16 10 . 179890 547 . 128100 0 . 089544 8 . 68960 46 . 60 10 . 532080 592 . 551800 0 . 089544 8 . 39980 50 . 47 11 . 692820 225 . 932500 0 . 409344 7 . 56843 19 . 24 12 . 670270 361 . 926000 0 . 102336 6 . 98668 30 . 83 14 . 316750 537 . 652200 0 . 102336 6 . 18668 45 . 80 14 . 751260 1174 . 011000 0 . 102336 6 . 00541 100 . 00 15 . 645660 347 . 928600 0 . 204672 5 . 66406 29 . 64 16 . 537910 485 . 586600 0 . 179088 5 . 36043 41 . 36 17 . 477180 328 . 731900 0 . 127920 5 . 07441 28 . 00 18 . 838670 252 . 134300 0 . 307008 4 . 71063 21 . 48 19 . 613670 351 . 448500 0 . 153504 4 . 52622 29 . 94 21 . 008230 254 . 102200 0 . 204672 4 . 22880 21 . 64 22 . 068870 130 . 646600 0 . 307008 4 . 02791 11 . 13 23 . 475460 151 . 601600 0 . 204672 3 . 78965 12 . 91 25 . 592960 130 . 952000 0 . 153504 3 . 48071 11 . 15 for example , the scy - 078 mesylate has an xrpd pattern comprising one or more peaks at d - spacings of 10 . 99 , 6 . 99 , and 6 . 01 å . in another example , the scy - 078 mesylate has an xrpd pattern comprising one or more peaks at degrees 2 theta of 8 . 04 , 12 . 67 , and 14 . 75 . the present disclosure further relates to calcium salts of scy - 078 . in one embodiment , the scy - 078 calcium has an xrpd pattern comprising peaks at one or more of the following locations : table h fwhm pos . [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 5 . 330948 1222 . 647000 0 . 063960 16 . 57768 100 . 00 8 . 684942 82 . 143680 0 . 307008 10 . 18170 6 . 72 9 . 624508 215 . 229600 0 . 127920 9 . 18975 17 . 60 10 . 625810 286 . 722000 0 . 153504 8 . 32591 23 . 45 13 . 358050 110 . 336200 0 . 307008 6 . 62846 9 . 02 14 . 092620 101 . 325400 0 . 307008 6 . 28456 8 . 29 15 . 952080 1188 . 492000 0 . 153504 5 . 55594 97 . 21 16 . 282720 334 . 685300 0 . 153504 5 . 44386 27 . 37 17 . 853110 104 . 842700 0 . 153504 4 . 96839 8 . 58 19 . 638160 74 . 407610 0 . 307008 4 . 52063 6 . 09 29 . 434800 171 . 668200 0 . 204672 3 . 03457 14 . 04 30 . 178030 59 . 353870 0 . 153504 2 . 96150 4 . 85 31 . 428330 37 . 765730 0 . 307008 2 . 84648 3 . 09 for example , the scy - 078 calcium has an xrpd pattern comprising one or more peaks at d - spacings of 16 . 58 , 5 . 56 , and 5 . 44 a . in another example , the scy - 078 calcium has an xrpd pattern comprising one or more peaks at degrees 2 theta of 5 . 33 , 15 . 95 , and 16 . 28 . the present disclosure further relates to citrate salts of scy - 078 , such as scy - 078 citrate type a , type b , type e , type f , type m , type n , type 0 , type q , type r , and type s . in one embodiment , the citrate salt of scy - 078 comprises at least one of type a , type b , type e , type f , type m , type n , type 0 , type q , type r , and type s . the present disclosure further relates to a citrate salt of scy - 078 comprising type a . in one embodiment , the citrate salt of scy - 078 consists essentially of type a . in another embodiment , the citrate salt of scy - 078 comprises at least 98 % type a . in a further embodiment , the citrate salt of scy - 078 comprises at least 99 % type a . in one embodiment , the scy - 078 citrate type a is stable for at least 1 week when stored at 60 ° c . in another embodiment , the scy - 078 citrate type a is stable for at least 1 week when stored at 25 ° c . and 60 % relative humidity . in a further embodiment , the scy - 078 citrate type a is stable for at least 1 week when stored at 40 ° c . and 75 % relative humidity . in a further embodiment , the scy - 078 citrate type a has an equilibrium solubility of 38 mg / ml in non - buffered water at ambient temperature . in yet another embodiment , the scy - 078 citrate type a has an approximate solubility of from 40 mg / ml to 42 mg / ml at room temperature in at least one solvent selected from methanol , isopropyl alcohol , acetic acid , tetrahydrofuran , 2 methyl - tetrahydrofuran , 1 , 4 - dioxane , n - methyl - 2 - pyrrolidone , dimethyl sulfoxide , and dimethylacetamide . in still another embodiment , the scy - 078 citrate type a has a water sorption of 6 % at 25 ° c . and 80 % relative humidity as determined by dvs . in one embodiment , the scy - 078 citrate type a has a kinetic solubility of 4 mg / ml at 4 hours in dextrose buffer at ph 5 . 5 . in another embodiment , the scy - 078 citrate type a has a kinetic solubility of 8 mg / ml at 24 hours in dextrose buffer at ph 5 . 5 . in a further embodiment , the scy - 078 citrate type a has a kinetic solubility of 5 mg / ml at 4 hours in phosphate buffer at ph 6 . 0 . in still another embodiment , the scy - 078 citrate type a has a kinetic solubility of 8 mg / ml at 24 hours in phosphate buffer at ph 6 . 0 . in one embodiment , the scy - 078 citrate type a has a kinetic solubility of 21 mg / ml at 1 hour in sgf media . in another embodiment , the scy - 078 citrate type a has a kinetic solubility of 4 mg / ml at 24 hours in fessif media . in yet another embodiment , the scy - 078 citrate type a has a kinetic solubility of 10 mg / ml at 1 hour in fassif media . in a further embodiment , the scy - 078 citrate type a has a kinetic solubility of 21 mg / ml at 4 hours in fassif media . the present disclosure further relates to a citrate salt of scy - 078 comprising scy - 078 citrate type a . in one embodiment , the scy - 078 citrate type a has an xrpd pattern comprising peaks at one or more of the following locations : table i pos . fwhm [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 5 . 400273 434 . 322700 0 . 102336 16 . 36502 3 . 34 7 . 453872 13000 . 820000 0 . 191880 11 . 86031 100 . 00 9 . 201639 691 . 948300 0 . 204672 9 . 61110 5 . 32 10 . 831710 404 . 555000 0 . 153504 8 . 16811 3 . 11 11 . 485080 936 . 115200 0 . 179088 7 . 70486 7 . 20 12 . 491050 954 . 805500 0 . 179088 7 . 08652 7 . 34 13 . 191360 1776 . 320000 0 . 204672 6 . 71184 13 . 66 15 . 020350 1342 . 537000 0 . 204672 5 . 89842 10 . 33 15 . 664830 532 . 278900 0 . 179088 5 . 65717 4 . 09 15 . 955570 613 . 057500 0 . 127920 5 . 55474 4 . 72 16 . 751250 951 . 729000 0 . 153504 5 . 29264 7 . 32 17 . 978130 170 . 323300 0 . 204672 4 . 93412 1 . 31 19 . 591770 472 . 971000 0 . 204672 4 . 53123 3 . 64 22 . 213400 146 . 982900 0 . 204672 4 . 00202 1 . 13 23 . 845740 34 . 469910 0 . 614016 3 . 73164 0 . 27 25 . 160050 117 . 741100 0 . 307008 3 . 53961 0 . 91 28 . 761350 129 . 234400 0 . 255840 3 . 10407 0 . 99 30 . 356250 332 . 945100 0 . 230256 2 . 94452 2 . 56 32 . 317870 87 . 151140 0 . 307008 2 . 77014 0 . 67 34 . 725480 74 . 664570 0 . 511680 2 . 58339 0 . 57 for example , the scy - 078 citrate type a has an xrpd pattern comprising one or more peaks at d - spacings of 11 . 86 , 7 . 70 , 7 . 09 , 6 . 71 , 5 . 90 , and 5 . 29 å . in another example , the scy - 078 citrate type a has an xrpd pattern comprising one or more peaks at degrees 2 theta of 7 . 45 , 11 . 49 , 12 . 49 , 13 . 19 , 15 . 02 , and 16 . 75 . the present disclosure further relates to a citrate salt of scy - 078 comprising scy - 078 citrate type b . in one embodiment , the scy - 078 citrate type b has an xrpd pattern comprising peaks at one or more of the following locations : table j fwhm pos . [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 5 . 561437 214 . 772000 0 . 127920 15 . 89114 18 . 87 6 . 920576 1138 . 274000 0 . 115128 12 . 77301 100 . 00 9 . 319721 77 . 009080 0 . 307008 9 . 48959 6 . 77 11 . 144180 155 . 075600 0 . 153504 7 . 93978 13 . 62 11 . 729970 201 . 281900 0 . 153504 7 . 54455 17 . 68 13 . 405240 187 . 402700 0 . 358176 6 . 60523 16 . 46 15 . 225970 237 . 746900 0 . 204672 5 . 81923 20 . 89 16 . 813690 449 . 144100 0 . 153504 5 . 27312 39 . 46 18 . 219030 148 . 764600 0 . 204672 4 . 86942 13 . 07 19 . 324790 108 . 017600 0 . 153504 4 . 59322 9 . 49 20 . 531330 143 . 254500 0 . 127920 4 . 32594 12 . 59 23 . 721410 34 . 728650 0 . 307008 3 . 75092 3 . 05 26 . 000800 68 . 151450 0 . 204672 3 . 42703 5 . 99 29 . 343000 18 . 852780 0 . 614016 3 . 04385 1 . 66 for example , the scy - 078 citrate type b has an xrpd pattern comprising one or more peaks at d - spacings of 15 . 89 , 12 . 77 , 7 . 54 , 5 . 82 , and 5 . 27 å . in another example , the scy - 078 citrate type b has an xrpd pattern comprising one or more peaks at degrees 2 theta of 5 . 56 , 6 . 92 , 11 . 73 , 15 . 23 , and 16 . 81 . the present disclosure further relates to a citrate salt of scy - 078 comprising scy - 078 citrate type e . in one embodiment , the scy - 078 citrate type e has an xrpd pattern comprising peaks at one or more of the following locations : table k fwhm pos . [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 5 . 524293 92 . 779970 0 . 307008 15 . 99790 5 . 74 7 . 256628 1616 . 341000 0 . 179088 12 . 18224 100 . 00 11 . 438900 216 . 111400 0 . 281424 7 . 73586 13 . 37 14 . 135060 246 . 012400 0 . 255840 6 . 26579 15 . 22 15 . 755470 336 . 295500 0 . 255840 5 . 62483 20 . 81 16 . 331430 208 . 920100 0 . 255840 5 . 42773 12 . 93 17 . 088060 99 . 712520 0 . 409344 5 . 18907 6 . 17 21 . 127980 46 . 130650 0 . 614016 4 . 20511 2 . 85 31 . 562360 23 . 421260 0 . 614016 2 . 83470 1 . 45 for example , the scy - 078 citrate type e has an xrpd pattern comprising one or more peaks at d - spacings of 12 . 18 , 7 . 74 , 6 . 27 , 5 . 62 , and 5 . 43 a . in another example , the scy - 078 citrate type e has an xrpd pattern comprising one or more peaks at degrees 2 theta of 7 . 26 , 11 . 44 , 14 . 14 , 15 . 76 , and 16 . 33 . the present disclosure further relates to a citrate salt of scy - 078 comprising scy - 078 citrate type f . in one embodiment , the scy - 078 citrate type f has an xrpd pattern comprising peaks at one or more of the following locations : table l fwhm pos . [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 3 . 633823 273 . 473300 0 . 204672 24 . 31535 100 . 00 8 . 094996 83 . 291080 0 . 307008 10 . 92235 30 . 46 14 . 004250 57 . 266020 0 . 818688 6 . 32402 20 . 94 17 . 742840 88 . 241520 0 . 307008 4 . 99902 32 . 27 for example , the scy - 078 citrate type f has an xrpd pattern comprising one or more peaks at d - spacings of 24 . 32 and 5 . 00 å . in another example , the scy - 078 citrate type f has an xrpd pattern comprising one or more peaks at degrees 2 theta of 3 . 63 and 17 . 74 . the present disclosure further relates to a citrate salt of scy - 078 comprising scy - 078 citrate type m . in one embodiment , the scy - 078 citrate type m has an xrpd pattern comprising peaks at one or more of the following locations : table m fwhm pos . [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 5 . 572099 251 . 586000 0 . 179088 15 . 86076 9 . 89 7 . 341430 2543 . 546000 0 . 332592 12 . 04171 100 . 00 9 . 506812 193 . 442600 0 . 307008 9 . 30326 7 . 61 11 . 507120 612 . 058600 0 . 281424 7 . 69016 24 . 06 12 . 151790 217 . 504900 0 . 255840 7 . 28359 8 . 55 14 . 166310 475 . 291100 0 . 179088 6 . 25204 18 . 69 15 . 796090 798 . 112100 0 . 255840 5 . 61046 31 . 38 16 . 373100 704 . 236700 0 . 179088 5 . 41401 27 . 69 17 . 342680 236 . 560600 0 . 511680 5 . 11346 9 . 30 18 . 264100 127 . 099200 0 . 307008 4 . 85751 5 . 00 20 . 028560 111 . 330700 0 . 307008 4 . 43338 4 . 38 21 . 230190 166 . 125100 0 . 255840 4 . 18509 6 . 53 22 . 124240 151 . 032300 0 . 358176 4 . 01795 5 . 94 23 . 019390 107 . 550400 0 . 307008 3 . 86369 4 . 23 25 . 286220 144 . 601600 0 . 511680 3 . 52223 5 . 69 27 . 656070 79 . 447100 0 . 358176 3 . 22556 3 . 12 28 . 430390 56 . 622940 0 . 409344 3 . 13945 2 . 23 29 . 646340 75 . 432070 0 . 614016 3 . 01339 2 . 97 32 . 376530 74 . 417430 0 . 307008 2 . 76525 2 . 93 36 . 534050 34 . 760060 0 . 614016 2 . 45955 1 . 37 38 . 139080 26 . 017290 0 . 614016 2 . 35966 1 . 02 for example , the scy - 078 citrate type m has an xrpd pattern comprising one or more peaks at d - spacings of 12 . 04 , 7 . 69 , 6 . 25 , 5 . 61 , and 5 . 41 a . in another example , the scy - 078 citrate type m has an xrpd pattern comprising one or more peaks at degrees 2 theta of 7 . 34 , 11 . 51 , 14 . 17 , 15 . 80 , and 16 . 37 . the present disclosure further relates to a citrate salt of scy - 078 comprising scy - 078 citrate type n . in one embodiment , the scy - 078 citrate type n has an xrpd pattern comprising peaks at one or more of the following locations : table n fwhm pos . [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 5 . 410849 486 . 098000 0 . 076752 16 . 33306 9 . 13 7 . 067553 5326 . 844000 0 . 089544 12 . 50771 100 . 00 10 . 838060 670 . 175200 0 . 063960 8 . 16333 12 . 58 11 . 383920 1260 . 568000 0 . 089544 7 . 77310 23 . 66 11 . 924900 315 . 766000 0 . 153504 7 . 42166 5 . 93 12 . 367310 352 . 822800 0 . 153504 7 . 15714 6 . 62 12 . 923310 1574 . 956000 0 . 089544 6 . 85044 29 . 57 14 . 132120 1282 . 157000 0 . 102336 6 . 26708 24 . 07 15 . 162450 1604 . 350000 0 . 102336 5 . 84346 30 . 12 16 . 256930 1496 . 153000 0 . 089544 5 . 45244 28 . 09 16 . 676790 891 . 116500 0 . 115128 5 . 31610 16 . 73 16 . 898590 608 . 961300 0 . 102336 5 . 24682 11 . 43 17 . 769210 633 . 106100 0 . 127920 4 . 99166 11 . 89 18 . 512560 1119 . 245000 0 . 102336 4 . 79287 21 . 01 20 . 764100 264 . 835400 0 . 102336 4 . 27797 4 . 97 21 . 599360 277 . 781400 0 . 127920 4 . 11439 5 . 21 22 . 726850 204 . 007000 0 . 102336 3 . 91276 3 . 83 23 . 066060 336 . 013100 0 . 153504 3 . 85598 6 . 31 24 . 489610 243 . 365100 0 . 127920 3 . 63497 4 . 57 28 . 491330 175 . 736200 0 . 179088 3 . 13287 3 . 30 30 . 668850 84 . 372280 0 . 307008 2 . 91522 1 . 58 33 . 097360 34 . 363080 0 . 614016 2 . 70666 0 . 65 36 . 308500 40 . 510880 0 . 716352 2 . 47431 0 . 76 for example , the scy - 078 citrate type n has an xrpd pattern comprising one or more peaks at d - spacings of 12 . 51 , 7 . 77 , 6 . 85 , 6 . 27 , 5 . 84 , 5 . 45 , and 4 . 79 å . in another example , the scy - 078 citrate type n has an xrpd pattern comprising one or more peaks at degrees 2 theta of 7 . 07 , 11 . 38 , 12 . 92 , 14 . 13 , 15 . 16 , 16 . 26 , and 18 . 51 . the present disclosure further relates to a citrate salt of scy - 078 comprising scy - 078 citrate type o in one embodiment , the scy - 078 citrate type o has an xrpd pattern comprising peaks at one or more of the following locations : table o fwhm pos . [° 2th .] height [ cts ] left [° 2th .] d - spacing [ å ] rel . int . [%] 3 . 214240 359 . 101800 0 . 409344 27 . 48844 9 . 56 5 . 562890 564 . 632100 0 . 102336 15 . 88699 15 . 03 7 . 082335 3757 . 717000 0 . 115128 12 . 48164 100 . 00 11 . 908250 1208 . 103000 0 . 089544 7 . 43200 32 . 15 14 . 197590 602 . 552700 0 . 115128 6 . 23833 16 . 04 16 . 178670 447 . 137400 0 . 179088 5 . 47864 11 . 90 16 . 755170 956 . 290800 0 . 115128 5 . 29141 25 . 45 28 . 567280 48 . 759020 0 . 307008 3 . 12472 1 . 30 for example , the scy - 078 citrate type 0 has an xrpd pattern comprising one or more peaks at d - spacings of 12 . 48 , 7 . 43 , and 5 . 29 a . in another example , the scy - 078 citrate type o has an xrpd pattern comprising one or more peaks at degrees 2 theta of 7 . 08 , 11 . 91 , and 16 . 76 . the present disclosure further relates to a citrate salt of scy - 078 comprising scy - 078 citrate type q . in one embodiment , the scy - 078 citrate type q has an xrpd pattern comprising peaks at one or more of the following locations : table p fwhm left pos . [° 2th .] height [ cts ] [° 2th .] d - spacing [ å ] rel . int . [%] 5 . 686347 449 . 970600 0 . 102336 15 . 54234 13 . 51 6 . 300879 3329 . 599000 0 . 140712 14 . 02779 100 . 00 6 . 890776 1871 . 585000 0 . 076752 12 . 82818 56 . 21 8 . 441730 95 . 233120 0 . 153504 10 . 47449 2 . 86 9 . 785571 136 . 396600 0 . 153504 9 . 03885 4 . 10 11 . 334590 1386 . 986000 0 . 140712 7 . 80682 41 . 66 11 . 733060 826 . 632000 0 . 102336 7 . 54257 24 . 83 12 . 939760 265 . 781600 0 . 409344 6 . 84177 7 . 98 13 . 691820 190 . 778000 0 . 153504 6 . 46762 5 . 73 14 . 156830 332 . 781500 0 . 153504 6 . 25620 9 . 99 14 . 496570 455 . 453300 0 . 102336 6 . 11034 13 . 68 15 . 135910 594 . 105600 0 . 153504 5 . 85365 17 . 84 15 . 903400 540 . 737100 0 . 127920 5 . 57284 16 . 24 17 . 010910 1588 . 263000 0 . 127920 5 . 21243 47 . 70 17 . 296950 476 . 914900 0 . 127920 5 . 12687 14 . 32 18 . 962100 570 . 585000 0 . 204672 4 . 68025 17 . 14 20 . 190720 395 . 466100 0 . 102336 4 . 39814 11 . 88 20 . 646480 601 . 591200 0 . 153504 4 . 30207 18 . 07 21 . 298380 208 . 197100 0 . 153504 4 . 17185 6 . 25 22 . 025220 160 . 183700 0 . 307008 4 . 03579 4 . 81 22 . 719750 205 . 611500 0 . 204672 3 . 91397 6 . 18 23 . 633070 128 . 288000 0 . 307008 3 . 76474 3 . 85 25 . 991160 157 . 744000 0 . 204672 3 . 42828 4 . 74 27 . 462080 37 . 389280 0 . 307008 3 . 24790 1 . 12 28 . 950740 597 . 140100 0 . 140712 3 . 08419 17 . 93 34 . 085010 29 . 835660 0 . 511680 2 . 63046 0 . 90 for example , the scy - 078 citrate type q has an xrpd pattern comprising one or more peaks at d - spacings of 14 . 03 , 12 . 83 , 7 . 81 , 7 . 54 , and 5 . 21 å . in another example , the scy - 078 citrate type q has an xrpd pattern comprising one or more peaks at degrees 2 theta of 6 . 30 , 6 . 89 , 11 . 33 , 11 . 73 , and 17 . 01 . the present disclosure further relates to a citrate salt of scy - 078 comprising scy - 078 citrate type r . in one embodiment , the scy - 078 citrate type r has an xrpd pattern comprising peaks at one or more of the following locations : table q fwhm left pos . [° 2th .] height [ cts ] [° 2th .] d - spacing [ å ] rel . int . [%] 6 . 143884 611 . 904200 0 . 153504 14 . 38589 100 . 00 11 . 248800 143 . 606900 0 . 255840 7 . 86616 23 . 47 14 . 059410 351 . 488100 0 . 204672 6 . 29933 57 . 44 14 . 636960 372 . 993000 0 . 204672 6 . 05205 60 . 96 16 . 413500 550 . 672100 0 . 102336 5 . 40078 89 . 99 17 . 742000 362 . 377400 0 . 614016 4 . 99926 59 . 22 19 . 697290 248 . 048100 0 . 307008 4 . 50719 40 . 54 22 . 159300 133 . 589200 0 . 409344 4 . 01167 21 . 83 30 . 197650 27 . 706020 0 . 614016 2 . 95963 4 . 53 for example , the scy - 078 citrate type r has an xrpd pattern comprising one or more peaks at d - spacings of 14 . 39 , 6 . 05 , 5 . 40 , and 5 . 00 å . in another example , the scy - 078 citrate type r has an xrpd pattern comprising one or more peaks at degrees 2 theta of 6 . 14 , 14 . 64 , 16 . 41 , and 17 . 74 . the present disclosure further relates to a citrate salt of scy - 078 comprising scy - 078 citrate type s . in one embodiment , the scy - 078 citrate type s has an xrpd pattern comprising peaks at one or more of the following locations : table r fwhm left pos . [° 2th .] height [ cts ] [° 2th .] d - spacing [ å ] rel . int . [%] 5 . 512446 1020 . 013000 0 . 089544 16 . 03226 16 . 16 7 . 296105 6310 . 710000 0 . 153504 12 . 11641 100 . 00 8 . 443163 252 . 219900 0 . 230256 10 . 47272 4 . 00 11 . 057440 582 . 228600 0 . 179088 8 . 00186 9 . 23 12 . 004950 2714 . 326000 0 . 166296 7 . 37235 43 . 01 14 . 346070 536 . 999100 0 . 204672 6 . 17410 8 . 51 16 . 812800 1626 . 861000 0 . 127920 5 . 27340 25 . 78 19 . 482230 106 . 142000 0 . 358176 4 . 55646 1 . 68 22 . 188280 88 . 048920 0 . 409344 4 . 00650 1 . 40 24 . 046320 53 . 183810 0 . 818688 3 . 70096 0 . 84 for example , the scy - 078 citrate type s has an xrpd pattern comprising one or more peaks at d - spacings of 16 . 03 , 12 . 12 , 7 . 37 , and 5 . 27 a . in another example , the scy - 078 citrate type s has an xrpd pattern comprising one or more peaks at degrees 2 theta of 5 . 51 , 7 . 30 , 12 . 00 , and 16 . 81 . the present disclosure further relates to a method for preparing a pharmaceutically acceptable salt of scy - 078 comprising combining at least components : ( i ) a free base of scy - 078 ; ( ii ) a weak organic acid ; and ( iii ) a liquid carrier . the weak organic acid may be chosen from those known in the art . in one embodiment , the weak organic acid is selected from citric acid , fumaric acid , methanesulfonic acid , and hippuric acid . in another embodiment , the weak organic acid is citric acid . in a further embodiment , the liquid carrier is a solvent or solvent mixture , and at least one of the free base of scy - 078 and the weak organic acid is soluble in the solvent or solvent mixture . in still another embodiment , the liquid carrier comprises at least one of ethanol , isopropyl alcohol , acetonitrile , acetone , ethyl acetate , and tetrahydrofuran / water mixture . in yet another embodiment , the liquid carrier comprises ethanol . in one embodiment , the method further comprises combining ( iv ) an anti - solvent . in another embodiment , the anti - solvent comprises n - heptane . in one embodiment , the method further comprises agitating the combination of at least components ( i )-( iii ). in a further embodiment , the method further comprises agitating the combination of at least components ( i )-( iii ) for at least 24 hours . in another embodiment , the method further comprises agitating and heating the combination of at least components ( i )-( iii ). in a further embodiment , the method further comprises agitating and heating the combination of at least components ( i )-( iii ) to a temperature of from 40 ° c . to 60 ° c . in still another embodiment , the method further comprises agitating and heating the combination of at least components ( i )-( iii ) to a temperature of from 40 ° c . to 60 ° c . for at least 60 minutes . in one embodiment , the method further comprises agitating and heating the combination of at least components ( i )-( iii ) and adding to the combination of at least components ( i )-( iii ) an anti - solvent after at least 14 hours . in yet another embodiment , the anti - solvent is n - heptane . in one embodiment , the method further comprises agitating and heating the combination of at least components ( i )-( iii ); adding to the combination of at least components ( i )-( iii ) an anti - solvent after at least 14 hours ; and cooling the combination of at least components ( i )-( iii ). in a further embodiment , the cooling is from 0 ° c . to 20 ° c . in another embodiment , the cooling is from 0 ° c . to 20 ° c . at a rate of 0 . 25 ° c ./ min . the present disclosure further relates to methods for preparing citrate type a salt of scy - 078 . in one embodiment , the method comprises desolvating at least one of type b , type n , and type q citrate salt of scy - 078 . in a further embodiment , the desolvating comprises drying under nitrogen . in yet another embodiment , the desolvating comprises drying under vacuum filtration . the present disclosure additionally relates to pharmaceutical compositions comprising a pharmaceutically acceptable salt of scy - 078 , and a pharmaceutically acceptable carrier . the pharmaceutically acceptable carrier may be chosen from , among other things , one or more of the following : water , saline solutions , buffers , and alcohols . in one embodiment , the pharmaceutically acceptable salt in the pharmaceutical composition is selected from citrate , hippurate , mesylate , and fumarate . in yet another embodiment , the pharmaceutically acceptable salt is a citrate salt . in still another embodiment , the pharmaceutically acceptable salt of scy - 078 is scy - 078 citrate type a . according to certain embodiments , the pharmaceutically acceptable salt of scy - 078 may consist essentially of a specified crystal form . according to certain embodiments , the pharmaceutically acceptable salt of scy - 078 may comprise a specified crystal in combination with one or more other crystal forms . the pharmaceutically acceptable salt of scy - 078 may , for example , contain a specified crystal form together with less than 10 % of another crystal form ( s ), such as less than 5 %, less than 2 %, or less than 1 %. in one embodiment , the pharmaceutical composition is made by dissolving the pharmaceutically acceptable salt of scy - 078 in a pharmaceutically acceptable carrier . the pharmaceutically acceptable carrier may be chosen from , among other things , one or more of the following : water , saline solutions , buffers , and alcohols . in another embodiment , the pharmaceutical composition is suitable for injection into a human . in a further embodiment , the pharmaceutical composition is suitable for intravenous injection into a human . in another embodiment , the pharmaceutically acceptable salt is a citrate salt . in still another embodiment , the pharmaceutically acceptable salt of scy - 078 is scy - 078 citrate type a . the present disclosure further relates to methods of preparing a pharmaceutical composition comprising pharmaceutically acceptable salts of scy - 078 , and a pharmaceutically acceptable carrier . the pharmaceutically acceptable carrier may be chosen from , among other things , one or more of the following : water , saline solutions , buffers , and alcohols . in one embodiment , the pharmaceutically acceptable salt of scy - 078 is dissolved in the pharmaceutically acceptable carrier within 1 hour . in another embodiment , the pharmaceutically acceptable salt of scy - 078 is dissolved in the pharmaceutically acceptable carrier within 24 hours . in a further embodiment , the pharmaceutically acceptable salt is a citrate salt . in still another embodiment , the pharmaceutically acceptable salt of scy - 078 is scy - 078 citrate type a . the present disclosure additionally relates to methods of treating a fungal infection in a patient in need thereof . for example , the methods include treating invasive candidiasis and invasive aspergillosis . in one embodiment , the method comprises administering to the patient in need thereof a pharmaceutical composition comprising an effective amount of a pharmaceutically acceptable salt of scy - 078 . in another embodiment , the pharmaceutically acceptable salt is a citrate salt . in a further embodiment , the pharmaceutically acceptable salt of scy - 078 is scy - 078 citrate type a . in another embodiment , the pharmaceutical composition is suitable for injection into a human . in yet another embodiment , the pharmaceutical composition is suitable for intravenous injection into a human . the following describes the materials and methods used for all examples unless otherwise stated . differential scanning calorimetry ( dsc )— dsc was performed with a ta q2000 dsc from ta instruments . to perform dsc , the sample was ramped from room temperature to the desired temperature at a heating rate of 10 ° c ./ min , using n 2 as the purge gas and with the pan crimped . universal analysis 2000 ( ta instruments ) was used to analyze the results . thermogravimetric analysis ( tga )— tga was performed with a ta q500 / q5000 tga from ta instruments . to perform tga , the sample was ramped from room temperature to the desired temperature at a heating rate of 10 ° c ./ min , using n 2 as the purge gas . universal analysis 2000 ( ta instruments ) was used to analyze the results . the temperature was calibrated using nickel and the weight using ta - supplied standard weights and verified against calcium oxalate monohydrate dehydration and decomposition . dynamic vapor sorption ( dvs )— the term “ dvs ” means the procedure described in below . the relative humidity at 25 ° c . was calibrated against deliquescence point of licl , mg ( no 3 ) 2 and kcl . the dvs of scy - 078 salts were tested according to the above method , using a 10 - 20 mg sample size . the dvs was measured using a surface measurement systems ( sms ) dvs intrinsic . high power liquid chromatography ( hplc ) method — an agilent 1260 hplc with dad detector was utilized to test solubility or to test purity and stability . for all compounds tested other than the trifluoroacetate salts ( type a and b ) and the hcl type i and ii salts , the conditions and parameters used for measuring solubility are shown in table 2a and for measuring stability are showing in table 3a . the conditions and parameters used for the solubility of the trifluoroacetate salts ( type a and b ) and the hcl type i and ii salts are shown in table 2b and for stability are shown in table 3b . system suitability was tested by injecting standard solutions five times in each sample sequence , and the relative standard deviation of the peak areas was less than 2 %. a : 0 . 1 % hclo 4 in h 2 o b : acn sgf media preparation — the term “ sgf media ” means a solution prepared according to the following method . sodium chloride ( 0 . 2 g ) and triton x - 100 ( 0 . 1 g ) were combined in a 100 ml flask . then deionized water was added . the mixture was stirred until all solids were dissolved . then 12 n hcl ( 200 μl ) was added and the ph value was checked with a ph meter . the ph was adjusted to 1 . 8 with 1n hcl or 1n naoh . once the desired ph was established , the solution was diluted to volume with deionized water . fassif media preparation — the term “ fassif media ” means a solution prepared according to the following method . a fassif dissolving buffer was prepared by dissolving maleic acid ( 0 . 222 g ) in 45 ml of purified water . the ph was adjusted to exactly 6 . 4 using 1n naoh . fassif media was prepared by adding sodium taurocholate ( 0 . 161 g ), sodium chloride ( 0 . 398 g ), and lecithin ( 0 . 0156 g ) into a 100 - ml volumetric flask . then 40 ml of deionized water was added . the solution was sonicated until clear . next 45 ml of the fassif dissolving buffer was added . the ph was adjusted to 6 . 5 with 1n naoh or 1n hcl . once the desired ph was reached , the solution was diluted to volume with deionized water . an alternative media (“ fassif alternative media ”) was used to study the trifluoroacetate salts ( type a and b ) and the hcl type i salt . more specifically , the media was prepared by weighing 0 . 17 g of sodium phosphate monobasic ( nah2po4 , anhydrous ), 0 . 021 g of sodium hydroxide , and 0 . 31 g of sodium chloride into a 50 - ml volumetric flask and was dissolve with approximately 48 ml of purified water . the ph was adjusted to exactly 6 . 5 using 1 m hcl or 1 m naoh and diluted to volume with purified water . 0 . 11 g of sif powder was then added , stirred and sonicated until all the powder was completely dissolved . the solution was equilibrated for 2 hours at rt before use . the solution can be stored at rt for 48 hours or 4 ° c . for 7 days and should be equilibrated to rt before use fessif preparation — the term “ fessif media ” means a solution prepared according to the following method . a fessif dissolving buffer was prepared by dissolving maleic acid ( 0 . 638 g ) and nacl ( 0 . 728 g ) in 100 ml of purified water . the ph was adjusted to exactly 5 . 8 using 1n naoh or 1n hcl . fessif media was prepared by adding sodium taurocholate ( 0 . 269 g ), lecithin ( 0 . 078 g ), sodium oleate ( 0 . 012 g ), and glyceryl monooleate ( 0 . 089 ) into a 50 - ml flask . then 2 . 5 ml of the fessif dissolving buffer was added . the solution was sonicated . an additional 12 . 5 ml of the fessif dissolving buffer was then added 1 ml stepwise forming an emulsion . the solution was transferred to a 50 - ml volumetric flask and diluted to volume with the fessif dissolving buffer . an alternative media (“ fessif alternative media ”) was used to study the trifluoroacetate salts ( type a and b ) and the hcl type i salt . more specifically , the media was prepared by transferring 0 . 41 ml of glacial acid and weighing 0 . 20 g of sodium hydroxide , 0 . 59 g of sodium chloride into a 50 - ml volumetric flask . this was dissolved with approximately 48 ml of purified water . the ph was adjusted to exactly 5 . 0 using 1 m hcl or 1 m naoh and diluted to volume with purified water . 0 . 56 g of sif powder was added , stirred and sonicated until all the powder is completely dissolved . the solution can be stored at rt for 48 hours or 4 ° c . for 7 days and should be equilibrated to rt before use . dextrose buffer ( ph 5 . 5 ) preparation — the terms “ dextrose buffer at ph 5 . 5 ” and “ dextrose buffer ( ph 5 . 5 )” mean a solution prepared according to the following method . dextrose ( 0 . 5 g ) was added to a 100 - ml volumetric flask . then 1m hcl or 1m naoh was added to adjust the ph of the buffer to ph 5 . 5 . acetate buffer ( ph 5 . 5 ) preparation — the acetate buffer ( ph 5 . 5 ) used for the trifluoroacetate salts ( type a and b ) and the hcl type i salt was prepared by placing 0 . 60 g sodium acetate ( nac 2 h 3 o 2 . 3h 2 o ) in a 100 - ml volumetric flask , adding 3 ml of 2 m acetic acid solution , and then adding purified water to volume . phosphate buffer ( ph 6 . 0 ) preparation — the terms “ phosphate buffer at ph 6 . 0 ” and “ phosphate buffer ( ph 6 . 0 )” mean a solution prepared according to the following method . a solution of 0 . 2 m kh 2 po 4 ( 25 ml ) and 0 . 2 m naoh ( 5 . 6 ml ) was prepared in a 100 - ml volumetric flask . the ph was checked by ph meter . then water was added to volume . an alternative media (“ phosphate ( ph 6 . 0 ) alternative media ”) was used to study the trifluoroacetate salts ( type a and b ) and the hcl type i salt . more specifically , the media was prepared by dissolving 2 . 72 g of 0 . 2 m monobasic potassium phosphate ( kh 2 po 4 ) in purified water , and diluting with purified water to 100 ml . 0 . 8 g of 0 . 2 m sodium hydroxide in purified water was diluted with purified water to 100 ml . then 50 ml of the 0 . 2 m monobasic potassium phosphate solution was placed in a 200 - ml volumetric flask , 5 . 6 ml of 0 . 2 m sodium hydroxide solution was added , and then purified water was added to volume . phosphate buffer ( ph 7 . 5 ) preparation — the terms “ phosphate buffer at ph 7 . 5 ” and “ phosphate buffer ( ph 7 . 5 )” mean a solution prepared according to the following method . a solution of 0 . 2 m kh 2 po 4 ( 25 ml ) and 0 . 2 m naoh ( 40 . 2 ml ) was prepared in a 100 - ml volumetric flask . the ph was checked by ph meter . then water was added to volume . kinetic solubility of scy - 078 salts — the term “ kinetic solubility ” with respect to scy - 078 salts means the following procedure . first , 15 mg , 50 mg , or 100 mg of one of the scy - 078 salts was placed into a 4 - ml plastic centrifuge tubes along with 1 . 7 ml of relevant media or 2 . 0 ml of water . for dextrose buffer at ph 5 . 5 , phosphate buffer at ph 6 . 0 , and phosphate buffer at ph 7 . 5 , 15 mg of the scy - 078 salt was used . for sgf media , fessif media , and fassif media , 50 mg of the scy - 078 salt was used . for water , 100 mg of the scy - 078 salt was used . the actual weight of each sample was recorded . the tube was subsequently capped and the suspension samples were stirred on a rolling incubator ( 25 rpm ) at room temperature . samples were taken at 1 hour , 4 hours , and 24 hours respectively . for each sample , a 0 . 5 ml aliquot of the suspension was transferred into a 1 . 5 - ml centrifuge filtration tube and centrifuged . the samples were then filtered through the centrifuge filtration tube ( 0 . 45 μm ) at 8 , 000 rpm at room temperature for 3 minutes . the trifluoroacetate salts ( type a and b ) and the hcl type i salt were tested using the following alternative procedure . first , 15 mg , 36 mg or 90 mg solid was weighted into a 4 - ml plastic tube , and 3 ml of relevant media was added before leaving the suspension on a rolling incubator ( 25 r / min ). for scf , 90 mg of solid was used . for fassif , acetate buffer ( ph 5 . 5 ), and phosphate buffer ( ph 6 . 0 ), 15 mg solid was used . for fessif , 36 mg of solid was used . 1 . 0 ml aliquot of the suspension was sampled for centrifugation with the supernatant submitted for hplc and ph measurement and solid for xrpd characterization at 1 hr , 4 hr and / or 24 hrs . approximate solubility of scy - 078 salts — the term “ approximate solubility ” with respect to scy - 078 salts means the procedure described in this paragraph . to conduct each experiment , a sample of a scy - 078 salt (˜ 2 mg ) was added into a 3 - ml glass vial . then a solvent was added step - wise ( 100 μl per step ) into the vials until the solids were dissolved or a total volume of 2 ml was reached . equilibrium solubility of scy - 078 salts — the term “ equilibrium solubility ” with respect to scy - 078 salts means the procedure described in this paragraph . the equilibrium solubility of a scy - 078 salt was evaluated in water at room temperature . first , the scy - 078 salt (˜ 50 mg ) was weighed into a 1 . 5 - ml vial followed by addition of 1 . 0 ml water , and then the sample was stirred ( 800 rpm ) at room temperature for 24 hours . the sample was centrifuged with the residual solid analyzed by xrpd and supernatant concentration measured by hplc . polarized light microscopic imaging — polarized light microscopic ( plm ) images was captured at room temperature using axio lab a1 upright microscope equipped with progres ® ct3 camera . the sample was sandwiched between a glass slide and a top cover before placed under the polarized light microscopy for imaging . scy - 078 phosphate : the phosphate salt of scy - 078 was prepared from scy - 078 freebase , which was prepared using known procedures . see , e . g ., u . s . pat . no . 8 , 188 , 085 . scy - 078 freebase ( 10 . 0 g ) was placed in a 250 ml reactor . ethanol ( 50 ml ), ethyl acetate ( 30 ml ), acetic acid ( 1 . 5 ml ) and water ( 1 ml ) were added and the mixture was stirred at room temperature over 10 minutes . the resulting homogeneous solution was heated to 50 ° c . and phosphoric acid ( 1 . 74 g ) solution in ethyl acetate was slowly added to the solution at 50 ° c . for 1 hour . the resulting slurry was slowly cooled to room temperature and stirred overnight at room temperature . the slurry was filtered , and the wet cake was washed with 20 ml mixed solvents ( ethanol : ethyl acetate : water = 5 : 5 : 0 . 1 ) two times , then twice with ethyl acetate ( 1 ml ). the wet cake was dried under vacuum with nitrogen sweep over three hours , and then dried in a vacuum oven overnight to obtain 11 . 08 g of an off - white crystal . the retention time of the compound was 4 . 08 minutes , as measured by hplc using an ascentis express c18 column with standard gradient : 10 - 95 % of b in 6 minutes ( a = 0 . 1 % phosphoric acid , b = acetonitrile ), 2 minute hold 2 minute post ; flow rate : 1 . 8ml / minute ( uv detection at 245 nm , 40 ° c .). scy - 078 phosphate was characterized by xrpd , which evidenced that the compound is crystalline ( fig1 ). the 2 theta and d - spacing values are summarized in table 4 . the dsc curve of scy - 078 phosphate exhibited two endothermic peaks at 48 . 1 ° c . and 267 ° c . ( fig2 ). a weight loss of 6 . 6 % was observed up to 155 . 4 ° c . in the tga curve ( fig2 ). scy - 078 crystalline freebase ( meoh desolvate ): the meoh desolvate was prepared as follows . scy - 078 phosphate salt ( 10 . 0 g ) was charged into a 250 ml reactor . sodium carbonate ( 50 ml of a 10 % solution ) was added at 20 ° c . and agitated . 2 - methyltetrahydrofuan ( 100 ml ) was added and agitated strongly at 20 ° c . until all the solids dissolved . the mixture was left to stand for 30 minutes to leave two clear layers which were separated and the organic layer was washed twice with deionized water ( 40 ml ). the washed organic layer was transferred to a 125 - ml reaction vessel and agitated at 500 rpm , heated to 50 ° c . and distilled under partial vacuum at 50 ° c . down to 40 ml volume . methanol ( 80 ml ) was added to the reaction vessel at 50 ° c ., which was then cooled to 40 ° c . ; after 2 hours , crystals formed . the volume was then distilled down to 50 ml at 40 ° c . under partial vacuum over 16 hours . there was then constant volume distillation at 40 ° c . while adding methanol ( 40 ml ) over 2 hours . water ( 20 ml ) was then added over 2 hours . the reaction vessel was then cooled to 20 ° c . over 2 hours and then slurry aged at 20 ° c . for 2 hours . the mixture was then filtered and the resulting wet cake washed with 20 ml of a 4 : 1 solution of methanol and water . the wet cake was dried under nitrogen sweep at room temperature for 16 hours . xrpd analysis confirmed that the dry cake is desolvated methanol solvate ( yield 89 %, purity : 99 . 1 %). two batches of meoh desolvate were prepared and characterized by xrpd , dsc , and tga ( fig3 - 5 ). xrpd patterns evidenced that the compound is crystalline . the 2 theta and d - spacing values from batch 1 and batch 2 are summarized in tables 5a and 5b , respectively . the dsc curve of meoh desolvate batch 1 exhibited an endotherm at ˜ 55 . 0 ° c . and an exotherm at ˜ 281 . 5 ° c . the dsc curve of meoh desolvate batch 2 exhibited an endotherm at ˜ 56 . 1 ° c . and an exotherm at ˜ 279 . 2 ° c . the tga curve of batch 1 showed a weight loss of 4 . 7 % before 120 ° c . the tga curve of batch 1 showed a weight loss of 6 . 6 % before 120 ° c . the tga curve of batch 2 showed a weight loss of 4 . 9 % before 120 ° c . scy - 078 amorphous freebase : to prepare scy - 078 amorphous freebase , meoh desolvate ( 50 mg ) was added to a 3 - ml vial . then dcm ( 0 . 5 ml ) was added to the vial of meoh desolvate . the resulting solution of meoh desolvate and dcm formed a clear solution . the solution was evaporated to dryness from an open vial at 50 ° c . the solid obtained after evaporation was characterized by xrpd , tga , dsc , and dvs . the xrpd pattern evidenced that the tested sample is amorphous . the dsc and tga curves of the amorphous sample exhibited a glass transition at ˜ 189 . 1 ° c . ( fig6 ). the tga curve demonstrated a weight loss of 4 . 2 % before 150 ° c . the dvs curve demonstrated that the sample is hygroscopic with a water uptake of ˜ 4 . 8 % at 80 % rh , 25 ° c . an xrpd pattern performed after dvs demonstrated no form change . kinetic solubility of scy - 078 freebase : the kinetic solubility of scy - 078 meoh desolvate and scy - 078 amorphous freebase was evaluated in sgf media , fassif media , fessif media , dextrose buffer ( ph 5 . 5 ), phosphate buffer ( ph 6 . 0 ), and phosphate buffer ( ph 7 . 5 ) at room temperature . first , solid scy - 078 meoh desolvate or scy - 078 amorphous freebase (˜ 15 mg ) was weighed into a 4 - ml vial . then the relevant media ( 3 . 0 ml ) was added and the suspensions were stirred on a rolling incubator ( 25 rpm ) at room temperature for 1 hour , 4 hours , and 24 hours respectively . after stirring , 0 . 5 ml of suspension was centrifuged and filtered ( 0 . 45 μm ). the residual solids were analyzed by xrpd , and the supernatant was measured by hplc and ph meter . the results ( table 6 ) suggested that both the meoh desolvate and the amorphous freebase display high solubility in sgf and fessif . the results also showed that both the meoh desolvate and the amorphous freebase are only sparingly soluble in fassif and ph 5 . 5 , ph 6 . 0 , and ph 7 . 5 buffers . solid form change was observed during the solubility measurements of the meoh desolvate in fessif , fassif , ph 5 . 5 and 6 . 0 buffers . additionally , three new crystal forms were discovered ( table 6 ). the three new forms are identified as new form 1 , 2 , and 3 . approximate solubility of scy - 078 meoh desolvate : the approximate solubility of scy - 078 meoh desolvate was measured in 20 solvents at room temperature ( 25 ± 3 ° c .). first , meoh desolvate (˜ 2 mg ) was added to a 3 - ml glass vial . then the corresponding solvent was added step wise ( 100 μl ) until the solution was visually clear or a total volume of 2 ml was reached . the results appear in table 7 . salt study of scy - 078 freebase : a salt study of the scy - 078 meoh desolvate freebase was performed using 108 different conditions developed through 18 acids in 6 solvents ( table 8 ). the salt study was performed by first preparing a solution of scy - 078 meoh desolvate freebase and mixing with an equi - molar acid solution . this solution was stirred at room temperature overnight . for precipitates , the solids were isolated and analyzed by xrpd . clear solutions were evaporated slowly to dryness at room temperature . the salt study ( table 8 ) showed that seven crystalline salts ( eight crystal forms ) of scy - 078 were found : hcl type a , citrate type a , hippurate type a , fumarate type a , fumarate type b , glycolate type a , mesylate type a , and ca salt type a . four crystal forms of scy - 078 freebase were discovered during the salt study and were identified as freebase (“ fb ”) type a , b , c , and d . scy - 078 hcl type a : scy - 078 hcl type a prepared from the salt study in example 6 was characterized by xrpd , dsc , and tga ( fig7 - 8 ). the resulting xrpd pattern evidenced that scy - 078 hcl type a is weakly crystalline and has a unique form as compared to the freebase meoh desolvate . the 2 theta and d - spacing values are summarized in table 9 . the dsc curve displayed an endotherm at 48 . 5 ° c . ( onset temperature ). the tga curve showed a weight loss of 14 . 4 % before 130 ° c . scy - 078 citrate type a ( molar equivalency — counter ion / api 1 ): scy - 078 citrate type a prepared from the salt study in example 6 was characterized by xrpd , dsc , and tga ( fig9 - 10 ). the resulting xrpd pattern evidenced that scy - 078 citrate type a is crystalline and is a unique form compared to the freebase meoh desolvate . the 2 theta and d - spacing values are summarized in table 10 . the dsc curve displayed two endotherms at 36 . 2 ° c . and 194 . 8 ° c . ( onset temperature ). the tga curve demonstrated 5 . 1 % before 100 ° c . a sample was heated to 100 ° c . and then cooled to room temperature . xrpd was performed after heating and cooling to room temperature . the resulting xrpd pattern showed that there was no change in form . dsc and tga characterization was also performed after heating and cooling . the dsc curve demonstrated two endotherms at 39 . 9 ° c . and 194 . 8 ° c . ( onset temperatures ). the tga curve showed a weight loss of 5 . 3 % before 100 ° c . scy - 078 hippurate type a ( molar equivalency counter ion / api 2 . 0 ): scy - 078 hippurate type a prepared from the salt study in example 6 was characterized by xrpd , dsc , and tga ( fig1 - 12 ). the xrpd pattern of scy - 078 hippurate type a indicated that the sample is crystalline and has a unique form as compared to the freebase meoh desolvate . the dsc curve displayed three endotherms at 36 . 3 ° c ., 104 . 6 ° c ., and 165 . 5 ° c . ( onset temperatures ) and one exotherm at 201 . 9 ° c . ( onset temperature ). the tga curve showed a weight loss of 4 . 9 % before 150 ° c . scy - 078 hippurate type b : scy - 078 hippurate type b is produced from heating hippurate type a to 150 ° c . and then cooling the sample to room temperature . scy - 078 hippurate type b was characterized by xrpd , dsc , and tga ( fig1 - 14 ). the xrpd pattern showed that the sample is crystalline and a unique form compared to scy - 078 hippurate type a . the dsc curve displayed two endotherms at 39 . 6 ° c . and 166 . 4 ° c . ( onset temperatures ) and one exotherm at 201 . 4 ° c . ( onset temperature ). the tga curve demonstrated a weight loss of 1 . 8 % before 150 ° c . scy - 078 hippurate type c : cycle dsc and xrpd were performed to investigate the phase transition events during the heating - cooling process of scy - 078 hippurate type b ( fig1 - 16 ). the xrpd overlay and dsc curve suggested the melting point of scy - 078 hippurate type b at 163 . 9 ° c . followed by amorphous phase recrystallizing at 208 . 8 ° c . and a new anhydrate phase being formed . the new anhydrate phase is scy - 078 hippurate type c . scy - 078 fumarate type a ( molar equivalency counter ion / api 1 . 0 ): scy - 078 fumarate type a prepared from the salt study in example 6 was characterized by xrpd , dsc , and tga ( fig1 - 18 ). the xrpd pattern indicated that the sample is crystalline and a unique form compared to the freebase meoh desolvate . the dsc curve of scy - 078 fumarate type a showed an endotherm at 33 . 1 ° c . and a melting point at 207 . 3 ° c . ( onset temperature ). the tga curve displayed a weight loss of 2 . 4 % before 120 ° c . a sample of scy - 078 fumarate type a was heated to 120 ° c . and then allowed to cool to room temperature . characterization by xrpd , dsc , and tga were then repeated . the xrpd pattern displayed no form change after heating and cooling . the dsc curve of heated - cooled scy - 078 fumarate type a exhibited two endotherms at 38 . 4 ° c . and 207 . 1 ° c . ( onset temperatures ). the tga curve of heated - cooled scy - 078 fumarate type a showed a weight loss of 2 . 0 % before 120 ° c . scy - 078 fumarate type b ( molar equivalency counter ion / api 0 . 8 ): scy - 078 fumarate type b prepared from the salt study in example 6 was characterized by xrpd , dsc , and tga ( fig1 - 20 ). the xrpd pattern of scy - 078 fumarate type b indicated that the sample is weakly crystalline and that it is a unique form compared to the freebase meoh desolvate . the dsc curve of scy - 078 fumarate type b showed two endotherms at 37 . 9 ° c . and 178 . 5 ° c . ( onset temperature ). the tga curve demonstrated a weight loss of 13 . 4 % before 300 ° c . scy - 078 glycolate type a ( molar equivalency counter ion / api 2 . 0 ): scy - 078 glycolate type a prepared from the salt study in example 6 was characterized by xrpd , dsc , and tga ( fig2 - 22 ). the xrpd pattern of scy - 078 glycolate type a indicated that the sample is crystalline and a unique form compared to the freebase meoh solvate . the dsc curve of the sample displayed two endotherms at 35 . 9 ° c . and 159 . 6 ° c . ( onset temperatures ). the tga curve showed a weight loss of 6 . 6 % before 100 ° c . scy - 078 mesylate type a ( molar equivalency counter ion / api 1 . 0 ): scy - 078 mesylate type a prepared from the salt study in example 6 was characterized by xrpd , dsc , and tga ( fig2 - 24 ). the xrpd pattern indicated that the sample is crystalline and a unique form compared to the freebase meoh desolvate . the dsc curve displayed an endotherm at 44 . 2 ° c . and a melting point at 260 . 0 ° c . ( onset temperatures ). the tga showed a weight loss of 4 . 5 % before 120 ° c . next , a sample of scy - 078 mesylate type a was heated to 120 ° c . and then allowed to cool to room temperature . characterization by xrpd , dsc , and tga was then repeated . the xrpd pattern displayed no form change after heating and cooling . the dsc curve of the heated - cooled scy - 078 mesylate type a exhibited an endotherm at 59 . 7 ° c . and a melting point at 257 . 4 ° c . ( onset temperatures ). the tga curve of the heated - cooled scy - 078 mesylate type a showed a weight loss of 9 . 4 % before 120 ° c . scy - 078 calcium type a : scy - 078 calcium type a prepared from the salt study in example 6 was characterized by xrpd , dsc , and tga ( fig2 - 26 ). the xrpd pattern indicated that the sample is crystalline and a unique form compared to the freebase meoh desolvate . the dsc curve displayed two endotherms at 147 . 3 ° c . and 230 . 8 ° c . ( onset temperatures ). the tga curve showed a weight loss of 5 . 3 % before 170 ° c . preparation and characterization of scaled - up scy - 078 hippurate type b : to scale - up scy - 078 hippurate type b , a solution of hippuric acid ( 122 . 8 mg ) and scy - 078 meoh desolvate ( 500 . 3 mg ) in acn ( 5 . 0 ml ) was prepared . the suspension was then stirred ( 500 rpm ) at room temperature for 28 hours . following stirring , some slurry was filtered and the isolated solid was checked by xrpd to confirm scy - 078 hippurate type a . the suspension was filtered and dried at 150 ° c . for 1 hour before characterization . finally , the solid was check by xrpd to confirm to scy - 078 hippurate type b . the scaled - up scy - 078 hippurate type b was analyzed by xrpd , dsc , tga , and dvs ( fig2 - 30 ). the resulting xrpd pattern evidenced that scy - 078 hippurate type b was successfully scaled up . the 2 theta and d - spacing values are summarized in table 11 . the dsc curve showed two endotherms at 34 . 5 ° c . and 164 . 4 ° c . and one exotherm at 205 . 2 ° c . ( onset temperatures ). the tga curve showed a weight loss of 0 . 9 % before 130 ° c . the dvs curve showed that the sample is hygroscopic with a water uptake of - 3 . 5 % at 25 ° c . and 80 % rh . a second xrpd pattern performed after dvs showed scy - 078 hippurate type b converted to scy - 078 hippurate type a after dvs experiment . preparation and characterization of scaled - up scy - 078 fumarate type a : to scale - up scy - 078 fumarate type a , a solution of fumaric acid ( 79 . 8 mg ) and scy - 078 meoh desolvate ( 501 . 9 mg ) in acn ( 15 . 0 ml ) was prepared . the suspension was then stirred ( 500 rpm ) at room temperature for 28 hours . following stirring , some slurry was filtered and the isolated solid was checked by xrpd to confirm scy - 078 fumarate type a . finally , the suspension was filtered and dried at 30 ° c . for 4 hours in vacuum before characterization . characterization of scaled - up scy - 078 fumarate type a included xrpd , dsc , tga , and dvs ( fig3 - 33 ). the resulting xrpd pattern evidenced that scy - 078 fumarate type a was successfully scaled up . the 2 theta and d - spacing values are summarized in table 12 . the dsc curve showed an endotherm at 39 . 9 ° c . and a melting endotherm at 208 . 4 ° c . ( onset temperatures ). the tga curve showed a weight loss of 1 . 7 % before 150 ° c . the dvs curve showed that the sample is hygroscopic with a water uptake of 2 . 5 % at 80 % rh , 25 ° c . a second xrpd pattern performed after dvs showed scy - 078 fumarate type a had no form change . preparation and characterization of scaled - up scy - 078 mesylate type a : to scale up scy - 078 mesylate type a , a solution of methanesulfonic acid ( 66 . 7 mg ) and scy - 078 meoh desolvate ( 500 . 00 mg ) in acn ( 6 . 0 ml ) was prepared . the suspension was then stirred ( 500 rpm ) at room temperature for 28 hours . following stirring , some slurry was filtered and the isolated solid was checked by xrpd to confirm to scy - 078 mesylate type a . finally , the suspension was filtered and dried at 30 ° c . for 4 hours in vacuum before characterization . characterization of scaled - up scy - 078 mesylate type a included xrpd , dsc , tga , and dvs ( fig3 - 36 ). the resulting xrpd pattern evidenced that scy - 078 mesylate type a was successfully scaled up . the 2 theta and d - spacing values are summarized in table 13 . the dsc curve showed an endotherm at 45 . 1 ° c . and a melting endotherm at 252 . 5 ° c . ( onset temperatures ). the tga curve showed a weight loss of 5 . 5 % before 150 ° c . the dvs curve showed that the sample is hygroscopic with a water uptake of 11 . 5 % at 25 ° c . and 80 % rh . a second xrpd pattern performed after dvs showed scy - 078 mesylate type a had no form change . preparation and characterization of scaled - up scy - 078 phosphate type a : to scale up scy - 078 phosphate type a , a solution of phosphoric acid ( 87 . 2 mg ) and scy - 078 meoh desolvate ( 501 . 1 mg ) in etoh / etoac / acetic acid / h 2 o ( 6 . 0 ml , 5 : 3 : 0 . 15 : 0 . 1 ; v / v / v / v ) was prepared . the suspension was then stirred ( 500 rpm ) at room temperature for 28 hours . following stirring , some slurry was filtered and the isolated solid was checked by xrpd and named as scy - 078 phosphate type a . finally , the suspension was filtered and dried at 30 ° c . for 4 hours in vacuum before characterization . characterization of scaled - up scy - 078 phosphate type a included xrpd , dsc , tga , and dvs ( fig3 - 39 ). the xrpd pattern of the scaled - up scy - 078 phosphate type a was compared with another phosphate sample . the comparison xrpd pattern evidenced certain peak shifts , which are signaled with an asterisk . the 2 theta and d - spacing values of scy - 078 phosphate type a are summarized in table 14 . the dsc curve showed two endotherms at 43 . 5 ° c . and 261 . 6 ° c . ( onset temperatures ). the tga curve showed a weight loss of 5 . 7 % before 100 ° c . the dvs curve showed that the sample is hygroscopic with a water uptake of 12 . 5 % at 25 ° c . and 80 % rh . a second xrpd pattern performed after dvs showed scy - 078 phosphate type a had no form change . preparation and characterization of scaled - up scy - 078 citrate type a ( molar equivalency — counter ion / api 1 . 0 ): to scale up scy - 078 citrate type a , a solution of citric acid ( 130 . 7 mg ) and scy - 078 meoh desolvate ( 501 . 6 mg ) in acn ( 15 . 0 ml ) was prepared . the suspension was then stirred ( 500 rpm ) at room temperature for 30 hours . following stirring , some slurry was filtered and the isolated solid was checked by xrpd to confirm scy - 078 citrate type a . finally , the suspension was filtered and dried at 30 ° c . for 4 hours in vacuum before characterization . characterization of scaled - up scy - 078 citrate type a included xrpd , dsc , tga , and dvs ( fig4 - 42 ). xrpd pattern evidenced that scy - 078 citrate type a was successfully scaled up . the 2 theta and d - spacing values are summarized in table 15 . the dsc curve showed an endotherm at 38 . 5 ° c . and a melting endotherm at 183 . 7 ° c . ( onset temperatures ). the tga curve showed a weight loss of 4 . 1 % before 110 ° c . the dvs curve showed that the sample is hygroscopic with a water uptake of 6 . 4 % at 80 % rh , 25 ° c . a second xrpd pattern performed after dvs showed scy - 078 citrate type a had no form change . chemical characterization of scy - 078 salts : the chemical purity of each of the scaled - up salts of scy - 078 ( hippurate type b , fumarate type a , mesylate type a , phosphate type a , and citrate type a ) was tested using hplc chromatographs . the chromatographs of the five compounds indicated that each compound has purity greater than 99 % ( table 16 ). evaluation of the ph value of scy - 078 salts in water : the ph value for the saturated salt solutions of scy - 078 ( i . e ., hippurate type b , fumarate type a , mesylate type a , phosphate type a , and citrate type a ) was tested . to test the ph , a solution of each compound was equilibrated at room temperature using a rolling incubator ( 25 rpm ) for 1 hour and 24 hours before measurement . the results ( table 17 ) suggested that the ph values of each of the salts tested is in the range of 3 . 0 to 5 . 0 . evaluation of the kinetic solubility of scy - 078 salts : the kinetic solubilities of scy - 078 hippurate type b , scy - 078 fumarate type a , scy - 078 mesylate type a , scy - 078 phosphate type a , and scy - 078 citrate type a were measured in dextrose buffer at ph 5 . 5 , phosphate buffer at ph 6 . 0 , phosphate buffer at ph 7 . 5 , sgf media , fessif media , and fassif media according to the method described above . after filtration , 0 . 2 ml of supernatant was collected for hplc quantification . the remaining solution was collected for ph measurement . the remaining solid was collected for xrpd characterization . the results appear in table 18 . evaluation of the stability of scy - 078 salts : to test the chemical and physical stability of the salts , samples of the salts were placed under three different conditions for one week : ( 1 ) open dish at 25 ° c . with 60 % rh ; ( 2 ) open dish at 40 ° c . with 75 % rh ; and ( 3 ) closed dish at 60 ° c . with no humidity control . the chemical and physical stability of scy - 078 fumarate type a and scy - 078 citrate type a were tested as described above ( table 19 ). xrpd indicated that neither scy - 078 fumarate type a nor scy - 078 citrate type a experienced form change during assessment . scaled - up scy - 078 citrate type a : a second scale - up of scy - 078 citrate type a was carried out to obtain 2 . 5 g via reactive acn . to scale - up , scy - 078 meoh desolvate ( 2 . 5 g ) and citric acid ( 660 mg ) were dissolved in acn ( 80 ml ). the resulting solution was stirred at a rate of 1000 rpm at room temperature for 30 hours and then the solid was isolated . the solid obtained was dried at 50 ° c . under vacuum overnight . an xrpd pattern ( fig4 ) showed that scy - 078 citrate type a was successfully scaled up and that it is highly crystalline . the 2 theta and d - spacing values are summarized in table 20 . dsc curve ( fig4 ) exhibited two endothermic peaks at 56 . 7 ° c . and 187 . 1 ° c . ( onset temperatures ). tga curve ( fig4 ) showed 7 . 9 % weight loss before 150 ° c . approximate solubility of scy - 078 citrate type a : the approximate solubility of scy - 078 citrate type a from example 26 was determined in 19 solvents at room temperature ( 25 ± 3 ° c .) according to the procedure described above and is reported in table 21 below . kinetic solubility of scy - 078 citrate type a in water : the kinetic solubility of scy - 078 citrate type a from example 26 was evaluated according to the procedure described above . after the samples were centrifuged , the residual solids analyzed by xrpd and the supernatant concentration measured by hplc . results ( table 22 ) indicated that scy - 078 citrate type a partially converted to amorphous in water after 24 hours , and exhibited a slow rate of dissolution and increasing solubility in water from 1 hour to 24 hours . then the kinetic solubility of scy - 078 citrate type a was compared with a mixture of scy - 078 amorphous freebase / citric acid . the kinetic solubility comparison was conducted in water at room temperature and was measured at 1 hour , 4 hours , and 24 hours with a ratio of solute to solvent of 20 mg / ml and 50 mg / ml . results ( table 23 ) indicated that scy - 078 citrate type a shows higher dissolution rate and equilibrium solubility in water than the mixture of scy - 078 amorphous freebase / citric acid . the remaining solids from the solubility measurement of physical mixture of freebase : citric acid at 1 : 1 molar ratio in water were amorphous . to determine the form of the amorphous , liquid nmr was performed on a bruker 400m nmr spectrometer using cd 3 od . the spectrum showed the number of hydrogen atoms assigned to citric acid as 3 . 12 , corresponding to 0 . 78 equivalent of citric acid . this is less than 1 : 1 for mono - citrate and suggests it is a mixture that comprises a majority of amorphous citrate salt with a small quantity of amorphous freebase . equilibrium solubility of scy - 078 salts in water : equilibrium solubility of scy - 078 citrate type a from example 26 in water was determined using the method described above . results showed that scy - 078 citrate type a exhibits 38 . 1 mg / ml solubility in water with the undissolved material having become amorphous after stirring in water for 24 hours . then to further study the solubility of scy - 078 citrate type a in water , citrate type a was tested for 24 hours at three ratios of solute to solvent : 0 . 3 mg / ml , 2 . 0 mg / ml , and 50 . 6 mg / ml . each test used magnetic stirring and began with an initial ph of 8 . 0 . the results ( table 24 ) indicated that scy - 078 citrate type a exhibits a concentration - dependent solubility in water . kinetic solubility of scy - 078 citrate amorphous in water : scy - 078 citrate amorphous was prepared under various conditions , including lyophilization from phosphate buffer ( ph 6 . 0 ), lyophilization from water , and fast evaporation in thf . the results appear in table 25 . where the table indicates “ limited solid ,” there was not sufficient solid for xrpd analysis of the solid form . lyophilization in phosphate buffer ( ph 6 . 0 )— for lyophilization in phosphate buffer ( ph 6 . 0 ), scy - 078 citrate amorphous was prepared by first preparing 50 mm ph 6 . 0 buffer . then citrate type a ( 30 mg ) was weighed into a 20 - ml vial . then ph 6 . 0 buffer ( 20 ml ) was added to the vial and was stirred at room temperature for 24 hours . the samples were filtered and the supernatant was cooled to − 15 ° c . for 2 hours . finally , the frozen samples were lyophilized at − 50 ° c . for 12 hours . a larger batch ( 150 mg ) was prepared using the same procedure noted above . the kinetic solubility of the second batch of the lyophilized product in water was measured according to the above procedure except that ˜ 150 mg of solid and 1 . 0 ml of water were used . after the samples were centrifuged , the residual solids were analyzed by xrpd and the supernatant concentration was measured by hplc . lyophilization in water — for lyophilization in water , amorphous citrate was prepared by first weighing citrate type a (˜ 150 mg ) into a 20 - ml vial . then 10 ml of water was added to dissolve the solid completely . the solution was filtered and put in a condition of − 20 ° c . until it froze . finally , the sample was lyophilized under - 50 ° c . for 24 hours . the kinetic solubility of the lyophilized product in water was measured according to the above procedure except that ˜ 120 mg of solid and 1 . 5 ml of water were used . after the samples were centrifuged , the residual solids were analyzed by xrpd and the supernatant concentration was measured by hplc . fast evaporation in thf — for fast evaporation in thf , amorphous citrate was prepared by first weighing citrate type a from example 26 (˜ 150 mg ) into a 20 - ml vial . then thf ( 3 ml ) was added to dissolve the solid completely . the solution was filtered under a fume hood for performance of fast evaporation . the kinetic solubility in water of the product in water was measured according to the above procedure except that ˜ 120 mg of solid and 1 . 5 ml of water were used . after the samples were centrifuged , the residual solids were analyzed by xrpd and the supernatant concentration was measured by hplc . slow evaporation of scy - 078 citrate type a : slow evaporation experiments were performed in 12 different solvent systems . scy - 078 citrate type a from example 26 ( 10 mg ) was dissolved with solvent ( 0 . 05 ml − 0 . 25 ml ) for each sample in a 3 - ml glass vial . the visually clear solutions were subjected to slow evaporation at room temperature to dryness . the solids obtained were then isolated for xrpd analysis , which showed that no crystalline form was obtained . the results appear in table 26 . slurry conversion of scy - 078 citrate type a : slurry conversion experiments were conducted under 50 conditions . scy - 078 citrate type a from example 26 (˜ 10 mg ) was suspended in each solvent ( 0 . 5 ml ). the suspensions were stirred for 3 days at either room temperature ( table 27 ) or 50 ° c . ( table 28 ). after stirring , the solids were isolated for xrpd analysis . if the suspensions turned into clear solutions upon slurry , the clear solutions were subjected to slow evaporation at room temperature . the results revealed that scy - 078 citrate type b and mixtures of scy - 078 citrate type a and scy - 078 citrate type b were discovered . all scy - 078 citrate type c that was discovered was identified as freebase form . reverse anti - solvent addition of scy - 078 citrate type a : reverse anti - solvent addition experiments were conducted under 14 conditions . scy - 078 citrate type a from example 26 (˜ 10 mg ) was dissolved in each solvent ( 0 . 1 ml ) to obtain a clear solution . this solution was added drop - wise into a glass vial containing 2 . 0 ml of each anti - solvent at room temperature . the precipitate was isolated for xrpd analysis . slow evaporation experiments were conducted for the clear solutions . the results , which appear in table 29 , suggested that scy - 078 citrate type e and scy - 078 citrate type f were obtained . scy - 078 citrate type d and scy - 078 citrate type j were identified as freebase form . solid vapor diffusion of scy - 078 citrate type a : solid vapor diffusion experiments were conducted using four solvents at room temperature . scy - 078 citrate type a from example 26 (˜ 10 mg ) was placed into a 3 - ml glass vial . then the vial was sealed into a 20 - ml glass vial with a solvent ( 3 ml ). the system was kept at room temperature for six days , which was sufficient time for organic vapor to interact with the solids . the solids were characterized by xrpd to identify crystalline forms . the results ( table 30 ) indicated that scy - 078 citrate type a and scy - 078 citrate type b were generated . solution vapor diffusion of scy - 078 citrate type a : solution vapor diffusion experiments were conducted under 5 conditions at room temperature . scy - 078 citrate type a from example 26 (˜ 10 mg ) was dissolved in a solvent to obtain a clear solution in a 3 - ml glass vial . the vial was then sealed into a 20 - ml glass vial with a volatile anti - solvent ( 3 ml ). the system was kept at room temperature for six days , which allowed sufficient time for precipitation . as no precipitation was observed , the samples were evaporated slowly to dryness at room temperature . the solids were separated and analyzed by xrpd . the results ( table 31 ) indicated that no crystalline form was obtained . polymer induced crystallization of scy - 078 citrate type a : polymer induced crystallization experiments were performed under four conditions . scy - 078 citrate type a from example 26 (˜ 10 mg ) was dissolved in a solvent ( 0 . 1 ml - 0 . 8 ml ) in a 3 - ml glass vial . a mixed polymer (- 1 . 0 mg ) was added into the visually clear solutions . the “ mixed polymer ” was a mixture of six polymers ( polyvinyl alcohol , polyvinylchloride , polyvinyl pyrrolidone , polyvinyl acetate , hypromellose , and methyl cellulose ) at the mass ration of 1 . 0 . all the samples were then evaporated slowly at room temperature to dryness . the solids obtained were isolated for xrpd analysis . the results ( table 32 ) showed that no crystalline form was observed . slow cooling of scy - 078 citrate type a : slow cooling experiments were conducted under 10 conditions ( table 33 ). scy - 078 citrate type a from example 26 (˜ 10 mg ) was suspended in a solvent ( 0 . 1 ml - 0 . 2 ml ) at 50 ° c . suspensions were filtered at 50 ° c ., and the filtrates were collected and cooled from 50 ° c . to 5 ° c . at a rate of 0 . 1 ° c ./ min . all solutions were clear and subjected to slow evaporation at room temperature to induce precipitation . the solids were isolated for xrpd analysis . the results ( table 33 ) indicated that scy - 078 citrate type c and scy - 078 citrate type j were produced and that both scy - 078 citrate type c and scy - 078 citrate type j are freebase forms . scy - 078 citrate type a via reactive crystallization : scy - 078 citrate type a was obtained by reactive crystallization in acn . the xrpd pattern showed distinctive diffraction peaks ( fig4 ). dsc curve showed two endothermic peaks at 56 . 7 ° c . and 187 . 1 ° c . ( onset temperatures ) ( fig4 ). tga curve displayed a 7 . 9 % weight loss up to 150 ° c . ( fig4 ). dvs plot showed a water uptake of 7 . 0 % at 80 % rh ( fig4 ). there was no form change after dvs analysis . scy - 078 citrate type a was also tested with variable temperature xrpd analysis . no form change was observed upon heating scy - 078 citrate type a to 120 ° c . and then cooling back to 25 ° c ., indicating that scy - 078 citrate type a is an anhydrate . after crystallization process development , scy - 078 citrate type a exhibited higher crystallinity and less surface moisture adsorption was produced ( fig4 ). dsc curve showed two endothermic peaks at 41 . 7 ° c . and 194 . 8 ° c . ( onset temperatures ). tga curve displayed 2 . 9 % weight loss up to 150 ° c . dvs analysis showed a water uptake of 6 . 5 % at 25 ° c . and 80 % rh . no form change was observed after dvs analysis . 1 h - nmr spectrum in cd 3 od showed the molar ration of freebase and citric acid is 1 : 1 , indicating that scy - 078 citrate type a is mono - citrate . scy - 078 citrate type b : scy - 078 citrate type b was obtained by slurry conversion at room temperature in acn . scy - 078 citrate type b can also be obtained by slurrying scy - 078 citrate type a in various organic solvents such as etoh , acn , acetone , mibk , etoac , ipac , dcm , toluene , heptane , meoh / acetone ( 1 / 19 , v / v ), ipa / heptane ( 1 / 19 , v / v ), and thf / toluene ( 1 / 19 , v / v ). scy - 078 citrate type b converts to type a rapidly under vacuum or upon n 2 flow at room or elevated temperature . the xrpd pattern of scy - 078 citrate type b showed distinctive diffraction peaks ( fig5 ). dsc curve exhibited three endothermic peaks at 70 . 8 ° c ., 190 . 6 ° c ., and 202 . 9 ° c . ( peak temperatures ) ( fig5 ). tga curve displayed 10 . 3 % weight loss up to 150 ° c . ( fig5 ). scy - 078 citrate type e : scy - 078 citrate type e was obtained by drying a metastable solvate scy - 078 citrate type r from meoh / ipac . the xrpd pattern shows the crystalline form of the sample ( fig5 ). scy - 078 citrate type e is not stable at ambient conditions , since it rapidly converts to a new form ( scy - 078 citrate type m ) after exposing to air for 2 days ( fig5 ). scy - 078 citrate type f : scy - 078 citrate type f was obtained by reverse anti - solvent addition in ipa / toluene according to the process described in example 33 and table 29 . the xrpd pattern indicated that scy - 078 citrate type f is weakly crystalline ( fig5 ). dsc curve exhibited a wide endothermic peak at 37 . 3 ° c . ( onset temperature )( fig5 ). tga curve displayed a weight loss of 11 . 8 % up to 120 ° c . ( fig5 ). scy - 078 citrate type m : scy - 078 citrate type m was obtained by storing scy - 078 citrate type e in ambient conditions for 2 days . the xrpd pattern of scy - 078 citrate type m displayed distinctive diffraction peaks ( fig5 ). dsc curve exhibited two endothermic peaks at 125 . 8 ° c . and 193 . 3 ° c . ( onset temperatures ) ( fig5 ). tga curve displayed a 11 . 4 % weight loss up to 150 ° c . ( fig5 ). dvs plot showed 11 . 0 % water uptake at 25 ° c . and 80 % rh ( fig5 ). after dvs , scy - 078 citrate type m converts to partially amorphous . xrpd analysis was also performed at variable temperatures wherein xrpd patterns were produced at 25 ° c ., then at 150 ° c ., and finally , again at 25 ° c . ( fig6 ). a shift in diffraction peaks was observed , indicating that type m is probably a channel hydrate . scy - 078 citrate type n : scy - 078 citrate type n was obtained by slurrying scy - 078 citrate type b in etoh at room temperature for two weeks . scy - 078 citrate type n can also be obtained by exposing scy - 078 citrate type a in etoh vapor for 8 days or slurrying scy - 078 citrate type a in etoh for 2 hours . the xrpd pattern of scy - 078 citrate type n indicates that it is highly crystalline ( fig6 ). scy - 078 citrate type n converts to scy - 078 citrate type a after vacuum drying at room temperature ( fig6 ), indicating scy - 078 citrate type n is a metastable etoh solvate , which rapidly converts to scy - 078 citrate type a under vacuum or upon air / n 2 drying at ambient temperature or elevated temperature . scy - 078 citrate type o : scy - 078 citrate type o was obtained by slurrying scy - 078 citrate type m in acetone at room temperature for 19 hours . the xrpd pattern of scy - 078 citrate type o indicated that it is highly crystalline with distinctive diffraction peaks ( fig6 ). scy - 078 citrate type o converts to scy - 078 citrate type s under ambient or vacuum conditions . scy - 078 citrate type q : scy - 078 citrate type q was obtained when performing reactive crystallization of freebase and citric acid ( 1 : 1 ) in etoh without seeds . scy - 078 citrate type n was consistently obtained when the reactive crystallization was performed using scy - 078 citrate type n or scy - 078 citrate type a seeds . the xrpd pattern showed scy - 078 citrate type q is highly crystalline with distinctive diffraction peaks ( fig6 ). scy - 078 citrate type q can convert to scy - 078 citrate type a after vacuum drying at room temperature , indicating that scy - 078 citrate type q is a metastable etoh solvate ( fig6 ). the stability of the two etoh solvates , scy - 078 citrate type n and scy - 078 citrate type q , was evaluated by measuring their solubility at 5 ° c . and 20 ° c . ( table 34 ). the solubility was measured by slurrying scy - 078 citrate type n and scy - 078 citrate type q samples in etoh for 24 hours with a magnetic stirring rate of 1000 rpm . scy - 078 citrate type q exhibited lower solubility than scy - 078 citrate type n in etoh at 5 ° c . and 20 ° c ., indicating that scy - 078 citrate type q is thermodynamically more stable in etoh from 5 ° c . to 20 ° c . xrpd analysis of the remaining wet cakes from the solubility experiments showed no form change for both scy - 078 citrate type q and scy - 078 citrate type n . scy - 078 citrate type r : scy - 078 citrate type r was obtained by slurrying scy - 078 citrate type m in meoh / ipac ( 1 / 14 , v / v ) for 17 hours . scy - 078 citrate type r can also be obtained by reverse anti - solvent addition in meoh / ipac . the xrpd pattern indicated that scy - 078 citrate type r is weakly crystalline ( fig6 ). xrpd analysis also indicated that scy - 078 citrate type r is a metastable solvate that can easily convert to scy - 078 citrate type s upon air drying and to scy - 078 citrate type m after vacuum drying ( fig6 ). scy - 078 citrate type s : scy - 078 citrate type s can be obtained by drying scy - 078 citrate type o sample under ambient or vacuum condition . the xrpd patterns showed shift of diffraction peaks after conversion from scy - 078 citrate type o to scy - 078 citrate type s ( fig6 ). dsc curve exhibited two endothermic peaks at 35 . 7 ° c . and 188 . 0 ° c . ( onset temperatures ) ( fig6 ). tga curve displayed 6 . 6 % weight loss up to 100 ° c . ( fig6 ). dvs plot showed 8 . 2 % water uptake at 25 ° c . and 80 % rh for scy - 078 citrate type s ( fig7 ). xrpd analysis after dvs showed peak shifts . xrpd analysis was further performed at variable temperatures 30 ° c . to 120 ° c . and back to 40 ° c ., which showed a shift of diffraction peaks ( fig7 ). disproportionation of scy - 078 citrate salt : crystalline forms of scy - 078 citrate named type c , type i , type j , and type p were observed either during polymorph study or when investigating the inter - conversion relationship of different scy - 078 citrate forms . xrpd patterns of the four forms ( fig7 ) demonstrated that scy - 078 citrate type c and scy - 078 citrate type j are freebase forms and that scy - 078 citrate type i and scy - 078 citrate type p are likely freebase forms . scy - 078 citrate type i was obtained in dmso / etoh system . scy - 078 citrate type p was obtained by slurrying scy - 078 citrate type m in acetone / h 2 o system . scy - 078 citrate type a disproportionated to the freebase ( scy - 078 citrate type c , which converts to scy - 078 citrate type j upon drying ) when slurrying in etoh / h 2 o , acetone / h 2 o , and buoh / h 2 o systems . slurrying scy - 078 citrate type a or evaporating the citrate solution in dmso , dmac and dcm - related co - solvents also resulted in disproportionation . inter - conversion between scy - 078 citrate type a and citrate type b : slurry experiments were performed with scy - 078 citrate type a in different organic solvents in order to understand the inter - conversion between scy - 078 citrate type a and scy - 078 citrate type b . scy - 078 citrate type a (- 20 mg ) was suspended into a solvent ( 0 . 5 ml ) in a 1 . 5 - ml glass vial . after the suspensions were ultrasonicated for 1 hour or stirred for 6 hours at room temperature , the remaining solids were isolated for xrpd analysis . the results ( table 35 ) indicated that scy - 078 citrate type b can be obtained from various organic solvents . scy - 078 citrate type b was also prepared from scy - 078 citrate type a by slurry in etoh , acn , acetone , mibk , etoac , ipac , dcm , toluene , heptane , meoh / acetone ( 1 / 19 ), ipa / heptane ( 1 / 19 ), thf / toluene ( 1 / 19 ) or by solid vapor diffusion in etoac . scy - 078 citrate type b can convert to scy - 078 citrate type a via drying under n 2 or vacuum at room temperature . inter - conversion between scy - 078 citrate type a and scy - 078 citrate type n and scy - 078 citrate type q : scy - 078 citrate type n can be obtained by slurrying scy - 078 citrate type a ( or scy - 078 citrate type b ) in etoh with ultrasonication or at room temperature for 1 hour . scy - 078 citrate type n rapidly converts to scy - 078 citrate type a via vacuum filtration ( fig7 ). scy - 078 citrate type q was obtained by reactive crystallization of freebase meoh desolvate and citric acid ( 1 : 1 ) in etoh without seeds . after drying in vacuum at room temperature , scy - 078 citrate type q converts to scy - 078 citrate type a ( fig7 ). the study of the inter - conversion between scy - 078 citrate type a and scy - 078 citrate type n and scy - 078 citrate type q is summarized below in table 36 . inter - conversion relationship around channel hydrate scy - 078 citrate type m : metastable solvate scy - 078 citrate type r was obtained by reverse anti - solvent addition in meoh / ipac . scy - 078 citrate type r converted to scy - 078 citrate type e after drying in vacuum at room temperature , and then scy - 078 citrate type m was obtained by storing scy - 078 citrate type e under ambient conditions for 2 days ( fig7 ). scy - 078 citrate type r was found to convert to scy - 078 citrate type m directly upon vacuum drying at room temperature . slurry experiments were performed on scy - 078 citrate type m in selected organic solvents . the results ( table 37 ) indicated that scy - 078 citrate type m converted to scy - 078 citrate type 0 after slurrying in acetone for 17 hours , and scy - 078 citrate type 0 converted to scy - 078 citrate type s after air drying ( fig7 ). scy - 078 citrate type m converted to scy - 078 citrate type a when slurried in acn ( fig7 ), and converted to metastable solvate scy - 078 citrate type r in meoh / ipac co - solvent ( fig7 ). scy - 078 citrate type r converted to scy - 078 citrate type s upon air drying and converted back to scy - 078 citrate type m through vacuum drying at room temperature . no form change was observed by slurrying scy - 078 citrate type m in heptane ( fig7 ). stability study of scy - 078 citrate type a , scy - 078 citrate type m , and scy - 078 citrate type s : as described in example 25 and table 19 , scy - 078 citrate type a is physically / chemically stable at the tested conditions for at least 1 week . to test the physical and chemical stability of scy - 078 citrate type m and scy - 078 citrate type s , each was placed under three different conditions : ( 1 ) open dish at 25 ° c . with 60 % rh ; ( 2 ) open dish at 40 ° c . with 75 % rh ; and ( 3 ) closed dish at 60 ° c . with no humidity control . scy - 078 citrate type m was tested for 4 days and scy - 078 citrate type s was tested for 1 week ( fig8 - 81 ). the results ( table 38 ) showed that scy - 078 citrate type m was physically and chemically stable at 25 ° c . and 60 % rh for at least 4 days . one diffraction peak change and partial crystallinity loss was observed in the xrpd pattern of scy - 078 citrate type m after storage at 40 ° c . and 75 % rh . this is consistent with the previous observation in example 42 that scy - 078 citrate type m partially converts to amorphous after dvs analysis . the impurity of scy - 078 citrate type m increased under closed conditions at 60 ° c . for 4 days . scy - 078 citrate type s is physically and chemically stable under 60 ° c . closed conditions for one week . diffraction peak shifts were observed for the samples stored at 25 ° c . and 60 % rh and 40 ° c . and 75 % rh . alternative preparation of scy - 078 citrate type a : a 10 - l reactor was charged with scy - 078 phosphate ( 450 g ; freebase content in phosphate was 85 . 6 % by hplc ). 2 - methf ( 2 . 25 l ) was charged into the same reactor . a 10 % na 2 co 3 water solution ( 2 . 25 l ) at 20 ° c . was charged into the reaction in 25 min . the suspension was stirred at 20 ° c . for 20 min and then allowed to settle for 30 min . the organic layer was collected and washed with 1 . 8 l of saturated nacl water solution twice , and then further washed with 1 . 8 l deionized water once . the organic layer was transferred to a 4 - l crystallizer . the reactor was rinsed with 250 ml 2 - methf and the liquid was transferred into the crystallizer containing the organic layer . the solution was concentrated in the crystallizer to 900 ml at 50 ° c . the crystallizer was charged with 900 ml methanol and the mixture was cooled to 40 ° c . the mixture was stirred at 40 ° c . for 1 hour ( clear ). 4 . 5 g of seeds were added to the crystallizer and the suspension was aged at 40 ° c . for 1 hour . the mixture was then concentrated to 900 ml at 40 ° c . the crystallizer was then charged with 900 ml methanol and again concentrated to 900 ml at 40 ° c . this step was repeated twice more and the mother liquor was assayed by gas chromatography . the mixture was cooled to 10 ° c . in 2 hours and then aged at 10 ° c . for no less than three hours . the mother liquor was sampled for solution concentration by hplc . the suspension was filtered and the cake was dried in a vacuum over at 35 ° c . for 12 hours . to generate the citrate salt , a 10 - l jacketed crystallizer with a twin - impeller over - head agitator was used . the diameter of the impeller is 13 cm . first , etoh ( 500 ml ) was added into a 10 - l crystallizer ( crystallizer 1 ) and was agitated ( 300 rpm ). the temperature of crystallizer 1 was maintained at 25 ° c . the scy - 078 freebase ( 242 . 09 g ) was added to crystallizer 1 . another volume of etoh ( 500 ml ) was charged into crystallizer 1 . crystallizer 1 was heated to 50 ° c . a citric acid solution , prepared by dissolving citric acid ( 58 . 22 g ) into etoh ( 758 ml ), was charged into crystallizer 1 in 35 min . crystallizer 1 was heated to 55 ° c . and stirred for 20 minutes . then crystallizer 1 was cooled to 50 ° c . for 20 minutes . after cooling , the extraneous matter was filtered ( pore size of 30 ˜ 50 μm ) and the filtrate was transferred to another 10 - l crystallizer ( crystallizer 2 ). the filter was washed with etoh ( 5 ml ) and transferred into crystallizer 2 . the mixture in crystallizer 2 was stirred at 50 ° c . for 30 minutes . next a seed slurry , which was prepared from seeds ( 13 . 22 g ) that were sonicated and dispersed in 50 / 50 etoh / n - heptane ( 68 ml ), was rapidly charged into crystallizer 2 . the mixture in crystallizer 2 was aged at 50 ° c . for 2 hours . crystallizer 2 was then charged with n - heptane ( 1758 ml ) for 12 hours at 50 ° c . the mixture was again aged at 50 ° c . for 2 hours . from the resulting mixture , a sample was taken for xrpd analysis and microscopy . the mixture was cooled to 20 ° c . in 2 hours and then stirred at 20 ° c . for 3 hours . the batch was filtered and the cake was washed with a solution of 1 : 1 etoh / n - heptune ( 500 ml ). the cake was blown with n 2 for 60 minutes . finally , the cake was dried at 45 - 55 ° c . with n 2 blowing . ultimately 241 grams of product was obtained with a 86 . 4 % yield . xrpd analysis showed that the product was highly crystalline scy - 078 citrate type a ( fig8 ). tga curve showed a weight loss of 2 . 2 % before 150 ° c . ( fig8 ). the dsc curve showed a melting point of 197 . 8 ° c . ( onset temperature ) ( fig8 ). the resulting crystals were rod - like with an average size of 34 . 2 pm ( fig8 ). preparation and characterization of scy - 078 trifluoroacetate type a : scy - 078 amorphous freebase ( 994 . 3 mg ) and trifluoroacetic acid ( freebase / acid molar ratio — 1 / 1 ) were weighted into a 5 - ml vial , followed by addition of 5 ml acetonitrile . the mixture was slurried at rt with a magnetic stirring rate of 1000 rpm for 4 days . the suspension was centrifuged and vacuum dried at rt overnight . scy - 078 trifluoroacetate type a is highly crystalline as shown in the xrpd ( fig8 ). a weight loss of 1 . 1 % is observed up to 120 ° c . in the tga curve ( fig8 ). the dsc ( fig8 ) shows two endothermic peaks , one at 65 . 8 ° c . and 229 . 8 ° c . trifluoroacetate type a converted to type b after stored under ambient conditions for 2 days ( fig8 ). the molar ratio of trifluoroacetate type a ( acid : freebase ) was determined to be 1 : 1 via hplc - ic confirmation . preparation and characterization of scy - 078 trifluoroacetate type b : trifluoroacetic acid ( 331 . 5 mg ) was added into acetonitrile ( 8 ml ) in a 20 - ml glass vial , followed by addition of amorphous scy - 078 freebase type a ( freebase / acid molar ratio = 1 / 1 ). the mixture was stirred at rt with a magnetic stirring rate of 600 rpm for 24 hours . the suspension was vacuum filtered and dried at rt for 20 hours . trifluoroacetate type a was obtained ( 2 . 18 g ), which converted to trifluoroacetate type b after storage at ambient conditions for almost 1 month . scy - 078 trifluoroacetate type b is highly crystalline as shown in the xrpd ( fig8 ). a weight loss of 4 . 7 % is observed up to 120 ° c . in the tga curve ( fig8 ). the dsc ( fig8 ) shows two endothermic peaks , one at 92 . 8 ° c . and 230 . 0 ° c . due to the reversible conversation of trifluoroacetate type a and type b , the molar ratio of trifluoroacetate type b ( acid : freebase ) is postulated to be 1 : 1 , same as type a . from the dvs ( fig9 ), 3 . 4 wt % of water uptake was observed at 25 ° c . 80 % rh , indicating that type b is moderately hygroscopic . the dvs revealed potential form change with respect to rh , estimated to be between 30 % rh and 40 % rh . scy - 078 trifluoroacetate type b converted to type a after dvs as shown in fig9 . to investigate transition relationship of trifluoroacetate type a and type b , both samples were stored in chambers with varying relative humidity to monitor any form change . summary of trifluoroacetate type b stored at varying relative humidity is listed in table 39 , and xrpd patterns overlay is displayed in fig9 . trifluoroacetate type b converted to type a only at high relative humidity ( 97 % rh ) while type b is stable at low relative humidity (& lt ; 22 % rh ). varying temperature ( vt )- xrpd of trifluoroacetate type a was performed . vt - xrpd patterns overlay is displayed in fig9 . type a converted to type b after heated to 120 ° c . preparation and characterization of scy - 078 hcl type i : 342 . 7 μl of concentrated hcl ( 37 . 5 %) was dispersed in 40 ml of acetone . 2 . 0 mg of scy - 078 freebase type a ( freebase / acid molar ratio = 1 / 1 . 5 ) was added . the suspension was settled in a biochemical incubator to perform heat - cooling cycles ( 50 ° c .˜ 20 ° c .) with a magnetic stirring rate of 600 rpm . the suspension was cooled to 5 ° c . at a rate of 0 . 1 ° c ./ min and aged at 5 ° c . for 17 hours . the wet cake was vacuum filtered and dried at rt for 20 hours . scy - 078 hcl type i ( 2 . 06 g ) was obtained . scy - 078 hcl type i is highly crystalline as shown in the xrpd ( fig9 ). a weight loss of 4 . 2 % is observed up to 120 ° c . in the tga curve ( fig9 ). the dsc ( fig9 ) shows three endothermic peaks , one at 46 . 2 ° c ., one at 115 . 5 ° c . and one at 274 . 3 ° c . the molar ratio of scy - 078 hcl type i ( acid : freebase ) was determined to be 1 . 5 : 1 via hplc - ic . from the dvs ( fig9 ), 6 . 1 wt % of water uptake was observed at 25 ° c ./ 80 % rh , indicating hcl type i is moderately hygroscopic . no form change was observed after dvs characterization as shown in fig9 . preparation and characterization of scy - 078 hcl type ii : scy - 078 hcl type ii was obtained by suspending hcl type i in acetate buffer ( ph 5 . 5 ) for 4 hours . the xrpd pattern ( fig9 ) indicates type ii is highly crystalline . the tga shows that hcl type ii exhibits a weigh loss of 6 . 9 % up to 150 ° c . and the dsc shows an endothermic peak at 48 . 3 ° c . ( onset temperature ), as shown in fig9 . the solubility of trifluoroacetate type a , type b and hcl type i was measured in sgf at ambient temperature . approximately 90 mg of solid sample was weighted into a 4 - ml centrifuge tube , and 3 ml of sgf buffer was added before leaving the suspension on a rolling incubator ( 25 r / min ). 1 . 0 ml aliquot of the suspension was sampled for centrifugation ( 10000 rpm , 3 mins ) the supernatant was analyzed by hplc and ph measurement and solid by xrpd characterization at 1 hr , 4 hr and 24 hrs , respectively . the results are summarized in table 40 and the solubility curves are displayed in fig1 . all three salts exhibit high solubility in sgf (& gt ; 20 mg / ml at 24 hrs ). trifluoroacetate type b converted to type a in sgf after an hour . however , no form change was observed of trifluoroacetate type a and hcl type i in sgf . the xrpd patterns of residual solid are shown in fig1 , fig1 , and fig1 . the solubility of trifluoroacetate type a , type b and hydrochloride type i was measured in the fassif alternative media at ambient temperature . approximately 15 mg of solid sample was weighted into a 4 - ml plastic tube , and 3 ml of the media was added before leaving the suspension on a rolling incubator ( 25 r / min ). 1 . 0 ml aliquot of the suspension was sampled for centrifugation with the supernatant submitted for hplc and ph measurement and solid for xrpd characterization at 1 hr , 4 hr and 24 hrs , respectively . the results are summarized in table 41 and the solubility curves are displayed in fig1 . all three salts exhibit poor solubility in the fassif alternative media (& lt ; 0 . 01 mg / ml at 24the kinetic hrs ). trifluoroacetate type b converted to type a after an hour . however , no form change was observed of trifluoroacetate type a and hcl type i . the xrpd patterns of residual solid are shown in fig1 , fig1 , and fig1 . the solubility of trifluoroacetate type a , type b and hcl type i was measured in the fessif alternative media at ambient temperature . approximately 36 mg of solid sample was weighted into a 4 - ml plastic tube , and 3 ml of the media was added before leaving the suspension on a rolling incubator ( 25 r / min ). 1 . 0 ml aliquot of the suspension was sampled for centrifugation with the supernatant submitted for hplc and ph measurement and solid for xrpd characterization at 1 hr , 4 hr and 24 hrs , respectively . the results are summarized in table 42 and the solubility curves are displayed in fig1 . all three salts exhibit a solubility of ˜ 3 mg / ml at first one hour . hcl type i exhibits an equilibrium solubility of 3 . 5 mg / ml at 24 hrs , while trifluoroacetate ( both type a and type b ) exhibit a decreasing solubility after an hour . trifluoroacetate type a converted to type b after an hour . however , no form change was observed of trifluoroacetate type b and hydrochloride type i . the xrpd patterns of residual solid were included in fig1 , fig1 , and fig1 . the solubility of trifluoroacetate type a , type b and hcl type i was measured in acetate buffer ( ph 5 . 5 ) at ambient temperature . approximately 15 mg of solid sample was weighted into a 4 - ml plastic tube , and 3 ml of acetate ph 5 . 5 buffer was added before leaving the suspension on a rolling incubator ( 25 r / min ). 1 . 0 ml aliquot of the suspension was sampled for centrifugation with the supernatant submitted for hplc and ph measurement and solid for xrpd characterization at 4 hr and 24 hrs , respectively . the results are summarized in table 43 and the solubility curves are displayed in fig1 . trifluoroacetate type a exhibits higher solubility in acetate ph 5 . 5 buffer , and no form change was observed . however , type b converted to type a in acetate ph 5 . 5 buffer . while hcl type i exhibits lower solubility in acetate ph 5 . 5 buffer comparing with trifluoroacetate , and hcl type i converted to type ii in acetate ph 5 . 5 buffer . the xrpd patterns of residual solid were included in fig1 , fig1 , and fig1 . the solubility of trifluoroacetate type a , type b and hcl type i was measured in the phosphate ( ph 6 . 0 ) alternative media at ambient temperature . approximately 15 mg of solid sample was weighted into a 4 - ml plastic tube , and 3 ml of media was added before leaving the suspension on a rolling incubator ( 25 r / min ). 1 . 0 ml aliquot of the suspension was sampled for centrifugation with the supernatant for hplc and ph measurement and solid for xrpd characterization at 4 hr and 24 hrs , respectively . the results are summarized in table 44 , and the solubility curves are displayed in fig1 . hcl type i exhibits higher solubility , while trifluoroacetate type a exhibits lower solubility . trifluoroacetate type a firstly converted to type b at 4 hrs and back to type a at 24 hrs , while type b converted to type a at 24 hrs . no form change was observed of hcl type i . the xrpd patterns of residual solid were included in fig1 , fig1 , and fig1 . physical and chemical stability evaluation of trifluoroacetate type a , trifluoroacetate type b , and hcl type i was performed at 25 ° c ./ 60 % rh , 40 ° c ./ 75 % rh and 60 ° c . for 1 , 2 , 4 and 8 weeks . in the experiments , approximately 20 mg of solid was placed into a 1 . 5 - ml glass vial . the vials were stored under 25 ° c ./ 60 % rh ( uncapped ), 40 ° c ./ 75 % rh ( uncapped ) and 60 ° c . ( capped ) conditions for 8 weeks . xrpd analysis was then employed to check the crystalline form of the solid , and hplc was utilized to determine the purity profile at 1 , 2 , 4 and 8 weeks . from the stability results summarized in table 45 , both trifluoroacetate type a and hcl type i are physically and chemically stable under 25 ° c ./ 60 % rh , 40 ° c ./ 75 % rh and 60 ° c . conditions for 8 weeks . the solid form change of trifluoroacetate type a at 2 and 4 weeks was postulated to the air - exposure when the sample was taken out for xrpd characterization . trifluoroacetate type b is chemically stable , however , physically unstable evidenced by conversion to type a under these conditions . xrpd patterns overlay of trifluoroacetate types a and b and hcl type i at stressed conditions are displayed from fig1 to fig1 .
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as conducive to a full understanding of the novelty and utility of the present invention , one example of a conventional valve device will first be briefly described with reference to fig1 . throughout the following description of the known valve device and the valve device according to the present invention , directions indicated by terms such as &# 34 ; upper &# 34 ;, &# 34 ; lower &# 34 ;, &# 34 ; above &# 34 ;, and &# 34 ; below &# 34 ; are those as viewed in the figures of the accompanying drawings . this known valve device 10 , which is a gate valve of the so - called outside screw yoke type , has a housing structure comprising a valve casing or body 11 and bonnet 12 fixed together , with a gasket 13 interposed therebetween , by screws 14 . centrally disposed partly within the body 11 and extending and beyond the bonnet 12 is a valve stem 15 . this stem 15 has a lower sliding part with a smooth outer surface and an upper screw - threaded part 20 . an annular gland packing 16 is fitted between the sliding part of the stem 15 and the upper part of the bonnet 12 in order to prevent leakage therebetween . the gland packing 16 is held in place by an annular packing retainer 17 , which in turn is pressed downward against the gland packing 16 by fixing bolts 18 . the stem 15 is connected at its inner end to a valve element , which in the example shown , is a gate 21 . a handle or handwheel 19 is screw engaged with the upper threaded part 20 of the stem 15 . by rotating the handwheel 19 the stem 15 can be raised or lowered together with the gate 21 thereby to open or shut the valve . in the valve device 10 of the above described construction , exchanging of the packing 16 is possible without removing the bonnet 12 , that is , with the valve in opened state , by loosening the fixing bolts 18 , swinging the same outward , and moving the packing retainer 17 upward . however , in order to replace the gasket 13 , it is necessary to remove the bonnet 12 . consequently , it is necessary to stop the flow of the fluid in the piping by shutting separate shut - off valves ( not shown ) provided in the piping on the upstream and downstream sides of the valve device 10 . as a result , at the time of replacement of the sealing members , it is necessary to temporarily stop the operation of the equipment in which the valve device 10 is installed , whereby this valve device 10 cannot be applied in equipment of continuous operation the interruption of which is undesirable . furthermore , in the above described valve device 10 , the assembly and attachment of the various parts with respect to the body 12 is complicated . moreover , the packing retainer 17 and related parts cannot be drawn out from the stem 15 , and an ample working space cannot be obtained . for this reason , the work of replacing the sealing members is troublesome and requires excessive time . thus , this valve device 10 is unsuitable for use in equipment handling fluids contaminated with radiation as , for example , the aforementioned equipment in a nuclear power plant . accordingly , it is contemplated in the present invention to provide a valve of a construction such that the work of periodically replacing its sealing members can be carried out with the rest of the equipment in continuous operation and , moreover , in a short time . in a first embodiment of the invention as illustrated in fig2 and 3 , a valve device 30 , which is of the inside screw type construction , comprises essentially a valve body 31 , a bonnet 32 fixed to the body 31 , a valve stem 33 , and a stem holding member 34 constituting an essential element of the present invention for holding the stem 33 in a screw - engaged manner . the body 31 is provided therein with a fluid flow passage 35 comprising a inflow passage 35a and an outflow passage 35b and a stem insertion bore 36 having a bottom and formed with a centerline axis intersecting substantially perpendicularly that of the flow passage 35 at the middle part thereof . a cylindrical valve seat 37 is provided at the part where the stem insertion bore 36 intersects the flow passage 35 . a valve element 38 , which is a wedge - shaped gate connected to the lower end of the stem 33 , is moved up or down together with the stem 33 to be separated from or seated against the valve seat 37 thereby to open or shut the flow passage 35 . the stem 33 can be rotated about its axis by turning a handwheel 39 fixed to its outer or upper end . the stem 33 is provided around a portion thereof somewhat above its lower end with square screw threads 33a . the aforementioned stem holding member 34 is generally of the shape of a hollow cylinder coaxially disposed around the stem 33 and having at its upper portion internal screw threads 34c meshed with the above mentioned screw threads 33a of the stem 33 . the lower portion of this stem holding member 34 is provided around its outer surface with external screw threads 34c , which are meshed with internal screw threads 36a formed on the wall surface of the above mentioned stem insertion bore 36 at the upper open part of the body 31 . thus the stem holding member 34 is fixed to the body 31 . this screw connection and fixing of the stem holding member 34 is adopted with consideration of work such as replacement of parts such as the valve gate 38 . the stem holding member 34 has at its lower end an annular contact surface 34b which , when this member 34 is fixed in place as described above , is pressed with a specific pressure in abutting state against an annular ledge 36b formed in the wall of the bore 36 , thereby being in a metal - contact state . in this case , the annular contact surface 34b and the annular ledge 36b are both precision finished to exact planar surfaces and thereby constitute a first metal - contact seal 40 . this first metal - contact seal 40 is continually in sealing state while the stem holding member 34 is fixed in position . the inner wall surface of the stem holding member 34 at the lower end of the internal screw threads 34c is increased in inner diameter , whereby a downwardly facing ledge is formed . the inner rim of this ledge is chamfered to form a bevel seat surface 34d to function as described hereinafter . the lower surface of the bonnet 32 is fixed by screws 42 to the upper surface of the body 31 with a spiral gasket 41 interposed therebetween . at the upper part of the bonnet 32 , a packing 43 of the shape of a hollow cylinder is fitted between the inner wall of the bonnet and the stem 33 and is held in place by a packing retainer 45 , which in turn is pressed downward against the packing 43 by a cap nut 44 screw engaged with the upper part of the bonnet 32 . when the handwheel 39 of the valve device 30 of the above described construction is turned , and the valve gate 38 is lifted off from the valve seat 37 to its fully - opened state , the fluid ( not shown ) in the piping flows into the flow passage 35 . in this valve device 30 , the bonnet 32 is of a double - seal construction afforded by the first metal - contact seal 40 serving as a first - stage barrier and the gasket 41 and the packing 43 serving as a second - stage barrier . in addition , the passage of infiltration of the fluid into a space 46 in the interior of the bonnet 32 and around the stem 33 is limited to only the meshing part 47 between the screw threads 33a and 34c , and the rate of infiltration of the fluid into the space 46 is very low . moreover , the pressure of the fluid infiltrating into the space 46 becomes low . for these reasons , the capability of the valve device 30 to prevent leakage of the fluid to the outside is markedly superior to that of the known valve device 10 . accordingly , this valve device 30 of the invention is highly suitable for use in places where fluids in piping must positively be prevented from leaking to the outside . furthermore , when the meshing part 47 of the screw threads 33a and 34c is made to be a very narrow flow passage , it acts to cushion the transmission of pressure therethrough . for this reason , the pressure of the fluid within the flow passage 35 does not act directly on the gasket 41 . as a result , the serviceable life of the gasket 41 is prolonged , and the period between replacements is lengthened . next , the procedure of replacing the packing 43 and the gasket 41 of this valve device 30 will be described with reference to fig3 . this replacement of exchanging of these sealing members is carried out as described below with the valve device 30 in its opened state without shutting off the flow of the fluid through the piping including the valve device 30 . first , the handwheel 39 is turned in the valve opening direction to cause the stem 33 to reach the upper limiting position of its movement . when the stem 33 thus reaches this limiting position , the rotation of the handwheel 39 is limited . at this instant , however , the handwheel 39 is not immediately released from the turning manipulation , but a specific torque in the valve opening direction is further applied thereto , after which the handwheel manipulation is stopped . by this handwheel manipulation , the annular edge part 33b - 1 of a flange part 33b of the stem 33 near the lower end thereof is brought into a state wherein it is pressed with a specific pressure into contact against the aforementioned chamfered seat surface 34d of the stem holding member 34 . these parts thus form a second metal - contact seal 48 , which seals the screw meshing part 47 . as a result of the functioning of the first and second metal - contact seals 40 and 48 , the space 46 is placed in a state wherein it is completely sealed off from the flow passage 35 , and the fluid in the flow passage 35 cannot leak out even when the bonnet 32 is disconnected and removed from the body 31 . to replace the replaceable sealing members , the handwheel 39 is first detached from the stem 33 , this detaching being possible because this valve device 30 is of the inside - screw type . next , the nut 44 is unscrewed off , and the packing 43 is extracted upward . the screws 42 are then unscrewed and removed , and the bonnet 32 is lifted straight upward , away from the body 31 , until it is free of the stem 33 . with the valve parts in this disassembled state , the gasket 41 and the packing 43 can be readily replaced . the disassembled valve parts are thereafter reassembled in the sequence which is reverse to that described above for disassembly . in this case , the work of replacing the sealing members can be carried out efficiently in a short time because the bonnet 32 can be handled as a single unitary structure . this feature is highly important in positively protecting the human body from harmful effects in hazardous environments such as that involving nuclear radiation . furthermore , this valve device 30 affords great safety because there is little possibility of leakage of the fluid to the outside at the time of replacement of the sealing members . since , as described above , the work of replacing the sealing members can be carried out while the valve device 30 is opened , that is , with the equipment in which the valve is installed in operation , the valve device 30 is highly suitable for use in the equipment of such facilities as nuclear power plants , facilities handling petroleum products , and city gas supplying facilities . if , in the machining of the stem 33 , the above described annular edge 33b - 1 of the flange part 33b is rounded with a radius of curvature of the order of 0 . 1 mm ., galling or scoring of the chamfered surface 34d of stem holding member 34 and damaging of the annular edge can be effectively prevented , and the metal - contact seal 48 will function with a positive sealing effect . furthermore , even when the valve device 30 is in its fully shut state , the space 46 is in a state wherein it is positively sealed from the flow passage 35 . for this reason , replacement of the sealing members can be carried out also in the fully - shut state of the valve . a second embodiment of the valve of the invention will now be described with reference to fig4 . in fig4 those structural parts which are essentially the same as corresponding parts in fig2 are designated by like reference numerals . detailed description of such parts will be omitted . a valve device 50 of the invention has a construction which is fundamentally the same as that of the aforedescribed valve device 30 and employs o - rings for its replaceable sealing members . this valve device 50 is suitabe for use in equipment handling fluids at lower temperatures than those in the case of the aforedescribed valve device 30 . in this valve device 50 , an o - ring 51 is interposed between the bonnet 32 and the body 31 . in the bonnet 32 , a ring 52 comprising a combination of an o - ring and a back - up ring is fitted in an annular recess formed in the inner surface of a through bore 32a through which the stem 33 is passed at the upper part of the bonnet . the replacement of the o - ring 51 and the ring 52 can be carried out rapidly , similarly as in the case of the aforedescribed valve device 30 . because of this sealing arrangement wherein use is made of the combined ring 52 as the sealing member in the through bore 32a of the bonnet 32 in this valve device 50 , the force needed to turn the handwheel 39 is less than that in the case of the valve device 30 in which a gland packing is used . the reason for this is that the gland packing is being pressed by the packing retainer in order to assure its sealing performance , and consequently this increases the resistance to rotation of the handwheel . in the valve device 50 , furthermore , there is little possibility of rusting of the stem 33 which tends to occur when a gland packing is used because of the halogen compounds contained in the asbestos , which is the principal constituent of the gland packing . in the case where the above described valve devices 30 and 50 are to used in nuclear power equipment , both the stem 33 and the stem holding member 34 are made of austenitic stainless steel in consideration of their corrosion resistance . for this reason , the screw meshing part 47 becomes a combination of parts of the same material , whereby galling or scoring would readily occur . accordingly , in the present embodiment of the invention , the threaded part 33a of the stem is roll threaded thereby to increase the surface hardness thereof ( for example , to a surface hardness of h r c 50 ). by this measure , a difference in hardness is established between the meshing screw thread parts 33a and 34c , and galling is suppressed . examples of modification of the second metal - contact seal 48 in the above described valve devices 30 and 50 will now be described with reference to fig5 , and 7 . in these figures , those constituent parts which are the same or equivalently similar to corresponding parts in fig3 are designated by like reference numerals . referring first to fig5 showing a first modification , the flange part 61 of this metal - contact seal 60 has a stellite - filled construction comprising a main body part 61a and a peripheral stellite - filled part 61b . the stellite - filled part 61b in the flange part 61 has an annular edge part 61b - 1 which is pressed against the chamfered seat surface 34d of the stem holding member 34 thereby to form the metal - contact seal 60 . in this case , since there is a difference between the hardnesses of the stellite - filled part 61b and the seat surface 34d , galling does not readily occur . furthermore , if the annular edge part 61b - 1 is rounded , galling and chipping of the contacting parts can be prevented with even greater effectiveness . a second modification of the second metal - contact seal 48 is illustrated in fig6 . in this metal - contact seal 70 , the stem holding member 34 has a ledge - like annular planar surface 34e formed therein instead of the annular chamfered seat surface 34d . an upwardly facing planar surface 33b - 2 of the flange part 33b of the stem 33 is adapted to be abuttingly pressed against this downwardly facing annular planar surface 34e . in this construction , the tendency for galling to occur is less , and , moreover , the machining is easier , than in the case of the metal - contact seal 48 shown in fig3 . fig7 illustrates a third modification . in this metal - contact seal 80 , a downwardly directed annular projection 34f is formed in the stem holding member 34 in place of the annular chamfered seat surface 34d , and the upwardly facing planar surface 33b - 2 of the flange part 33b of the stem 33 is adapted to be abuttingly pressed against the lower planar surface 34f - 1 of this annular projection 34f with a margin of a width d left around the periphery . by this construction , a metal - contact seal can be obtained with a uniform width around the entire periphery thereof even when the centerline axes of the stem 33 and its flange part 33c are out of alinement .
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the following description provides embodiments of apparatus that provide protection for building subject to events that increase the load on conduit hangers . specifically , methods and apparatuses for supporting conduits using frangible hanger assemblies are described . such methods and apparatus allow the conduit hanger to fail before the buildings to which they are attached . fig2 a is an elevational view of a first embodiment conduit hanger assembly 30 installed to support conduit 12 from concrete deck 14 . conduit hanger assembly 30 includes anchor 16 which may be placed within concrete deck 14 . anchor 16 can , in general , be a drill - in , shoot - in or glue - in type anchor for attaching to poured concrete or a cast - in - place type anchorage that is set into the concrete during pouring . anchor 16 is attached to a first threaded rod 21 that extends downwards from the anchor , and a connector assembly 32 attached to the first threaded rod and which supports bracket 18 . more specifically , connector assembly 32 includes a connector link assembly 40 threadable into first threaded rod 21 and threaded rod 22 and threaded nuts 26 which are used to support bracket 18 . connector link assembly 40 and the various embodiments and combinations described here function as a tension component for supporting conduits up to some maximum load . when the maximum load is exceeded , the connector link assembly 40 , which is frangible breaks . in certain embodiments , the connector link assembly 40 breaks by a ductile fracture . this invention facilitates the design of utility hanger assemblies and the like so that in the serial chain of components supporting a load , the link assembly will meet the load requirements and be the first to fail in an overload condition . connector link assembly 40 , as discussed subsequently in greater detail , includes a connector piece 42 having a first end 421 and a second end 423 , and a pair of connector links shown as an upper link 44 a having a first end 441 a and a second end 443 a , and a lower link 44 b having a first end 441 b and a second end 443 b . first end 441 a has internal threads and is threadably connected to threaded rod 21 and second end 443 a is attached to first end 421 using fastener ( s ) 53 . first end 441 b has internal threads and is threadably connected to threaded rod 22 and second end 443 b is attached to second end 423 using fastener ( s ) 51 , as discussed subsequently . conduit hanger assembly 30 is designed to be able to hold the load of conduit 12 from concrete deck 14 and , in the case of a sufficiently large tensile force , fail before the concrete fails . in this way , conduit hanger assembly 30 does not damage the integrity of concrete deck 14 . in certain embodiments , connector link assembly 40 undergoes testing to determine the maximum load that it may support in a seismic event . the actual tests may vary according to local building codes . in general , one may determine a maximum permissible load for any configuration of connector link assembly 40 by , for example , seismic testing . thus , in one embodiment , connector piece 42 is frangible and , specifically , is designed to be the weakest part of conduit hanger assembly 30 under tension . fig2 b is the view of fig2 a , where connector piece 42 is subjected to a sufficient force to fail before the concrete deck fails . the inventive conduit hanger assembly 30 thus fails with a break in connector piece 42 , leaving anchor 16 , threaded rod 21 , and upper link 44 a attached to concrete deck 14 . this is in contrast to the prior art conduit hanger assembly , as shown in prior art fig1 b . the failure of connector piece 42 near upper connector link 44 a is illustrative , and the failure mode of conduit hanger assembly 30 may be at some other place in the conduit hanger assembly , such as in connector piece 42 near lower connect link 44 b , some other location in the connector piece , or some other location within the conduit hanger assembly that does not result in damage to concrete deck 14 . in certain embodiments , connector links 44 a and 44 b are identical , and are shown in fig3 a through 3e as one embodiment of a connector link 44 , where fig3 a is a perspective view , fig3 b is a front elevational view , fig3 c is a side elevational view of the connector link of fig3 a , fig3 d is a top plan view , and fig3 e is a bottom plan view . connector link 44 has a first end 4401 , which is generally similar to first ends 441 a and 441 b of fig2 a and a second end 4403 , which is generally similar to second ends 443 a and 443 b of fig2 a . first end 4401 has a bore 49 that is threaded to accept a male threaded rod , stud or bolt , such as a threaded rod 21 or 22 , and two legs 45 defining a narrow gap 46 ( as , for example , second ends 443 a and 443 b of fig2 a ) between the two legs , and transverse holes 47 through legs 45 that align on either side of the gap 46 . while fig3 a , 3b , and 3c show two holes 47 , various embodiments may have one hole or may have three or more holes . first end 4401 also includes an upper portion 48 which is hexagonally shaped along a longitudinal axis to facilitate cooperation with wrenches and tools for engagement and tightening a threaded connection . alternatively , upper portion 48 may be cylindrical , square or other shape depending on the type of connection method . the gap 46 is designed to accept a connector piece , such as connector piece 42 . in certain embodiments , an end of gap 46 provides a seat against which connector piece 42 rests when the connector piece is fully inserted into gap 46 . a pin placed through transverse hole 47 can also pass through a hole in the connector piece 42 , as discussed subsequently , for retaining connector piece 42 . fastener ( s ) 51 and 53 and transverse hole 47 may , in alternative embodiments , be unthreaded , partially threaded , or threaded throughout . in a second embodiment conduit hanger assembly , connector link 44 a and first threaded rod 21 of conduit hanger assembly 30 are replaced with a second embodiment connector link 54 , which combines the function of connector link 44 a and the first threaded rod 21 . fig4 a is a front elevational view of second embodiment connector link 54 , and fig4 b is a side elevational view of the connector link of fig4 b . connector link 54 is generally similar to connector link 44 and first threaded rod 21 , except as explicitly stated . connector link 54 has a first end 5401 and a second end 5403 . first end 5401 includes an integral or attached threaded stud 56 that is threadable into anchor 16 . second end 5403 is generally similar to second end 4403 and supports connector piece 42 . fig6 a is a side elevational view of the connector link of fig4 a and 4b attached to a drill - in type anchor 16 . in a third embodiment conduit hanger assembly , connector link 44 a , first threaded rod 21 , and anchor 16 of conduit hanger assembly 30 are replaced with a third embodiment connector link 64 , which combines the function of connector link 44 a , the first connector rod , and the anchor . fig5 a is a front elevational view of a third embodiment connector link 64 , and fig5 b is a side elevational view of the connector link . connector link 64 is generally similar to connector link 54 and / or 44 , except as explicitly stated . connector link 64 includes an anchor 66 , at a first connector link end 6401 , and two legs 45 defining a narrow gap 46 at a second connector link end 6403 . anchor 66 of first connector link end 6401 can be anchored directly in the concrete pour of concrete deck 14 , and second connector link end 6403 can support connector piece 42 . fig6 b is a side elevational view of the connector link of fig5 a and 5b cast into a concrete deck 14 . a wide variety of geometries may be used for connector piece 42 . thus , for example and without limitation , fig7 a is a sectional view 7 a - 7 a of fig2 a , where connector piece 42 , is a length of electrical conduit disposed in the gap 46 of the legs 45 legs 45 may which may be , for example and without limitation , the legs of connector link 44 , 54 , or 64 . as further examples of connector piece 42 : fig7 b is similar to fig7 a , where connector piece 42 is a length of pipe 72 ; fig7 c is similar to fig7 a , where connector piece 42 is a length of rectangular tubing 74 ; fig7 d is similar to fig7 a , where connector piece 42 is a length of strut channel 76 ; and fig7 e is similar to fig7 a , where connector piece 42 is a length of an angle piece 78 . fig8 a , 8b , and 8c are illustrative of one method of assembling the pieces of connector assembly 40 using connector piece 42 . fig8 c is a side view of connector piece 42 , and fig8 a and 8c are a front elevation view and side elevational view , respectively , of connector assembly 40 . it will be appreciated that the following description applies , for example and without limitation , to any of the other connector pieces , such as connector piece 42 , 74 , 76 , or 78 . as shown in fig8 c , connector piece 42 has , or is provided with , one or more holes 52 and , as shown in fig8 a and 8b , connector piece 42 is attached to links 44 a and 44 b by placing each end of connector piece 42 is positioned all of the way into gap 46 of each connector link 44 . next , fastener ( s ) 51 and 53 , which may be , for example , one or more fasteners 50 which are self - drilling , self - tapping , standard threaded , pins or rivets . in any case , hole or holes 52 in connector piece 42 are provide to will align with holes 47 in the connector links 44 a / 44 b . in certain embodiments , hole 52 is positioned at a predetermined distance d from first end 421 by pre - drilling the hole . in the embodiments , where hole 52 is not pre - drilled , connection piece 42 may be inserted into gap 46 such that a desired distance d is achieved by advancing the fastener into the connection piece . in certain embodiments , the distance d determines when connection piece 42 fails , as shown in fig2 b . since larger distances d correspond to a higher load before failure , a user may select a distance d that determines when conduit hanger assembly 30 will fail under a tensile load . one example of the desired structural failure of frangible connector piece 42 , which is not meant to limit the scope of the present invention , is illustrated in fig8 c , 9a , and 9b , where fig8 c is a side view of connector piece 42 prior to failure , and fig9 a and 9b are a front elevation view and side elevational view , respectively , of connector assembly 40 after the structural failure of connector piece 42 . regardless of how hole 52 is formed , under a sufficient tensile load , the hole may first elongate as it undergoes ductile fracture , as shown in fig8 d . as the load increases , connector assembly 40 will ultimately fail when the strength of the connector assembly is exceeded , as shown in fig9 a and 9b . in certain embodiments , the maximum load which connector assembly 40 may support is determined by several parameters , which may be , for example , the thickness t of connector piece 40 ( see fig7 a - 7 e ), the material of the connector piece , the distance d between hole 52 and first end 421 , and details of fastener 50 , such as the fastener size and material . thus , as described above , failure loads for specific connector assembly 40 may be determined as a function of the various parameters noted in the previous paragraph ( fastener type , thickness , materials , hole locations and diameters , etc .). the selection of parameters thus provides a calibration indicating the failure of the connector assembly and a user can be provided with configurations which may fail at certain loadings . fig1 a - 10c illustrate a first alternative embodiment of connector link 44 of fig3 a including aperture 82 at upper portion 48 , where fig1 a is a perspective view , fig1 b is a front elevational view , and fig1 c is a side elevational view of the connector link as upper connector link 44 a attached to a concrete anchor 16 . first alternative connector link 44 may , in general , be used as upper link 44 a or lower link 44 b . aperture 82 intersects the bore 49 , and may alternatively continue through the opposite side of upper portion 48 . aperture 82 permits visual inspection of the engagement of anchor 16 threads , as shown in fig1 c . fig1 a - 11c illustrate a second alternative embodiment of connector link 44 of fig3 a including a threaded aperture 82 a , where fig1 a is front elevational view , fig1 b is a top plan view , and fig1 c is a side elevational view of the connector link as upper connector link 44 a attached to concrete anchor 16 . second alternative connector link 44 may , in general , be used as upper link 44 a or lower link 44 b . connector link 44 of fig1 a - 11c is useful for further securing the connector link to anchor 16 . threaded aperture 82 a can accept a threaded fastener 86 that can act as a set - bolt when tightened against a rod inserted into a bore 49 a , which may be threaded or non - threaded . as in the second alternative embodiment link 44 , aperture 82 a may pass through upper portion 48 to bore 49 a , or may pass through the opposite wall . the set - screw arrangement will work well securing non - threaded rods . fig1 a - 12c illustrate the second alternative embodiment connector link 44 of fig1 a with a clevis - type attachment , where fig1 a is a front elevational view , fig1 b is a side elevational view , and fig1 c is a front elevational view of the connector link attached to concrete anchor 16 . fig1 a - 12c show the second alternative embodiment connector link 44 a of fig1 a and a clevis 94 , formed by the combination of a u - shaped bracket 90 , a bolt 88 and a nut 89 pivotally attached to the connector link at aperture 82 . the top of bracket 90 includes an aperture 92 to allow connection to anchor 16 or other components in a hanger assembly . fig1 a , 13b , and 13c are front elevational views of a first , second , and third alternative embodiment of connector assembly 40 . from either calculations or from trial - and - error , the amount of tensile load required for connector piece 42 to fail at that location can be determined , and can be considered to be a calibrated strength of conduit hanger assembly 30 . in the embodiment of fig1 a , there are two fasteners 53 near first end 421 and one fastener 51 located a distance d 1 from second end 423 . with this embodiment , the weakest part of connector piece 42 is between second end 423 and the hole that is at the distance d 1 from the second end . in the embodiment of fig1 b , there is one fasteners 53 located a distance d 2 from first end 421 and two fasteners 51 located near second end 423 . with this embodiment , the weakest part of connector piece 42 is between first end 421 and the hole that is at the distance d 2 from the first end . in the embodiment of fig1 c , there is one fasteners 53 located a distance d 2 from near first end 421 and one fastener 51 located a distance d 3 from second end 423 . for this embodiment , the distances d 2 and d 3 determine the load factor at each end of the connector piece . fig1 a is a side elevational view of any of the connector link assemblies described herein with indicia 100 . thus , for example , connector link assembly 40 of fig1 b is shown with indicia 100 on connector piece 42 . a user may user indicia 100 to align connector piece 42 with end 4403 of upper link 44 a , prior to inserting one fastener 53 . this allows the user to be sure that the proper spacing is provided for fastener 53 . another advantage of indicia 100 is shown in fig1 b , which shows connector link assembly 40 after a seismic event that did not result in the complete failure of connector piece 42 . thus , for example , if there is partial tearing of connector piece 42 , connector link assembly 40 may stretch without breaking . thus , upper link 44 a and lower link 44 b may , as a result of the stretching or tearing of connector piece 42 , move apart by a distance 102 , as a user would clearly see by inspection of the connector piece as shown in fig1 b . an alternative indicia 106 is shown in fig1 a , which is a side elevational view of the connector link assembly 40 with alternative indicia as a sprayed - on contrast such as paint or dye . indicia 106 has the similar benefits as indicia 100 , in that it can be used to align connector link assembly 40 , as in fig1 a . further , as shown in fig1 b , which is a side elevational view of the connector link assembly of fig1 a after a seismic event ( as in fig1 b ), a gap 108 in indicia 106 is easily seen to indicate structural damage to connector piece 42 . the conduit hanger assembly component described herein are easily arranged and adapted to support conduits in a building . typically , the location and run of utilities in a building are only generally specified by the building designers , and installers came decide how to make each hanger for each location . thus , for example , the connector links described herein could be provided to a job site in bulk , and connector link assemblies could be entirely made on - site with commonly available material for connector pieces . as a result , frangible conduit hanger assemblies could be easily constructed in most circumstances for a variety of applications and situations . fig1 , 17 , 18 , 19 , and 20 illustrate a few of the many examples of applications of the inventive frangible members . fig1 is an elevational view of an installed alternative conduit hanger assembly 120 with two connector link assemblies 40 in series . fig1 is an elevational view of an installed other alternative conduit hanger assembly 140 with one link 44 . conduit hanger assembly 130 includes a connector piece 42 that is attached directly to bracket 18 without an intervening lower bracket . fig1 is an elevational view of an installed version of yet another conduit hanger 150 with inventive links 40 as used for supporting ducting 152 . fig1 is an elevational view of an installed version of another conduit hanger 160 as used for supporting a trapeze 152 including several conduits . the following examples are results of tests on several embodiments described herein . specifically , conduit hanger assembly 30 , as in fig2 a and 2b was tested with a ½ inch anchor 16 and for various dimensions of connector piece 42 . it was previously determined that , for a bolt 16 comprising a ½ inch diameter , a trubolt + carbon steel seismic wedge type anchor ( itw commercial construction , glendale heights , ill .) will fail under tension with a load of 8 , 925 lbs . when the bolt has an embedment of 3½ inches into a minimum concrete thickness of 6 inches , the concrete surrounding an embedded bolt will fail at a cracked concrete strength of 5 , 455 lbs . including a factor of safety , which are required by building codes , the maximum load on such an anchor must be less than 2 , 659 lbs . tests were performed on by placing threaded rods 21 and threaded rod 22 of conduit hanger assembly 30 in tension of increasing amounts until the assembly failed . if the conduit hanger assembly 30 fails under a load less than 2 , 659 lbs ., then the conduit hanger assembly can safely be used to support loads without causing failure of the concrete . a number of conduit hanger assemblies 30 , similar to that of fig2 a and 2b were assembled . in each conduit hanger assembly , connector piece 42 was formed from electrical metallic tubing ( emt ) conduit , which is a commonly available thin - walled steel tube having a circular cross section . specifically , tests were conducted with emt conduit sizes of ¾ ″, 1 ″, 1¼ ″, 1½ ″ and 2 ″, with one fastener 53 , which was a ¼ inch screw that was screwed through the conduit wall at a location , d , ⅜ ″ from center of screw hole to cut end of conduit ( see fig8 c ). the test results are presented in table 1 . table 1 shows that each of the assemblies failed with loads less than 2 , 659 lbs ., thus ensuring that the conduit hanger assembly will fail before the concrete near the anchor fails . table 1 also shows that failure load increases with wall thickness , as the 1¼ ″, 1½ ″ and 2 ″ connector pieces all have the same wall thickness and the same load for ductile failure of the connector piece . reference throughout this specification to “ one embodiment ” or “ an embodiment ” means that a particular feature , structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention . thus , appearances of the phrases “ in one embodiment ” or “ in an embodiment ” in various places throughout this specification are not necessarily all referring to the same embodiment . furthermore , the particular features , structures or characteristics may be combined in any suitable manner , as would be apparent to one of ordinary skill in the art from this disclosure , in one or more embodiments . similarly , it should be appreciated that in the above description of exemplary embodiments of the invention , various features of the invention are sometimes grouped together in a single embodiment , figure , or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects . this method of disclosure , however , is not to be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim . rather , as the following claims reflect , inventive aspects lie in less than all features of a single foregoing disclosed embodiment . thus , the claims following the detailed description are hereby expressly incorporated into this detailed description , with each claim standing on its own as a separate embodiment of this invention . further , those skilled in the art will recognize that other and further modifications may be made thereto without departing from the spirit of the invention , and it is intended to claim all such changes and modifications as fall within the scope of the invention .
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referring to fig1 through 5 for illustrating one preferred embodiment , there is shown a tool rack organizer 10 mounted on a vertical support surface 12 , such as a garage or storage wall , and supporting and organizing various articles 14 typically housed therein such as lawn and garden implement , tools and the like . the organizer 10 includes a support bracket assembly 20 supporting an inner or rear arm 22 , a middle arm 24 and an outer or front arm 26 aligned in horizontal rows parallel to the surface 12 . as shown in fig1 and 2 , the organizer has a closed storage position whereat the arms are in vertically aligned , uniformly horizontally transversely spaced relationship . as shown in fig3 the outer arm 26 may be pivoted outwardly to a partially opened position to gain access to the middle arm 24 . as shown in fig4 thereafter the middle arm 24 may pivoted outwardly to a fully opened position to gain access to the articles on the inner arm 22 . the support bracket assembly 20 is attached to the support surface 12 and typically the studs therebehind by suitable threaded fasteners 28 . referring additionally to fig5 the support bracket assembly 20 includes a support plate 30 having a triangular base leg 32 fastened to the surface 12 and a triangular front leg 34 integrally connected and transversely disposed with respect thereto . both legs are provided with mounting holes 36 for attachment to adjacent support surfaces with the fasteners 28 . it will be appreciated that the support bracket assembly 20 may also be corner mounted or along a side wall using the front leg 34 as the mounting surface . moreover , the organizer may be assembled and mounted as a mirror image of the orientation shown in fig1 . a u - shaped mounting bracket 40 is centrally attached to the support plate 30 by suitable means such as weldments . the bracket 40 includes a rectangular horizontal top plate 42 interconnected with a rectangular bottom plate 44 by a rectangular vertical center plate 46 . the inner side of the center plate 46 is forwardly spaced from the base leg 32 to establish therebetween a rectangular slot for receiving the inner end of the rear arm 22 . the outer side of the center plate 46 is spaced inwardly from the outer sides of the plates 42 and 44 for receiving the inner ends of the middle arm 24 and outer arm 26 . the arms 22 , 24 and 26 are formed of rectangular tubing and include a longitudinal series of hook mounting holes 50 on the front and rear walls for supporting conventional peg - board type mounting hooks 51 . the rear arm 22 is formed of a single length of tubing and includes vertically aligned cylindrical bushing 52 at the inner end having a sliding fit within the inner slot in the mounting bracket 40 . a bolt 54 extends through apertures in the plates 42 , 44 and bushings 52 and threaded to nut 56 to fixedly capture the inner end of the rear arm 22 fixedly locating the arm adjacent the surface 12 . the middle arm 24 is formed of a single length of tubing and includes vertically aligned cylindrical bushing 60 at the inner end having a sliding fit within the outer slot in the mounting bracket 30 . a bolt 62 extends through apertures in the outer front edges of the plates 42 , 44 and the bushing 60 and threaded to nut 64 to pivotally support the inner end of the middle arm 24 . the upper end of the bushing 60 includes a detent sector 66 having a series of indents that cooperate with an upper detent ball assembly 68 threaded in a nut in the upper plate 42 to establish detented positions for the middle arm as shown in fig3 and 4 . accordingly , the middle arm is pivotal about a vertical axis 69 ( fig3 and located at the various detent positions the outer arm 26 is generally l - shaped having an outer portion 70 and an inner portion 72 transverse thereto , both formed of rectangular tubing . the outer portion 70 is comparable to the rear and middle arms including the aligned mounting holes 50 . the inner portion 72 includes vertically aligned cylindrical bushing 74 at the inner end having a sliding fit within the outer slot in the mounting bracket 30 . a bolt 76 extends through apertures in the outer front edges of the plates 42 , 44 , aligned with and outward of the apertures for the middle arm , and bushing 74 and threaded to nut 78 to pivotally support the inner end of the middle leg 24 . the lower end of the bushing 74 includes a detent sector 80 having a series of indents that cooperate with an upper detent ball assembly 82 threaded into a nut on the lower plate 44 to establish detented positions for the outer arm as shown in fig3 and 4 . the outer or front arm 26 is thus pivotable about a vertical axis 83 ( fig3 ) through the detented positions . in use , the organizer may be mounted at a convenient location with the arms horizontally aligned . the organizer may be selectively assembled in either left hand or right hand orientations . the mounting hooks may be arrayed on the arms to receive associated articles for storage . the outer and middle arms may be selectively pivoted to separately and selectively present the arm carrying a desired article for storage or removal . after completion , the arms may be returned to the compact closed position . a further embodiment of the invention is shown in fig6 through 12 . therein , fig6 illustrates a tool rack organizer 110 mounted on a vertical surface 112 , such as a garage storage wall , for the compact storage and easy accessibility of a variety of tools and implements of the type commonly used in the maintenance of a household and grounds . for example , the organizer 110 may hold various handled lawn tools , such as hoes and rakes , and home tools , such as hammers and hand tools . it will also be appreciated that the organizer may be beneficially used in connection with businesses and trades in a commercial setting for the storage of equipment used in such pursuits . more particularly , the organizer 110 comprises a rack assembly 120 attached to the wall 112 at a rectangular mounting plate 122 and vertically reinforced by triangulated leg assemblies 124 ( fig8 ). the rack assembly 120 includes a fixed inner support arm 126 , a pair of pivotal middle support arms 134 , and a pair of outer support arms 136 . the arms 134 and 136 are pivotable between the closed position shown in solid lines and the open position shown by dashed lines . the inner arm 126 is an elongated rectangular tube that is attached by suitable means , such as welds , at a rear surface to the front surface of the mounting plate 122 . the rack assembly 120 includes a pair of longitudinally spaced , frontally and outwardly diverging support brackets 128 attached at rear ends to the outer ends of the base arm 126 . each support bracket 128 includes in spaced relation a middle support plate assembly 130 and an outer support plate assembly 132 , respectively pivotally carrying in transversely aligned and parallel spaced relationship arms 134 , 136 . the arms 134 , 136 are connected at inner ends to the support brackets 128 by vertical pin connections 138 and 139 , respectively , with the pin connection 139 lying longitudinally and frontally outward of the pin connection 138 . the rack arms 134 , 136 are disposed in pivotal in non - overlapping , phase opposition for movement between the closed storage position shown in solid lines and the open handling position shown in dashed lines . the side brackets 128 are outwardly inclined with respect to the base arm 126 in the range of about 30 ° to 70 °, to allow full non - interfering pivotal movement between storage and open positions . a divergence around 45 ° to 60 ° is preferred . for compactness , a spacing of about 4 to 12 inches is preferred . the arms 126 , 134 and 136 , and the side brackets 128 are formed of rectangular galvanized steel tubing , or like construction components suitable for the application . the inner arm 126 is attached to the mounting plate 122 by welds 140 . the ends of the inner arm 126 are beveled for attachment to the inner sidewalls of the side brackets 128 . the mounting plate 122 is provided with a longitudinal series of apertures 140 for receiving conventional and suitable fasteners 142 for attaching the organizer 110 at a desired and convenient location on the vertical surface 112 . the front vertical surface of the inner arm 126 is provided with a longitudinal series of attachment holes 144 for receiving conventional mounting hooks 146 for suspending the tools and equipment . suitable hooks may be of the two - leg type used for pegboard applications , in which instance the hole spacing is appropriate for selective , variable location on the inner arm 126 . referring to fig9 and 10 , the side brackets 130 include support arm holder 130 , 132 for pivotally supporting the arms 136 , 136 . each support arm holder includes an upper support plate assembly 150 including a a top plate 152 attached to the top surface of the side bracket 128 and a bottom plate 154 attached to the bottom surface of the side bracket 128 . the top plate 152 and the bottom plate 154 are interconnected at the rear margins by a vertical rear sidewall 156 . the plates 152 , 154 and the sidewall 156 form inwardly and frontally opening pockets for slidably receiving the inner ends of the arms . the plates 152 , 154 and the inner ends of the arms are provided with aligned vertical apertures for receiving the shanks of the pivotal connectors 138 . a suitable connector is an appropriately sized threaded fastener 158 ( fig1 ). to maintain the arms in the desired storage or handling position , as shown in fig9 and 10 , a detent 160 is provided in the bottom plate 154 having a detent head 162 at the top surface thereof . in the closed storage position , the detent head 162 engages the front wall of the arms to resist outer pivoting . in the open handling positions , the detent head 162 engages the rear wall the arms to maintain the extended position . as illustrated , a threaded fastener is a suitable mechanism . the position of the detents may vary to prescribe the desired angularity of the rack arms in the handling position . the inner opposed ends of the arms 134 , 136 are slightly spaced in the closed positions and may be covered with suitable end caps , if desired . the front walls of the arms are provided with a longitudinal series of holes for receiving the aforementioned mounting hooks . referring to fig8 the leg assemblies 124 includes a support strut 170 connected at a lower end to a base plate 172 at bracket 174 and connected at an upper end to the front lower wall of the side bracket 128 at bracket 176 . the base plate 172 is fixedly connected to the support surface 112 by threaded fasteners 178 . the length of the strut 170 may be provided with axial adjustability , for horizontally orienting and structurally supporting the legs 128 in operative position . in use , with the organizer attached at a desired location on the surface 112 , the hooks 144 are attached at desired locations on the support arms for the convenient mounting of the user &# 39 ; s equipment . thereafter , the arms are folded to the closed storage position and disposed in parallel rows . when a desired item is required , the arms are opened as required to gain access and removal , and the opened arms returned to storage positions . the sequence is reversed for return storage of the items . having thus described a presently preferred embodiment of the present invention , it will now be appreciated that the objects of the invention have been fully achieved , and it will be understood by those skilled in the art that many changes in construction and widely differing embodiments and applications of the invention will suggest themselves without departing from the sprit and scope of the present invention . the disclosures and description herein are intended to be illustrative and are not in any sense limiting of the invention , which is defined solely in accordance with the following claims .
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referring now to fig1 - 4 , the interconnection arrangement of the present invention is generally referred to at 10 and is illustrated as installed with pad - mounted gear 12 including an enclosure 14 . in the illustrative configurations of fig1 - 3 , the enclosure 14 of the pad - mounted gear 12 has affixed thereto illustrative modules or assemblies 16 , 18 , 20 , and 22 . in a specific example for purposes of illustrating the application and utility of the present invention , the modules or assemblies 18 , 20 and 22 are switch operators for power operation of switches ( not shown ) within the enclosure 14 . further , the module or assembly 16 is an auxiliary enclosure that houses a communication and control unit ( not shown ) having , for example , a remote terminal unit ( rtu ) and a radio transceiver . in an illustrative arrangement to provide remote supervisory control , the pad - mounted gear 12 , the interconnection arrangement 10 , the switch operators 18 , 20 and 22 , and the rtu in the module 16 provide a self - contained arrangement for an automated distribution system that is responsive to signals from a remote location , such as a master station computer , to operate the switches of the pad - mounted gear 12 . additionally , the arrangement permits monitoring of circuit conditions at the location . the interconnection arrangement 10 defines enclosed cable pathways for the routing of the electrical conductors to accomplish the interconnection of the various modules or assemblies 16 , 18 , 20 and 22 so as to provide control paths between the switch operators and the communication and control unit and to route operating power between the switch operators and the communication and control unit . the defined cable pathways of the interconnection arrangement 10 not only provide efficient routing of the various conductors for the interconnection between the predetermined points , but also provide shielding of the low - voltage interconnection conductors from the medium voltage present within the pad - mounted gear 12 . in accordance with important aspects of the present invention , the interconnection arrangement 10 is capable of installation with the pad - mounted gear 12 either during manufacture of the pad - mounted gear 12 in a manufacturing environment , or as a field retrofit installation to existing installed pad - mounted gear . that is , if the pad - mounted gear 12 is either already , presently installed at a location or otherwise available in the field , the modules or assemblies 16 , 18 , 20 and 22 may be affixed to the enclosure 14 and the interconnection arrangement 10 may be assembled with the pad - mounted gear 12 , the interconnection arrangement 10 being positioned below and supporting the pad - mounted gear 12 . interconnections are then made between the modules and assemblies by the connection of the routed conductors to the appropriate points of the modules and assemblies via preassembled and routed cable harnesses within the cable pathways , as will be explained in more detail hereinafter . further , the interconnection arrangement 10 , when assembled , has no externally accessible fasteners . of course , it should be understood that the field retrofit is performed with the pad - mounted gear 12 de - energized . further , as to an installed pad - mounted gear 12 , the cable terminations to the power system need to be disconnected and the pad - mounted gear 12 lifted off the pad to attach the interconnection arrangement 10 . referring now additionally to fig2 - 6 , the interconnection arrangement 10 includes a base member 24 defined by upstanding wall members and having a periphery essentially congruent to the pad - mounted gear 12 . in the illustrative configuration , the enclosure 14 of the pad - mounted gear 12 includes a generally rectangular base and thus the interconnection arrangement 10 also includes a base 24 that is of similar dimensions as defined by upstanding wall members 26 , 28 , 30 , and 32 . the wall members 26 , 28 , 30 and 32 include turned edges or flanges 34 , 35 at the top and bottom , respectively , of each of the wall members . the wall members 26 , 28 , 30 and 32 are appropriately affixed to each other by the use of fasteners or the like . a structural support member 36 , best seen in fig5 is affixed to and spans the wall members 26 , 30 for providing additional rigidity and strength to the base 24 . four structural members 38 , best seen in fig6 are affixed to the structural support member 36 , span the wall members 28 , 32 , and are of approximately the same height as the wall members and the structural support member 36 . the structural members 38 each include upper and lower flanges 39 , 41 respectively . additionally , covers 40 and 46 are affixed to the tops of the members 38 and covers 42 , 44 are affixed to the bottoms of the members 38 so as to define an enclosed cable pathway or duct 48 within the central section of the base 24 of the interconnection arrangement 10 . the structural support member 36 includes an appropriate central opening 37 for the continuation of the cable pathway 48 . the members 36 and 38 also divide the base 24 into compartments corresponding to the predetermined compartments of the enclosure 14 of the pad - mounted gear 12 . internal duct members 52 , best seen in fig7 - 8 , are provided at the ends of the cable pathway 48 adjacent the walls members 28 , 32 and are each respectively affixed to one of the structural members 38 and one of the wall members 28 , 32 so as to span an opening 54 provided in the structural members 38 to continue the cable pathway 48 into the internal ducts 52 . specifically , a flange 53 of the internal duct 52 is affixed to the member 38 and a flange 55 is affixed to the wall 28 or 32 . cableway openings at 56 , 57 , 58 and 59 are provided through the wall members 28 and 32 at the appropriate locations of the modules and assemblies 16 , 18 , 20 , and 22 . referring now to fig9 external ducts 60 are affixed to the exterior of the wall members 28 , 32 of the base 24 over the cableway openings 56 , 57 , 58 , and 59 . the external ducts 60 are dimensioned to extend upward to the bottom of the respective modules and assemblies 16 , 18 , 20 , and 22 . in this manner , the external ducts 60 provide an extension of the cable pathway 48 into and through appropriate openings in the bottom of the enclosures of the respective modules and assemblies 16 , 18 , 20 and 22 via the open top portions 62 of the external ducts 60 . for example , an opening 64 is provided in the bottom of the module 22 , as seen in fig3 . in accordance with the features of the present invention , it should be noted that the cable pathway 48 extends between all the modules and assemblies 16 , 18 , 20 , and 22 via the external ducts 60 , the internal ducts 52 , and the central enclosed portion of the base 24 defined by the members 38 and the covers 40 , 42 , 44 , and 46 . thus , whatever interconnections are needed for particular configurations can be readily accomplished via the provision of predetermined , preassembled cable harnesses of conductors . for example , as shown in fig4 the cable harnesses 66 , 68 , and 70 are provided for the necessary interconnection of control paths between the communication and control unit 16 and the respective switch operators 18 , 20 , and 22 . appropriate strain relief and protection for the cable harnesses 66 , 68 , and 70 are provided at the cableway openings 56 , 57 , 58 , and 59 via suitable strain - relief members , bushings , grommets , or the like . the cable harnesses 66 , 68 , and 70 include appropriate connectors , e . g ., connectors 72 , 74 for the cable harness 70 , which are arranged to interfit with respective connectors or the like 76 in the switch operator 22 and 78 in the communication and control unit 16 . additionally , power control interconnections are provided via cable harnesses 80 and 82 between the respective switch operators 20 and 22 and the switch operator 18 . in a specific configuration , the switch operators 20 , 22 receive operating power from the switch operator 18 such that the switch operators 20 , 22 are designated as companion operators . considering now in more detail the field retrofit installation of the interconnection arrangement 10 , after the pad - mounted gear 12 has been de - energized and the cable terminations to the power conductors disconnected , the modules and assemblies 16 , 18 , 20 , and 22 are attached to the enclosure 14 of the pad - mounted gear 12 and suitably connected to the switch - operating shafts . of course , the modules and assemblies may optionally have already been attached to the pad - mounted gear 12 prior to the time of installation of the interconnection arrangement 10 . next , the pad - mounted gear 12 is physically and structurally disconnected from the pad or other mounting structure . at this point , the pad - mounted gear 12 is lifted off the pad so that the interconnection arrangement 10 may be attached to the mounting pad . prior to the attachment of the interconnection arrangement 10 to the pad - mounted gear 12 , the interconnection arrangement 10 is prepared in the field . this entails applying appropriate gasketing to various parts , feeding and extending the cable harnesses 66 , 68 , 70 , 80 and 82 through the holes 56 , 57 , 58 , and 59 in the base 24 , affixing the external ducts 60 to the base 24 , and also attaching the internal ducts 52 . for example , the external ducts 60 are affixed to the base 24 via bolts 61 ( fig4 ) that are inserted from the inside of the base and threaded into clip nuts 63 ( fig9 ) carried by the external ducts 60 . at this point in the installation , bottom access plates of the modules and assemblies 16 , 18 , 20 , and 22 , such as an access plate 67 ( fig3 ) overlying the opening 64 of module 22 , are removed and the pad - mounted gear 12 lowered onto the base 24 which has been positioned on the pad . the base 24 is attached to the enclosure 14 of the pad - mounted gear 12 via suitable fasteners or the like that are assembled through holes 88 in the base 24 and the enclosure 14 . as the enclosure 14 is lowered onto the base 24 , the various cable harnesses are passed through the openings 64 of the modules and assemblies 16 , 18 , 20 , and 22 . the ground bus connector 84 of the base 24 is connected to the respective ground bus connector of the enclosure 14 . the connectors of the cable harnesses are then connected into the mating connectors of the modules and assemblies . after these steps , the external ducts 60 are affixed to the modules and assemblies and the external ducts 60 are also now firmly affixed to the base 24 ; e . g ., the external ducts 60 are affixed to the modules via bolts 90 ( fig9 ) that are inserted from the inside of the module 20 and threaded into clip nuts 92 ( fig4 and 9 ) carried by the external ducts 60 . next , the internal ducts 52 are positioned for final affixing and then tightened into place , the internal ducts 52 having been loosely attached previously but oriented so as to provide access to the interior for any necessary cable harness manipulation . finally , the pad - mounted gear 12 with attached interconnection arrangement 10 is physically secured to the pad . the desired current and / or voltage sensors are installed , and suitable interconnections accomplished . for example , the cable harnesses 66 , 68 , and 70 are provided with appropriate cable conductors and connectors , for example , connector 86 on cable harness 70 for interconnection to a mating connector of the various installed sensors . it should be noted that there are no externally accessible fasteners . regarding the different configurations of the interconnection arrangement 10 that are possible for the same or different configurations of pad - mounted gear 12 and to illustrate the flexibility of the invention to accommodate different configurations , the interconnection arrangement 10 in one specific illustration is arranged to accommodate from one to four locations of switch operators . where only one switch operator is provided , at the location of assembly 18 , only the cable harness 66 is provided and the internal and external ducts 52 and 60 and the covers 44 , 46 on the right - hand side of the base 24 in fig4 are deleted . referring now additionally to fig1 , a cover plate 90 may be provided that can be affixed over either selected ones of the openings 54 of the structural members 38 or the central opening 37 of the structural support member 36 as desired to form a particular configuration . this illustrates that in the various configurations , the cable pathway 48 is totally closed within the base 24 . thus , where two switch operators are provided , at locations 18 , 20 , the cable harness 70 is omitted , the internal and external ducts are omitted at the location for the operator 22 , and the cover plate 90 is installed at the opening 54 of the structural member 38 at the upper right in fig4 . considering other structural details , it should be noted that the internal ducts 52 are not of identical sizes , as can be seen from fig4 . additionally , for the module 16 , the external duct 60 is not the same size as the remaining ducts due to the dimensions of the enclosure of the module 16 . for example , if four switch operators are provided at the locations 16 , 18 , 20 , and 22 , the external ducts 60 would all be identical . as will be apparent to those familiar with the underground distribution art , sufficient cable termination length must be available to accommodate the interconnection arrangement 10 . for example , the interconnection arrangement could replace an existing base spacer or be added to the height of the pad - mounted gear 12 above the pad , assuming sufficient extra length of cable is available . turning now to a discussion of the assembly of the interconnection arrangement 10 in a manufacturing environment , the kit of components can be identical to the field retrofit kit or may be slightly different . for example , for manufacturing assembly , the internal duct 52 may be omitted and the routing of cable harnesses performed by direct entry from the central duct between the structural members 38 and into the external duct 60 , which is then positioned to 60 &# 39 ; from the position as shown in fig4 ( i . e ., in a downward direction in fig4 ). while there have been illustrated and described various embodiments of the present invention , it will be apparent that various changes and modifications will occur to those skilled in the art . accordingly , it is intended in the appended claims to cover all such changes and modifications that fall within the true spirit and scope of the present invention .
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referring to fig1 there is shown a preferred embodiment of a phase - difference detecting circuit 11 in accordance with the present invention . the phase - difference detecting circuit 11 comprises a phase - difference detecting part 12 for detecting a phase difference between a first signal ina with a first frequency and a second signal inb with a second frequency , and a latching part 13 for latching an output of the phase - difference detecting part 12 and outputting it as an output &# 34 ; out &# 34 ; of the phase - difference detecting circuit 11 . the phase - difference detecting part 12 is constituted by a first d flip - flop ( dff1 ) 14 , a second d flip - flop ( dff2 ) 15 , a delay circuit ( delay means ) 18 comprising inverters 16 and 17 , and a 3 - input nand gate ( logic means ) 19 . the first d flip - flop ( dff1 ) 14 has a data terminal d to which the first signal ina different in frequency from the second signal inb is input , a clock terminal ck to which the second signal inb is input , a reset terminal to which a reset signal res is input , and an output terminal xq1 connected to an input terminal of the 3 - input nand gate 19 . likewise , the second d flip - flop ( dff2 ) 15 has a data terminal d into which the first signal ina is input , a clock terminal ck to which a third signal inc delayed from the second signal inb by a predetermined time ( phase ) difference dt by the delay circuit 18 is input , a reset terminal to which the reset signal res is input , and an output terminal q2 connected to an input terminal of the 3 - input nand gate 19 . the first signal ina with a first frequency is also input to the 3 - input nand gate 19 . the output x of the 3 - input nand gate 19 is output to the latching part 13 , which is constituted by cross - coupled nand gates 20 , 21 and an inverter 22 . the nand gate 20 has an input terminal to which the output x of the 3 - input nand gate 19 is input , while the nand gate 21 has an input terminal to which the reset signal res is input . accordingly , the same first signal ina is input to both the first flip - flop 14 and the second flip - flop 15 , and the clock of the second flip - flop 15 is delayed from the clock of the first flip - flop 14 by the time difference dt between the signals inb and inc . fig2 schematically illustrates a pll frequency synthesizer to which the phase - difference detecting circuit 11 is applied . the parts substantially identical to corresponding parts of fig1 are designated by the same reference numerals and therefore a detailed description of the identical parts will not be given . in fig2 a pll integrated circuit ( ic ) 31 comprises a first and gate 32 to which a signal osc in and a power save control signal ps respectively corresponding to the signals ina and res of fig1 are input , a second and gate 33 to which the power save control signal ps and a signal f in ( corresponding to the signal inb of fig1 ) output from a vco are input , a programmable reference frequency divider 2 to which the output of the first and gate 32 is input , and a programmable comparison frequency divider 4 to which the output of the second and gate 33 is input . the outputs of the and gates 32 and 33 and the power save control signal ps are input to a phase - difference detecting circuit 11 , which detects the phase difference between the two signals osc in and f in and outputs a control signal ps1 corresponding to the output ( out ) of the phase - difference detecting circuit 11 of fig1 to the reference frequency divider 2 and the comparison frequency divider 4 . the output f r of the reference frequency divider 2 , the output f v of the comparison frequency divider 4 , the power save control signal ps , and the control signal ps1 are input to a phase comparator 3 . the phase comparator 3 is connected to a charge pump 5 , which outputs the pll ic output d o to a low - pass filter 6 connected to the vco 7 . note that the standby control of the phase comparator 3 may be performed by the power save control signal ps instead of the control signal ps1 , as shown by the broken line in fig2 . in that case , the phase comparator 3 becomes active earlier than the frequency dividers 2 and 4 , but there is no problem because the frequency dividers 2 and 4 do not become active until the phases of the signals osc in and f in become small . fig3 schematically illustrates the structure of the divide - by - n frequency divider 4 , which is substantially the same as that of the divide - by - r frequency divider 2 . the output control signal ps1 from the phase - difference detecting circuit 11 goes low in the standby mode ( when ps = 0 ). if the set terminals of a first flip - flop fl and a second flip - flop f2 are low and the clear terminal of a third flip - flop is low , then the q1 output of the first flip - flop f1 and the q2 output of the second flip - flop f2 go high , and the q3 output of the third flip - flop f3 goes low . the q3 output of the third flip - flop f3 is connected to the load terminals of flip - flops f1 through fn and a nor gate 34 . the q outputs of the flip - flops f1 through fn are connected through inverters to the inputs of a detecting circuit det for detecting a digital value 4 . the output of the circuit det is connected to the d input of the first flip - flop f1 . at the time of the load state ( load = low ), the flip - flops f1 through fn is in the dividing - ratio data reading state , and do no go to the counting state even if the clock signal f in is input . since the two inputs of the nor gate 34 are low and high at that time , the output f v of the frequency divider 4 goes to low . if in the active mode ( when ps = 1 ) the input signals to the frequency dividers 2 and 4 rise at the same time , the control signal ps1 will go high . as a result , the output f v goes high because the two inputs of the nor gate 34 are both low at the time the control signal ps1 goes high , and therefore the output f v is output . if the control signal ps1 is high , the flip - flops f1 , f2 and f3 are all reset , and the count will start when the clock signal f in makes a low - to - high transition . if the load terminals of the flip - flops f1 through fn go to high level , the flip - flops f1 through fn are all reset and the dividing operation will start thereafter , the dividing operation is performed according to a predetermined dividing ratio . fig4 schematically illustrates the structure of the phase comparator 3 and the charge pump 5 . in the standby mode ( when ps = 0 ), the flip - flops fa and fb of the phase comparator 3 go to the clear state because the control signal ps1 is low . the q output of the flip - flop fa goes low , and the xq output of the flip - flop fb goes high . at this time , the p - channel and n - channel mos transistors of the charge pump are both cut off , and the pll ic output d o goes to the high impedance state . if the control signal ps1 goes high , then flip - flops fa and fb are reset ( because one of the two inputs of a nand gate 35 goes high ), and the normal phase comparison operation for detecting the phase difference between the reference signal f r and the variation signal f v is performed . note that the pll ic output d o is held to the high impedance state until the phase comparison operation starts . fig5 and 6 are timing diagrams showing how the phase - difference detecting circuit 11 is operated . fig5 shows waveforms when the phase difference t1 between the input signals ina and inb is greater that the phase difference dt between the input signals inb and inc , while fig6 shows waveforms when the phase difference t2 between the input signals ina and inb is less than the phase difference dt between the input signals inb and inc . suppose that the signals ina and inb are different signals which are not the same in frequency and phase . if , with such a condition , the res input is not asserted and the two signals ina and inb are input , the relationship between the two signals will go to the state shown in fig5 and 6 . since in fig5 the phase difference t1 between the two signals ina and inb is above the phase difference dt between the signals inb and inc , the xq1 output of the d flip - flop 14 or dff1 is low and the q output of the d flip - flop 15 or dff2 is high , so that the output ( out ) of the phase - difference detecting circuit 11 remains low . if , as shown in fig6 the rising edge of the signal inb leads the rising edge of the signal ina and the phase difference t2 between the two signals ina and inb is within the phase difference dt between the signals inb and inc , the xq1 output of the dff1 will go high because the dff1 reads the level of the signal ina before the rising edge of the signal ina , and the q2 output of the dff2 will go high because the dff2 reads the level of the signal ina after the rising edge of the signal ina . since at this time the signal ina is high , the output x of the nand gate 19 goes low and the output ( out ) of the detecting circuit 11 thus goes low . in this way , the state where the phase difference between the two signals ina and inb is within the phase difference dt between the signals inb and inc is detected . if , as shown in fig7 ( a ), the frequencies of the input signals ina and inb both do not vary and the phase difference t1 is greater than dt , the pll will not be operated because the phase difference is always above a predetermined time difference dt . in order to avoid this condition , the signals ina and inb are not the same in frequency and phase , and therefore there is a moment that a phase difference t6 becomes less than dt , as shown in fig7 ( b ). in fact , in the intermittent operation of a pll , the charge pump output goes to the high impedance state at the standby time , and the low - pass filter can hold the output voltage when the loop is locked , by the capacity . however , the condition of fig7 ( a ) that the phase difference is always above the predetermined time difference dt cannot occur because the output voltage slightly varies due to the leak current and thus the frequency slightly varies . note that the phase difference dt between the signals inb and inc can be easily varied by simply increasing and decreasing the number of the inverters 16 and 17 of the delay circuit 18 . the phase difference dt between the signals inb and inc is set so that the two low - to - high transitions or high - to - low transitions can quickly match depending on the frequencies of the two signals . for example , when the low - to - high transition of the signal ina does not match with the low - to - high transition of the signal inb , a larger phase difference dt is set . in the phase - difference detecting circuit 11 , the low - to - high transitions of the signals ina and inb are detected at the same time . if the output ( out ) of the phase - difference detecting circuit 11 changes , it will be necessary to reset the circuit to detect the low - to - high transition after that time . the reset signal res is therefore input to the dff1 , dff2 and the latching part 13 , as shown in fig1 . in the embodiment of fig1 in addition to the xq1 output of the dff1 and the q2 output of the dff2 , the signal ina is input to the 3 - input nand gate 19 . the reasons are as follows . that is , if the signal ina is left unconnected and only the xq1 and q2 outputs are connected , the output x of the circuit 11 will go low regardless of the phase difference between the signals ina and inb , as shown in the point a of fig8 . consequently , the output ( out ) of the circuit 11 that is to change at the point b of fig8 will change . the reason is that , when the q2 output of the dff2 goes high at the point ( a ) of fig8 and at the point a the xq1 output of the dff1 goes high and the q2 output goes low , the q2 output is delayed by the phase difference dt between the signals inb and inc and therefore the output x of the nand gate 19 goes to a low level . in the embodiment of fig1 the signal ina is input to the nand gate 19 to eliminate this incorrect operation , and the above described problem is thus overcome . fig9 shows a timing diagram when the phase - difference detecting circuit 11 is applied to the pll ic 31 . in the figure , suppose now that the pll ic 31 is in the standby mode ( ps = low ). with this state , each counter goes to the reset state , the charge pump output goes to the high impedance state . therefore , since the voltage at the time of lock is held by the cr time constant of the low - pass filter 6 , the external vco 7 ideally oscillates at a frequency f in of the lock time , but in fact the vco oscillating frequency slightly changes due to leak . if the standby mode is switched to the operating mode , each input gate is then opened , the oscillating output of the external osc is input by the osc in signal and enters the phase - difference detecting circuit 11 . the vco oscillating output is also input by the f in signal and enters the phase - difference detecting circuit 11 . if the rising edges of the two signals become the relationship of fig6 then the control signal ps1 is output from the circuit 11 to the frequency dividers 2 and 4 . if the frequency dividers 2 and 4 are operated at the same time as the input of the control signal ps1 to the frequency dividers 2 and 4 to output the signals f r and f v to the phase comparator 3 , an error signal will become very small and thus the lock - up time can be greatly quickened . thus , in the present invention , the transition state where two different frequency signals go high or low at the same time with a predetermined range is detected , and at the same time the counters of the reference frequency divider 2 and comparator frequency divider 4 are operated . therefore , if the phase - difference detecting circuit 11 according to the present invention is used , for example , in an intermittently operated pll ic , the reference signal f r and the comparison signal f v which are the same in phase can be produced for a very short time . consequently , the error signal can be made very small and the lock - up time is thus greatly shortened , so that the performance of the pll synthesizer is greatly enhanced . the invention has been described with reference to the preferred embodiment . obviously modifications and alternations will occur to others upon a reading and understanding of this application . it is intended to include all such modifications and alternations insofar as they come within the scope of the appended claims or the equivalents thereof .
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fig1 illustrates an exploded view of a targeted eye drop dispenser 10 including a reservoir assembly 12 and a cap 14 . the reservoir assembly 12 includes a flexible plastic reservoir bottle 16 , a neck 18 extending vertically from the top surface 20 of the reservoir bottle 16 , a threaded surface 22 encompassing the neck 18 , tubular extension member 24 extending from the neck 18 , and a tubular passage 25 having a dispensing orifice 27 aligned in the tubular extension member 24 . the tubular extension member 24 includes a target tip 26 , which can be radiused as illustrated , and having a plurality of highly visible targets , such as rings 28a - 28n aligned coaxially on the target tip 26 . the target rings 28a - 28n are of highly visible colors such as phosphorescent orange , lime or other suitable highly visible colors . alternatively , the target tip 26 can include a flat surface or any other shaped surface suitable for bearing of a highly visible color , whether the colors are displayed in the form of concentric rings , a solid color , or any other suitable design which would lend itself toward visual capture during the process of eye drop application by an individual . the target tip 26 can also have target rings or surfaces which contain glow - in - the - dark visual surfaces for application in low light or complete darkness situations where a person &# 39 ; s eyes cannot tolerate bright lights . fig2 illustrates a top view of the reservoir assembly 12 along line 2 -- 2 of fig1 where all numerals correspond to those elements previously described . illustrated in particular is the target tip 26 including the highly visible target rings 28a - 28n . fig3 an alternative embodiment , illustrates an exploded cross - sectional view of a targeted eye drop dispenser 50 having at least one or more lighted targets 52 . the targeted eye drop dispenser 50 includes a reservoir assembly 54 and a cap 56 . the reservoir assembly 54 includes a flexible plastic reservoir bottle 58 , a neck 60 extending vertically from the top surface 62 of the reservoir bottle 58 , a threaded surface 64 encompassing the neck 60 , and a tubular extension member 66 extending from the neck 60 . a tubular passage 68 in the neck 60 connects the interior of the reservoir bottle 58 and a target tip 70 to allow for dispensing of eye drop medication from the reservoir assembly 54 . the lighted target 52 , in the form of a light emitting diode ( led ), aligns in the upper portion of the tubular extension member 66 at the target tip 70 in very close proximity to the dispensing orifice 72 at one end of the tubular passageway 68 . the lighted target 52 aligns in a passageway 74 in the tubular extension member 66 . wires 75 and 77 from the lighted target 52 also align in the passageway 74 and connect to a switch assembly 76 actuated by a push button 78 and to a small battery 80 aligned in the structure of the reservoir bottle 58 . the lighted target 52 can be in the form of a steady or pulsating led of any desirable eye attracting color such as , but not limited to , white , red , green , yellow , or other desirable colors . in the alternative , the lighted target could be a lighted crystal display ( lcd ) which could be steady or pulsating . it is appreciated that an lcd could be applied in place of the plurality of target rings 28a - 28n of fig1 and flash sequentially from the outside ring to the inside ring , thus providing an eye catching target . in another embodiment , the energy source , such as a battery for activating the lighted target , is placed in a separate carrier configured to receive at least a portion of the eye drop dispenser . specifically , the battery is placed in the carrier with its leads exposed so that upon placing the dispenser in the carrier , the battery leads contact opposite leads on the dispenser that are in electrical communication with the light source . preferably the carrier does not extend completely about the dispenser , in order that the reservoir remain partially exposed to enable squeezing of the same so as to dispense the eye drop solution . the carrier / dispenser combination can be constructed so that the light source always illuminates upon placing the dispenser in the carrier , or an additional switching mechanism such as that described previously can be used so that the dispenser can remain in the carrier without discharging the battery . fig4 illustrates the mode of operation of the targeted eye drop dispenser where all numerals correspond to those elements previously described . the cap 14 of fig1 is first removed and then the reservoir assembly 12 is inverted by the user . the user then tilts their head back and the reservoir assembly 12 is placed in the region over the user &# 39 ; s eye 82 . the user then visually acquires the plurality of target rings 28a - 28n and focuses upon them . after visual capture of the target rings , as portrayed by lines 82 - 88 , the reservoir bottle is gently squeezed causing the desired eye wash solution 92 to be dispensed into the user &# 39 ; s eye 82 from the aligned dispensing orifice 27 . various modifications can be made to the present invention without departing from the apparent scope hereof .
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in low power circuit applications , it is very important to reduce a gate bias voltage of the mos transistors which are employed by the current mirror circuit . that &# 39 ; s because that once the gate bias voltage is reduced , the operating power will also be automatically reduced . thus , the present invention set forth a current mirror circuit which can reduce the threshold voltage through providing a substrate bias voltage higher than the source bias voltage . please refer to fig2 a which illustrates a schematic view of a current mirror circuit in a preferred embodiment according to the present invention . the current mirror circuit is employed to receive an input current i in so as to produce an output current identical to the input current and includes a first transistor n 1 , a second transistor n 2 , a third transistor n 3 , a fourth transistor n 4 , a resistor r , an input current source i in , a first power supply vss and a second power supply vdd . a first end of the resistor r is employed to receive the input current source i in . the gate electrode of the first transistor n 1 is coupled to the second end of the resistor r to receive a first bias voltage , the drain electrode thereof id coupled to the first power supply vss and the substrate electrode thereof is coupled to the drain electrode thereof . the gate electrode of the second transistor n 2 is coupled to the gate electrode of the first transistor n 1 , the source electrode thereof is coupled to the first power supply vss and the substrate thereof is coupled to the substrate electrode of the first transistor n 1 . the gate electrode of the third transistor n 3 is coupled to the first end of the resistor r to receive a second bias voltage , the source electrode thereof is coupled to the drain electrode of the first transistor n 1 , the substrate electrode thereof is coupled to the substrate electrode of the first transistor n 1 and the drain electrode is coupled to the second end of the resistor r . the gate electrode of the fourth transistor n 4 is coupled to the gate electrode of the third transistor n 3 , the source electrode thereof is coupled to the drain electrode of the second transistor n 2 , the substrate electrode thereof is coupled to the source electrode thereof and the output current i out is generated from the drain electrode thereof . meanwhile , the first power supply vss is coupled to the ground , and the first transistor n 1 , the second transistor n 2 , the third transistor n 3 and the fourth transistor n 4 are n - type metal - oxide semiconductor transistors . according to the circuit described above and further based on the body effect , the threshold voltage is equal to : v th = v th0 γ ({ square root }{ square root over ( v sb +| 2φ f |)}−{ square root }{ square root over ( 2φ f )}) furthermore , because the substrate electrode of the third transistor n 3 is coupled to the drain electrode thereof in the present invention , the threshold voltage of the third transistor n 3 is equal to v th0 . identically , the substrate electrode of the fourth transistor n 4 is coupled to the drain electrode thereof , and thus the threshold voltage of the fourth transistor n 4 is also equal to v th0 . as to the threshold voltage of the first transistor n 1 , it is equal to : v th , n1 = v th - 0 + γ ({ square root }{ square root over ( v sd , n1 + 2φ f )}−{ square root }{ square root over ( 2φ f )}) since the voltage v sd , n1 of the first transistor n 1 is negative , the threshold v th , n1 thereof is lower than v th0 , which is generally equal to 0 . 7 v ). depending on the same theory , the v sd , n1 of the second transistor n 2 is also negative , and thus the threshold v th , n2 thereof is lower than v th0 . furthermore , both the threshold voltages of the first transistor n 1 and the second transistor n 2 are the same . consequently , the gate bias voltage of the first transistor n 1 and the second transistor n 2 is equal to : v g , n1 = v g , n2 = v th0 + γ ( v sd , n1 + 2 φ f - 2 φ f ) + 2 i i n μ n c ox ( l w ) n1 based on the formula described above , because v sd , n1 & lt ; 0 , γ ({ square root }{ square root over ( v sd , n1 +| 2φ f |)}−{ square root }{ square root over ( 2φ f )} is also negative . therefore , the gate bias voltage of the first transistor n 1 and the second transistor n 2 can be reduced so as to reduce the operating power of the whole system . another embodiment according to the present invention is shown in fig2 b . a current mirror circuit includes a first transistor pt , a second transistor p 2 , a third transistor p 3 , a fourth transistor p 4 , a resistor r , an input current source i in , a first power supply vss and a second power supply vdd . the difference from that in fig2 a is the first transistor p 1 , the second transistor p 2 , the third transistor p 3 and the fourth transistor p 4 are p - type metal - oxide semiconductor transistors . now , if each element in both fig1 b and fig2 a is adjusted to suit the input current i n equal to 10 μa and r is supposed as 40 kω , the result of voltage variation is shown in fig3 . the simulation method is to vary the input current from 0 μa to 40 μa . as shown in fig3 the node voltage of v 1a is restricted under the threshold voltage ( 0 . 7 v ) of the mos transistor and when the input current i in is larger than 1 . 8 ma , because the first transistor n 1 and the second transistor n 2 shown in fig2 a can not maintain a normal function , the current will flow through the drain electrode to the substrate electrode so as to cause a latch - up . however , when in the present invention , the desired input current is equal to 10 μa , v 1a is equal to 0 . 3 v , and thus the first transistor n 1 and the second transistor n 2 will not lose efficiency . moreover , the voltage variations of v 2b and v 2a respectively in fig1 b and fig1 a are shoves in fig4 . as shown in fig4 when the input current i in is equal to 10 μa , v 2a will 150 mv lower than v 1a . that means , if v sb of the mos transistor is set as − 0 . 3v , the original threshold voltage will be reduced from 0 . 75 v to 0 . 6 v so as to reduce 0 . 15 v of the operating voltage due to the body effect . a low power operating system like this should be very practical . please refer to fig5 which is a comparison plot of the input current and the output current in fig1 b and fig2 a . as shown in fig5 when the input current i in is larger than 18 μa , part of the current is already flow into the substrate electrode . in view of the aforesaid , the circuit structure according to the present invention can be employed as the input current is lees variable so that the gate bias voltage of the transistor can be reduced through reducing the threshold voltage thereof so as to reduce the operating voltage of the system . thus , the present invention can effectively overcome the defects in the prior arts . consequently , the present invention conforms to the demand of the industry and is industrial valuable . while the invention has been described in terms of what is presently considered to be the most practical and preferred embodiments , it is to be understood that the invention needs not be limited to the disclosed embodiment . on the contrary , it is intended to cover various modifications and similar arrangements included within the spirit and scope of the appended claims which are to be accorded with the broadest interpretation so as to encompass all such modifications and similar structures .
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the fig1 shows a diagrammatic sketch of an internal combustion engine having turbocharging and having low - pressure exhaust - gas recirculation . although the exemplary embodiment relates to a diesel engine , the description may however also be applied to other types of internal combustion engine . a schematically illustrated multi - cylinder diesel engine 2 has inlet ducts 4 and outlet ducts 6 . the outlet ducts 6 open out via a collector 8 into an exhaust line 10 , which opens out into a turbine 12 of a turbocharger 14 . the turbine 12 is coupled by means of a shaft 16 to a compressor 18 of the turbocharger 14 . the turbocharger 14 may be a turbocharger with fixed geometry ( fgt ) or a turbocharger with variable geometry ( vgt ). the outlet of the turbine 12 is adjoined by an exhaust section 20 in which are arranged , in this sequence , a diesel oxidation catalytic converter 22 , a diesel particle filter 24 , a control system for controlling the exhaust - gas back pressure , which control system comprises a throttle flap 26 and a bypass 28 , which leads past the throttle flap 26 , with an integrated valve , and a silencer 30 . a low - pressure egr line 32 is connected to the exhaust section 20 downstream of the turbine 12 and upstream of the diesel oxidation catalytic converter 22 , which low - pressure egr line 32 opens out via an egr valve 34 into a fresh - air line 36 that conducts fresh air from an air filter 38 into the compressor 18 of the turbocharger 14 . the mixture of fresh air and recirculated exhaust gas that is compressed by the compressor 18 passes via an air inlet line 40 into a combined inlet air cooler and distributor 42 , where said mixture is cooled and distributed between the inlet ducts 4 . the inlet air cooler and distributor 42 comprises a bypass ( not shown ), with the inlet air mixture being conducted , as required , either through the inlet air cooler and distributor 42 or through the bypass and past the inlet air cooler and distributor 42 . a throttle flap 44 may also be provided in the inlet line 40 in order to close the inlet line 40 when the diesel engine 2 is shut down . the low - pressure egr line 32 comprises a heatable particle filter 46 that is traversed by the recirculated exhaust gas . the particle filter 46 comprises an electric heater , for example in the form of grids , which are integrated into the filter matrix , composed of heating or glow wires 47 , by means of which any soot and oil particles in the recirculated exhaust gas are burned . the low - pressure egr line 32 may also comprise , downstream of the particle filter 46 and upstream of the egr valve 34 , a heat exchanger 48 that dissipates the heat contained in the exhaust gas to an arbitrary heat sink — such as for example the inlet air collector and cooler 40 . the heat exchanger 48 comprises a bypass ( not shown ), with the inlet air mixture being conducted selectively either through the heat exchanger 48 or through the bypass and past the heat exchanger 48 . referring now to fig2 , a method to control egr for an internal combustion engine is shown . routine 200 begins at 202 where engine operating conditions are determined . engine operating conditions are determined from sensors and actuators . in one example , routine 200 determines engine temperature , ambient temperature , the pressure drop across a particulate filter in the high pressure egr loop , the pressure drop across a particulate filter in the exhaust system , time since engine start , engine load , engine torque demand , engine speed , and amount of air inducted to the engine . in other example embodiments , additional or fewer operating conditions may be determined based on specific objectives . at 204 , the routine judges whether or not to flow egr . the decision to flow egr may be based on the operating conditions determined at 202 . in one example , egr is activated after the engine has been operating for a threshold amount of time and after engine coolant temperature reaches a threshold level . in addition , other conditions may be used to activate or enable the egr system . for example , egr may be enabled after engine load is greater than a threshold or after engine speed exceeds a threshold . routine 200 then proceeds to 206 if egr is activated . otherwise , routine 200 proceeds to exit . at 206 , the egr valve is controlled in response to engine operating conditions . in one example , the egr valve position is related to engine speed and driver demand torque . the egr valve positions may be stored in a table or function indexed by engine speed and driver demand torque . the egr valve positions correspond to an empirically determined egr flow rate . the egr valve position may be controlled by a vacuum actuator or by a stepper motor , for example . at 208 , routine 200 judges whether or not to regenerate a particulate filter in the egr loop . in one embodiment , routine 200 makes a decision based on the pressure drop across a particulate filter . in another embodiment , routine 200 may decide to regenerate the particulate filter in response to a model . for example , a soot accumulation model that estimates the amount of soot produced by an engine may be the basis for regenerating a particulate filter . if the estimated amount of soot exceeds a threshold , particulate filter regeneration is initiated . on the other hand , if a pressure across the particulate filter is determined from a sensor or an estimating model , particulate filter regeneration may be initiated after the observed or estimated pressure exceeds a threshold . in addition , other conditions may be included that determine when to regenerate the particulate filter . for example , filter regeneration may not proceed if engine temperature is above a threshold temperature or if engine temperature is below a threshold temperature . in one embodiment an electrically heated particulate filter is activated after egr begins flowing in the egr tube so that oxidized particulate matter may be oxidized and released from the filter and then flow back into the engine before being exhausted . further , in one embodiment , the temperature of the particulate filter may be elevated by flowing egr into the engine for a predetermined amount of time before the electrical heater is activated to heat the particulate filter . in other words , current is not supplied to the particulate filter heater until exhaust gases have flowed from the exhaust system to the intake system for a threshold amount of time or until the particulate filter reaches a threshold temperature . by elevating the particulate filter temperature with exhaust gases , it is possible to lower the thermal gradient that the filter is exposed to and therefore degradation of the particulate filter and particulate filter heater may be reduced . in one example , the rate that current is applied to the particulate filter heater may be related to the temperature of the particulate filter at a time when regeneration is requested . for example , as the temperature of the particulate filter increases , the amount of current supplied to the particulate filter over a period of time can be increased . if particulate filter regeneration is desired and conditions are met , routine 200 proceeds to 210 . otherwise , routine 200 proceeds to exit . at 210 , current is ramped to the electrical particulate filter heater that is in the egr loop . for example , current may be applied at a low level and increased over a period of time . in one example , the heater current is ramped when the engine is relatively cold . for example , if the engine is started at 20 ° c . the particulate filter heater current may be slowly ramped so that heater or particulate filter performance does not degrade . at higher temperatures , the particulate filter heater current may be ramped at a higher rate of current per second . thus , under a first condition of a particulate filter heater current is ramped at a first rate of current , and under a second condition of a particulate filter heater current is ramped at a second rate . at 212 , routine 200 judges whether or not particulate filter regeneration is complete or if conditions for regeneration are no longer present . in one embodiment , regeneration is determined complete when the pressure difference across the particulate filter is less than a predetermined amount . if routine 200 judges that regeneration is complete , routine 200 proceeds to exit . otherwise , routine continues to loop back . it will be appreciated that the configurations disclosed herein are exemplary in nature , and that these specific embodiments are not to be considered in a limiting sense , because numerous variations are possible . for example , the above systems can be applied to v - 6 , i - 4 , i - 6 , v - 12 , opposed 4 , and other engine types . the subject matter of the present disclosure includes all novel and nonobvious combinations and subcombinations of the various systems and configurations , and other features , functions , and / or properties disclosed herein . the following claims particularly point out certain combinations and subcombinations regarded as novel and nonobvious . these claims may refer to “ an ” element or “ a first ” element or the equivalent thereof . such claims should be understood to include incorporation of one or more such elements , neither requiring nor excluding two or more such elements . other combinations and subcombinations of the disclosed features , functions , elements , and / or properties may be claimed through amendment of the present claims or through presentation of new claims in this or a related application . such claims , whether broader , narrower , equal , or different in scope to the original claims , also are regarded as included within the subject matter of the present disclosure .
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referring to fig3 an improved a / d converter in accordance with principles of the present invention is described . a / d converter 50 includes analog chopper 12 ′, buffer amplifier 14 , quantizer 52 , digital filter and decimator 1 54 , fir filter 56 and decimator 2 58 . analog chopper 12 ′ chops analog input signal v in with a square wave of frequency f chop , which successively reverses the polarity of v in . analog chopper 121 may be implemented using any well - known analog chopping circuitry . for example , as shown in fig4 if input signal v in is a differential signal v in =( v in + − v in − , analog chopper 12 ′ may be implemented using cross - coupled switches 24 , 25 , 26 , and 27 . switch 24 is controlled by chop signal q , and is coupled between v in + and v cout + . switch 25 is controlled by chop signal q , and is coupled between v in − and v cout − . switch 26 is controlled by complementary chop signal { overscore ( q )}, and is coupled between v in + and v cout − . switch 27 is controlled by complementary chop signal { overscore ( q )}. and is coupled between v in − and v cout + . chop signals q and { overscore ( q )} are complementary logic signals of frequency f chop . for example , when q is high and { overscore ( q )} is low , v cout + = v in + , and v cout − = v in − . when { overscore ( q )} is high and q is low , v cout + = v in − and v cout − = v in + . analog chopper 12 ′ alternatively may be implemented using multiplexer circuitry as described by mccartney , analog multiplier circuitry , or any other suitable analog chopper circuitry . buffer amplifier 14 couples the output of analog chopper 12 ′ to quantizer 52 , which may be any conventional oversampling quantizer , such as a single or multi - bit δ - σ modulator , successive approximation quantizer , flash quantizer , pipelined quantizer , or other suitable oversampling quantizer . quantizer 52 provides a digital output at a rate f quant that is substantially higher than f chop . the digital output of quantizer 52 is the input to digital filter and decimator 1 54 , which includes a digital filter and a decimator that reduces the output data rate by a factor of m . for example , digital filter and decimator 1 54 may be implemented using sinc 3 filter and decimator 20 ( fig1 ), in which m equals the oversampling ratio n of quantizer 52 . alternatively , digital filter and decimator 1 54 may be any other suitable digital filter and decimator . digital filter and decimator 1 54 provide an output sequence x ′( n ) at a rate f quant / m . if control frequency f chop to analog chopper 12 ′ equals f quant /( 2 × m ) then successive output samples x ′( n ) of digital filter and decimator 1 54 are digital representations of the analog signals ( v in + v os ) and −( v in − v os ), where v os is the input - referred offset of buffer amplifier 14 and quantizer 52 . for example , x ′( n ) for n = 0 , − 1 , − 2 , 3 , − 4 may be expressed as : comparing equations ( 1 ) and ( 7 ), sequence x ′( n ) may be expressed as : x ′ ( n )=(− 1 ) n x ( n ), n = 0 , − 1 , − 2 , ( 8 ) fir filter 56 removes v os from sequence x ( n ) if fir filter 56 has l coefficients h ′( n ), n = 0 , 1 , 2 , . . . , l − 1 , output z ′( n ) of fir filter 56 may be expressed as : z ′ ( n ) = ∑ k = 0 l - 1 h ′ ( k ) × ′ ( n - k ) ( 9 ) combining equations ( 8 ) and ( 9 ), output z ′( n ) may be expressed as : z ′ ( n ) = ( - 1 ) n ∑ k = 0 l - 1 ( - 1 ) - k h ′ ( k ) × ( n - k ) ( 10 ) decimator 2 58 reduces the data rate by a factor p , which is an even integer greater than or equal to 2 . that is , from every block of p successive samples z ′( n ), decimator 2 58 provides the first sample at its output y ′( n ), and discards the remaining p − 1 samples . output y ′( n ) is at a rate f quant /( m × p ). for example , if p = 2 , output y ′( n ) is at a rate f chop . because p is an even integer , the phase relation between analog chopper 12 ′ and decimator 2 58 may be set so that y ′( n ) is chosen for n always even or n always odd . if n is even , output y ′( n ) may be expressed as : y ′ ( n ) = ∑ k = 0 l - 1 ( - 1 ) - k h ′ ( k ) × ( n - k ) ( 11 ) from equations ( 2 ), ( 6 ), ( 11 ) and ( 12 ), therefore , ∑ k = 0 l - 1 h ( k ) × ( n - k ) = ∑ k = 0 l - 1 ( - 1 ) - k h ′ ( k ) × ( n - k ) ( 13 ) h ′ ( n )=(− 1 ) n h ( n ), n = 0 , 1 , 2 , . . . , l − 1 ( 14 ) thus , for n even , coefficients h ′( n ) of fir filter 56 equal coefficients h ( n ) of prior art fir filter 22 , but with the sign reversed for all odd coefficients . alternatively , if n is odd , output y ′( n ) may be expressed as : y ′ ( n ) = ∑ k = 0 l - 1 ( - 1 ) - ( k - 1 ) h ′ ( k ) × ( n - k ) ( 15 ) from equations ( 2 ), ( 6 ), ( 15 ) and ( 16 ), therefore , ∑ k = 0 l - 1 h ( k ) × ( n - k ) = ∑ k = 0 l - 1 ( - 1 ) - ( k - 1 ) h ′ ( k ) × ( n - k ) ( 17 ) h ′ ( n )=(− 1 ) ( n 1 ) h ( n ), n = 0 , 1 , 2 , . . . , l − 1 ( 18 ) thus , for n odd , coefficients h ′( n ) of fir filter 56 equal coefficients h ( n ) of prior art fir filter 22 , but with the sign reversed for all even coefficients . fig5 illustrates another converter circuit of this invention that includes a sensor within the chopped conversion chain . circuit 60 includes excitation source 32 , analog chopper 34 ′ and sensor 36 , and a / d converter 62 . a / d converter 62 includes chop synch 40 ( as in fig2 ), and includes buffer amplifier 14 , quantizer 52 , digital filter and decimator 1 54 , fir filter 56 and decimator 2 58 ( as in fig3 ). converter 60 reduces thermal emf errors due to sensor interconnects and also reduces offset , offset drift and 1 / f noise errors produced by buffer amplifier 14 and quantizer 52 . in another aspect of the invention , a method of attenuating a converted digital signal over a wide null band — e . g ., from 48 hz to 62 hz — is provided . using conventional methods to produce a wide null band requires complex filter circuitry that is difficult to fabricate and occupies a substantial amount of die space . in a method for producing a wide null band according to the invention , the band is produced using substantially fewer components and less complex circuitry than by conventional methods . two examples of circuits which can be used to implement the method according to the invention are shown in fig1 and 3 . to produce the desired null band , this method requires only a cascade connection of the two digital filters / decimators . therefore , the method of the invention can operate with or without the second digital chopper 18 ( as in the circuit shown in fig1 ) or by modifying the sign of the coefficients of the second digital filter / decimator ( as in the circuit in fig3 ). more specifically , the circuit shown in fig1 can be used in a method according to the invention by implementing fir filter 22 with two equal coefficients of ½ { h ( 0 )= h ( 1 )= 0 . 5 } and , filter 20 as a sinc 4 filter . alternatively , the method can be implemented using the circuit shown in fig3 . to accomplish this , the digital filter / decimator 54 can be implemented as a sinc 4 with an impulse response of total length 4 * k and a decimation factor m = 4 * k ( f 1 = fs /( 4 * k )) and the digital filter / decimator 58 can be implemented as an fir of length 2 with coefficients h ( 0 )=− h ( 1 )= 0 . 5 or h ( 0 )=− h ( 1 )=− 0 . 5 and decimation factor p = 2 ( fout = fs /( 8 * k )). the actual value of k typically has little influence over the described invention . nevertheless , a common value selected in such configurations is k = 256 . the notch , or center , frequency fo can again be defined as fo = fs / k . the attenuation of the input signal magnitude around the notch frequency , fo , due to such an implementation can be written as : h ( f ) = 20 × log 10 ( sin ( π × f / fo ) k × sin ( π × f / k × fo ) ) 4 × sin ( 8 × π × f / fo ) 2 × sin ( 4 × π × f / fo ) ( 19 ) it should be noted that the method according to invention is not limited to these particular circuit configurations but , rather , these are only exemplary configurations of circuits that produce the results required by the method of the invention . fig6 shows one preferable frequency response that is obtainable according to the method of the invention . in this particular response , an fclk signal is selected such that fs = 55 * k hz , which provides a corner frequency of fo = fs / k = 55 hz . it is shown in fig6 that an implementation according to the invention provides better than about 87 db of input perturbation rejection in a frequency range of 48 hz (= 50 hz − 4 %) to 62 . 5 hz (= 60 hz + 4 %), or about +− 14 % of the corner frequency . for many applications , this level of rejection is sufficient . furthermore , in this particular embodiment , attenuation that extends about +− 14 % around a center frequency of about 55 hz , or other center frequency chosen to provide coverage of the 50 hz and 60 hz power line frequencies , also provides a substantial advantage . it should be noted that the invention is not limited to this particular range . persons skilled in the art further will recognize that the circuitry of the present invention may be implemented using circuit configurations other than those shown and discussed above . all such modifications are within the scope of the present invention , which is limited only by the claims that follow .
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the present principles are directed to determining the span of the user profiles of a single account based on binary feedback . embodiments of the present invention identify composite accounts within , e . g ., a movie delivery system , and furthermore identify the individuals sharing such an account to learn accurate profiles of different users &# 39 ; behaviors . the present description illustrates the present principles . it will thus be appreciated that those skilled in the art will be able to devise various arrangements that , although not explicitly described or shown herein , embody the present principles and are included within its spirit and scope . all examples and conditional language recited herein are intended for pedagogical purposes to aid the reader in understanding the present principles and the concepts contributed by the inventor ( s ) to furthering the art , and are to be construed as being without limitation to such specifically recited examples and conditions . moreover , all statements herein reciting principles , aspects , and embodiments of the present principles , as well as specific examples thereof , are intended to encompass both structural and functional equivalents thereof . additionally , it is intended that such equivalents include both currently known equivalents as well as equivalents developed in the future , i . e ., any elements developed that perform the same function , regardless of structure . thus , for example , it will be appreciated by those skilled in the art that the block diagrams presented herein represent conceptual views of illustrative circuitry embodying the present principles . similarly , it will be appreciated that any flow charts , flow diagrams , state transition diagrams , pseudocode , and the like represent various processes which may be substantially represented in computer readable media and so executed by a computer or processor , whether or not such computer or processor is explicitly shown . the functions of the various elements shown in the figures may be provided through the use of dedicated hardware as well as hardware capable of executing software in association with appropriate software . when provided by a processor , the functions may be provided by a single dedicated processor , by a single shared processor , or by a plurality of individual processors , some of which may be shared . moreover , explicit use of the term “ processor ” or “ controller ” should not be construed to refer exclusively to hardware capable of executing software , and may implicitly include , without limitation , digital signal processor (“ dsp ”) hardware , read - only memory (“ rom ”) for storing software , random access memory (“ ram ”), and non - volatile storage . other hardware , conventional and / or custom , may also be included . similarly , any switches shown in the figures are conceptual only . their function may be carried out through the operation of program logic , through dedicated logic , through the interaction of program control and dedicated logic , or even manually , the particular technique being selectable by the implementer as more specifically understood from the context . in the claims hereof , any element expressed as a means for performing a specified function is intended to encompass any way of performing that function including , for example , a ) a combination of circuit elements that performs that function or b ) software in any form , including , therefore , firmware , microcode or the like , combined with appropriate circuitry for executing that software to perform the function . the present principles as defined by such claims reside in the fact that the functionalities provided by the various recited means are combined and brought together in the manner which the claims call for . it is thus regarded that any means that can provide those functionalities are equivalent to those shown herein . reference in the specification to “ one embodiment ” or “ an embodiment ” of the present principles , as well as other variations thereof , means that a particular feature , structure , characteristic , and so forth described in connection with the embodiment is included in at least one embodiment of the present principles . thus , the appearances of the phrase “ in one embodiment ” or “ in an embodiment ”, as well any other variations , appearing in various places throughout the specification are not necessarily all referring to the same embodiment . referring now to fig1 , a block diagram is shown of a system 100 for delivering content to a home or end user in connection with determining user information and profiles . the content originates from a content source 102 , such as a movie studio or production house . the content may be supplied in at least one of two forms . one form may be a broadcast form of content . the broadcast content is provided to the broadcast affiliate manager 104 , which is typically a national broadcast service . the broadcast affiliate manager may collect and store the content , and may schedule delivery of the content over a deliver network , shown as a first delivery network 106 . the first delivery network 106 may include satellite link transmissions from a national center to one or more regional or local centers . the first delivery network 106 may also include local content delivery using local delivery systems such as over - the - air broadcast , satellite broadcast , or cable broadcast . the locally delivered content is provided to a receiving device 108 in a user &# 39 ; s home , where the content will subsequently be searched by the user . it is to be appreciated that the receiving device 108 can take many forms and may be embodied as a set top box / digital video recorder ( dvr ), a gateway , a modem , etc . further , the receiving device 108 may act as entry point , or gateway , for a home network system that includes additional devices configured as either client or peer devices in the home network . a second form of content is referred to as special content . special content may include content delivered as premium viewing , pay - per - view , or other content not otherwise provided to the broadcast affiliate manager such as , e . g ., movies , video games or other video elements . in many cases , the special content may be content requested by the user . the special content may be delivered to a content manager 110 . the content manager 110 may be a service provider , such as an internet website , affiliated , for instance , with a content provider , broadcast service , or delivery network service . the content manager 110 may also incorporate internet content into the delivery system . the content manager 110 may deliver the content to the user &# 39 ; s receiving device 108 over a separate delivery network , second delivery network 112 . the second delivery network 112 may include high - speed broadband internet type communications systems . it is important to note that the content from the broadcast affiliate manager 104 may also be delivered using all or parts of the second delivery network 112 and content from the content manager 110 may be delivered using all or parts of the first delivery network 106 . in addition , the user may also obtain content directly from the internet via the second delivery network 112 without necessarily having the content managed by the content manager 110 . several adaptations for utilizing the separately delivered content may be possible . in one possible approach , the special content is provided as an augmentation to the broadcast content , providing alternative displays , purchase and merchandising options , enhancement material , etc . in another embodiment , the special content may completely replace some programming content provided as broadcast content . finally , the special content may be completely separate from the broadcast content , and may simply be a media alternative that the user may choose to utilize . for instance , the special content may be a library of movies that are not yet available as broadcast content . the receiving device 108 may receive different types of content from one or both of the delivery networks . the receiving device 108 processes the content , and provides a separation of the content based on user preferences and commands . the receiving device 108 may also include a storage device , such as a hard drive or optical disk drive , for recording and playing back audio and video content . further details of the operation of the receiving device 108 and features associated with playing back stored content will be described below in relation to fig2 . the processed content is provided to a display device 114 . the display device 114 may be a conventional 2 - d type display or may alternatively be an advanced 3 - d display . the receiving device 108 may also be interfaced to a second screen such as a touch screen control device 116 . the touch screen control device 116 may be adapted to provide user control for the receiving device 108 and / or the display device 114 . the touch screen device 116 may also be capable of displaying video content . the video content may be graphics entries , such as user interface entries , or may be a portion of the video content that is delivered to the display device 114 the touch screen control device 116 may interface to receiving device 108 using any well - known signal transmission system , such as infra - red ( ir ) or radio frequency ( rf ) communications and may include standard protocols such as infra - red data association ( irda ) standard , wi - fi , bluetooth and the like , or any other proprietary protocols . in the example of fig1 , the system 100 also includes a back end server 118 and a usage database 120 . the back end server 118 includes a personalization engine that analyzes the usage habits of a user and makes recommendations based on those usage habits . the usage database 120 is where the usage habits for a user are stored . in some cases , the usage database 120 may be part of the back end server 118 . in the present example , the back end server 118 ( as well as the usage database 120 ) is connected to the system the system 100 and accessed through the second delivery network 112 . referring now to fig2 , a block diagram of an embodiment of a receiving device 200 is shown . receiving device 200 may operate similar to the receiving device described in fig1 and may be included as part of a gateway device , modem , set - top box , or other similar communications device . the device 200 shown may also be incorporated into other systems including an audio device or a display device . in either case , several components necessary for complete operation of the system are not shown in the interest of conciseness , as they are well known to those skilled in the art . in the device 200 shown in fig2 , the content is received by an input signal receiver 202 . the input signal receiver 202 may be one of several known receiver circuits used for receiving , demodulation , and decoding signals provided over one of the several possible networks including over the air , cable , satellite , ethernet , fiber and phone line networks . the desired input signal may be selected and retrieved by the input signal receiver 202 based on user input provided through a control interface or touch panel interface 222 . touch panel interface 222 may include an interface for a touch screen device . touch panel interface 222 may also be adapted to interface to a cellular phone , a tablet , a mouse , a high end remote or the like . the decoded output signal is provided to an input stream processor 204 . the input stream processor 204 performs the final signal selection and processing , and includes separation of video content from audio content for the content stream . the audio content is provided to an audio processor 206 for conversion from the received format , such as compressed digital signal , to an analog waveform signal . the analog waveform signal is provided to an audio interface 208 and further to the display device or audio amplifier . alternatively , the audio interface 208 may provide a digital signal to an audio output device or display device using a high - definition multimedia interface ( hdmi ) cable or alternate audio interface such as via a sony / philips digital interconnect format ( spdif ). the audio interface may also include amplifiers for driving one more sets of speakers . the audio processor 206 also performs any necessary conversion for the storage of the audio signals . the video output from the input stream processor 204 is provided to a video processor 210 . the video signal may be one of several formats . the video processor 210 provides , as necessary , a conversion of the video content based on the input signal format . the video processor 210 also performs any necessary conversion for the storage of the video signals . a storage device 212 stores audio and video content received at the input . the storage device 212 allows later retrieval and playback of the content under the control of a controller 214 and also based on commands , e . g ., navigation instructions such as fast - forward ( ff ) and rewind ( rew ), received from a user interface 216 and / or touch panel interface 222 . the storage device 212 may be a hard disk drive , one or more large capacity integrated electronic memories , such as static ram ( sram ), or dynamic ram ( dram ), or may be an interchangeable optical disk storage system such as a compact disk ( cd ) drive or digital video disk ( dvd ) drive . the converted video signal , from the video processor 210 , originating either from the input or from the storage device 212 , is provided to the display interface 218 . the display interface 218 further provides the display signal to a display device of the type described above . the display interface 218 may be an analog signal interface such as red - green - blue ( rgb ) or may be a digital interface such as hdmi . it is to be appreciated that the display interface 218 can generate the various screens for presenting the search results in a three dimensional gird as will be described in more detail below . the controller 214 is interconnected via a bus to several of the components of the device 200 , including the input stream processor 202 , audio processor 206 , video processor 210 , storage device 212 , and a user interface 216 . the controller 214 manages the conversion process for converting the input stream signal into a signal for storage on the storage device or for display . the controller 214 also manages the retrieval and playback of stored content . furthermore , as will be described below , the controller 214 performs searching of content and the creation and adjusting of the gird display representing the content , either stored or to be delivered via the delivery networks , described above . the controller 214 is further coupled to control memory 220 ( e . g ., volatile or non - volatile memory , including ram , sram , dram , rom , programmable rom ( prom ), flash memory , electronically programmable rom ( eprom ), electronically erasable programmable rom ( eeprom ), etc .) for storing information and instruction code for controller 214 . control memory 220 may store instructions for controller 214 . control memory may also store a database of elements , such as graphic elements containing content . the database may be stored as a pattern of graphic elements . alternatively , the memory may store the graphic elements in identified or grouped memory locations and use an access or location table to identify the memory locations for the various portions of information related to the graphic elements . further , the implementation of the control memory 220 may include several possible embodiments , such as a single memory device or , alternatively , more than one memory circuit communicatively connected or coupled together to form a shared or common memory . still further , the memory may be included with other circuitry , such as portions of bus communications circuitry , in a larger circuit . referring now to fig3 , the user interface process of the present disclosure employs an input device that can be used to express functions , such as fast forward , rewind , etc . to allow for this , a tablet or touch panel device 300 ( which is the same as the touch screen device 116 shown in fig1 ) may be interfaced via the user interface 216 and / or touch panel interface 222 of the receiving device 200 . the touch panel device 300 allows operation of the receiving device or set top box based on hand movements , or gestures , and actions translated through the panel into commands for the set top box or other control device . in one embodiment , the touch panel 300 may simply serve as a navigational tool to navigate the grid display . in other embodiments , the touch panel 300 will additionally serve as the display device allowing the user to interact directly with the navigation through the grid display of content . the touch panel device may be included as part of a remote control device containing more conventional control functions such as activator buttons . the touch panel 300 can also include at least one camera element . as described in further detail below , content displayed on the touch panel device 300 may be zapped or thrown to the main screen ( e . g ., display device 114 shown in fig1 ). referring now to fig4 , the use of a gesture sensing controller or touch screen , such as that shown above , provides for a number of types of user interaction . the inputs from the controller are used to define gestures and the gestures , in turn , define specific contextual commands . the configuration of the sensors may permit defining movement of a user &# 39 ; s fingers on a touch screen or may even permit defining the movement of the controller itself in either one dimension or two dimensions . two - dimensional motion , such as a diagonal , and a combination of yaw , pitch and roll can be used to define any 4 - dimensional motion , such as a swing . a number of gestures are illustrated in fig4 . gestures are interpreted in context and are identified by defined movements made by the user . bumping 420 is defined by a two - stroke drawing indicating pointing in one direction , either up , down , left or right . the bumping gesture is associated with specific commands in context . for example , in a time shifting mode , a left - bump gesture 420 indicates rewinding , and a right - bump gesture indicates fast - forwarding . in other contexts , a bump gesture 420 is interpreted to increment a particular value in the direction designated by the bump . checking 440 is defined as in drawing a checkmark . it is similar to a downward bump gesture 420 . checking is identified in context to designate a reminder , user tag or to select an item or element . circling 440 is defined as drawing a circle in either direction . it is possible that both directions could be distinguished . however , to avoid confusion , a circle is identified as a single command regardless of direction . dragging 450 is defined as an angular movement of the controller ( a change in pitch and / or yaw ) while pressing a button ( virtual or physical ) on the tablet 300 ( i . e ., a “ trigger drag ”). the dragging gesture 450 may be used for navigation , speed , distance , time - shifting , rewinding , and forwarding . dragging 450 can be used to move a cursor , a virtual cursor , or a change of state , such as highlighting outlining or selecting on the display . dragging 450 can be in any direction and is generally used to navigate in two dimensions . however , in certain interfaces , it is preferred to modify the response to the dragging command . for example , in some interfaces , operation in one dimension or direction is favored with respect to other dimensions or directions depending upon the position of the virtual cursor or the direction of movement . nodding 460 is defined by two fast trigger - drag up - and - down vertical movements . nodding 460 is used to indicate “ yes ” or “ accept .” x - ing 470 is defined as in drawing the letter “ x .” x - ing 470 is used for “ delete ” or “ block ” commands . wagging 480 is defined by two trigger - drag fast back - and - forth horizontal movements . the wagging gesture 480 is used to indicate “ no ” or “ cancel .” depending on the complexity of the sensor system , only simple one - dimensional motions or gestures may be allowed . for instance , a simple right or left movement on the sensor as shown here may produce a fast forward or rewind function . in addition , multiple sensors could be included and placed at different locations on the touch screen . for instance , a horizontal sensor for left right movement may be placed in one spot and used for volume u / down , while a vertical sensor for up down movement may be place in a different spot and used for channel up / down . in this way , specific gesture mappings may be used . as discussed in further detail below , a two finger swipe gesture may be utilized to initiate the throwing or moving of content from the tablet 300 to the main screen or display device 114 . referring now to fig5 , a method is shown that may be implemented by , e . g ., a content distribution service , an online market service , etc . ( e . g ., content manager 110 or the broadcast affiliate manager 104 ) to ascertain information about multiple users associated with a single account using binary feedback information . block 502 receives a set of binary labels as an input . these labels are provided by one or more users sharing an account and are associated with a set of items . for example , the items in question may be movies , and the labels can indicate whether the account has viewed these movies or not . alternatively , the items could be products advertised to the account and the labels may indicate whether the account purchased the products or not . the label for an item i is denoted herein as y i . block 504 receives a set of item descriptors , one of each of labeled item . these descriptors could be , e . g ., vectors describing the genre or actors participating in a movie or other features of the product advertised . this feature descriptor may be represented as a vector of real - valued numbers of dimension d ( where d is the number of features ). the descriptor of item i will be shown herein as x i . using this information , block 506 estimates the mean and covariance of the underlying features x i . to do this , block 506 constructs estimates of the feature mean and covariance over the features and labels . a standard gaussian version of the features may then be constructed as { circumflex over ( σ )} − 1 / 2 ( x i −{ circumflex over ( μ )}), where { circumflex over ( σ )} is the covariance and { circumflex over ( μ )} is the feature mean . using the calculated estimates , block 508 identifies a vector r that belongs to a convex code spanned by the vectors profiling each user . the vector may be calculated as where n is the number of labels , and this vector lies in the interior of the convex cone spanned by the parameter profiles . the vector r may then be used to perform a mirroring operation , where all labels lying in the negative half space determined by r are flipped , for example by changing + 1 to − 1 and − 1 to + 1 in block 510 . the flipped labels are denoted herein by z i . block 512 computes a weighted covariance matrix q over all x i , where each point &# 39 ; s contribution is weighed by the mirrored labels . the matrix q is determined as the spectrum of q has a specific structure that reveals the span of the users . in particular , q converges to a matrix that contains an eigenvalue with multiplicity n - k , where n is the number of labels and k is a number of remaining eigenvalues . block 514 calculates eigenvectors and eigenvalues of the matrix q . most eigenvalues of q will be equal to each other ( i . e ., a number of eigenvalues having multiplicity n - k ), but a small number of eigenvalues will differ . the standout eigenvalues are calculated by finding the median value of all the eigenvalues and identifying the k values furthest from the median . the number of eigenvalues that “ stand out ” in this respect is interpreted as being a number of users associated with the account . the eigenvectors corresponding to the stand - out eigenvalues yield the span of the user profiles . block 516 rotates the eigenvectors by multiplying by to obtain the span and outputs these quantities . the resulting span is a set of vectors that are in the subspace defined by all linear combinations of the vectors . the span output by block 516 can be used for several tasks . for example , the span may be used to predict a label for an item given a new feature vector ( in other words , predicting whether a user would watch this movie ). the span may also be used for clustering , allowing the content provider to identify which user associated with an account generated a particular label . any algorithm that does either clustering or prediction will run with improved accuracy if one first projects the features to the span defined by profiles . using such information allows the content provider to make a recommendation using well known techniques . for example , if a user choose a movie with a certain actor , the content provider could recommend other movies with that actor . these and other features and advantages of the present principles may be readily ascertained by one of ordinary skill in the pertinent art based on the teachings herein . it is to be understood that the teachings of the present principles may be implemented in various forms of hardware , software , firmware , special purpose processors , or combinations thereof . most preferably , the teachings of the present principles are implemented as a combination of hardware and software . moreover , the software may be implemented as an application program tangibly embodied on a program storage unit . the application program may be uploaded to , and executed by , a machine comprising any suitable architecture . preferably , the machine is implemented on a computer platform having hardware such as one or more central processing units (“ cpu ”), a random access memory (“ ram ”), and input / output (“ i / o ”) interfaces . the computer platform may also include an operating system and microinstruction code . the various processes and functions described herein may be either part of the microinstruction code or part of the application program , or any combination thereof , which may be executed by a cpu . in addition , various other peripheral units may be connected to the computer platform such as an additional data storage unit and a printing unit . it is to be further understood that , because some of the constituent system components and methods depicted in the accompanying drawings are preferably implemented in software , the actual connections between the system components or the process function blocks may differ depending upon the manner in which the present principles are programmed . given the teachings herein , one of ordinary skill in the pertinent art will be able to contemplate these and similar implementations or configurations of the present principles . although the illustrative embodiments have been described herein with reference to the accompanying drawings , it is to be understood that the present principles is not limited to those precise embodiments , and that various changes and modifications may be effected therein by one of ordinary skill in the pertinent art without departing from the scope or spirit of the present principles . all such changes and modifications are intended to be included within the scope of the present principles as set forth in the appended claims .
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referring now to the drawings , and particularly to fig1 - 4 , a concrete discharge chute employing a preferred embodiment of the concrete chute apparatus of the present invention is shown and generally designated by the reference numeral 10 . in fig1 , a concrete discharge chute 10 is shown concrete discharge chute 10 is arranged in cooperation with a conventional cement truck ( not shown ) and includes a main chute section 12 to which is hingeably coupled to over - chute section 14 . main chute section 12 and over - chute section 14 form an elongated chute having a concave interior through which cement can be dispensed when over - chute section 14 is in the down position . main chute section 12 has a distal end 22 and a proximal end 20 , where the proximal end is that end closest to the cement truck . similarly , over - chute section 14 has a distal end 26 and a proximal end 24 , where the distal end is that end furthest from the truck when over - chute section 14 is in its down position . the chute sections further include distal end surfaces substantially orthogonally oriented relative to a chute axis . in fig1 , over - chute section 14 is shown in its up position . this position is used when the concrete truck is traveling on roads and highways . to place the discharge chute 10 in this position , over - chute section 14 rotates counter - clockwise about chute hinge 16 and comes to rest on the main chute section 12 as shown . in an embodiment , the discharge chute 10 may have oversized hinge portions of the chute sections such that the length of the chute section sidewalls are not in contact with one another . when over - chute section 14 is in this up position , a circular opening is formed between the over - chute section 14 and the main chute section 12 . the new and improved concrete chute apparatus 18 , located at the distal end of the main chute 22 , is shown obscuring the aforementioned opening . such apparatus may also be referred to as abutment plate 18 , as the apparatus abuts an inner surface of main chute section 12 to prevent the discharge of cement or cement debris . consequently , plate 18 is shown in fig1 in its “ in use ” position . that is , abutment plate 18 is shown in that position that prevents concrete debris from falling from concrete discharge chute 10 . by positioning the abutment plate 18 within the main chute 12 , cement debris and residue in concrete discharge chute 10 is prevented from accidentally discharging from the truck . abutment plate 18 is mounted to over - chute section 14 such that abutment plate 18 remains stationary with respect to over - chute section 14 . abutment plate 18 is mounted to a chute first edge 36 spaced from and parallel to a chute second edge 38 . abutment plate 18 may be welded or riveted or otherwise directly mounted onto over - chute section 14 using any metal fastening method . alternately , abutment plate 18 may be mounted via plate - mounting bracket 28 and plate - mounting means 30 . in the preferred embodiment shown , plate - mounting means 30 may be a bolt . plate 18 is mounted to the proximal end 24 of over - chute section 14 such that abutment plate 18 is arranged within the distal end 22 of main chute 12 when over - chute section 14 is in the up , or traveling , position . placement at the distal end 22 of main chute 12 allows abutment plate 18 to accommodate a larger volume of concrete debris within the main chute section 12 than would be possible if abutment plate 18 were arranged at , for example , the proximal end 20 of main chute 12 . referring to fig2 , the over - chute section 14 is shown in the down , or dispensing , position . chute handle 32 would be used to rotate the over - chute section 14 about the chute hinge 16 , thus positioning over - chute section 14 in either the up or down position . as noted above , plate 18 remains stationary with respect to over - chute section 14 . consequently , abutment plate 18 is arranged above the concrete discharge chute 10 when the over - chute section is in the down position more particularly , abutment plate 18 is arranged above over - chute section 14 . abutment plate 18 includes an arcuate bottom wall orthogonally oriented between the front and rear parallel walls of the plate . it is noted that the arcuate abutment plate bottom wall is arranged to form complementary reception within the concave interior surface of the main chute section 12 . abutment plate 18 may have an arcuate top wall 42 configured to allow the material dispensed from the discharge chute 10 to extend somewhat above the level of the sidewall extents of the chute sections . in an embodiment , abutment plate 18 may include a straight top wall . in yet another embodiment , abutment plate 18 may include an arcuate portion coupled with at least one linear portion , as shown . fig3 is a cross sectional view taken on line 3 of fig1 . shown in fig3 is the abutment plate 18 in use . that is , abutment plate 18 is in the down position , and is preventing discharge of cement 40 located within main chute section 12 . abutment plate 18 may retain cement 40 unless the level of cement 40 exceeds the height of arcuate top wall 42 . abutment plate 18 is therefore constructed of a rigid material having sufficient strength to hold material dispensed from discharge chute 10 . in an embodiment , abutment plate may be of the same material as the discharge chute 10 . in an embodiment , abutment plate may be metal , metal alloy , rigid plastic , or composite . also shown in fig3 by way of example is plate - mounting means 30 in a position offset from abutment plate 18 . in an alternate embodiment , plate - mounting means 30 may be commensurate with abutment plate 18 . plate mounting means 30 may be any means known in the art to attach abutment plate 18 to over - chute 14 . fig4 is a cross - sectional view of fig2 along line 4 . fig4 illustrates dispense of cement from concrete discharge chute 10 while abutment plate 18 is in use . as shown , abutment plate 18 is arranged above over - chute chute section 14 . the material dispensed may pass unaffected by the presence of abutment plate 18 . this may also be true in those cases in which a large volume of material is discharged , such that the discharge chute is completely full and material extends above the sidewalls in those areas of the chute closest to the chute axis . for example , arcuate top wall 42 of abutment plate 18 will allow dispense of cement , for example , to pass beneath , even if the level of the cement rises above the sidewalls of the chute . in use , it can now be understood that the concrete chute apparatus described herein would provide a substantially maintenance free apparatus which would in function provide a means to prevent debris from falling from the chute of a cement truck or similar vehicle having an articulated chute . the abutment plate 18 would not require independent adjustment , and would therefore always be in the correct position . the abutment plate 18 has no moving parts which could malfunction or which would require servicing . further , the abutment plate 18 is attached to the discharge chute 10 and therefore could not become lost . while a preferred embodiment of the concrete chute apparatus inline water treatment system has been described in detail , it should be apparent that modifications and variations thereto are possible , all of which fall within the true spirit and scope of the invention . with respect to the above description then , it is to be realized that the optimum dimensional relationships for the parts of the invention , to include variations in size , materials , shape , form , function and manner of operation , assembly and use , are deemed readily apparent and obvious to one skilled in the art , and all equivalent relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by the present invention . for example , any suitably rigid material may be used for the concrete chute apparatus . further , the apparatus may be attached to the over - chute using any metal fastening means known in the art . therefore , the foregoing is considered as illustrative only of the principles of the invention . further , since numerous modifications and changes will readily occur to those skilled in the art , it is not desired to limit the invention to the exact construction and operation shown and described , and accordingly , all suitable modifications and equivalents may be resorted to , falling within the scope of the invention .
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the following detailed description and appended drawings describe and illustrate various exemplary embodiments of the invention . the description and drawings serve to enable one skilled in the art to make and use the invention , and are not intended to limit the scope of the invention in any manner . in respect of the methods disclosed , the steps presented are exemplary in nature , and thus , the order of the steps is not necessary or critical . one possible overall arrangement of an elevator installation is illustrated in fig1 and fig1 a . fig1 shows the elevator installation 1 in a schematic side view and fig1 a shows the same elevator installation 1 in a schematic plan view . the illustrated elevator installation 1 comprises an elevator car 3 which moves in a vertical direction in a shaft 2 along guide tracks 7 . the elevator car 3 is supported by support means 5 and is connected with a counterweight 4 . the counterweight 4 and the elevator car 2 are driven by a drive 6 by way of the support means 5 and move in opposite sense in the elevator shaft 2 . the elevator car 3 is provided with braking equipment 11 which brakes the elevator car or keeps it at standstill . the braking equipment 11 comprises at least two brake units 12 which each act on a respective one of the guide tracks 7 . the brake units 12 co - operate as a single braking equipment 11 , wherein the braking equipment 11 can optionally define the braking force requirement for a single individual brake unit 12 . the brake units 12 are , in the illustrated example , attached below the car body 3 . however , attachment laterally and / or above the elevator car 3 is also possible . obviously , combinations of these attachment locations are also conceivable . this would be useful above all if , for extending the braking performance , several brake units 12 are used . the elevator car is provided with guide shoes which guide the car 2 along the guide track 7 . in the illustrated example the guide track 7 is formed by a t - shaped guide rail , which at the same time is also a brake track 8 . other forms of elevator installations are obviously possible . an automotive elevator car , for example with a linear motor , can be used and the elevator shaft can be partly open , or separate tracks for guiding ( guide track 9 ) and braking ( brake track 8 ) can be used . fig2 shows the elevator brake unit 12 as used in correspondence with the present invention in the elevator installation 1 according to fig1 . the brake unit 12 is attached to the car 3 . the brake unit 12 comprises a brake housing 13 , a brake plate 14 movable with respect to the brake housing 13 and a brake plate 15 fixed with respect to the brake housing 13 . the brake plates 14 and 15 are , in the case of need , brought by means of an advance device 19 into contact with the brake track 8 . the brake plates 14 and 15 are connected by means of fastening plates 16 with the brake housing 13 and the advance device 19 , respectively . the brake track 8 in the illustrated example is at the same time the guide track 7 , wherein a conventional t - shaped guide rail is used . the brake unit 12 further comprises a guide support 17 . the guide support 17 serves for fastening or connecting the brake housing 13 with the car 3 . it is fixedly connected with the car 3 . a wear - compensating device 30 is , in the illustrated example , arranged between the guide supports 17 and the brake housing 13 . the guide support 17 at the same time comprises the guide shoe 9 which guides the elevator car 3 along the guide track 7 . the guide shoe 9 is resiliently mounted with respect to the car 3 . this enables insulation from guidance vibrations . a resilient intermediate element 10 allows the car 3 oscillatory deviations ( distance “ a ”) relative to the guide track 7 . a clearance “ if ”, “ ib ” of the brake unit is in this case set to be of such a size that even in the case of outward oscillation of the car within the scope of the guidance resilience “ a ” and possible guidance plays “ f ” as well as offsets in the meeting of guide track parts no contact of the brake plates 14 , 15 with the guide track 7 or brake track 8 takes place . the wear - compensating device 30 now keeps the fixed clearance “ if ”, during release of the brake 12 , substantially constant on the side of the fixed brake plate 15 . the illustrated brake unit 12 further consists of electromechanical components . it comprises advance regulating means 21 which keeps a predetermined total clearance “ it ” constant by actuating the advance device 19 . the total clearance “ it ” is formed by the sum of the fixed clearance “ if ” and the movable clearance “ ib ”, wherein the fixed clearance “ if ” corresponds with the side of the fixed brake plate 15 and the movable clearance “ ib ” corresponds with the side of the movable brake plate 14 . the terms “ fixed ” and “ movable ” are used in this connection merely for definition . the advance regulating means 21 moves the movable brake plate 14 directly perpendicularly to the brake or guide surface 7 , 8 . as a rule , several wear - compensating devices 30 are arranged in parallel , preferably one above the other . the brake unit 12 is an electromechanical brake unit in which the movable brake lining 14 is advanced by means of an electromechanical drive , such as , for example , a spindle drive . in the case of need the advance spindle is actuated by way of a gear stage . the brake unit 12 preferably comprises advance checking means in the advance regulating means 21 . by means of this advance checking means a brake plate wear and / or deviations from a normal behavior of the brake unit 12 can be ascertained and a signal generated on an advance checking signal line 24 so that the overall wear can be checked by this method . as a rule the wear - compensating device 30 is set in such a manner that the clearance “ if ” of the side of the fixed brake plate 15 is equal to the clearance “ ib ” of the movable brake plate 14 . it thus corresponds with half the total clearance “ it ”. this setting is advantageous when centrally suspended or centrally guided elevator cars 3 are concerned . however , the wear - compensating device 30 also enables asymmetric settings , whereby an uneven division of the clearances ( if , ib ) can be achieved . this is useful particularly in the case of asymmetrically suspended elevator cars , where a possible wear of the guide shoes 9 makes itself noticeable on one side . the guide support 17 further comprises a holder 18 . the holder 18 supports the brake plates 14 , 15 or the fastening plates 16 and conducts braking forces directly into the guide support 17 and further into the car 3 . the brake housing 13 itself is thereby relieved of the actual braking force ; merely the normal force acting in one direction and generating the braking force by way of friction has to be accepted . fig3 illustrates the settable wear - compensating device 30 in detail . the wear - compensating device 30 consists of a positioning part 31 , a restoring unit 32 , a first abutment 33 and a second abutment 34 . the wear - compensating device 30 produces a connection of the brake housing 13 with the guide support 17 . in this embodiment the positioning part 31 is connected by a slip connection 35 with the guide support 17 . the positioning part 31 is preferably produced from a plastic material . it can be displaced relative to the guide support 17 only by a substantial force of , for example , approximately 25 n to 50 n . the positioning part 31 itself is slidably arranged in the brake housing 13 to be easy - running . the brake housing 13 can thereby displace relative to the guide support 17 in two stages . the direction of displacement is in that case oriented in the direction of the normal force . in a first displacement stage the brake housing 13 can be displaced by a small force slidingly relative to the positioning part 31 and thus also slidingly relative to the guide support 17 . this sliding displacement is limited by the first abutment 33 and the second abutment 34 . this first displacement stage corresponds with the desired clearance “ if ” of the fixed brake plate side . in the example , this first displacement stage or the clearance “ if ” is settable by means of a clearance play setting screw 36 . the restoring unit 32 , which is arranged between the brake housing 13 and the positioning part 31 , in the form of a spring in this connection displaces the brake housing 13 up to the boundary mark of the first abutment 33 . in a second displacement stage the brake housing 13 together with the positioning part 31 can be displaced in slipping manner relative to the guide support 17 . the fig4 series — comprising fig4 . 1 to 4 . 4 a - now explain by way of example the functional sequence for compensation of wear . fig4 . 1 , 4 . 2 , 4 . 3 and 4 . 4 each show a working setting , by way of example , of the brake unit and the details according to fig4 . 1 a , 4 . 2 a , 4 . 3 a and 4 . 4 a show the respectively associated setting of the wear compensation device . fig4 . 1 and fig4 . 1 a show the brake unit 12 in the working setting , i . e . the brake is open . the brake linings 14 , 15 are spaced on both sides of the brake track 8 by the clearance ( if , ib ). the positioning part 31 of the wear compensating unit 30 is pressed against the first abutment 33 defined by the clearance play setting screw 36 . the possible free displacement path or slide path of the positioning part 31 is set in correspondence with the desired fixed clearance “ if ”. in the case of actuation of the brake unit 12 there thus takes place in a first step ( s 1 ) advance of the movable brake plate 14 by means of the advance device 19 until the movable plate 14 contacts the brake track 8 , and then , by further actuation of the advance device 19 , the brake housing 13 together with the fixed brake plate 15 is urged towards the opposite side of the brake track 8 ( s 2 ) until the fixed brake plate 15 contacts the opposite side of the brake track 8 . tightening of the brake plates 14 , 15 relative to the brake track 8 now takes place by a further advance movement , whereby braking is carried out . this work setting is illustrated in fig4 . 2 and 4 . 2 a . it is illustrated in the following how now compensation is provided for the clearance in the wear compensating unit 30 . the positioning part 31 stands against the second abutment 34 . compensation for abrasion or wear of the movable brake plate 14 is now , as illustrated in fig4 . 3 and 4 . 3 a , provided directly by a further advance of the movable brake plate 14 by the advance device 19 . compensation of wear “ v ” of the fixed brake plate 15 is carried out indirectly in that the advance device 19 further advances the brake housing 13 together with the fixed brake plate 15 ( s 3 ) or pulls this tight and this advance of the brake housing 13 produces in the wear - compensating device 30 a slipping in the slip connection 35 between the brake housing 13 and the guide support 17 , since the slide path of the positioning part 31 is already applied . the advanced position of the brake housing 13 together with the fixed brake plate 15 thus now achieved forms the final working position of the fixed brake lining 15 in this braking sequence . this final working position now necessarily forms the basis for resetting of the brake housing 13 together with the fixed brake plate 15 . on opening of the brake unit 12 the reverse sequence takes place analogously , which leads to the state according to fig4 . 4 and 4 . 4 a . the advance device 19 relieves the brake plates 14 , 15 , and thereafter the brake housing 13 together with the fixed brake plate 15 , beginning from the final working position , is reset in correspondence with the set clearance “ if ” of the fixed brake plate 15 ( s 4 ). this resetting is produced by the restoring unit 32 which , acting against the positioning part 31 , displaces the brake housing 13 in acting in correspondence with the set clearance path “ if ” back to the first abutment 33 . as is apparent in fig4 . 4 a , the positioning part 31 now slips relative to the guide support 17 by the wear amount “ v ”. the fixed brake plate 15 has reached its clearance “ if ” and the movable brake plate 14 can now be drawn back by the residual amount of the total clearance ( ib = it − if ). the brake unit is ready for the next braking action and the advance travels correspond with the new state . thus , actuating times , which were applicable to the new brake , can also be maintained for a worn brake . fig5 shows a schematic view of a second embodiment brake unit 12 a with a wear - compensating device and an elevator car guide integrated in the brake unit . the guide support 17 is guided along the brake and guide track 7 , 8 directly by the guide shoe 9 , whilst the car 3 is fastened relative to the guide support 17 by way of a resilient element 10 a , for example a rubber spring , a damper or an active vibration damping means . the function of the braking equipment 12 a itself corresponds with the foregoing illustrations . the advantage of this solution results from the fact that the clearance “ if ” can be executed to be smaller , since an oscillatory path of the car does not have to be taken into consideration . obviously the coupling of the guide support 17 is designed in such a manner that vertical braking and retaining forces can be transmitted . fig6 shows a schematic view of a third embodiment brake unit 12 b with a wear - compensating device and a separate guidance for the brake unit and the elevator car . the guide support 17 b is guided along the brake and guide track 7 , 8 directly by the guide shoe 9 and the car 3 is guided by own guide elements ( not illustrated ). the function of the brake equipment 12 b itself corresponds with the preceding illustrations . the advantage of this solution results from the fact that the clearance “ if ” can similarly be formed to be small , since an oscillatory path of the car 3 does not have to be taken into consideration and a design of the guide shoe 9 of the brake can be undertaken independently of the car 3 . fig7 shows a fourth of embodiment of a brake unit 12 c with wear - compensating device . the guide support 17 is fastened relative to the car 3 . the brake housing 13 is connected with the guide support 17 by way of the positioning part 31 c and a support pin 37 . the support pin 37 is analogously a part of the guide support 17 . the brake housing 13 is slidingly displaceable on the sleeve - shaped positioning part 31 c , wherein the displaceability on the positioning part 31 c is limited by a slide limitation , which can be set by means of clearance play setting screw or clearance play setting nut 36 in correspondence with the desired clearance “ if ”. the restoring unit 32 urges the brake housing 13 , when the advance device 19 is relieved , into the release position with respect to the first abutment 33 . when the wear “ v ” occurs , the positioning part 31 c can slip on the support pin 37 , which leads to a wear compensation , as analogously explained in the fig4 series . two support pin arrangements of that kind are preferably arranged one above the other , whereby braking forces are also directly transmissible . the slip connection 35 in this example of embodiment is solved in particularly economic manner . o - rings 38 are inserted in the positioning part 31 c and the positioning part 31 c is pushed by light pressure onto the support pin 37 , which is advantageously produced from metal or steel . this slip connection 38 is preferably lubricated . the definition of the required slip force takes place in co - ordination with the definition of the restoring unit . the force required for slipping lies by more than approximately 40 % above the force able to be applied by the restoring unit . instead of the illustrated slip connection 35 on a friction basis , use could also be made of detent connections . detent connections re - adjust in steps . fig8 shows the brake unit according to fig7 with an integrated holder . the guide support 17 already illustrated in fig7 is provided with the holder 18 , which directly supports the brake plates 14 , 15 during braking and thus introduces braking and holding forces into the guide support 17 . the brake housing 13 together with the wear - compensating device 30 and the entire advance device 19 is thereby loaded merely by normal forces . fig9 shows another embodiment of a brake unit with a wear - compensating device and a support pin according to the present invention . the brake housing 13 is , similarly to that shown in fig7 , connected with the guide support 17 by way of the positioning part 31 and a support pin 37 d . the support pin 37 d is analogously a part of the guide support 17 . the brake housing 13 is arranged on the sleeve - shaped positioning part 31 d to be slidingly displaceable . the displaceability on the positioning part 31 d is limited by a slide limitation , which can be set by means of clearance play setting screw or clearance play setting nut 36 in correspondence with the desired clearance “ if ”. the functionality of the slide limitation in this example is integrated in the support pin 37 d and the functionality of the slipping is integrated between brake housing 13 and the positioning part 31 d . the restoring unit 32 urges the brake housing 13 , when the advance device 19 is relieved , towards the first abutment 33 into the clearance position . when the wear “ v ” occurs , the brake housing 13 can slip on the positioning part 31 d , which leads to a wear compensation as explained analogously in the fig4 series . here , too , two support pin arrangements of that kind are preferably arranged one above the other , whereby the braking forces were transmitted directly to the guide support . with knowledge of the present invention and the illustrated variants of embodiment the elevator expert can change and combine the set forms and arrangements as desired . for example , the illustrated use of o - rings , the solution of the support pin and also the arrangement of guide elements or the use of a holder can be combined with the illustrated arrangements of wear - compensating devices . similarly , the guide shoe can be formed with use of known technologies . in particular , use can be made of a sliding guide shoe or a roller guide shoe 9 a in fig5 . the guide shoe 9 a can comprise a measuring system on the basis of which a travel speed of the braking equipment or of the car can be ascertained to generate a signal on a line 25 . this information can be used , for example , by a regulating unit of the braking equipment . in addition , a regulated clearance play setting with use of a servomotor is possible . in that case , for example , a clearance play “ if ” of the fixed brake plate side would be changed in dependence on the operational state of the elevator installation in that the clearance play setting screw 36 would be screwed in or out by means of the servomotor . in accordance with the provisions of the patent statutes , the present invention has been described in what is considered to represent its preferred embodiment . however , it should be noted that the invention can be practiced otherwise than as specifically illustrated and described without departing from its spirit or scope .
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referring to fig1 an engine 7 has a throttle body 1 having a throttle valve 2 communicated with an intake pipe 3 . in the intake system , an air cleaner 4 and intake air temperature sensor 5 are provided . the throttle body 1 is further communicated with an intake manifold 6 which is communicated with a combustion chamber of each cylinder ( not shown ) in the engine 7 . in an exhaust pipe 17 , an o 2 - sensor 13 is provided . fuel is supplied to fuel injectors 8 from a fuel tank 9 by a fuel pump 10 , and returned to the tank 9 through a passage 12 and a pressure regulator 11 which is opened by intake manifold pressure applied through a pipe 12a . an intake manifold pressure sensor 14 is provided in the throttle body 1 for detecting intake manifold pressure p . a coolant temperature sensor 16 is provided in the engine 7 for detecting of temperature of the coolant . the coolant temperature sensor 16 produces an output signal , the voltage of which is dependent on the temperature . output signals of the sensors 5 , 13 , 14 and 16 are applied to a control unit 15 for controlling fuel injectors 8 . the control unit 15 is further applied with a pulse signal from crank angle sensor ( engine speed sensor ) 18 representing engine speed n and with a signal from an idle switch 19 which is turned on when an accelerator pedal of the vehicle is released . referring to fig2 showing the control unit 15 , a fuel injection pulse width calculator 20 is applied with output signals of the intake air temperature sensor 5 , intake manifold pressure sensor 14 , coolant temperature sensor 16 , o 2 - sensor 13 and crank angle sensor 18 . the fuel injection pulse width calculator 20 calculates a basic pulse width dependent on the intake manifold pressure p and the engine speed n from sensors 14 and 18 , respectively . the basic pulse width is corrected in accordance with output signals of the coolant temperature sensor 16 intake air temperature sensor 5 and o . sub . 2 - sensor 13 to obtain an appropriate fuel injection pulse width in the engine operating condition . a fuel injection pulse width signal from the fuel injection pulse width calculator 20 is applied to fuel injectors 8 through a driver 21 to inject the fuel to operate the engine . in order to cut off the fuel at idling of the engine , a fuel cutoff control section 22 is provided in the control unit 15 . the fuel cutoff control section 22 has a fuel cutoff deciding section 23 to which output signals of the coolant temperature sensor 16 , crank angle sensor 18 and idle switch 19 are applied . the fuel cutoff deciding section 23 determines that the vehicle is under a fuel cutoff condition when an engine speed n exceeds a predetermined cutoff engine speed n c ( n ≧ n c ) while the accelerator pedal is released in the engine warmed - up state . the engine speed n and the output signal of the idle switch 19 are also supplied to an engine speed increase calculator 24 where increment δn or increasing rate of the engine speed is obtained by either of the following equations . where n e is the engine speed after a predetermined time from closing of idle switch 19 , n id is the engine speed when the idle switch is turned on , t is the elapsed time and θ is the crank angle . the output signals of the deciding section 23 and the calculator 24 are fed both to an immediate cutoff deciding section 25 and a delayed cutoff deciding section 26 to which a set delay time signal is applied from a timer 27 . an output signal from the cutoff deciding sections 25 or 26 is applied to the injection pulse width calculator 20 in order to compulsively cutoff the fuel injection . the operation of the system will be described hereinafter with reference to a flowchart shown in fig3 and to graphs shown in fig4 a to 4d . referring to fig3 at a step s101 , it is determined whether the idle switch is on or off . when the accelerator pedal is depressed for the acceleration of the vehicle , the idle switch 19 is off so that the program proceeds to a step s106 . thus , the fuel cutoff deciding section 23 determines that the engine is not under a condition for the fuel cutoff so that a fuel signal is applied to the fuel injection pulse width calculator 20 . accordingly , the injection pulse width obtained in dependence on the intake manifold pressure p and engine speed n and others is fed to the injector 8 so as to provide an appropriate air - fuel ratio in relation to the amount of intake air , in any engine operating conditions . when the accelerator pedal is released while the vehicle is driven or at a stop , idle switch is turned on . therefore , the program proceeds to a step s102 where it is determined whether engine speed n is larger than the predetermined cutoff speed n c . when the engine speed n is smaller than the speed n c ( n & lt ; n c ), the program goes to the step s106 , so that fuel injection is continued . when the acceleration pedal is suddenly released to close the throttle valve at a time t o ( fig4 a ), while the engine speed n is larger than the fuel cutoff speed n c ( n ≧ n c ) fig4 c ), the fuel cutoff deciding section 23 determines that the vehicle is under the fuel cutoff condition , thereby applying a signal to the immediate cutoff deciding section 25 and delayed cutoff deciding section 26 . in the electronic fuel injection system for an engine having a large intake manifold volume , engine torque gradually decreases as shown in fig4 b . at a step s103 , the engine speed increment δn is calculated at the engine speed increase calculator 24 and the increment δn is compared with a predetermined reference value k . the output of the calculator 24 is applied to the deciding sections 25 and 26 . when the clutch is engaged during the release of the accelerator pedal , the load of a transmission system exerted on the engine restrains the increase of the engine speed as shown in fig4 c . when the increment δn is smaller than the reference value k ( δn & lt ; k ), counting of the delay time set in the timer 27 is started . when the set time has elapsed , the program proceeds to a step 105 where a fuel cut flag fcut is set . therefore , a cutoff signal from the delayed cutoff deciding section 26 is applied to the fuel injection pulse width calculator 20 to stop the injection as shown by a dotted line in fig4 c . if the clutch is disengaged at a time t 1 immediately after the release of the accelerator pedal in order to shift the change speed gear , the remaining torque of the engine speeds up the engine as shown in fig4 d . when the engine speed increment δn becomes larger than the predetermined value k , the program proceeds directly to the step s105 . accordingly , the fuel is cutoff at a time t 2 as shown by a dotted line in fig4 d . thus , the engine speed decreases until the gear shift operation is completed at a time t 3 . when the accelerator pedal is depressed , the idle switch 19 is turned off , thereby injecting the fuel ( steps s101 , s106 ). thus , the engine speed increases in accordance with the depression of the accelerator pedal . during the cutoff of the fuel while coasting , if the engine speed n becomes lower than the predetermined cutoff speed n c , the fuel injection is restored by the signal from the fuel cutoff deciding section 23 ( steps s102 , s106 ). the system of the present invention may also be applied to an engine provided with a carburetor . in accordance with the present invention , when the clutch is disengaged in order to shift gears of the manual transmission , the speed up of the engine is prevented without fail . while the presently preferred embodiment of the present invention has been shown and described , it is to be understood that this disclosure is for the purpose of illustration and that various changes and modifications may be made without departing from the scope of the invention as set forth in the appended claims .
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the block diagram of a system for generating a periodic sequence y n is illustrated in fig1 . register 10 , in its most general form , is a parallel - in - parallel - out analog register of k stages . this is the memory of the system . the output signal of register 10 is an x n vector signal whose components denote the stages of the register at time n . the periodic sequence y . sub . n is produced by a transversal operation h ( in general , nonlinear ) on x n in h network 30 . the next state of the memory , x n + 1 , is generated in f network 20 by operating on the signal vector x n with a vector function f , and by substituting x n + 1 for x n in register 10 . the equations that mathematically describe the system of fig1 are the operator f of equation ( 1 ) may be nonlinear , although for purposes of this invention , it is restricted to have a fixed point at 0 ( i . e . f ( 0 ) = 0 ) and to be analytic in the neighborhood of 0 . for the sequence x n to be periodic , there must exist a smallest integer p such that x n + p = x n . this , of course , is one definition of periodicity . since x n + 1 = f ( x n ) by equation ( 1 ), x n + p may be rewritten as x n + p = f p ( x n ), where f p is a p - fold composition of f . this implies that x n + p = x n = f p ( x n ), or that f p = i , where i is the identity map . it can be said , therefore , that f p is p periodic , where periodicity is defined as the smallest integer p which renders f p equal to the identify map i . the linear term in the taylor expansion of f , designated l , is called the linear part of f . it can be shown that replacing f by l does not change the period of recursion , and that accordingly , nonlinearities in f cannot increase the period , or for a given period , nonlinearities in f cannot reduce the required memory . for convenience and ease of implementation , therefore , f is restricted to be a linear map l . it can also be shown that for any desired period p ( which can be represented by the canonical prime number decomposition ## equ1 ## the minimum required memory , k , is ## equ2 ## where δ = 1 if the greatest common divisor of p and 4 is equal to 2 ( designated ( p , 4 )= 2 ), and where δ = 0 otherwise . equation ( 3 ) can also be expressed as k = σk i - δ , where k i = φ ( p i . sup . α . sbsp . i ). the euler function φ ( p i . sup . α . sbsp . i ) has a value equal to the number of positive integers which are less than and relatively prime to p i . sup . α . sbsp . i . in close form , it is known that φ ( p i . sup . α . sbsp . i ) is equal to ( p i . sup .. sup . α . sbsp . i - 1 )( p - 1 ). from the above , given a period p , the minimum memory required for the implementation of the system of fig1 can be computed . table 1 depicts the required memory for periods ranging from 1 through 61 . table 2 depicts the maximum period obtainable for given memory size , ranging from k = 1 to k = 50 . table 2 is generated by searching through an expanded table 1 for the maximum period at each given memory size . for example , k = 8 in table 1 corresponds to periods 16 , 21 , 28 , 36 , 40 , 42 , and 60 . in fact , 60 is the maximum period achievable with memory k = 8 . table 1______________________________________period memory period memory1 1 31 302 1 32 163 2 33 124 2 34 165 4 35 106 2 36 87 6 37 368 4 38 189 6 39 1410 4 40 811 10 41 4012 4 42 813 12 43 4214 6 44 1215 6 45 1016 8 46 2217 16 47 4618 6 48 1019 18 49 4220 6 50 2021 8 51 1822 10 52 1423 22 53 5224 6 54 1825 20 55 1426 12 56 1027 18 57 2028 8 58 2829 28 59 5830 6 60 8 61 60______________________________________ table 2______________________________________ memory maximum period 1 2 2 6 4 12 6 30 8 60 10 120 12 210 14 420 16 840 18 1260 20 2520 24 5040 26 9240 28 13860 30 27720 32 32760 34 55440 36 65520 38 120120 40 180180 42 360360 46 720720 50 942480______________________________________ in accordance with the principles of this invention , for the generation of sequences having a period ## equ3 ## r independent subperiods must be generated and combined to form the period p ( with the only exception that r - 1 subperiods are generated when ( p , 4 )= 2 ). each subperiod i is generated with an independant register i of memory k i and an independent linear feedback network l i . if l i is chosen to have the form 0 1 . . . 0 0 0 . . . . . . . . . . . . . . . . l . sub . i = 0 0 . . . 1 0 0 ( 4 ) 0 0 . . . 0 1 0 0 0 . . . 0 0 1 β . sub . k . sbsb . i . sup . i α . sub . k . sbsb . i . sbsb . 1 . sup . i . . . β . sub . 3 . sup . i β . sub . 2 . sup . i β . sub . 1 . sup . i where x i n + 1 = l i x i n , and x i n + 1 and x i n are column vectors starting with the terms ( x i n + 1 ) k . sbsb . i and ( x i n ) k . sbsb . i and decrementing to ( x i n + 1 ) 1 and ( x i n ) 1 , respectively , the following observations can be made . a . l i represents the mapping of an x i n vector ( of a sequence of period p i . sup . α . sbsp . i ) onto an x i n + 1 vector wherein each component of x i n + 1 , except the last component , is derived from a single component of x i n . more specifically , ( x i n + 1 ) j = ( x i n ) j - 1 for all k i & gt ; j & gt ; 1 , while ( x . sup . i . sub . n . sub .+ 1 ). sub . 1 = β . sup . i . sub . 1 ( x . sup . i . sub . n ). sub . 1 + β . sup . i . sub . 2 ( x . sup . i . sub . n ). sub . 2 + β . sup . i . sub . 3 ( x . sup . i . sub . n ). sub . 3 + . . . β . sup . i . sub . k . sbsb . i ( x . sup . i . sub . n ). sub . k . sbsb . i ( 5 ) b . this choice of l i greatly simplifies the circuitry since the parallel register of fig1 can be substituted with a shift register which inherently provides the function ( x i n + 1 ) j = ( x i n ) j - 1 6 c . the ( x i n + 1 ) 1 vector component can be implemented in an l i feedback network connected to each shift register stage via a multiplication network multiplying each ( x i n ) j by a constant β i j and an addition network performing the sum in accordance with equation ( 5 ). this arrangement is illustrated in fig2 wherein the product signals β 1 j ( x 1 n ) j are summed in accordance with equation ( 5 ) and inserted into the first shift register &# 39 ; s first stage , and the product signals β i j ( x i n ) j are summed in accordance with equation ( 5 ) and inserted into the ith register &# 39 ; s first stage . it can further be shown that if the coefficients β i j are restricted to be integers then , necessary requirements on the roots of ψ ( λ ) cause the determinant l i - λi to be equal to the cyclotomic polynomial of order p i . sup . αi , i . e ., ## equ4 ## since all the coefficients of a cyclotomic polynomial of power - of - prime order are 0 or 1 , all the β &# 39 ; s are either 0 or - 1 . in fact , it can be shown that every ( p i . sup .. sup . α . sbsp . i - 1 ) th tap , viewing the shift register in the direction of signal transfer , ( left to right in fig2 ), has a multiplicative factor - 1 , or a polarity reversal , and all other taps have a multiplicative factor 0 . the above is correct for all p such that ( p , 4 )≠ 2 . if ( p , 4 ) = 2 , the canonical prime number decomposition of p must contain the factor 2 1 , in which case p can be written ## equ5 ## and only r - 1 registers are necessary for implementing the period p . the lone factor 2 may be combined with any one of the p i . sup . α . sbsp . i terms and be implemented via an l i matrix whose characteristic polynomial is a cyclotomic polynomial of order 2p . sup . α . the coefficients of a cyclotomic polynomial of order 2p . sup . α are ± 1 or 0 . as related to the hardware implementation , the particular p i . sup . α . sbsp . i chosen to be combined with the factor 2 is constructed in exactly the same manner as if it were not combined , except that in the feedback path the signal of every odd nonzero tap is multiplied by + 1 instead of - 1 . the above derived cyclotomic polynomials and the resultant cyclotomic circuits are merely a specie of a class of circuits whose characteristic functions are cyclotomic polynomials . these circuits , herein called cyclotomic circuits are circuits having a shift register of a specified number of stages , integer feedback coefficients associated with each stage and multiplying the output signal of each stage , and a nonmodulo summer responsive to the integer multiplied signals impressing its output signal onto the first stage of the shift register . cyclotomic circuits , in general , do not utilize minimum memory in their sequence generation without the above described power - of - prime decomposition . these circuits , however , have the distinct advantage over prior art circuits in that they always utilize integer coefficient factors . this allows for easy implementation and error free operation . a cyclotomic (&# 34 ; circle - dividing &# 34 ;) polynomial of order m , denoted f m ( λ ), is defined as a polynomial with integer coefficients , all of whose roots are primitive m th roots of unity ( that is , r m = 1 , and r n ≠ 1 for 0 & lt ; n & lt ; m ). from this definition , it can be explicitly determined that ## equ6 ## where the product is taken over all d &# 39 ; s occurring in the range 1 ≦ d & lt ; m , such that d and m are relatively prime . the number of d &# 39 ; s determines the degree of the f m ( λ ) polynomial . the number of d &# 39 ; s within the range is found by evaluating the euler function φ ( m ) and adding 1 to the result . the euler function φ ( m ) is defined , in fact , as an integer equal to the number of positive integers less than or equal to m and having no integer factors , other than 1 , common to m ( such integers are said to be relatively prime to m ). when m is written as a product of powers of prime ## equ7 ## it can be shown that ## equ8 ## for example , if m = 30 , φ ( m ) = 7 and thus , the number of numbers relatively prime to 30 is 7 + 1 , or 8 . indeed , the numbers that are relatively prime to 30 are 1 , 7 , 11 , 13 , 17 , 19 , 23 , and 29 . this list in fact contains exactly eight numbers . in view of equation ( 9 ), the function f m ( λ ) of equation ( 7 ) can be rewritten as ## equ9 ## for m = 30 , equation ( 11 ) can be rewritten as , ## equ10 ## note that all roots appear in complex conjugate pairs , i . e . ## equ11 ## which is the complex conjugate of ## equ12 ## conversion of equation ( 12 ) to cartesian coordinates yield f . sub . 30 ( λ ) = λ . sup . 8 + λ . sup . 7 - λ . sup . 5 - λ . sup . 4 - λ . sup . 3 + λ + 1 ( 13 ) with the expected real integer coefficients . interestingly , all the nonzero coefficients of f ( λ ) in equation ( 13 ) are either + 1 , - 1 , or zero . these coefficients correspond to the β j coefficients of equations ( 5 ) and ( 7 ). thus , an order 30 cyclotomic circuit , though not of minimum memory , can be implemented with a single shift register ( of length 8 ) and a single l i network of the type shown in fig2 . specifically , correlating equations ( 7 ) and ( 13 ), in the l 1 network of fig2 β 1 = - 1 , β 2 = 0 , β 3 = 1 , β 4 = 1 , β 5 = 1 , β 6 = 0 , β 7 = 1 and β 8 = - 1 . as illustrated by the above example , cyclotomic polynomials , happily , make very desirable characteristic polynomials because of their extreme simplicity . for example , for k & lt ; 105 , or for a k that is a product of two prime numbers , the coefficients of f ( λ ) are all 0 or ± 1 . for a k that is a power of a single prime , the coefficients are all 0 and + 1 ; and for k & lt ; 385 , the coefficients do not exceed 2 in absolute value . this means , of course , that in all cases of practical interest , the feedback coefficients of network 20 in fig1 will be 0 and ± 1 ; which means that there is either no connection , a direct connection or a negative connection . equation ( 2 ), supra , defines the operation h which transforms the multilevel vector signal x n to a multilevel scalar signal y n . the use of the h operator also allows for the shaping of nonlinearities into the output signal y n in order to satisfy other conditions , such as the fit of y n to a desired norm , the spreading of the energy of the output signal in the frequency domain , etc . periodicity of the output signal is guaranteed , of course , independent of h , by the periodicity of the sequence x n . the only requirement on h , therefore , is that it not decrease the period of the recursion . it can be shown that a sufficient condition on h for preserving the period p is that the linear part of h preserves the period of x n . it can further be shown that this condition is satisfied if h is made a function of a single output from each of the shift registers which generate the sequences of relatively prime periods . since the sequences generated by the shift registers of fig2 are relatively prime , having been designed in accordance with the prime number decomposition of the period p , the h function of fig2 need be responsive to only single outputs of each of the shift registers of fig2 to produce no reduction in the output signal &# 39 ; s period . fig3 illustrates the sequence generator of this invention for a period p = 90 . shift register 11 generates the period ( 2 )( 5 ), while shift register 12 generates the period 3 2 . the h function chosen is simply the sum function of a single output of the registers 11 and 12 . as has been indicated , supra , the utilization of only a single output from each register assures that the transversal network h will not reduce the period p . in accordance with this invention , the number of stages required for shift register 11 is ( 5 1 - 1 )( 5 - 1 ), or 4 . every 5 1 - 1 , or 1 th , tap is nonzero , and since the period has a multiplicative factor 2 , every odd nonzero tap ( counting in the direction of signal flow ) has a + 1 multiplicative factor , while every even nonzero tap has a - 1 multiplicative factor . this feedback arrangement is illustrated in fig3 with two summers ; an inverting ( polarity reversing ) summer 14 connected to taps 2 and 4 of register 11 and a noninverting summer 15 connected to taps 1 and 3 of register 11 and to the output port of summer 14 . the output signal of summer 15 is applied to the input port of register 11 . the number of stages in shift register 12 is ( 3 2 - 1 )( 3 - 1 ), or 6 , and every 3 2 - 1 , or 3 rd , tap has a - 1 multiplicative factor . accordingly , in the illustration of fig3 an inverting ( polarity reversing ) summer 16 is connected and made responsive to taps 3 and 6 of register 12 , and the output signal of summer 16 is applied to the input port of register 12 . the output signals of registers 11 and 12 are connected to analog adder 13 which combines the output signals of register 11 and 12 to develop the desired sequence of period 90 . in addition to the displayed capability of generating a signal sequence of any desirable period , it can also be shown that the apparatus of this invention may be arranged to provide both a desirable sequence period and a specific amplitude sequence . in concept , this capability is easily realizable via the h function , because with any chosen initial state for the generator , a particular sequence of period p is developed ; and from the developed sequence , the desired sequence can be derived from an h network comprising a read - only memory of large enough storage . in practice , however this brute force technique is unattractive because the resultant h network would be extremely complex , large , and expensive , and because any changes in the desired sequence would entail drastic changes in the h network . it can be shown , that even with a restricted h function which simply comprises the sum of single outputs of the independent registers in the sequence generator , an innumerable number of sequences can be generated by judiciously controlling the initial state of the sequence generator . not all possible sequences are generatable in this manner because in order to generate all sequences of length p , p ° of freedom are necessary , whereas the available memory in the sequence generator of this invention offers only k degrees of freedom . however , it can shown that for a given desired sequence w of length p , a best approximation w ( in the least square sense ) can be realized by controlling the initial conditions in the following manner . 1 . having a memory of length k , generate a set of k orthonormal unit vectors , d u , forming an orthonormal basis and defining a linear space . 2 . compute the projection of w on the space defined by the set of d u vectors by computing the normal inner products of w with each of the d u vectors , i . e ., compute & lt ; w , d u & gt ; for u = 1 , 2 . . . k . for purposes of clarity , the immediately following description depicting the generation of an orthonormal basis is limited to a period p which is a single power of a prime number , i . e ., p = q v . it has been shown , supra , that when p = q v , the l matrix has k distinct roots ρ n , where k =( q v - 1 )( q - 1 ), and that these roots are the primitive roots of unity of the cyclotomic polynomial of order q v . it can be shown that vectors generated from powers of different roots are orthogonal , i . e ., ( ρ 1 i , ρ 2 i , ρ 3 i . . . ρ p i ) is orthogonal to ( ρ 1 j , ρ 2 j , ρ 3 j . . . ρ p j ) when i ≠ j , and that the set of vectors 1 / p ( ρ 1 n , ρ 2 n , ρ 3 n . . . ρ p n ) for n = 1 , 2 , 3 , . . . k forms a valid orthonormal basis . another orthonormal basis can be derived from sequences of length p generated by inserting the following set of initial conditions in the shift register of the sequence generatorvector shiftno reg . 1 2 3 . . . k loc . ______________________________________1 1 0 0 . . . 02 0 1 0 . . . 03 0 0 1 . . . 0k 0 0 0 . . . 1______________________________________ it can be shown that this generated set of k sequences can be orthonormalized by the graham - schmitt orthonormalization procedure and that the resultant orthonormal basis b n defines the same linear space defined by the d u basis . since b n and d n define the same linear space , it can be shown that for a given desired sequence w , the best approximation sequence w can be generated by computing ## equ14 ## for purposes of illustration , the use of the above method is described for a sequence generator having a period 5 where the desired sequence is (- 5 , 0 , 4 , 2 , - 1 ). in accordance with the principles of this invention , the sequence generator of period 5 has 4 stages . the 4 initial conditions are the initial conditions , therefore , are the first k components of w , in this instance (- 5 , 0 , 4 , 2 ,). these initial conditions yield the sequence w = (- 5 , 0 , 4 , 2 , - 1 ), which in this case is exactly equal to w . the above procedure for p = q v may be generalized ## equ16 ## when it is realized that the orthonormal basis for one register generated by its ρ vectors ( which are the ( p i . sup . α . sbsp . i ) th roots of unity ) is orthogonal to the orthonormal basis for another register generated by its ρ vectors ( which are the ( p j . sup . α . sbsp . j ) th roots of unity ). similar results can be shown to be true for orthonormal bases composed of b u vectors generated in the same manner as in the p = q v case . thus , when ## equ17 ## each of the r ( or r - 1 ) registers has k i stages of memory , and r ( or r - 1 ) independent orthonormal bases must be generated , with each basis having k i vectors . the remainder of the procedure is the same as for p = q v cases . namely , compute the factors & lt ; w , b u & gt ; and construct the approximated function ## equ18 ## for example , if a sequence generator is constructed to provide a period of 12 , and if it is further desired that the output sequence be it can be shown that the generator will comprise two registers of length 2 , one ( register a ) connected to develop a period 3 and the other ( register b ) connected to develop a period 4 . the orthonormal basis of register a may be derived from the initial conditions 10 and 01 which yield the sequences from the above , the inner products & lt ; w , b u & gt ; can be computed , which when carried out , results in the above indicates that the initial condition for register a is + 2 and - 1 and the initial condition for register b is - 1 and 0 . carrying out the computation , it can be seen that in this example w is exactly equal to w . the above discussion has been limited , until now , to ideal analog shift registers , in the sense that no errors have been assumed to exist . in a physical implementation of the sequence generator of this invention , errors will be introduced by interstage transmission losses within the shift register and by gain variations in the feedback amplifier . the problems raised by the nonidealness of such practical systems are not critical in many applications , but in applications where idealness is critical a skilled artisan can easily resolve the problems associated therewith . however , for the sake of completeness , fig4 is presented to illustrate one way of overcoming the loss problem . therein , a quantizer 22 is interposed between the summing gain unit 23 and register 24 . the quantizer must be a staircase quantizer which is sensitized to resolve and quantize all the levels that are expected to be encountered in the operation of the generator . quantizer 22 may comprise , for example a plurality of voltage comparators which one input of each connected to summing unit 23 and the other input of each connected to the various desired quantizer threshold voltages . the output currents of the voltage comparators may be summed and applied to a resistor to provide the necessary staircase quantization function . it is understood , of course that the embodiments shown and disclosed herein are only illustrative of the principles of this invention , and that modifications may be implemented by those skilled in the art without departing from the spirit and scope of the invention . for example , although the virtues and advantages of the subject apparatus have been associated with analog shift registers , in any particular application where , subject to known initial conditions , the maximum value for the output sequence is known , a bank of shift registers , somewhat akin to those used by the aforementioned nakamura patent , may be used , thereby eliminating the need for a quantizer . also , although a particular signal of the disclosed embodiments has been described , it is to be understood that any avilable signal in the disclosed embodiments can serve as the output signals , since that signal would differ from the described signal only be a time delay and , possibly , by a multiplicative constant .
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referring now to the drawings , and more particularly , to fig1 and 2 , one embodiment of a collapsable table 10 , made according to the present invention is disclosed . table 10 includes a table top 20 , a pair of interlocking legs 30 and 40 , and a leg receiving block 50 , see fig2 . table top 20 includes substantially planar top surface 22 and bottom surface 24 . in the preferred embodiment , table top 20 includes a downwardly depending flange 21 about the perimeter of the table top . the depth of the flange below the undersurface of the table top is preferably equal to the combined thicknesses of the essentially flat legs 30 and 40 for storing purposes , as will hereinafter be explained . the table may be made of any of the common materials such as wood , plastics , or metals . it is also contemplated that the top surface 22 of table top 20 may be venerred , as in standard table tops . referring now to fig2 , and 4 , the leg receiving block of one preferred embodiment of the present invention may be seen to advantage . leg receiving block 50 may be round in configuration , in which case the diameter of block 50 must be slightly smaller than the central openings 31 and 41 of legs 30 and 40 , respectively , as shown in fig1 . it is an essential element of the present invention that the receiving block 50 be of lesser width than the openings in the legs for proper storage of the legs on the undersurface of the table top . block 50 includes two notches 51 which extend the complete diameter of the block and intersect one another at substantially right angles . depth of the notches should be sufficient to prevent any rotation or lateral movement of the legs in respect to the block . block 50 may be mounted to the undersurface 24 of table top 20 in the center of the undersurface by means of glue , screws , or other conventional fastening means . leg receiving block 50 may be made of any suitable material . as may be seen in fig1 and 3 legs 30 and 40 of collapsable table 10 are essentially plate like , having vertical coplanar opposing surfaces . each of the legs 30 and 40 , contain at their uppermost edge a pair of horizontally extending , rectilinear , table top contacting surfaces separated by a recede portion 32 and 42 , respectively . the recede portions are flat and extend horizontally parallel with the table top contacting surfaces . leg 30 includes a pair of oppositely disposed grooves 33 extending vertically from the center of recede portion 32 to an opening 31 located in the center of the leg . leg 30 also contains a vertical slit 35 , in alignment with grooves 33 , extending from opening 31 to a second recede portion 34 which defines two floor contacting shoes 36 and 37 . leg 40 has the same general configuration and the same dimensions as leg 30 . leg 40 includes a vertical slit 45 extending from first recede portion 42 to a centrally located opening 41 , and a pair of oppositely disposed grooves 43 extending from opening 41 to a second recede portion 44 which defines a pair of floor contacting shoes 46 and 47 . in assembling collapsable table 10 , leg 30 is lowered onto leg 40 so that the edges of the leg which define slit 35 interlockingly engage the grooves 43 of leg 40 . in the process , the edges of leg 40 defining slit 45 interlockingly engage grooves 33 of leg 30 . it will therefore be seen that legs 30 and 40 are locked together at right angles one to the other in an immovable relationship . table top 20 is then lowered onto the uppermost surfaces of legs 30 and 40 so that the horizontally extending , rectilinear , top surfaces of recede portion 32 and 42 mate with and interlockingly engage notches 51 of leg receiving block 50 . the rectilinear top edges of the legs protruding above the recede portions concurrently make flush contact with bottom surface 24 of table top 20 . the process is simply reversed for dismanteling . for storage , or for carrying , legs 30 and 40 are placed flat against one another with the planar side surfaces of the legs laying flush against one another and against the bottom surface 24 of table top 20 as may be seen to advantage in fig4 . the centrally located circular openings 31 and 41 of legs 30 and 40 respectively , encase leg receiving block 51 in a snug relationship . the uppermost surface of the outermost leg is flush with the top surface of leg receiving block 51 and depending flange 21 of table top 20 while in this stored position . referring now to fig5 and 6 , a second preferred embodiment of the present invention may be seen . the second embodiment differs from the above described embodiment primarily in the square shapes of top and legs and in the configuration of leg receiving block 50 &# 39 ; and central openings 31 &# 39 ; and 41 &# 39 ; of legs 30 &# 39 ; and 40 &# 39 ;, respectively . in the second embodiment the central leg openings and the leg receiving block are both square , the openings being slightly larger than the block for convenient storage as previously mentioned . the square configuration of the block and openings , while lacking the advantage found in the circular block and openings as previously described of storage of the legs at any angle relative to the block , does have the particular advantage of holding the legs in a secure and non rotatable position relative to the block and to the undersurface of the table top . in either embodiment , the table may include a first locking means , locking flanges 70 located on the bottom surface of receiving blocks 50 or 50 &# 39 ; as may be seen in fig4 and 6 . flanges 70 are horizontally rotatable about pins 71 , and in operation are rotated so that the undersurface of the flange comes in contact with the uppersurface of the side of a leg to hold the legs flush against the undersurface of the table top for storage and for carrying . the table may also contain a second locking means to lock the legs to the undersurface of the table top and leg receiving block to maintain the table in an assembled position . for this purpose , a flange 80 is mounted on the bottom surface of the receiving block adjacent the intersecting notches 51 as may be seen in fig2 and 6 . flange 80 is rotated to engage flange receiving slots 84 which are located adjacent to and parallel with the top surface of the first recede portion of the legs and transverse to the vertical grooves and slits of the legs as may best be seen in fig1 and 5 . having thus described in detail a preferred selection of embodiments of the present invention , it is to be appreciated and will be apparent to those skilled in the art that many physical changes could be made in the apparatus without altering the inventive concepts and principles embodied therein . the present embodiments are therefore to be considered in all respects as illustrative and not restrictive , the scope of the invention being indicated by the appended claims rather than by the foregoing description , and all changes which come within the meaning and range of equivalency of the claims are therefore to be embraced therein .
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referring now to the drawings , and more particularly to fig1 one embodiment of the line storage device in accordance with the present invention is shown and referenced generally by numeral 10 . by way of example , line storage device 10 will be described for its use with a rocket - deployed line charge system , the basic elements of which are illustrated in fig1 . however , it is to be understood that line storage device 10 can be used with any similar line charge or other deployment system having a propulsion unit tethered to a distributed and tethered set of individual masses . more generally , the present invention will also be of use in any system requiring the storage of excess line and tangle - free payout of the line as is the case with a parachute system . in terms of the illustrated line charge system , a rocket 100 has a line 102 coupled on one end thereof to an aft end of rocket 100 . the other end of line 102 is coupled to the forward end of distributed line charge 104 . briefly , line charge 104 includes a fuze or detonator 106 coupled to a plurality of distributed explosive charges 108 by means a detonating cord 110 . a substantial amount of line 102 ( e . g ., eight feet or more ) extends between rocket 100 and fuze 106 . for proper operation of line charge 104 , rocket 100 must travel down range with line 102 being paid out thereafter . payout of line 102 must be tangle - free in order to assure proper placement of line charge 104 and activation of fuze 106 . that is , if line 102 becomes entangled with itself during payout , line charge 104 may not be placed in its anticipated location . if line 102 becomes entangled with line charge 104 , failure of fuze 106 as well as inaccurate placement of line charge 104 can result . accordingly , it is necessary to store line 102 in a tangle - free fashion as well as provide for its payout in a tangle - free fashion . to achieve tangle - free storage and payout of line 102 , line storage device 10 is provided . in the embodiment illustrated in fig1 line storage device 10 is a piece or block 12 of material having a channel 14 formed in a surface 16 thereof . channel 14 is laid out in a non - overlapping zigzag pattern over the length of block 12 . laid into channel 14 is the excess amount of line 102 between rocket 100 and fuze 106 . the width w of channel 14 can be formed so that line 102 and channel 14 are in press - fit engagement . alteratively or additionally , line 102 can be secured in channel 14 by , for example , a light tacking glue ( not shown ) or by tape covering channel 14 and adhered to surface 16 . such tape can be wrapped about block 12 . the optional tape feature is illustrated in fig1 by dashed lines 18 which indicate the edges of the wrapped tape . channel 14 is accessed from either end of block 12 so that line 102 can extend from either end of block 12 . the zigzag pattern presented by channel 14 can be any nonoverlapping zigzag pattern into which line 102 can be nondestructively formed . block 12 is made from a material that supports line 102 prior to the deployment of line charge 104 and that fails or ruptures during the deployment of line charge 104 . by doing so , the present invention provides a means to absorb and release launch energy that produces a standing wave in line 102 as discussed above in the background of the invention . more specifically , when rocket 100 begins to travel down range , line 102 between rocket 100 and line storage device 10 is placed in tension by the forward momentum of rocket 100 and the resting weight of line charge 104 . as line 102 is pulled taut at block 12 by rocket 100 at one end and by line charge 104 at the other end , line 102 exerts force on each successive “ loop ” formed by channel 14 in block 12 . due to the extreme tensile force , block 12 ruptures sequentially from both ends thereof at each successive loop of channel 14 effectively paying out line 102 while insuring against entanglement and absorbing / releasing launch energy to reduce the loading imparted by the standing wave . the energy is released during the sequential rupturing of block 12 . to support line 102 prior to deployment and failure at time of deployment as described above , block 12 is made from a solid material that will rupture as line 102 achieves a threshold tension . one suitable material is polystyrene which is lightweight , inexpensive , easily formed in terms of both overall shape and channel 14 , and is readily ruptured when line 102 achieves its threshold tension . other suitable materials include plaster and low density frangible plastics such as polypropylene , acrylic , vinyl , polyvinyl chloride and cellulose acetate just to name a few . block 12 can be formed from a piece of the selected stock material or could be molded into its specific shape and size . block 12 could also be formed or molded about a pre - shaped zigzag pattern of line 102 to thereby fully encase line 102 in block 12 . if there is a substantial amount of line 102 that must be stored or if the overall size of block 12 is of concern , the present invention can be extended to store parallel layers of line 102 . for example , line storage device 20 shown in top and bottom plan view in fig2 a and 2b , respectively , creates two layers of channels for storing line 102 . however , as will be appreciated by one of ordinary skill in the art , the following two - layer description can easily be extended to three or more layers . referring simultaneously to fig2 a and 2b , block 22 has zigzag channel 24 formed in top surface 26 as illustrated in fig2 a . channel 24 terminates at a feed through hole 28 that passes through to bottom surface 27 into which zigzag channel 25 is formed as illustrated in fig2 b . since line 102 must still extend from opposing ends of block 20 , line 102 is led across block 20 by a straight channel 29 in bottom surface 27 . by using feed through hole 28 to carry line 102 to its next layer of channel , all of line 102 is kept within and protected by block 102 . alternatively , line 102 can be led outside of block 102 to the next layer . the advantages of the present invention are numerous . as purely a line storage device , the present invention provides for ease of handling excess line . as a line payout control device , the present invention ensures that no slack develops during payout of the line by holding the line in a frangible package that ruptures in accordance with the sequential storing / payout of the line . thus , line snags or entanglement during deployment of a line charge system are eliminated thereby providing a high degree of confidence in terms of line charge placement and detonation . although the invention has been described relative to a specific embodiment thereof , there are numerous variations and modifications that will be readily apparent to those skilled in the art in light of the above teachings . it is therefore to be understood that , within the scope of the appended claims , the invention may be practiced other than as specifically described .
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inbred corn line lh185 is a yellow dent corn with superior characteristics , and provides an excellent parental line in crosses for producing first generation ( f 1 hybrid corn . lh185 was developed from the single cross lh59 × lh123ht by selfing and using the pedigree system of plant breeding . selfing and selection were practiced within the above f 1 cross for seven generations in the development of lh185 . some of the criteria used to select ears in various generations include : yield , stalk quality , root quality , disease tolerance , late plant greenness , late season plant intactness , ear retention , pollen shedding ability , silking ability , and corn borer tolerance . during the development of the line , crosses were made to inbred testers for the purpose of estimating the line &# 39 ; s general and specific combining ability , and evaluations were run by the williamsburg , iowa research station . the inbred was evaluated further as a line and in numerous crosses by the williamsburg and other research stations across the corn belt . the inbred has proven to have a very good combining ability in hybrid combinations . the inbred has shown uniformity and stability for all traits , as described in the following variety description information . it has been self - pollinated and ear - rowed a sufficient number of generations , with careful attention to uniformity of plant type to ensure homozygosity and phenotypic stability . the line has been increased both by hand and sibbed in isolated fields with continued observation for uniformity . no variant traits have been observed or are expected in lh185 . inbred corn line lh185 has the following morphologic and other characteristics ( based primarily on data collected at williamsburg , iowa ): lh185 is a line developed from the parents lh59 and lh123 . lh185 as a plant resembles more closely the lh123 parent except lh185 is a shorter plant with a very low ear placement . lh185 is earlier flowering than lh123 . in hybrid combination , the ear type is somewhat like lh123 ( relatively short and girthy ). lh185 has a much greater area of adaptability than lh123 had when lh123 was used commercially . one particular agronomic trait that increases lh185 &# 39 ; s area of adaptation over lh 123 is lh 185 &# 39 ; s improved resistance to summer stalk brittling . this was a particularly limiting problem that was characteristic of lh123 in a number of hybrids . lh185 has very good general combining ability . lh185 &# 39 ; s yield to moisture ratio is improved over either parent . in the tables that follow , the traits and characteristics of inbred corn line lh185 are given in hybrid combination . the data collected on inbred corn line lh185 is presented for the key characteristics and traits . the tables present yield test information about lh185 . lh185 was tested in several hybrid combinations at numerous locations , with two or three replications per location . information about these hybrids , as compared to several check hybrids , is presented . the first pedigree listed in the comparison group is the hybrid containing lh185 . information for the pedigree includes : 2 . a mean for the percentage moisture (% m ) for the hybrid across all locations . 3 . a mean of the yield divided by the percentage moisture ( y / m ) for the hybrid across all locations . 4 . a mean of the percentage of plants with stalk lodging (% sl ) across all locations . 5 . a mean of the percentage of plants with root lodging (% rl ) across all locations . 6 . a mean of the percentage of plants with dropped ears (% de ). 7 . the number of locations indicates the locations where these hybrids were tested together . the series of hybrids listed under the hybrid containing lh185 are considered check hybrids . the check hybrids are compared to hybrids containing the inbred lh 185 . the (+) or (-) sign in front of each number in each of the columns indicates how the mean values across plots of the hybrid containing inbred lh185 compare to the check crosses . a (+) or (-) sign in front of the number indicates that the mean of the hybrid containing inbred lh185 was greater or lesser , respectively , than the mean of the check hybrid . for example , a + 4 in yield signifies that the hybrid containing inbred lh185 produced 4 bushels more corn than the check hybrid . if the value of the stalks has a (-) in front of the number 2 , for example , then the hybrid containing the inbred lh185 had 2 % less stalk lodging than the check hybrid . table 1______________________________________overall comparisons oflh185 × lh195 hybrid vs . check hybrid mean % hybrid yield % m y / m % sl % rl de______________________________________lh185 × lh195 227 20 . 95 10 . 82 1 6 0 ( at 16 loc &# 39 ; s ) as compared to : lh195 × lh212 + 7 -. 67 +. 64 - 3 + 1 0lh132 × lh212 + 16 -. 43 +. 53 - 3 + 1 0lh195 × lh59 + 14 +. 64 +. 36 - 1 + 3 0lh195 × lh184 + 14 +. 67 +. 34 - 1 + 3 0______________________________________ table 2______________________________________overall comparisons oflh185 × lh198 hybrid vs . check hybrid mean % hybrid yield % m y / m % sl % rl de______________________________________lh185 × lh198 221 20 . 54 10 . 78 1 7 0 ( at 21 loc &# 39 ; s ) as compared to : lh132 × lh82 + 29 - 1 . 34 + 2 . 02 - 1 + 1 0lh204 × lh212 + 7 -. 63 +. 65 - 2 + 2 0lh132 × lh59 + 15 -. 37 +. 92 - 1 + 2 0lh205 × lh216 + 21 -. 34 + 1 . 17 0 + 1 0lh198 × lh59 + 12 -. 04 +. 59 0 + 1 0lh198 × lh82 + 27 +. 09 + 1 . 29 - 1 - 4 0______________________________________ table 3______________________________________overall comparisons oflh185 × lh132 hybrid vs . check hybrid mean % hybrid yield % m y / m % sl % rl de______________________________________lh185 × lh132 211 21 . 42 9 . 85 1 6 0 ( at 17 loc &# 39 ; s ) as compared tolh132 × lh212 + 3 -. 86 +. 51 - 1 + 3 0lhe136 × lh82 + 22 -. 03 + 1 . 05 - 1 + 3 0lh132 × lh59 + 17 +. 44 +. 61 - 1 + 1 0lh204 × lh212 + 2 +. 91 -. 37 - 2 + 1 0______________________________________ table 4______________________________________overall comparisons oflh185 × lh74 hybrid vs . check hybrid mean % hybrid yield % m y / m % sl % rl de______________________________________lh185 × lh74 189 20 . 91 9 . 03 3 4 0 ( at 21 loc &# 39 ; s ) as compared tolh74 × lh51 + 1 - 2 . 31 +. 95 - 1 - 1 0lh216 × lh206 + 1 - 1 . 84 +. 76 + 2 0 0lh132 × lh165 + 11 - 1 . 09 +. 96 0 - 1 0lh132 × lh167 + 1 -. 34 +. 18 - 1 - 1 0lh202 × lh82 + 14 -. 08 +. 64 - 4 - 2 0______________________________________ inbred seeds of lh185 have been placed on deposit with the american type culture collection ( atcc ), rockville , md . 20852 , under deposit accession number 75618 on dec . 3 , 1993 . a plant variety protection certificate is being applied for with the united states department of agriculture . although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity and understanding , it will be obvious that certain changes and modifications may be practiced within the scope of the invention , as limited only by the scope of the appended claims .
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as hereinbefore set forth , the present invention is concerned with a process for the hydration of olefinic hydrocarbons to prepare the corresponding alcohols . the process is effected by treating an olefinic hydrocarbon containing from about 2 to about 6 carbon atoms with water in the presence of certain catalytic compositions of matter of the type hereinafter set forth in greater detail . examples of olefinic hydrocarbons which may be employed as the starting materials in the process of this invention will include ethylene , propylene , butene - 1 , butene - 2 , pentene - 1 , pentene - 2 , hexene - 1 , hexene - 2 , hexene - 3 , etc . it is also contemplated within the scope of this invention that mixtures of the aforesaid olefins such as mixtures of ethylene and propylene , propylene and butene , etc . may also be used as the starting materials . in the preferred embodiment of this invention , the olefins will comprise the off - gases from refinery operations and may include mixtures of olefins and paraffins such as ethylene / ethane or propylene / propane . the hydration of the olefins by treatment with water is effected at hydration conditions which will include operating parameters such as temperatures in the range of from about 100 ° to about 300 ° c ., pressures ranging from about 10 to about 500 pounds per square inch gauge ( psig ), liquid hourly space velocities ranging from about 0 . 1 to about 10 . 0 hrs . - 1 based upon the olefin charged , and water to hydrocarbon ratios ranging from about 10 : 1 to about 50 : 1 moles of water per mole of hydrocarbon . the catalytic composition of matter which is used to effect the hydration of the olefin will comprise an alpha - zirconium phosphate , some specific examples of these compounds including alpha - zirconium orthophosphate , alpha - zirconium metaphosphate , alpha - zirconium pyrophosphate , ortho - zirconium hypophosphate , etc . the catalytic compositions of matter comprise solids which possess a layered or sheet - type structure in which the distance between the layers may be varied depending upon the preparative techniques which are employed in forming the catalyst . various methods of preparing the catalyst may be employed including those which are well known in the art . by forming the catalyst in a layered structure and by utilizing a cross - linking agent , it is possible to obtain a catalytic composition of matter which possesses excellent thermal stability and thus may be employed to effect the desired hydration reaction at temperatures well in excess of those which have heretofore been used in hydration reactions . the process of the present invention may be effected in any suitable manner and may comprise either a batch or continuous type of operation . for example , when a batch type operation is employed , a quantity of the catalyst is placed in an appropriate apparatus such as an autoclave of the rotating , mixing or stirring type along with water in an amount sufficient to afford the desired ratio of water to hydrocarbon . the autoclave is sealed and the hydrocarbon charge comprising an olefin containing from 2 to about 6 carbon atoms along with , if so desired , a paraffin which acts as a diluent , is charged to the reactor until the desired operating pressure has been attained . in the preferred embodiment of the invention , the operating pressure is afforded by the autogeneous pressure of the olefin , if in gaseous form . however , it is also contemplated within the scope of this invention that the olefinic charge stock may afford only a partial operating pressure , the remainder being produced by the introduction of a substantially inert gas such as nitrogen , helium , argon , etc . upon attaining the desired operating pressure , the apparatus is heated to a predetermined operating temperature within the range hereinbefore set forth , higher operating temperatures being possible due to the heretofore stated thermal stability of the catalytic compositions of matter . after allowing the hydration reaction to proceed for a predetermined period of time which may range from about 0 . 5 up to about 10 hours or more in duration , the reaction time being dependent upon the operating parameters chosen , heating is discontinued . after the apparatus has returned to room temperature , the excess pressure is vented , the apparatus is opened and the reaction mixture is recovered therefrom . the liquid reaction mixture is separated from the catalyst by conventional means such as filtration , decantation , centrifugation , etc ., and subjected to conventional means of separation such as fractional distillation , whereby the desired alcohol is separated from unreacted water and / or undesirable side products which may have been formed , and recovered . it is also contemplated that the hydration reaction of the present invention may be effected in a continuous manner of operation . when such a type of operation is employed , a quantity of the catalyst is placed in an appropriate reaction apparatus which is maintained at the desired operating conditions of temperature and pressure . the olefinic charge stock and the water are continuously charged to the reactor through separate means and , after passage through the reactor for a predetermined period of time , the reactor effluent is continuously withdrawn . the effluent is then subjected to conventional means of separation whereby unreacted starting materials comprising the olefinic hydrocarbon and water are separated from the alcohol product and recycled to the reaction zone to form a portion of the feedstock , while the desired product is recovered . a continuous type of operation may be effected in any suitable manner , one type of operation comprising a fixed bed mode in which the catalytic composition of matter is positioned in the reactor as a fixed bed and the reactants are passed through said bed in either an upward or downward flow . alternatively , a moving bed type of operation may be employed in which the catalyst and the reactants are passed through the reaction zone either concurrently or countercurrently to each other . a third method of operation which may be employed comprises the slurry type of operation in which the catalytic composition of matter is charged to the reactor as a slurry in either the water or the olefinic hydrocarbon . examples of alcohols which may be produced by utilizing the process of this invention will include ethanol , isopropanol , sec - butanol , sec - pentanol and sec - hexanol . the following examples are given for purposes of illustrating the process of this invention . however , it is to be understood that these examples are given merely for purposes of illustration and that the present process is not necessarily limited thereto . isopropanol may be prepared by placing the catalytic composition of matter comprising alpha - zirconium orthophosphate in a rotating autoclave along with a sufficient amount of water necessary to maintain a ratio of 25 : 1 moles of water per mole of hydrocarbon . the autoclave may then be sealed at a 65 / 35 mixture of propylene / propane charged thereto until a pressure of 100 psig is attained . the autoclave may then be heated to a temperature of 200 ° c . and maintained thereat for a period of four hours . at the end of this period , heating may be discontinued and after the autoclave has returned to room temperature , the excess pressure may be vented . the autoclave may then be opened and the reaction mixture recovered therefrom . after separating the liquid mixture from the catalyst , the former may then be subjected to fractional distillation and the desired isopropanol may be recovered therefrom . in this example , a catalyst comprising alpha - zirconium metaphosphate may be placed in an autoclave along with water in an amount sufficient so as to maintain a mole ratio of 50 moles of water per mole of hydrocarbon which may be charged to the reactor . the autoclave may then be sealed and a mixture of butene - 2 and butane may be charged to the reactor until an initial operating pressure of 250 psig has been reached . the autoclave may then be heated to a temperature of 300 ° c . and maintained thereat for a period of four hours . at the end of this time , heating may be discontinued and , after the autoclave has reached room temperature , the excess pressure may be vented . the autoclave may then be opened and the reaction mixture recovered therefrom . after separation from the catalyst , the liquid reaction mixture may again be subjected to fractional distillation and the desired sec - butanol may be separated from water and recovered . in a manner similar to that hereinbefore set forth , alpha - zirconium pyrophosphate may be used to catalyze the hydration of pentene - 2 and hexene - 1 by treating these compounds at an elevated temperature of about 250 ° c . and a pressure of 500 psig for a period of four hours . after recovery of the liquid product and separation from the catalyst , the product may be subjected to fractional distillation and the desired sec - pentanol and sec - hexanol recovered therefrom .
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the present invention relates generally to database systems and more particularly to deletion of data from child tables with multiple parents . the following description is presented to enable one of ordinary skill in the art to make and use the invention and is provided in the context of a patent application and its requirements . various modifications to the preferred implementations and the generic principles and features described herein will be readily apparent to those skilled in the art . thus , the present invention is not intended to be limited to the implementations shown , but is to be accorded the widest scope consistent with the principles and features described herein . when running applications against data in database environments , data is oftentimes operated on as groups of related data . these groups are typically defined by how tables containing the data are related to one another . in groups of related tables , there are parent tables and child tables . parent tables are tables that are related to another table where the relationship extends from the parent to the child . fig1 illustrates a system 100 with an application 102 , a database management system ( dbms ) 104 , and a database 106 . stored in database 106 is a plurality of tables . dbms 104 is operable to control access to and manipulation of data stored in database 106 . as seen in fig1 , application 102 is in communication with dbms 104 and is submitting a query 108 against one or more of the plurality of tables stored in database 106 . query 108 may be seeking to retrieve , modify , and / or delete one or more rows from a table in database 106 . query 108 may be written in structured query language ( sql ) or other database query languages . some applications , such as archiving applications , use a parent table to qualify data in a child table in order to copy the qualified data to another storage location , then delete the archived data from the parent and child tables . in one implementation , a row of a child table is qualified by a parent table when a column in the row of the child table and a related column in a row of the parent table have the same value and the row of the parent table satisfies a query on the parent table . the query may be from an application , such as an archiving application . depicted in fig2 is an example concerning three tables , table - a 202 , table - b 204 , and table - c 206 . as seen from fig2 , table - c 206 has two parent tables , table - a 202 and table - b 204 , assume , for instance , each of the tables in fig2 includes two columns — c 1 and c 2 . assume also that column c 1 in table - a 202 is related to column c 1 in table - c 206 and that column c 2 in table - b 204 is related to column c 2 in table - c 206 . if a query requests every row in table - a 202 where c 1 = x , then each row in table - c 206 where c 1 = x is a row qualified by table - a 202 and will be returned along with each row in table - a 202 where c 1 = x . when a child table has multiple parent tables , as with table - c 206 in fig2 , a special situation arises when deleting data from the child table because the child table is qualified by different parents , i . e ., each parent qualifies a set of data in the child . data sought to be deleted by an application can be defined as the intersection of all qualified sets plus the data qualified by each parent that does not exist in the intersection . to put it another way , the data subject to deletion can be thought of as the union of all qualified sets minus any duplicates in the intersection . when deleting qualified sets of data from a child table with multiple parents , special considerations have to be made not to delete data related to one parent if the data is also related to data in another parent that is not being deleted by the application . deleting the data could lead to inconsistencies in the overall data . in addition , other applications may not be able to locate data that have been improperly deleted and consequently , inaccurate results may be returned . fig3 shows a process 300 for deleting data in a child table with a plurality of parent tables according to an implementation of the invention . at 302 , data from the child table that is qualified by each parent table is deleted . data from the child table that is qualified by only one parent table and is not related to data from any other parent table is deleted at 304 . to help illustrate , four tables , table - a 402 , table - b 404 , table - c 406 , and table - d 408 , are depicted in fig4 . as seen in fig4 , table - d 408 is a child table with three parent tables . in order to find out whether any data in child table - d 408 , which is qualified by data in at least one of the parent tables 402 - 406 that an application seeks to delete , can be safely deleted by the application without breaking any relationship to data in one of the parent tables 402 - 406 that is not sought by the application , a determination is made as to whether a set of data in child table - d 408 that is qualified by data in at least one of the parent tables 402 - 406 sought by the application , which is denoted as d ′ in fig4 , includes a subset of data qualified by each of the parent tables , table - a 402 , table - b 404 , and table - c 406 . a subset - 1 410 representing the intersection of data in child table - d 408 qualified by parent table - a 402 ( ad ′), data in child table - d 408 qualified by parent table - b 404 ( bd ′), and data in child table - d 408 qualified by parent table - c 406 ( cd ′) is depicted in fig4 . thus , subset - 1 410 includes data in child table - d 408 qualified by each of the parent tables 402 - 406 . this subset of data can be deleted from child table - d 408 because none of the data in the subset has a relationship to data in a parent table that the application is not seeking to delete . fig4 also depicts a subset - 2 412 , which represents data in child table - d 408 qualified solely by parent table - a 402 , a subset - 3 414 , which represents data in child table - d 408 qualified solely by parent table - b 404 , and a subset - 4 416 , which represents data in child table - d 408 qualified solely by parent table - c 406 . before deleting data in one of the subsets 412 - 416 , a determination is made as to whether data in the subset is related to data in one of the other parent tables not qualifying the data in the subset . in one implementation , a row in a child table is related to a row in a parent table when a column in the row of the child table and a related column in the row of the parent table have the same value . for instance , assume that each of tables 402 - 408 has three columns , c 1 , c 2 , and c 3 , and that parent table - a 402 and child table - d 408 are related by column c 1 , parent table - b 404 and child table - d 408 are related by column c 2 , and parent table - c 406 and child table - d 408 are related by column c 3 . hence , with respect to subset - 2 412 , to determine whether a row in subset - 2 412 of child table - d 408 is related to a row in parent table - b 404 or parent table - c 406 , the value in column c 2 of the row in subset - 2 412 can be compared to column c 2 values in table - b 404 to determine if there is a match , and the value in column c 3 of the row in subset - 2 412 can be compared to column c 3 values in table - c 406 to determine if there is a match . a row in subset - 2 412 can be deleted from child table - d 408 if it is not related to a row in parent table - b 404 or parent table - c 406 . a row in subset - 3 414 can be deleted from child table - d 408 if it is not related to a row in parent table - a 402 or parent table - c 406 . a row in subset - 4 416 can be deleted from child table - d 408 if it is not related to a row in parent table - a 402 or parent table - b 404 . this ensures that the data deleted from child table - d 408 data will not include data that may be accessed by another application . child table - d 408 may also have additional subsets of data ( not shown ) that are qualified by two of the parent tables 402 - 406 . these subsets of data , however , cannot be safely deleted from child table - d 408 because a row in one of these subsets of data may be related to a row in a qualifying parent table that is not being sought by the application , i . e ., the row in child table - d 408 is , for instance , qualified by a row in parent table - a 402 and a row in parent table - b 404 , and related to another row in parent table - a 402 that is a non - qualifying row ( i . e ., a row that the application is not seeking to delete ). the above methodology can be generalized to a case where a child table c ahs a set of data c ′ sought by an application and parent tables a to n . to delete data from child table c : determine ac ′, . . . , nc ′ in c ′ determine whether ac ′, . . . , nc ′ exists in c ′ delete data in ac ′, . . . , nc ′ from c delete data in nc ′ from c if it is not related to data in parent tables of c other than parent table n data is represented in tables as rows of data with columns of information . as discussed above , tables may be related to one another by specifying a column in one table and relating it to a column in another table . the relationship can be described as a tuple and represented as { a . c 1 , b . c 1 }, where a . c 1 is a column ‘ c 1 ’ in a table ‘ a ’ that is related to b . c 1 , which is a column ‘ c 1 ’ in a table ‘ b ’. fig5 illustrates an exmaple of a child table - c 506 with a parent table - a 502 and a parent table - b 504 . in the example of fig5 , a relationship exists between column ‘ a ’ in table - a 502 and column ‘ a ’ in table - c 506 , depicted as { a . a , c . a } in fig5 . a relationship also exists between column ‘ b ’ in table - b 504 and column ‘ b ’ in table - c 506 , depicted as { b . b , c . b } in fig5 . using the examples and relationship principles described above , a delete methodology can be expressed as the following : { c . a , c . b } is an element of c ′ if an only if ( a . a = c . a ) or ( b . b = c . b ) { c ′. a , c ′. b } is an element of ac ′ intersection bc ′ if an only if { ac ′. a , ac ′. b }={ bc ′. a , bc ′. b } if { c ′. a , c ′. b } is an element of ac ′ intersection bc ′, delete { c ′. a , c ′. b } from c if ({ c ′. a , c ′. b } is an element of c ′) and ({ c ′. a , c ′. b } is not an element of ac ′ intersection bc ′) and ( for every c ′. b where { a . a , c ′. a } is not an element of a or for every c ′. a where { b . b , c ′. b } is not an element of b ), delete { c ′. a , c ′. b } from c . c ′ is a set of data in child table - c 506 sought by an application . the set of data in table - c 506 sought by the application may be less than all of the data in child table - c 506 . the invention can take the form of an entirely hardware implementation , an entirely software implementation , or an implementation containing both hardware and software elements . in one aspect , the invention is implemented in software , which includes , but is not limited to , firmware , resident software , microcode , etc . furthermore , the invention can take the form of a computer program product accessible from a computer - usable or computer - readable medium providing program code for use by or in connection with a computer or any instruction execution system . for the purposes of this description , a computer - usable or computer - readable medium can be any apparatus that can contain , store , communicate , propagate , or transport the program for use by or in connection with the instruction execution system , apparatus , or device . the medium can be an electronic , magnetic , optical , electromagnetic , infrared , or semiconductor system ( or apparatus or device ) or a propagation medium . examples of a computer - readable medium include a semiconductor or solid state memory , magnetic tape , a removable computer diskette , a random access memory ( ram ), a read - only memory ( rom ), a rigid magnetic disk , and an optical disk . current examples of optical disks include dvd , compact disk — read - only memory ( cd - rom ), and compact disk — read / write ( cd - r / w ). shown in fig6 is a data processing system 600 suitable for storing and / or executing program code . data processing system 600 includes a processor 602 coupled to memory elements 604 a - b through a system bus 606 . in other implementations , data processing system 600 may include more than one processor and each processor may be coupled directly or indirectly to one or more memory elements through a system bus . memory elements 604 a - b can include local memory employed during actual execution of the program code , bulk storage , and cache memories that provide temporary storage of at least some program code in order to reduce the number of times the code must be retrieved from bulk storage during execution . as shown , input / output or i / o devices 608 a - b ( including , but not limited to , keyboards , displays , pointing devices , etc .) are coupled to data processing system 600 . i / o devices 608 a - b may be coupled to data processing system 600 directly or indirectly through intervening i / o controllers ( not shown ). in the implementation , a network adapter 610 is coupled to data processing system 600 to enable data processing system 600 to become coupled to other data processing systems or remote printers or storage devices through communication link 612 , communication link 612 can be a private or public network . modems , cable modems , and ethernet cards are just a few of the currently available types of network adapters . by performing an existence check for relationships to a parent table before deleting a row in a child table , integrity of data in the child table can be assured without having to implement rules or constraints in a database management system . in addition , the methodologies described above can be implemented independent of the database management system and only in those applications that require data consistency to be maintained . hence , all applications are not impacted as with the rules approach . further , there is no need for complex error checking , nor is there a dependency on rollback to restore previously deleted data . while various implementations for deleting data from child tables with multiple parents have been described , the technical scope of the present invention is not limited thereto . it is to be understood by those skilled in the art that various modifications or improvements can be added to the above implementations . it is apparent from the appended claims that such modified or improved implementations fall within the technical scope of the present invention
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a preferred embodiment of the present invention will be described with reference to the accompanying drawings . fig1 is a cigarette manufacturing machine comprising tobacco content control devices according to an embodiment of the present invention . in the cigarette manufacturing machine shown in fig1 cut tobacco is sucked upward through chimney 100 and adhered by suction to the lower side of perforated cigarette conveyor 103 which is located beneath suction chamber 102 . the adhered tobacco layer is transferred to the left in the drawing toward trimmer 104 . the density of the tobacco layer is measured by first radiometric density detector 106 located in the upstream side of trimmer 104 . the thickness of the cut tobacco layer is adjusted to a proper thickness by trimmer 104 . the cut tobacco layer having the proper thickness is transferred onto and rolled in cigarette paper which is fed from paper roll 108 and stacked on cloth tape 110 . the cigarette paper is glued by glue applicator 112 and the glued portions are dried by heater 114 to form a stick - like cigarette . the thus formed stick - like cigarette is transferred to the left and passed through second radiometric density detector 116 to check its density and to cut the cigarettes into the required length with cutter 118 . the cigarettes from cutter 118 are transferred to a tray by a conveyor ( not shown ). fig2 shows the construction of first radiometric density detector 106 . detector 106 mainly comprises radiation source 106a which emits radiant rays , and ionization box 106b which receives the radiant ray from radiation source 106a . radiation source 106a and ionization box 106b are spaced apart from each other by a predetermined distance . aperture windows 106c and 106d are located between ionization box 106b and radiation source 106a and serve as a radiation path . aperture windows 106c and 106d oppose each other and are spaced apart from each other by a predetermined distance . metal films 106e and 106f , preferably consisting of titanium foils , are adhered to aperture windows 106c and 106d , respectively . a channel for passing trimmed tobacco t on perforated conveyor 103 is provided between thin metal films 106e and 106f . shutter 106g is provided between radiation source 106a and aperture window 106c to prevent leakage of radiation . the operation of first radiometric density detector 106 will be described below . when shutter 106g is open , the radiant rays emitted from radiation source 106a is transmitted through thin metal film 106e of aperture window 106c and is incident on trimmed tobacco t . the radiation rays are transmitted through trimmed tobacco t in accordance with the density of tobacco t and are incident on ionization box 106b through metal film 106f of aperture window 106d . the outer periphery of ionization box 106b is maintained at a high potential by high voltage power supply 106h , so that an ionization current corresponding to the measured density of trimmed tobacco t is generated , and this current is supplied to amplifier 106i . a trimmer ( not shown ) is controlled and driven by this signal current . a detection output from first radiometric density detector 106 represents a density signal representing the density of the tobacco layer prior to formation of cigarettes . fig3 shows the construction of second radiometric density detector 116 . detector 116 is similar to that which is used on known cigarette manufacturing machines as described above and mainly comprises radiation source 116a and ionization box 116b which oppose each other and are spaced apart from each other by a predetermined distance . stick - like cigarette s is located between radiation source 116a and ionization box 116b . shutter 116c for shielding radiation rays are provided between radiation source 116a and stick - like cigarette s . in addition to radiation source 116a and ionization box 116b which are used to detect the density of stick - like cigarette s , detector 116 also includes reference object 116e , radiation source 116d , and ionization box 116f , which are used to provide a target value of the cigarette density . radiation source 116d and ionization box 116f oppose each other through reference object 116e . ionization box 116f detects the density of reference object 116e and is electrically connected through lead wires to ionization box 116b for detecting the cigarette density . the operation of the second radiometric density detector will be described below . radiation rays emitted from detector 116 are incident on stick - like cigarette s and is transmitted therethrough according to the cigarette density . the transmitted rays are incident on ionization box 116b . a negative voltage is applied by high voltage power supply to the outer periphery of ionization box 116b . when the radiation rays are incident on ionization box 116b , an ionization current is generated according to an intensity of the incident ray . the radiation rays from reference radiation source 116d are transmitted through reference object 116e and incident on ionization box 116f . a positive voltage is applied from the high voltage power supply to the outer periphery of ionization box 116f . upon reception of a radiant ray , ionization box 116f generates an ionization current corresponding to the target value . the ionization current generated upon application of the negative voltage to ionization box 116b and the ionization current generated upon application of the positive voltage to ionization box 116f are electrically coupled by the lead wires connected to the rear portions of ionization boxes 116b and 116f . a composite current is then supplied to amplifier 116g located in the upper portion of the detector . if stick - like cigarette s has the reference density , an output signal from amplifier 116g is set to zero . however , if the density of stick - like cigarette s is higher than the reference density , an output signal from amplifier 116g has a negative level ; and if the density of stick - like cigarette s is lower than the reference density , an output signal from amplifier 116g has a positive level . therefore , the output signal from amplifier 116g corresponds to a deviation in density of stick - like cigarette s from the reference density . fig4 shows a control circuit of the tobacco content control device of this embodiment . the same reference numerals as in fig1 to 3 denote the same parts in fig4 . as described above , cut tobacco t is sucked upward through chimney 100 and adhered in a stratiform on the lower side of perforated cigarette conveyor 103 which is located beneath suction chamber 102 . tobacco t is transferred in the allowed direction , and the density of the tobacco layer is detected by first radiometric density detector 106 . the radiation rays emitted from radiation source 106a provided in first radiometric density detector 106 are transmitted through tobacco t and incident on ionization box 106b . since a high voltage is applied to ionization box 106b , a small ionization current is generated thereby . the small current signal is amplified by amplifier 106i and the amplified signal is added to the reference signal from standard signal generator 200 . the sum signal is supplied to amplifier 202 . an output signal as an amplified signal from amplifier 202 is a voltage signal having a polarity and a magnitude , both of which correspond to the deviation of the density of the tobacco layer from the reference density . the cut tobacco , the density of which is detected by first radiometric density detector 106 , is transferred to the left and excessive tobacco is shaved off by trimming disc 104a . thereafter the tobacco is rolled in cigarette paper and glue is applied to the paper to form the stick - like cigarette . the density of the stick - like cigarette is measured by second radiometric density detector 116 . as described above , in second radiometric density detector 116 , radiation rays emitted from radiation source 116a are transmitted through stick - like cigarette s and incident on ionization box 116b . radiation rays emitted from radiation source 116d are transmitted through reference object 116e and are incident on ionization box 106f . the voltages having opposite polarities are applied to the outer peripheries of ionization boxes 106b and 106f , and the rear portions of these ionization boxes are electrically connected to each other . an amplified output signal from amplifier 116g serves as a voltage signal having a polarity and a magnitude , both of which represent a deviation of the measured density of stick - like cigarette s from the density of the reference object . an output signal from amplifier 116g is amplified by amplifier 204 and is integrated by integrator 222 . the integrated output signal from integrator 222 represents a sum of signals corresponding to a deviation of the measured density of the stick - like cigarette from the reference density , i . e ., the average deviation of the tobacco density . the operation terminal in the latter stage is driven such that the sum becomes zero , thereby always maintaining the density of the cigarette constant . the output signal from integrator 222 is amplified by amplifier 224 and is supplied as a second detection signal to adder 226 . the output signal from amplifier 202 is supplied to a high pass filter constituted by capacitor 251 , resistor 252 , and voltage follower 253 . the filter is provided for allowing a high frequency component of the output signal to pass therethrough and preventing a low frequency component of the output signal , which is also contained in the output signal from amplifier 204 , from passing therethrough . thus , the instantaneous change of the output signal is delivered from the high pass filter . the time constant of this filter is preferably about one minute . switch 205 is provided to inhibit the filter function during calibration . the deviation detection signal free from the dc component is amplified by amplifiers 254 and 255 , and the amplified signal is supplied to adder 226 as a first detection signal in the same manner as in the second detection signal . a sum output from adder 226 is amplified by amplifier 228 , and the amplified signal is further amplified by amplifier 230 . the output from amplifier 230 is supplied to electrohydraulic servo valve 232 . electrohydraulic servo valve 232 selectively supplies the pressurized oil from gear pump 234 to the upper and lower chambers of cylinder 236 according to the applied voltage , thereby displacing piston 238 upward or downward within cylinder 236 . the upward or downward movement of piston 238 is transmitted to trimming disc 104a of trimmer 104 through link 240 , shaft 242 , link 244 , and connecting rod 246 to move trimming disc 104a upward or downward . the position of trimming disc 104a is detected by differential transformer 248 having a primary coil , which is applied with a reference alternative voltage signal of several khz from oscillator 250 and has its center core connected to piston 238 through shaft 242 and link 240 . therefore , in response to the upward and downward movement of piston 238 , a corresponding signal appears in the secondary coil of differential transformer 248 by a mutual induction coupling , and this signal is amplified by amplifier 257 . half - wave portions of the output from amplifier 257 are dropped off to ground by switch 259 which is operate by the output signal of amplifier 250 , and the remaining half - wave portions are flattened by low pass filter 256 . an output from amplifier 258 is applied to adder 226 as a third input signal . with the above arrangement , when the sum of the first and second input signals of adder 226 is positive , that is to say , when the tobacco contents are deficient , a voltage appears at the output terminal of adder 226 . as a result , the output from amplifier 230 is increased in a positive direction , so that electrohydraulic servo valve 232 slowly changes the flow of oil to push up piston 238 , lowering trimming disk 104a through link 240 , shaft 242 , link 244 , and connecting rod 246 to increase the tobacco content . trimming disc 104a is lowered until the third signal becomes equal to the sum of the signal ( i . e ., the first signal ) from the first radiometric density detector and the signal ( i . e ., the second signal ) from the second radiometric density detector . when the tobacco contents are excessive , the polarities in the foregoing operation are inverted . the second signal generated by the above arrangement , i . e ., the signal generated by second radiometric density detector 116 is obtained by integrating a signal corresponding to the density deviation by integrator 222 . the first signal , i . e ., the signal generated by first radiometric density detector 106 is a signal corresponding to the density deviation . accordingly , when there is a difference between the first and second signals , the first signal may be dominant during a short time period , but the second signal is gradually increased by integration to a value which overwhelms the first signal . therefore , the tobacco content can be determined and controlled according to the first signal with respect to variations of a short period and according to the second signal with respect to variations of a long period . in this embodiment , first radiometric density detector 106 is arranged in the upstream side of trimmer 104 due to the following reason . in the practical control device , delay ( delay time ) td occurs from the detection by the first radiometric density detector to driving of the trimmer o the basis of the detection signal . it is therefore difficult to accurately control the tobacco content of the cigarettes due to the delay time td . in particular , in order to eliminate variations in higher frequencies , the delay time td cannot be neglected . in the cigarette manufacturing machine , the first radiometric density detector is located in the upstream side of the trimmer , so that the first detection signal can be feed forwarded and the tobacco contents of cigarettes can be controlled . however , in the feed forward control system mentioned with reference to fig1 and 4 , the tobacco content is transferred along conveyor 103 from first radiometric density detector 106 to trimming device 104 . therefore , transfer time tt is required between the tobacco content density detection performed by first radiometric density detector 106 and the trimming performed by trimming device 104 . that is , transfer time tt is the time required from the tobacco content to be transferred from detector 106 to trimming device 104 . in the case where a trimming device operates at a high speed , as in the case of this embodiment , transfer time tt is long in comparison with delay time td . transfer time tt and delay time td can be controlled by adjusting the response speed of amplifier 254 of the feed forward control system . in this case , however , amplifier 254 cannot be set at the maximum response speed , so that the frequency response characteristics are not satisfactory . in the control device of the present invention , delay circuit 400 delays the detection signal output from first radiometric density detector 106 by difference time δt such that difference time δt corresponds to the difference between transfer time tt ( i . e ., a mechanical delay ) and delay time td ( i . e ., an electrical delay ). in this manner , the transfer time required for the tobacco content to be transferred from first radiometric density detector 106 to trimming device 104 is compensated for . as a result of this compensation , only high frequency components , which are picked up from the detection signal supplied from the first radiometric density detector by use of the high pass filter and correspond to an instantaneous variation in the density of the tobacco content , are delayed by difference time δt , so that the response speed of the feed forward control system is prevented from lowering . fig5 shows an example of the construction of delay circuit 400 shown in fig4 . as is shown in fig5 delay circuit 400 operates on the basis of reference power source voltage vref and can delay a signal by maximum transfer time tt ( td = 0 ). in delay circuit 400 , the high frequency signal picked up by the high pass filter is input through input terminal 401 and its amplitude is adjusted by amplifier 402 . the amplitude - adjusted signal is supplied to analog delaying element 403 , which is a charge transfer element such as a bbd , and is then output from output terminal 404 after predetermined difference time δt . analog delaying element 403 is connected to clock 405 , and this clock 405 is connected to variable resistor circuit 406 for adjusting the signal transmitting frequency of clock 405 . therefore , the signal transmitting frequency of clock 405 is adjusted by varying the resistor of variable resistor circuit 406 , and the transfer speed controlled by analog delaying element 403 is adjusted by the clock signal supplied from clock 405 . as a result , difference time δt is adjusted . in delay circuit 400 shown in fig5 the analog signal is delayed and output as it is . however , the present invention is not limited to this . for example , the analog signal may be converted into a digital signal by means of an a / d converter before it is delayed , and the delayed digital signal may be converted again into an analog signal by means of a d / a converter . fig6 shows a drive unit for driving trimming disc 104a for controlling the thickness of the tobacco layer . referring to fig . s , piston 238 is vertically slidable in cylinder 236 which is mounted on outer casing 306 . piston 238 is pushed down when pressurized oil is introduced into cylinder chamber 236a through pipe 300 , so that the oil in cylinder chamber 236b is drained into the tank through pipe 302 and return pipe 304 . similarly , when pressurized oil is introduced into cylinder chamber 236b to push piston 238 up , the oil in opposite cylinder chamber 236a is drained into the tank through pipe 300 and return pipe 304 . the hydraulic system is kept at a predetermined oil pressure . when an oil pressure exceeding the preset pressure is applied from the gear pump , the oil pressure acts on relief valve 314 through pipe 312 , connected midway along pipe 310 between gear pump 234 and electrohydraulic servo valve 232 , and is drained through return pipe 316 and filter 308 . the pressure in the hydraulic system is controlled by pressure adjusting screw 318 . the upward and downward movement of piston 238 moves connecting rod 320 which is pivotally connected to piston 238 . the other end of connecting rod 320 is pivotally connected to link 240 , so that upward and downward movement of piston 238 causes link 240 to vertically rock along with shaft 242 . shaft 242 is axially supported by outer casing 306 . the rocking movement is transmitted by shaft 242 through link 244 which is fixed to the end of shaft 242 to vertically move connecting rod 246 which is pivotally supported at the other end of the arm . trimming disc 104a is vertically moved by the upward and downward movement of connecting rod 246 . link 330 is axially supported at the other end of shaft 242 and is rockable upon rotation of shaft 242 . link 332 is attached to link 330 and is moved vertically upward or downward by the rocking movement of link 330 . the center core of differential transformer 248 is fixed to link 332 so that the core can be vertically moved the same manner as in link 332 . for example , differential transformer 248 is adapted to produce a positive voltage when the core is moved upward and a negative voltage when the core is moved downward , in proportion to the distance of movement . in other words , differential transformer 248 generates a positive voltage when connecting rod 246 is moved upward and a negative voltage when connecting rod 246 is moved downward . motor 336 is connected to gear pump 234 through universal joint 338 . as described above , unlike the density detector utilizing air - permeability properties or an electrostatic capacitance change , the second radiometric density detector according to the present invention can generate an accurate detection signal and performs very stable measurement . a deviation of the measured value from the target value is integrated , and the integrated value is fed back to accurately control the average density of the produced cigarettes . delay ( delay time ) occurs until the trimmer is started in response to the detection signal after the signal is measured by the radiographic density detector . this delay time degrades control performance because the control system undesirably oscillates when the response time is shortened to 1 / 5 or less of the idle time as the reference for the response of the control system as a whole is increased . a device disclosed by u . s . ser . no . 705 , 877 ( japanese patent disclosure ( kokai ) no . 60 - 234574 and epc laid open publication no . 160 , 799 ) serves to improve response characteristics so as to minimize the delay time . feedforward control in the present invention is open loop control . the deviation from the target value cannot be integrated . however , the response time of the control system can be shortened to a time required for feeding the cut tobacco between the radiometric density detector as the detection terminal and the trimmer as the operation terminal . an arrangement of feedforward control is described in japanese patent publication no . 40 - 14560 , wherein pressure variations in the air chamber are converted by a bellows into variations in position , and the variations are feed forwarded by a hydraulic unit . however , precision of the signal is poor , and a satisfactory effect cannot be obtained . according to the present invention , the advantages of feedback control of the radiometric density detector , the electrohydraulic servo mechanism operated as an operation terminal with a short response time , and feed - forward control are combined to obtain an ideal control system operated at high speed in response to the detection signal . further , in the feed forward control system , the transfer time , i . e ., the time required for the density - detected tobacco content to be transferred to the trimming device is compensated for in consideration of both the mechanical and electrical time delays . as a result , the control system of the present invention operates at a high speed and with high accuracy . as a result of the above - mentioned control , the response speed of the control device is ten times as high as the control speed of the prior art control device . in addition , the irregularities of the tobacco content of cigarettes can be reduced from 2 . 5 % ( prior art ) to 1 . 8 %. in the control device shown in fig4 no delay circuit is incorporated in the feed forward control system . in this case , the irregularities of the tobacco content of cigarettes is reduced to 2 . 0 %. in view of this value , it can be understood that the present invention can remarkably reduce the irregularities of the tobacco content . therefore , the tobacco contents can be reduced by about 1 . 7 % in the present invention . as described above , a very high - speed control system can be arranged according to the present invention , and the irregularities of the tobacco content of cigarettes can also be minimized .
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in the following description , like reference characters designate like or corresponding parts throughout the several views shown in the figures . it is also understood that terms such as “ top ,” “ bottom ,” “ outward ,” “ inward ,” and the like are words of convenience and are not to be construed as limiting terms . referring to the drawings in general and fig1 in particular , it will be understood that the illustrations are for the purpose of describing the preferred embodiment of the invention and are not intended to limit the invention thereto . an infiltrated polycrystalline diamond composite tool 10 of the prior art is shown in fig1 . the infiltrated polycrystalline diamond composite tool 10 includes a plurality of uncoated diamonds 2 with an infiltrant 4 disposed between the diamonds 2 . free space 16 may exist between the uncoated diamond particles 2 . the infiltrated polycrystalline diamond composite tool 10 has a working surface 18 . depending on the intended application of the infiltrated polycrystalline diamond composite tool 10 , the working surface may be a cutting edge , an abrasive surface , or the like . the infiltrated polycrystalline diamond composite tool 10 may also include a support 6 , which generally comprises the infiltrant material . the support 6 may also include a hard material 8 , such as a carbide . the support 6 serves as a backing layer and ultimately provides a degree of support and rigidity to the infiltrated polycrystalline diamond composite tool 10 . in the prior - art infiltrated polycrystalline diamond composite tool 10 , the infiltrant 4 has partially in , filtrated most of the free space 16 between the diamonds 2 . during the formation of the infiltrated polycrystalline diamond composite tool 10 , the diamonds 2 are partially dissolved by the infiltrant 8 and subsequently precipitated , resulting in diamond - to - diamond bonding 12 and grain growth , which in turn forms a continuous polycrystalline diamond matrix 13 . because the matrix material 4 does not wet the surface of the diamonds 2 well , infiltration of the pre - form is incomplete . as a result , diamond - to - diamond bonding 12 within the infiltrated polycrystalline diamond composite tool 10 is incomplete and the polycrystalline diamond matrix 13 does not completely form . in addition , some free space 16 remains within the infiltrated polycrystalline diamond composite tool 10 . consequently , the durability of the infiltrated polycrystalline diamond composite tool 10 is limited . fig2 is a schematic representation of a coated diamond particle 20 of the present invention . the coated diamond particle 20 comprises a diamond 22 having a palladium - free wetting - enhancement coating 24 disposed on and substantially covering the outer surface of the diamond 22 . the wetting enhancement coating 24 may comprise the same material as that is later used as the infiltrant in the tool . the wetting enhancement coating 24 is preferably formed from either nickel , cobalt , iron , or combinations thereof , with cobalt being the most preferred material . the palladium - free wetting - enhancement coating 24 can be deposited directly onto the surface of the diamond 22 using vapor deposition techniques such as , but not limited to , chemical vapor deposition , physical vapor deposition , plasma assisted chemical vapor deposition , and combinations thereof . a schematic view of another coated diamond particle 30 of the present invention is shown in fig3 . the diamond 22 is coated with a palladium - free activation layer 34 and a palladium - free wetting - enhancement coating 24 to form the coated diamond particle 30 . the surface of the diamond 22 is a sensitized surface 32 , formed by treating the diamond 22 with a sensitizing agent . the sensitizing agent typically has two stable valence states , is capable of reacting with the activation layer 34 , and is stable in water . in the present invention , the surface of the diamond 22 is preferably sensitized by immersing the diamond 22 in a solution of tin dichloride ( sncl 2 ) and hydrochloric acid ( hcl ) at room temperature for approximately five minutes . other metals having two stable valence states , including manganese , iron , cobalt , nickel , copper , and cadmium , may be used as sensitizing agents as well . during sensitization , sncl 2 is physically absorbed onto the surface of the diamond 22 . following immersion , the diamond is then washed with distilled water and dried . following sensitization , the palladium - free activation layer 24 is deposited onto the sensitized surface 32 of the diamond 22 . the palladium - free activation layer 34 is preferably formed from silver , although other metals , such as copper , gold , cobalt , and platinum , may be used to form the palladium - free activation layer 34 . when silver is used to form the palladium - free activation layer 34 , the sensitized diamond 22 is immersed in a silver nitrate ( agno 3 ) solution at room temperature for approximately five minutes . tin dichloride ( sncl 2 ), which is the preferred sensitizer of the present invention , forms the species sn ( iv ) on the sensitized surface 32 of the diamond 22 , thereby preventing the oxidation of the metal activator species in the palladium - free activation layer 34 . the palladium - free activation layer 34 comprising silver is precipitated onto the diamond surface according to the reaction . to form elemental silver on the sensitized surface 32 of the diamond 22 . the palladium - free activation layer 34 comprising silver may be alternatively deposited from a colloidal suspension of silver . following precipitation of the palladium - free activation layer 34 , the diamond 22 is again washed with distilled water and dried . the palladium - free activation layer 34 formed from silver may comprise between about 0 . 01 and about 10 weight percent of the diamond particle . following deposition of the palladium - free activation layer 34 on the diamond 22 , the palladium - free wetting - enhancement coating 24 is deposited over the palladium - free activation layer 34 . the palladium - free wetting - enhancement coating 24 is preferably deposited by an electroless plating process . as described above , the palladium - free wetting - enhancement coating 24 may be comprised of the same material as the metallic infiltrant that will ultimately be used to form an infiltrated tool . the palladium - free wetting - enhancement coating 24 may be formed from either nickel , cobalt , iron , or combinations thereof , with cobalt being the preferred material . the electroless plating procedure is a simple reduction reaction , in which the cobalt ( ii ) ion from cobalt ( ii ) sulfate is reduced to elemental cobalt while dimethylamineborane ( dmab ) is oxidized to ( ch 3 ) 2 nh 2 + and b ( oh ) 3 : 3co 2 + + 3 ( ch 3 ) 2 nhbh 3 + 6h 2 o → 3co o + b + 3 ( ch 3 ) 2 nh 2 + + 2b ( oh ) 3 + 9 / 2h 2 + 3h + the reduction of cobalt continues in the presence of the reducing agent as long as the catalytic reduction of the metal is possible . in the present invention , the catalytic sites at which the electroless plating takes place are provided by first depositing the palladium - free activation layer 34 . in the absence of such catalytic sites , little if any coverage of the diamond 22 by the palladium - free wetting - enhancement coating 24 could be achieved by electroless plating . the palladium - free wetting - enhancement coating 24 may further include either phosphorus or boron . in the present invention , the palladium - free wetting - enhancement coating 24 preferably comprises cobalt and boron . boron , which is produced by the reduction of co ( ii ) by dmab , may comprise up to 30 weight percent of the palladium - free wetting - enhancement coating 24 . to achieve the optimum abrasion resistance , a palladium - free wetting - enhancement coating 24 comprising up to about 5 weight percent boron is preferred . the palladium - free wetting - enhancement coating 24 preferably has a thickness of between about 0 . 01 microns and about 5 microns . the coated diamond particles 20 , 30 of the present invention have an average diameter in the range of between about 0 . 0001 and about 1 millimeter . for use in a cutting tool , the average diameter of the coated diamond particles 20 , 30 is preferably greater than about 10 microns and less than about 100 microns , as coated diamond particles 20 , 30 in this size range provide optimal abrasion resistance for the tool . in addition to use in a cutting tool application , the coated diamond particles 20 , 30 of the present invention may be used for mesh products , such as grit for abrasives , which utilize diamond particles having an average diameter between about 10 microns and about 1 millimeter . infiltrated polycrystalline diamond composite tools of the present invention include cutting tool blanks , wire dies , drill blanks , and the like . these infiltrated polycrystalline diamond composite tools are formed from a preform that is prepared using the coated diamond particles 20 , 30 described above and a metallic infiltrant source that infiltrates the : free space 16 between the coated diamond particles 20 , 30 under the application of ; high temperature and pressure . fig4 is a schematic representation of a preform 40 of the present invention . a plurality of coated diamond particles 20 are placed in a refractory container 52 to form a bed 53 . coated diamond particles 30 , having a sensitized surface 32 , palladium - free activation layer 34 , and palladium - free wetting - enhancement coating 24 can be substituted for part or all of the coated diamond particles 20 . the refractory container 52 is formed from a refractory material , such as a ceramic or metal , having a melting temperature above that of the metallic infiltrant 44 and the temperatures used in the infiltration process . a metallic infiltrant source 54 , comprising the metallic infiltrant 44 , is placed in the refractory container 52 , such that the metallic infiltrant source 54 contacts the bed 53 of coated diamond particles 20 . preferably , the metallic infiltrant source 54 , is placed in the refractory container 52 such that the metallic infiltrant source 54 is positioned on top of and in contact with the bed 53 of coated diamond particles 20 . the metallic infiltrant 44 is substantially palladium - free and preferably comprises cobalt , although iron , nickel , and combinations of iron , nickel , and cobalt may also be used . the pre - form 40 is then heated to a temperature above the melting point of the metallic infiltrant 44 and pressure is applied to the metallic infiltrant source 54 , thereby forcing the molten metallic infiltrant 44 into the free space 16 between the coated diamond particles 20 . the preform 40 is preferably heated to a temperature between about 1300 ° c . and about 1700 ° c . pressures in the range of between about 40 kbar to about 70 kbar are applied to the preform 40 in order to achieve infiltration by the metallic infiltrant 44 . during the infiltration process , the palladium - free wetting - enhancement coating 24 melts and combines with the molten metallic infiltrant 44 . the presence of the palladium - free wetting - enhancement coating 24 on the diamonds 22 permits the molten metallic infiltrant 44 to completely wet the diamonds 22 . at the same time , the combination of molten metallic 44 and palladium - free wetting - enhancement coating 24 acts as a liquid - state sintering aid , dissolving some of the diamonds 22 . the diamonds 22 then ; re - crystallize to form a continuous polycrystalline diamond matrix 56 in which diamond - to - diamond bonding 58 between individual diamonds 22 is present . upon cooling , the combined molten metallic infiltrant 44 and palladium - free wetting - enhancement coating 24 materials resolidify to form a contiguous , fully dense metallic phase 62 ! that interpenetrates the continuous polycrystalline diamond matrix 56 , as shown in fig5 to form a fully infiltrated polycrystalline diamond composite tool blank 59 . a working surface 68 , such as a cutting edge or an abrasive surface , can then be provided to form the infiltrated polycrystalline diamond composite tool 60 . the continuous polycrystalline diamond matrix 56 formed from the diamonds 22 comprises between about 85 and about 95 volume percent of the infiltrated polycrystalline diamond composite tool 60 . the infiltrated polycrystalline diamond composite tool 60 is preferably a supported infiltrated polycrystalline diamond composite tool 60 , having an infiltrated support layer 46 , as shown in fig5 . the infiltrated support layer 46 comprises a continuous matrix formed by a plurality of hard particles 48 that is interpenetrated by the metallic infiltrant 44 . the hard material 48 is preferably tungsten carbide , although other carbides , such as silicon carbide , titanium carbide , zirconium carbide , niobium carbide , combinations thereof , and the like may be used . the supported infiltrated polycrystalline diamond composite tool 60 is formed by including particles of the hard material 48 in the metallic infiltrant source 54 that is used to assemble the preform 40 . during the infiltration process , the infiltrated support layer 46 fuses to the remainder of the infiltrated polycrystalline diamond composite tool 60 . the features of the present invention are illustrated by the following example . an activated layer of palladium was precipitated onto a first group of diamond particles . a second group of diamond particles was provided with a silver activation layer precipitated from solution . both the first and second groups of diamond particles were then electrolessly plated with a cobalt / boron coating . scanning electron microscopy ( sem ) was used to study the integrity of the cobalt / boron coatings on the two groups of particles . similarly , auger spectroscopy scans were used to investigate the continuity of the cobalt / boron coatings . a representative sem micrograph and auger spectroscopy scan obtained for the palladium - activated diamond particles are shown in fig5 and 6 , respectively . fig7 and 8 are a sem micrograph and auger spectroscopy scan , respectively , obtained for silver - activated diamond particles . there was no discernible difference in the contiguity of the cobalt / boron coatings deposited on the silver - activated particles and the contiguity of the cobalt / boron coatings deposited on the , palladium - activated particles . the integrity of the coating appears to be the same , or perhaps superior for the silver activated material . the experiment also showed no distinct difference in the apparent continuity of the coatings . polycrystalline diamond composite tools were also produced using these coated diamond particles , with no adverse sintering affects noted . abrasion tests were then conducted on these polycrystalline diamond composite tools . the tests indicated that the polycrystalline diamond composite tools of the present invention had abrasion resistances that were at least as good as those of tools made using uncoated diamond particles . while various embodiments are described herein , it will be appreciated from the specification that various combinations of elements , variations or improvements therein may be made by those skilled in the art , and are within the scope of the invention .
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the waveguide holographic telltale display 50 shown in fig1 embodies the present invention . the windshield 50 comprises bottom and top windshield singlets 52 and 54 , sandwiching the other elements , including a solar coating or holographic solar control film 64 adjacent the top singlet 54 , which is preferably a tinted singlet . a layer of polyvinyl butyral ( pvb ) 70 is adjacent the film 64 . a halfwave layer 66 is disposed adjacent the bottom singlet 52 . a hologram 62 is in turn disposed next to the layer 66 . the hologram 62 has several sections . section 62a is the telltale hologram , providing a predetermined telltale image when illuminated by the light source 56 . the telltale image conveys some predetermined message , such as a low fuel indication , a seatbelt warning , or the like . section 62b is a mirror hologram . the hologram in section 62c can be a solar control reflection hologram , or an inert film which tapers from full - thickness adjacent to hologram 62a down to zero thickness one to two inches away from hologram 62a . this tapering is to avoid any abrupt discontinuities in thickness within the two singlets that will result in objectionable seethrough distortion . hologram layer 62 can be made of one single piece of film , as described below ; otherwise , sections 62a , 62b and 62c can be made separately . the bottom windshield glass singlet 52 comprising the vehicle windshield is made of clear glass instead of the conventional tinted glass . the top glass singlet 54 can either be tinted or clear ; however , if it is clear , then some other means for blocking ir light from entering the passenger cabin , such as a dielectric or holographic ir reflecting layer , will be employed in a typical application . the light source 56 can be an incandescent bulb ( halogen or non - halogen ), a high - intensity discharge bulb , or the fiber optic output of a remotely - located incandescent or high - intensity discharge bulb . light from the source 56 is collimated by a collimating lens , a parabolic reflector , or a non - imaging reflecting concentrator cavity . the use of a non - imaging reflector is described in commonly assigned , co - pending application ser . no . 07 / 994 , 816 , filed dec . 22 , 1992 , entitled &# 34 ; linear lamp holographic trapped beam chmsl ,&# 34 ; by r . t . smith and a . daiber . this application is incorporated herein in its entirety by this reference . see also &# 34 ; the optics of non - imaging concentrators ,&# 34 ; w . t . welford and r . winston , academic , new york , 1978 , for more information on non - imaging concentrators . the collimated light is injected into the lower windshield singlet 52 by a wedged prism 60 attached to the lower singlet , or alternatively by a prismatic notch cut in the lower singlet , or by an input coupling hologram located directly above the lower singlet . fig8 shows the prism 60 in further detail . the prism 60 is a right angle prism characterized by a length dimension l , a height dimension h and a prism angle θ . if the windshield inner singlet 52 has a thickness dimension w , the prism parameters are determined as follows : light from the light source 56 is trapped inside the windshield by total internal reflection from the air / glass interface for singlet 52 . a majority of the internally trapped collimated light is confined within the clear lower glass singlet 52 by the photopolymer zero - degree reflection hologram 62b . this is mainly to avoid the light from being absorbed by the tinted upper singlet 54 and / or the dielectric / metal solar control film 64 . the zero - degree reflection hologram 62b is a mirror reflection hologram whose fringes are parallel to the hologram surface . the reflection hologram 62b need not extend across the full width of the windshield , but rather need only extend across the lateral extent of the telltale hologram layer 62a between that layer and the light source . the reflection hologram 62b is designed to reflect very efficiently ( greater than 90 %) the light incident on it at a highly off - axis angle , e . g ., in this exemplary embodiment , 48 degrees . the hologram spectral bandwidth is tailored to cover the spectral range of the desired telltale image or the spectral bandwidth of the lamp , whichever is smaller . this reflection hologram 62b reflects very strongly over the wavelength range of the telltale hologram 62a for s - polarized light , but is not as effective a reflector for p - polarized light . therefore , the s - polarized light will essentially be confined to the inner glass singlet 52 ( assuming for the moment there is no halfwave film 66 ). however , the p - polarized light will partially transmit beyond the hologram 62 , through the polyvinyl butyral ( pvb ) 70 , and be reflected either by the dielectric or holographic solar control film 64 or the outer glass / air singlet back through the telltale and / or mirror hologram layer 62 into the lower singlet 52 . in this manner , the p - polarized light is allowed to bounce back and forth on both sides of the hologram layer 62 as it propagates up the windshield glass . the s - polarized light is diffracted strongly by the telltale hologram 62a as seen in fig2 which illustrates the path of light from the light source 56 through the system of fig1 under the assumption there is no halfwave film 66 installed therein . the foregoing configuration , assuming again there is no halfwave film 66 , would cause two problems . first of all , the strongly diffracted s - polarized light from the telltale hologram 62a which is headed for the driver would reflect fairly strongly off the inner and outer glass / air interfaces ( or solar control film 64 ), creating an objectionable ghost image . secondly , since the telltale image arriving at the driver would be primarily s - polarized , when the driver puts on his s - polarized sunglasses , the telltale image will be virtually extinguished . these problems are partially solved by placing the polyvinyl alcohol ( pva ) halfwave film layer 66 between the inner glass singlet 52 and the telltale / mirror hologram layer 62 . referring now to fig3 a and 3b , and starting at the point where the light is injected into the lower singlet 52 , the p - polarized light incident on the halfwave layer 66 is flipped to s - polarization , is reflected strongly by the mirror hologram 62b , and is flipped back to p - polarized light as it passes back through the halfwave layer 66 into the lower singlet 52 . the s - polarized light ( fig3 b ) entering the lower singlet 52 gets flipped to p - polarized light as it passes through the halfwave layer 66 , and partially transmits through the telltale hologram layer 62a , where it reflects off the solar control film 64 and / or the outer glass / air interface and passes back through the hologram 62 and halfwave 66 layers where it re - enters the lower singlet 52 as s - polarized light again . s - polarized light incident on the telltale hologram 62a gets diffracted strongly toward the driver , but is flipped to p - polarization as it passes through the halfwave layer 66 . the p - polarized light reflects weakly off the inner glass / air singlet . the weakly reflected p - light gets flipped back to s - polarization before reflecting fairly strongly off the outer glass / air interface and to the driver . the net effect is to reduce the ghost image brightness . therefore , the result is a bright p - polarized image at the driver with a very weak p - polarized ghost image ( fig3 a ). the p - polarized light incident on the hologram 62a from the bottom is diffracted weakly by the hologram 62a , gets flipped back to s , reflects fairly strongly off the inner glass 52 / air interface , gets flipped back to p - polarization , reflects weakly off the outer glass / air interface , gets flipped back to s - polarization , and finally reaches the driver . the result is a weak s - polarized image with a much weaker ghost image ( fig3 b ). the halfwave film layer 66 is only a partial solution because even an ideal halfwave layer will rotate the s - polarized light totally to p - polarized light from one incident angle and one wavelength only . for a range of wavelengths , such as are generated by the light sources referred to above , the majority of light will be rotated to p but it will not be 100 %. therefore , there will be some residual s - polarized light to cause ghosting and reduced brightness with polarized sunglasses . furthermore , the lamp light incident on the halfwave layer covers a range of angles , not just one . finally there may uncertainties in the production fabrication of these halfwave layers that will cause their retardance to deviate from a perfect halfwave . the exact wavelength at which the halfwave film layer 66 is designed will depend on what lamp is used . if it is an incandescent bulb , the limiting bandwidth is the telltale bandwidth . if a telltale image covers 600 - 630 nm , then the midband wavelength would be at 615 nm , and this is the wavelength for which the halfwave layer will be designed . if an led source with a peak brightness at 660 nm is used as the light source 56 , then the halfwave layer &# 39 ; s midband wavelength is at 660 nm . fig3 a , 3b , 4a and 4b and tables 1 and 2 show a comparison in image brightness results , respectively including , and not including a halfwave layer for the example of light incident on the windshield at 72 . 8 ° in air and a telltale hologram 62a which diffracts 100 % of s - polarized light and 50 % of p - polarized light . clearly the halfwave layer improves the situation . it even slightly improves the image brightness . table 1______________________________________ s - polarization p - polarization average pol______________________________________main image 0 . 928 0 . 32 1 . 248ghost image 0 . 024 0 . 008 0 . 032main / ghost ratio 38 . 7 40 39______________________________________ table 2______________________________________ s - polarization p - polarization average pol______________________________________main image 0 . 64 0 . 464 1 . 104ghost image 0 . 083 0 . 0024 0 . 0854main / ghost ratio 7 . 71 193 . 3 12 . 9______________________________________ the p - polarized light that is incident on the telltale hologram 62a from its top side ( adjacent the outer singlet 54 ) is weakly diffracted by the hologram , is weakly reflected off the upper glass / air interface , is flipped back to s - polarization , and arrives at the driver as an extra ghost image . for the example of fig4 a and 4b , if the value of light incident on the hologram from the top side is one , then the value of light reaching the driver is 0 . 023 . this is a non - negligible ghost image . however , by the time the p - polarized light reaches the top surface of the telltale 62a it has been appreciably attenuated by the tinted upper singlet 54 and / or the solar control film 64 and the pvb 70 . therefore , there is no need for a polarizer in the light source 56 lamp to eliminate this component . fig9 is a top view of a telltale hologram exposure system 200 suitable for fabricating the telltale hologram 62a . the collimated reference beam 202 illuminates the film plate 208 ( illustrated in fig1 ), and is provided via a collimating lens 204 and spatial filter 206 . the reference beam illuminates the holographic film layer 212 through a prism liquid gate comprising prism 210 . the hologram film 212 is mounted on plate 208 which is immersed in an index matching liquid 214 within layer 216 . the object beam 210 is provided via a spatial filter 220 , a focusing lens 222 , a high gain diffusing screen 224 , an image reticle 226 , and plano - convex spherical lenses 228 and 232 . the focusing lens 222 takes the spherically diverging wave from the spatial filter 220 and focuses it to a point at the center of the aperture mask 230 , i . e ., if the high gain screen is not present . this ensures that maximum illumination is arriving at the eyebox 234 . the high gain screen 224 diffuses the light , and the image reticle 226 is a transparency mask with clear openings and opaque areas that define a telltale image . the diffuse light from the screen that exits this reticle mask 226 is focused by the two lenses 228 and 232 so that an image of the reticle mask bisects the film 212 plane . an aperture mask 230 is placed on the exiting face of the first lens 228 , and defines the size of the eyebox 234 . the outline of the aperture mask 230 is focused by the second lens 232 through the film plate to a point in space far away from the film plate ( thirty inches or more ), where the image of the aperture mask is located . this image defines the eyebox for the playback of the hologram . fig1 is a side view of the exposure system 200 of fig9 . fig1 is an expanded side view of a portion of the exposure system of fig1 . fig1 shows an expanded view of the prism 210 and film plate 208 . the object beam 218 creates an evenly illuminated image 236 that bisects the hologram film plane which can be seen from a well - defined eyebox 234 behind the hologram . when this hologram is played back in reverse in the system of fig1 the light is diffracted by the telltale hologram 62a so that a viewer located inside a well - defined eyebox in the driver &# 39 ; s head area sees a vertical telltale image 236 bisecting the plane of the windshield . outside of the hologram &# 39 ; s eyebox the driver sees nothing . dielectric / metal solar control coatings of windshields suitable for the film 64 are made by libbey owens ford ( lof ) and others . one exemplary lof coating is marketed as the &# 34 ; ez - kool &# 34 ; brand of solar control glass , lof automotive center , 35715 stanley drive , sterling heights , mich . 48312 . the mirror hologram 62b is exposed merely by roll - laminating a piece of photopolymer film onto a metal mirror ( the film has some self - adhesion ) and illuminating the film / mirror with a collimated laser beam incident at the angle which will yield the correct peak wavelength for playback . a layer of pva may need to be placed between the hologram layer and pvb to avoid plasticizers from the pvb from entering the hologram layer 62 and causing undesirable peak wavelength and spectral bandwidth changes . it makes sense that the halfwave pva layer 66 below the hologram layer 62 should also serve as the barrier layer between the hologram 62 and the pvb 70 . therefore , it might be advantageous to place the hologram layer 62 next to the underside of the upper glass singlet 54 . however , it may be difficult to bond the hologram layer 62 directly to a dielectric solar control coating 64 on the underside of the singlet 54 . a preferred alternative approach is to use a broadband ir reflective photopolymer holographic mirror to reject ir light instead of the dielectric coating , as shown in fig5 . the display 100 of fig5 comprises the inner and outer windshield singlets 102 and 104 , with the outer singlet 104 comprising tinted glass , and the inner singlet 102 of clear glass . light from the light source 106 is collimated by reflector 108 and fed into the inner singlet 102 by prism 110 , as in the embodiment of fig1 . a halfwave pva layer 114 is disposed between the hologram layer 116 and the pvb layer 112 disposed adjacent the inner singlet 102 . in fig5 the mirror hologram 116b , telltale hologram 116a , and holographic solar control mirror hologram 116c are all incorporated in one single hologram 116 layer which is attached to the inner surface of the outer glass singlet 104 by any one of a variety of adhesives and / or primers . each hologram comprising layer 116 can be fabricated by contact printing , i . e ., roll - laminating the hologram film against a rigid hologram master and illuminating with a collimated laser beam . the laser beam passes through the film , reflectively diffracts off the master and back onto the film to create the replicated hologram . in the case of the mirror reflection hologram and the solar control hologram , the master plate is a zero - degree mirror hologram , or else it can be replaced by a simple aluminum mirror . in the case of the telltale hologram , the master plate incorporates the telltale holograms in it . the holographic film is threaded onto a replication system that has three contact - copy exposure modules , one for each hologram type . once the film passes through the three exposure modules , it is uv cured and rolled onto an output spool . as an option , the roll of exposed film can be oven heated to enhance the hologram efficiency . fig6 is a graph illustrating a typical type of performance achievable with a solar control ir reflection hologram of fig5 as used in the embodiment and its advantages over a tinted windshield . as an added benefit the outer glass singlet can be made tinted if desired to increase the blockage of ir light . a cross - sectional view of the system mounted in a vehicle is shown in fig7 . the windshield 150 includes inner and outer singlets 152 and 154 . a hologram layer 156 disposed between the singlets comprises a mirror hologram 156b except in the vicinity of the telltale holograms 156a . a light source 160 , reflector 162 and prism 164 provide a means for injecting light into the windshield singlet 152 . if one desires the road glare to arrive at the driver in s - polarization instead of in p - polarization , then an additional halfwave layer would need to be placed between the hologram layer and the inner surface of the outer singlet . normally road glare is s - polarized ; therefore , polarized sunglasses are designed to absorb s and pass p . if a halfwave layer in the windshield causes the road glare to be flipped to p - polarization , it will pass through the polarized sunglasses virtually unattenuated . therefore , an additional halfwave layer could flip the polarization sense back to p - polarized light . this layer would also serve to modify the ghost image brightnesses as shown in table 3 for the example of fig4 . table 3______________________________________ s - polarization p - polarization average pol______________________________________main image 0 . 32 0 . 928 1 . 248ghost image 0 . 0415 0 . 0048 0 . 0463main / ghost ratio 7 . 71 193 . 3 27______________________________________ in either case , the thickness of the halfwave layer or layers can be gradually tapered down to zero outside of the hologram area to avoid any appreciable see - through distortion when looking through the windshield from the driver &# 39 ; s vantage point . another embodiment of the invention is shown in fig1 . in this case the layer 252 in which the light propagates toward the telltale hologram is physically separated from the windshield by an air gap g . in this case , once the light is injected into this layer 252 , it propagates up the layer by total internal reflection , and does not need a mirror reflection hologram to confine it . this greatly simplifies the design for customers who do not mind a physically separated layer from the windshield . fig1 shows the waveguide telltale hologram assembly 250 , separated by the air gap g from the inside surface of the conventional windshield 280 . the assembly 250 thus comprises a plastic light guide 252 , into which collimated light is injected from a light source 254 , reflector 256 and plastic prism 258 , in a manner similar to the light source arrangement of fig1 . the halfwave layer 260 is disposed on the surface 252a of the light guide facing the windshield 280 . the telltale hologram 262 is in turn disposed on the exterior surface of the halfwave layer 260 , between the air gap and the halfwave layer . as shown in fig1 , light from the light source propagates up the light guide by total internal reflection , until it reaches the telltale hologram and is diffracted from the hologram toward the viewer . the assembly could be secured in the position shown by various convention means , e . g ., by use of spacers and adhesives . it is understood that the above - described embodiments are merely illustrative of the possible specific embodiments which may represent principles of the present invention . for example , some applications may not require the half - wave plate , and in this case the half - wave plate may be omitted , thereby providing a simpler and cheaper display . other arrangements may readily be devised in accordance with these principles by those skilled in the art without departing from the scope and spirit of the invention .
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please refer to fig1 to fig6 , which are a structural view showing a preferred embodiment according to the present invention ; views showing states of use under a scan mode and a normal mode ; a view showing a state of use when a through - silicon - via ( tsv ) fails ; and views showing an area size and a wire length for a test tsv used as a redundant tsv . as shown in the figures , the present invention is an apparatus of three - dimensional integrated - circuit ( 3d - ic ) chip using a fault - tolerant test tsv , where a test tsv for a 3d - ic test structure is used as a redundant tsv for repairing signals of a 3d - ic chip . the present invention comprises a 3d - ic chip 1 , a tsv part 2 , two normal logic function circuits 3 and two 3d - ic test logic circuits 4 . the 3d - ic chip 1 comprises a first sub - chip 11 and a second sub - chip 12 , where the second sub - chip 12 is stacked on the first sub - chip 11 . the tsv part 2 is set between the first sub - chip 11 and the second sub - chip 12 to transfer signals between the first sub - chip 11 and the second sub - chip 12 . the tsv part 2 comprises a plurality of tsvs 21 ˜ 24 and a test tsv 25 . each of a second to a fourth tsvs 22 ˜ 24 is set with a first multiplexer 212 ˜ 214 at an input terminal . the first multiplexer 212 ˜ 214 is coupled to the input terminals of the second to the fourth tsvs 22 ˜ 24 through a shared terminal . each of a first to the fourth tsvs 21 ˜ 24 is set with a second multiplexer 221 ˜ 224 at an output terminal . the second multiplexer 221 ˜ 224 is coupled to the output terminals of the first to the fourth tsvs 21 ˜ 24 through a selecting terminal . the test tsv 25 has a third multiplexer 215 at an input terminal and a demultiplexer 225 at an output terminal . the third multiplexer 215 is coupled to the input terminal of the test tsv 25 through the shared terminal . the demultiplexer 225 is coupled to the output terminal of the test tsv 25 through the shared terminal . the test tsv 25 is used as a redundant tsv to repair signal of one of the first to the fourth tsvs 21 ˜ 24 when the one of the first to the fourth tsvs 21 ˜ 24 fails . the normal logic function circuits 3 are set in the first and the second sub - chips 11 , 12 and are connected to the first to the fourth tsvs 21 ˜ 24 , the first multiplexers 212 ˜ 214 and the second multiplexers 221 ˜ 224 , where signals are transferred through the first to the fourth tsvs 21 ˜ 24 . the 3d - ic test logic circuits 4 are set in the first and the second sub - chips 11 , 12 and are connected to the test tsv 25 with the third multiplexer 215 and the demultiplexer 225 for transferring test data between the first and the second sub - chips 11 , 12 and outputting test results through the test tsv 25 . thus , a novel apparatus of 3d - ic chip using a fault - tolerant test tsv is obtained . in fig2 , on using the present invention , the test tvs 25 provides circuit test for the 3d - ic chip 1 under a scan mode by adjusting selecting signals of the third multiplexer 215 and the demultiplexer 225 to 0 ; transferring test data between the first sub - chip 11 and the second sub - chip 12 ; and outputting test result . in fig3 , when none of the tsvs fails , the selecting signals of the first multiplexers 212 ˜ 214 and the second multiplexers 221 ˜ 224 are adjusted to 0 with the third multiplexer 215 and the demultiplexer 225 un - activated . thus , all the signals between the first and the second sub - chips 11 , 12 are normally transferred along the original paths of the tsvs 21 ˜ 24 . in fig4 , when one of the tsvs fails , such as the first tsv 21 , the selecting signals of the first multiplexers 212 ˜ 214 , the second multiplexers 221 ˜ 224 , the third multiplexer 215 and the demultiplexer 225 are adjusted to 1 so that all the signals between the first and the second sub - chips 11 , 12 are shifted to neighboring tsvs , where the signal of the failed first tsv 21 is shifted to the second tsv 22 . the test tsv 25 is used as a redundant tsv for shifting the signal of the neighboring tsv . in another word , the signal of the fourth tsv 24 is transferred through the redundant tsv so that all signals are normally transferred as are repaired . in fig5 , the present invention uses different test bandwidth ( 32 - bits , 48 - bits and 64 - bits ); and , by using the test tsv in a two - layer structure and a four - layer structure , 3 . 4 % and 4 . 1 % of the chip area can be reduced , respectively , due to no extra area occupied by redundant tsvs . traditionally , in order to achieve a certain yield of tsv , redundant tsvs are used so that the test tsv is placed at a worse position in the test wiring design ; but , in fig6 , the present invention achieves an average reduction of 21 . 8 % of the total length of the test wiring by using the test tsv . the present invention uses a test tsv , which will transfer test data for a 3d - ic chip when being operated under a scan mode , to repair another failed tsv when being operated under a normal mode . since the test tsv does not transfer signal under the normal mode , the present invention provides a structure for repairing the failed tsv without increasing the chip area . the test tsv is functioned as a redundant tsv for repairing signal . through replacing the failed tsv with the test tsv used for testing the 3d - ic chip , the chip area is not increased and the yield is improved as well . besides , the number of redundant tsvs used is apparently reduced with lowered production cost . to sum up , the present invention is an apparatus of 3d - ic chip using a fault - tolerant test tsv , where a failed tsv is repaired without increasing chip area ; a test tsv is functioned as a redundant tsv for repairing signal ; through replacing the failed tsv with the test tsv , the chip area is not increased and yield is improved as well ; and the number of redundant tsvs used is apparently reduced with lowered production cost . the preferred embodiment herein disclosed is not intended to unnecessarily limit the scope of the invention . therefore , simple modifications or variations belonging to the equivalent of the scope of the claims and the instructions disclosed herein for a patent are all within the scope of the present invention .
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the present invention relates to methods and devices for inhibition of overgrowth of vascular tissue , e . g ., fibrointimal proliferation or neointimal hyperplasia , in transplanted vascular tissue . the treatments described in the present invention occur during the surgical grafting procedure , but their effect is often not detected clinically for many months after successful completion of the surgery . the present invention also relates to revascularization procedures such as bypass grafting of the femoral artery to the popliteal artery , aortofemoral bypass grafting procedures utilizing transplanted autologous vascular tissues , such as the autologous saphenous vein . the present invention relates to a method of reducing overgrowth of vascular repair tissue , e . g ., fibrointimal proliferation or neointimal hyperplasia , in autologous coronary bypass conduit grafts , comprising the steps of : ( b ) subjecting the graft to irradiation with a dose effective for reducing fibrointimal proliferation or neointimal hyperplasia , to give a treated graft ; and in one embodiment of the method of the present invention , the coronary bypass conduit graft is removed from the long saphenous vein , the short saphenous vein , the cephalic vein , the brachiocephalic vein , or radial artery . in another embodiment of the method of the present invention , the irradiation is beta irradiation from within the lumen of the graft . in another embodiment of the method of the present invention , the irradiation is x irradiation from a micro x - ray source within the lumen of the graft . in another embodiment of the method of the present invention , the irradiation is from the gamma emitting radionuclide 125 i . in another embodiment of the method of the present invention , the mammal is a human . in another embodiment of the method of the present invention , the dose is limited to a range of between about 1 . 0 gy and about 60 . 0 gy . in another embodiment of the method of the present invention , the dose is limited to a range of between about 3 . 0 gy and about 30 . 0 gy . in another embodiment of the method of the present invention , the dose is limited to a range of between about 6 . 0 gy and about 20 . 0 gy . in another embodiment of the method of the present invention , the radiation source is 90 sr . one specific embodiment of the present invention is a method of reducing fibrointimal proliferation or neointimal hyperplasia in autologous coronary bypass vein grafts , comprising the steps of : ( a ) providing a vein harvested ex vivo from a human , said vein selected from the long saphenous vein and the short saphenous vein ; ( b ) subjecting the vein to beta irradiation from within the lumen of the vein , with a dose effective for reducing fibrointimal proliferation or neointimal hyperplasia , said dose ranging from between about 6 . 0 gy and about 20 . 0 gy of 90 sr , to give a treated vein ; and the present invention also relates to a device for irradiating ex vivo autologous coronary bypass conduit grafts of a mammal , comprising ( a ) a sterile sleeve insertable ex vivo into the lumen of the graft ; and ( b ) a radiation source capable of delivering a dose effective for reducing fibrointimal proliferation or neointimal hyperplasia in the graft , said source insertable into said sleeve for endovascular delivery of the radiation dose to the graft . in one embodiment of the device of the present invention , the coronary bypass conduit graft is removed from the long saphenous vein , the short saphenous vein , the cephalic vein , the brachiocephalic vein , or radial artery . in another embodiment of the device of the present invention , the radiation source produces beta irradiation . in another embodiment of the device of the present invention , the radiation is x rays from a micro x - ray source . in another embodiment of the device of the present invention , the radiation source is the gamma emitting radionuclide 125 i . in another embodiment of the device of the present invention , the mammal is a human . in another embodiment of the device of the present invention , the radiation source delivers a dose of between about 1 . 0 gy and about 60 . 0 gy . in another embodiment of the device of the present invention , the radiation source delivers a dose of between about 3 . 0 gy and about 30 . 0 gy . in another embodiment of the device of the present invention , the radiation source delivers a dose of between about 6 . 0 gy and about 20 . 0 gy . in another embodiment of the device of the present invention , the radiation source is 90 sr . the present invention also relates to a device for irradiating ex vivo an autologous coronary bypass vein graft in a human , comprising ( a ) a sterile sleeve insertable ex vivo into the lumen of the vein graft ; and ( b ) a radiation source capable of delivering a dose effective for reducing fibrointimal proliferation or neointimal hyperplasia in the vein graft , said source comprising radiation seeds of 90 sr , said source insertable into said sleeve for endovascular delivery of the radiation dose to the vein graft , said dose ranging from between about 6 . 0 gy and about 20 . 0 gy . the present invention also relates to a second device for irradiating ex vivo an autologous coronary bypass conduit graft of a mammal , comprising ( a ) a sterile sleeve for holding ex vivo the graft during its irradiation , wherein the sleeve is insertable ex vivo into the graft lumen ; ( b ) a radiation seed safe module attached , with or without fixed or detachable adaptor means , to the sleeve with locking or screwing means , said module containing a radiation source capable of being driven into and through the lumen of the sterile sleeve to provide endovascular delivery of a radiation dose to the graft , said radiation dose suitable for reducing fibrointimal proliferation or neointimal hyperplasia in the graft ; and ( c ) a radiation shield attached at or near the junction of the sleeve and the radiation seed safe module . in one embodiment of the second device of the present invention , the coronary bypass conduit graft is removed from the long saphenous vein , the short saphenous vein , the cephalic vein , the brachiocephalic vein , or radial artery . in another embodiment of the second device of the present invention , the radiation source produces beta irradiation . in another embodiment of the second device of the present invention , the radiation is x - rays from a micro x - ray source . in another embodiment of the second device of the present invention , the radiation comes from the gamma emitting radionuclide 125 i . in another embodiment of the second device of the present invention , the mammal is human . in another embodiment of the second device of the present invention , the radiation source comprises radiation seeds of 90 sr . in another embodiment of the second device of the present invention , the radiation dose is limited to the range between about 1 . 0 gy and about 60 . 0 gy . in another embodiment of the second device of the present invention , the radiation dose is limited to the range between about 3 . 0 gy and about 30 . 0 gy . in another embodiment of the second device of the present invention , the radiation dose is limited to the range between about 6 . 0 gy and about 20 . 0 gy . the present invention also relates to a device for beta irradiating ex vivo an autologous vein graft of a human , comprising ( a ) a sterile sleeve for holding ex vivo the graft during its irradiation , wherein the sleeve is insertable ex vivo into the graft lumen ; ( b ) a radiation seed safe module attached , with or without fixed or detachable adaptor means , to the sleeve with locking or screwing means , said module containing a radiation source comprising one or more radiation seeds of 90 sr capable of being driven into and through the lumen of the sleeve to provide endovascular delivery of a radiation dose to the graft , said radiation dose suitable for reducing fibrointimal proliferation or neointimal hyperplasia in the graft , said radiation dose between about 8 . 0 gy and about 20 . 0 gy ; and ( c ) a radiation shield attached at or near the junction of the sleeve and the radiation seed safe module . the present invention also relates to a third device for irradiating ex vivo autologous coronary bypass conduit grafts of a mammal , comprising ( a ) a sterile slender elongated means insertable ex vivo into the lumen of the graft , for the purpose of mounting and positioning the graft ; ( b ) a cylinder with one or more attached radiation sources , said elongated means with mounted graft insertable into the inside of the cylinder for exovascular delivery of the radiation dose to the graft , said radiation sources capable of delivering a dose effective for reducing fibrointimal proliferation or neointimal hyperplasia in the graft . fig1 shows schematically a sterile disposable sleeve 1 , according to a preferred embodiment of the present invention . sleeve 1 may be formed of any desired material , including plastic or other polymeric material , preferably plastic . the sleeve 1 is optionally covered with balloon 4 . the sleeve 1 without balloon varies between about 1 and about 8 mm in outer diameter . it may be inserted by the surgeon into the coronary bypass conduit , e . g ., the saphenous vein segment . the balloon 4 is placed to account for varying inner diameters of the bypass conduit lumen , in order to enhance uniform irradiation of the graft . the balloon 4 can be inflated according to the size of the graft lumen , and the pressure within the balloon can optionally be monitored with a conventional manometer . the sleeve 1 is sealed closed at one end and is open at the other so that the shielded radiation , e . g ., strontium , source can be inserted into the sleeve after the bypass conduit graft is placed upon it . the sleeve 1 can be screw - locked ( luer lok type ) if desired into a sterile 1 . 2 cm thick clear plastic “ test - tube ” structure that protects the vein during the procedure , and attenuates any beta particles that pass through the vein segment during the radiation treatment ( not shown ). optionally , the irradiation procedure can be performed with a hinged clear plastic hood 29 that attenuates beta rays , such as that exemplified in fig8 . the clear plastic hood 29 is typically at least about 1 . 2 cm thick . lumen 2 of the sleeve 1 is a hollow cavity inside of the sleeve 1 , with the purpose of providing a way to insert , inside the vein , a radiation source , such as radiation seeds , for endovascular delivery of radiation . typically lumen 2 is a cavity with a uniform inner diameter , formed , for example , by drilling at one end of an elongated means to form the sleeve 1 . placement of a graft 5 on the plastic sleeve 1 is shown schematically in fig2 a , according to a preferred embodiment of the invention . the graft is shown in cross - section . a pressure measuring device , e . g ., a manometer , is also shown for balloon 4 . it will be understood from this and other figures that the size and pressure of the balloon are adaptable to the size of the particular graft about to be reimplanted into its autologous host . alternatively , the balloon 4 may be manufactured to inflate to a predetermined external diameter and length . in some cases , a balloon is not necessary to the method and procedure of the present invention , e . g ., a solid plastic rod with lumen or cavity for radiation source may be sufficient . instead of a balloon , appropriate placement of mesh or filaments are readily employed to position the vein to receive a substantially uniform radiation dose . for example , fig2 b schematically shows , according to one embodiment of the present invention , a sterile sleeve 1 with mesh 36 bounded by a fixed collar 37 and a slidable collar 38 . to expand the mesh 36 , the slidable collar 38 is moved toward the fixed collar 37 . an illustration of an expanded mesh is schematically shown in fig2 c , according to one preferred embodiment of the present invention , with slidable collar 38 moved away from the distal end of sterile sleeve 1 . to give an example of the filaments , fig2 c schematically shows , according to one embodiment of the present invention , a sterile sleeve 1 . a radiation seed safe module 34 , depicted schematically in fig3 houses radiation seeds 8 in a detachable safe 6 , prior to endovascular delivery of the radiation seeds 8 into the lumen 2 of the sleeve 1 . see also fig2 . an end cap 7 , which can be metallic or formed of other desired material , protects handlers from unwanted irradiation when the adaptor 3 or other attachment means is removed . an internal source stop 9 prevents retraction of the radiation source , e . g ., seeds , beyond and outside of the detachable safe 6 . within the lumen 2 of the detachable safe 6 , is an outer cable sleeving 11 , and an inner cable 10 , typically epoxied . the adaptor 3 when present , may have a threaded fitting 33 for attachment to the sterile sleeve 1 , or it may lock onto the sterile sleeve 1 . there are a variety of ways to attach sleeve 1 to the detachable safe 6 . the sleeve 1 can be directly attached to the detachable safe 6 as illustrated schematically in fig7 and 8 . alternatively , the sleeve 1 can be attached to the base and pedestal 30 , to which is attached the detachable safe 6 , such that a lumen 2 forms a continuous passageway to allow insertion of radiation seeds into the lumen 2 of the sleeve 1 , as illustrated in fig4 . another means of attachment is with an adaptor 3 that is fixed or detachable , as illustrated in fig1 - 3 . the attachment means in each such situation includes , but is not limited to , any permanent or detachable fitting , such as a threaded fitting , screw lock , luer lok , luer slip , john guest ® quick disconnect fitting , keck ® connector , a barbed fitting , a flared fitting , a combination of a flared female end and male end , an asti teflon ® connector , a loose collar capable of tightening the junction when screwed tight , a keyed fitting with one or more pins , a snap lock , and the like . the radiation shield 12 can serve several other uses during the procedure . the radiation shield 12 can contain niches for thermolucent dosimeter diodes or for scintillation dosimeters ( not shown ) for the measurement of dose at the surface to provide a measure of irradiation that is transmitted through the vein . such an arrangement provides an indirect measure of the dose absorbed by the vein fig4 schematically shows a cross - section of an assembled device 13 , according to a preferred embodiment of the present invention , with its component parts . the sleeve 1 with graft 5 is shown attached to a base and pedestal 30 , with housing 12 serving as a radiation shield . base and pedestal 30 is made of any desired material . housing 12 is made of any desired material , preferably clear plastic . a tube 15 to an air inflator ( not shown ) provides means to inflate balloon 4 . on the outside of the housing 12 is the radiation safe seed module 34 with detachable safe 6 , end cap 7 , outer cable sleeving 11 , inner cable 10 and exemplary radiation seed 8 . the lumen 2 forms a continuous passageway from the distal end of the detachable safe 6 , which connects to the driver ( not shown ), through the base and pedestal 30 and into the sleeve 1 . the inner cable 10 with radiation seeds 8 at or near its tip is driven into the lumen 2 of the sleeve 1 , to deliver a radiation dose to graft 5 . typically , appropriate dosing can be achieved by one pass of the inner cable 10 with radiation seeds 8 into and out of the lumen 2 of the sleeve 1 . when dosing is complete , the inner cable 10 is withdrawn from the lumen 2 of the sleeve 1 into the lumen 2 of the detachable safe 6 . the graft at this point has been suitably irradiated and is ready for removal by the surgical staff for reimplanting in the patient . the beta source control device 16 of fig5 exemplifies an electronic apparatus for automating the methods and devices of the present invention . related afterloading devices suitable for different uses are disclosed and claimed in u . s . pat . no . 5 , 103 , 395 , herein incorporated by reference . the device 16 has the detachable safe 6 with attached cable and sheathing 20 wound around a drive cable capstand 21 , which is rotatably driven by a drive stepping motor 22 for insertion and withdrawal of radiation source ( not shown ) into the sleeve 1 with graft 5 ( not shown ). an emergency retract handle 19 provides manual control of the endovascular delivery system of the present invention . a liquid crystal display readout 17 with data entry and control panel 18 are also set forth in fig5 . the control box for driving or inserting radiation seeds into the lumen of the sleeve is set forth in fig6 . the inner cable 10 , which contains radiation seeds 8 ( shown , for example , in fig3 and 4 ) is driven by a cable driver pinion 24 and motor , into and out of the lumen 2 of the sleeve 1 ( not shown ). inner cable 10 is secured by outer cable sleeving 11 . inner cable 10 is held in place against the cable driver pinion 24 by a pinch idler 23 . pinch idler 23 rotates freely as the inner cable 10 is moved . encoder 25 monitors the position of the inner cable 10 and is part of the position control circuit . using the radiation seed safe module attached to a computer - controlled stepping motor for the purpose of pushing or driving via cable , cam or high precision gear - driven telescoping device , such as is used to telescope a cameral lens , the source train of 90 sr seeds , wire , or a single high - intensity source delivers the dose of irradiation in a more precisely controlled and more accurate manner than by manual manipulation . one illustration of this apparatus is schematically shown in fig5 and 6 . the computer - controlled stepping motor prevents undesirable irradiation occurring during extrusion and retraction of the source train , which would add a small level of dose inhomogeniety along the length of the treated vessel graft . the stepping motor may be connected to the push - rod by a cam or a inner cable 10 . the inner cable 10 is on a spool within the unit containing the drive stepping motor 12 . the outer cable sleeving 11 is uncoiled out of the motor module to be attached to the radiation seed safe module . ( the radiation seed safe module may also be kept within the central unit with only a connector at the end of the outer cable sleeving 11 ). the drive stepping motor is a high speed , high precision device to deliver the radiation dose , by driving a spool of hard metal wound about which the inner cable is coiled . the inner cable extends into the outer cable sleeving and can be optionally attached to the end of the radiation source train ( not shown ) within the radiation seed safe module . the radiation seed safe module can be made so that the inner cable connects to the source train by screw lock or permanently fixed , or other conventional attachment means . a variety of safety features are readily added to the devices of the present invention . in one model with a permanently attached radiation seed safe module , the radiation seed safe module can be machined so that the exit is smaller than the strontium seed casing so it cannot be retracted beyond the safe , e . g ., an internal source stop 9 of fig3 . an encoder monitors the position of the inner cable and is part of the position control circuit . a screw clamp at each end of the radiation seed safe module prevents the radiation source from leaving the radiation seed safe module between treatments . another interlock within the radiation seed safe module prevents accidental extrusion of the seeds until correctly connected . the drive stepping motor has a key that must be turned to the “ on ” position before it will drive the inner cable into and through the lumen of the sterile sleeve . the control panel also has a mechanical key control to prevent accidental activation of the drive stepping motor . an optional second channel in the radiation seed safe module allows the manual or automated advancement of a check cable prior to advancing the radiation seeds into and through the lumen of the sleeve . an illustration of manual control of radiation treatment in the methods and devices of the present invention is set forth in fig7 and 8 . a knob 29 for manual grasping terminates a removable plunger 26 for insertion and removal of radiation seeds 8 . detent plunger 27 and grooves 28 for distance detents locks the radiation seeds 8 at the desired position . the plunger may be removed by releasing the spring - loaded detent plunger 27 . the assembled apparatus of fig9 shows attachment of a housing 29 , and a base and pedestal 30 suitable for a desk top procedure . care in preventing overstretching of the vessel graft on the sleeve 1 with balloon 4 is readily accomplished by appropriate selection of one or more balloons from a series of graduated diameter balloons of fixed size when inflated . the selected balloon or balloons can be either a single balloon or a series of balloons . an alternative arrangement is one or more spiral balloons of appropriate size that wind around the sleeve . the balloons preferably range in size from about 15 mm maximum outer diameter to about 90 mm outer diameter , in 0 . 5 mm increments . the surgeon measures the vessel graft diameter , selects the correct size balloon , places the balloon on the sleeve 1 and then places the vessel graft on the balloon . the balloon is inflated after complete placement within the lumen or cavity of the vessel graft . thereafter the vessel graft is ready for irradiation . the goal of selecting the appropriate balloon is to distend the vessel graft to almost but no more than its normal diameter . another embodiment of the present invention covers a different class of devices that utilize radiation administered external to and outside of the vessel graft , as schematically illustrated by fig9 a , 9 b and 10 . this apparatus is a cylinder 32 , with radiation wire or linear arrays 34 of seeds placed longitudinally and in parallel to the inner central pin 31 . a cross section of cylinder 32 is set forth in fig9 b . during irradiation treatment , the vessel graft mounted on the sleeve 1 is placed inside of the cylinder 32 . in this fashion , beta or gamma irradiation can be administered from outside the vessel graft , i . e ., an exovascular delivery of a radiation dose . the vessel graft ( not shown ) is mounted on a sleeve 1 and is then protected with a sterile thin - walled plastic cylinder ( not shown ) by inserting thereon the sleeve 1 with already mounted vessel graft . once sealed in a sterile fashion within the cylinder and placed within the cylinder 32 , an optional retractable shield ( not shown ) is removed to expose the radiation source . administration of the dose to the vessel graft is achieved by a number of approaches , e . g ., 90 sr in the form of seeds , wire or foil , or transmuted red phosphorus ( 32 p ) combined with malleable thermoplastic material . several long linear sources ( wires or seeds in a row ) in the inner wall of the cylinder 32 are arranged so that a homogeneous dose distribution is achieved where the vessel graft is treated . besides the cylinder 32 with linear rows of radiation sources , other configurations for radiation delivery in the present invention readily occur to the skilled artisan . for example , a variety of chambers lined with fabricated 90 sr foil are suitable ( not shown ), including containers such as a cylinder , tube , or a box . these liners may be installed in a configuration to achieve multiple treatments , e . g ., a beta dose distribution to allow treatment of one to six vein segments . the vessel graft 5 mounted on a sleeve 1 is placed within the inside of the chamber , a sterile plastic liner placed therebetween to protect the mounted vessel graft from microbiological contamination of the chamber . the chamber , be it a cylinder , tube , or box may be hinged and the “ clam - shell or “ lid ” closed to administer the dose of therapeutic irradiation . the simplest design is a 90 sr foil - lined cylinder , sealed at one end with a thin center - post ( not shown ). thin 0 . 5 mm sterile plastic liners can be inserted onto the sleeve and over the post . over the post , the vessel graft on a sleeve with optional balloon is inserted and left in place for the length of time required to administer the desired dose . in one embodiment , a strontium source is utilized to administer a therapeutic dose of beta irradiation between about 6 . 0 to about 18 . 00 gy , preferably between about 10 . 0 to about 14 . 0 gy . a segment of saphenous vein ( usually 15 cm long but sometimes longer ) is irradiated from within the lumen of the vein via an apparatus that houses and provides endovascular delivery of 90 sr radiation sources . the sources are uncovered by a retractable shield or are protruded from a housing that serves as a radiation shield . the methods and devices of the present invention are adaptable to a variety of beta and gamma irradation sources , including , but not limited to , 90 sr , 90 y , 106 ru , 32 p , 192 ir , 125 i , 198 au , or 103 pd . one preferred radiation source is 90 sr . preferred dosage ranges are between about 1 . 0 gy and about 60 . 0 gy , preferably between about 3 . 0 gy and about 30 . 0 gy , most preferably between about 6 . 0 gy and about 20 . 0 gy . selecting the appropriate isotope and dosage is within the skill of the art . the desired exposure time is readily calculated for a given graft diameter , radioisotope , and sleeve geometry and size . the outward configuration of the radiation source is typically in the form of a seed , a piece of foil , a ring , a pin , or a rod . the selected radioactive material may be contained within glass , foil , or ceramics , or , alternatively , within a powder or liquid medium , such as microparticles in liquid suspension . when solid materials are used , the preferred outer diameter of the material is approximately 0 . 5 mm , allowing it to be inserted into the central lumen of the vein sleeve . such radioactive materials may be formed into pellets , spheres , and / or rods in order to be placed into the chamber of the treating element . various alternative treating elements may also be used to contain the radioactive material without departing from the present invention . for example , the treating elements may be toroidal , spherical , or in the form of elongated rings , and in such configurations , the radioactive material may be actually impregnated in a metal and formed into the desired shape . alternatively , a radioactive powder may be fired to fuse the material so that it may be formed into the desired shape , which may then be encapsulated in metal , such as titanium , stainless steel or silver , or in plastic , as by dipping in molten or uncured plastic . in still another embodiment , the treating elements may be formed from a ceramic material which has been dipped in a radioactive solution in a still further alternative , the treating elements may be constructed in the form of two piece hollow cylindrical capsules having a larger - diameter half with a central cavity and a smaller - diameter half also having a central cavity , the smaller half slidably received within the larger half and bonded or welded to form the capsule structure . the methods and devices of the present invention are suitable for any autologous coronary bypass conduit , provided that the bypass conduit is large enough . suitable veins and arteries include , but are not limited to the long saphenous vein , the short saphenous vein , the cephalic vein , the brachiocephalic vein , or radial artery . ex vivo irradiation of saphenous vein graft during coronary artery bypass surgery the technique of ex vivo irradiation requires few modifications from the conventional bypass coronary artery procedure . the patient is brought into the surgery room . monitors are attached and intravenous lines are started . the patient is put to sleep . once the patient is asleep , the surgeon performs a median sternotomy or in some cases a lateral mini - thoractomy . the pericardium is incised and the beating heart is exposed . canulas are positioned into the right atrium and into the aorta . the heart is stopped with cardioplege solution and the bypass perfusion pump is started to circulate blood through the body in the place of the beating heart . incisions are made on the inner aspect of one or both legs . the saphenous vein is dissected from the fatty tissues of the medial leg . the vein is checked for leaks by distending with saline or thereafter sterile fluid under pressure . branching venules are ligated and leaks are repaired . the vein is cut to a 15 cm length . after the vein is resected , inspected , and repaired , a radiation treatment sleeve is selected by the surgeon based upon the diameter of the saphenous vein when it was filled with blood when still in the patient &# 39 ; s leg . after the correct sleeve is selected , it is placed into the lumen of the graft so that the vein is “ impaled ” upon the sleeve . then , the sleeve mounted with saphenous vein is attached via adaptor to the base and pedestal with clear plastic hood . then , a detachable safe ( containing radiation seeds ) with mechanical or automated control units is attached via adaptor to the sleeve mounted with saphenous vein . a treatment time and treatment plan are selected from an atlas or devised upon a miniature treatment planning computer for a treatment upon the size of the treatment sleeve . then , after the clear plastic hood is lowered , radiation seeds of 90 sr are placed by remote control into the sleeve mounted with saphenous vein , and thus in effect into the lumen of the saphenous vein graft segment . a dose of 20 . 0 gy is administered . the radiation seeds are then withdrawn by remote control from the lumen of the saphenous vein graft segment . the vein is removed from the sleeve and handed to the surgeon . then , one end of the vein is sewn to an incision into the aorta and the other end is sewn to the coronary artery just beyond an angiographically detected blockage of the artery . this procedure is repeated until all coronary arteries with significant blockages are bypassed , so that blood coming through the saphenous vein graft from the aorta to the coronary artery bypasses the blocked or occluded areas to perfuse the heart muscle . then , the heart beat is restarted , the perfusion pump is removed , the patient &# 39 ; s heart begins to circulate his own blood . chest tubes are placed through the chest wall to drain any blood into the thoracic cavity to a sealed collecting system outside of the patient . the chest incision is then closed with sternal wires and with sutures . the patient is taken the cardiovascular intensive care unit and allowed to awaken . while the foregoing specification teaches the principles of the present invention , with examples provided for the purpose of illustration , it will be understood that the practice of the invention encompasses all of the usual variations , adaptations , modifications or deletions as come within the scope of the following claims and its equivalents .
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in a rabbit model of chf obtained by rapid ventricular pacing , we previously demonstrated that caspase - 3 activation is associated with a reduction in contractile force of failing myocytes . using in vivo transcoronary adenovirus - mediated gene delivery of the potent caspase inhibitor p35 , we could correct caspase - 3 activation in failing myocardium with a positive impact on sarcomeric organization and contractile performance ( laugwitz et al ., 2001 ). the beneficial effect was observed at the level of the intact heart in vivo , but also at the level of single cells isolated from in vivo ad - p35 - infected myocardium . therefore , extranuclear , cytosolic mechanisms independent of the execution of nuclear apoptosis must have mainly accounted for the negative effects of caspase - 3 activation in heart failure . to better understand the mechanism that may cause cytosolic caspase - 3 - mediated sarcomeric disarray , we performed a screening for caspase - 3 interacting proteins expressed in the heart . we employed a modified yeast two - hybrid system utilizing , as bait vector , the plasmid pbtm - casp3 - p12p17 m , which has already been succesfully used to identify gelsolin as a substrate for caspase - 3 ( kamada et al ., 1998 ). both large ( p17 ) and small ( p12 ) subunits of active caspase - 3 were separately expressed in yeast at equimolar ratios under adh1 promoters . the small subunit was fused to the lexa dna - binding domain , and a point mutation in the active site of the enzyme ( cys - 163 to ser ) prevented proteolytic cleavage of interacting substrates . the bait plasmid was cotransfected into yeast with a human heart cdna expression library fused to the gal4 activation domain . by screening 30 millions transformants , we obtained 125 positive clones which were divided into 22 groups on the base of inserted fragment size and restriction enzyme digestion pattern . dna sequencing analysis showed that six of the positive clones encoded overlapping c - terminal parts ( clone # 7 , # 12 , and # 20 ) or the complete sequence ( clones # 3 , # 9 , and # 17 ) of vmlc1 . mlc1 is one of the six polypeptide chains of the myosin molecule , and is proposed to function as an actin / myosin tether regulating cross - bridge cycling events ( morano , 1999 ). in this study we further analysed the vmlc1 clones , and the others will be described elsewhere . to examine cleavage of vmlc1 candidates by caspase - 3 in vitro , proteins encoded by the cdnas were produced by in vitro transcription / translation - reaction . as shown in fig1 a , clones # 3 , # 9 and # 17 , which contained the complete sequence of human vmlc1 , were cleaved by human recombinant active caspase - 3 , and this cleavage was blocked in the presence of its tetrapeptide inhibitor devd - fmk , suggesting that vmlc1 is a substrate for caspase - 3 . immunoblot analysis of protein extracts from left ventricle , incubated with active caspase - 3 , confirmed this result ( fig1 b ). a ˜ 20 kd cleavage product for vmlc1 was already evident with 5 ng / μl active caspase - 3 . indeed , other structurally related sarcomeric proteins , ventricular regulatory myosin light chain ( vmlc2 ), or β myosin heavy chain , were not cleaved , demonstrating that cleavage of vmlc1 was not due to a generalized degradation of proteins ( fig1 c ). to determine caspase - 3 cleavage site of vmlc1 , purified human vmlc1 was incubated with recombinant active enzyme ( fig2 a ). cleavage of purified vmlc1 resulted in two fragments at ˜ 20 kd and ˜ 5 kd . edman sequence analysis of the cleavage products revealed that caspase - 3 cleaved vmlc1 at e 135 of the c - terminal motif dfve 135 g , which is highly conserved ( fig2 b ). this result was confirmed by immunoblot analysis , using a monoclonal antibody for vmlc1 ( clone f 109 . 16 a 12 ) directed against the sequence v 134 eglrv 139 at the caspase - 3 cleavage site . the antibody detected the intact vmlc1 protein but did not detect either of the two cleavage fragments ( data not shown ). the mapped cleavage site corresponds to the caspase - 3 consensus sequence dxxd ( cohen , 1997 ) with exception of substituting the last aspartate residue for the similar acidic glutamate residue at position 135 . recently , cleavage of lens connexin 45 . 6 by caspase - 3 has also been identified at the e 367 residue of deve 367 g ( yin et al ., 2001 ). an extensive screening of several databases did not , however , show any other known substrate of caspase - 3 to be cleaved at the same , atypical cleavage site ( motif dfve ). to determine the functional relevance of vmlc1 cleavage by caspase - 3 in the heart in vivo , we investigated the evidence of vmlc1 cleavage products in extracts from rabbit failing ventricular myocardium , where we have previously documented a ˜ 6 - fold increase in caspase - 3 activity ( laugwitz et al ., 2001 ). as shown in fig3 a , the intact vmlc1 protein of ˜ 27 kd was relatively stable in healthy control hearts . in contrast , a main ˜ 20 kd fragment , corresponding to the n - terminal cleavage product , was present in failing myocardium . myosin is the major component of the thick filaments of sarcomeres , and consists of two heavy chains ( α and β ), each associated with two types of light chains , the essential ( mlc1 ) and the regulatory ( mlc2 ). x - ray crystallographic analyses demonstrated that essential and regulatory myosin light chains are spatially close , and are both associated with the neck region of the myosin heavy chain globular head ( rayment et al ., 1993 ). to examine whether in failing myocytes a morphological disruption of the organized vmlc1 staining of a - bands in sarcomeres occurred and whether it correlated with caspase - 3 activation , single cardiomyocytes from control and chf hearts were isolated . fig3 b shows confocal laser scanning microscopy of isolated ventricular myocytes after staining for activated caspase - 3 and immunostaining for vmlc1 or vmlc2 . in cardiomyocytes isolated from control hearts , there was no evidence of caspase - 3 activation , and both myosin light chains appeared organized in the sarcomeric units ( fig3 b , panels a - b and e - f ). in contrast , failing myocytes with activated caspase - 3 presented a loss of the characteristic localization of vmlc1 in sarcomeres , and the a - band vmlc2 staining , which was maintained , showed a reduced sarcomeric organization compared to that of control cells ( fig3 b , panels c - d and g - h ). sarcomeric disarray in failing cells presenting caspase - 3 activation was confirmed by phalloidin staining , which visualizes actin filaments ( fig3 b , panels k - l ). single - cell shortening experiments in failing cardiomyocytes showed a reduction of basal and isoproterenol - stimulated contraction correlated to the amount of caspase - 3 activation in the cytosol of the failing cells ( fig3 c ). a lot of data suggests that myosin light chains play an important role in cardiac and skeletal muscle function . removing mlcs from chicken skeletal muscle myosin reduces the velocity of actin filament movement by 90 % without significant loss of the myosin atpase activity in an in vitro motility assay ( lowey et al ., 1993 ). furthermore , mlc2 removal has little effect on isometric force , whereas mlc1 removal reduces the isometric force by over 50 % ( vanburen et al ., 1994 ). mutations in the human essential light chain ( met149val ) or regulatory light chain ( glu22lys , pro94arg ) of myosin are associated with rare variants of inherited cardiac hypertrophy , characterized by midventricular cavity obstruction , and correlate with disruption of the stretch activation response of the cardiac papillary muscles ( potter et al ., 1996 ). transgenic mice expressing the human mutant mlc1 met149val faithfully replicate the cardiac disease of the patients with this mutant allele ( vemuri et al ., 1999 ). in the human heart , two different essential myosin light chain isoforms exist : ( a ) an atrial specific isoform ( amlc1 ), which is expressed in the fetal heart and decreases to undetectable levels during early postnatal development in the ventricle , but persists in the atrium for the whole life , and ( b ) a ventricular specific isoform ( vmlc1 ), which is the same isoform present in adult slow skeletal muscle ( price et al ., 1980 ). the reexpression of amlc1 in adult human ventricles has been reported in patients with ischemic or dilative cardiomyopathy and valvular heart disease ( schaub et al ., 1987 ; sutsch et al ., 1992 ). interestingly , in such patients with end - stage heart failure caspase - 3 activation has also been documented ( narula et al . 1999 ). the isoform shift of vmlc1 to amlc1 correlates with an increase in cross - bridge cycling kinetics as measured in skinned fibers derived from the diseased muscle ( morano et al ., 1997 ). postsurgical return to a normal hemodynamic state decreases amlc1 expression in these patients ( sütsch et al ., 1992 ). the functional significance of this isoform switch is not completely clear , but may be a direct compensatory mechanism to caspase - 3 induced vmlc1 cleavage , triggered when the heart attempts to maintain normal cardiac function . the molecular mechanism for mlc1 to affect the cross - bridge kinetics seems to reside in its ala - pro - rich extended n - terminus , which has been shown to interact with the c - terminus of actin ( trayer et al ., 1987 ; milligan et al ., 1990 ). the extended mlc1 n - terminus may provide a tether between the myosin and actin filaments , serving to position the two filament systems for cross - bridge interaction and to amplify small movements of the myosin globular head ( sweeney 1995 ). the mlc1 c - terminus anchors the protein to the myosin globular head . destruction of vmlc1 at the c - terminal motif dfve 135 g by activated caspase - 3 could alter myosin / actin cross - bridge interactions by modifying myosin head stability and thereby lead to reduced force transmission . taken together , this data clearly illustrates that minute changes in vmlc1 structure or composition , particularly in the c terminal anchoring moiety of vmlc1 , can have a dramatic impact on myocyte function and heart contractility . we have therefore demonstrated that vmlc1 is a cellular target for activated caspase - 3 . vmlc1 is cleaved , and its localization in sarcomeres is partially lost in failing cardiomyocytes , presenting caspase - 3 activation and reduced contractile performance . it is plausible that vmlc1 disruption could alter the stiffness of the myosin neck region and therefore reduce the full range of myosin movement during contraction . our findings suggest that caspase - 3 - mediated cleavage of vmlc1 may represent a molecular mechanism contributing to the deterioration of cardiac function prior to myocyte cell death ( summarized in fig4 ). as we had found that the atypical vmlc1 cleavage site dfve did not occur in any other known substrate of caspase - 3 , we intended to identify specific mlc protectants for the treatment of heart failure . the atypical novel cleavage site was therefore used to establish a high throughput - scaleable in vitro assay to differentially screen for caspase - 3 inhibitors which do not inhibit the physiological execution of cell death , but can protect vmlc1 from destruction in heart failure ( summarized in fig5 ). compounds identified in such a screen could be used to treat heart failure and other cardiac diseases , without having a pro - oncogenic potential . to this end , fluorimetric in vitro assays using the specific cleavage sites coupled to indicator dyes were established . caspase - 3 and the structurally almost identical caspase - 7 ( wei et al ., 2000 ) cleaved both substrates , devd and dfve , with a highly reproducible michaelis - menten kinetic . fig6 shows an example of the kinetic course and a lineweaver - burk plot for the substrate dfve cleaved by caspase - 3 . to our surprise , we found that the k m - values for caspase - 3 induced cleavage of both substrates differed markedly . we measured a k m - value for devd which compared well to existing literature data ( table 1 ), whereas the k m - value for dfve was in the range of some other rare substrates of caspase - 3 ( table 1 ). this differential substrate affinity allows to screen for specific inhibitors of vmlc1 cleavage , which would , however , not affect the cleavage of most other known substrates of caspase - 3 and 7 . in such a screen , every compound would be tested at identical concentrations for the inhibition of both reactions ( first assay ), and compounds which specifically inhibit dfve , but not devd cleavage would be selected and tested in cardiomyocytes ex vivo upon coinjection of active caspase - 3 for their capacity to protect against vmlc1 cleavage ( 2nd assay ). as p35 inhibits all effector caspases ( subtypes 1 , 3 , 6 , 7 , 8 and 10 ; e . g ., zhou et al ., biochemistry 1998 ; 37 : 10757 ), our concern was whether the observed beneficial effects of p35 in heart failure were really due to inhibition of caspase - 3 and of the structurally almost identical caspase - 7 . especially , we sought to exclude that the decrease in vmlc1 cleavage in the presence of p35 was due to predominant inhibition of a different caspase , and to exclude that the cleavage of vmlc1 was induced by caspase - 3 only indirectly acting via other effector caspases . therefore , we tested all these enzymes for their capacity to cleave ac - dfve - amc . we found that only caspase - 3 and 7 , which are structurally very similar , can specifically cleave this substrate , whereas no cleavage was detectable with other caspases nor with the related protease calpain - i at physiological substrate concentrations . however , the highly homologous caspase - 7 cleaved the new substrate dfve with almost 1 log scale lower affinity compared to caspase - 3 . table i kinetic constants for chromogenic peptide substrates ( j biol chem . 1997 apr 11 ; 272 ( 15 ): 9677 - 82 ) substrate km ( μm ) ac - devd - pna 11 ac - dqmd - pna 44 ac - vdvad - pna 67 ac - veid - pna 250 ac - yevd - pna 370 ac - vqvd - pna 510 yeast two - hybrid screening using pbtm - casp3 - p12p17 m as bait vector was performed with a human heart cdna library , fused to the gal4 activation domain in the pact2 plasmid ( clontech , heidelberg , germany ), following the hybrid hunter two - hybrid system protocol ( invitrogen , groningen , the netherlands ) in l40 yeast cells ( mata trp1 lue2 his3 ade2 lys2 :: 4lexaop - his3 ura3 :: 81exaop - lacz ). a total of 30 × 10 6 independent clones were screened by selective growth on trp − / leu − / his − / ura − / lys − / ade + synthetic dropout medium plates and expression of β - galactosidase activity . to construct expression plasmids for positive clones obtained from the two - hybrid screening , ecori - xhol fragments of positive clones were inserted into the ecori - xhol cloning sites of pyes2 / nt - a plasmid ( invitrogen ), in which the sequences were under control of the t7 promoter . biotinylated lysine - labeled proteins were prepared from expression plasmids using a tnt t7 quick coupled transcription / translation system ( promega , mannheim , germany ), according to the manufacturer &# 39 ; s instructions . five μl of biotinylated lysine - labeled protein were incubated for 1 h at 37 ° c . with 15 ng / μl recombinant active caspase - 3 ( bd pharmingen , heidelberg , germany ) and optionally with 25 μm tetrapeptide caspase - 3 inhibitor devd - fmk , in a tris - cl reaction buffer , ph 7 . 5 ( 6 mm tris - cl , ph 7 . 5 , 1 . 2 mm cacl 2 , 5 mm dtt , 1 . 5 mm mgcl 2 and 1 mm kcl ). the reaction was stopped by addition of sds - page sample buffer , and cleaved products were size fractionated by sds - 15 % page and blotted to a nitrocellulose membrane . colorimetric detection of biotinylated products was performed on blots with transcend colorimetric translation detection system ( promega ). rabbit ventricle protein extracts were prepared by homogenization in tris - cl reaction buffer , ph 7 . 5 . to examine the cleavage by caspase - 3 , 150 μg protein from control heart extracts were incubated for 1 hr at 37 ° c . with different amounts of recombinant human caspase - 3 , in presence or absence of the caspase - 3 inhibitor devd - fmk ( 25 μm ). after size - fractionation by sds - page , proteins were electrophoretically transfered to a nitrocellulose membrane and blots were incubated for 1 h at room temperature with mouse monoclonal antibodies against vmlc1 ( 0 . 2 μg / ml , clone 2c8 , biospacific , emeryville , calif . ; 1 : 10 dilution , clone f109 . 16a12 , biocytex , marseille , france ), vmlc2 ( 1 : 10 dilution , clone f109 . 3e1 , biocytex ), cardiac α / β myosin heavy chain ( 1 : 10 dilution , clone f26 . 4f4 , biocytex ), α - sarcomeric actin ( 1 : 2 , 500 dilution , clone 5c5 , sigma , munchen , germany ) or cardiac troponin t ( 0 . 4 μg / ml , clone 9b1 , biospacific ). bound antibodies were detected with horseradish peroxidase - conjugated antibody against mouse igg ( 1 : 10 , 000 dilution , sigma ) and visualized by chemiluminescence ( ecl detection kit , amersham pharmacia , freiburg , germany ). left ventricle lysates from control and 15 days paced failing male new zealand white rabbits were prepared by homogenization in denaturing lysis buffer ( 50 mm tris - cl , ph 7 . 4 , 5 mm edta , 1 % sds , 10 mm dtt , 1 mm pmsf , 2 μg / ml leupeptin and 15 u / ml dnase i ), heated at 95 ° c . for 5 min , diluted 1 : 10 with nondenaturing lysis buffer ( 50 mm tris - cl , ph 7 . 4 , 300 mm nacl , 5 mm edta , 1 % triton x - 100 , 10 mm iodoacetamide , 1 mm pmsf , 2 μg / ml leupeptin and 0 . 02 % sodium azide ) and centrifuged at 15 , 000 × g for 10 min at 4 ° c . after dilution to 3 . 5 mg protein / ml , supernatants were precleared with excess of protein g - sepharose beads ( sigma ) and incubated for 2 h at 4 ° c . with protein g - sepharose beads ( 30 μl beads / ml lysate ), preconjugated with 100 μg anti - vmlc1 monoclonal antibody ( clone 2c8 , biospacific ). beads containing the immunocomplex were extensively washed with ice - cold nondenaturing lysis buffer , boiled in sds sample buffer and subjected to sds - 15 % page and immunoblotting for vmlc1 , as described above . medtronic pacemakers were implanted into new zealand white rabbits ( weight 3 . 6 ± 0 . 3 kg ; from harlan , munich , germany ). two days afterwards , rapid pacing was initiated at 320 beats / min . under this protocol , a tachycardia - induced heart failure ( hf ) develops reproducibly over one week . pacing was then continued at 360 beats / min , which predictably led to a further deterioriation of heart failure . the average contractility in failing hearts was 2200 ± 320 mmhg / sec ( vs . 4000 ± 390 mmhg / sec in healthy controls ; p & lt ; 0 . 05 ), and lvedp increased from 3 . 6 ± 0 . 4 mmhg to 13 . 5 ± 1 . 2 ( p & lt ; 0 . 05 ). single myocytes were isolated from the left ventricle of control and 15 days paced failing rabbits , and cultured in m199 culture medium ( supplemented with mem vitamins , mem non - essential aminoacids , 25 mm hepes , 10 μg / ml insulin , 100 iu / ml penicillin , 100 μg / ml streptomycin and 100 μg / ml gentamicin ) on laminin - precoated glass slides ( 5 μg / cm 2 ; density of 10 5 cells / cm 2 ) in a humidified atmosphere ( 5 % co 2 ) at 37 ° c . ( laugwitz et al ., 1999 ). two hours after plating , cells were subjected to detection of activated caspase - 3 . activated caspase - 3 was detected in living cells by using caspatag caspase - 3 activity kit ( intergen , oxford , united kingdom ), according to the manufacturer &# 39 ; s instructions . freshly isolated ventricular cardiomyocytes were incubated at 37 ° c . ( 5 % co 2 ) with fam - devd - fmk , a carboxyfluorescein labeled fluoromethyl ketone tetrapeptide inhibitor of caspase - 3 , which is cell permeable and irreversibly binds to activated caspase - 3 . after 1 h incubation , cells were washed , fixed in 4 % paraformaldehyde , permeabilized in 100 % methanol ( at − 20 ° c .) and subjected to hoechst 33258 staining and either to immunofluorescence staining for vmlc1 / vmlc2 , or to phalloidin staining . vmlcs were detected by labeling with specific mouse monoclonal antibodies anti - vmlc1 ( 4 μg / ml , clone 2c8 , biospacific ) and anti - vmlc2 ( 1 : 2 dilution , clone f109 . 3e1 , biocytex ), followed by incubation with texas red goat anti - mouse - igg conjugate ( 10 μg / ml , molecular probes , leiden , the netherlands ). polymerized actin fibers were visualized by texas red - phalloidin ( 3 units / ml , molecular probes ), according to the manufacturer &# 39 ; s instructions . fractional shortening was measured in rabbit adult cardiomyocytes isolated from left ventricle of control and 15 days paced failing myocardium , after detection of activated caspase - 3 . experiments were performed in a temperature - controlled cuvette ( 37 ° c . ), at constant medium flow ( 1 . 8 mm ca 2 + - tyrode &# 39 ; s solution ) and constant electrical field , using an electro - optical monitoring system ( scientific instruments , heidelberg , germany ), as described ( laugwitz et al ., 1999 ). left ventricular contractility was examined before the initiation of rapid pacing and at the end of the protocol ( two weeks after the start of pacing ). the rabbits were anesthetized as described before ; ecg was monitored continuously . the rate of caspase - 3 enzyme activity could be measured by enzymatic cleavage and release of amc from the ac - devd - amc caspase substrate ( biosyntan , berlin , germany ). this parameter was measured as emission at 460 nm upon excitation at 380 nm using u . v . spectrofluorometry . ac - dfve - amc was synthesized by biosyntan , berlin , germany , with a purity of 93 . 5 %. the peptide lyophilised as trifluoracetic acid salt was reconstituted in dmso to 100 mm . 5 μg of purified , active recombinant human caspase - 3 ( cpp32 ) from bd biosciences pharmingen , heidelberg , germany , were diluted in 100 μl 50 mm tris , ph 8 . 0 , with 100 mm nacl , 50 mm imidazole . the reaction buffer contained 20 mm hepes , 100 mm nacl , 10 mm dtt , 1 mm edta , 0 . 1 % ( w / v ) chaps , 10 % sucrose , ph 7 . 2 and the indicated concentrations of ac - dfve - amc . caspase - 3 was added to reaction mixture at a final concentration of 3 nm . after preincubation for 10 min at 37 ° c ., the released fluorogenic amc was monitored every second minute for 20 min in a spectrofluorometer at an excitation wavelength of 380 nm and an emission wavelength of 460 nm . initial velocities and substrate concentrations were fit by non linear regression to the michaelis - menten equation . lineweaver - burk plots were calculated . cesselli , d ., i . jakoniuk , l . barlucchi , a . p . beltrami , t . h . hintze , b . nadal - ginard , j . kajistura , a . leri , and p . anversa . 2001 . oxidative stress - mediated cardiac cell death is a major determinant of ventricular dysfunction and failure in dog dilated cardiomyopathy . cir . res . 89 : 279 - 286 . chien , k . r . 2000 . genomic circuits and the integrative biology of cardiac diseases . nature 407 : 227 - 232 . cohen , g . m . 1997 . caspases : the executioners of apoptosis . biochem . j . 326 : 1 - 16 . haunstetter , a ., and s . izumo . 1998 . apoptosis : basic mechanisms and implications for cardiovascular disease . circ . res . 82 : 1111 - 1129 . hengartner , m . o . 2000 . the biochemestry of apoptosis . nature 407 : 770 - 776 . kamada , s ., h . kusano , h . fujita , m . ohtsu , r . c . koya , n . kuzumaki , and y . tsujimoto . 1998 . a cloning method for caspase substrate that uses the yeast two - hybrid system : cloning of the antiapoptotic gene gelsolin . proc . natl . acad . sci . usa . 95 : 8532 - 8537 . laugwitz , k . l ., a . moretti , h . j . weig , a . gillitzer , k . pinkernell , t . ott , i . pragst , c . stadele , m . seyfarth , a . schömig , and m . ungerer . 2001 . blocking caspase - activated apoptosis improves contractility in failing myocardium . hum . gene ther . 12 : 2051 - 2063 . laugwitz , k . l ., m . ungerer , t . schoneberg , h . j . weig , k . kronsbein , a . moretti , k . hoffmann , m . seyfarth , g . schultz , and a . schömig . 1999 . adenoviral gene transfer of the human v2 vasopressin receptor improves contractile force of rat cardiomyocytes . circulation 99 : 925 - 933 . lowey , s ., g . s . waller , and k . m . trybus . 1993 . function of skeletal muscle myosin heavy and light chain isoforms by an in vitro motility assay . j . biol . chem . 268 : 20414 - 20418 . mallat , z ., a . tedgui , f . fontaliran , r . frank , m . durigon , and g . fontaine . 1996 . evidence of apoptosis in arrhythmogenic right ventricular dysplasia . n . engl . j . med . 335 : 1190 - 1196 . milligan , r . a ., m . whittaker , and d . safer . 1990 . molecular structure of f - actin and location of surface binding sites . nature . 348 : 217 - 221 . morano i , k . hadicke , h . haase , m . böhm , e . erdmann , and m . c . schaub . 1997 . changes in essential myosin light chain isoform expression provide a molecular basis for isometric force regulation in the failing human heart . j . mol . cell cardiol . 29 : 1177 - 1187 . morano , i . 1999 . tuning the human heart molecular motors by myosin light chains . j . mol . med . 77 : 544 - 555 . mittl p r , di marco s , krebs j f , bai x , karanewsky d s , priestle j p , tomaselli k j , grutter m g . structure of recombinant human cpp32 in complex with the tetrapeptide acetyl - asp - val - ala - asp fluoromethyl ketone . j biol chem . 1997 mar 7 ; 272 ( 10 ): 6539 - 47 . narula , j ., p . pandey , e . arbustini , n . haider , n . narula , f . d . kolodgie , b . dal bello , m . j . semigran , a . bielsa - masdeu , g . w . dec , s . israels , m . ballester , r . virmani , s . saxena , and s . kharbanda . 1999 . apoptosis in heart failure : release of cytochrome c from mitochondria and activation of caspase - 3 in human cardiomyopathy . proc . natl . acad . sci . usa . 96 : 8144 - 8149 . nicholson , d . w ., a . ali , and n . a . thornberry . 1995 . identification and inhibition of the ice / ced - 3 protease necessary for mammalian apoptosis . nature 376 : 37 - 43 . olivetti , g ., r . abbi , f . quaini , j . kajstura , w . cheng , j . a . nitahara , e . quaini , c . de loretto , c . a . beltrami , s . krajewski , t . c . reed , and p . anversa . 1997 . apoptosis in the failing human heart . n . engl . j . med . 336 : 1131 - 1141 . potter , k ., h . jiang , s . hassanzadeh , s . r . master , a . chang , m . c . dalakas , i . rayment , j . r . sellers , l . fananapazir , and n . d . epstein . 1996 . mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle . nat . gen . 13 : 63 - 69 . price , k . m ., w . a . littler , and p . cummins . 1980 . human atrial and ventricular myosin light chains subunits in the adult and during development . biochem . j . 191 : 571 - 580 . rayment , i ., w . r . rypniewski , k . schmidt - bäase , r . smith , d . r . tomchick , m . m . benning , d . a . winkelmann , g . wesenberg , and h . m . holden . 1993 . three - dimensional structure of myosin subfragment - 1 : a molecular motor . science . 261 : 50 - 58 . schaub , m . c ., and h . o . hirzel . 1987 . atrial and ventricular isomyosin composition in patients with different forms of cardiac hypertrophy . basic res . cardiol . 82 ( suppl . 2 ): 357 - 367 . sütsch , g ., u . t . brunner , c . von schulthess , h . o . hirzel , o . m . hess , m . turina , h . p . krayenbuehl , and m . c . schaub . 1992 . hemodynamic performance and myosin light chain - 1 expression in the hypertrophied left ventricle in aortic valve disease before and after valve replacement . cir . res . 70 : 1035 - 1043 . sweeney , h . l ., 1995 . function of the n terminus of the myosin essential light chain of vertebrate striated muscle . biophys . j . 68 ( suppl . 4 ): 112s - 119s . talanian r v , quinlan c , trautz s , hackett m c , mankovich j a , banach d , ghayur t , brady k d , wong w w . substrate specificities of caspase family proteases . j biol chem . 1997 apr 11 ; 272 ( 15 ): 9677 - 82 . trayer , i . p ., h . r . trayer , and b . a . levine . 1987 . evidence that the n - terminal region of al - light chain of myosin interacts directly with the c - terminal region of actin . a proton magnetic resonance study . eur . j . biochem . 164 : 259 - 266 . vanburen , p ., g . s . waller , d . e . harris , k . m . trybus , d . m . warshaw , and s . lowey . 1994 . the essential light chain is required for full force production by skeletal muscle myosin . proc . natl . acad . sci . usa . 91 : 12403 - 12407 . vemuri , r ., e . b . lankford , k . potter , s . hassanzadaeh , k . takeda , z . x . yu , v . j . ferrans , and n . d . epstein . 1999 . the stretch - activation responce may be critical to the proper funtioning of the mammalian heart . proc . natl . acad . sci . usa . 96 : 1048 - 1053 . wei y , fox t , chambers s p , sintchak j , coll j t , golec j m , swenson l , wilson k p , charifson p s . the structures of caspases - 1 , - 3 , - 7 and - 8 reveal the basis for substrate and inhibitor selectivity . chem biol . 2000 jun ; 7 ( 6 ): 423 - 32 . yin , x ., s . gu , and j . x . jiang . 2001 . the development - associated cleavage of lens connexin 45 . 6 by caspase - 3 - like protease is regulated by casein kinase ii - mediated phosphorylation . j . biol . chem . 276 : 34567 - 34572 .
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referring to fig1 a tiller generally indicated as 11 is comprised of a main housing 13 and an extention housing 15 . tine shafts carry a plurality of tine teeth 17 and are rotatably supported in the housings 13 and 15 . the tine shafts are driven by hydraulic motor 19 fixably mounted to the tiller housing 13 . an input line 21 is received by the hydraulic motor delivering pressurized hydraulic fluid from a remotely located hydraulic pump ( not shown ). a return line 23 receives spent fluid from the hydraulic motor 19 and delivers it to a filter 25 which thereafter delivers the fluid to a reservoir chamber 27 formed by the housing 13 . a suction line 29 receives cold hydraulic fluid and delivers the hydraulic fluid to the input of the remotely located pump . referring more particularly to fig2 and 3 , the housing 13 is comprised of top wall 30 having fixably mounted atop wall 30 an expansion chamber 31 including filler cap 32 . the reservoir 27 is formed in combination with the top wall 30 , forward wall 35 and rear wall 37 , and end walls 39 and 41 respectively . a bottom wall 33 is fixably mounted to the walls 35 , 37 , 39 and 41 by any conventional means and has a generally arched cross - sectional configuration . a baffle plate 42 extending longitudinally is fixably mounted by any conventional means particularly along the apex of the bottom wall 33 and to the underside of top wall 30 , and also , to end wall 41 separating the reservoir into sections a and b . one end of baffle plate 42 is in spaced apart relationship to end wall 39 . the housing top wall 30 forms the underside of the expansion chamber 31 and has a plurality of apertures 38 extending through wall 30 to each side of baffel 42 to allow communication between reservoir 27 and expansion chamber 31 . a filter line 43 to which filter 25 is fixably mounted to by any conventional means extends through the top wall 30 into section a of the reservoir on one side of baffle plate 42 . the suction line 29 extends through the top wall 30 substantially into section b of the reservoir 27 on the other side of baffle plate 42 . fixably mounted transversely across the top wall 30 of the housing 13 in spaced apart opposite relationship are mounting members 45 , 46 , 47 and 48 . hydraulic motor 19 is fixably mounted in sidewall 41 within a formed mounting sleeve 51 by any conventional means such as by bolts . the motor output shaft 55 extends into the housing 11 and is splined within the tine shaft 59 at 57 . the tine shaft 59 is of conventional design carrying a plurality of tine blade 61 in spaced apart relationship , each tine blade 61 having a plurality of tine teeth 63 fixably mounted thereto in spaced apart relationship . a conventional bearing set 65 is mounted into the lower portion of housing wall 39 and rotatably supports the other end of tine shaft 59 . the housing wall 39 contains a flange 67 extending transversely along the end of top surface 30 . the extention 15 comprised of housing extension 78 . one other end of the extension tine shaft 73 contains a portion 74 which receives a portion of tine shaft 59 extending through end wall 39 and extention end wall 80 and is pinned to shaft 59 at 75 . the two housings are joined along respective walls 39 and 80 by fixably mounting respective wall flanges 67 and 69 by any conventional means such as by bolts . referring now to fig4 it is observed that a tractor can be mounted to either side of the tiller 11 such that the tractor rear wheel 70 can rotate either in the same direction as the tine shaft , or as shown in phantom in the opposite direction of the tine shaft . further , the tiller 11 can be centered relative to the tractor by securing hitch arms 85 to mounting members 46 and 48 , or mounting members 45 and 47 when the tiller extension 15 is also be used . it is further observed that the tiller offers the further advantage of having a segregated hydraulic system which reduces contaminant problems . also , the tiller housing offers good cooling properties which eliminates the necessity to have a separate hydraulic fluid cooling system by providing the reservoir as part of the tiller housing and requiring the fluid to flow longitudinally in section a , over the apex of under surface 33 , between baffel 42 and end wall 39 , and longitudinally in section b before being received in line 29 .
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as shown in fig1 - 8 , a system 10 and method converting exhaust waste of a combustion engine 12 to carbon nanotubes within an exhaust system 14 in fluid communication with the combustion engine 12 is disclosed . in at least one embodiment , the system 10 may include a filter 16 and a process that converts waste exhaust of combustion engines 12 into carbon nanotubes . the combustion engine 12 may be used in numerous applications , such as , but not limited to , being used as an automotive combustion engine . in at least one embodiment , aspects of the system 10 and method include the filter material 16 , treatment of the filter material , alignment of the filter material and process that yields the maximum amount of carbon nanotubes . the system 10 and method may also include use of a fuel 18 with one or more metal salts that once combusted within a combustion engine 12 produce carbon nanotubes downstream of a combustion chamber , such as , but not limited to , within the exhaust system 14 . in at least one embodiment , the system 10 may include a filter 16 placed downstream of the combustion engine 12 . the filter 16 may be formed from any appropriate material capable of withstanding the environment , such as the heat generated by the combustion engine 12 . in at least one embodiment , the filter 16 may be formed from filter material that is thin , such as less than one mm in thickness , and may be formed from a metal , such as but not limited to iron metal . in at least one embodiment , the filter material forming the filter 16 may be formed from pure iron such as , but not limited to , pure iron sheets . in another embodiment , the filters 16 may be formed from carbonated steal with low percentage of carbon , such as , but not limited to , 0 . 05 or less carbon . in yet another embodiment , a thin layer of iron may be posted on a polymeric or metallic sheet . the thin layer may be produced by one or more physical processes , such as , but not limited to , pulse laser deposition or ablation processes . in the event of using carbonated steel , or iron , a polishing scheme may be used to expose the iron grains on the surface . such processes may not be needed for thin layer depositions as described before . the filter 16 may be positioned in the path of the exhaust waste of a combustion engine , such as an automotive engine . the filter 16 may be placed at an angle below 45 degrees and , in at least one embodiment , may be placed below 15 degrees measured from the streamline of the exhaust waste . in at least one embodiment , the filter 16 may be placed at an angle to the exhaust flow of between 5 degrees and 15 degrees . as such , combustion engine exhaust may be directed past the filter 16 having a surface skewed relative to exhaust flow an angle between 5 degrees and 15 degrees . localized heating of the filter 16 or its surrounding is required to activate the carbon nanotubes formation . though a temperature in the range of 700 degrees celsius is preferred , temperatures as low as 200 degrees celsius have shown carbon nanotubes formation . the efficiency of the tube formation is a function of the filter angle and the temperature at the filter location . in at least one embodiment , carbon nanotubes may form on an exposed surface of the filter 16 such that the carbon nanotubes may be formed from multiwall carbon nanotubes having an average diameter of between 20 and 50 nm and average length of between one micrometer and 10 micrometers . the method of converting exhaust waste of combustion engines 12 to carbon nanotubes , as shown in fig5 - 7 , within an exhaust system 14 in fluid communication with the combustion engine 12 includes generating combustion engine exhaust through combustion of a fuel 18 including a metal salt and heating one or more filters 16 to at least 200 degrees celsius . the method also includes passing combustion engine exhaust past the filter 16 positioned within the exhaust system 14 of the combustion engine 12 , wherein carbon nanotubes form on an exposed surface of the filter 16 . in at least one embodiment , the method may include a process for converting diesel engine exhaust gases into carbon nanotubes . as shown in fig8 , one or more filters 16 may be placed downstream of the combustion engine 12 in at least a portion of the exhaust gases flowing from the combustion engine 12 . the method may include generating combustion engine exhaust through combustion of a fuel 18 including a metal salt whereby the metal salt may be , but is not limited to being , an iron salt . the metal salt may be , but is not limited to being , used in a concentration between about one mg of metal salt / ml of fuel 18 and four mg of metal salt / ml of fuel 18 . concentrations less than this range and without a metallic substrate do not generate carbon nanotubes . in at least one embodiment , the metal salt may have a concentration of two mg of metal salt / ml of fuel 18 . the metal salt may be used together with a fuel 18 , such as , but not limited to , diesel fuel 18 . in at least one embodiment , at least a portion of the fuel 18 may be an algal biodiesel . in another embodiment , at least a portion of the fuel 18 may be a fossil diesel fuel 18 . in yet another embodiment , the fuel 18 may be a mixture of algal biodiesel fuel 18 and fossil diesel fuel 18 . the utilization of algal biodiesel fuel 18 promotes formation of carbon nanotubes by suspending the iron salt within the fossil diesel fuel 18 . in still another embodiment , the fuel 18 may be a mixture of algal biodiesel fuel 18 , ethanol and fossil diesel fuel 18 . the fuel 18 may be formed by introducing one or more metal salts into algal biodiesel to form a mixture . the mixture of one or more metal salts into algal biodiesel may then be mixed into the fossil diesel fuel 18 to form a homogenous suspension . the algal biodiesel creates a homogenous suspension of the iron salt in fossil fuel 18 diesel . the presence of the metal salt increases the formation of carbon nanotubes on the filer 16 . in at least one embodiment , the diesel fuel 18 may be formed from a mixture of between one percent and ten percent algal biodiesel fuel 18 , between one percent and ten percent ethanol and remainder fossil diesel fuel 18 . in another embodiment , the diesel fuel 18 may be formed from a mixture of about five percent algal biodiesel fuel 18 , about five percent ethanol and about 90 percent fossil diesel fuel 18 . combustion of fuel 18 , such as but not limited to diesel fuel 18 , with metal salts , such as , but not limited to one or more iron salts , improves the combustion quality and reduces the formation of soot . the inclusion of biodiesel together with the fossil fuel 18 diesel may help to reduce environmental hazards , such as , but not limited to , co ( x ) and so ( x ). the following examples are not to limit the scope of the invention but to illustrate the invention . a filter made out of a solid structure such as , but not limited to , carbonated steel , was placed in the pathway of a diesel engine exhaust . the engine was allowed to run at normal operation condition for half an hour . the filter was recovered and evaluated using sem . fig1 shows a monograph of the material collected on the solid filter . it showed clumps of carbon particulates . a filter made out of carbonated steel was polished using techniques known in the literature . the surface was examined using optical microscopy . the grains were clearly shown . the filter was placed in the pathway of a diesel engine exhaust . the engine was allowed to run for half an hour under normal operation conditions . the filter was collected and examined using sem . fig2 shows sem monograph of the materials collected on the surface of the filter . it shows clumps of carbonated materials . a similar filter made out of carbonated steel was polished and placed in the pathway of the exhaust horizontally to the exhaust streamlines . the filter zone was heated using a gas burner . the diesel engine was allowed to run in normal condition for half an hour . the filter material was collected and examined using sem . fig3 shows sem monograph showing the formation of carbon nanotubes . a similar filter made out of carbonated steel was polished and placed in the pathway of the exhaust of a diesel engine at an angle of 5 degrees to the streamlines of the exhaust . a diesel engine was allowed to run under normal operating conditions for half an hour . the filter location was heated using a gas burner . the filter was collected an examined using sem . fig4 shows a monograph of the filter surface with carbon nanotubes formed on the surface . it is noticeable that the angle of 5 degrees influenced the formation of more carbon nanotubes . the produced carbon nanotubes are purified by immersing the filter plate in a ionic liquid bath . the purification process using ionic liquids produces 95 % purified carbon nanotubes . without limitation to the composition , ionic liquids have the ability to dissolve carbonated materials other than carbon nanotubes leaving a highly purified carbon nanotube stock . the system and method are not limited to the details of construction or process steps set forth in the following description . instead , the system and method is capable being practiced or carried out in other ways and via other embodiments of the system . as used in this specification and the appended claims , the singular forms “ a ”, “ an ” and “ the ” include plural referents unless the context clearly indicates otherwise . thus , for example , reference to “ a filter ” includes a mixture of two or more filters , and the like . the foregoing is provided for purposes of illustrating , explaining , and describing embodiments of this invention . modifications and adaptations to these embodiments will be apparent to those skilled in the art and may be made without departing from the scope or spirit of this invention .
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referring now to the drawings and particularly to fig1 and 2 , a lighting fixture is seen generally at 10 to comprise a recessed lighting fixture such as is described in u . s . pat . no . 5 , 690 , 423 , the disclosure of which is incorporated hereinto by reference as aforesaid , the fixture 10 being a particular fixture with which the present invention functions to produce the objects and advantages referred to herein . it is to be understood , however , that lighting fixtures , particularly downlighting fixtures , employing painted steel pans such as are conventional in the art and other pans such as the pan described in u . s . pat . no . 5 , 662 , 414 , assigned to the assignee of the present application and incorporated hereinto by reference , can also be improved through use therewith of the present invention . as shown best in fig2 the lighting fixture 10 is provided with a wire frame pan 12 such as is disclosed in detail in aforesaid u . s . pat . no . 5 , 690 , 423 . the pan 12 mounts a junction box 14 and a can 16 for &# 34 ; rough - in &# 34 ; above a ceiling ( not shown ) to produce downlighting in an environmental space below the ceiling . a standard conduit ( not shown ) extends from the junction box 14 to the can 16 in a conventional manner to allow access of insulated wiring ( not shown ) into the interior of the can 16 to provide power to a lamp ( not shown ) mounted within the interior of the can 16 . the connection of electrical power to lamping within the can 16 through the junction box 14 as well as the provision of finishing trim and the like ( not shown ) is conventional and need not be described in detail herein . the junction box 14 is essentially identical as shown to that junction box described in u . s . pat . no . 5 , 690 , 423 , the main body of the junction box 14 being formable from a flat , stamped piece of metal which is then bent to assemble the junction box 14 with mounting plates 20 and 22 being formed integrally with the junction box 14 . each of the mounting plates 20 and 22 are respectively formed with slots 24 and 26 which align on assembly of the junction box 14 to receive a bar hanger assembly 28 to thus mount said assembly 28 to the fixture 10 . at the opposite end of the lighting fixture 10 , a bar hanger assembly 30 is mounted by the wire frame pan 12 as is described in detail in u . s . pat . no . 5 , 690 , 423 . the bar hanger assembly 30 is thus mounted to the fixture 10 through direct connection to the wire frame pan 12 while the bar hanger assembly 28 is mounted by the junction box 14 by means of the mounting plates 20 and 22 which can be integrally formed with the junction box 14 . the structure and function of the bar hanger assemblies 28 and 30 are essentially identical . while the bar hanger assemblies shown in the aforesaid patents and described in detail in co - pending u . s . patent application ser . no . 08 / 690 , 314 , filed jul . 25 , 1996 , all of these entities being incorporated hereinto by reference , are particularly suited to use with the present invention , it is to be understood that the bar hanger assemblies 28 and 30 can take other forms and can vary from the bar hanger assemblies described in detail in said patent application . a brief discussion of the function of the bar hanger assembly 30 will be provided herein , only one of the bar hanger assemblies 28 , 30 being necessarily described since the structure and function thereof are essentially identical . the bar hanger assembly 30 is formed of a slide element 32 and a track element 34 , the elements 32 and 34 being often referred to as &# 34 ; bar &# 34 ; elements . the track element 34 has a guideway or track 36 formed by the bending over of opposite lateral edges of said track element 34 to form said track 36 . the track 36 receives the slide element 32 thereinto for sliding movement therein . each of the elements 32 , 34 are provided with nailing plates 38 and 40 on respective outermost ends thereof , the nailing plates 38 , 40 being respectively bent at angles of 90 ° relative to the longitudinal axes of the elements 32 , 34 . while these nailing plates can take different forms , it is desirable to stamp barbs 40 , 44 from the respective planar body portions of the nailing plates 38 , 40 , the structure thus described facilitating rapid mounting to wooden joists ( not shown ). the mounting of the lighting fixture 10 to wooden joists in a ceiling is essentially conventional . the bar hanger assemblies 28 , 30 can be adjusted lengthwise by virtue of the ability of the elements 32 , 34 to slide relative to each other . the bar hanger assembly 30 is also capable of sliding relative to the wire frame pan 12 . similarly , the bar hanger assembly 28 can slide within the slots 24 , 26 formed in the mounting plates 20 , 22 of the junction box 14 . when the lighting fixture 10 is to be mounted above a suspended ceiling , j - channel notches ( not shown ) formed at ends of the bar elements 32 , 34 allow mounting in a conventional manner to t - bar structures ( not shown ) of such suspended ceilings . a scale can be formed on the element 34 ( the scale not being shown ) to allow estimation of the degree of elongation necessary for appropriate fitting of the bar hanger assemblies 28 , 30 between joists or between t - bar structures of a suspended ceiling as is conventional in the art . referring now to fig1 through 9 , a bar hanger clip is seen at 50 to comprise a single piece of 0 . 020 inch zinc - plated spring steel formed by stamping or similar operations and the like to comprise a flat , planar base portion 52 joined to a planar body portion 54 by means of a first arcuate section 56 , the plane of the body portion 54 being disposed at slightly less than 90 ° from the plane of the base portion 52 . a second arcuate section 58 joins the other end of the planar body portion 54 to an angled distal portion 60 which is also planar and which rounds at corners 62 and 64 with a radius of approximately 0 . 15 inch . the base portion 52 joins at the end thereof opposite the juncture with the first arcuate section 56 with an angled proximal section 66 which terminates in a third arcuate section 68 , the arcuate section 68 then terminating in recurving fashion to form a terminal planar section 70 which then terminates with a recurved end portion 72 . a portion of the angled proximal section 66 , the entirety of the third arcuate section 68 , the terminal planar body portion 70 and the recurved end portion 72 can be notched at 74 to form spaced hinging legs 76 and 78 . the hinging legs 76 and 78 are clipped over a portion of the wire frame pan 12 as best seen in fig1 and in adjacent relationship to the bar hanger assembly 30 . the clip 50 can then pivot about that portion of the wire frame pan 12 to which it is mounted to be positioned in an unlatched configuration ( seen in fig2 ) such that the bar hanger assembly 30 is not latched in position and can be moved relative to the fixture 10 to an appropriate position as aforesaid . as has also been discussed , the slide element 32 and the track element 34 of the bar hanger assembly 30 can be moved relative to each other to desired positions as long as the clip 50 is maintained in the unlatched position . the bar hanger clip 50 can be pivoted about that portion of the wire frame pan to which it is attached to engage in a snap - fitting manner the bar hanger assembly 30 . in the event that extension of the bar hanger assembly 30 causes the track element 34 to be disposed in opposing relation to the clip 50 , the clip 50 latches to the bar hanger assembly 30 by means of engagement between the second arcuate section 58 of the clip 50 and upper edge portions of the bar hanger assembly 30 , thereby locking the track element 34 in place . this mounting is seen in fig1 in relation to the clip 50 to the left of the drawing . in the event that extension of the bar hanger assembly 30 causes the slide element 32 to oppose the bar hanger clip 50 , the first arcuate section 56 of the clip 50 is caused to engage upper edge portions of the slide element 32 , thereby to lock the slide element 32 in place . this mounting is seen in fig1 in relation to the clip 50 which is shown to be clipped to the slide element 32 . manipulation of the clip 50 can occur through the use of thumb pressure exerted against the angled distal portion 60 of said clip 50 . the clip 50 thus functions in the manner described herein in an unlatched configuration such that the bar hanger assembly 30 and the elements 32 , 34 comprising said assembly 30 can be fitted to the particular dimensions of an installation . the clip 50 is then employed to engage either the slide element 32 or the track element 34 of the bar hanger assembly 30 to produce the locking function described herein . as can best be seen in fig2 an identical bar hanger clip 50 can be employed to perform the same functions relative to the bar hanger assembly 28 mounted by the junction box 14 . a base plate 80 forming the &# 34 ; floor &# 34 ; of the junction box 14 is provided with a slot 82 near an outer edge of the base plate 80 , the elongated piece of material disposed between an outer edge of the slot and an outer edge of the base plate 80 forming a mounting bar 84 which is capable of receiving the hinging legs 76 , 78 thereabout to mount the clip 50 in place adjacent to the bar hanger assembly 28 . the clip 50 can then function in a manner identical to that described previously relative to the operation of the clip 50 and the bar hanger assembly 30 to latch and unlatch the bar hanger assembly 28 . two of the bar hanger clips 50 are therefore normally employed to latch the respective bar hanger assemblies 28 and 30 in place to the lighting fixture 10 once the elements 32 , 34 of each of the assemblies 28 , 30 are appropriately extended to fit the dimensions of a particular installation . the clips 50 are normally latched in position after the fixture 10 has been &# 34 ; roughed in &# 34 ;, that is , after the bar hanger assemblies 28 and 30 have been fixed in place . referring now to fig3 through 6 , a typical bar hanger clip such as the clip 50 is described herein as having certain relative dimensions which allow functioning with bar hanger assemblies of essentially standard dimensions in the art . it is to be understood that the clip 50 can be configured with dimensions other than will be specified hereinafter in order to function with bar hanger assembly structures of given dimensions . a typical width of the clip 50 such as across the flat base portion 52 or the angled distal portion 60 is approximately 0 . 63 inch , the length of the clip 50 as seen from plan or bottom views being approximately 0 . 78 inch . the width of the hinging legs 76 , 78 are each taken to be approximately 0 . 20 inch with the width of the notch 74 , if the clip 50 is so configured , being approximately 0 . 23 inch . inner corners of the hinging legs 76 , 78 are rounded with a radius of approximately 0 . 03 inch . the radius of each of the rounded corners 62 , 64 is approximately 0 . 15 inch . placement of the flat base portion 52 along the x - axis of a cartesian coordinate system would result in the angled distal portion 60 of the clip being approximately 30 ° to the y - axis . the first arcuate section 56 would then have a radius of 0 . 08 inch with the centerline thereof falling on a line which is 0 . 10 inch in the direction of the x - coordinate from a line tangent to the curvature of the first arcuate section and parallel to the y - axis . this same tangent line would be approximately 0 . 04 inch from a line parallel to the y - axis and which intersects the clip 50 at the juncture of the first arcuate section 56 and the planar body portion 54 , the planar body portion 54 being angled slightly toward the y - axis from a position to the left of the y - axis . the plane of the angled distal portion 60 is spaced from a line tangent to the second arcuate section 58 and parallel to said plane at a distance of 0 . 06 inch , the second arcuate section 58 having a radius of 0 . 10 inch . a line perpendicular to the terminal planar body portion 70 and extending to intersect an edge portion of the recurved end portion 72 is spaced a distance of approximately 0 . 28 inch from a tangent line drawn relative to the third arcuate section 68 . the terminal planar body portion 70 extends relative to the plane of the base portion 52 at an angle of approximately 19 °. the third arcuate section 68 has a radius of approximately 0 . 08 inch with the radius of the recurved arcuate end portion 72 being approximately 0 . 04 inch . placement of the center of the circular arc of the first arcuate section 56 at the 0 , 0 juncture of a cartesian coordinate system , causes the center of the circular arc of the second arcuate section 58 to be spaced 0 . 04 inch from the y - axis and 0 . 34 inch from the x - axis . the center of the third arcuate section 68 would be located 0 . 08 inch from the x - axis and 0 . 58 inch from the y - axis . the distance from the plane of the base portion 52 to the distal end of the angled distal portion 60 would be approximately 0 . 1 inch with said distal end of the section 66 being approximately 0 . 19 inch from the y - axis along a normal drawn thereto . the center of the second arcuate section 58 would be approximately 0 . 37 inch from the normal drawn from the distal end of the portion 60 to the y - axis . the distance of the center of the second arcuate section 58 to a line parallel to the x - axis and extending through the center of the first arcuate section 56 would have a length of approximately 0 . 34 inch , the distance from the center of the first arcuate section 56 and the lower face of the base portion 52 being approximately 0 . 10 inch . the distance between a plane parallel to a lower face of the terminal planar body portion 70 and a tangent to the arc of the recurved end portion 72 would be approximately 0 . 12 inch . all other radii are approximately 0 . 06 inch unless particularly specified . given the relative dimensions specified above , the clip 50 is therefore shaped in order to readily allow mounting of the hinging legs 76 , 78 about structural elements which allow pivoting of the clip 50 . the relative dimensions further allow engagement respectively of the first arcuate section 56 or the second arcuate section 58 with the aforesaid portions of the bar hanger assemblies 28 , 30 to produce the functions described herein . while particular clip structures have been described herein as being useful according to the invention , it is to be understood that other structural conformations could readily be devised to provide the function provided by the clip 50 which is explicitly described and shown herein . similarly , other structure herein explicitly described can be configured other than as expressly shown and described herein . accordingly , it can be readily understood in view of the particular embodiments of the invention which are expressly described hereinabove that the invention can be formed in a wide variety of configurations without departing from the intended scope of the invention , the scope of the invention being defined by the recitations of the appended claims .
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