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From DDO wiki
Jump to: navigation, search
I realize this doesn't really add anything, but that "Nudged Raid Roll" looks like it was designed specifically to break up guilds. -- Shade (ContributionsMessage)
Regarding the looting page (which has been redirected here?), the Dragonmark of Finding now says that it gives +1 loot boost as quoted from Eladrin. However, there seems to be a common belief that it is +2 as it is mentioned extensively in the forums as such. But I am inclined to give priority to a Dev comment (unless the setting was changed in a subsequent update) over general chat when it is difficult to independently verify. -- Highlander (ContributionsMessage)
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Wikia
SRD:Bag of Tricks
Talk0
9,502pages on
this wiki
This material is published under the OGL
Bag of Tricks: This small sack appears normal and empty. However, anyone reaching into the bag feels a small, fuzzy ball. If the ball is removed and tossed up to 20 feet away, it turns into an animal. The animal serves the character who drew it from the bag for 10 minutes (or until slain or ordered back into the bag), at which point it disappears. It can follow any of the commands described in the Handle Animal skill. Each of the three kinds of a bag of tricks produces a different set of animals. Use the following tables to determine what animals can be drawn out of each.
The heavy warhorse appears with harness and tack and accepts the character who drew it from the bag as a rider.
Animals produced are always random, and only one may exist at a time. Up to ten animals can be drawn from the bag each week.
Faint or moderate conjuration; CL 3rd (gray), 5th (rust), 9th (tan); Craft Wondrous Item, summon nature’s ally II (gray), summon nature’s ally III (rust), or summon nature’s ally V (tan); Price 900 gp (gray); 3,000 gp (rust); 6,300 gp (tan).
––— Gray —— –——— Rust —–—– ———– Tan ———–
d% Animal d% Animal d% Animal
01–30 Bat 01–30 Wolverine 01–30 Brown bear
31–60 Rat 31–60 Wolf 31–60 Lion
61–75 Cat 61–85 Boar 61–80 Heavy warhorse
76–90 Weasel 86–100 Black bear 81–90 Tiger
91–100 Badger 91–100 Rhinoceros
Back to Main PageSystem Reference DocumentMagic Items
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Research news
Haplotype blocks
Jonathan B Weitzman
Genome Biology 2002, 3:spotlight-20020524-01 doi:10.1186/gb-spotlight-20020524-01
The electronic version of this article is the complete one and can be found online at:
Published:24 May 2002
© 2002 BioMed Central Ltd
Research news
Advances in medicine will undoubtedly be linked to our ability to correlate human genetic variation with disease. In the May 23 ScienceXpress, Gabriel et al. report a large-scale analysis of haplotypes in the human genome (Sciencexpress 23 May 2002, DOI:10.1126/science.1069424). They characterized haplotype patterns for 51 genomic regions with an average size of 250 kb (covering 13 megabases) from African, European and Asian DNA samples. They genotyped thousands of single nucleotide polymorphisms (SNPs) in 275 individuals by mass spectrometry, and found hundreds of blocks containing only a few haplotypes and low historical recombination rates. The majority of SNP pairs were concordant across population samples. The striking similarity in SNP polymorphisms, recombination sites and haplotypes supports the 'Out of Africa' model for human history. The existence of extensive haplotype blocks will greatly facilitate the study of human variation. This study provides the foundations for construction of a haplotype map of the human genome using common SNP markers, providing insights into human populations and diseases.
References
1. The new genomics: global views of biology.
PubMed Abstract | Publisher Full Text
2. [http://www.sciencexpress.org] webcite
ScienceXpress
3. The emergence of modern humans.
PubMed Abstract
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For the half-year to 30 June 2013, the IPKat's regular team is supplemented by contributions from guest bloggers Stefano Barazza, Matthias Lamping and Jeff John Roberts.
Two of our regular Kats are currently on blogging sabbaticals. They are Birgit Clark and Catherine Lee.
Thursday, 21 February 2008
Boehringer Ingelheim v Swingward decision: and the show's not over yet...
The Court of Appeal has delivered its verdict in Boehringer Ingelheim v Swingward. (Readers will be excused if they have a sense of deja vu as they read those words). This is in the light of the ECJ's reponse to the second set of questions referred to it in this case. The ultimate result is Jacob LJ's statement "what I would do for the present is hold that the defendants have complied with BMS condition 4 and in particular that their activities by way of re-boxing and re-labelling have not caused and will not cause damage to the reputation of the claimants' trade marks.". The for now element is a result of a request from the claimants that the Court of Appeal hold off from making its final decison in the light of the fact that there is a pending Austrian reference to the ECJ asking the following questions:
1(a) Are Article 7 of the Trade Marks Directive [full title set out] and the case-law of the Court of Justice of the European Communities which has been pronounced on it to be interpreted as meaning that proof that reliance on the trade mark would contribute to an artificial partitioning of the market must be furnished not only as regards the repackaging in itself, but also as regards the presentation of the new packaging?
If the answer to this question is in the negative:
(b) Is the presentation of the new packaging to be measured against the principle of minimum intervention or (only) against whether it is such as to damage the reputation of the trade mark and its proprietor?
The IPKat can only agree with Jacob LJ's introductory comments:
Notwithstanding the two references to the ECJ and its answers, each "side" claims to have won...That is a sorry state of affairs. European trade mark law seems to have arrived at such a state of uncertainty that no one really knows what the rules are, outside the obviously core case of straightforward infringement (the use of a mark as a trade mark for the defendant's goods which is the same as or confusingly similar to a plaintiff's registered mark registered for the same or similar goods). Big brand owners want bigger rights; smaller players, no change or less. The compromises which have emerged have very fuzzy lines. So it is that in this case, notwithstanding two references (and a host of cases about relabelling parallel imports going back at least 30 years...), there is still room for argument. There is indeed a yet further reference about the subject still pending before the ECJ, see below.
The only winners here seem to be the lawyers (and of course the academics who get to write about the whole sorry mess).
Subscribe to the IPKat's posts by email here
Just pop your email address into the box and click 'Subscribe':
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Become a Fan
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« Found Art (Chelsea): Unmonumental 185 | Main | Closings (Tribeca) 172 »
September 19, 2009
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User:Pranav Rathi
From OpenWetWare
Revision as of 01:32, 22 January 2013 by Pranav Rathi (Talk | contribs)
Jump to: navigation, search
Contents
About Me
This user is a DNA unzipper
Contact Info
Education
• Planning on getting PhD, Optical Science&Engineering, University Of New Mexico, Albuquerque-NM working at Koch Lab at UNM.
• 2010, MS, Optical Science&Engineering, University Of New Mexico, Albuquerque-NM
• 2005, MS, Applied-Physics, Northern Arizona University, Flagstaff-AZ
• 2003, MA, Mathematical Sciences, MJP-Rohalkhand University, Uttar Pradesh-UP, India
Research interests
Optical Trap
1. Optics: nano, nonlinear, photonics and optoelectronics.
2. Bio-optics.
3. Spiritual science.
Publications
1. Goldbeter A and Koshland DE Jr. . pmid:6947258. PubMed HubMed [Paper1]
2. JACOB F and MONOD J. . pmid:13718526. PubMed HubMed [Paper2]
leave a comment about a paper here
3. Mark Ptashne. A genetic switch. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2004. isbn:0879697164. [Book1]
All Medline abstracts: PubMed HubMed
Useful links
• [Project Pages[1]]
• [Lab NoteBook [2]]
• [Mendeley [3]]
Personal tools
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Tara's bookmarks
"Charm is a way of getting the answer yes without having asked any clear question."
Camus, Albert on charm
16 fans of this quote
"But what is happiness except the simple harmony between a person and life they lead."
Camus, Albert on happiness
16 fans of this quote
"Everyone thinks of changing the world, but no one thinks of changing himself."
Tolstoy, Count Leo on change
26 fans of this quote
"The young do not know enough to be prudent, and therefore they attempt the impossible -- and achieve it, generation after generation."
Buck, Pearl S. on youth
49 fans of this quote
Tara's quote collection
I'm female and made my book on 29th May 2007.
My book as a pdf
My feed
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Talk:Epistemic closure
From RationalWiki
Jump to: navigation, search
Do we have (and should we have) an article about unintended consequences? Totnesmartin (talk) 09:37, 27 April 2010 (UTC)
Dunno. I've added a sentence on the concept, though - David Gerard (talk) 11:07, 27 April 2010 (UTC)
[edit] Rollback
I rolled back ListenerX's edits. Epistemic closure isn't the same as completeness; the former is a property of knowledge, the latter of formal systems. They're not analogous, either; completeness means that all the tautologies in a system are theorems.TallMan (talk) 07:00, 7 November 2012 (UTC)
Ah, I see that now. I made the error of assuming that the illustrative example actually described epistemic closure. ListenerXTalkerX 07:18, 7 November 2012 (UTC)
It did, and I'm not sure why you removed it. Epistemic closure means that knowledge is closed under consequence. As the article says, to say that knowledge is closed under consequence means that if:
1. A knows that p
2. A knows that p entails q
then
3. A knows that q.
If knowledge were closed under consequence, then that would mean the following would be valid:
1. I know the axioms of mathematics.
2. I know that the axioms of mathematics entail all the truths of mathematics.
therefore
3. I know all the truths of mathematics.
Note that this is all about what is known. It's a distinct notion from completeness and from consequence.TallMan (talk) 00:57, 8 November 2012 (UTC)
To quote the example: "If epistemic closure were true in mathematics, then if we knew a set of axioms, we would know all of the theorems which follow from the axioms. In propositional logic, this is true for the set of all propositions."
That makes perfect sense to describe completeness, but not epistemic closure — just knowing a set of axioms in propositional logic does not entail knowledge of all the theorems or tautologies that may be inferred from those axioms, which is why we have automatic provers. ListenerXTalkerX 04:19, 8 November 2012 (UTC)
Completeness has nothing to do with knowledge. Conventional propositional logic is complete. That means that every logical truth in propositional logic is provable in that system. Saying a formal system is complete says something about the relationship between its syntax and its semantics. But the example has to do with what is known and has nothing to do with the formal properties of a system.
The example says what would be true if epistemic closure held. I think your confusion has to do with the fact that epistemic closure doesn't hold, and the mathematical example gives a prima facie case against it. I'm not particularly attached to the example; I suspect I could put together a better one, if I cared enough.TallMan (talk) 13:11, 8 November 2012 (UTC)
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"uncompressed_offset": 253974172,
"url": "wiki.openstreetmap.org/wiki/OpenStreetMap_in_the_media",
"warc_date": "2013-11-22T19:23:59.000Z",
"warc_filename": "<urn:uuid:8faeb66e-e4aa-45a7-b2f3-f603ce928c8d>",
"warc_url": "http://wiki.openstreetmap.org/wiki/OpenStreetMap_in_the_media"
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OpenStreetMap in the media
From OpenStreetMap Wiki
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Press
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OpenStreetMap in the Media: +/-
• 2013 • 2012 • 2011 • 2010 • 2009 • 2008 • 2007 • 2006 • 2005
For scientific papers, see Research.
For books about OSM or mapping, see Books.
For press kit, see Press.
Here we list articles in major or even local medias. To see a trendbar have a look at Google trends. To find a periodical at your local library, refer to WorldCat.
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Help Wikitravel grow by contributing to an article! Learn how.
Szépasszonyvölgy
From Wikitravel
Europe : Central Europe : Hungary : Northern Hungary : Szépasszonyvölgy
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This topic may not meet the Wikitravel criteria for a separate article and should be merged into Eger. If you have an opinion, please discuss on this article's talk page. Please do not add new content to this article, but instead add it to Eger. You can help by copying any relevant information from this page to the new page. Once all content has been copied, this article should be made into a redirect. Please do not remove this merge notice without first gaining consensus for the removal on the article's talk page.
Szepasszonyvolgy, The Valley of the Beautiful Maidens, is in Hungary and is famous for their wine. A great place to get silly with a few friends provided you're not driving. Wines superb value at maybe 100 forints a glass.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
1345.4 - SA Stats, Dec 2009
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 22/12/2009
Page tools: Print Page Print All RSS Search this Product
CONSUMPTION
RETAIL TRADE
In seasonally adjusted terms, retail turnover in South Australia has remained relatively stable over the last two months with a turnover of $1,414.7m recorded in October 2009. Nationally, retail turnover rose slightly (0.3%) to $19,750.7m in October 2009. South Australia's contribution to total retail turnover in Australia was 7.2%.
RETAIL TURNOVER, Seasonally adjusted, South Australia
Comparing October 2009 with October 2008, the industry groups with the largest percentage increases in retail turnover (in seasonally adjusted terms) in South Australia were Clothing, footwear and personal accessory retailing which rose 11.8% to $91.4m; and Other retailing which rose 5.6% to $211.6m.
Over the same period, Food retailing and Household goods retailing were the only industry groups to record a decline in South Australia, falling 0.9% and 0.1%, respectively.
RETAIL TURNOVER, Seasonally adjusted, Change from October 2008 to October 2009, South Australia
NEW MOTOR VEHICLE SALES
In October 2009, 3,200 new passenger vehicles and 5,475 new vehicles in total (in seasonally adjusted terms) were sold in South Australia.
In Australia, 46,892 new passenger vehicles and 81,122 new vehicles in total (in seasonally adjusted terms) were sold in October 2009.
NEW MOTOR VEHICLE SALES, South Australia
Note: Suspension of Trend Estimates
Following the Federal Government Budget in May 2009, the eligibility period for the Small Business and General Business Tax Break was extended to December 2009. The rebate level was also increased for small businesses, allowing eligible businesses to claim an increased tax deduction on the purchase of new motor vehicles.
The trend series attempts to measure the underlying behaviour in new motor vehicle sales. In the short term, this measurement may be significantly affected by unusual influences in the original and seasonally adjusted data, like those observed in May and June 2009. If the trend estimates in the publication were to be calculated without fully accounting for this irregular event, they would be likely to provide a misleading view of the underlying trend in new motor vehicle sales activity.
The new motor vehicle sales trend series has therefore been suspended from May 2009. The trend series will be reintroduced when more certainty emerges in the underlying behaviour of new car sales.
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
6291.0.40.001 - Labour Force, Selected Summary Tables, Australia, Jun 2001
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 19/07/2001
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• About this Release
ABOUT THIS RELEASE
Contains selected final labour force tables -- labour force status for regions; duration of unemployment for Australia, States and Territories (every month); and industry of employment for Australia (in February, May, August and November).
© Commonwealth of Australia 2013
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Global: All Antweb > Formicidae > Amblyoponinae > Adetomyrma > Adetomyrma venatrix
See all Adetomyrma venatrix in Bolton World Catalog
or in
Species: Adetomyrma venatrix
Name Status:
Taxonomic Hierarchy:
Subfamily: Amblyoponinae Genus: Adetomyrma
Taxonomic History (provided by Barry Bolton, 2013)
Adetomyrma venatrix Ward, 1994 PDF: 161, figs. 1-7, 12, 13, 18, 24, 30, 36, 41 (w.) MADAGASCAR. AntCat AntWiki
Taxonomic history
Taxon Page Author History
Taxonomic Treatment (provided by Plazi)
Ward, P. S., 1994:
Holotype worker. MADAGASCAR , Zombitse Forest, along Route Nationale 7. 15 km E Sakaraha , 760 m, 22 ° 54 ' S , 44 ° 41 ' E , 15 February 1993 , P. S. Ward no. 11932 , ex rotten log, tropical dry forest ( MCZC ) .
Paratypes . Series of twenty workers, same data as holotype (to be deposited in ANIC , BMNH , LACM , MCZC , MNHN , PBZT , PSWC , UCDC ) .
Worker measurements (n = 13). HW 0.40 - 0.49, HL 0.48 - 0.56, SL 0.29 - 0.34, PW 0.28 - 0.33, DPW 0.20 - 0.27, LHT 0.32 - 0.37, CI 0.83 - 0.90, SI 0.66 - 0.73.
Description (worker). Small (HW <0.50 mm), pale and blind. Mandibles subfalcate, without distinct basal and masticatory margins (Fig. 12); inner margin with 3 or (more commonly) 4 teeth, equally spaced and lying in the same plane as the front of the head, followed by a gap (0.05 - 0.06 mm) and two longer (subapical and apical) teeth which, as a consequence of the curvature of the mandibles, lie in the dorsoventral plane when the mandibles are closed. Closed mandibles with apices overlapping. Clypeus very short, its principal surface deflected vent rally, anterior margin broadly convex and furnished with a row of about 20 small, specialized, conical setae (Figs 7, 12). Frontal carinae short, low, expanded laterally as small frontal lobes that over no more than about a third of the antennal insertions (dorsal view). Medial portion of the antennal sclerite (torulus) upturned and fusing with the frontal carinae. Scape notably shorter than head length (SL / HL 0.59 - 0.61); first funicular segment c. 2.3 times longer than broad, and approximately equal to the combined length of the next three funicular segments; funicular segments 2 - 8 broader than long, segments 8 - 11 becoming gradually enlarged but not forming a distinct club. Terminal funicular segment c. 2.5 times longer than penultimate segment, and about half the scape length. Head subquadrate (Fig. 6), longer than wide (CI 0.83 - 0.90), widest near the mandibular insertions; sides slightly convex, converging posteriorly and rounding into the concave posterior margin. Mesosoma dorsum somewhat flattened in profile, lateral margins rounded; in dorsal view pronotum longer than broad, with convex sides, mesonotum very short and twice as wide as long (Fig. 4). Basal (= dorsal) face of propodeum narrower than pronotum, about 1.5 times longer than wide, with subparallel sides that converge slightly towards the mesonotum; basal face of propodeum about 2.5 times the length of the declivitous face, and rounding gently into the latter (Figs 1, 24). Metapleuron fully fused with propodeum, the two not distinguishable in lateral view. Metapleural gland bulla conspicuous, manifested as a large circular patch on the lower posterolateral corner of the mesosoma, its dorsoventral height about two-thirds the length of the declivitous face of the propodeum. Inferior propodeal (' metapleural') lobes essentially undeveloped. Abdominal tergum 2 c. 1.4 times broader than long, in dorsal view. Abdominal sternum 2 with a conspicuous subpetiolar process, shaped like an irregular axe blade (Fig. 2). Abdominal sternum 3 with anteroventral surface evenly convex, lacking protuberant ridges near the helcium.
Mandibles smooth with scattered punctures. Most of body smooth and shining; head and mesosoma dorsum with numerous piligerous punctures (c. 0.010 - 0.015 mm diameter) separated by one to several times their diameters, densest on the head (except for a smooth puncture-free median strip). A few scattered punctures on abdominal tergum 2, remainder of metasoma with small, less con- sulcuous punctalae preceded on the exposed portions or the interior margins of each sclerite by fine transverse reticulate-striolate sculpture. Sides of propodeum and metapleuron with weak reticulations. Body with a rather dense cover of pale erect and suberect hairs; more than 30 standing hairs visible in profile on the mesosoma dorsum: anterior margin of clypeus with a row of long (up to 0.12 mm), slender, curved setae (dorsad of the specialized
tooth like setae) that exceed the closed mandibles; erect setae also present on the scapes, funiculi and extension surfaces of the tibiae. Colour: light yellow-brown, with narrow darker bands at the posterior margins of abdominal segments 2 to 4 or 5.
Comments. Features of Adetomyrma venatrix that are likely to be species-specific include the small size, man-dibular dentition, body sculpture, dense standing pilosity, size and density of clypeal setae, and shape of the antero-ventral petiolar tooth.
Larva. A single ant larva, recovered from the vial con-taining the workers, may be that of A. venatrix . It is 2.46 mm long and essentially " leptanilloid " (Wheeler & Wheeler, 1976) in shape, i. e. long, slender, and club-shaped, widest neat the posterior end (at abdominal segments 8 and 9). The thorax is slender and curved ventrally. The body hairs are numerous, short and inconspicuous. No thoracic protuberances or specialized dorsal tubercles were detected.
Biology. The twenty-one workers were collected from the lower surface of a rotten log. at the log / soil interface, in a tract of tropical dry forest in western Madagascar. The workers appeared to be foraging as a group, much in the manner of several small Cerapachys species that are characteristic of the dry forest of western Madagascar, although it is possible that they were recruiting to a prey item (not seen). Unfortunately time did not permit a detailed search for the colony. One of the workers stung my finger and this produced a noticeable stinging sensation (and later a slight swelling that persisted for several days) despite the minute size of the worker. It seems reasonable to surmise thai Adetomyrma venatrix is a specialized
predator or ground-dwelling arthropods. The apparent group foraging behaviour is suggestive of the habits of leptanilline ants (Masuko. 1990) and true army arm (Got-wald. 1982) and leads to the prediction that the queen of Adetomyrma will prove to be a morphologically specialized wingless female.
The collection took place after a period of exceptionally heavy rains on this part of the island that effectively broke a 2 - year drought. It seems likely that this ant is usually subterranean and elusive, and that its discovery was aided by the wet soil conditions. A Winkler litter sample taken at the same site faded to produce additional material of Adetomyrma .
The Zombitse Forest where Adetomyrma was found (see illustration in Tattersall. 1982: 31). although falling within the bounds of what is considered tropical dry forest, is nevertheless more [[ ... ]] than most of the dry forests of western Madagascar. Moreover, the forest is under severe threat from human activities. Large swaths of the forest along Route Nationale 7 east of Sakaraha have been destroyed by slash-and-burn agriculture. After a few cycles of corn and other crops the land becomes a degraded savannah woodland. It seems certain that the collection site for Adetomyrma which is located no more than 100 m from the main road will suffer the same fate unless urgent protective measures are taken.
Relationship to other formicids
Adetomyrma presents something of a puzzle. At first glance it would appear to be unplaceable in any of the existing ant subfamilies since it possesses none of the derived traits that individually characterize them (Baroni Urbani et al.
incompleta .
1992; Bolton, 1994), In Bolton's (1994) subfamily key, for example, it stalks at couplet 11 - a terminal couplet for Apomyrminae and Ponerinae (part) - because it dis-plays a mixture of features from both lugs of the couplet. The lack of tergosternal fusion of abdominal segment 4 would seem to preclude placement of Adetomyrma in the Ponerinae . At the same time Adetomyrma exhibits almost none of the distinctive characteristics of the ' doryline section' of subfamilies (Bolton, 1990 b) such as a horizontal torulus. protruding helcial sternite specialized pygidium. reduction / loss of furcula, metatibial gland, or cuticular flap over the metapleural gland. The exposed spiracle on abdominal segment 5 is reminiscent of the greater exposure that occurs, presumably convergently, in the doryline section. Finally, the unfused condition of abdominal segment 3 in Adetomyrma indicates that it does not even belong to the more inclusive ' poneroid group' (Bolton, 1990 b), i. e. that group of subfamilies, comprising Ponerinae , Leptanillinae , Apomyrminae and the ' doryline section', whose workers show tergosternal fusion of abdominal segment 3 and all castes of which exhibit fusion of the presclerites of the same segment (Bolton, 1990 b; Ward, 1990; Baroni Urbani et al., 1992). Since Adetomyrma has an apparently fused helcium (presclerites 3) this could imply that it is in a basal position, perhaps as a sister of the entire poneroid group.
A survey of additional character systems, beyond those used for subfamily characterization, became necessary for clarifying the phylogenetic affinities of Adetomyrma . Focussing in particular on the morphology of the clypeal setae, metapleural gland, metacoxal cavities and petiolar sclerites, this survey revealed striking similarities (documented below) between Adetomyrma and members of the ponerine tribe Amblyoponini , but not between Adetomyrma and any other ants. The results support placement of Adetomyrma in this tribe, and hence in the subfamily Ponerinae , despite the absence of tergosternal fusion.
Specimen Data Summary
Found most commonly in these habitats: 4 times found in tropical dry forest, 6 times found in spiny deciduous forest, 5 times found in deciduous spiny forest, 1 times found in forest edge, mixed tropical forest, open area, 1 times found in gallery forest, 2 times found in Gallery forest on sandy soil, 1 times found in montane rainforest, 1 times found in rainforest, 1 times found in transition forest
Collected most commonly using these methods or in the following microhabitats: 12 times Malaise trap, 2 times Malaise, 1 times 10 MaxiWinks, mixed samples, 1 times 7 MaxiWinks, mixed samples, 1 times Malaise trap 1
Elevations: collected from 177 - 1300 meters, 776 meters average
8 Specimens Imaged | View All 43 Specimens for this species
CASENT0079480
CASENT0101400
CASENT0151606
CASENT0172771
CASENT0249634
CASENT0260442
CASENT0489808
MCZTYPE34786
Enlarge Map
TOOLS:
View:
- Browse Specimens for this species (43 examples)
- View Adetomyrma venatrix in Google Earth
Comparison Tool:
- Compare images of the Specimens within this species
Catalog:
- See Hymenoptera Name Server
Download:
Specimen Data:
- KML
- Tab-delimited
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Tuesday, August 16, 2005
We're In Business!
$13.00, 5 forms, and one hour later we officially have a business! Wow, it's truly amazing how easy it is to setup a business.
What are we doing? Well, computer programming, of course. Visit: http://i2x.blogspot.com for the whole story.
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< Wait For The Wagon
Hummus Take 2 >
So Rich And Green: Because Beautiful Soup's reception greatly exceeded expectations (I think I tapped a real market need here), I made a cute little web page for it with lots of examples and Tenniel graphics. I finally get to pay tribute to the line from Carroll that made me actually roll around on the floor laughing when I was 9 and my father was reading The Annotated Alice aloud, one chapter a week, complete with all the incomprehensible-to-children annotations.
Filed under: ,
[Main] [Edit]
Unless otherwise noted, all content licensed by Leonard Richardson
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About this Journal Submit a Manuscript Table of Contents
ISRN Gastroenterology
Volume 2012 (2012), Article ID 628317, 9 pages
doi:10.5402/2012/628317
Review Article
What Really Causes Necrotising Enterocolitis?
General Medicine, King’s College Hospital, London SE5 9RS, UK
Received 11 October 2012; Accepted 19 November 2012
Academic Editors: A. Nakajima and W. Vogel
Copyright © 2012 Thomas Peter Fox and Charles Godavitarne. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background. One of the most serious gastrointestinal disorders occurring in neonates is necrotising enterocolitis (NEC). It is recognised as the most common intra-abdominal emergency and is the leading cause of short bowel syndrome. With extremely high mortality and morbidity, this enigmatic disease remains a challenge for neonatologists around the world as its definite aetiology has yet to be determined. As current medical knowledge stands, there is no single well-defined cause of NEC. Instead, there are nearly 20 risk factors that are proposed to increase the likelihood of developing NEC. Aims and Objectives. The aim of this project was to conduct a comprehensive literature review around the 20 or so well-documented and less well-documented risk factors for necrotising enterocolitis. Materials and Methods. Searches of the Medline, Embase, and Science direct databases were conducted using the words “necrotising enterocolitis + the risk factor in question” for example, “necrotising enterocolitis + dehydration.” Search results were ordered by relevance with bias given to more recent publications. Conclusion. This literature review has demonstrated the complexity of necrotising enterocolitis and emphasised the likely multifactorial aetiology. Further research is needed to investigate the extent to which each risk factor is implicated in necrotising enterocolitis.
1. Background
One of the most serious disorders and the single most serious gastrointestinal disorder occurring in neonates is necrotising enterocolitis [13]. This enigmatic disease remains a challenge for neonatologists around the world as its definite aetiology has yet to be determined. It is recognised as the most common intra-abdominal emergency effecting neonates and it is the leading cause of short bowel syndrome [4, 5]. Necrotising enterocolitis is characterised by the bowel wall necrosis of variable thickness, which leads to perforation in up to one-third of cases [6].
The condition was first described by Paltauf in 1888 but the term “necrotising enterocolitis” was used for the first time by Schmid and Quaiser in 1953 [7, 8]. Since then, there has been a tremendous increase in the incidence of NEC. This has been attributed largely to two factors. The first is the increase in the number of premature births by Caesarean section for therapeutic reasons resulting in the delivery of premature babies. The second reason is due to the advancement in technology of neonatal care, for example, intensive care units and surfactant therapy have enabled most premature babies to overcome a number of previously fatal conditions and survive, making them highly susceptible to developing NEC [9, 10].
2. Epidemiology
The incidence of NEC varies not only from country to country but also among different NICUs in the same country. Research by the National Institute of Child Health and Human Development observed variations from 4 to 20% in the prevalence of NEC at centres across northern America, suggesting that iatrogenic factors may play a large role. These have yet to be identified [11, 12]. The incidence in the population as a whole is estimated to be between one to three cases per 1000 live births. However, NEC occurs in 2–5% of very low birth weight infants (VLBW) and in 1–8% of neonatal intensive care unit admissions (NICU) [13]. A survey carried out in 1994 by the British Paediatric Surveillance Unit reported 300 new cases of NEC in the UK in one year with an overall death rate of 22% [14]. Median gestation was 29 weeks and 65% of babies weighed under 1500 g. However, 12% of babies that developed NEC were born at term [1517].
3. Pathology
NEC can arise in any area of the GI tract; however, the most common sites are the terminal ileum, caecum, and ascending colon [18]. Pneumatosis intestinalis (the presence of submucosal and subserosal gas within the bowel wall) is the most characteristic appearance of the gut radiologically and on laparotomy. The gas is mainly nitrogen and hydrogen formed by gas producing bacteria in the GI tract [19]. Histologically, the earliest signs of NEC are necrosis of the mucosa with microthrombus formation, leading to oedema, patchy ulceration and haemorrhage [20].
Important elements in modulating the damage that results from NEC are the inflammatory cytokines interleukin 1, 3, 6, tumour necrosis factor (TNF), and platelet activating factor (PAF). Indeed, these markers can be used to predict the severity of the disease [21]. PAF is a proinflammatory cytokine and has been shown to be of a particular importance [22]. Stool levels of PAF rise sharply with the onset of NEC and the administration of PAF to rats in a hypoxic atmosphere has shown to induce NEC [23]. Furthermore, PAF antagonists reduce the incidence and severity of NEC in rats [24]. This may also explain why enteral feeding is a risk factor for NEC; as stool concentrations of PAF increase, enteral feeding is commenced [25].
4. Aetiology
Many potential risk factors have been explored in relation to the aetiology of NEC; however, the definite aetiology still eludes modern medical research. It is possible that no individual factor is sufficient to precipitate NEC. Risk factors identified so far are shown in Table 1, [26].
Table 1: From Roberton’s Textbook of Neonatology. Risk factors for necrotising enterocolitis.
5. Literature Review
At present there is no single, well-defined cause of necrotising enterocolitis. Instead, we have nearly 20 risk factors that are proposed to increase the likelihood of developing NEC [26]. In this literature review, the various risk factors that are thought to be most significant will be discussed as well as certain parameters that may change with the onset of NEC.
6. Birth Weight and Prematurity
Low birth weight and prematurity have been identified as among the most important risk factors for NEC [2730]. NEC occurs in up to 5% of VLBW infants and the median gestation is around 29 weeks [31]. 65% of cases had a birth weight under 1500 g and only 12% of cases are born at term. Indeed, preterm infants born under 30 weeks who develop NEC usually have no other risk factors [32].
7. Gender
Carter and Holditch-Davis published a study in 2008 involving 134 preterm infants which concluded that there was no relationship between gender and NEC [33]. Ballot et al. conducted a study of 474 preterm infants in Johannesburg and were able to determine minor discrepancies between gender incidence of NEC (OR 3.21; 95% CI 1.6–6.3) [34]. However, most research has concluded that no differences are noted in the incidence of NEC according to gender [35]. Therefore gender is not thought to be a risk factor for NEC.
8. Neonatal Hypoxia
Recurrent apnoea, respiratory distress, assisted ventilation, and umbilical artery catheterisation are all known to contribute to hypoxic events in the first few weeks of life [26]. Palmer and Thomas conducted a study in 1987 which identified all of the above as risk factors for VLBW infants [36]. An adverse intrauterine environment can lead to chronic foetal hypoxia and IUGR. This can result in a diversion of cardiac output away from the gut which could precipitate necrotising enterocolitis [37].
In the term infant with NEC, risk factors for gut hypoxia are invariably present. NEC may follow severe generalised hypoxia, maternal cocaine use, or exchange transfusion [38]. An early study by Goldberg and Thomas into 5 infants born at term who developed NEC in 5–7 days found that they had all suffered from severe hypoxia during birth [39].
The use of hyperbaric oxygen therapy trialled in rat models has been shown to significantly reduce the severity of NEC [40]. However, further research is required before this can progress to human trials.
9. Maternal Milk versus Formula Milk
Breast milk protects against NEC [41]. In a study by Lucas and Cole involving 926 preterm infants, the exclusively formula fed group had a 6–10-fold increase in the rates of NEC than those fed with breast milk alone and 3 times the rates of those fed on a mixture of breast milk and formula. In the same study, delayed enteral feeding was also associated with a decreased incidence of NEC [42]. A systematic review conducted in 2003 also found a 3-fold increase in the likelihood of developing NEC if the infant is solely fed on formula [43]. When the general health of the infant is considered, breast milk also appears to be far superior [26]. There are significant benefits to infant host defence; sensory-neural development, gastrointestinal maturation, and some aspects of nutritional status are observed when premature infants are fed with their mothers’ own milk. A reduction in infection-related morbidity in human milk-fed premature infants has been reported in nearly a dozen descriptive, as well as some RCTs in the past 25 years [44].
Trophic feeding is defined as the use of minimal enteral feeds (continuous drip of less than 1 mL/hour) with parenteral nutrition. This has been shown to lower the incidence of feeding intolerance, shorten the duration of time to regain birth weight, and decrease the incidence of NEC [45, 46]. Little is gained nutritionally from trophic feeding; however, some degree of nutrient exposure is essential even to the immature gut to prevent intestinal mucosal atrophy [47]. A recent trial by Berseth and Bisquera investigating the benefits of trophic feeding over standard milk advancement had to be stopped because babies receiving the standard regimen had a higher rate of NEC (10% versus 1.4%) [48]. Henderson et al. suggested that the duration of trophic feeding and the rate of the advancement of feed volumes are key modifiable risk factors for NEC in preterm infants [49].
Manipulating the chemical composition of formula milk, by reducing protein content, adding prebiotics, growth factors, or secretory IgA, can modulate an intestinal development. This has been suggested to reduce the differential responses between breast-fed and formula-fed neonates [50].
Mothers of preterm infants produce milk that has a higher protein content, higher caloric density, and higher calcium and sodium content than milk from mothers who deliver at term [51]. This matches (to a certain extent) the increased needs of the premature infant. This has led to the development of specialised preterm infant formulae.
When infants on the NICU do not show adequate growth and weight gain there are a number of things that can be considered: firstly, increasing the volume of feeds. When the volume cannot be advanced any further there are two options: use donor hind milk or add commercial fortifiers. There have been a number of reports of infants developing NEC following the addition of commercial fortifiers [52, 53].
A key component of feeds that may be a modifiable risk factor for NEC is osmolarity [54]. There is a concern that additives to maternal milk may alter the osmolarity and hence remove the protective effect against NEC [55]. A number of studies have found that human milk and formula milk interact to induce a rapid increase in osmolarity higher than that which would be expected from composition alone. This rise could be explained by the amylase activity of human milk, inducing the hydrolysis of the dextrin content of formula milk, leading to small osmotically active molecules of oligosaccharides. Routine additives can significantly increase the osmolarity of EBM to levels that exceed current guidelines for premature infant feeding. The high osmolarity of fortified human milk should therefore be considered in the nutritional management of preterm infants [56, 57].
10. Blood Results
Anaemia is associated with an increased risk of developing NEC [26]. Blau et al. also found that neonatal transfusion of packed red blood cells could be a trigger for NEC [58]. A further study in December 2010 by Josephson et al. concluded that PRBC transfusions were merely a marker of disease severity and that there was no correlation with NEC [59]. Such conflicting views, published within weeks, of each other highlight the need for a further research in this area.
Polycythaemia was first suggested as a risk factor for NEC in 1975 [60] although initial studies failed to confirm this suggestion [61]. A review of 36 premature infants born over a period of 5 years dismissed polycythaemia as a risk factor in the development of NEC [62]. However more recently, many studies have identified increased incidences of polycythaemia in groups of infants that develop NEC compared to a control group [6366]. The aetiology of neonatal polycythaemia is related either to intrauterine hypoxia, or secondary to fetal transfusion. There is a linear relationship between hematocrit and viscosity until 65% after which it is exponential. It is the increased viscosity of blood that is responsible for reduced mesenteric perfusion [67, 68]. As viscosity increases so does the tendency to form microthrombi which can further impede mesenteric perfusion. At present, polycythaemia is widely regarded as a significant risk factor and current guidelines recommend the prompt diagnosis and management to avoid adverse outcomes [69].
Platelets are an acute phase reactant, and thrombocytosis can represent physiologic stress to an infant. However, acute NEC is more commonly associated with thrombocytopenia (<100,000/μL) [70]. The evidence behind thrombocytosis directly causing NEC is scanty; however, it stands to reason that a thrombogenic state could reduce mesenteric blood flow [71].
80–90% of cases of NEC are associated with thrombocytopenia to some degree [72]. Kenton et al. conducted a study on 91 infants and found that severe thrombocytopenia is a valuable prognostic indicator of mortality associated with NEC and may influence management options. Thrombocytopenia may become more profound in severe cases that become complicated with consumption coagulopathy [73]. This report suggested that prospective studies of infants with early and severe thrombocytopenia may help determine the optimal timing of laparotomy in infants with NEC. Ververidis et al. concluded that a platelet count of less than or a sudden fall in platelets was a poor prognostic indicator [74]. It therefore seems that while thrombocytosis is a risk factor because it induces a thrombogenic state that may impede mesenteric blood flow, thrombocytopenia is perhaps more useful as a prognostic indicator.
11. Dehydration/Electrolyte Disturbances
Dehydration is a risk factor for NEC [75]. When severe, it increases the viscosity of blood. Increased viscosity has been shown to decrease mesenteric perfusion and hence may precipitate NEC. There are numerous case studies demonstrating this phenomenon [76, 77]. Interestingly, hyperhydration has also been shown to increase the risk of NEC in a Cochrane review [78]. The conclusions to this review were that the careful restriction of water intake is required so that physiological needs are met without allowing significant dehydration.
12. Acute Phase Proteins
C-Reactive Protein (CRP) is one of the acute phase reactants which has been proven to be a useful marker of inflammation, not only in the gastrointestinal system but also systemically [79]. CRP is usually elevated in NEC [26]. It has not been found useful in predicting the onset of NEC as the rise in CRP appears to lag behind the clinical onset [80]. This study showed that CRP has increasing sensitivity but remains a nonspecific marker of NEC [81]. Many studies have analysed the serial changes in CRP before and after the diagnosis of NEC and it is thought that it may be more useful in predicting outcome and determining severity [82]. A retrospective analysis of data ranging from January 2001 to July 2006 on preterm (gestation < 32 weeks) neonates with definite NEC found that serial changes in CRP may predict the progression to surgery as well as death [83].
There are many other neonatal conditions which are associated with an elevated CRP: septicaemia, meningitis, urinary tract infection, pneumonia, meconium aspiration syndrome, or presumptive infection [84, 85].
The usefulness of CRP in diagnosing NEC seems to be in conjunction with radiographic changes, classically pneumatosis intestinalis. CRP is also useful in discriminating BeII’s stage II NEC from the benign form of pneumatosis intestinalis, NEC suspect, or spuriously suggestive GI conditions [86].
13. Liver Function Tests
Liver function tests (LFTs) incorporate albumin, alanine transaminase, aspartate transaminase, alkaline phosphatise, and total bilirubin. They allow physicians to gain information about the functional state of a patient’s liver. Unsurprisingly, they often become deranged following the onset of NEC, but there is little evidence regarding their value in contributing to a diagnosis [87]. Unfortunately, many premature infants may already have abnormal LFTs because of parenteral feeding regimens; the link between PN and deranged liver enzymes is well established [8891]. This could limit their usefulness in the diagnosis and monitoring of NEC.
14. The Use of Stool Inflammatory Markers inDiagnosing Necrotising Enterocolitis
Faecal calprotectin (FC) is a cytosolic component of neutrophils and is a useful marker for the exacerbation of inflammatory bowel disease. It is measured by a noninvasive biochemical test and is widely used to differentiate between functional bowel problems and inflammatory bowel disease. Thuijls et al. conducted a study in 2010 of 14 confirmed cases of NEC and concluded that faecal calprotectin is a potential diagnostic marker for NEC in neonates [92]. Its value in allowing early diagnosis of NEC has been alluded to by further trials [93, 94]. FC has been shown to be elevated in neonates with NEC but what remains unknown is its value in predicting the onset of NEC. Does the rise in FC precede clinical symptoms and other biochemical tests? Research involving larger cohorts is necessary to certify its true value and is an area of further interest to the author.
15. Umbilical Catheterisation
There are conflicting reports of the extent to which umbilical catheterisation is potentially a risk factor for developing necrotising enterocolitis. Inherently it is extremely difficult to assess because of the challenges of isolating it as a variable. Early research showed an impairment in mesenteric blood flow was, associated with an umbilical catheter insertion [95]. Roberton’s Textbook of Neonatology clearly states that it is a risk factor as do other sources [96]. However, other studies have shown the opposite to be true. Guthrie et al. studied 15072 neonates and found lower rates of NEC in those who had received an UAC at birth [97]. This conveys a potential protective effect of the catheters. However, a Cochrane review found that UAC was not a contributing factor in the aetiology of NEC [98]. With such conflicting research, the jury is clearly still “out” on the true risks of an umbilical catheterisation.
16. Clinical Risk Indicator in Babies
The Clinical Risk Index for Babies (CRIBs) score is a well-validated risk-adjustment instrument widely used in neonatal intensive care. Its appropriateness with contemporary data has been questioned so in 2003, a revised CRIB II score was developed [99]. This new scoring system was found to be a good predictive instrument for mortality in preterm infants by a large validation study in 2010 [100].
17. Congenital Disease (PDA)
The evidence behind a congenital persistent patent ductus arteriosis (PDA) as a cause for NEC is well established and has been confirmed by several prospective studies [101103]. The left-to-right shunt that occurs in PDA results in the decreased velocity of mesenteric blood flow [104]. The intestinal mucosa has high metabolic activity and requires about 80% of total intestinal blood flow. When this is decreased, it becomes more susceptible to the disruption of its immune barrier functions [105].
18. Antibiotics
The immature immune system of preterm neonates puts them at the higher risk of neonatal sepsis. Benzylpenicillin and Gentamicin are given to most preterm babies because of the increased risk of sepsis. A recent retrospective cohort study involving 5693 premature babies found that the prolonged use (greater than 5 days) of antibiotic therapy was associated with and increased the risk of NEC [106]. The use of antibiotics for 5 days or less in premature infants was thoroughly assessed in a large RCT and no increase in the incidence of NEC was found between the control group and the study group [107].
19. Indomethacin
Exposure to indomethacin can occur prenatally as a tocolytic agent or postnatally to affect the closure of a PDA [108, 109]. The efficacy of this treatment has been demonstrated in several prospective trials [110, 111]. Perinatal exposure has been documented as a risk factor for intestinal injury in VLBW infants [112114]. However, other studies have not been able to support these claims [115, 116]. With increasing usage, reports emerged the linking indomethacin use to isolated intestinal perforation (IIP) and necrotising enterocolitis [117119]. However, most of these were retrospective studies and did not carefully differentiate between IIP and NEC. Furthermore, one of these studies failed to eliminate PDA as a confounding variable, a well-documented risk factor for NEC [120]. In contrast, a thorough prospective analysis over 12 years into the exact effect of perinatal indomethacin use found a positive association with IIP but a negative association with NEC using multivariate logistic regression analysis (exposed: 14.6% unexposed: 9.9%) [121]. These findings were independent of maternal milk feeding and have been supported by subsequent research [122]. It appears therefore that the protective benefits of indomethacin for NEC have potentially been masked by confounders such as IIP and PDA.
20. Dexamethasone
Chronic lung disease (CLD) remains a major problem in neonatal intensive care units. The most likely underlying pathogenesis involves persistent inflammation in the lungs. Corticosteroids have been used to either prevent or treat CLD because of their potent anti-inflammatory effects [123]. Early studies appeared to show a link between dexamethasone use and NEC, one reporting a 7.4% increase in the group exposed to steroids [124]. Increased frequency of sepsis and neonatal infections was also seen in this group. Despite this finding, many other studies have reported an overall decrease in perinatal mortality in the group treated with steroids [125]. More recently, the topic of steroid use perinatally has been the focus of an extensive Cochrane review. It demonstrated that steroids are effective both prenatally and/or postnatally in promoting lung maturation, and that they were not found to be associated with increased incidence of NEC [126, 127].
Other identified risk factors that are not possible to discuss within the confines of this report include maternal cocaine use, variations in blood glucose levels, sepsis, IgA supplementation, and the stool cultures of pathogenic micro-organisms [128, 129].
21. Conclusions
This paper highlights just one of the many challenges involved in neonatal intensive care. Necrotising enterocolitis has proven itself as an immensely enigmatic and morbid disease, the aetiology of which is tied up in a minefield of medical literature, much of it conflicting in its findings. This paper has demonstrated the paramount importance nutrition in the first few weeks of life and what a fine balance needs to be struck between malnourishment and high risk aggressive feeding.
There still remain many potential risk factors for NEC; however, the extent to which these risk factors are important in the aetiology of NEC continues to elude medical research. It seems that no individual factor alone is sufficient to precipitate NEC pointing to a multifactorial aetiology. However, with the management of premature neonates being aggressively monitored and standardised, possibilities or a more intrinsic nutrient-gene interaction arises, which we have yet to understand. By understanding this in the future, we might be able to develop targeted therapies for individuals who are most susceptible to NEC.
Abbreviations
NEC:Necrotising enterocolitis
EBM: Expressed breast milk
DEBM: Donor expressed breast milk
RACH: Royal Alexandra children’s hospital
RSCH: Royal Sussex County hospital
TPN: Total parenteral nutrition
EN: Enteral nutrition
RDS: Respiratory distress syndrome
CLD: Chronic lung disease
PDA: Patent ductus arteriosus
IVH: Intraventricular haemorrhage
BPD: Bronchopulmonary dysplasia
GOR: Gastro-oesophageal reflux
PTX: Pneumothorax
FC: Faecal calprotectin
IIP:Isolated intestinal perforation.
Disclosure
The authors confirm that the submitted work is all their own work and is in their own words. They confirm that the sources (books, journals, websites, etc.) they have referred to and from which they have quoted are listed in the citations submitted with this piece of work.
References
1. J. L. Grosfeld, “Jejumoilial atresia and stenosis,” in Paediatric Surgery, p. 838, Chicago, Ill, USA, 4th edition, 1986.
2. L. W. Martin and J. T. Zerella, “Jejunoilial atresia: a proposed classification,” Journal of Pediatric Surgery, vol. 11, p. 1149, 1967.
3. N. McIntosh, P. Helms, S. Rosalind, and S. Logan, Textbook of Paediatrics, Churchill Livingston, London, UK, 7th edition, 2008.
4. P. W. Wales and E. R. Christison-Lagay, “Short bowel syndrome: epidemiology and etiology,” Seminars in Pediatric Surgery, vol. 19, no. 1, pp. 3–9, 2010. View at Publisher · View at Google Scholar · View at Scopus
5. B. P. Modi, M. Langer, Y. A. Ching et al., “Improved survival in a multidisciplinary short bowel syndrome program,” Journal of Pediatric Surgery, vol. 43, no. 1, pp. 20–24, 2008. View at Publisher · View at Google Scholar · View at Scopus
6. D. A. Kafetzis, C. Skevaki, and C. Costalos, “Neonatal necrotizing enterocolitis: an overview,” Current Opinion in Infectious Diseases, vol. 16, no. 4, pp. 349–355, 2003. View at Scopus
7. A. Paltauf, “Die spontane dickdarmruptur der neugebornen,” Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin, vol. 111, no. 3, pp. 461–474, 1888. View at Publisher · View at Google Scholar · View at Scopus
8. O. Schmid and K. Quaiser, “Uer eine besondere schwere verlaufende Form von Enteritis beim saugling,” Oesterr Z Kinderh, vol. 8, p. 114, 1953.
9. A. M. Kosloske, “Epidemiology of necrotizing enterocolitis,” Acta Paediatrica, Supplement, vol. 83, no. 396, pp. 2–7, 1994. View at Scopus
10. R. C. Holman, B. J. Stoll, M. J. Clarke, and R. I. Glass, “The epidemiology of necrotizing enterocolitis infant mortality in the United States,” American Journal of Public Health, vol. 87, no. 12, pp. 2026–2031, 1997. View at Scopus
11. R. D. Uauy, A. A. Fanaroff, S. B. Korones, E. A. Phillips, J. B. Philips, and L. L. Wright, “Necrotizing entercolitis in very low birth weight infants: biodemographic and clinical correlates,” Journal of Pediatrics, vol. 119, no. 4, pp. 630–638, 1991. View at Publisher · View at Google Scholar · View at Scopus
12. J. Rennie, Roberton’s Textbook of Neonatology, Elsevier, Beijing, China, 4th edition, 2005.
13. A. M. Kosloske, “Epidemiology of necrotising enterocolitis,” Acta Paediatrica, vol. 83, no. s396, pp. 2–7, 1994. View at Publisher · View at Google Scholar
14. A. Lucas and R. Abbott, “British paediatric surveillance unit,” Annual Report, Royal College of Paediatrics and Child Health, 1997, http://bpsu.inopsu.com/publications/reports/nnec.html.
15. P. J. Beeby and H. Jeffery, “Risk factors for necrotising enterocolitis: the influence of gestational age,” Archives of Disease in Childhood, vol. 67, no. 4, pp. 432–435, 1992. View at Scopus
16. D. A. Clark and M. Miller, “What causes NEC and how can it be prevented? Current topics,” in Neonatology 1, pp. 160–176, Saunders, London, UK, 1996.
17. R. M. Kliegman, W. A. Walker, and R. H. Yolken, “Necrotizing enterocolitis: research agenda for a disease of unknown etiology and pathogenesis,” Pediatric Research, vol. 34, no. 6, pp. 701–708, 1993. View at Scopus
18. T. V. Santulli, J. N. Schullinger, and W. C. Heird, “Acute necrotizing enterocolitis in infancy: a review of 64 cases,” Pediatrics, vol. 55, no. 3, pp. 376–387, 1975. View at Scopus
19. R. Engel, N. Virnig, C. Hunt, and M. Levitt, “Origin of mural gas in NEC,” Paediatric Research, vol. 7, p. 292, 1975.
20. G. B. Hopkins, V. E. Gould, J. K. Stevenson, and T. K. Oliver Jr., “Necrotizing enterocolitis in premature infants. A clinical and pathologic evaluation of autopsy material,” American Journal of Diseases of Children, vol. 120, no. 3, pp. 229–232, 1970.
21. J. A. Morecroft, L. Spitz, P. A. Hamilton, and S. J. K. Holmes, “Plasma interleukin-6 and tumour necrosis factor levels as predictors of disease severity and outcome in necrotizing enterocolitis,” Journal of Pediatric Surgery, vol. 29, no. 6, pp. 798–800, 1994. View at Publisher · View at Google Scholar · View at Scopus
22. A. K. Ewer, “Role of platelet-activating factor in the pathophysiology of necrotizing enterocolitis,” Acta Paediatrica. Supplement, vol. 91, no. 437, pp. 2–5, 2002.
23. W. MacKendrick, N. Hill, W. Hsueh, and M. Caplan, “Increase in plasma platelet-activating factor levels in enterally fed preterm infants,” Biology of the Neonate, vol. 64, no. 2-3, pp. 89–95, 1993. View at Scopus
24. M. S. Caplan, E. Hedlund, L. Adler, M. Lickerman, and W. Hsueh, “The platelet-activating factor receptor antogonist WEB 2170 prevents neonatal necrotizing enterocolitis in rats,” Journal of Pediatric Gastroenterology and Nutrition, vol. 24, no. 3, pp. 296–301, 1997. View at Publisher · View at Google Scholar · View at Scopus
25. M. D. Amer, E. Hedlund, J. Rochester, and M. S. Caplan, “Platelet-activating factor concentration in the stool of human newborns: effects of enteral feeding and neonatal necrotizing enterocolitis,” Biology of the Neonate, vol. 85, no. 3, pp. 159–166, 2004. View at Publisher · View at Google Scholar · View at Scopus
26. J. Rennie, Roberton’s Textbook of Neonatology, Elsevier, Beijing, China, 4th edition, 2005.
27. I. R. Holzman and D. R. Brown, “Necrotizing enterocolitis: a complication of prematurity,” Seminars in Perinatology, vol. 10, no. 3, pp. 208–216, 1986. View at Scopus
28. D. A. Clark and M. J. S. Miller, “What causes neonatal necrotising enterocolitis and how can it be prevented? Current topics,” in Neonatology 1, pp. 160–176, WB Saunders, London, UK, 1996.
29. V. Y. H. Yu, R. Joseph, and B. Bajuk, “Perinatal risk factors for necrotizing enterocolitis,” Archives of Disease in Childhood, vol. 59, no. 5, pp. 430–434, 1984. View at Scopus
30. A. Bajraktarevic, A. D. Djulepa, H. Boloban et al., “Low birth weight is the most important risk factor for developing necrotizing enterocolitis in Bosnia,” Early Human Development, vol. 86, p. S71, 2010.
31. P. J. Beeby and H. Jeffery, “Risk factors for necrotising enterocolitis: the influence of gestational age,” Archives of Disease in Childhood, vol. 67, no. 4, pp. 432–435, 1992. View at Scopus
32. J. Rennie, Roberton’s Textbook of Neonatology, Elsevier, Beijing, China, 4th edition, 2005.
33. B. M. Carter and D. Holditch-Davis, “Risk factors for necrotizing enterocolitis in preterm infants: how race, gender, and health status contribute,” Advances in Neonatal Care, vol. 8, no. 5, pp. 285–290, 2008. View at Publisher · View at Google Scholar · View at Scopus
34. D. E. Ballot, T. F. Chirwa, and P. A. Cooper, “Determinants of survival in very low birth weight neonates in a public sector hospital in Johannesburg,” BMC Pediatrics, vol. 10, article no. 30, 2010. View at Publisher · View at Google Scholar · View at Scopus
35. A. R. Llanos, M. E. Moss, M. C. Pinzòn, T. Dye, R. A. Sinkin, and J. W. Kendig, “Epidemiology of neonatal necrotising enterocolitis: a population-based study,” Paediatric and Perinatal Epidemiology, vol. 16, no. 4, pp. 342–349, 2002. View at Publisher · View at Google Scholar · View at Scopus
36. S. R. Palmer, S. J. Thomas, R. W. I. Cooke, et al., “Birthweight-specific risk factors for necrotising enterocolitis,” Journal of Epidemiology and Community Health, vol. 41, no. 3, pp. 210–214, 1987. View at Scopus
37. G. A. Hackett, S. Campbell, H. Gamsu, T. Cohen-Overbeek, and J. M. Pearce, “Doppler studies in the growth retarded fetus and prediction of neonatal necrotising enterocolitis, haemorrhage, and neonatal morbidity,” British Medical Journal, vol. 294, no. 6563, pp. 13–16, 1987. View at Scopus
38. P. J. Beeby and H. Jeffery, “Risk factors for necrotising enterocolitis: the influence of gestational age,” Archives of Disease in Childhood, vol. 67, no. 4, pp. 432–435, 1992. View at Scopus
39. R. N. Goldberg, D. W. Thomas, and F. R. Sinatra, “Necrotizing enterocolitis in the asphyxiated full-term infant,” American Journal of Perinatology, vol. 1, no. 1, pp. 40–42, 1983. View at Scopus
40. A. Guven, G. Gundogdu, B. Uysal et al., “Hyperbaric oxygen therapy reduces the severity of necrotizing enterocolitis in a neonatal rat model,” Journal of Pediatric Surgery, vol. 44, no. 3, pp. 534–540, 2009. View at Publisher · View at Google Scholar · View at Scopus
41. S. Sullivan, R. J. Schanler, J. H. Kim et al., “An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products,” Journal of Pediatrics, vol. 156, no. 4, pp. 562.e1–567.e1, 2010. View at Publisher · View at Google Scholar · View at Scopus
42. A. Lucas and T. J. Cole, “Breast milk and neonatal necrotising enterocolitis,” The Lancet, vol. 336, no. 8730-8731, pp. 1519–1523, 1990. View at Scopus
43. W. McGuire and M. Y. Anthony, “Donor human milk versus formula for preventing necrotising enterocolitis in preterm infants: systematic review,” Archives of Disease in Childhood: Fetal and Neonatal Edition, vol. 88, no. 1, pp. F11–F14, 2003. View at Scopus
44. R. J. Schanler, “Outcomes of human milk-fed premature infants,” Seminars in Perinatology, vol. 35, no. 1, pp. 29–33, 2011. View at Publisher · View at Google Scholar · View at Scopus
45. R. J. McClure, “Trophic feeding of the preterm infant,” Acta Paediatrica. Supplement, vol. 90, no. 436, pp. 19–21, 2001. View at Scopus
46. R. J. McClure and S. J. Newell, “Randomised controlled study of clinical outcome following trophic feeding,” Archives of Disease in Childhood: Fetal and Neonatal Edition, vol. 82, no. 1, pp. F29–F33, 2000. View at Scopus
47. M. G. MacDonald, M. D. Kullet, and M. M. Seshia, Avery’s Neonatology. Pathophysiology and Management of the Newborn, Williams and Wilkins, Philadelphia, Pa, USA, 6th edition, 2005.
48. C. L. Berseth, J. A. Bisquera, and V. U. Paje, “Prolonging small feeding volumes early in life decreases the incidence of necrotizing enterocolitis in very low birth weight infants,” Pediatrics, vol. 111, no. 3, pp. 529–534, 2003. View at Publisher · View at Google Scholar · View at Scopus
49. G. Henderson, S. Craig, P. Brocklehurst, and W. McGuire, “Enteral feeding regimens and necrotising enterocolitis in preterm infants: a multicentre case-control study,” Archives of Disease in Childhood: Fetal and Neonatal Edition, vol. 94, no. 2, pp. F120–F123, 2009. View at Publisher · View at Google Scholar · View at Scopus
50. I. Le Hurou-Luron, S. Blat, and G. Boudry, “Breast- v. formula-feeding: impacts on the digestive tract and immediate and long-term health effects,” Nutrition Research Reviews, vol. 23, no. 1, pp. 23–36, 2010. View at Publisher · View at Google Scholar · View at Scopus
51. S. J. Gross, R. J. David, L. Bauman, and R. M. Tomarelli, “Nutritional composition of milk produced by mothers delivering preterm,” Journal of Pediatrics, vol. 96, no. 4, pp. 641–644, 1980. View at Scopus
52. J. van Acker, F. de Smet, G. Muyldermans, A. Bougatef, A. Naessens, and S. Lauwers, “Outbreak of necrotizing enterocolitis associated with Enterobacter sakazakii in powdered milk formula,” Journal of Clinical Microbiology, vol. 39, no. 1, pp. 293–297, 2001. View at Publisher · View at Google Scholar · View at Scopus
53. E. Weir, “Powdered infant formula and fatal infection with Enterobacter sakazakii,” Canadian Medical Association Journal, vol. 166, no. 12, p. 1570, 2002. View at Scopus
54. A. Fernández Polo, M. J. Cabañas Poy, S. Clemente Bautista, M. Oliveras Arenas, F. Castillo Salinas, and E. Hidalgo Albert, “Osmolality of oral liquid dosage forms to be administered to newborns in a hospital,” Farmacia Hospitalaria, vol. 31, no. 5, pp. 311–314, 2007. View at Publisher · View at Google Scholar · View at Scopus
55. C. Bruns, “Hyperosmolarity—a cause of necrotising enterocolitis? Osmolarity of therapeutic additives in premature infant feeding,” Krankenhauspharmazie, vol. 27, no. 2, pp. 63–69, 2006. View at Scopus
56. M. de Curtis, M. Candusso, C. Pieltain, and J. Rigo, “Effect of fortification on the osmolality of human milk,” Archives of Disease in Childhood: Fetal and Neonatal Edition, vol. 81, no. 2, pp. F141–F143, 1999. View at Scopus
57. L. Srinivasan, R. Bokiniec, C. King, G. Weaver, and A. D. Edwards, “Increased osmolality of breast milk with therapeutic additives,” Archives of Disease in Childhood: Fetal and Neonatal Edition, p. 89, 2004.
58. J. Blau, J. M. Calo, D. Dozor, M. Sutton, G. Alpan, and E. F. La Gamma, “Transfusion-related acute gut injury: necrotizing enterocolitis in very low birth weight neonates after packed red blood cell transfusion,” Journal of Pediatrics, vol. 158, no. 3, pp. 403–409, 2011. View at Publisher · View at Google Scholar · View at Scopus
59. C. D. Josephson, A. Wesolowski, G. Bao et al., “Do red cell transfusions increase the risk of necrotizing enterocolitis in premature infants?” Journal of Pediatrics, vol. 157, no. 6, pp. 972.e3–978.e3, 2010. View at Publisher · View at Google Scholar · View at Scopus
60. R. D. Leake, B. Thanopoulos, and R. Nieberg, “Hyperviscosity syndrome associated with necrotizing enterocolitis,” American Journal of Diseases of Children, vol. 129, no. 10, pp. 1192–1194, 1975. View at Scopus
61. T. Gunn and E. Outerbridge, “Polycythemia as a cause of necrotizing enterocolitis,” Canadian Medical Association Journal, vol. 117, no. 5, p. 438, 1977. View at Scopus
62. Z. Ali, “A review of 36 babies with necrotizing enterocolitis,” Journal of Tropical Pediatrics, vol. 35, no. 6, pp. 274–276, 1989. View at Scopus
63. D. K. Lambert, R. D. Christensen, E. Henry et al., “Necrotizing enterocolitis in term neonates: data from a multihospital health-care system,” Journal of Perinatology, vol. 27, no. 7, pp. 437–443, 2007. View at Publisher · View at Google Scholar · View at Scopus
64. N. A. Buch, S. M. Ahmad, S. W. Ali, and H. M. Hassan, “An epidemiological study of neonatal necrotizing enterocolitis,” Saudi Medical Journal, vol. 22, no. 3, pp. 231–237, 2001. View at Scopus
65. T. E. Wiswell, C. F. Robertson, T. A. Jones, and D. J. Tuttle, “Necrotizing enterocolitis in full-term infants. A case-control study,” American Journal of Diseases of Children, vol. 142, no. 5, pp. 532–535, 1988. View at Scopus
66. A. J. Clarke and J. R. Sibert, “Hypernatraemic dehydration and necrotizing enterocolitis,” Postgraduate Medical Journal, vol. 61, no. 711, pp. 65–66, 1985. View at Scopus
67. S. P. Dunn, K. R. Gross, L. R. Scherer, S. Moenning, A. Desanto, and J. L. Grosfeld, “The effect of polycythemia and hyperviscosity on bowel ischemia,” Journal of Pediatric Surgery, vol. 20, no. 4, pp. 324–327, 1985. View at Scopus
68. M. H. LeBlanc, C. D'Cruz, and K. Pate, “Necrotizing enterocolitis can be caused by polycythemic hyperviscosity in the newborn dog,” Journal of Pediatrics, vol. 105, no. 5, pp. 804–809, 1984. View at Scopus
69. WHO, “Polycythemia in the Newborn,” AIIMS- NICU protocols, 2007, http://www.newbornwhocc.org/.
70. S. C. Springer, “Necrotizing Enterocolitis: Differential Diagnoses & Workup,” 2011, http://emedicine.medscape.com/article/977956-diagnosis.
71. Y. Bayraktar and O. Harmanci, “Etiology and consequences of thrombosis in abdominal vessels,” World Journal of Gastroenterology, vol. 12, no. 8, pp. 1165–1174, 2006. View at Scopus
72. R. F. Burrows and J. G. Kelton, “Perinatal thrombocytopenia,” Clinics in Perinatology, vol. 22, no. 3, pp. 779–801, 1995. View at Scopus
73. A. B. Kenton, D. O'Donovan, D. L. Cass et al., “Severe thrombocytopenia predicts outcome in neonates with necrotizing enterocolitis,” Journal of Perinatology, vol. 25, no. 1, pp. 14–20, 2005. View at Publisher · View at Google Scholar · View at Scopus
74. M. Ververidis, E. M. Kiely, L. Spitz, D. P. Drake, S. Eaton, and A. Pierro, “The clinical significance of thrombocytopenia in neonates with necrotizing enterocolitis,” Journal of Pediatric Surgery, vol. 36, no. 5, pp. 799–803, 2001. View at Publisher · View at Google Scholar · View at Scopus
75. R. Saxena, M. Kannan, and V. P. Choudhry, “Neonatal thrombosis,” Indian Journal of Pediatrics, vol. 70, no. 11, pp. 903–907, 2003. View at Scopus
76. A. J. Clarke and J. R. Sibert, “Hypernatraemic dehydration and necrotizing enterocolitis,” Postgraduate Medical Journal, vol. 61, no. 711, pp. 65–66, 1985. View at Scopus
77. S. Oddie, S. Richmond, and M. Coulthard, “Hypernatraemic dehydration and breast feeding: a population study,” Archives of Disease in Childhood, vol. 85, no. 4, pp. 318–320, 2001. View at Publisher · View at Google Scholar · View at Scopus
78. E. F. Bell and M. J. Acarregui, “Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants,” Cochrane Database of Systematic Reviews, no. 1, Article ID CD000503, 2008. View at Publisher · View at Google Scholar · View at Scopus
79. D. Isaacs, J. North, D. Lindsell, and A. R. Wilkinson, “Serum acute phase reactants in necrotizing enterocolitis,” Acta Paediatrica Scandinavica, vol. 76, no. 6, pp. 923–927, 1987. View at Scopus
80. M. Hällström, A. M. Koivisto, M. Janas, and O. Tammela, “Laboratory parameters predictive of developing necrotizing enterocolitis in infants born before 33 weeks of gestation,” Journal of Pediatric Surgery, vol. 41, no. 4, pp. 792–798, 2006. View at Publisher · View at Google Scholar · View at Scopus
81. N. Evennett, N. Alexander, M. Petrov, A. Pierro, and S. Eaton, “A systematic review of serologic tests in the diagnosis of necrotizing enterocolitis,” Journal of Pediatric Surgery, vol. 44, no. 11, pp. 2192–2201, 2009. View at Publisher · View at Google Scholar · View at Scopus
82. P. H. Schober and J. Nassiri, “Risk factors and severity indices in necrotizing enterocolitis,” Acta Paediatrica. Supplement, vol. 83, no. 396, pp. 49–52, 1994. View at Scopus
83. R. Srinivasjois, E. Nathan, D. Doherty, and S. Patole, “Prediction of progression of definite necrotising enterocolitis to need for surgery or death in preterm neonates,” Journal of Maternal-Fetal and Neonatal Medicine, vol. 23, no. 7, pp. 695–700, 2010. View at Publisher · View at Google Scholar · View at Scopus
84. M. Pourcyrous, H. S. Bada, S. B. Korones, V. Baselski, and S. P. Wong, “Significance of serial C-reactive protein responses in neonatal infection and other disorders,” Pediatrics, vol. 92, no. 3, pp. 431–435, 1993. View at Scopus
85. M. Pourcyrous, H. S. Bada, S. B. Korones, F. F. Barrett, W. Jennings, and T. Lockey, “Acute phase reactants in neonatal bacterial infection,” Journal of Perinatology, vol. 11, no. 4, pp. 319–325, 1991. View at Scopus
86. M. Pourcyrous, S. B. Korones, W. Yang, T. F. Boulden, and H. S. Bada, “C-reactive protein in the diagnosis, management, and prognosis of neonatal necrotizing enterocolitis,” Pediatrics, vol. 116, no. 5, pp. 1064–1069, 2005. View at Publisher · View at Google Scholar · View at Scopus
87. R. N. Goldberg, D. W. Thomas, and F. R. Sinatra, “Necrotizing enterocolitis in the asphyxiated full-term infant,” American Journal of Perinatology, vol. 1, no. 1, pp. 40–42, 1983. View at Scopus
88. B. Stoll, D. A. Horst, L. Cui et al., “Chronic parenteral nutrition induces hepatic inflammation, steatosis, and insulin resistance in neonatal pigs,” Journal of Nutrition, vol. 140, no. 12, pp. 2193–2200, 2010. View at Publisher · View at Google Scholar · View at Scopus
89. P. J. Javid, S. Collier, D. Richardson et al., “The role of enteral nutrition in the reversal of parenteral nutrition-associated liver dysfunction in infants,” Journal of Pediatric Surgery, vol. 40, no. 6, pp. 1015–1018, 2005. View at Publisher · View at Google Scholar · View at Scopus
90. P. J. Clarke, M. J. Ball, and M. G. W. Kettlewell, “Liver function tests in patients receiving parenteral nutrition,” Journal of Parenteral and Enteral Nutrition, vol. 15, no. 1, pp. 54–59, 1991. View at Scopus
91. D. A. K. Watters, S. Chamroonkul, and C. D. M. Griffith, “Changes in liver function tests associated with parenteral nutrition,” Journal of the Royal College of Surgeons of Edinburgh, vol. 29, no. 6, pp. 339–344, 1984. View at Scopus
92. G. Thuijls, J. P. M. Derikx, K. van Wijck et al., “Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis,” Annals of Surgery, vol. 251, no. 6, pp. 1174–1180, 2010. View at Publisher · View at Google Scholar · View at Scopus
93. D. Carroll, A. Corfield, R. Spicer, and P. Cairns, “Faecal calprotectin concentrations and diagnosis of necrotising enterocolitis,” The Lancet, vol. 361, no. 9354, pp. 310–311, 2003. View at Publisher · View at Google Scholar · View at Scopus
94. Q. Yang, P. B. Smith, R. N. Goldberg, and C. M. Cotten, “Dynamic change of fecal calprotectin in very low birth weight infants during the first month of life,” Neonatology, vol. 94, no. 4, pp. 267–271, 2008. View at Publisher · View at Google Scholar · View at Scopus
95. T. Rand, M. Weninger, C. Kohlhauser et al., “Effects of umbilical arterial catheterization on mesenteric hemodynamics,” Pediatric Radiology, vol. 26, no. 7, pp. 435–438, 1996. View at Publisher · View at Google Scholar · View at Scopus
96. A. Gentili, V. Landuzzi, L. Pasini, A. Pigna, A. Cacciari, and A. S. Corticelli, “Risk factors and protective factors in a population a risk for newborn necrotizing enterocolitis,” La Pediatria Medica e Chirurgica, vol. 18, no. 5, pp. 487–492, 1996. View at Scopus
97. S. O. Guthrie, P. V. Gordon, V. Thomas, J. A. Thorp, J. Peabody, and R. H. Clark, “Necrotizing enterocolitis among neonates in the United States,” Journal of Perinatology, vol. 23, no. 4, pp. 278–285, 2003. View at Publisher · View at Google Scholar · View at Scopus
98. N. S. Kabra, M. Kumar, and S. S. Shah, “Multiple versus single lumen umbilical venous catheters for newborn infants,” Cochrane Database of Systematic Reviews, no. 3, Article ID CD004498, 2005. View at Scopus
99. G. Parry, J. Tucker, and W. Tarnow-Mordi, “CRIB II: an update of the clinical risk index for babies score,” The Lancet, vol. 361, no. 9371, pp. 1789–1791, 2003. View at Publisher · View at Google Scholar · View at Scopus
100. P. K. Rastogi, V. Sreenivas, and N. Kumar, “Validation of CRIB II for prediction of mortality in premature babies,” Indian Pediatrics, vol. 47, no. 2, pp. 145–147, 2010. View at Publisher · View at Google Scholar · View at Scopus
101. J. Madan, J. Fiascone, V. Balasubramanian, J. Griffith, and J. I. Hagadorn, “Predictors of ductal closure and intestinal complications in very low birth weight infants treated with indomethacin,” Neonatology, vol. 94, no. 1, pp. 45–51, 2008. View at Publisher · View at Google Scholar · View at Scopus
102. S. E. G. Hamrick and G. Hansmann, “Patent ductus arteriosus of the preterm infant,” Pediatrics, vol. 125, no. 5, pp. 1020–1030, 2010. View at Publisher · View at Google Scholar · View at Scopus
103. R. L. Meyers, G. Alpan, E. Lin, and R. I. Clyman, “Patent ductus arteriosus, indomethacin, and intestinal distension: effects on intestinal blood flow and oxygen consumption,” Pediatric Research, vol. 29, no. 6, pp. 569–574, 1991. View at Scopus
104. D. O'Donovan, A. Baetiong, K. Adams et al., “Necrotizing enterocolitis and gastrointestinal complications after indomethacin therapy and surgical ligation in premature infants with patent ductus arteriosus,” Journal of Perinatology, vol. 23, no. 4, pp. 286–290, 2003. View at Publisher · View at Google Scholar · View at Scopus
105. P. T. Nowicki, C. E. Miller, and R. C. Edwards, “Effects of hypoxia and ischemia on autoregulation in postnatal intestine,” American Journal of Physiology, vol. 261, no. 1, pp. G152–G157, 1991. View at Scopus
106. C. Michael Cotten, S. Taylor, B. Stoll et al., “Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants,” Pediatrics, vol. 123, no. 1, pp. 58–66, 2009. View at Publisher · View at Google Scholar · View at Scopus
107. A. Tagare, S. Kadam, U. Vaidya, and A. Pandit, “Routine antibiotic use in preterm neonates: a randomised controlled trial,” The Journal of Hospital Infection, vol. 74, no. 4, pp. 332–336, 2010. View at Scopus
108. J. Madan, J. Fiascone, V. Balasubramanian, J. Griffith, and J. I. Hagadorn, “Predictors of ductal closure and intestinal complications in very low birth weight infants treated with indomethacin,” Neonatology, vol. 94, no. 1, pp. 45–51, 2008. View at Publisher · View at Google Scholar · View at Scopus
109. G. A. Macones, S. J. Marder, B. Clothier, and D. M. Stamilio, “The controversy surrounding indomethacin for tocolysis,” American Journal of Obstetrics and Gynecology, vol. 184, no. 3, pp. 264–272, 2001. View at Publisher · View at Google Scholar · View at Scopus
110. W. J. Morales and H. Madhav, “Efficacy and safety of indomethacin compared with magnesium sulfate in the management of preterm labor: a randomized study,” American Journal of Obstetrics and Gynecology, vol. 169, no. 1, pp. 97–102, 1993. View at Scopus
111. T. Kurki, M. Eronen, R. A. Lumme, and O. Ylikorkala, “A randomized double-dummy comparison between indomethacin and nylidrin in threatened preterm labor,” Obstetrics and Gynecology, vol. 78, no. 6, pp. 1093–1097, 1991. View at Scopus
112. S. Abbasi, J. S. Gerdes, H. M. Sehdev, S. S. Samimi, and J. Ludmir, “Neonatal outcome after exposure to indomethacin in utero: a retrospective case cohort study,” American Journal of Obstetrics and Gynecology, vol. 189, no. 3, pp. 782–785, 2003. View at Publisher · View at Google Scholar · View at Scopus
113. S. B. Amin, R. A. Sinkin, and J. C. Glantz, “Metaanalysis of the effect of antenatal indomethacin on neonatal outcomes,” American Journal of Obstetrics and Gynecology, vol. 197, no. 5, pp. 486.e1–486.e10, 2007. View at Publisher · View at Google Scholar · View at Scopus
114. A. M. Fujii, E. Brown, M. Mirochnick, S. O'Brien, and G. Kaufman, “Neonatal necrotizing enterocolitis with intestinal perforation in extremely premature infants receiving early indomethacin treatment for patent ductus arteriosus,” Journal of Perinatology, vol. 22, no. 7, pp. 535–540, 2002. View at Publisher · View at Google Scholar · View at Scopus
115. S. T. Vermillion and R. B. Newman, “Recent indomethacin tocolysis is not associated with neonatal complications in preterm infants,” American Journal of Obstetrics and Gynecology, vol. 181, no. 5, pp. 1083–1086, 1999. View at Publisher · View at Google Scholar · View at Scopus
116. B. V. Parilla, W. A. Grobman W., R. B. Holtzman, H. A. Thomas, and S. L. Dooley, “Indomethacin tocolysis and risk of necrotizing enterocolitis,” Obstetrics and Gynecology, vol. 96, no. 1, pp. 120–123, 2000. View at Publisher · View at Google Scholar · View at Scopus
117. N. A. Shorter, J. Y. Liu, D. P. Mooney, and B. J. Harmon, “Indomethacin-associated bowel perforations: a study of possible risk factors,” Journal of Pediatric Surgery, vol. 34, no. 3, pp. 442–444, 1999. View at Scopus
118. Y. Kawase, T. Ishii, H. Arai, and N. Uga, “Gastrointestinal perforation in very low-birthweight infants,” Pediatrics International, vol. 48, no. 6, pp. 599–603, 2006. View at Publisher · View at Google Scholar · View at Scopus
119. J. L. Grosfeld, M. Chaet, F. Molinari et al., “Increased risk of necrotizing enterocolitis in premature infants with patent ductus arteriosus treated with indomethacin,” Annals of Surgery, vol. 224, no. 3, pp. 350–357, 1996. View at Publisher · View at Google Scholar · View at Scopus
120. M. E. Norton, J. Merrill, B. A. B. Cooper, J. A. Kuller, and R. I. Clyman, “Neonatal complications after the administration of indomethacin for preterm labor,” New England Journal of Medicine, vol. 329, no. 22, pp. 1602–1607, 1993. View at Publisher · View at Google Scholar · View at Scopus
121. R. Sharma, M. L. Hudak, J. J. Tepas 3rd et al., “Prenatal or postnatal indomethacin exposure and neonatal gut injury associated with isolated intestinal perforation and necrotizing enterocolitis,” Journal of Perinatology, vol. 30, no. 12, pp. 786–793, 2010. View at Publisher · View at Google Scholar · View at Scopus
122. P. C. Tsao, S. J. Chen, C. F. Yang et al., “Comparison of intravenous and enteral indomethacin administration for closure of patent ductus arteriosus in extremely-low-birth-weight infants,” Journal of the Chinese Medical Association, vol. 73, no. 1, pp. 15–20, 2010. View at Publisher · View at Google Scholar · View at Scopus
123. H. L. Halliday, R. A. Ehrenkranz, and L. W. Doyle, “Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants,” Cochrane Database of Systematic Reviews, no. 1, Article ID CD001146, 2009. View at Publisher · View at Google Scholar · View at Scopus
124. D. E. da Costa, P. A. K. Nair, and S. M. Al Khusaiby, “Effects of antenatal steroids on the complications of prematurity in an era of surfactant replacement therapy in Oman,” Journal of Tropical Pediatrics, vol. 46, no. 6, pp. 375–377, 2000. View at Publisher · View at Google Scholar · View at Scopus
125. R. C. Pattinson, J. D. Makin, M. Funk et al., “The use of dexamethasone in women with preterm premature rupture of membranes—a multicentre, double-blind, placebo-controlled, randomised trial,” South African Medical Journal, vol. 89, no. 8, pp. 865–870, 1999. View at Scopus
126. D. Roberts and S. Dalziel, “Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth,” Cochrane Database of Systematic Reviews, vol. 3, Article ID CD004454, 2006. View at Scopus
127. H. L. Halliday, R. A. Ehrenkranz, and L. W. Doyle, “Late (>7 days) postnatal corticosteroids for chronic lung disease in preterm infants,” Cochrane Database of Systematic Reviews, no. 1, Article ID CD001145, 2009. View at Scopus
128. G. Deshpande, S. Rao, and S. Patole, “Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials,” The Lancet, vol. 369, no. 9573, pp. 1614–1620, 2007. View at Publisher · View at Google Scholar · View at Scopus
129. C. Czyrko, C. A. Del Pin, J. A. O'Neill Jr., G. J. Peckham, and A. J. Ross 3rd, “Maternal cocaine abuse and necrotizing enterocolitis: outcome and survival,” Journal of Pediatric Surgery, vol. 26, no. 4, pp. 414–421, 1991. View at Publisher · View at Google Scholar · View at Scopus
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More than six months after the Rangarajan panel recommended deregulating the R80,000-crore sugar sector, at least one state has initiated reforms in cane pricing.
Bombay High Court (HC) asked Maharashtra Water Resources Regulatory Authority (MWRRA) Wednesday to hear Solapur farmers aggrieved by the parched Ujjani dam that has allegedly created a drought-like
The state government has increased the crop loan limit of farmers by 15% which will come into effect from the coming kharif season starting from mid June this year.
The parliamentary panel says govt has failed to understand the urgency of timely infusion of capital in the system
Acknowledging that the iron ore project of National Mineral Development Corporation (NMDC) in South Bastar is causing contamination of rivers, Chhattisgarh government has ordered a survey of the af
There was a time when the banks of Chitrapuzha near Irumpanam were blessed by the green and yielding paddy fields.
A parched paddy field at Puzhakkal near Thrissur.— PHOTO: K.C. Sowmish
Many places in the district are facing acute water shortage as the mercury level is soaring.
Farmers of Sivarakottai on Tuesday registered their protest against the State Government’s proposal to acquire around 1,500 acres of land for setting up an industrial estate covering the villages o
The state will get Rs 700-crore loan from National Bank for Agriculture and Rural Development (NABARD) for the current financial year to give a fillip to agriculture, healthcare, communication and
BRAI will regulate research, transport, import, manufacture, use of organisms and products of modern biotechnology
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Bibliography: Camouflage
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Title: Camouflage
Author: Henry Kuttner
Year: 1945
Type: SHORTFICTION
Select 2 publications to diff:
Copyright (c) 1995-2011 Al von Ruff.
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Publication Listing
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• Title: Short Stories
• Authors: Saki
• Year: 1978-00-00
• ISBN-10: 0-460-11105-1
• ISBN-13: 978-0-460-11105-8
• Publisher: J. M. Dent
• Pub. Series: Everyman's Library
• Pages: 250
• Binding: tp
• Type: COLLECTION
• Title Reference: Short Stories
• ISFDB Record Number: 274905
• Notes: First printing.
Entry based on data from the verified 4th printing.
• Bibliographic Comments: Add new Publication comment (SHRTSTRSLT1978)
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Nano Express
Accelerated Hydrolysis of Aspirin Using Alternating Magnetic Fields
Uwe M Reinscheid
Author affiliations
Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077, Göttingen, Germany
Citation and License
Nanoscale Research Letters 2009, 4:854-857 doi:10.1007/s11671-009-9332-8
Published: 7 May 2009
Abstract
The major problem of current drug-based therapy is selectivity. As in other areas of science, a combined approach might improve the situation decisively. The idea is to use the pro-drug principle together with an alternating magnetic field as physical stimulus, which can be applied in a spatially and temporarily controlled manner. As a proof of principle, the neutral hydrolysis of aspirin in physiological phosphate buffer of pH 7.5 at 40 °C was chosen. The sensor and actuator system is a commercially available gold nanoparticle (NP) suspension which is approved for animal usage, stable in high concentrations and reproducibly available. Applying the alternating magnetic field of a conventional NMR magnet system accelerated the hydrolysis of aspirin in solution.
Keywords:
Gold nanoparticle; Magnetic field; Relaxation; Hydrolysis; Pro-drug
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27. According to this, they concluded to go the next morning and relieve it. Phrynichus, when he had certain word from Derus of the arrival of those galleys, his colleagues advising to stay and fight it out with their fleet, said that he would neither do it himself nor suffer them to do it, or any other, as long as he could hinder it. [2] For seeing he might fight with them hereafter, when they should know against how many galleys of the enemy and with what additions to their own, sufficiently and at leisure made ready, they might do it, he would never, he said, for fear of being upbraided with baseness (for it was no baseness for the Athenians to let their navy give way upon occasion; [3] but by what means soever it should fall out, it would be a great baseness to be beaten), be swayed to hazard battle against reason and not only to dishonour the state but also to cast it into extreme danger, seeing that since their late losses it hath scarce been fit with their strongest preparation, willingly, no nor urged by precedent necessity, to undertake, how then without constraint to seek out voluntary, dangers? [4] Therefore he commanded them with all speed to take aboard those that were wounded and their landmen and whatsoever utensils they brought with them; but to leave behind whatsoever they had taken in the territory of the enemy to the end that their galleys might be the lighter; [5] and to put off for Samos, and thence, when they had all their fleet together, to make out against the enemy as occasion should be offered. As Phrynichus advised this, so he put it in execution, and was esteemed a wise man, not then only, but afterwards, nor in this only, but in whatsoever else he had the ordering of. [6] Thus the Athenians presently in the evening, with their victory unperfect, dislodged from before Miletus. From Samos the Argives, in haste and in anger for their overthrow, went home.
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load focus Notes (T. G. Tucker, 1892)
load focus Greek (1942)
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hide References (43 total)
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[5] When he had set the brands on fire, he let them go into the standing grain of the Philistines, and burnt up both the shocks and the standing grain, and also the olive groves.
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Place:Sizewell, Suffolk, England
Watchers
NameSizewell
TypeVillage
Located inSuffolk, England
the text in this section is copied from an article in Wikipedia
Sizewell is a small fishing village with a few holiday homes in the county of Suffolk, England. It is located on the East Anglian coast just north of the larger holiday villages of Thorpeness and Aldeburgh, and two miles from the town of Leiston. It is within the Suffolk Coast and Heaths AONB.
The village was part of the Ogilvie estate, which extended as far south as Aldeburgh. Sizewell Hall, now used as a Christian conference centre, is still owned by the Ogilvie family.
Research Tips
This page uses content from the English Wikipedia. The original content was at Sizewell. The list of authors can be seen in the page history. As with WeRelate, the content of Wikipedia is available under the Creative Commons Attribution/Share-Alike License.
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IT's Role in Improving Elections
I posted an article at ZDNet's Government and Technology blog about the Carter-Baker report on voting:
Former President Jimmy Carter and former Secretary of State James Baker released the final version of a bipartisan election reform report today. The two led a 21-member, privately funded Commission that offered 87 recommendations to strengthen the country's electoral system and build confidence in the political process. Of the five primary recommendations, three have implications for government IT.
From IT's role in improving elections | ZDNet Government Blog | ZDNet.com
Referenced Tue Sep 20 2005 12:16:46 GMT-0600 (MDT)
There's been much said of late on eVoting. I find the conclusions in this report to be well-thought out, but I'm troubled by the march to federalizing the election process. Perhaps it's inevitable given its importance, but I'm of a mind that states could do a better job of this and figure this out on their own through some coordinating group like the National Association of Secretaries of State.
As I mention in the article, the most controversial of the proposals is probably the use of Real ID as the sole means of authenticating voters:
While Real ID generally has implications for IT, this proposal just adds to that requirement list. There are, as usual, privacy concerns. Most people don't realize that information about whether they voted or not and in which elections, along with their party affiliation, is a public record in most jurisdictions. This proposal would make that data much more accurate, linkable and transferable between states than it has been in the past.
From IT's role in improving elections | ZDNet Government Blog | ZDNet.com
Referenced Tue Sep 20 2005 12:21:37 GMT-0600 (MDT)
This is the very real danger that any national ID card system, even one cobbled together like Real ID posses. Once you've got a universal identifier, you can link all kinds of information. Even if you restrict the government, someone else will. Soon we'll be correlating whether people vote with the kind of breakfast cereal they eat.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Catalogue Number
4182.4.40.001 - Australian Housing Survey: South Australia--Data Report on Hardcopy, 1999
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A set of standard tables produced for South Australia which, where confidentiality permits, are consistent with those included in the publication 'Australian Housing Survey: Housing Characteristics, Costs and Conditions, 1999' (cat. no. 4182.0). Data are provided on the physical characteristics and condition of dwellings, housing costs, affordability and adequacy. These are cross-classified by various characteristics such as demographics, tenure and income.
A standard set of Data Reports is available for each State and Territory
© Commonwealth of Australia 2013
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
8752.0 - Building Activity, Australia, Dec 1999
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 17/04/2000
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• About this Release
ABOUT THIS RELEASE
Presents building activity statistics, for each state and territory, and for private and public sectors for Australia. Includes number of dwelling units commenced and completed and value of building work commenced, completed, done and yet to be done, all by state and territory. Information is provided for new residential buildings (houses and other residential), alterations and additions to residential buildings and non-residential buildings by type of building (e.g. offices, warehouses, accommodation, etc.). In addition, many series are shown in seasonally adjusted and trend terms, while the value of building work commenced and done is also shown in chain volume measures terms. It includes more comprehensive and updated information to that contained in cat. nos. 8755.0 and 8750.0.
Additional time series are available on AusStats.
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Error!
Success!
Design Patterns - Factory Method Pattern
0
kicks
Design Patterns - Factory Method Pattern (Unpublished)
First of all, the definition: “Define an interface for creating an object, but let the subclasses decide which class to instantiate. The Factory method lets a class defer instantiation to subclasses.“ Illustrated by adding a building to our game, which creates various GameUnits for each faction.
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FMM_flow_diagram.pdf
There is a newer version of this article.Go to newer version
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FMM_flow_diagram.pdf. Rio Yokota, Lorena A. Barba. figshare.
http://dx.doi.org/10.6084/m9.figshare.91441
Retrieved 09:00, May 18, 2013 (GMT)
Description
Diagram illustrating the algorithmic flow of the fast multipole method, FMM, showing all the operations (kernels) required: P2M is the transformation of points to multipole expansions (point-to-multipole); M2M is the translation of multipole expansions from a deep level in the tree to parent levels (multipole-to-multipole); M2L is the transformation of multipole expansions (valid far from an evaluation point) to local expansions (valid nearby an evaluation point); L2L is the translation of local expansions down the tree; L2P is the evaluation of local expansions at evaluation points.
This figure appeared in the following paper, under (c) 2011 The Authors.
“A tuned and scalable fast multipole method as a preeminent algorithm for exascale systems”, Rio Yokota, L A Barba. Int. J. High-perf. Comput. (2011) Preprint arXiv:1106.2176 - doi:10.1177/1094342011429952
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hpr0853 :: Pat Volkerding of Slackware Linux chats with Klaatu
Hosted by klaatu on 2011-11-08
Filed under Episode | Comments (7)
Pat Volkerding of Slackware Linux chats with Klaatu and whomever happens to wander by (Maco, Vincent Batts, Chad Wallenberg, and others) at the SELF afterparty.
Slackware
From Wikipedia, the free encyclopedia
Slackware is a free and open source Linux-based operating system. It was one of the earliest operating systems to be built on top of the Linux kernel and is the oldest currently being maintained. Slackware was created by Patrick Volkerding of Slackware Linux, Inc. in 1993. The current stable version is 13.37, released on April 27, 2011.
Slackware aims for design stability and simplicity, and to be the most "Unix-like" Linux distribution, making as few modifications as possible to software packages from upstream and using plain text files and a small set of shell scripts for configuration and administration.
Warning: this is not a proper interview, just 40 minutes of aimless and fairly noisy chit chat at a party. So it's probably not for everyone, although if you're a Slackware fan then it might be of some interest.
http://www.slackware.com/
http://en.wikipedia.org/wiki/Patrick_Volkerding
http://en.wikipedia.org/wiki/Slackware
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[maemo-developers] Which Scratchbox for 64bit?
From: Luca Donaggio donaggio at gmail.com
Date: Wed Mar 14 15:28:36 EET 2007
I've just finished setting up my shiny new amd64 box with Ubuntu Feisty and
I'm wondering which options do I have to install Maemo SDK:
- installing Scratchbox Apophis by hand using the i386 .debs (using dpkg -i
--force-architecture)
- installing Scratchbox Apophis by hand using the *.tar.gzs
- installing Scratchbox2 using Lauri Leukkunen's toolchain for amd64 (it
seems that it can generate compatible arm debs, but can I develop under sb2
as well? I mean can I setup an i386 target and launch af-sb-init.sh etc.?)
- use a chrooted 32bit environment and the maemo sdk installation script
Thanks,
Luca
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Quotation added by staff
Why not add this quote to your bookmarks?
I have tried to know absolutely nothing about a great many things, and I have succeeded fairly well. Benchley, Robert
This quote is about knowledge · Search on Google Books to find all references and sources for this quotation.
A bit about Benchley, Robert ...
Robert Charles Benchley (September 15, 1889 in Worcester, Massachusetts November 21, 1945) was an American humorist, newspaper columnist, film actor, and drama editor.
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Quotation added by Mary_Katherine
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Do not search for the truth, only cease to cherish opinions. Saying, Zen
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It's easy! Just pick the product you like and click-through to buy it from trusted partners of Quotations Book. We hope you like these personalized gifts as much as we do.
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He that can work is born to be king of something. Carlyle, Thomas
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212 - The Extra Degree
The one extra degree makes the difference. This simple analogy reflects the ultimate definition of excellence. Because it's the one extra degree of effort, in business and life, that can separate the good from the great. This powerful book by S.L. Parker and Mac Anderson gives great examples, great quotes and great stories to illustrate the 212° concept. A warning - once you read it, it will be hard to forget. Your company will have a target for everything you do ... 212°
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It's easy! Just pick the product you like and click-through to buy it from trusted partners of Quotations Book. We hope you like these personalized gifts as much as we do.
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Nothing destroys authority more than the unequal and untimely interchange of power stretched too far and relaxed too much. Bacon, Francis
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212 - The Extra Degree
The one extra degree makes the difference. This simple analogy reflects the ultimate definition of excellence. Because it's the one extra degree of effort, in business and life, that can separate the good from the great. This powerful book by S.L. Parker and Mac Anderson gives great examples, great quotes and great stories to illustrate the 212° concept. A warning - once you read it, it will be hard to forget. Your company will have a target for everything you do ... 212°
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212 - The Extra Degree
The one extra degree makes the difference. This simple analogy reflects the ultimate definition of excellence. Because it's the one extra degree of effort, in business and life, that can separate the good from the great. This powerful book by S.L. Parker and Mac Anderson gives great examples, great quotes and great stories to illustrate the 212° concept. A warning - once you read it, it will be hard to forget. Your company will have a target for everything you do ... 212°
Click here to buy this »
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The Legend of Zelda: A Link to the Past/Death Mountain
From StrategyWiki, the video game walkthrough and strategy guide wiki
Jump to: navigation, search
You first discover how to travel between the Dark and Light Worlds when you reach the summit of Death Mountain. There, you will come upon a mysterious tile that glimmers in the light. Step on it to discover its mysterious properties.
Contents
[edit] The Western Mountain
[edit] The lonely tunnel
Collecting the Magic Mirror for your good deed
The sign outside the Mountain Tunnel (A) forbade travelers to pass unless they had permission from the King. Knowing that the King has been deposed by Agahnim, feel free to forge ahead, pull up the big stone that blocks the path and enter the tunnel.
The tunnel is dark, with only a small area for visibility. To go through the cave, turn east, take the south-east fork, followed by the small north path. You will then find an Old Man who needs help. After you escort him to a cave further up the mountain, he will give you the Magic Mirror. The Mirror is used for warping to the Light World from the Dark World or to the beginning of a dungeon.
[edit] Mountain caves
The caves, long thought to be refuge for early Hyruleans, have been taken over by mountain beasts. Many of them still hold treasures and tools left by the Hyruleans when they moved to lower ground. Some of the caves were single dwellings, but others are multi-leveled networks of rooms. You should also seek refuge and treasure in the caves during your long climb to the top of Death Mountain.
[edit] A tower of terror
Door to the Dark World
When you finally discover how to use the mysterious Warp Tiles, it opens up a whole new world: the Dark World. You will find, though, that in the Dark World, all beings, including yourself, are transformed into creatures that reflect what is in their hearts. You become a rabbit and are unable to wield your weapon, so you are not able to battle evil forces there — unless you find a way to retain your human form. The solution to this problem, comes by way of a telepathic message from Sahasrahla, the Elder.
Carefully make your way through the dark mountain tunnels towards the top of the mountain. Explore the many caves and ledges along the way, uncovering treasures and clues as you go. Boulders many times larger than you crash down from above. An odd formation of rocks at the top of the mountain, which looks like a pair of eyeglasses, is dubbed Spectacle Rock. It stands between the climber and the Tower of Hera, and it appears that there is no way to scale its sheer sides. When you finally climb to the high plateau near Spectacle Rock, you'll see the glimmering tile that transports you to a different, but strangely familiar, world. You will find yourself transformed as well.
[edit] Into the darkness
Transformed in the Dark World
When you reach the top of Death Mountain, you will discover that there is no way to reach the Tower of Hera. You will find a circle of stones surrounding a Warp Tile to the dark dimension where you will be turned into a helpless rabbit. To the left of the place where you appear in the Dark World, you will find a patch of ground that mirrors the shape of Spectacle Rock. Use the Magic Mirror there to warp back to the Light World. When you arrive, you will be able to collect a Piece of Heart. By jumping off the north side of Spectacle Rock, you can now reach the Tower of Hera.
[edit] A Hylian Monolith
The massive tower
Standing six stories tall, the Tower of Hera dominates the mountain region. It was built in traditional Hyrulean style, with a brick facade, carved stone pillars and elaborate marble tile. Because the stone and marble were hand quarried by Hyrulean miners, it took many years to finish the building.
A bridge stretches from the west of the Tower of Hera to an island in the clouds. Cross the bridge after defeating a Tail Worm. You will find another Hylian Monolith that was erected by the Hylian people on a peak west of Spectacle Rock. Like the others, this Monolith is inscribed with a message in the old tongue, so only one who has the Book of Mudora can decipher it. By translating the message with the Book, it advises you to return when you have the Master Sword.
[edit] The mysterious Moon Pearl
Legends tell of a magic Moon Pearl that allows people to retain their human forms in the Dark World. There are many tales about the location of the pearl, and one of the most persistently retold is that it lies in a chest somewhere in the Tower of Hera. Sahasrahla will send you a telepathic message urging you to find the famous pearl.
[edit] The Eastern Mountain
[edit] Caves found in the crags
A portion of the bridge that leads to the eastern peak had long ago washed out, making it impossible for anyone to explore that area. You will eventually discover a way to cross the gaping hole in the bridge. When you reach the other side, you will discover another system of caves and tunnels.
[edit] More Dark World doors
While exploring the Death Mountain region, you will discover more tiles that you can use to travel back and forth between the Dark and Light Worlds. One is hidden under a rock, one is situated in plain sight (on the west side), and another appears only after you pound pegs into the ground.
[edit] Tower of Hera
The multi-leveled Tower of Hera is an intimidating structure that has many block barriers controlled by Crystal Switches. It also has Star Tiles that suddenly change the floor plans, sometimes creating pits that have claimed many intruders. You enter the tower in the 2nd floor. From the grand foyer, a stairway on the left leads down, another on the right leads up to the 3rd floor and beyond. The huge Moldorm, which is not fond of guests, occupies the entire 6th floor.
[edit] 1st Floor
Floor 1
You do not start the Tower of Hera on the 1st floor. Instead, the entrance is found on the 2nd floor.
Your first visit to the 1st floor will take place in the lower-left hand room. Two Stalfos and a Tail Worm will be guarding a key. In order to get the key, you must hit the Crystal Switch and lower the orange blocks that surround it. But this will also free the Tail Worm in the process. Defeat all of the enemies, and collect the Small Key. Before you return to the second floor, remember to hit the switch back to blue, or you won't be able to move freely through the 2nd floor.
You will return here once you use the key you just collected to unlock the door near the map on the second floor. When you arrive, the tiles of the floor will begin to rise and attack you. You've dealt with this before, and this time is no different. If you stand in the doorway the tiles will not hit you. Simply wait until the tiles all finish then continue. You'll probably need to hit the crystal switch in the corner to lower the blue fence that blocks the door to the right.
Head through, and you'll encounter a room with three Tail Worms, two of which are located behind orange blocks. You can take them on at whatever rate you are comfortable, but you'll need to hit the orange Crystal Switch at some point to make the lower door accessible.
When you enter through, you will see two Stalfos, and four unlit torches. Destroying the Stalfos does nothing to change the room, but there is one other trick to try. If you recall, lighting all four torches was the key to completing the Desert Palace dungeon. That trick works here too. Quickly light all four torches to make a treasure chest appear. Open it up, and discover the Big Key inside. Now you have a choice. You may either return to the 2nd floor the way that you came, or take a little shortcut back to the entrance, courtesy of the Magic Mirror.
[edit] 2nd Floor
Floor 2
This is the floor upon which you start. You will immediately notice an arrangement of raised blue blocks and lowered orange tiles, as well as a Crystal Ball at the entrance. Blue and orange Crystal Switches are found in several Hyrulean palaces, and the Tower of Hera is no exception. The beautiful switches are the key to raising and lowering the blue and orange Switch Fences that pop up in places. When you strike the Blue Crystal Switch, all of the blue Switch Fences fall and the orange ones rise; when you strike an orange switch, the orange Switch Fences fall and the blues ones rise.
Ultimately, you'd like to go up, but before you can do that, you must visit floor 1... twice. The door at the top, next to the Map is locked, so you must first take the stairs through the door on the left and grab a key.
When you return, You need to visit the top half of the room. There is a Tail Worm and two small fire-breathing Kodondos trapped behind barriers. You can defeat them if you'd rather not have to deal with their fire breath. When it's safe, unlock the door at the top and proceed back downstairs.
Finally, when you will return to the 2nd floor once more, you may climb the stairs through the door on the right, and complete the remainder of the Tower.
[edit] 3rd Floor
Floor 3
You will be introduced to two new things on the third floor: Pons and Star Switches. All of the enemies on Floor 3 are the deadly Pons. They have a thick rubbery hide that causes you to bounce backwards, even when you strike them with your sword. You can hurt them and dispose of them easily enough, but you must always take care to notice what lies directly behind you, because you are sure to hit it when you strike the Pons.
When you arrive on the third floor, you will encounter three Pons, three holes, and a Crystal Switch. The Crystal Switch does not directly affect anything in this room, but it does affect the next. Make sure to leave the Switch set to the orange color before you leave. Carefully destroy the three Pons in the room. It is always safest to keep your back to the wall when trying to fight them. If you happen to fall through the floor, you will land on the floor below, and may reattempt the room as long as you have at least one heart remaining. When you defeat the three Pons, the shutter door to the left will open.
In the next room, you will see three Pons, two holes, one blue and one orange block, and a Star Switch. Depending on the state of the Crystal Switch in the previous room, one of the blocks will be raised, and the other lowered. You may find that a hole is situated in front of the block that's lowered, and you may think that your only solution is to return to the previous room to give the Switch a whack. However, if you instead step on the Star Switch, you will discover that the holes move about the floor, and that it is now the raised block which has a hole in front of it, which will allow you to pass over the lowered block to the room above.
This next room can be difficult if you are unaccustomed to dealing with Star and Crystal Switches. If you left the Crystal Switch in the orange state, this room will be substantially easier. If not, return to the third floor entrance and change the Switch. Make sure that you step on a Star Switch so that there is no hole in front of the lowered block. When you reach the opposite side of the room, hit the Switch if your access to the door is blocked by the fence.
[edit] 4th Floor
Floor 4
When you reach this floor, you will notice that you have a number of Tail Worms and Kodondos to deal with. Nothing is a tremendous threat, and the biggest obstacle to your crossing the floor are variously laid out jars of pottery, some of which may contain hearts. Proceed carefully down the right side of the room and to the center.
Once there, you can easily grab the Compass out of the small chest. You can also receive a message from Sahasrahla telling you to collect the Moon Pearl. Alas, the treasure chest that holds the magical item is blocked off by a hole in the floor. Even by playing with the Star Switches, all you accomplish is moving the floor holes closer or farther from the chest. No matter how you approach it, there does not appear to be any way to collect the treasure from this floor.
If you continue up to the fifth floor, you will discover many holes there, as well. By stepping on the Star Switch on the left, you can make a new hole appear above the Bumper in the middle of the room. Then, from the top side of the hole, jump down to the platform with the treasure chest and retrieve the Moon Pearl. With the Moon Pearl, you can retain your shape in the Dark World.
[edit] 5th Floor
Floor 5
Approach the pit from the top
There are four regular blue Pons here and one even stronger red Pon to deal with, in addition to the usual holes. There is also a Star Switch situated precariously next to a rotating bar of fire. As if the Pons weren't bad enough to deal with, a few Bumpers are also placed on the floor for good measure. Before you race off to the sixth floor where Moldorm awaits, there are some aspects of the floor you may wish to investigate.
The floors in the Tower of Hera are riddled with holes, and people who fall into them disappear from sight and land elsewhere in the tower. Some even report falling several floors and finding Faeries in a room that was completely sealed off, and others deliberately jump into the pits to land in places that they could reach no other way. Stepping on Star Tiles changes the position of some pits.
If you drop through the top left hole in the floor, you will fall a long way down. When you finally land, you will find yourself in a Faerie pond room. Use the Faeries to restore your power, or fill your bottles, and take the Warp Tile back to the 5th floor. This will be a big help during the battle with Moldorm on the 6th floor.
Also helpful are the jars of pottery, all full of hearts. There is no excuse not to travel up to the sixth floor with anything less than full health. When you are ready, head upstairs to fight for the final pendant.
[edit] 6th Floor
Floor 6
[edit] Boss: Moldorm
Moldorm boss fight
Moldorm appears to be a gigantic Tail Worm. In addition to his enormous size, he also has exceptional defense. He mindlessly wanders around his den, but he likes to keep it clean. Any invader on his floor is treated the same; brushed off the edge. As a result of Moldorm's thick impenetrable skin, there is only one weak point on his body that can take damage: his tail.
As Moldorm wiggles and writhes across the floor, you must do your best to situate yourself behind him in order to strike his tail. This is no easy task, as Moldorm never holds still, and rarely travels in a straight line. He prefers to turn frequently, and his motion is hard to predict. Naturally, if you want to get through this fight fairly quickly, the biggest thing you'll want to avoid is getting pushed over the edge and down to the floor below. You will be able to return if that happens, but Moldorm will return to his full strength if you leave the room.
One effective way is to wait by the edge facing inward and wait for Moldrom to charge straight for you. This is the only time he straightenes himself. Use the pegasus boots to dash quickly, and you will go through Moldrom without getting knocked aside and pierce through his tail. Be sure to stop before you charge off the edge of the stage and face inward again. Doing this horizontally seems to be more comfortable than vertically.
Once you manage to land six blows to his tail, he will be destroyed, leaving behind a precious Heart Container. Once you collect it, the final pendant, the Pendant of Wisdom will drop from the ceiling.
[edit] One last step
Collect the pendant as reward for the difficult fight. When you do, Sahasrahla will contact you to congratulate you on the splendid accomplishment. With all three pendants in hand, access to the Master Sword may yet be yours. But to find it, you must return to the Lost Woods, where the sword slumbers.
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"A REALLY INTELLIGENT INTERVIEWER." -- Lance Henriksen
"QUITE SIMPLY, THE BEST HORROR-THEMED BLOG ON THE NET." -- Joe Maddrey, Nightmares in Red White & Blue
**Find The Vault of Horror on Facebook and Twitter, or download the new mobile app!**
**Check out my other blogs, Standard of the Day, Proof of a Benevolent God and Lots of Pulp!**
Tuesday, February 10, 2009
Announcing the Nominees for the First-Ever Cyber Horror Awards!
Dear readers, I'm a simple man, with simple dreams. One of those dreams was to create the first horror film awards ever determined by the online horror community. And now, thanks to the associations I've made via the VoH, that dream is soon to become a reality.
It's simple, really. There has never been a set of awards recognizing excellence in horror, as voted upon by the writers/bloggers whose passion it is to cover the genre on the internet. With our world transforming the way it has, online writers and bloggers have gained an amazing level of visibility in mainstream culture--some would say even supplanting the role enjoyed by traditional film critics. They have their awards, why shouldn't we have ours?
To that end, I have assembled some of the best and brightest of those who dedicate themselves to all things terrifying, many of which have taken part in the past in the Vault's "Cyber-Horror Elite" lists. As I write this, in fact, they are deliberating the list of nominees you're about to read. The results will be tallied at the end of he month.
It's an idea whose time has come: The web's first horror movie awards.
2008 Cyber Horror Award Nominees
Val Lewton Award for Best Film
Eden Lake, Rollercoaster Films
Let the Right One In, EFTI
The Midnight Meat Train, Lions Gate
The Strangers, Rogue Pictures
Tokyo Gore Police, Fever Dreams/Nikkatsu
David Cronenberg Award for Best Director
Tomas Alfredson, Let the Right One In
Bryan Bertino, The Strangers
Ryuhei Kitamura, The Midnight Meat Train
Matt Reeves, Cloverfield
James Watkins, Eden Lake
Jamie Lee Curtis Award for Best Actress
Jennifer Carpenter, Quarantine
Mylene Jampanoi, Martyrs
Lina Leandersson, Let the Right One In
Kelly Reilly, Eden Lake
Liv Tyler, The Strangers
Vincent Price Award for Best Actor
Simon Callow, Chemical Wedding
Kare Hedebrant, Let the Right One In
Andy Serkis, The Cottage
Keifer Sutherland, Mirrors
Jonathan Tucker, The Ruins
Dwight Frye Award for Best Supporting Actor
Anthony Head, Repo! The Genetic Opera
Vinnie Jones, The Midnight Meat Train
Jack
O’Connell, Eden Lake
Linnea Quigley Award for Best Supporting Actress
Morjana Alaoui, Martyrs
Julie Benz, Saw V
Lizzy Caplan, Cloverfield
Curt Siodmak Award for Best Screenplay
Jeff Buhler, The Midnight Meat Train
Pascal Laugier, Martyrs
John Ajvide Lindqvist, Let the Right One In
Scott B. Smith, The Ruins
James Watkins, Eden Lake
Karl Freund Award for Best Cinematography
Maxime Alexandre, Mirrors
David A. Armstrong, Saw V
Michael Bonvillain, Cloverfield
Hoyte van Hoytema, Let the Right One In
Peter Sova, The Strangers
Bernard Hermann Award for Best Score
Charlie Clouser, Saw V
Johan Soderqvist, Let the Right One In
Darren Smith & Terrance Zdunich, Repo! The Genetic Opera
Tom Savini Award for Best Makeup
Paul Hyett, Eden Lake
Greg Nicotero, Diary of the Dead & Mirrors
Yoshihiro Nishimura, Tokyo Gore Police
Albert S. D'Agostino Award for Best Production Design
David Hackl, Repo! The Genetic Opera
Tony Ianni, Saw V
Grant Major, The Ruins
Ray Harryhausen Award for Best Visual Effects
Mirrors
The Ruins
Shutter
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Help Wikitravel grow by contributing to an article! Learn how.
Shropshire
From Wikitravel
Jump to: navigation, search
Shropshire [1] is England's largest inland county, covering an area of 1,347 square miles. To the west it borders Wales and to the south rural Herefordshire and Worcestershire. In the north is Cheshire and, to the east, Staffordshire and the West Midlands conurbation.
[edit] Towns and villages
Map of Shropshire
[edit] Towns
• Shrewsbury - Shropshire's county town (population: 70,000) and the birthplace of Charles Darwin
• Bridgnorth - a town divided into low and high towns, described by Charles I as providing 'the finest view'
• Church Stretton - Shropshire's "Little Switzerland"
• Ludlow - gastronomic capital of the Midlands and an official "slow" town
• Much Wenlock - birthplace of the modern Olympics
• Newport - one of Shropshire's market towns
• Oswestry - a market town near the Shropshire/Wales border
• Telford - the largest town (population: 130,000) and named after the engineer Thomas Telford
• Whitchurch - market town on the Llangollen Canal
• Wem - a small market town and home to the modern sweet pea
• Ellesmere - in the heart of Shropshire's "meres and mosses" and home to 9 glacial meres (small lakes)
• Market Drayton - a market town on the Shropshire Union Canal and the home of gingerbread
• Shifnal - a town to the east of Telford, once an important staging post on the London to Holyhead road
• Bishop's Castle - a traditional and very small old English town near the Welsh border
• Clun - a tiny town in the southwest corner of the county, described by A.E. Housman as "the quietest place under the sun"
• Cleobury Mortimer - a small town in southeast Shropshire, between the Clee Hills and Wyre Forest
[edit] Villages
• Whittington - a pretty little village near Oswestry and home to the impressive Whittington Castle situated in the heart of the village
[edit] Other destinations
Must see's in Shropshire include:
• The Ironbridge Gorge Valley, home to the World's first Iron Bridge and home to the 10 Ironbridge Gorge Museums
• The Shropshire Hills with magnificent views of Shropshire and its neighbouring counties
• Stokesay Castle, near Craven Arms and the oldest and best preserved manor house in England
• Ludlow, Shropshire's gastronomic town and the first UK Cittaslow town. Specialist food and drink shops and markets can all be found here.
• Shrewsbury, Shropshire's county town and home to over 660 listed buildings including magnificent black and white examples.
• Royal Air Force Museum Cosford [2], home of the National Cold War Exhibition.
[edit] Understand
Since 1998, Shropshire has been administratively divided into Telford & Wrekin and Shropshire County Council. However for most purposes it is still one county with the same media, press, emergency services, records service, etc.
[edit] Talk
Some parts of West Shropshire have a Welsh influence in their place names, though the people living there speak English like the rest of the county.
[edit] Get in
Shropshire is relatively easy to get to by road and rail.
The A49 (which runs from Herefordshire to Lancashire) runs through Shropshire from north to south, while from the M6 the M54 and A5 run east to west.
Railways also run from the south to Shrewsbury, stopping primarily in Ludlow and Church Stretton. The main line from Birmingham and Wolverhampton also runs to Shrewsbury and then north to Chester or west to Wales. Shropshire does have a direct link to London, albiet it only a few times a day, and it taking approximately four hours direct (the 'scenic route'), when switching at Birmingham New Street and taking two trains, arriving at London Euston would be just over two hours. The direct service is called Wrexham and Shropshire and runs from Shrewsbury to London, stopping at Wellington and Telford in Shropshire, before continuing to Banbury and then London Marylebone
Air travellers will normally fly to Manchester Airport, Birmingham International and possibly John Lennon Airport, Liverpool. East Midlands Airport is also a possibility.
[edit] Get around
Shropshire is a predominantly rural area and sparsely populated. Car transport remains essential for travellers wanting to take full advantage of the county, despite recent efforts to increase public transport usage.
It is possible to see most of the major sites by public transport. However, trains and buses can be infrequent or seasonal.
Most towns in Shropshire have their own public transport and taxi service.
Seasonal shuttle buses give access to areas of Shropshire including the Shropshire Hills Area of Outstanding Natural Beauty (see Church Stretton).
[edit][add listing] See
With Shropshire home to over 32 castles, there is plenty of history and heritage to be found in Shropshire.
If gardens are more your thing, then you won't be disappointed. Shropshire is home to some 20 national collections including English Roses, Clematis and Tulips. Choose from the award winning Wollerton Old Hall Garden near Market Drayton, the Dorothy Clive Garden near Market Drayton and Hawkstone Park and Follies near Shrewsbury to name a few.
With over 90 attractions to visit, here is a taster of just some of the attractions that you can explore and discover:
Stokesay Castle. A very romantic 13th Century fortified manor house.
The Ironbridge Gorge Museums. The world's first iron bridge (oddly beautiful) spanning the River Severn. Birth place of the industrial revolution, Ironbridge is a UNESCO World Heritage Site. The Ironbridge Gorge Museums are nine award winning museums and sites that tell this momentous story.
The Severn Valley Railway. Britains premier steam railway, 16 miles of glorious countryside and restored stations. Shropshire has many other steam train attractions besides.
Wroxeter Roman City (Viroconium). The fourth largest Roman city in Britain. Wroxeter was also the city of Camelot from the ledgend of King Arthur. Much to see and learn. You can follow the trail of the Real King Arthur.
The Royal Airforce Museum Cosford. Aviation history brought to life, the largest collection of missiles in the country. Exciting displays of civil and military planes…Last of the few.
Weston Park. Ancestral home of the Earls of Bradford. Lots of events, concerts and the occasional world summit too.
Hawkstone Historic Park and Follies. Wooded magical land of Grottoes, caves, cliffs and follies. Setting for the TV Chronicles of Narnia. Awesome.
Wroxeter Roman Vineyard. One of the worlds most northerly vineyards producing red, white and sparkling wines.
A working watermill, Victorian Judges Lodgings and a Nuclear Bunker. Just how diverse can we get?
[edit] Itineraries
[edit][add listing] Do
[edit][add listing] Eat
Shropshire is is an excellent place to find locally grown produce, farmer's markets and delis. The county is home to the National winner of the retail cheese awards and a national finalist in the Taste of England awards.
Shropshire specialties include Shrewsbury biscuits, Gingerbread, Whimberry Pie and Fidget Pie.
Traditional pubs and inns, tearooms and fine dining restaurants can all be found in Shropshire.
[edit][add listing] Drink
Shropshire is renowned for its real ale and leads the way in the "home brew" revival. Here you'll find traditional pubs and inns and micro-breweries. The South Shropshire town of Bishops Castle has been happily brewing since 1642 and is home to some of the county's breweries.
You can even try Shropshire wine at Wroxeter Roman Vineyard, an historic site near Shrewsbury. Choose from a whole host of wines including Shropshire Gold, Wrekin Reserve and Wroxeter Medium. The vineyard also offers tours and tastings.
[edit] Stay safe
Shropshire is a rural county and generally safe with a low crime rate.
[edit] Get out
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
1363.0 - Book Publishers, Australia, 1999-2000
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 09/08/2001
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• About this Release
ABOUT THIS RELEASE
Contains details on financial and employment data of book publishers, as well as on industry structure, growth and numbers of books published and sold by type.
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
3412.0 - Migration, Australia, 2009-10 Quality Declaration
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 16/06/2011
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MEDIA RELEASE
16 June 2011
Embargoed: 11.30 am (Canberra time)
75/2011
6 million migrants call Australia home
Almost 6 million migrants, born in over 200 countries, live in Australia. According to figures released today by the Australian Bureau of Statistics (ABS), 27% of Australia's resident population were born overseas, as at June 2010.
People born in the United Kingdom continued to be the largest group of overseas-born residents, accounting for 1.2 million people. The next largest group was born in New Zealand with 544,000 people, followed by China (380,000 people), India (341,000) and Italy (216,000).
Over the last decade, the proportion of those born in the UK declined from 5.9% of Australia's population in 2000 to 5.3% in 2010. In contrast, the proportions increased for people born in New Zealand (from 1.9% to 2.4%), China (from 0.8% to 1.7%) and India (from 0.5% to 1.5%).
The majority (76%) of overseas-born residents were of working age, 15–64 years at June 2010. Migrants born in Asia, America and Africa had proportionally larger young (0–14 years) and working age (15–64 years) populations compared to those from Europe.
In 2009–10, net overseas migration contributed the greatest number of people to the most populous states: New South Wales with a net of 66,000 persons, followed by Victoria (60,400) and Queensland (39,700). The Northern Territory had the lowest contribution with a net of 1,300 persons.
In 2008–09, the net contribution of international students to the Australian population reached a record high of 122,400 students, contributing 27% of Australia's total population growth for the year. The top three countries of birth of these students were from India with a net of 43,000 students followed by China (24,700 students) and Nepal (10,500).
Victoria recorded the highest net contribution of international students in 2008–09 (43,600 people), followed by New South Wales (40,400) and Queensland (18,300).
More information on migrants living in Australia, data on overseas and interstate migration, or international students who have contributed to net overseas migration estimates can be found in Migration, Australia 2009-10 (cat. no. 3412.0).
Media notes:
• Net overseas migration (NOM) is the net gain or loss of population through immigration to Australia and emigration from Australia.
• Net is the number of arrivals less the number of departures.
• When reporting ABS data you must attribute the Australian Bureau of Statistics (or the ABS) as the source.
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
4430.0 - Disability, Ageing and Carers, Australia: Summary of Findings, 2003
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 15/09/2004
Directory of Statistical Sources
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
6461.0 - Australian Consumer Price Index: Concepts, Sources and Methods, 2005
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 17/08/2005
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CONTENTS
Contents
1. Introduction
2. Historical Background
3. Price Index Theory
4. Consumer Price Indexes
5. The Australian CPI
6. Estimating Weights
7. Areas for Special Consideration
8. Collection Methodology
Communication to Miscellaneous
Food to Clothing and Footwear
Housing toTransportation
9. Compiling the CPI
10. Using the CPI
Appendix 1: Weighting pattern for the CPI - June quarter 2000
Appendix 2: Price indexes and contract price indexation
Appendix 3 - Tradables, non tradables and volatile items
Glossary
Bibliography
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
4390.0 - Private Hospitals, Australia, 1993-94
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 07/11/1995
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• About this Release
Provides details of the operation of private, acute, psychiatric and day hospitals. Information is included about facilities and activities, types of inpatients and non-inpatients treated, staffing and finances.
This publication has been converted from older electronic formats and does not necessarily have the same appearance and functionality as later releases.
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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< Worst Episode Ever
Incorrectly Regarded As Good >
Beautiful Soup 4 Beta 8: I didn't even mention beta 7 on NYCB because it was oriented towards getting rid of test failures. Test failures that had a lot to do with what versions of what parsers were installed, but nothing to do with whether or not Beautiful Soup itself was broken.
Beta 8 adds very basic namespace awareness. By "basic" I mean:
1. Handle documents that include namespaced tags and attributes without crashing or mangling the document on output.
2. If the parser provides namespace information for a tag or attribute, store it for the user's reference instead of discarding it.
That's it. No one responded to my request for namespace-related feature requests, so I'm doing the bare minimum.
Filed under:
[Main] [Edit]
Unless otherwise noted, all content licensed by Leonard Richardson
under a Creative Commons License.
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ECE497 SLAM via ROS
From eLinux.org
Revision as of 17:35, 2 November 2012 by Whiteer (Talk | contribs)
Jump to: navigation, search
Team members: Elias White
Contents
Executive Summary
In autonomous navigation understanding the robot's surrounding environment, as well as its position in this environment, is of paramount importance. This project attempts to leverage the open-source efforts resulting in simultaneous localization and mapping (SLAM) algorithms and use them, in collaboration with the Beagleboard -xm, to develop a 3-D model of the world surrounding the board as it moves through space. Obviously the more (quality) sensory data used in a SLAM algorithm the better the results, but at this time a camera will be the only sensor device, although there is the possibility of incorporating a gyroscope. A primary objective of this project is to test the feasibility of using the Beagleboard -xm as the "brain" for an autonomous quad-copter.
Installation Instructions
Give step by step instructions on how to install your project on the SPEd2 image.
• Include your github path as a link like this: https://github.com/MarkAYoder/gitLearn.
• Include any additional packages installed via opkg.
• Include kernel mods.
• If there is extra hardware needed, include links to where it can be obtained.
User Instructions
Once everything is installed, how do you use the program? Give details here, so if you have a long user manual, link to it here.
Highlights
While there are currently no highlights, this video provides an idea of what I would like to do, although the quality of their results is much higher than I am expecting to achieve.
Theory of Operation
Give a high level overview of the structure of your software. Are you using GStreamer? Show a diagram of the pipeline. Are you running multiple tasks? Show what they do and how they interact.
Work Breakdown
As a solo group I'll be the only one working on this project.
Future Work
In order to improve performance once could bolster the sensory profile of the platform. Useful sensors include:
1. Laser scanning range-finder
2. IMU (Inertial measurement unit)
3. Digital Compass
4. GPS
The incorporation of the data gathered from these sensors will improve the robot's model of the world and decrease the uncertainty it has about its location in the model.
Conclusions
Nothing yet.
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Heap memory
From eLinux.org
Revision as of 10:34, 28 October 2011 by Cschalle (Talk | contribs)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Jump to: navigation, search
Heap is the memory allocated in runtime during program execution. When memory is allocated using malloc() or calloc() for any pointer in a program, the size of the memory is allocated from the heap memory area and is assigned to the pointer. Until the pointer is freed using free() the heap memory is used by the pointer variable.
See Memory Debuggers for tools that help analyze memory usage patterns, detect unbalanced allocations and frees, report buffer over- and under-runs, etc.
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Minerals Alert December 2012
A monthly online newsletter with product news, data releases and projects relating to the minerals and energy exploration industry.
1. Geo-Region of the month – Paterson Province, Western Australia
2. In situ iron ore resources maps (2012 edition) released
3. Seismic data released for Lower Lesueur Survey in Western Australia
4. Workshop on new seismic and MT datasets in the northern Yilgarn Craton region, Western Australia
5. Update on geophysical data releases
6. About Minerals Alert
1. Geo-Region of the Month – Paterson Province, Western Australia
Each month Geoscience Australia will highlight a range of significant products released over the past 10 years which relate to key Australian mineral provinces and may be of interest to current explorers.
This month’s Geo-Region is the highly endowed Paterson Province in Western Australia. The work was conducted as part of the Onshore Energy Security Program and the National Geoscience Agreement with the Geological Survey of Western Australia. Highlighted products, which are available as free downloads, include:
1. Paterson airborne electromagnetic survey - interpretation report. This report documents data acquisition parameters of the 2007–08 Paterson airborne electromagnetic (AEM) survey along with summaries of the geology and mineral systems of the Paterson Province and interpretations of AEM data.
2. Paterson airborne electromagnetic survey - data. Data from the Paterson AEM survey was collected along both east-west (Paterson North area) and northeast-southwest (Paterson South area) flight lines spaced mostly between one and six kilometres. It covers the Paterson Province with the exception of the Rudall River (Karlamilyi) National Park.
3. Palaeovalley map of Western Australia, Northern Territory and South Australia. This thematic map shows the distribution of Australia's arid and semi-arid zone palaeovalley systems in Western Australia, South Australia and the Northern Territory, including those in the Paterson Province. This map, which was compiled for the Palaeovalley Groundwater Project funded by the National Water Commission, provides information about water resources to support mining in the region as well as the distribution of palaeovalleys that may have potential for sandstone-hosted uranium deposits.
4. Solid geology interpretation of the Paterson Province at a 1:250 000 scale. This report presents a solid geology interpretation of the Paterson Province, extending from the Canning Basin in the north to the Officer Basin in the south.
5. Paterson drill hole database. This contains digital data, including geological logs, for more than 4300 public domain historical drill holes.
6. Ages of gold-copper mineralisation and associated granite magmatism in the Paterson Province. This document reports the age of the Telfer gold-copper deposit (850–840 Ma) using U–Pb analyses of monazite and xenotime that form part of the ore assemblage. It also reports age determinations for a suite of granites from the O'Callaghan's Supersuite, including the granite associated with the O'Callghan's wolfram–copper–zinc skarn (~805 Ma).
7. Age of uranium mineralisation at Kintyre. These documents report the age of mineralisation at the Kintyre deposit (840–830 Ma), which appear to coincide with the inversion of the Yeneena Basin during the Miles Orogeny (see (1) above).
For further information, please email narelle.neumann@ga.gov.au; or phone +61 2 6249 9429.
2. In situ iron ore resources maps (2012 edition) released
Geoscience Australia has released two new 1:10 million scale colour map sheets, Australian In Situ Iron Ore Resources 2012. Sheet 1 shows in situ iron resources (hematite) of geological regions. Major hematite-type iron deposits are classified according to the resource size and plotted on the regions. Sheet 2 shows in situ iron resources (magnetite) of geological regions. Major magnetite-type iron deposits are classified according to the resource size and plotted on the regions.
The map sheets are available as a free download.
For further information, please email Subhash.Jaireth@ga.gov.au, or phone +61 2 6249 9419.
3. Seismic data released for Lower Lesueur Survey in Western Australia
The Lower Lesueur Seismic Reflection survey was undertaken during February and March 2011 to evaluate the carbon capture and storage (CCS) potential of the southern Perth Basin. This project was a collaboration between Geoscience Australia and Geological Survey of Western Australia and is linked to the Western Australian Department of Mines and Petroleum’s South West Hub Project [PDF 3.25MB]. Funding was provided from the Western Australian Government’s Exploration Incentive Scheme and the Commonwealth Department of Resources, Energy and Tourism’s Pre-competitive geological storage data acquisition program.
Seismic reflection data was recorded along six traverses near the townships of Harvey, Yarloop and Cookernup to define a target site for further investigation into a possible site for a CCS pilot project. In addition, the new seismic data in the area will expand the scientific knowledge for water resources, potential geothermal sites, oil and gas prospectivity and natural gas deposits. The interpreted survey results were used to define the location of a stratigraphic data well, GSWA Harvey 1, which was successfully completed in March 2012 at a depth of 2945 metres.
The processed SEG-Y data, TIFF images, location information and gravity data are available as a free download.
For further information, please email tristan.kemp@ga.gov.au or phone +61 2 6249 9029
4. Workshop on new seismic and MT datasets in the northern Yilgarn Craton region, Western Australia
There will be a full day workshop on Wednesday, 27 February 2013 in Perth to present the results of new seismic reflection and magnetotelluric data collected for the 2010 Youanmi and 2011 Southern Carnarvon seismic surveys. These surveys extended across the northern Yilgarn Craton in Western Australia from the Southern Carnarvon Basin, across the Narryer and Youanmi terranes and into the Kalgoorlie Terrane of the Eastern Goldfields Superterrane. The survey and workshop are a joint venture involving Geoscience Australia and the Geological Survey of Western Australia.
To obtain details on the workshop, please email narelle.neumann@ga.gov.au; or phone +61 2 6249 9429.
Registrations are through the Geological Survey of Western Australia.
5. Update on geophysical data releases
Geoscience Australia is managing the data acquisition programs in New South Wales, Queensland, Western Australia and South Australia.
The current status of Geoscience Australia's geophysical survey data acquisition is available in a comprehensive table.
Minerals Alert Geophysical Surveys Table - survey boundary polygons in MapInfo TAB format.
To obtain further details on the survey acquisition, please email murray.richardson@ga.gov.au or phone +61 2 6249 9229.
6. About Minerals Alert
For more information, email roger.skirrow@ga.gov.au; or phone +61 2 6249 9442.
To read past editions of Geoscience Australia's Minerals Alert, visit the Minerals Alert Newsletter Archive.
To subscribe/unsubscribe visit the online subscription page and follow the instructions.
Topic contact: minerals@ga.gov.au Last updated: January 25, 2013
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Updated: 1 December 2007
2.7.1 Intensive Animal Production
2.7.1.6 Example 6
Location of Example: 149o20'42" East, 28o31'07" South
Distinctive Characteristics:
• The shade shelters that are evenly spaced throughout the feedlots. These are not permanent structures and should not be captured.
• The effluent settling ponds in proximity to the Intensive Animal Production (IAP) facility.
Regional Considerations:
Figure: 2.7.1.6 Representation of a Cattle Farm in association with surrounding features.
Unless otherwise noted, all Geoscience Australia material on this website is licensed under the Creative Commons Attribution 3.0 Australia Licence.
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About this Journal Submit a Manuscript Table of Contents
Prostate Cancer
Volume 2011 (2011), Article ID 918707, 13 pages
doi:10.1155/2011/918707
Review Article
New Insights into the Androgen-Targeted Therapies and Epigenetic Therapies in Prostate Cancer
1Department of Pharmaceutical Sciences, Jefferson School of Pharmacy, Thomas Jefferson University, 130 South 9th Street, Edison Building, Suite 1510F, Philadelphia, PA 19107, USA
2Department of Pharmacology and Experimental Therapeutics, University of Maryland and School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201-1559, USA
3Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
Received 22 June 2011; Accepted 27 July 2011
Academic Editor: Fazlul H. Sarkar
Copyright © 2011 Abhijit M. Godbole and Vincent C. O. Njar. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Prostate cancer is the most common cancer in men in the United States, and it is the second leading cause of cancer-related death in American men. The androgen receptor (AR), a receptor of nuclear family and a transcription factor, is the most important target in this disease. While most efforts in the clinic are currently directed at lowering levels of androgens that activate AR, resistance to androgen deprivation eventually develops. Most prostate cancer deaths are attributable to this castration-resistant form of prostate cancer (CRPC). Recent work has shed light on the importance of epigenetic events including facilitation of AR signaling by histone-modifying enzymes, posttranslational modifications of AR such as sumoylation. Herein, we provide an overview of the structure of human AR and its key structural domains that can be used as targets to develop novel antiandrogens. We also summarize recent findings about the antiandrogens and the epigenetic factors that modulate the action of AR.
1. Introduction
Prostate cancer (PC) is the second most prevalent cause of death in men in the USA and Europe. The dependence of PC on androgens has been recognized for more than 7 decades. Medical and surgical androgen deprivation therapy (ADT) has been a standard palliative therapy for metastatic PC. However, an estimated 217,730 new cases and 32,050 PC-related deaths in the USA alone in 2010 despite ADT [1] make the need for finding new targets and novel therapies an absolute priority.
Androgen, the male steroid hormone, is responsible for male sexual differentiation and development, as well as the maintenance and support of sexual tissues in the adult. Moreover, androgens are important for the development and progression of age-associated pathologies in men, including benign prostatic hyperplasia and prostate cancer (PC). Androgen action is exerted through the androgen receptor (AR), a 110-kDa member of the steroid receptor family of transcription factors [2]. The physiological ligands for the AR are testosterone and dihydrotestosterone (DHT). The later has at least 10-fold stronger binding affinity.
The most commonly used therapies in metastatic prostate cancer involve androgen deprivation through medical (LHRH agonists), surgical castration, or disruption of androgen binding to AR [3]. Such treatments are temporarily effective, but, over time, most prostate cancers evolve into a castration-resistant state [4, 5]. Resistance mechanisms include AR, gene mutation or amplification, ligand independent activation of AR and persistent intraprostatic androgens [68]. Importantly, even in castration resistant prostate cancer (CRPC), AR still plays an essential role in cancer progression [6]. Recent work indicates that epigenetic enzymes are important coactivators of AR and may represent targets to influence AR stability and activity, thus providing new therapeutic opportunities to overcome mechanisms of resistance.
Histone-deacetylating and DNA-methylating enzymes, act to modify certain histone and nonhistone proteins such as the chaperone protein HSP90, which leads to enhanced protein stability of client proteins including AR [911]. Due to the central role of AR in all phases of prostate cancer, modulating AR protein stability or AR cofactor activity represents an effective strategy to overcome most of the mechanisms of resistance and may have therapeutic implications in this disease.
This paper discusses the structure of androgen receptor, current antiandrogen therapies, the emerging therapies that target the AR, epigenetic modulation of AR, and therapies targeting epigenetic modulation.
2. Androgen Receptor (AR)
AR is a nuclear hormone receptor, which is activated by binding of androgen ligands. Upon androgen binding, AR dissociates from the cytoplasmic chaperone protein HSP90, self-dimerizes and translocates to the nucleus. AR then binds to consensus sequences in the genome called AREs (androgen response elements) to activate transcription of its target genes, which is essential for prostate development and maintenance [12].
Structure of AR
The AR shares an overall modular organization which has an N-terminal domain (NTD) containing the activation function (AF)-1, a central DNA binding domain (DBD), a short hinge region, and a COOH terminal domain (CTD), which contains both the AR ligand-binding domain (LBD) and AF-2 coactivator binding surface (Figure 1) [13]. The three-dimensional structures of peptides representing the LBD and AF-2 folds of the AR have been determined by X-ray crystallography. The three-dimensional structure of a peptide representing the AR DBD has also been determined [14, 15]. The AR NTD, on the contrary, is unstructured in solution, and thus it has been difficult to predict its structure accurately. Nevertheless, several critical functional domains have been described and characterized within the AR NTD. Posttranslational modifications of the AR, including phosphorylation, acetylation, ubiquitylation, and sumoylation, add additional layers of regulation and are likely to influence the structure and function of these domains [16] (Figure 1).
Figure 1: Schematic representation of the structure of human androgen receptor NTD: N-terminal domain, DBD: DNA-binding domain, LBD: ligand-binding domain, CTE: C-terminal extension, CTD: C-terminal domain, AF-1: activation function-1, AF-2: activation function-2.
2.1. AR C-Terminal Domain (CTD)
The role of the AR CTD is of particular importance for PC, because the current androgen ablation therapies target this domain of the AR. This prevents both AR nuclear translocation and the exposure of AF-2. Antiandrogens such as bicalutamide bind the LBD, block the activity of AF-2 [12], and cause AR to recruit corepressor molecules such as nuclear receptor corepressor (NCoR) to the promoters of AR-regulated genes [17, 18]. This inhibits AR activity and thus halts the growth and survival of androgen-dependent PC cells. Binding of ligand to the AR LBD causes a conformational change in the AR CTD, which induces formation of the AF-2 coactivator binding surface. The AF-2 surface serves as a docking site for LxxLL motifs present in transcriptional coactivators and corepressors. Unlike the LBD of other nuclear receptors, the AR LBD displays very weak ligand-dependent transcriptional activity unless stimulated by p160 coactivators such as steroid receptor coactivator (SRC)-1 or SRC-2 [19, 20]. This is in absolute contrast to the potent inherent transcriptional activity of an isolated AR NTD fragment [2022].
The transcriptional activity of most steroid hormone receptors is predominantly through the activation function AF-2 region in the LBD. However, in the AR, it is the AF-1 region in the NTD that contributes most to the transcriptional activity [23]. AR LBD functions independently of the NTD and can still bind ligand even if the AF-1 region is deleted or mutated; however, AF-1 region in the NTD is an absolute requirement for the transcriptional activity to take place.
2.2. AR N-Terminal Domain (NTD)
The AR NTD is highly flexible and displays intrinsic disorder in solution, which has hampered elucidation of its three-dimensional structure [13, 24]. In other words, it represents a rigid secondary structure which is either exposed or concealed depending on various factors such as androgen levels, cell type, posttranslational modifications, and presence or absence of transcriptional modulators. The AR NTD accounts for more than 60% of the AR protein. Therefore, understanding the dynamic nature of the AR NTD is critically important. It functions as a potent transcriptional activator independent of the CTD. The AF-1 domain serves as a binding site for the transcriptional repressors- N-CoR (nuclear corepressor) and SMRT (silencing mediator of retinoic acid and thyroid hormone receptor). Sumoylation (SUMO-small ubiquitin-like modifier) is a type of posttranslational modification. Sumoylation by SUMO-1 protein requires two discrete lysine residues—K386 and K520. These modifications inhibit AR activity through a mechanism that may involve SMRT’s interaction with the AR NTD [25, 26]. To sum up, the AR NTD plays a multifunctional and dynamic role in regulating AR activity and is a very important target.
2.3. AR-DBD
The AR DBD/hinge region plays important roles in mediating AR nuclear localization, receptor dimerization, and DNA binding. All the hormone receptor DBDs are highly conserved. It consists of two zinc-fingers and a loosely structured carboxy-terminal extension (CTE) [27]. It is responsible for dimerization of AR and tight binding of AR dimer to the DNA.
Ligand binding induces a conformational change in AR inducing phosphorylation [28], nuclear translocation [29], and dimerization. As described above, AR dimmer then binds to androgen response elements (AREs) located in the regulatory regions of target genes [30] and actively recruits essential cofactors and assembles the transcriptional machinery required to regulate the expression of androgen-regulated genes [31, 32]. A critical component of this signaling axis is the ability of the receptor to undergo dimerization.
2.4. AR Dimerization
Dimerization mediated through the AR-DBD is an absolute requirement for AR signaling. By assembling on DNA targets, the AR homodimer specifically binds DNA to regulate the expression of AR target genes. Whereas the N/C (NTD/CTD) interaction provides a potential mechanism for regulation of AR activity, further studies are necessary to determine the precise role and contribution of each model of AR N/C interaction to AR signaling. Based on evidence that AR-LBD dimerization can occur, it is likely that this interaction also contributes to AR signaling. Centenera et al. showed that interaction of multiple AR domains is required for optimal AR-mediated signaling [33].
3. Therapies Targeting Androgen Signaling
Currently, all conventional therapy has been focused on androgen-dependent activation of the AR through its C-terminal LBD. A schematic of their mechanism of action is shown in (Figure 2).
Figure 2: Therapeutic approaches to block the AR. EPI-001 interacts with the AR NTD to block AR transcriptional activity through this domain. Inhibitors of the LBD include androgen ablation and antiandrogens, DHT, and dihydrotestosterone.
Below is a summary of the currently used therapies targeting androgen signaling.
3.1. Androgen Deprivation Therapy (ADT)—Castration
Several studies have attempted to surgically or pharmacologically target androgenic stimulation. The goal of these interventions is to slow disease progression, and to treat the disease. Surgical castration completely eliminates testosterone production by the testes, whereas administration of an LHRH agonist (medical castration) generates castrate levels of serum testosterone (<20 or <50 ng/dL, resp.) by having a negative hormonal feedback on the hypothalamus [34]. There was no statistically significant difference in disease-free or overall survival for metastatic patients treated with either of the these testosterone-lowering treatments [35]. Castration was associated with a number of adverse effects like hot flashes, loss of libido, and decreased quality of life.
3.2. CYP17 Inhibitors
Blocking the in situ production of androgens by inhibition of CYP 17 enzyme is a critical key in the treatment of patients with advanced and/or metastatic prostate cancer. The following section describes the currently used CYP17 inhibitors and relevant data about them in clinical trials. The structures of ketoconazole, abiraterone acetate and VN/124-1 (TOK-001) are presented in Figure 3.
Figure 3: Structures of Inhibitors of CYP17.
3.2.1. Ketoconazole
Ketoconazole is a broad spectrum antifungal agent that has been extensively used off-label as second-line hormonal therapy for prostate cancer. Ketoconazole inhibits 11-β hydroxylation, cholesterol side chain cleavage to pregnenolone and CYP17 [36]. Two single-center trials on the use of HDK in CRPC found PSA declines >50% in 55% (11/20) [37] and 63% (30/48) of patients [38]. A larger phase III study of HDK therapy in 260 patients with post-ADT metastatic PC on antiandrogen withdrawal (AAWD) demonstrated a PSA decline >50% in 27% of patients treated with HDK plus AAWD. Overall survival was not different between the treatment groups; however, those patients with a >50% PSA decline had a median survival of 41 months compared to 13 months for those without a PSA decline. Time to PSA progression in PSA responders was 5.9 versus 8.6 months in AAWD alone and AAWD + HDK groups, respectively [39]. Androstenedione, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) levels decreased with HDK therapy. However, there was no change in testosterone level from baseline in either treatment groups.
3.2.2. Abiraterone Acetate
Abiraterone, a highly selective irreversible CYP17 inhibitor, was developed as a mechanism-based steroidal inhibitor of CYP17 following observations that nonsteroidal 3-pyridyl esters had improved selectivity for inhibition [40]. Abiraterone has been shown to reduce serum testosterone levels to below a detection threshold of 1 ng/dL [41]. Promising results from clinical trials of abiraterone acetate in CRPC patients have recently been reported. In a phase I trial of abiraterone acetate treatment of both ketoconazole-pretreated and ketoconazole-naïve CRPC patients [42], PSA declines of ≥50% were seen in 18 (55%) of 33 patients, including nine (47%) of 19 patients with prior ketoconazole therapy and nine (64%) of 14 patients without prior ketoconazole therapy. Significantly, the antitumor activity was nearly equivalent in both populations. The activity observed in castrate, ketoconazole-naïve patients confirms that abiraterone acetate is an active agent, whereas the activity in ketoconazole pre-treated patients implies that a more selective and potent inhibitor of CYP17 may be an improvement beyond ketoconazole, or an additional sequential therapeutic option.The most common adverse events in patients treated with abiraterone acetate were fatigue, hypertension, headache, nausea, and diarrhea. In addition to chemotherapy-naïve patients, a multicenter phase II study evaluated the efficacy of abiraterone in patients with docetaxel-treated CRPC [43]. All patients were treated with 1000 mg/d. Forty-seven patients were enrolled, and treatment resulted in observed PSA declines ≥50% in 51% (24/47) of patients at least once. Partial responses (by RECIST criteria) were reported in 27% (8/30) patients with measurable disease. Decreases in circulating tumor cell (CTC) counts were also observed [43].
Two phase III clinical trials of abiraterone acetate are now in progress. The first of these trials is designed to evaluate abiraterone + prednisone against a placebo + prednisone in patients with progressive CRPC after docetaxel chemotherapy. This trial has an estimated study completion date of June 2011 [44]. The second study will evaluate abiraterone + prednisone against a placebo + prednisone in CRPC patients prior to chemotherapy. The estimated study completion date is in 2014. Both trials list prior ketoconazole treatment in their exclusion criteria. Abiraterone was recently approved by US Food and Drug Administration (FDA) in April 2011.
3.2.3. VN/124-1 (TOK-001)
VN/124-1 was rationally designed as an inhibitor of androgen biosynthesis via inhibition of CYP17. Utilizing intact CYP17 expressing Escherichia coli, VN/124-1 was shown to be a potent inhibitor of the enzyme with an IC50 value of 300 nM compared to abiraterone which had an IC50 value of 800 nM. The high efficacy of VN/124-1 in several prostate cancer models is believed to arise from its ability to downregulate the AR as well as competitively block androgen binding. In competitive binding studies against the synthetic androgen [3H] R1881, VN/124-1 was equipotent to bicalutamide in LNCaP cells. Transcriptional activation assays showed VN/124-1 to be a pure AR antagonist of the wild-type AR and the T877A mutation found in LNCaP cells [45, 46]. VN/124-1 inhibited the growth of CRPCs, which had increased AR and were no longer sensitive to bicalutamide [47].
VN/124-1 (0.13 mmol/kg twice daily) caused a 93.8% reduction () in the mean final LAPC-4 xenograft volume compared with controls. In another antitumor efficacy study, treatment of VN/124-1 (0.13 mmol twice daily) was very effective in preventing the formation of LAPC4 tumors. VN/124-1 (0.13 mmol/kg twice daily) and VN/124-1 (0.13 mmol/kg twice daily) + castration induced regression of LAPC4 tumor xenografts by 26.55 and 60.67%, respectively [46]. This impressive preclinical data led to further clinical development of VN/124-1 by Tokai Pharmaceutical Cambridge, Mass. Tokai Pharmaceuticals initiated ARMOR1 (Androgen Receptor Modulation Optimized for Response 1) phase 1/2 trials in castrate-resistant prostate cancer patients on November 5, 2009 [48]. The results of this clinical trial are awaited. The study is expected to be completed by July 2012.
3.3. AR Antagonists
There is ample evidence in the literature that prostate cancer growth can be inhibited by blocking the AR. AR antagonists compete with dihydrotestosterone (DHT) for binding to the AR and thus block AR signaling. Despite the significant reduction in circulating testosterone, castration does not affect adrenal androgen production. Therefore, antiandrogens were introduced to directly prevent the binding of testosterone to the AR. Antiandrogens competitively inhibit ligand binding to the AR and may also prevent ligand-independent AR activation through various pathways, such as inhibiting the recruitment of coactivators or activating corepressors [49]. Antiandrogens are classified as steroidal or nonsteroidal based on their respective chemical structures [50]. The major antiandrogens in clinical use worldwide are the nonsteroidal bicalutamide, flutamide and nilutamide and the steroidal cyproterone acetate (CPA) (Figure 4). Bicalutamide is the most extensively studied nonsteroidal antiandrogen [51]. Lowered percentages of hot flashes as compared with castration have been reported with bicalutamide, flutamide and CPA treatment. Patients treated with bicalutamide have reported better preservation of sexual interest compared with LHRH agonist alone [52]. It is also important to note that a meta-analysis of randomized trials comparing CPA and ADT with ADT alone showed a survival decrease in the CPA group [53]. Overall, the nonsteroidal antiandrogens appear to be better tolerated than castration [54]. Agents targeting AR that are in clinical trials are summarized in Table 1. As monotherapy with an AR antagonist is not yet a standard treatment for patients with advanced or metastatic prostate cancer, it has been combined with medical (or surgical) castration, initially in studies conducted in the late 1980s and early 1990s (complete androgen blockade). These clinical trials showed that the combination of surgical or medical castration plus the administration of an AR antagonist resulted in only a limited improvement in disease-specific and overall survival in patients with advanced and/or metastasized prostate cancer compared to those who receive castration only [55].
Table 1: Agents targeting AR in clinical development for CRPC.
Figure 4: Structures of currently used antiandrogens and clinical candidate MDV3100.
Following the evidence that AR expression is increased in CRPC, the diarylthiohydantoin MDV3100 (Figure 4) was developed as a second-generation antiandrogen capable of sustained AR antagonism under conditions of AR over-expression. In preclinical evaluation, MDV3100 was shown to bind to the AR with a five- to eightfold higher affinity than bicalutamide [18, 56]. In a phase I/II study in CRPC, antitumor activity of MDV3100 was assessed by time on treatment, PSA, soft tissue and osseous disease and circulating tumor cells (CTC). Doses of up to 600 mg/day were investigated. Out of 114 patients treated with 30–360 mg/day and followed for over 12 weeks, 65 were chemotherapy-naïve and 49 were post chemotherapy. At 12 weeks, reduced PSA levels were seen in both groups, with a 57% (37/65) decline in the naïve group and 45% (22/49) in the postchemotherapy patients [18, 57]. No progression was noted in 74% (35/47) of patients with evaluable soft-tissue legions and 62% (50/81) of patients with bone lesions. Dose-limiting toxicity was observed at 600 mg/day. Fatigue was noted at 360 and 480 mg/day. Hence, the dose was reduced. At concentrations of 60, 150, and 240 mg/day, MDV3100 was well tolerated and no serious adverse events related to the drug were reported. Of the 73 patients, 63 had available CTC counts. A total of 85% of those with favorable pretreatment CTC counts maintained favorable posttreatment CTC counts, and 58% of patients treated at 240 mg/day converted from unfavorable to favorable, post-treatment. Bone scans revealed stable disease in 29% (6/21) patients with osseous disease on 240 mg/day. A half-life of 1 week was established, and the current reported data suggest a dose-response trend. Ultimately, 240 mg/day was selected for the phase III trials, and the results are much anticipated.
Although castration and antiandrogens are very effective strategies, it is well known that PC eventually acquires resistance. The possible mechanisms of the resistance include amplification or overexpression of AR; gain-of-function mutations allowing AR to be activated by steroids or antiandrogens, ligand-independent activation by growth factors, cytokines, or kinases; intracrine signaling by increased intratumoral androgens; overexpression of AR coactivators; and/or expression of constitutively active splice variants of AR that lacks LBD may be expressed solely or in mixed populations with full-length receptor to form a heterodimer [5860]. Although, various spliced variants of AR is reported, Sawyer’s group showed that the expression of the spliced variants of the AR are controlled by full-length AR [61]. Clearly, more studies are required to unravel the impact of spliced variants in the development and progression of CRPC.
For PC that has progressed to a CRPC phenotype, novel strategies of AR inhibition could be based on knowledge regarding the mechanisms of AR activation in this phase of the disease. Several studies have implicated the AR NTD as a key mediator of ligand-independent AR activity in PC cells [6265]. Quayle et al. showed that a decoy molecule representing the AR NTD inhibited tumor incidence, growth, and hormonal progression in an LNCaP xenograft model of PC [65]. Moreover, intratumor injection of lentivirus expressing the AR NTD decoy fragment inhibited the growth of established LNCaP xenografts. Although preclinical studies about the decoy NTD are impressive, future improvements will rely on more precise modes of inhibition, for example, targeting specific NTD transcriptional activation domains with combinations of smaller peptide decoys or drug-like small molecules. These types of approaches would be greatly facilitated by structural knowledge of the entire AR protein. Decoy AR1-558 inhibits full-length AR and blocks both androgen-dependent and CRPC tumor growth, most likely by a mechanism of mopping up essential proteins required for transcriptional activity [65]. Development of shorter decoy peptides (~100 amino acids in length) to the AR NTD that retain specificity for AR and still have antitumor activity has been difficult due to multiple factors, including peptide lability and the possible requirement of multiple, nonlinear regions of the AR NTD necessary for protein-protein interactions. Consistent with inhibiting AR activity, a small molecule inhibitor of AR NTD, EPI-001 (Figure 5) blocks AR-dependent proliferation in human prostate cancer cells that express AR and has no effect on the proliferation of cells that do not express functional AR or do not rely on the AR for growth and survival [66].
Figure 5: Structure of EPI-001.
Intravenous injection of EPI-001 significantly reduced the weight of benign prostates from noncastrated mature mice compared with control-treated animals [66]. EPI-001 also blocked the growth of prostate cancer xenografts in the presence of androgen (noncastrated mature male mice) and, most importantly, caused tumor regression of CRPC. EPI-001 had no effect on PC3 human prostate cancer xenografts that are insensitive to androgen and do not express functional AR indicating that its action is specific for AR proficient cells [66].
The aforementioned antiandrogens can have synergistic or additive effects if combined with other antiandrogens or with transcriptional modulators.
4. Epigenetic Regulators of AR-Mediated Signaling
To regulate transcription, the receptors bind to specific hormone response elements of target genes and exhibit crosstalk with other transcription factors through protein-protein interactions. Several coregulatory proteins recognized by different functional domains of the AR (the N-terminal transactivation region, the central DNA-binding domain (DBD), and the C-terminal ligand-binding domain) mediate transactivation and transrepression functions of AR and other nuclear receptors [67]. The mechanisms by which steroid receptors compartmentalize in the nuclei and find their specific binding motifs, hormone response elements, from a vast number of base pairs of chromosomal DNA have remained elusive.
Recent work indicates that epigenetic enzymes are important coactivators of AR and may represent targets to affect AR function or stability, thus providing new therapeutic opportunities to overcome mechanisms of resistance and to target AR with nonhormonal therapies. Epigenetics is defined as the study of changes produced in gene expression caused by mechanisms other than changes in the underlying DNA sequence [68]. Among the different types of epigenetic changes, the most important are DNA methylation and histone modifications, both of which have been shown to be important for cancer progression [68]. A histone octamer, composed of two copies of histone H2A, H2B, H3, and H4, is wrapped by approximately 146 base pairs of DNA to form the core particle of a nucleosome, the fundamental structural unit of eukaryotic chromatin [69]. The N-terminal tails of histones extend from the nucleosome core, providing sites for posttranslational modifications such as acetylation, methylation, ubiquitination, and phosphorylation. Such modifications affect chromatin structure and gene transcription [70]. Histone lysine acetylation generally activates gene transcription, whereas lysine methylation can have different effects depending on the position and status of methylation. Methylation of Lys4, Lys36, or Lys79 on histone H3 usually results in transcriptional activation, whereas methylation of Lys9 or Lys27 on histone H3 or Lys20 on histone H4 is usually linked to transcriptional inhibition. On a general note, methylation inhibits gene transcription [68]. The homologues of histone-modifying enzymes, such as HDAC6, may act to deacetylate nonhistone substrates such as the chaperone protein HSP90, which leads to enhanced protein stability of client proteins including AR [911, 71]. The balance between repressive and active histone modifications (also known as the histone code) ultimately determines whether a gene will be actively transcribed or repressed.
4.1. Histone Deacetylases (HDAC)
HDACs catalyze the deacetylation of the acetylated lysine residues of histones and nonhistone proteins and are involved in various fundamental life phenomena, such as gene expression and cell cycle progression. To date, eighteen HDAC family members (HDAC1—11 and SIRT1—7) have been identified. They are grouped into four classes based on function and homology to their yeast counterparts: class I includes HDAC1, 2, 3, and 8; class II includes HDAC4, 5, 6, 7, 9, and 10; class III includes Sirt1-7 class IV includes HDAC11 [72]. The functions of the HDAC isoforms are not yet fully understood. Some of the HDAC isoforms have been suggested to be associated with various disease states, including cardiac diseases and cancer [73].
Some HDACs deacetylate nonhistone substrates. More than 50 nonhistone HDAC substrates have been identified thus far, including key transcription factors such as p53, E2F, alpha-tubulin, and the chaperone protein HSP90 [73]. To sum up, HDACs regulate gene expression by modifying histone and nonhistone proteins. HDACs are upregulated in many cancers. Halkidou et al. showed that HDAC1 is overexpressed in prostate cancer [74]. Another type of HDAC- HDAC6 is an important protein for AR activity. It is described below.
4.1.1. HDAC6
Histone deacetylase 6 (HDAC6) is a cytoplasmic enzyme that regulates many important biological processes, including cell migration, immune synapse formation, and the degradation of misfolded proteins. HDAC6 deacetylates tubulin, Hsp90, and cortactin and forms complexes with other partner proteins. It is the only HDAC that possesses two functional deacetylase domains and a zinc finger (ZnF) motif [75, 76]. In vivo, the enzymatic activity of HDAC6 is exerted on tubulin, heat shock protein 90 (Hsp90), and cortactin substrates; however, in vitro, HDAC6 is also able to deacetylate histones [7577]. The Zn2+ chelator trichostatin A (TSA) reversibly inhibits HDAC6 deacetylase activity [77, 78].
AR requires peculiar cellular machinery to achieve the appropriate conformation for binding ligand [79]. Heat shock protein 90 (Hsp90) plays a central role in the formation of a multichaperone complex essential for stabilizing steroid receptors in a conformation receptive to ligand [80, 81]. Hsp90 regulates the AR protein half-life by forming conformation-dependent higher-order chaperone complexes. Hsp90 inhibition prevents the ligand-dependent nuclear translocation of AR, suggesting a role for Hsp90 in the nuclear import of AR [82].
HDAC6 reversibly deacetylates Hsp90, modulating Hsp90 regulation of nuclear receptors, including AR and glucocorticoid receptor (GR) [10, 83, 84]. Inactivation of HDAC6 results in the accumulation of acetylated Hsp90, which no longer forms a stable complex with GR, leading to defective GR ligand binding, nuclear translocation, and transactivation [10]. These findings strongly implicate HDAC6-mediated acetylation/deacetylation of Hsp90 as a potential mechanism regulating steroid hormone signaling. AR forms chaperone complexes with Hsp90 [85]. Recently, it was reported that HDAC6 is required for stabilization of AR protein [86], Ai et al. demonstrated that inactivation of HDAC6 inhibited AR nuclear localization and subsequent transactivation in PC and mouse embryonic fibroblast (MEF) cells [87]. Reexpressing HDAC6 or a deacetylation-mimic Hsp90 mutant alleviated the inhibition. Furthermore, HDAC6 knockdown also inhibited the establishment of C4-2 xenograft tumors in castrated, but not testis-intact, nude mice. These findings together provide evidence for an important role for HDAC6 in AR hypersensitivity and nuclear localization in castration-resistant PC cells, and thus HDAC6 is a very important target which can be exploited in CRPC treatment.
4.1.2. HDAC Inhibitors
To date, SAHA and romidepsin are the only FDA-approved HDAC inhibitors (Figure 6) [88, 89].
Figure 6: FDA-approved HDAC inhibitors.
On a general note, HDAC inhibitors cause histone hyperacetylation, activating many genes, which leads to growth inhibition, differentiation, or apoptosis [73]. Clinical outcome with HDAC inhibitors to fight prostate cancer has yielded disappointing results. However, HDAC inhibitor therapy in prostate cancer still holds great promise due to recent developments. A recent report showed that class I HDACs are essential coactivators of AR (Table 2) [90]. Two widely used HDAC inhibitors, SAHA and LBH589, block transcriptional activation of many AR targets, such as TMPRSS2-ERG [90]. This effect was recapitulated by siRNA to HDAC1, and, to a lesser extent, by siRNA to HDAC3 [90]. Further, Welsbie et al. also showed that these HDAC inhibitors do not block AR recruitment to its targets, rather, they suppress AR target gene activation by blocking the recruitment of AR coactivators and RNA polymerase II [90]. These findings highlight the need for more specific and less toxic HDAC inhibitors in the treatment of PC.
Table 2: List of HDACs that play a role in AR signaling.
Some of the HDAC inhibitors serve the dual functions of disrupting AR signaling and reducing AR protein levels in the cell. Multiple reports have shown that HDAC inhibitors suppress AR expression [11, 9092]. Gibbs et al. reported that sulforaphane—an important constituent in cruciferous vegetarian diet, enhances HSP90 acetylation through HDAC6 inactivation, which leads to disruption of AR binding to HSP90, eventual AR degradation, and reduced expression of AR target genes [93]. Unlike other compounds with HDAC inhibitory function, sulforaphane treatment led to reduced AR binding to its target gene AREs [93]. To sum up, HDAC inhibitors, including compounds such as sulforaphane with effects on HDAC6, inhibit prostate cancer cell growth, which is at least partially explained by effects on AR signaling. Isoform-selective HDAC inhibitors are of great interest as candidate therapeutic agents with few side effects.
Kang et al. [95] showed that transcriptional activation by AR is accompanied by a cascade of distinct covalent histone modifications. Korkmaz et al. [96] studied the role of histone acetylation on AR function. Using three independent HDAC inhibitors: depsipeptide (FR901228), sodium butyrate (NaB), and TSA, they found that inhibition of HDAC activity caused significantly increase in the transcription ability of AR in the LNCaP cell. They found dose-dependent effects of NaB and depsipeptide on AR activity: low doses caused increase in levels of PSA mRNA, whereas high doses of NaB completely inhibited PSA expression. This implies that HDAC inhibitors repress both AR expression and AR-dependent expression of PSA in a dose-dependent manner [96, 97]. Another mechanism of AR suppression by HDAC inhibitors was shown by Welsbie et al. [90]. HDAC inhibitors, vorinostat (SAHA), and LBH589 block AR activity through suppression of the coactivator/RNA polymerase II complex assembly after binding of AR to the promoters of target genes. Rokhlin et al. [91] found that TSA sharply reduced AR gene expression after 24 hours treatment, with partial recovery after 48 hours and returned to normal levels after 72 hours later.
4.2. SUMO-1 (Small Ubiquitin-Like Modifier-1)
The SUMO-1 modification (sumoylation) pathway resembles that of ubiquitin conjugation, but the enzymes involved in the two processes are distinct [98]. SUMO-1 (also known as sentrin, GMP1, PIC1, and Ubl1, or in yeast as Smt3) is activated for conjugation by E1 enzymes and subsequently transferred to the E2-conjugating enzyme Ubc9 [99]. Sumoylation is reversible [100]. The sumoylation appears to play multiple roles, including (i) protein targeting, (ii) protein stabilization, and (iii) transcriptional activation. Poukka et al. showed that AR is covalently modified by SUMO-1. They identified that sumoylation sites are present in the N-terminal domain of AR, and they further showed that the SUMO-1 modification in certain contexts indeed inhibits the activity of AR [26].
4.3. N-CoR and SMRT
N-CoR and SMRT are well characterized corepressors. Given the evidence that SMRT and NCoR form complexes with HDAC3 [76, 101, 102], these corepressors could have an additive effect on the inhibition of transcription and histone acetylation. However, despite the roles of SMRT and NCoR in regulating the transcriptional activity of several nuclear receptors, the significance of SMRT and/or NCoR on AR transcriptional activity is less clear. Both SMRT and NCoR proteins interact with AR. The AR specific domain binds to the PSA promoter or to various AREs of AR target genes [97, 103]. Trtková et al. analyzed the binding of AR-SMRT complex to PSA promoter and/or binding AR alone to PSA promoter using various NaB concentrations. The ChIP analysis coupled with qPCR of LNCaP and C4-2 cells demonstrated that NaB promoted the formation of the AR-SMRT complex [104]. In summary, N-CoR and SMRT also provide additional epigenetic targets which need to be explored.
4.4. Histone Methylation and Demethylases
Histone methylation was originally thought to be a stable, irreversible mark as only histone methyltransferases had been identified with no known data about demethylases. However, the discovery of the first histone demethylase LSD1 (lysine-specific demethylase 1) confirmed that histone methylation is reversible [105, 106]. The status of histone lysine methylation has been shown to be important for AR signaling, and several histone demethylase proteins are upregulated in prostate cancer. These include LSD1 and the Jumonji class of proteins [107109]. While the transcriptional targets of these proteins are largely unknown, these proteins complex with AR and facilitate its activation of downstream signaling pathways. While LSD1 may demethylate the active dimethyl lysine 4 (2MK4) mark on histone H3, which leads to reduced gene expression of AR-regulated genes, several reports show that LSD1 binds to AREs, the site where AR binds to the DNA and facilitates demethylation of the repressive mono-(1MK9) and dimethyl lysine 9 (2MK9) marks on histone H3 upon recruitment of ligand-bound AR, which results in transcriptional derepression [107, 108]. Given the importance of these enzymes in the activation of AR target genes, inhibition of these enzymes may be a rational, nonhormonal strategy to disrupt AR signaling. MAOIs (monoamine oxidase inhibitors) and polyamine analogues are some of the currently known compounds that inhibit LSD1 activity [107]. These agents need to be further evaluated for their potential to treat prostate cancer.
5. Conclusions
Androgen deprivation has been the major therapy for prostate cancer for 7 decades. After a few months of ADT, PC progresses despite castrate serum levels of testosterone. We now have a greater understanding of the mechanisms of sustained AR signaling in these CRPCs that have progressed despite androgen deprivation. Cofactors such as HDACs, SUMO-1, N-CoR, and SMRT provide additional level of control of AR signaling. Upregulation of cofactors such as HDACs that facilitate AR target gene activation is an important event in the development of CRPC. Whether targeting histone deacetylases and other AR coactivators or AR protein stability will be safe and efficacious remains unknown, but their preclinical data holds a great promise. Most of the currently developed therapies targeting AR signaling aim at the LBD of AR. However, with the knowledge that AR NTD can function independent of AR LBD, newer therapies such as EPI-001 and decoy AR NTD are being developed to target AR NTD. All of these antiandrogens and HDAC inhibitors may show synergistic/additive activities when used in combination. There is a great interest to combine these agents to effectively treat CRPC.
References
1. ACS. American Cancer Society, “Prostate cancer key statistics,” 2010.
2. A. O. Brinkmann, P. W. Faber, H. C. J. van Rooij, et al., “The human androgen receptor: domain structure, genomic organization and regulation of expression,” Journal of Steroid Biochemistry, vol. 34, no. 1–6, pp. 307–310, 1989. View at Scopus
3. M. E. Taplin, “Drug insight: role of the androgen receptor in the development and progression of prostate cancer,” Nature Clinical Practice Oncology, vol. 4, no. 4, pp. 236–244, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
4. B. J. Feldman and D. Feldman, “The development of androgen-independent prostate cancer,” Nature Reviews Cancer, vol. 1, no. 1, pp. 34–45, 2001. View at Scopus
5. J. D. Debes and D. J. Tindall, “Mechanisms of androgen-refractory prostate cancer,” The New England Journal of Medicine, vol. 351, no. 15, pp. 1488–1490, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
6. H. I. Scher and C. L. Sawyers, “Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis,” Journal of Clinical Oncology, vol. 23, no. 32, pp. 8253–8261, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
7. E. A. Mostaghel, S. T. Page, D. W. Lin et al., “Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer,” Cancer Research, vol. 67, no. 10, pp. 5033–5041, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
8. Z. Guo, X. Yang, F. Sun et al., “A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth,” Cancer Research, vol. 69, no. 6, pp. 2305–2313, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
9. P. Bali, M. Pranpat, J. Bradner et al., “Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors,” Journal of Biological Chemistry, vol. 280, no. 29, pp. 26729–26734, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
10. J. J. Kovacs, P. J. M. Murphy, S. Gaillard et al., “HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor,” Molecular Cell, vol. 18, no. 5, pp. 601–607, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
11. L. Chen, S. Meng, H. Wang et al., “Chemical ablation of androgen receptor in prostate cancer cells by the histone deacetylase inhibitor LAQ824,” Molecular Cancer Therapeutics, vol. 4, no. 9, pp. 1311–1319, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
12. S. M. Dehm and D. J. Tindall, “Molecular regulation of androgen action in prostate cancer,” Journal of Cellular Biochemistry, vol. 99, no. 2, pp. 333–344, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
13. D. L. Bain, A. F. Heneghan, K. D. Connaghan-Jones, and M. T. Miura, “Nuclear receptor structure: implications for function,” Annual Review of Physiology, vol. 69, pp. 201–220, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
14. P. M. Matias, P. Donner, R. Coelho et al., “Structural evidence for ligand specificity in the binding domain of the human androgen receptor: implications for pathogenic gene mutations,” Journal of Biological Chemistry, vol. 275, no. 34, pp. 26164–26171, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
15. E. Hur, S. J. Pfaff, E. S. Payne, H. Grøn, B. M. Buehrer, and R. J. Fletterick, “Recognition and accommodation at the androgen receptor coactivator binding interface,” PLoS Biology, vol. 2, no. 9, p. E274, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
16. H. Faus and B. Haendler, “Post-translational modifications ofsteroid receptors,” Biomedicine and Pharmacotherapy, vol. 60, no. 9, pp. 520–528, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
17. Y. Shang, M. Myers, and M. Brown, “Formation of the androgen receptor transcription complex,” Molecular Cell, vol. 9, no. 3, pp. 601–610, 2002. View at Publisher · View at Google Scholar · View at Scopus
18. C. D. Chen, D. S. Welsbie, C. Tran et al., “Molecular determinants of resistance to antiandrogen therapy,” Nature Medicine, vol. 10, no. 1, pp. 33–39, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
19. B. He, J. A. Kemppainen, J. J. Voegel, H. Gronemeyer, and E. M. Wilson, “Activation function 2 in the human androgen receptor ligand binding domain mediates interdomain communication with the NH2-terminal domain,” Journal of Biological Chemistry, vol. 274, no. 52, pp. 37219–37225, 1999. View at Publisher · View at Google Scholar · View at Scopus
20. C. L. Bevan, S. Hoare, F. Claessens, D. M. Heery, and M. G. Parker, “The AF1 and AF2 domains of the androgen receptor interact with distinct regions of SRC1,” Molecular and Cellular Biology, vol. 19, no. 12, pp. 8383–8392, 1999. View at Scopus
21. P. Alen, F. Claessens, G. Verhoeven, W. Rombauts, and B. Peeters, “The androgen receptor amino-terminal domain plays a key role in p160 coactivator-stimulated gene transcription,” Molecular and Cellular Biology, vol. 19, no. 9, pp. 6085–6097, 1999. View at Scopus
22. L. Callewaert, N. van Tilborgh, and F. Claessens, “Interplay between two hormone-independent activation domains in the androgen receptor,” Cancer Research, vol. 66, no. 1, pp. 543–553, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
23. J. A. Simental, M. Sar, M. V. Lane, F. S. French, and E. M. Wilson, “Transcriptional activation and nuclear targeting signals of the human androgen receptor,” Journal of Biological Chemistry, vol. 266, no. 1, pp. 510–518, 1991. View at Scopus
24. D. N. Lavery and I. J. McEwan, “The human androgen receptor AF1 transactivation domain: interactions with transcription factor IIF and molten-globule-like structural characteristics,” Biochemical Society Transactions, vol. 34, part 6, pp. 1054–1057, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
25. H. Dotzlaw, U. Moehren, S. Mink, A. C. B. Cato, J. A. I. Lluhí, and A. Baniahmad, “The amino terminus of the human AR is target for corepressor action and antihormone agonism,” Molecular Endocrinology, vol. 16, no. 4, pp. 661–673, 2002. View at Publisher · View at Google Scholar
26. H. Poukka, U. Karvonen, O. A. Jänne, and J. J. Palvimo, “Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1),” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 26, pp. 14145–14150, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
27. G. Verrijdt, A. Haelens, and F. Claessens, “Selective DNA recognition by the androgen receptor as a mechanism for hormone-specific regulation of gene expression,” Molecular Genetics and Metabolism, vol. 78, no. 3, pp. 175–185, 2003. View at Publisher · View at Google Scholar · View at Scopus
28. D. Gioeli, S. B. Ficarro, J. J. Kwiek et al., “Androgen receptor phosphorylation. Regulation and identification of the phosphorylation sites,” Journal of Biological Chemistry, vol. 277, no. 32, pp. 29304–29314, 2002. View at Scopus
29. M. Marcelli, D. L. Stenoien, A. T. Szafran et al., “Quantifying effects of ligands on androgen receptor nuclear translocation, intranuclear dynamics, and solubility,” Journal of Cellular Biochemistry, vol. 98, no. 4, pp. 770–788, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
30. F. Claessens, G. Verrijdt, E. Schoenmakers et al., “Selective DNA binding by the androgen receptor as a mechanism for hormone-specific gene regulation,” Journal of Steroid Biochemistry and Molecular Biology, vol. 76, no. 1–5, pp. 23–30, 2001. View at Publisher · View at Google Scholar · View at Scopus
31. C. K. Glass and M. G. Rosenfeld, “The coregulator exchange in transcriptional functions of nuclear receptors,” Genes and Development, vol. 14, no. 2, pp. 121–141, 2000. View at Scopus
32. M. G. Rosenfeld, V. V. Lunyak, and C. K. Glass, “Sensors and signals: a coactivator/corepressor/epigenetic code for integrating signal-dependent programs of transcriptional response,” Genes and Development, vol. 20, no. 11, pp. 1405–1428, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
33. M. M. Centenera, J. M. Harris, W. D. Tilley, and L. M. Butler, “The contribution of different androgen receptor domains to receptor dimerization and signaling,” Molecular Endocrinology, vol. 22, no. 11, pp. 2373–2382, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
34. W. B. Peeling, “Phase III studies to compare goserelin (Zoladex) with orchiectomy and with diethylstilbestrol in treatment of prostatic carcinoma,” Urology, vol. 33, no. 5, pp. 45–52, 1989. View at Scopus
35. J. Seidenfeld, D. J. Samson, V. Hasselblad et al., “Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis,” Annals of Internal Medicine, vol. 132, no. 7, pp. 566–577, 2000. View at Scopus
36. R. J. Santen, H. van sen Bossche, J. Symoens, J. Brugmans, and R. DeCoster, “Site of action of low dose ketoconazole on androgen biosynthesis in men,” Journal of Clinical Endocrinology and Metabolism, vol. 57, no. 4, pp. 732–736, 1983.
37. E. J. Small, A. Baron, and R. Bok, “Simultaneous antiandrogen withdrawal and treatment with ketoconazole and hydrocortisone in patients with advanced prostate carcinoma,” Cancer, vol. 80, no. 9, pp. 1755–1759, 1997. View at Publisher · View at Google Scholar · View at Scopus
38. E. J. Small, A. D. Baron, L. Fippin, and D. Apodaca, “Ketoconazole retains activity in advanced prostate cancer patients with progression despite flutamide withdrawal,” Journal of Urology, vol. 157, no. 4, pp. 1204–1207, 1997. View at Publisher · View at Google Scholar · View at Scopus
39. E. J. Small, S. Halabi, N. A. Dawson et al., “Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583),” Journal of Clinical Oncology, vol. 22, no. 6, pp. 1025–1033, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
40. M. G. Rowlands, S. E. Barrie, F. Chan et al., “Esters of 3-pyridylacetic acid that combine potent inhibition of 17α- hydroxylase/C17,20-lyase (cytochrome P45017α) with resistance to esterase hydrolysis,” Journal of Medicinal Chemistry, vol. 38, no. 21, pp. 4191–4197, 1995. View at Publisher · View at Google Scholar · View at Scopus
41. G. Attard, A. H. M. Reid, T. A. Yap et al., “Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven,” Journal of Clinical Oncology, vol. 26, no. 28, pp. 4563–4571, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
42. C. J. Ryan, M. R. Smith, L. Fong et al., “Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy,” Journal of Clinical Oncology, vol. 28, no. 9, pp. 1481–1488, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
43. A. H. Reid, G. Attard, D. C. Danila et al., “Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate,” Journal of Clinical Oncology, vol. 28, no. 9, pp. 1489–1495, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
44. Abiraterone Acetate in Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy, http://www.clinicaltrials.gov.
45. T. S. Vasaitis, R. D. Bruno, and V. C. O. Njar, “CYP17 inhibitors for prostate cancer therapy,” Journal of Steroid Biochemistry and Molecular Biology, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
46. T. Vasaitis, A. Belosay, A. Schayowitz et al., “Androgen receptor inactivation contributes to antitumor efficacy of 17α-hydroxylase/17,20-lyase inhibitor 3β-hydroxy-17-(1H- benzimidazole-1-yl)androsta-5,16-diene in prostate cancer,” Molecular Cancer Therapeutics, vol. 7, no. 8, pp. 2348–2357, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
47. A. Schayowitz, G. Sabnis, V. C. O. Njar, and A. M. H. Brodie, “Synergistic effect of a novel antiandrogen, VN/124-1, and signal transduction inhibitors in prostate cancer progression to hormone independence in vitro,” Molecular Cancer Therapeutics, vol. 7, no. 1, pp. 121–132, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
48. ARMOR1: Study of TOK-001 to Treat Castration Resistant Prostate Cancer, http://www.clinicaltrials.gov.
49. M. C. Hodgson, I. Astapova, A. N. Hollenberg, and S. P. Balk, “Activity of androgen receptor antagonist bicalutamide in prostate cancer cells is independent of NCoR and SMRT corepressors,” Cancer Research, vol. 67, no. 17, pp. 8388–8395, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
50. M. Gaillard-Moguilewsky, “Pharmacology of antiandrogens and value of combining androgen suppression with antiandrogen therapy,” Urology, vol. 37, no. 2, pp. 5–12, 1991. View at Scopus
51. J. Anderson, “The role of antiandrogen monotherapy in the treatment of prostate cancer,” BJU International, vol. 91, no. 5, pp. 455–461, 2003. View at Publisher · View at Google Scholar · View at Scopus
52. P. Iversen, “Quality of life issues relating to endocrine treatment options,” European Urology, vol. 36, supplement 2, pp. 20–26, 1999. View at Publisher · View at Google Scholar · View at Scopus
53. O. Dalesio, H. van Tinteren, M. Clarke, R. Peto, and F. H. Schroder, “Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials,” The Lancet, vol. 355, no. 9214, pp. 1491–1498, 2000.
54. D. Gillatt, “Antiandrogen treatments in locally advanced prostate cancer: are they all the same?” Journal of Cancer Research and Clinical Oncology, vol. 132, supplement 1, pp. S17–S26, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
55. O. Dalesio, H. van Tinteren, L. Denis, et al., “Maximum androgen blockade in advanced prostate cancer: an overview of 22 randomised trials with 3283 deaths in 5710 patients,” The Lancet, vol. 346, no. 8970, pp. 265–269, 1995.
56. T. S. Vasaitis and V. C. Njar, “Novel, potent anti-androgens of therapeutic potential: recent advances and promising developments,” Future Medicinal Chemistry, vol. 2, no. 4, pp. 667–680, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
57. H. I. Scher, T. M. Beer, C. S. Higano, et al., “Antitumor activity of MDV3100 in a phase I/II study of castration-resistant prostate cancer (CRPC),” in Proceedings of the ASCO Annual Meeting, 2009.
58. B. Carver, C. Chapinski, J. Wongvipat, et al., “Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer,” Cancer Cell, vol. 19, no. 5, pp. 575–586, 2011. View at Publisher · View at Google Scholar · View at PubMed
59. Z. Guo, B. Dai, T. Jiang et al., “Regulation of androgen receptor activity by tyrosine phosphorylation,” Cancer Cell, vol. 10, no. 4, pp. 309–319, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
60. K. R. Lamont and D. J. Tindall, “Minireview: alternative activation pathways for the androgen receptor in prostate cancer,” Molecular Endocrinology, vol. 25, no. 6, pp. 897–907, 2011. View at Publisher · View at Google Scholar · View at PubMed
61. P. A. Watson, Y. F. Chen, M. D. Balbas et al., “Constitutively active androgen receptor splice variants expressed in castration-resistant prostate cancer require full-length androgen receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 39, pp. 16759–16765, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
62. S. M. Dehm and D. J. Tindall, “Ligand-independent androgen receptor activity is activation function-2-independent and resistant to antiandrogens in androgen refractory prostate cancer cells,” Journal of Biological Chemistry, vol. 281, no. 38, pp. 27882–27893, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
63. M. D. Sadar, “Androgen-independent induction of prostate-specific antigen gene expression via cross-talk between the androgen receptor and protein kinase A signal transduction pathways,” Journal of Biological Chemistry, vol. 274, no. 12, pp. 7777–7783, 1999. View at Publisher · View at Google Scholar · View at Scopus
64. T. Ueda, N. R. Mawji, N. Bruchovsky, and M. D. Sadar, “Ligand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells,” Journal of Biological Chemistry, vol. 277, no. 41, pp. 38087–38094, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
65. S. N. Quayle, N. R. Mawji, J. Wang, and M. D. Sadar, “Androgen receptor decoy molecules block the growth of prostate cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 4, pp. 1331–1336, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
66. M. D. Sadar, D. E. Williams, N. R. Mawji et al., “Sintokamides A to E, chlorinated peptides from the sponge Dysidea sp. that inhibit transactivation of the N-terminus of the androgen receptor in prostate cancer cells,” Organic Letters, vol. 10, no. 21, pp. 4947–4950, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
67. L. P. Freedman, “Increasing the complexity of coactivation in nuclear receptor signaling,” Cell, vol. 97, no. 1, pp. 5–8, 1999. View at Scopus
68. M. Esteller, “Molecular origins of cancer: epigenetics in cancer,” The New England Journal of Medicine, vol. 358, no. 11, pp. 1148–1159, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
69. K. Luger, A. W. Mäder, R. K. Richmond, D. F. Sargent, and T. J. Richmond, “Crystal structure of the nucleosome core particle at 2.8 Å resolution,” Nature, vol. 389, no. 6648, pp. 251–260, 1997. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
70. T. Jenuwein and C. D. Allis, “Translating the histone code,” Science, vol. 293, no. 5532, pp. 1074–1080, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
71. B. T. Scroggins, K. Robzyk, D. Wang et al., “An acetylation site in the middle domain of Hsp90 regulates chaperone function,” Molecular Cell, vol. 25, no. 1, pp. 151–159, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
72. X. Zhou, P. A. Marks, R. A. Rifkind, and V. M. Richon, “Cloning and characterization of a histone deacetylase, HDAC9,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 19, pp. 10572–10577, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
73. P. A. Marks, R. A. Rifkind, V. M. Richon, R. Breslow, T. Miller, and W. K. Kelly, “Histone deacetylases and cancer: causes and therapies,” Nature Reviews Cancer, vol. 1, no. 3, pp. 194–202, 2001. View at Scopus
74. K. Halkidou, L. Gaughan, S. Cook, H. Y. Leung, D. E. Neal, and C. N. Robson, “Upregulation and nuclear recruitment of HDACl in hormone refractory prostate cancer,” Prostate, vol. 59, no. 2, pp. 177–189, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
75. A. Verdel, S. Curtet, M. P. Brocard et al., “Active maintenance of mHDA2/mHDAC6 histone-deacetylase in the cytoplasm,” Current Biology, vol. 10, no. 12, pp. 747–749, 2000. View at Publisher · View at Google Scholar · View at Scopus
76. Y. Zhang, B. Gilquin, S. Khochbin, and P. Matthias, “Two catalytic domains are required for protein deacetylation,” Journal of Biological Chemistry, vol. 281, no. 5, pp. 2401–2404, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
77. S. J. Haggarty, K. M. Koeller, J. C. Wong, C. M. Grozinger, and S. L. Schreiber, “Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 8, pp. 4389–4394, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
78. C. Hubbert, A. Guardiola, R. Shao et al., “HDAC6 is a microtubule-associated deacetylase,” Nature, vol. 417, no. 6887, pp. 455–458, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
79. J. J. Kovacs, T. J. Cohen, and T. P. Yao, “Chaperoning steroid hormone signaling via reversible acetylation,” Nuclear Receptor Signaling, vol. 3, Article ID e004, 4 pages, 2005. View at Publisher · View at Google Scholar · View at PubMed
80. W. B. Pratt and D. O. Toft, “Steroid receptor interactions with heat shock protein and immunophilin chaperones,” Endocrine Reviews, vol. 18, no. 3, pp. 306–360, 1997. View at Publisher · View at Google Scholar · View at Scopus
81. D. B. DeFranco, C. Ramakrishnan, and Y. Tang, “Molecular chaperones and subcellular trafficking of steroid receptors,” Journal of Steroid Biochemistry and Molecular Biology, vol. 65, no. 1–6, pp. 51–58, 1998. View at Publisher · View at Google Scholar · View at Scopus
82. V. Georget, B. Térouanne, J. C. Nicolas, and C. Sultan, “Mechanism of antiandrogen action: key role of hsp90 in conformational change and transcriptional activity of the androgen receptor,” Biochemistry, vol. 41, no. 39, pp. 11824–11831, 2002. View at Publisher · View at Google Scholar · View at Scopus
83. S. Aoyagi and T. K. Archer, “Modulating molecular chaperone Hsp90 functions through reversible acetylation,” Trends in Cell Biology, vol. 15, no. 11, pp. 565–567, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
84. V. D. Kekatpure, A. J. Dannenberg, and K. Subbaramaiah, “HDAC6 modulates Hsp90 chaperone activity and regulates activation of aryl hydrocarbon receptor signaling,” Journal of Biological Chemistry, vol. 284, no. 12, pp. 7436–7445, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
85. Y. Fang, A. E. Fliss, D. M. Robins, and A. J. Caplan, “Hsp90 regulates androgen receptor hormone binding affinity in vivo,” Journal of Biological Chemistry, vol. 271, no. 45, pp. 28697–28702, 1996. View at Publisher · View at Google Scholar · View at Scopus
86. S. Basak, D. Pookot, E. J. Noonan, and R. Dahiya, “Genistein down-regulates androgen receptor by modulating HDAC6-Hsp90 chaperone function,” Molecular Cancer Therapeutics, vol. 7, no. 10, pp. 3195–3202, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
87. J. Ai, Y. Wang, J. A. Dar et al., “HDAC6 regulates androgen receptor hypersensitivity and nuclear localization via modulating Hsp90 acetylation in castration-resistant prostate cancer,” Molecular Endocrinology, vol. 23, no. 12, pp. 1963–1972, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
88. M. Duvic, R. Talpur, X. Ni et al., “Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL),” Blood, vol. 109, no. 1, pp. 31–39, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
89. J. M. Wagner, B. Hackanson, M. Lübbert, and M. Jung, “Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy,” Clinical Epigenetics, vol. 1, no. 3-4, pp. 117–136, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
90. D. S. Welsbie, J. Xu, Y. Chen et al., “Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer,” Cancer Research, vol. 69, no. 3, pp. 958–966, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
91. O. W. Rokhlin, R. B. Glover, N. V. Guseva, A. F. Taghiyev, K. G. Kohlgraf, and M. B. Cohen, “Mechanisms of cell death induced by histone deacetylase inhibitors in androgen receptor-positive prostate cancer cells,” Molecular Cancer Research, vol. 4, no. 2, pp. 113–123, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
92. D. L. Marrocco, W. D. Tilley, T. Bianco-Miotto et al., “Suberoylanilide hydroxamic acid (vorinostat) represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer cell proliferation,” Molecular Cancer Therapeutics, vol. 6, no. 1, pp. 51–60, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
93. A. Gibbs, J. Schwartzman, V. Deng, and J. Alumkal, “Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 39, pp. 16663–16668, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
94. H. Y. Lin, C. S. Chen, S. P. Lin, J. R. Weng, and C. S. Chen, “Targeting histone deacetylase in cancer therapy,” Medicinal Research Reviews, vol. 26, no. 4, pp. 397–413, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
95. Z. Kang, O. A. Jänne, and J. J. Palvimo, “Coregulator recruitment and histone modifications in transcriptional regulation by the androgen receptor,” Molecular Endocrinology, vol. 18, no. 11, pp. 2633–2648, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
96. C. G. Korkmaz, K. Frønsdal, Y. Zhang, P. I. Lorenzo, and F. Saatcioglu, “Potentiation of androgen receptor transcriptional activity by inhibition of histone deacetylation—rescue of transcriptionally compromised mutants,” Journal of Endocrinology, vol. 182, no. 3, pp. 377–389, 2004. View at Publisher · View at Google Scholar · View at Scopus
97. H. G. Yoon and J. Wong, “The corepressors silencing mediator of retinoid and thyroid hormone receptor and nuclear receptor corepressor are involved in agonist- and antagonist-regulated transcription by androgen receptor,” Molecular Endocrinology, vol. 20, no. 5, pp. 1048–1060, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
98. F. Melchior, “SUMO—nonclassical ubiquitin,” Annual Review of Cell and Developmental Biology, vol. 16, pp. 591–626, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
99. J. M. P. Desterro, M. S. Rodriguez, G. D. Kemp, and R. T. Hay, “Identification of the enzyme required for activation of the small ubiquitin-like protein SUMO-1,” Journal of Biological Chemistry, vol. 274, no. 15, pp. 10618–10624, 1999. View at Publisher · View at Google Scholar · View at Scopus
100. D. Mukhopadhyay and M. Dasso, “Modification in reverse: the SUMO proteases,” Trends in Biochemical Sciences, vol. 32, no. 6, pp. 286–295, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
101. J. Li, J. Wang, J. Wang et al., “Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3,” EMBO Journal, vol. 19, no. 16, pp. 4342–4350, 2000. View at Scopus
102. H. G. Yoon, D. W. Chan, Z. Q. Huang et al., “Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1,” EMBO Journal, vol. 22, no. 6, pp. 1336–1346, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
103. G. Liao, L. Y. Chen, A. Zhang et al., “Regulation of androgen receptor activity by the nuclear receptor corepressor SMRT,” Journal of Biological Chemistry, vol. 278, no. 7, pp. 5052–5061, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
104. K. Trtková, L. Pašková, N. Matiješčuková, and Z. Kolář, “Formation of AR-SMRT binding in prostate cancer cells treated with natural histone deacetylase inhibitor,” Cancer Biomarkers, vol. 7, no. 2, pp. 79–90, 2010. View at Publisher · View at Google Scholar · View at PubMed
105. Y. Shi, F. Lan, C. Matson et al., “Histone demethylation mediated by the nuclear amine oxidase homolog LSD1,” Cell, vol. 119, no. 7, pp. 941–953, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
106. L. Gao and J. Alumkal, “Epigenetic regulation of androgen receptor signaling in prostate cancer,” Epigenetics, vol. 5, no. 2, pp. 100–104, 2010. View at Publisher · View at Google Scholar · View at Scopus
107. E. Metzger, M. Wissmann, N. Yin et al., “LSD1 demethylates repressive histone marks to promote androgen-receptor- dependent transcription,” Nature, vol. 437, no. 7057, pp. 436–439, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
108. M. Wissmann, N. Yin, J. M. Müller, et al., “Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression,” Nature Cell Biology, vol. 9, no. 3, pp. 347–353, 2007.
109. Y. Xiang, Z. Zhu, G. Han et al., “JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 49, pp. 19226–19231, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
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The report on climate change by the council appointed by Prime Minister Manmohan Singh is likely to be announced in June, which will pave the way for a national policy on climate change.
India could lead the world in renewable energy technologies as part of a solution to the climate change crisis, said the former United States Vice-President, Al Gore.
Last year, the Intergovernmental Panel on Climate Change (IPCC) was awarded the Nobel Peace Prize along with Albert Gore Jr., sending a strong message about the importance of the world's future climate. Indeed, for two decades, international scientists and policy-makers contributing to the IPCC process have provided assessments of climate change science, impacts and mitigation, addressing one of the most far-reaching and complex challenges that society has ever faced. Yet this is no time for IPCC to rest on its laurels.
Scientific evidence on climate change leading to drying up of rivers in Gujarat is overwhelming, as it points to significant risks of water scarcity.
Gujarat is a waterstressed state going by the definition of such areas as those having water availability below 1700 cum/ca/annum (cubic meter per capita per year).
When R K Pachauri, chairman of the Intergovernmental Panel on Climate Change (IPCC) received the Nobel Peace Prize in December last year on behalf of the IPCC, which bagged the award jointly with Al Gore, he had clearly mentioned that he would first want to pay tribute to the thousands of experts and scientists who have contributed to the work of the panel over almost two decades. Two Puneites figure in the long list of experts who have contributed to the IPCC in the area of climate change. The Indian government has taken special cognizance of these scientists and Prime Minister Manmohan Singh has issued certificates "recognising their contribution.' Two MeT officers from Pune
Global warming is already taking its toll. In Darfur, where several hundred thousand people have died in recent years from the internal conflict, climate change has exacerbated water and land shortages (because of growing desertification), undermined agriculture, and fueled conflict over these scarce resources among the poor. March 2008
Studies show that soil fertilized with organic materials, such as compost, could increase the amount of stored carbon and potentially help slow down greenhouse emissions. Los Angeles, London, New Delhi, and Singapore (25 February, 2008)
The 18-hole golf course close to Nal Sarovar, that is driving an unfettered property development near the bird sanctuary, threatens to upset the delicate ecology there. Environmentalists say that the amount of fertilizers, pesticides, fungicides and other chemicals required to maintain this vast, artificially created, landscape is a threat to the bio-diversity of the lake. According to experts, the usage of chemicals in maintaining golf courses at times even exceeds the amount used in agriculture. With such intensive use, golf courses threaten to pollute ground and surface waters. Member of Intergovernmental Panel on Climate Change (IPCC) and IIM-A faculty Prof Priyadarshi Shukla says this type of projects causes gradual and irreversible damage which breaks sustainability, putting pressure on the ecosystem. "Our green assets are under threat with a lot of property deve l o p m e n t h ap p e n i n g closer to ecosystems. If special laws are made for SEZs, which are productive assets, special laws are also needed for luxury assets, our ecosystems,' he says. "The golf course is being developed as a private property, but that should not happen at the cost of the ecology of Nal. Development should take place without compromising on the existence and sustainability of the ecology' says Shukla. According to environmentalist Kandarp Kathju, the golf course is more detrimental to the health of Nal Sarovar than any other project coming up there, such as the Film City. "Nal Sarovar and its downstream water bodies are at the heart of the delicate ecological system of the area. Today's golf requires tabletop greenery and this requires pesticides and fertilizers to maintain the course,' he says. Golf courses also require huge amount of water, which can result in depletion of underground as well as surface water levels. The entire area of Nal Sarovar with 360 islets is extremely shallow and seldom more than two metres deep, most of which get submerged during monsoon. Traditionally, farmers in the area have used water from the lake for cultivation. There are around 20,000 buffaloes in surrounding villages that feed on the aquatic plants and grass on the edges of Sarovar eight months of the year."The pesticides are likely to flow into the water bodies, besides percolating into the water table. Not just the aquatic environment, but the entire ecology, of which local communities are an integral part, is facing the risk of toxic chemicals polluting the water bodies,' says Kathju. Shukla says, "Developing a market requires foresight, and it is time the policy makers started
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Why Not Raise Taxes On The Super-Wealthy?
By Frank Hill
American Attitude Towards Higher Taxation
One of the most illuminating and humorous comment ever made by a US politician came from the colorful Senator Russell B. Long of Louisiana (of course!)
He was the long-term running Chairman of the Senate Finance Committee from 1966-1981 who once said no one really ever wants to pay higher taxes. Instead, here's what they really want Congress to do:
'Don't tax you. Don't tax me. Tax that fellow behind that tree!'
He was a Southern Democrat who also understood that 'you can't have capitalism without capital!' as he once said as well...
He was a Democrat who understood that money does not grow on trees and it doesn't come free from countries such as China when we borrow from them. Would it be that the Democrat Party would return to such sound fiscal understanding sometime in the near future.
We have been intrigued and somewhat bemused by the following argument for a long, long time:
'We simply have to raise taxes on the wealthy in order to close this budget deficit!'
'Why?' we typically ask such people.
'Because it is the fair thing to do!' they usually throw back as well-worn bromide they have picked up along the way from college or MSNBC or one of their friends or colleagues.
Let's pick at this scab a little and see if a little logic might seep into this discussion perhaps:
1. When you are spending too much money in your household budget, what do you do first?
Precisely. You stop overspending your income first and right away! Sell your new car and buy a good used jalopy. Put your kids in public school and take them out of private school. No more vacations in Majorca when going to Dollywood is within a day's drive and back.
2. If a company you had invested in has been losing money because of poor management, do you keep shoveling your hard-earned money into it before or after they have committed to cleaning up their act and stop wasting so much of your money?
Afterwards, of course, silly. You would have to be a dumbbell of the first order to just open up your wallet and checkbook and say: 'Go ahead. Take it. Take ALL of it! I know you need more money to waste and fritter away so take mine. I don't need it or want it since I can't think of anything better I could do with it like cure cancer or solve world peace!'
3. If you had cut previous deals with advocates of higher taxes in Congress (Democrats), and then they had failed completely to ever cut any spending as a result of your 'deal made in good faith'...would you do it again without ironclad 100% guarantees that spending will be cut first before any higher taxes are collected?
Heck no! That would be more stupid than Charlie Brown going to kick the football held by Lucy after about 1000 times. Even conservative Republicans aren't that stupid! They may be thick as a brick but even an old dog that has been scalded a couple of times won't go near the stove anymore.
4. Just how much money are we talking about anyway when it comes to socking it to the wealthy? Will it come close to balancing the budget and delivering us to the utopian nirvana its advocates always seem to roar about?
Darned little revenue when it is compared to the sheer magnitude of what we are facing nowadays. If we went back to the higher tax rates just on the wealthy that were in place during the Clinton Administration, we can expect to maybe collect less than $60 billion per year for 10 years, assuming the wealthy are not smart enough to figure out how to shelter it from taxation anymore (which is highly doubtful).
Such 'bold thinking' (sic) would reduce our annual deficits from $1.2 trillion to maybe $1.140 trillion per year. About 5%. Per year. Congratulations for making this the biggest mountain out of the smallest molehill in history.
Here's our favorite 'unintended consequence' of raising taxes on business or other people who run a business or invest in them or own one:
'Each and every time taxes are raised on a business sector, they don't pay the tax. YOU DO! In the form of higher prices for the goods or services they provide. They just add that tax on to the price of everything they sell to you and then you pay a small part of it with each and every purchase.'
Keep in mind that while it might 'feel good' to stick it to 'The Man' or the rich people running big businesses or even small businesses, it will come back to haunt you in various and sundry ways. It always does.
To be absolutely honest about it, aside from the fact that we are not real fans of raising taxes to pay for more government and we don't think raising taxes will balance the budget when over-spending is our prime problem to begin with, we really could care less about what happens to the Hollywood stars, the Silicon Valley superstars or the NBA/NFL/MLB players who make $100 million in any given year. Or even just $10 million/year.
Super-wealthy people can more than take care of themselves...and they should. They should not be eligible for any taxpayer-funded support or subsidy or bailout whether it is in the form of Social Security payments down the road or Medicare which is subsidized at about an 85% clip today or any federally-sponsored bailout ever if they make the wrong business decisions and have to declare bankruptcy to get out of it.
If they voted for Obama, then they have given their assent to being taxed at higher rates. Maybe we should just let them get their wish. (But don't let any of the pro athletes transfer to play in the state of Florida like LeBron James did since Florida doesn't have an income tax...that is what is really 'not fair!')
The really odd thing, in a classic Mephistophelian 'Bargain with the Devil' sort of way, is that now we have conservative Republicans, Club for Growth and Tea Party members digging in their heels for a concrete 'No More Taxes On The Wealthy!' stance, even though a majority of people making over $100,000/year in annual income voted for President Obama on November 6! It is the truth...just saw it in some polling briefings recently.
The higher the income, and the more liberal the area such as Hollywood, San Francisco/Silicon Valley, Washington DC and New York City, the more likely it is that these wealthy people voted for President Obama over Mitt Romney for some reason.
Maybe we should just let them get their wish.
(Editor's Note: Frank Hill's resumé includes working as chief of staff for Senator Elizabeth Dole and Congressman Alex McMillan, serving on the House Budget Committee and serving on the Commission on Entitlement and Tax Reform. He takes on politics from a fiercely independent perspective at the blog Telemachus).
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Zangezur Copper & Molybdenum Combine Armenia’s largest taxpayer
PanARMENIAN.Net - As of 2012, Zangezur Copper and Molybdenum Combine topped the list of Armenia’s 1000 largest taxpayer, replenishing the state budget with AMD 31,7 bln against AMD 29,8bln of 2011.
According to the data published by RA State Revenue Committee, it is followed by ArmRosGazprom – over AMD 30,9 bln and K-Telecom CJSC (VivaCell-MTS) – AMD 21,7 bln, Alex Grig Co.Ltd. – over AMD 17,4 bln and ArmenTel CJSC (Beeline trademark) – about AMD 11,4 bln.
All of Armenia-based major commercial banks (21 banks) were included in the list of 1000 major taxpayers, replenishing the state budget with about AMD 25,8 bln against AMD 21,5 bln in 2011.
According to the report, 1000 major taxpayers of Armenia paid over AMD 558,5 bln against AMD 483,5 bln in 2011, with 16,6% growth reported.
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[155e] to search out the hidden truth of the thought of a famous man or, I should say, of famous men?
Theaetetus
Of course I shall be grateful, very grateful.
Socrates
Look round and see that none of the uninitiated is listening. The uninitiated are those who think nothing is except what they can grasp firmly with their hands, and who deny the existence of actions and generation and all that is invisible.
Theaetetus
Truly, Socrates, those you speak of are very stubborn
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[2] Let it then be taken to be the feeling in accordance with which one who has it is said to render a service to one who needs it, not in return for something nor in the interest of him who renders it, but in that of the recipient. And the favor will be great
if the recipient is in pressing need, or if the service or the times and circumstances are important or difficult, or if the benefactor is the only one, or the first who has rendered it, or has done so in the highest degree.
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Google Is Really Leaving China, Well 99.999% Chance
Mar 15, 2010 • 8:11 am | (0) by | Filed Under Other Google Topics
In mid-January Google said they are leaving China after being part of a hack by the Chinese government. Since then, Google has been trying to work out details with the Chinese government to stay. Part of Google's requirements to stay was to stop or limit the censorship required there, but it appears that Google and China cannot see eye to eye.
The Financial Times reported:
Google has drawn up detailed plans for the closure of its Chinese search engine and is now "99.9 per cent" certain to go ahead as talks over censorship with the Chinese authorities have reached an apparent impasse, according to a person familiar with the company’s thinking.
Pulling out of China has huge financial concerns for Google.
Google's executives have made it clear that they still hope to stay in the country, whatever the fate of Google.cn. "It's very important to know we are not pulling out of China," Eric Schmidt, Google’s chief executive, told the Financial Times at the time. "We have a good business in China. This is about the censorship rules, not anything else."
A WebmasterWorld thread takes issue with that last quote. Google first went into China fully aware about the censorship requirements. They complied with the Chinese government then, and now they are saying they will leave because of it?
Now China is pushing back even harder, warning Google partners that they must also leave if they do not comply with Chinese law.
Forum discussion at WebmasterWorld.
Previous story: Google's Real Time Results Too Spammy?
blog comments powered by Disqus
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Sunday, March 20, 2011
U.S. Dollar Devaluation and the I.M.F.
Dollar Devaluation, Protests, Riots, Gun Confescation, Civil War, Nuclear First Strike
by Brain Bender
IMF Calls for New World Reserve Currency
This week we were informed that the International Monetary Fund (IMF) is calling for a new world reserve currency. Since WW2, the Dollar (USD) filled that role. And with the USD as the world currency, the United States has had the luxury of expanding our global military presence and funding large social programs beyond what we could afford. When the US Congress appropriated money beyond revenues, the US Treasury simply issued bonds to the FED to sell on the world market. Because countries like Germany, China, and Japan had trade deficits with the US, and had lots of USD laying around, and because many resources like oil can only be purchased with USD (Petro-Dollar System), these countries are interested in maintaining a strong USD. Therefore, for the last 65 years, they have been induced into financing our yearly national deficits. However, now that the IMF is calling for a new World Reserve Currency, the Special Drawing Right (SDR), the Dollar and the US is doomed.
US Dollar Devaluation
I am not sure most people understand how precarious our economy is right now. Since the housing collapse in 2007-8 due to the Goldman Sachs fraud and the Bank of International Settlement "Basil II Accords", the only thing that has been propping up our economy thus far has been the TARP bailouts, Quantitative Easing, and Multinational Companies bringing in 1 Trillion in offshore profits tax-free and buying their own stock on the right hand, and selling off their stock options with the left. And finally, the fact that the USD is the world reserve currency.
Special Drawing Rights (SDR)
However, the TARP money is spent, Quantitative Easing has already devalued the USD since 2006. The last leg supporting the US economy is about to be cut out from under us by the IMF. The SDR is not new. Those who are acquainted with the power of the G20/World Bank/IMF/Bank of International Settlement have known about the SDR and have been watching for this move for some time. The US Postal Service has had its clerks converting USD into SDR to determine insurance rates for at least the last year.
Hyperinflation Not Necessary
Some doom and gloomers out there are claiming that the US is poised to experience massive hyperinflation like the Veimar Republic in the 1920's and Zimbabwe in 2000's. This may occur, I can't say for sure one way of another. My point, is that hyperinflation is not necessary to greatly damage our country. All we would need is 6-10$/gal gas. Since WTO, NAFTA, and GAD, the US has lost much of its manufacturing infrastructure, and we import much of our natural resources, including oil and food. If oil is priced in SDR in the near future, the demand for, and value of the USD will fall, and the price for oil will increase. With a higher price of gas, US companies will still be manufacturing and importing, but many in the US will not be able to afford to purchase basic necessities.
US Government Bankrupt
According to Wiki, there are over 50 million Americans receiving some sort of Federal Assistance through Medicare, Social Security, Disability, or Unemployment. As the dollar is devalued, the higher prices will stretch the poor in America to the breaking point. There will be more unemployment, more bankruptcies, and more home foreclosures. However eventually, there just won't be enough money to support all the poor and support our global military goals at the same time. The US can continue to print USD, but the value of the USD in relation to other currencies will continue to drop. High oil prices is all it takes to cause high food and energy prices.
Weak USD => Famine
If the USD is replaced by the SDR, and no longer accepted by foreign countries in exchange for natural resources or finished goods, I cannot see how the USD will not become even more devalued. And with the weak, devalued dollar, I just don't see how millions of Americans don't begin to go hungry. And hungry people, especially if government subsidies are cut, will set the stage for what happens next.
Famine => Protests => Riots
As we have seen on TV in many countries already, hungry people will peacefully take to the streets in demonstration just like Egypt, Great Britain, Greece, and Iran. With a great many demonstrators on the streets or our large cities like Chicago, it wouldn't take much for a handful of anarchists/agent provocateurs to break a few windows and torch a few cars to turn a peaceful demonstration into a riot. With a riot, comes police, and possibly military engagement against the citizenry to quell the violence. However, there is a difference between Egypt vs the US, and that is that while Egyptians had plenty of rocks to through, Americans have guns. If there are street clashes, I hope and pray that civil unrest does not break out all over the country.
Riots => Martial Law => Gun Confiscation => Civil War
With riots going in throughout the country, these could easily spill over into suburban areas. The national guard and US military will be called in to put down these insurrections, and will likely go door-to-door confiscating guns. If the US Government tries to enforce a policy of widespread gun confiscation, there would be all out civil war. The Federal Government has been encroaching on our civil liberties such as freedom of speech, press, religion, assembly, and from illegal searches and seizures for too long. While I am not so passionate on this one issue, I fear any further encroachment on the 2nd Amendment would be the straw that breaks the camel's back.
Soviet Union Staged its Own Death
Many American's hold the false belief that the Soviet Union fell in 1989. That would be a grave misconception. It is true that the Soviet Union was under great economic stress to keep up with the massive US military buildup during the Cold War as well as support millions of impoverished people in the Balkans and Kazakhstan. However, the Communists pulled off an ingenious ploy by faking their own death. So, all this time, what they really accomplished was cutting loose many impoverished countries which allowed them to concentrate even more money into the building of their Military Industrial Complex. However, the Russians still are very sensitive toward wealthier countries like the Ukraine and Georgia with pro-western governments. If Communist Russia really dies in 1989, then why is the US continuing to surround and provoke them, and why did Russia try to Assassinate the Prime Minister of Ukraine, decapitate the government of Poland, and invade Georgia in 2008.
Provoking the Great Russian Bear
I am sure, many will not forget the great drought and fires that burned all over Russia last summer. Weather you believe in weather modification/manipulation technology or not, is really not important. The issue at hand is, "do the Russian's believe that the US can modify the weather?" And, the feeling is that not only does Russia believe that the US directly caused the drought and fires in their country in 2010, they also believe the US has been secretly supporting Chechen Terrorism in the same way elements associated with the US are suspected of supporting Al Qaeda. The Russians also believe the the US was supporting mercenaries in Georgia, which led to conflict in 2008. Again, it doesn't matter what is true here, what matters is what the Russians believe is true. If the Russian government has bought into the conspiracy theory, then this suspicion will result in a response; true or false. The US is being framed.
Surprise Nuke Attack
If the IMF institutes the SDR this next year resulting in the further devaluation of the USD, we can expect demonstrations, riots, and martial law. If the imposition of martial law brings door-to-door gun confiscation, we will have civil war. If all this occurs in the next 2 years before the election, the time for Russia to attack, assuming President Obama looses the election, the window of opportunity to attack for the Russians will be before the inauguration of the newly elected president. The country will be divided, the the Russians and Chinese may feel like there is an opportunity to neutralize this constant annoyance of the US once and for all.
In their mind, the Globalists have convinced them that they could rid themselves of all nuclear weapons once and for all by everyone launching them at the US while we are divided and are not likely to have the capacity, ability, or will to counter attack. The Chinese have already demonstrated an EMP device, totally paralyzing a Cruise ship (Carnival Splendor) in the middle of the ocean. Later last year, we saw another missile launched by a Chinese submarine right off the coast of Los Angeles. The first action by China was before G20 in Korea in response to the US printing 1 Trillion USD to devalue its currency (QE2) and monetize its debt. The second action off Los Angeles was in response to Pres. Obama's visit to India.
Read the rest @ Brain Bender
Please also visit The Freedomist for more information on the Devaluation of our Dollar
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Ehlers-Danlos syndrome
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For the WikiPatient page for this topic, click here
Ehlers-Danlos syndrome
ICD-10 Q79.6
ICD-9 756.83
MedlinePlus 001468
MeSH D004535
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Overview
Ehlers-Danlos syndrome is a group of rare genetic disorders affecting humans and domestic animals caused by a defect in collagen synthesis. Depending on the individual mutation, the severity of the disease can vary from mild to life-threatening. There is no known cure. Treatment is supportive.
Historical Perspective
The disease is named after two doctors, Edward Ehlers of Denmark, and Henri-Alexandre Danlos of France, who identified it at the turn of the 20th century. [1]
Classification
In the past, there were more than 10 recognized types of Ehlers-Danlos syndrome. In 1997, researchers proposed a simpler classification that reduced the number of major types to six and gave them descriptive names.[2] These six major types are listed below. Other types of the condition may exist, but they have been reported only in single families or are not well characterized. Except for hypermobility, the specific mutations involved have been identified and they can be precisely identified by genetic testing; this is valuable due to a great deal of variation in individual presentation of symptoms which may confuse classification of individuals on purely symptomatic basis. In order of prevalence in the population, they are:
Name Number Description OMIM Gene(s)
Hypermobility type 3 Affects 1 in 10,000 to 15,000 and is caused by an autosomal dominant mechanism. Mutations in either of two separate genes (which are also involved in Vascular EDS and Tenascin-X deficiency EDS, respectively) may lead to this variant; it is the only type of EDS that cannot be diagnosed through skin / tissue samples but is rather diagnosed through use of clinical observations. Symptoms can include easy bruising, velvety-smooth skin, mildy hyperextensible skin, and loose, unstable joints. Joint dislocations and subluxations are common. Degenerative joint disease can occur; the pain associated with this condition is a serious complication. Unfortunately, pain medications are frequently underprescribed. Some individuals have mitral valve prolapse, which creates an increased risk for infective endocarditis during surgery, particularly dental surgery, as well as possibly progressing to a life-threatening degree of severity of the prognosis of mitral valve prolapse. 130020 COL3A1, TNXB
Classical types 1 and 2 Affects approximately 2 to 5 in 100,000 people. In addition to the joint and cardiac effects noted above for hypermobility, this variant is characterized by soft, highly elastic, velvety skin which may tear, bruise, or scar easily and/or be slow to heal, and which has a tendency to develop benign fatty growths as well as benign fibrous growths on pressure areas. Pregnancy can be life-threatening in this variant. It affects type-V collagen, as well as type I. 130000, 130010 COL5A1, COL5A2, COL1A1
Vascular type 4 Is an autosomal dominant defect in the type 3 collagen synthesis; affecting approximately 1 in 100,000 people, it is clinically serious, reducing life expectancy to around 40 years. Joint symptoms are usually limited to the fingers or toes, but the delicate skin noted above is joined by fragile blood vessel walls and organ membranes, with a tendency to rupture or develop aneurysms. Thin, translucent skin, Arterial/intestinal/uterine fragility or rupture, Extensive bruising, Characteristic facial appearance - Distinctive facial features are associated with this variant; large eyes, small chin, thin nose and lips, and may also have lobeless (attached) ears, midline (betwen the eyes) facial flattening. Along with the above characteristics, a majority have reported that they sleep with their eyes half (partially) open. Pregnancy can be life-threatening in this variant as well. 130050 COL3A1
Kyphoscoliosis type 6 Is an autosomal recessive defect due to deficiency of an enzyme called lysyl hydroxylase; it is very rare, with fewer than 60 cases reported. Symptoms include progressive scoliosis, progressive severe weakness of muscles, and fragile sclera. 225400, 229200 PLOD1
Arthrochalasis types 7A and 7B Is also very rare, with about 30 cases reported. This variant may result in very loose and unstable joints, including the hips, which may lead to early and/or severe osteoarthritis and fractures, and stretchy, fragile skin. It affects type-I collagen. 130060 COL1A1, COL1A2
Dermatosparaxis type 7C Also very rare, with about 10 cases reported. This variant combines the loose and unstable joints with extremely fragile skin which loses elasticity. 225410 ADAMTS2
It is very important to note that while the above symptomatology is clean and defined the disease itself rarely obeys these neat categorizations. Cross-over symptoms for all types are prevalent and lead to under-diagnosis or mis-diagnosis. No patient should assume or rely on the "fact" they have a certain type of EDS when cross-over symptoms are evident and can be life-threatening.
"The large number of distinct types of the Ehlers-Danlos syndrome that have already been identified indicates great heterogeneity, but clearly that heterogeneity is not exhausted by the present classification." [3] Examples of types of related syndromes other than those above reported in the medical literature include:
Pathophysiology
Genetics
Mutations in the ADAMTS2, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, PLOD1 and TNXB genes cause Ehlers-Danlos syndrome.
Mutations in these genes usually alter the structure, production, or processing of collagen or proteins that interact with collagen. Collagen provides structure and strength to connective tissue throughout the body. A defect in collagen can weaken connective tissue in the skin, bones, blood vessels, and organs, resulting in the features of the disorder.
Inheritance patterns depend on the type of Ehlers-Danlos syndrome. Most forms of the condition are inherited in an autosomal dominant pattern, which means only one of the two copies of the gene in question must be altered to cause the disorder. The minority are inherited in an autosomal recessive pattern, which means both copies of the gene must be altered for a person to be affected by the condition. Please refer to the summary for each type of Ehlers-Danlos syndrome for a discussion of its inheritance pattern.
Epidemiology and Demographics
The overall prevalence of all types of Ehlers-Danlos syndrome may be about 1 in 5,000 births worldwide. The prevalence of the six types differs dramatically. The most common are the hypermobile forms (the classical and hypermobility types). Other forms are very rare. For example, fewer than 10 infants and children with the dermatosparaxis type have been described worldwide. It affects both males and females of all racial and ethnic backgrounds.
Diagnosis
Symptoms
Symptoms vary widely based on which type of Ehlers Danlos Syndrome (EDS) the patient has. In each case, however, the symptoms are ultimately due to faulty or reduced amounts of collagen. For example, in the most common type of EDS, Hypermobility Type, symptoms often include unstable, flexible joints with a painful tendency to dislocate and subluxate. This is due to ligaments which, because they are lacking proper collagen--the molecule that provides strength to ligaments--are overly stretchable. The so-called Classic EDS Type features skin that forms cigarette-paper-like scars. Another type of collagen is usually responsible for lending strength to skin (and scars). The most serious type of EDS, Vascular EDS, can result in premature death via vascular (blood vessel) and organ rupture. [3] Again, another type collagen is necessary to give strength to the walls of blood vessels and the walls of hollow organs (such as the large bowel, aka colon). (It should be noted that Vascular EDS is also one of the most rare types of the disease.) See table below for a more extensive list of symptoms for each type of EDS. You will see some cross-over or similarity of symptoms among the various types. For instance, many of the types feature velvety or hyperextensible skin. In addition, persons with Hypermobility Type often have very stretchy ligements (leading to frequent subluxations/dislocations) while those with Vascular Type have ligaments that rupture.
See also
References
1. "Uncovered: How U.S. Health System Can Fail Even the Insured - A Woman Endures 16-Month Odyssey To Get a Diagnosis", John Carreyrou, Wall Street Journal, November 16, 2007
2. Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ (1998). "Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK)". Am J Med Genet 77 (1): 31-7. PMID 9557891.
3. Lawrence EJ (2005). "The clinical presentation of Ehlers-Danlos syndrome". Adv Neonatal Care 5 (6): 301-14. PMID 16338669.
External links
de:Ehlers-Danlos-Syndromnl:Syndroom van Ehlers-Danlossr:Елерс-Данлос синдром
fi:Ehlers-Danlosin syndrooma sv:Ehlers-Danlos syndrom
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learn more… | top users | synonyms
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Where to find a template for a general-purpose Independent Contractor Agreement?
We want to hire some freelancers in the US, Germany, Russia and Japan. The book "The Business of iPhone App Development" from Apress references an Imdependent Contractor Agreement template. The goal ...
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Ask Your Question
0
Calc problem when change data type
asked 2012-02-23 14:23:39 +0200
Jeferson
1 1 1
Hi all,
I have a problem with LO Calc.
I have copied/pasted an other table, from web, that contains text and monetary data, in text form. Then I've replaced the currency form to appear only as an integer, finally to change to monetary form to classify them.
Example: Was: R$ 5.321,00 To: 5321
But when I set monetary form LO Calc puts a character ' on each start of number, to make it literal, but they don't be text!!! They're numbers!!!
What can I do to shoot out this conversion???
Tks a lot
delete close flag offensive retag edit
1 Answer
Sort by » oldest newest most voted
1
answered 2012-02-23 18:57:09 +0200
drone27of1
216 6
updated 2012-02-23 19:02:19 +0200
Select the column
Click Data
Select Text to Columns...
Highlight the column and change the type from Text to Standard
You could also edit the cells one by one and remove the ' in front of the number
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Asked: 2012-02-23 14:23:39 +0200
Seen: 269 times
Last updated: Feb 23 '12
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Konstantin Kakaes:
Math and science can be hard to learn—and that’s OK. The proper job of a teacher is not to make it easy, but to guide students through the difficulty by getting them to practice and persevere. “Some of the best basketball players on Earth will stand at that foul line and shoot foul shots for hours and be bored out of their minds,” says Williams. Math students, too, need to practice foul shots: adding fractions, factoring polynomials. And whether or not the students are bright, “once they buy into the idea that hard work leads to cool results,” Williams says, you can work with them.
There are plenty of lines to cringe at in Kakaes' article. PJ Karafiol knocks down most of them in a great post that was eventually syndicated by Slate. (Good for Slate. Good for Karafiol.) Mr. Williams' metaphor deserves extra scrutiny, though. Here are just two of its most screwy aspects:
1. Drills aren't a basketball player's first, only, or most prominent experience with basketball. Drills come after a student has been sufficiently enticed by the game of basketball — either by watching it or playing it on the playground — to sign up for a more dedicated commitment. If a player's first, only, or most prominent experience with basketball is hours of free-throw and perimeter drills, she'll quit the first day — even if she's six foot two with a twenty-eight inch vertical and enormous potential to excel at and love the game.
2. Basketball players aren't bored shooting foul shots. Long before "math teacher" was on my resume, I was a lanky high school basketball player trying to get his foul shooting above 50%. I'd shoot for hours but I wouldn't get bored, as Williams suggests I must have been. That's because I knew my practice had a purpose. I knew where that practice would eventually be situated. I knew it would pay off in a game where I'd be called to the line for a shot that had consequences.
There is a place for drills and explanation in mathematics, as in basketball. But consider what little good they do in either arena if the student isn't first made aware of the larger, more enticing purposes they serve.
BTW. The worked examples literature leans heavily on De Groot's research into chess masters who, it turns out, have memorized an enormous number of board configurations relative to casual players. This is unsurprising in the same way it's unsurprising that professional basketball players practice their free throws much more often than amateurs. But it doesn't necessarily follow from either of those facts that the best way to start inducting new members into either of those groups is to force novice chess players to memorize board configurations for hours or new basketball players to shoot hours of free throws from the line.
BTW. Max Ray articulates a strong framework for technology use in the math classroom at the end of his recent post at the Math Forum.
2012 Jul 11. PJ Karafiol follows up.
Featured Comment.
Jeff de Varona:
Am I the only one who is reminded of The Karate Kid? Mr. Miagi has Daniel do crazy, de-contextualized drills without knowing their purpose. In the end it works (because it’s a movie), but in the meantime Daniel gets extremely frustrated and wants to give up. Perhaps if Mr. Miagi had made it more clear what the “cool results” would be or how he would be “painting the fence” and “sanding the floor” in a tournament, Daniel-san would have been more than happy to wax all his cars.
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Vol 8, No 3 (2012)
Vol. 8, No. 3, March 2012
Table of Contents
Articles
Benchmarking Electric Distribution Utilities in the Philippines PDF
Larry Blank, Doug Gegax, Benjamin Widner p3
Framing and Experimentation in Economic Policy: The Case of the New Deal Agricultural Regulation PDF
Ivan D. Trofimov p14
Tales of the Survivors: The Bumiputera Entrepreneurs’ Experience PDF
Suraiya Ishak, Ahmad Raflis Che Omar, Azhar Ahmad p25
Intercultural Relationship, Prejudice and Ethnocentrism in a Computer-Mediated Communication (CMC): A Time-Series Experiment PDF
Hasrina Mustafa, Hamidah A. Hamid, Jamilah Ahmad, Kamaliah Siarap p34
A Textual Analysis of the Coverage of SARS and the Image of China --- A Comparative Analysis PDF
Chia-ju Lin p49
Chinese People’s Understanding of the Korean Unification Issue PDF
Debin Zhan, Hun Kyung Lee p63
Functional Ability, Participation in Activities and Life Satisfaction of the Older People PDF
Nestor Pabiona Blace p75
The Effect of Process Writing Practice on the Writing Quality of Form One Students: A Case Study PDF
Majid Pour-Mohammadi, Mohamad Jafre Zainol Abidin, Cheong Lai Fong p88
Impact of Cultural Value System on the Personality Development of Ogoni Adolescents PDF
Mary Basil Nwoke p100
Better Policing through a Paradigm Shift in Public Perception of the Police PDF
Gopala Krishnan Sekharan Nair, Azyanee Luqman, Thenmolli Vadeveloo, Rasaya Marimuthu, Saravanan Shanmuggam p113
An Analysis of Double Impacts of Rural Clan in New Rural Construction PDF
Na Ning p118
Board of Directors and Capital Structure: Evidence from Leading Malaysian Companies PDF
Teh Boon Heng, Shabnam Azrbaijani, Ong Tze San p123
Communicational Role of Mosques Architecture PDF
Mandana Saniei, Ali Delavar p137
Exploring the Technology Transfer Mechanisms by the Multinational Corporations: A Literature Review PDF
Sazali Abdul Wahab, Raduan Che Rose, Suzana Idayu Wati Osman p142
The Influences of the Internalization of International Structure to Malaysia’s National Security PDF
Chen Ou p151
Historical and Religious Archeological Sites and Their Role in the Process of Touristic Attraction in Jordan (Madaba as a Case Study) PDF
Mohammad Nayef ALsarayreh, Marwan Ataf AL Dalaeen p156
An Empirical Study of Internet Use in Saudian's Small and Mediums Enterprises PDF
Mohammad. J. Adaileh p169
Coursebook Appraisal: Case of Hung Vuong University PDF
Luu Trong Tuan p192
Attitude of Students towards Technical Education in Osun State PDF
B.O. Lawal p208
Participation of Workers’ and Employers’ Organizations in Poverty Reduction Strategies in Uganda PDF
Gerald Kagambirwe Karyeija, Benon C. Basheka p218
Economic Analysis of Wheat Forecasting Analysis and Price Shocks in Wheat Market in Pakistan: A Survey PDF
Abdul Latif, Nadeem Bhatti, Ghulam Murtaza Maitlo, Muhammad Suhail Nazar, Faiz Muhammad Shaikh p225
The Significance Difference on Entrepreneurial Profile toward Entrepreneurial Personality in Micro and Small Business: Malaysia Creative Industry PDF
Muhammad Abi Sofian Abdul Halim, Shaladin Muda, Wan Abd Aziz Wan Mohd Amin, Ahmad Munir Mohd Salleh p236
Organizing the Tourism Line from Chenar Village to Tar Lake of Damavand, Iran PDF
Azita Rajabi, Taraneh Sanei p246
Impact of the Global Crisis on Overseas Workers and the Families-Left-Behind: A Snapshot of the Philippine Case PDF
Alfie Maria R. Custodio, Alvin P. Ang p251
Brief Analysis of Urban Ecological Civilization Construction PDF
Yanhua Liu p265
Social Protection and Poverty Reduction in Four Selected Southeast Asian Countries: An Analysis of the Healthcare Sector towards Pro-Poor Growth PDF
Senadjki Abdelhak, Jamalludin Sulaiman p270
Teaching of Symmetry at Mathematics Lessons in the First Forms of Azerbaijan Primary Schools PDF
Raisa Eldar Bagirova p285
Interest Rate Liberalization, Financial Development and Economic Growth in Nigeria (1970-2008) PDF
Elijah Udoh, Uchechi R. Ogbuagu p292
Interest in the Management Accounting Profession: Accounting Students’ Perceptions in Jordanian Universities PDF
Khaled Abed Hutaibat p303
An Assessment of the Extent of Integration, Application and Utilization of Web-Based Learning Systems in Post Basic Institutions in Nigeria PDF
Olaniyi Alaba Sofowora p317
Critical Evaluation of the New Rural-Urban Labor Mobility in China: Reasons and Effect of Rural-Urban Labor Migration on Urban and Rural Labor Market PDF
Lili Ma p321
The Effects of Text Length and Picture on Reading Comprehension of Iranian EFL Students PDF
Maryam Jalilehvand p329
Discussions on Strengthening the Practical Engineering Capabilities of Chemical Engineering Instructors PDF
Yu'e Qiu, Xiuling Zhang p338
This work is licensed under a Creative Commons Attribution 3.0 License.
Asian Social Science ISSN 1911-2017 (Print) ISSN 1911-2025 (Online)
Copyright © Canadian Center of Science and Education
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rgenoud (5.7-9)
0 users
R version of GENetic Optimization Using Derivatives.
http://sekhon.berkeley.edu/rgenoud/
http://cran.r-project.org/web/packages/rgenoud
A genetic algorithm plus derivative optimizer
Maintainer: Jasjeet Singh Sekhon
Author(s): Walter R. Mebane, Jr. <wmebane@umich.edu>, Jasjeet Singh Sekhon <sekhon@berkeley.edu>
License: GPL-3
Uses: snow
Reverse depends: anchors, corHMM, DiceOptim, FAiR, gamlss.util, ivivc, JOP, KrigInv, Matching, multinomRob, PKfit, qpcR
Reverse suggests: BARD, boolean, DiceKriging, fitdistrplus, MuFiCokriging, pnn, SPOT, Synth
Released 11 days ago.
12 previous versions
Ratings
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Related packages: dclone, caret, GAMBoost, varSelRF, gafit, kernlab, rgp, RSNNS, rminer, RInside, OpenCL, doSMP, ahaz, BARD, bcp, biglm, bigmemory, biopara, bnlearn, ccems(20 best matches, based on common tags.)
Search for rgenoud on google, google scholar, r-help, r-devel.
Visit rgenoud on R Graphical Manual.
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T 4 beginners – part 1 - [Export] Bnaya Eshet
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T 4 beginners – part 1 - [Export] Bnaya Eshet (Unpublished)
T 4 beginners – part 1T 4 beginners – part 1 this is the first post of a series that will focus on T4 template. this post discuss the T4 in general while the following pose will focus on the T4 practice. the code for this post can be found here. What is T4 template? T4 is sanding for Text Template Transformation Toolkit. T4 is all about automating code or content generation. the usual extension for T4 files is the *.tt When to use T4? whenever you identify repeatable pattern of code or conte...
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Insert Master-Detail Data using Transact-SQL
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Insert Master-Detail Data using Transact-SQL (Unpublished)
Many applications have components that connect, manage, and consume data from a database. If you are designing/building an application that connects to a database to continuously insert, update or delete data, you should keep in mind that each operation will need a round-trip to the database and will consume valuable resources (e.g., network traffic, memory, CPU, etc.). Microsoft SQL Server 2000 SQLXML allows among other things to manage batch operations in a database, which reduces significantly the need of more than one round-trip to a database. OpenXML is a Transact-SQL statement that allows to represent data in XML format and can be used to insert, update, and delete more than one row (represented by an element) in a table or group of tables.
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Montgomery County, MarylandEdit This Page
From FamilySearch Wiki
Revision as of 20:54, 15 November 2010 by Murphynw (Talk | contribs)
United States > Maryland > Montgomery County
Contents
County Courthouse
Executive Office Building
101 Monroe Street, 2nd Floor
Rockville, MD 20850
History
• Named for Richard Montgomery, general in the American Revolutionary War.
Parent County
• Created 6 September 1776 from Frederick County.
Boundary Changes
• 1791, portions of the county (including Georgetown) along with portions of Prince George's County were ceded to form District of Columbia.
Record Loss
Places/Localities
Populated Places
Cities
• Gaithersburg
• Rockville
• Takoma Park
Towns
• Barnesville
• Brookeville
• Chevy Chase
• Chevy Chase View
• Chevy Chase Village
• Garrett Park
• Glen Echo
• Kensington
• Laytonsville
• Poolesville
• Somerset
• Washington Grove
Villages & Special Tax Districts
• Chevy Chase Section Three
• Chevy Chase Section Five
• Drummond
• Friendship Heights
• Martin's Additions
• North Chevy Chase
• Oakmont
Census Districts
• Ashton-Sandy Spring
• Aspen Hill
• Bethesda
• Brookmont
• Burtonsville
• Cabin John
• Calverton
• Chevy Chase
• Clarksburg
• Cloverly
• Colesville
• Damascus
• Darnestown
• Fairland
• Forest Glen
• Friendship Village
• Germantown
• Hillandale
• Kemp Mill
• Montgomery Village
• North Bethesda
• North Kensington
• North Potomac
• Olney
• Potomac
• Redland
• Rossmoor
• Silver Spring
• South Kensington
• Travilah
• Wheaton-Glenmont
• White Oak
Communities
• Ashton
• Beallsville
• Boyds
• Derwood
• Dickerson
• Hyattstown
• Sandy Spring
• Shady Grove
Neighboring Counties
Frederick | Howard | Prince George's | Virginia counties: Arlington | Fairfax | Loudoun | District of Columbia
Resources
Cemeteries
• "Brown Family Cemetery, Montgomery County, Maryland," The American Genealogist, Vol. 51, No. 2 (Apr. 1975):110. FHL 973 D25aga v. 51
• Riggs, Ronald Paul and John Frederick Dorman. "Two Montgomery County, Maryland, Cemeteries," The American Genealogist, Vol. 50, No. 2 (Apr. 1974):91. FHL 973 D25aga v. 50 [Peter Family Cemetery and Offutt Family Cemetery.]
Census
Federal Census reports available 1790-1930 including slave and veterans schedules.
Church
Maryland State Archives' Guide to Maryland Religious Institutions identifies all churches known to have existed in Montgomery County, Maryland. It covers all denominations and includes record descriptions.
Court
Gazetteers
Immigration
• Coldham, Peter Wilson. "Intercepted Letters Relating to America 1777-1811," The Genealogist, Vol. 14, No. 2 (Fall 2000):184-200; Vol. 15, No. 1 (Spring 2001):53-74. [Overseas correspondence of residents of Georgetown with the following surnames: Beatty, Deakins, Forrest, Johns, Levy, Magruder, Mason, and Stoddert.]
• List of imported servants and convicts from Europe who served labor terms in Colonial Montgomery County, Maryland (work in progress), courtesy: Immigrant Servants Database.
Land
Through a Joint eGovernment Service of the Maryland Judiciary and the Maryland State Archives, free images and indexes of the complete series of Montgomery County Deed Books (1777-present) have been uploaded to their website: MDLandRec.Net: A Digital Image Retrieval System for Land Records in Maryland. (Requires free registration.)
Local Histories
Maps
Military
Revolutionary War
• A Census of Pensioners for Revolutionary or Military Services: With their Names, Ages, and Places of Residence, as Returned by the Marshalls of the Several Judicial Districts, Under the Act for Taking the Sixth Census]. 1841. Digital version at Google Books. 1967 reprint: FHL Collection 973 X2pc 1840. [See Maryland, Montgomery County on page 127.]
War of 1812
• List of Pensioners on the Roll, January 1, 1883; Giving the Name of Each Pensioner, the Cause for Why Pensioned, the Post-Office Address, the Rate of Pension Per Month, and the Date of Original Allowance... Washington, D.C.: Government Printing Office, 1883. FHL Collection 973 M2Lp v. 5; digital versions at Google Books and Internet Archive. [See Vol. 5, Maryland, Montgomery County, pp. 152-153. Identifies War of 1812 veterans living in this county in 1883.]
Newspapers
Probate
Taxation
Vital Records
Death
Societies and Libraries
Web Sites
References
Need additional research help? Contact our research help specialists.
Need wiki, indexing, or website help? Contact our product teams.
Did you find this article helpful?
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GlobalVoices in Learn more »
Mobile Libraries Help Haitians Overcome Major Earthquake
This post also available in:
Español · Bibliotecas móviles ayudan a haitianos a superar el gran terremoto
Français · Des "BiblioTaptaps" pour aider les Haïtiens à se remettre du tremblement de terre de 2010
Malagasy · Bibliotaptap Manampy Ny Haitiana Hiatrika Ny Horohorontany Lehibe.
繁體中文 · 海地：行動圖書館撫慰震災創傷
简体中文 · 海地：行动图书馆抚慰震灾创伤
Português · Bibliotecas móveis ajudam haitianos a superarem o grande terremoto
If today were 12 January, 2010, the world would be about to stop speechless on hearing news of the earthquake that would have destroyed Port-au-Prince, the capital of Haiti. The images would be heart-breaking, which would not stop an even greater shock following estimates that, in only a few minutes, 222 thousand people would have lost their lives and 2 million their homes. And if estimates were made with the heart, the calculation would be that all 9 million Haitians had been left wounded by the fear and uncertainty for their own lives, as well as for those of their friends and relatives.
The story of this earthquake would not fit into a book, but it is reading itself that is helping the Haitian population overcome it. This is because Libraries Without Borders is launching mobile libraries to circulate through the country's capital supplying books and, in doing so, offering a means of access to information and knowledge.
BiblioTaptap Bookmobiles in Haiti. Photo from the Libraries Without Borders website.
Operating in countries in the Americas, Africa and Asia, projects like these are carried out in developing countries and those left at risk from disasters and conflicts. In Haiti, the organisation acts in partnership with the country's National Library, which is being reconstructed, the Haitian National Bureau for Books and the Foundation for Knowledge and Freedom (FOKAL).
When faced with catastrophes, governments and international organisations join forces to distribute medicine, water, food, clothes and shelter for victims. However, people's basic needs extend beyond their bodies to their minds, spirits, hearts or wherever they have chosen to keep their feelings about what they have gone through. Badis Boussouar, Head of Communications at Libraries Without Borders, explains the role of reading in this context:
For Libraries Without Borders, there is no question that organizations and governments must devote the majority of their efforts to promoting the physical wellbeing of disaster victims. But more attention should be given to nourishing the mind as a second measure to help victims cope with catastrophe and move forward. Books and expression help sustain intellectual stimulation and promote self-worth and resilience in times of crisis. Through books, computers or training, access to information and cultural resources empowers individuals and gives them the tools to reconstruct what has been lost.
BIBLIOTAPTAPS
The organisation's mobile libraries have been inspired by the book buses that exist in other countries, especially in rural areas, and have arisen from the sad fact that most of Haiti's libraries were destroyed by the earthquake, along with 4,000 schools. 80% of the schools in Port-au-Prince and 60% of the schools in the south and west of the country were destroyed or damaged, according to data from the Disasters Emergency Committee.
They have been named BiblioTaptaps in homage to the typical local taxis. The first was launched in July 2012, and two more will be launched by this March. As can been seen in the video below [fr], the project mobilises Haitians of all ages, especially children, who are often the most affected.
While travelling through the Port-au-Prince neighbourhoods, each BiblioTaptap carries 400 books, including romances, poetry collections and plays, with half of them in the native language. In addition to literary topics, there are books on history, politics, economics and culture, both Haitian and from around the world. Users of the service also have access to photography catalogues, books on the arts and dictionaries, among other things. Books are chosen daily by the activity leaders based on the scheduled itinerary, so that reading is always simulating, whether for children participating in BiblioTaptap activities, youth wanting to better understand their country's reality in order to change it, or even adults or the elderly seeking information on health or how to care for their communities or the environment.
Book donations are welcome, but care is taken not to harm local book economies by providing excessive amounts of books.
THE URGENCY OF READING
This all forms part of the belief in the power of books to provide basic self-care knowledge along with other vital information for overcoming the trauma caused by the earthquake, which naturally, can neither be forgotten nor rectified in such a short space of time.
UNICEF supports education in post-disaster contexts and collaborates with Libraries Without Borders in Haiti.
The recent Libraries Without Borders initiative called The Urgency of Reading reaffirms the organisation's conviction that books and reading are an important means for victims to overcome this type of catastrophe. They appeal to international organisations involved in humanitarian work to: “1) expand reading, cultural and educational programs, which activate the human spirit and help individuals cope with trauma; and 2) make the provision of access to information and books a priority for international humanitarian relief”.
They can be helped in this endeavour by signing an international petition, as Tzvetan Todorov, Mario Vargas Llosa, Zygmunt Bauman, J.M. Coetzee, Robert Darnton, Roger Chartier and many others have already done.
It makes you think about what book would help in this situation. Maybe someone in Bangladesh is thinking of giving the Haitian people a poem by Rabindranath Tagore, perhaps someone in Russia is considering something by Maiakovski, but the first thing that came to my mind was a verse by the Brazilian poet Manuel Bandeira, which will be amazing when true for the entire world: Belo belo belo tenho tudo quanto quero (Beautiful, beautiful, beautiful, I have everything I want). In the meantime, recognition of the importance of books and reading in situations involving natural disasters and calamities is increasing. Queens Library, for example, is offering books to the victims of Hurricane Sandy in the USA. To bring them hope, Walt Whitman.
World regions
Countries
Languages
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User:Nkuldell:SB starter kit
From OpenWetWare
Jump to: navigation, search
Use this space as a scratch pad for your ideas and thoughts and experiences as we develop some teaching materials geared for SB starters (e.g. iGEM teams without resident synthetic biology community, or social scientists trying to understand technology that underlies the field).
The slate is still nearly blank, though I've seeded this site with some organizational ideas....all subject to change and heavy editing.
look at resourced listed on James Brown's "getting started" site: [1]
One thought offered by Caroline, "the limits of your language are the limits of your world"-Ludwig Wittgenstein
Contents
"front page"
• welcomes to synthetic biology
• two sentence overview of the field
• two sentence overview of goals of tutorial
• two sentence overview of how to use tutorial
Tab: Biology for Engineers
• culture celebrates understanding and description of natural world
• central dogma
• start with "this is a cell"
• unifying example to ground details?
Tab: Engineering for Biologists
• culture celebrates building things
• predictable
• modular, interchangeable components
• measurement
• standards
Tab: Lab techniques/Registry Starter kit
• mRFP cloning examples
• BBa_J16000 and BBa_J16002 are the two parts which I'd like students to start with for the following reasons:
• Employs the idea of putting both basic parts and component ("inverter device") parts together.
• Both systems can be controlled using externally added chemicals (IPTG, Tetracycline) with measurable flourescence output
• All parts well-characterized
• mCherry protein has LVA tag for fast degradation
• Non-linear behaviour exhibits complexity beyond electronic parts
• Contains almost all canonical part categories (RBS, regulatory, device, terminator, protein coding, reporter...)
Social implications
• might direct to Q/A from PoET/SB collaboration
• this may not need a tab or section of its own
Notes/comments
I think we could exemplify the concept of abstraction and stress its importance by designing the iGEM tutorial / primer in a hierarchical way, such that any step in an initially superficial "high-level" recipe for constructing an archetypal device out of parts from the registry could be deepened and explored for more sophisticated, complicated "low-level" information. Maybe we could use AJAX to facilitate the expansion and compression of the levels of abstaction. Or maybe we should just use normal hyperlinks. In any case, I think it would be really neat if the whole primer initially took up no more than one page when printed out. I think that degree of simplification would necessitate a mature abstraction hierarchy (and hence could be a good goal for us) and its initial brevity would make it less overwhelming for newcomers. --Macowell 00:37, 23 June 2006 (EDT)
Useful teaching resources already freely available
books
These books are online at ncbi (searchable, but not directly browseable):
protocols
papers & presentations
other websites
• DNAi - excellent interactive explanations of the science of basic molecular biology. For instance, check out the "Recombining DNA" animation under Manipulation->Techniques->Cutting & Pasting
• Registry Help page - start here!
• Teaching Resources at the iGEM wiki
• Blogs
misc
Personal tools
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Dyson and his Vacuum Cleaner
Posted 16 Nov 2001 at 04:18 UTC by steve
Business Day, a UK publication, has an article with some interesting background on James Dyson. Dyson, described as an oddball inventor, came up with the "cyclone" bagless vacuum cleaner. His company is now working on an automous robot vacuum cleaner called the DC06.
What's the mood light for?, posted 16 Nov 2001 at 19:39 UTC by The Swirling Brain » (Master)
A robotic vacuum is a cool item for sure. Just don't make it mad or its mood light will go out! Then it would really suck!
See more of the latest robot news!
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Thursday, September 16, 2010
IPO Association Annual Meeting, Ethics session
Moderator: Lynn Alstadt, Buchanan Ingersoll & Rooney, PC, Pittsburgh, PA
Frank E. Quirk, University of Akron School of Law, Akron, OH
Model Rule 5.1 and 5.3: duties of lawyers as supervisors. Have to ensure measures in effect giving reasonable assurance that all lawyers in the firm conform to the Rules of Professional Conduct. Applies to all lawyers with comparable managerial authority to partners in firms, not just partners in firms. Lawyers subject to the Rule have to establish internal policies and procedures designed to detect and resolve conflicts of interest, identify dates by which actions must be taken in pending matters, protect client funds and property, and ensure that inexperienced lawyers are properly supervised. For IP practice groups/firms: calendaring/docketing aspect is probably the most important. Then practices and procedures for issuance/review of opinion letters.
Comment 3: additional measures will depend on firm size, structure, and nature of practice. Partners may not assume that all lawyers associated with the firm must inevitably conform to the rules. Most complaints are about small firms. Managing partner may be in the bullseye for misconduct by others (gave example), but that’s rare. Alabama: lawyer disciplined for overburdening associates and having a quota system for opening files, not giving them enough time to do the work responsibly; DC: supervisory lawyer disciplined for failing to offer even rudimentary ethics training; NJ: supervisory lawyer disciplined for having no plan for systematic periodic review of assigned files.
Whether a lawyer has supervisory authority is a question of fact. Pushing a heavy caseload on undertrained and overburdened lawyers is a problem, especially in the public defender system.
Appropriate remedial action must be taken, which depends on immediacy of the lawyer’s involvement and seriousnes of the misconduct. Supervisor and subordinate both have responsibility to correct misrepresentation by the subordinate.
Responsibilities for nonlawyer assistants: you have to put measures in effect giving reasonable assurance that the person’s conduct is compatible with the professional obligations of the lawyer. Very important for outsourcing.
Must give assistants appropriate instruction and supervision on ethical aspects, especially nondisclosure—these people aren’t lawyers, don’t know the rules, aren’t bound by the rules: this means more supervision is required than that for lawyers. A lawyer can be held responsible for assistants’ misconduct if knows/ratifies/fails to supervise appropriately.
Outsourcing and offshoring. Some claim that $1 billion of work will be going to India within a few years. ABA approves of outsourcing so long as the lawyer remains ultimately responsible. Must comply with 5.1 and 5.3 specficially: take reasonable efforts to ensure that lawyers’ conduct is compatible with their obligations. Lawyers must disclose outsourcing to clients. If they’ll communicate confidential information, that requires client consent. Standard terminology is coming into play: outsourcing generally refers to domestic agencies; offshore outsourcing refers to going out of the country; offshoring refers to establishing offices outside the country to undertake activities that would otherwise be outsourced offshore.
ABA: Substantial due diligence must be taken to establish providers’ competence. State opinions approving outsourcing consider them to be nonlawyers under 5.3 rather than lawyers under 5.1, addressing a concern over the unauthorized practice of law. No confidential information may be revealed without client consent.
Major issues to be addressed: Competence of outsourcing agency; unauthorized practice of law/aiding and abetting same; client confidentiality; reasonableness of fees and expenses.
Prof. David Hricik, Mercer University School of Law, Macon, GA
“Better them than us”: things that can go wrong in patent, and IP, practice in general. He monitors filings, talks to insurance companies, etc.: things are happening that should make you pause. First, the number of claims is clearly increasing dramatically. Second, the types of claims are changing: not typical missed deadline case where someone lost a PCT date. More focused on substantive errors: claims were not properly drafted; didn’t pursue broad claims early in prosecution, costing client money in licensing. Third, less noticeable but still a trend, is that big firms are no longer untargeted. Maybe it’s because boutiques have been swallowed up.
Number one source of problems: missed deadlines. Always have a double check: don’t let one person enter the data. Could keep a paper and a computer log. Be really careful if you have an FDA practice where you’re dealing in days, not months; people get confused sometimes and calculate based on the wrong unit. 90 days is not the same thing as 3 months.
Vaxxion v. Foley Lardner: A number of wrinkles. West Coast FL was retained to file a provisional application for Vaxxion on a technology known as mini-cells. Next, filed nonprovisional application, and 1-year bar for filing PCT application passed (there’s a fight over whose fault it is); filed a bit late. Consequence: can reach back only to the nonprovisional filing date. If there’s any intervening art in the period between provisional and nonprovisional, there’s client harm. East Coast office of FL was hired to represent a client, and missed the conflicts check. FL filed a provisional application for EnGeneIC in between Vaxxion’s provisional and nonprovisional; it was cited against Vaxxion as prior art.
Patent conflict checks are an art, not a science, on subject matter: but look at this disaster. The judge in the case said that knowledge was imputed among all lawyers in the firm for purposes of malpractice claims. The lawyers who filed their application on time “knew” that they were harming Vaxxion. The lawyers who missed the deadline “knew” it would help EnGeneIC. For some purposes this makes sense, but for malpractice these mistakes were turned into deliberately harming one’s own client. Case settled after that ruling.
What are the odds of 2 clients in the same field coming to the same firm? Pretty high! If a firm is known as being good in a certain area.
Cases pending now where claim drafting errors are alleged. In one case the firm used “consisting of” instead of “comprising,” which narrows the scope of the claim. Several cases: claim is that the spec wasn’t drafted broadly enough to support the scope of the invention disclosed to the lawyer. A lot more botched litigation claims being brought—patent firm retained to prosecute an infringement suit and gets in a ditch; client sues for improper handling, especially if the client was sanctioned for having brought the suit. Some of this is judgment call, though he doesn’t think consisting/comprising is.
One pending case involving due diligence is pending in Texas. Facts: Company A retains firm A to do stock purchase of company; its principal asset is IP, a couple of patents. The firm is retained to do due diligence, including making sure company owns its IP. Firm fails to realize that the principals of the company own the IP in their own names. Worse, then, the statute of limitations on specific performance/breach of warranty runs. Thereafter, without explanation, firm A comes to principals and asks them to assign the patents, without saying that firm A doesn’t represent the principals, that they might want a lawyer, or that they’re under no legal obligation to sign (though there may be a moral obligation). Not clear whether firm realized the problem on its own or went to the company and confessed. Next, principals sue firm and its client for fraud for saying that the principals should sign the assignment without explaining.
Disputes/motion practice over client identity: be clear about who the client is. Inventors: well-known problem. Individual claimants often try to disqualify firms because they allegedly represented the individuals as well as the company during prosecution: maybe they executed a power of attorney; maybe you sent an email to them marked ATTORNEY-CLIENT, and in some states their expectations can make a difference. Inventors subject to assignment who give power of attorney are not, without more, clients, but they do regularly sue and seek to disqualify firms claiming they were clients. Mostly they lose, but it still costs a lot of money.
What can you do to reduce these claims for disqualification/malpractice? One: have the invention assigned to the company, don’t get power of attorney. Other firms say that’s not practicable with big companies. Other thing: when you send power of attorney, stamp on it and put on the cover letter in big letters: WE ARE NOT YOUR LAWYERS; this doesn’t make you my client; I represent only the company and I don’t represent you. Also remember: some people may be legitimately confused about your role; a clear statement is a good thing in that circumstance.
Another client identity issue being litigated more often: do you represent General Electric just because you represent General Electric Credit Corporation? For patent, the question arises with joint development agreements. Your client enters into a JDA with some other company. That company has its own law firm. Its scientists will be named on the patent application with yours. Normally, the agreement will say that one party has control of patent prosecution, subject to an obligation to confer with/confer in good faith with/keep the other side informed. If everything goes fine, great. But 80% of these JDAs fail. You think the other guy’s scientists aren’t clients, because all you have is a power of attorney and the other guy’s scientists are represented/subject to assignment. But in litigation it may be argued that you represented the other guy’s scientists. You would think that these arguments would fail—how could you owe a fiduciary duty where the agreement says you have control? But in one case, the court granted SJ to the other side, holding that the other scientists were also clients. Lawyers use poor language: record “met with client” in work records when they weren’t clients.
Reduce risk of this mess: send out letters to the scientists and the other law firm: we only represent our client, though we understand our client has contractual obligations to the other side. Those are our client’s obligations and our fiduciary duty is only to our client. There can be a lot of ambiguity; there’s bad law out there now.
Growing area: misuse of trade secrets. Not Pepsi’s lawyers running off to Coca-Cola, but firms are getting sued because they’re taking closer and closer applications. When you’re prosecuting 2 cases close together, you’re setting yourself up for a trade secret misuse argument. Even public information you learn while representing a client can be a client confidence. Lawyer can be disciplined for disclosing something in a public court record learned while representing a client.
Background information about how technology works: court has ruled that information can be confidential even if it’s known to those with ordinary skill in the art. Don’t reuse “back in the day, here’s how they did it” in different applications. He’s not saying that’s properly decided but you should be aware of the state of the law.
Grievance committee of the PTO, the OED. Aggressive organization, sometimes surprising choices. OED is going around and looking at firm webpages. If you say “Bob prosecutes applications” and Bob isn’t registered, they’ll come after you for aiding unauthorized practice of law and false advertising, even if Bob helps people. They want you to say “Bob assists in the prosecution of applications, with supervision.” Scientific advisors: don’t use the words “prosecutes applications.” If they send you a letter, be careful about how you respond: the slightest misstep in response becomes a second allegation against you. He’s not sure this is a big problem, but they are going after it.
Reported case, half a year back: clamping down on people submitting art in cases that aren’t theirs. Narrow form of filing protest to get art in front of the examiner. Any other way will be deemed a violation of the rules. You can do “poor man’s reexamination” and mail the art to the applicant, informing them of material art and hope that works, but otherwise be careful.
Guy gets a case and hands it off to his litigation partners, but stays on the case/shows up for hearings/listed as lead counsel. Client and law firm get sanctioned for bringing the case. The OED sends a letter to the lawyer asking why he shouldn’t be sanctioned for failure to supervise his partners, who weren’t registered and thus weren’t within the scope of the OED’s authority. What’s this got to do with patent prosecution?
Q: how many of these claims are related to fee disputes?
Hricik: none of the ones he discussed. However, it’s not one to one that suing for fees invites a malpractice claim, but it’s close enough that you should count on it.
Q: What happens when you want attorney-client privilege to protect communications between counsel and the scientists? Joint interest defense?
Hricik: the common interest privilege is designed to protect privilege when there is disclosure to a non-client; otherwise we’d be talking about the joint client privilege: in fact an element of the privilege is that you didn’t represent the other guy. So it’s consistent to claim the privilege without agreeing that you represented the other guy.
Q: if you get waivers from both clients in a related field, are you clean?
Hricik: Maybe from a disciplinary perspective, if there’s full disclosure—we may, while prosecuting the other claim, say bad things about your patents or try to antedate another of your patents. Would still worry about trade secret misuse allegations. Possible also that you’d be charged with deliberate blindness in not learning relevant information.
Q: if you’re reading the Official Gazette on behalf of a client and see a reference, that’s now confidential and you can’t disclose it to the Office without consent from your client?
Quick: question is what the expectation of the client was. Cases are now coming down where the information is publicly available: e.g., disclosing a former client’s criminal conviction—you learned about it in the course of the attorney-client relationship and the client expected it to be confidential.
Hricik: Gazette probably won’t ever be in that category, but what if you find a dissertation on a shelf in Michigan and the client doesn’t want it disclosed (but doesn’t take unethical action and just declines to file an application), and then later you have another client to whom this is material? Cases are in direct conflict: one requires disclosure, another requires suppression. Patent Office has taken the position that you have to go to the first client. If the client says no, you have to noisily withdraw from that prosecution—which seems to send a signal about case/client #2, but is it the right signal?
Q: Can you use boilerplate? At some point, that was originally drafted for another client.
Hricik: the court in the relevant case wasn’t going to hold it was boilerplate on a 12(b)(6) motion; client sufficiently alleged it was more than that. Be careful copying text anyway, because you can end up limiting claims.
Q: if you want to take advantage of offshoring for document review/prosecution, what steps do you have to take re: US export laws?
Alstadt: you can’t export products/information within certain categories. When you file a patent application, you get a foreign filing license. So he’s filed a provisional application and gotten his license, which then makes it ok under export control laws. If not that, have someone review it for compliance with the export controls, and keep a record of having done that.
Hricik: Calendaring maintenance fees for clients—he doesn’t think you should do it. PTO and Oregon bar has said that you have to count them as an active client if you’re calendaring their maintenance fees. Might also toll the statute of limitations because you’re actively representing them. Sometimes the PTO has said this doesn’t create an attorney-client relationship, but it’s also said the opposite. Maintenance fees are missed all the time; if you miss one, you’ll lose every penny of profit you ever made by doing maintenance. What you can do if you really want to do this: in engagement letter and when sending a reminder, say: if you ask, we’ll calendar your maintenance fees but this is a non-legal service and it isn’t part of our attorney-client relationship. Missed maintenance fees = malpractice claim; it’s amazing that the fees are only missed on really valuable patents (if you look at the complaints).
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
1307.6 - Tasmanian State and Regional Indicators, Jun 2010 Quality Declaration
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 29/07/2010
Page tools: Print Page Print All RSS Search this Product
ECONOMIC ACTIVITY
GROSS STATE PRODUCT (GSP)
In 2008-09, Tasmania's Gross State Product (GSP) reached $22.6 billion, an increase of $0.3 billion or 1.4% from the 2007-08 figure of $22.3 billion. Household final consumption expenditure was the largest component of GSP, contributing $13.4 billion (59.2%). At the same time, government final consumption expenditure accounted for $5.0 billion (22.1%).
Tasmanian State final demand in 2008-09 increased by 2.1% on the 2007-08 estimate of $23.9 billion.
GROSS STATE PRODUCT (percentage change), Tasmania
(chain volume measures)
STATE FINAL DEMAND, Tasmania
(chain volume measures)
Over the year ending 30 June 2009, manufacturers contributed $2.6 billion or 12.7% of the $20.6 billion in gross value at basic prices added by producers in the Tasmanian economy.
Of the $3.0 billion in private business investment expenditure in Tasmania in 2008-09, $1.3 billion was accounted for by private new capital expenditure on buildings, structures, equipment and plant and machinery in Mining, Manufacturing and other selected industries. The $1.3 billion expenditure in 2008-09 represents a 12.4% increase on private new capital expenditure in 2007-08.
CONSUMER AND LABOUR PRICES
In the June 2009 quarter, the Consumer Price Index (CPI) (all groups) in Hobart increased by 1.7% on the corresponding quarter in 2008. Rises in costs in education (8.1%), health (5.1%) and food (5.0%), and the decreases in transportation (-6.4%) and financial and insurance services (-5.3%) were the main contributors to this change.
CONSUMER PRICE INDEX (all groups), Hobart
CONSUMER PRICE INDEX (selected groups), Hobart
Total hourly rates of pay (excluding bonuses) paid by Tasmanian employers rose by 4.3% between 2007-08 and 2008-09. This compares with a national increase of 4.0% during the same period.
HOUSE PRICE INDEX
Preliminary data showed the price index for established houses in Hobart in June 2009 increased slightly (up 1.0% on June 2008 price level) compared to a slight decrease nationally (down 0.7% on June 2008). At the same time, the price index for project homes in Hobart showed a year to year increase of 1.6% compared to 2.6% nationally.
HOUSE PRICE INDEX (established houses)
HOUSE PRICE INDEX (project homes)
HOUSING FINANCE COMMITMENTS
The number of first home buyers' houses (owner occupied) financed in Tasmania in 2008-09 increased significantly, by 49% from 2,141 in 2007-08 to 3,181 in 2008-09. At the same time, non-first home buyers' dwellings (owner occupied) financed decreased by 17% from 13,145 in 2007-08 to 10,946 in 2008-09.
FIRST HOME BUYERS, Tasmania,
Number of dwellings financed
NON-FIRST HOME BUYERS, Tasmania,
Number of dwellings financed
INTERNATIONAL MERCHANDISE TRADE
In 2008-09, the value of Tasmanian goods exported overseas was $3,506.7 million, a decrease of 3.5% on the 2007-08 value of $3,635 million. At the same time, the value of goods imported into Tasmania was $956.0 million, an increase of 38% from 2007-08.
In 2008-09, Japan remained Tasmania's main export destination purchasing $532.6 million worth of Tasmanian goods. China was the second most favourable export destination with $470.2 million (a 61% increase from the previous financial year). Tasmania's major source of imports in 2008-09 was Japan ($163.7 million).
Zinc was the major export commodity in 2008-09, contributing $562.0 million or 16% of total Tasmanian exports. Cocoa was the highest value commodity imported contributing $81.9 million or 8.6% of total imports.
VALUE OF MERCHANDISE EXPORTS(a), Tasmania
VALUE OF MERCHANDISE IMPORTS(a), Tasmania
SOURCES
Australian Industry (ABS cat. no. 8155.0)
Australian National Accounts, State Accounts (ABS cat. no. 5220.0)
Consumer Price Index, Australia (ABS cat. no. 6401.0)
House Price Indexes, Eight Capital Cities (ABS cat. no. 6416.0)
Housing Finance, Australia (ABS cat. no. 5609.0)
Labour Price Index, Australia (ABS cat. no. 6345.0)
Lending Finance, Australia (ABS cat. no. 5671.0)
Private New Capital Expenditure and Expected Expenditure, Australia (ABS cat. no. 5625.0)
© Commonwealth of Australia 2013
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Research article
Amygdala and fusiform gyrus temporal dynamics: Responses to negative facial expressions
Jennifer C Britton1, Lisa M Shin1,2, Lisa F Barrett1,3, Scott L Rauch1,4 and Christopher I Wright1,5*
Author Affiliations
1 Psychiatric Neuroimaging Research Program and Martinos Biomedical Imaging Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
2 Department of Psychology, Tufts University, Medford, MA, USA
3 Department of Psychology, Boston College, Chestnut Hill, MA, USA
4 Current: McLean Hospital, Belmont, MA, USA
5 Division of Cognitive and Behavioral Neurology, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA
For all author emails, please log on.
BMC Neuroscience 2008, 9:44 doi:10.1186/1471-2202-9-44
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2202/9/44
Received:1 November 2007
Accepted:12 May 2008
Published:12 May 2008
© 2008 Britton et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
The amygdala habituates in response to repeated human facial expressions; however, it is unclear whether this brain region habituates to schematic faces (i.e., simple line drawings or caricatures of faces). Using an fMRI block design, 16 healthy participants passively viewed repeated presentations of schematic and human neutral and negative facial expressions. Percent signal changes within anatomic regions-of-interest (amygdala and fusiform gyrus) were calculated to examine the temporal dynamics of neural response and any response differences based on face type.
Results
The amygdala and fusiform gyrus had a within-run "U" response pattern of activity to facial expression blocks. The initial block within each run elicited the greatest activation (relative to baseline) and the final block elicited greater activation than the preceding block. No significant differences between schematic and human faces were detected in the amygdala or fusiform gyrus.
Conclusion
The "U" pattern of response in the amygdala and fusiform gyrus to facial expressions suggests an initial orienting, habituation, and activation recovery in these regions. Furthermore, this study is the first to directly compare brain responses to schematic and human facial expressions, and the similarity in brain responses suggest that schematic faces may be useful in studying amygdala activation.
Background
Human faces provide key social and emotional information via the expressions portrayed. In a single encounter, an individual's facial expressions change rapidly, requiring a quick deduction of meaning. This ability to process facial expressions quickly or automatically is particularly advantageous when the expressions predict threat (e.g., fear or anger) [1]. Given the importance of processing social threat cues in facial expressions quickly, the meaning may be conveyed by several key features (e.g., raised eyebrows, angry eyes and gaping mouth).
Schematic faces, simple line drawings or caricatures of faces, extract these features from a complex facial expression. A schematic face capturing the key components of a facial expression may be useful in studies of emotion because the prototype is relatively devoid of confounding characteristics (e.g., ethnicity, age, attractiveness). Several studies have discovered that schematic faces still retain emotional meaning [2] and schematic faces activate brain structures involved in processing human facial expressions (e.g., amygdala, prefrontal cortex) [3], providing evidence that a simple representation of a facial expression can be used to study emotion.
It is well-established that the amygdala response habituates (i.e., decreases over time) to repeated presentations of human facial expressions; however, it is unclear whether the brain's response to schematic faces is maintained or habituates over time. Amygdala single cell recordings show reduced activity to repeated human faces [4]. Additionally, neuroimaging studies have reported early vs. late within-block habituation in the amygdala and hippocampal formation in response to repeated fearful and neutral human faces [5,6]. To our knowledge, only two studies have reported on habituation effects in response to schematic faces. In an event-related study involving both human and schematic faces, significant amygdala habituation was reported to schematic faces of anger relative to neutral in individuals with social phobia [7]. In a block-design study of healthy individuals, the amgydala response to schematic faces (angry, happy, and neutral) was maintained across time [3]; however, the presentation order (i.e., neutral blocks bracketing alternating emotional states) may have inhibited habituation.
In this fMRI block-design study, we examined the brain responses (i.e., amygdala and fusiform gyrus) to schematic and human facial expressions using a within-run facial expression (negative, neutral) and between-run face type (schematic, human) counterbalanced design. This design allowed examination of habituation and of face type in a single experiment without potentially confounding influences of presentation order. We hypothesized within-run habituation effects would be detected in response to the alternating blocks of schematic facial expressions as well as the human facial expressions in the amygdala.
Results
Face Recognition and Emotion Ratings
During the post-scanning recognition task, participants identified the faces viewed with high accuracy rates (human: 99.0% ± 4.2, schematic: 100% ± 0.0).
The negative faces [Schematic Negative: M = 3.4, SD = 1.3, Human Negative: M = 3.6, SD = 1.2] were rated as being more arousing than the neutral faces [Schematic Neutral: M = 1.9, SD = 1.3, Human Neutral: M = 1.9, SD = 1.3, expression effect: F(1,15) = 20.2, p < 0.004)]. No differences in arousal ratings between face type (i.e., schematic vs. human) were detected [face type effect: F(1,15) = 0.1, p > 0.77]. No interaction effects were noted [face type x expression: F(1,15) = 0.2, p > 0.66].
The negative faces [Schematic Negative: M = -2.6, SD = 1.3, Human Negative: M = -2.4, SD = 0.7] were rated as being more negative than the neutral faces [Schematic Neutral: M = 0.6, SD = 0.9, Human Neutral: M = -0.3, SD = 0.8, expression effect: F(1,15) = 254.0, p < 0.001]. The human faces tended to be rated more negatively than the schematic faces [face type effect: F(1,15) = 3.4, p = 0.09]. In addition, the valence rating difference between angry and neutral faces was greater for schematic faces than for human faces [face type x expression: F(1,15) = 11.8, p < 0.004]. This difference was due to greater negative valence ratings of the human neutral faces compared to more positive ratings of neutral schematic faces [t(15) = 3.1, p < 0.008].
BOLD Activation
A temporal effect of responses across blocks within the run were detected in amygdala [time effect, Left: F(3,45) = 11.3, p < 0.001; Right: F(3,45) = 11.7, p < 0.001] and fusiform gyrus [time effect, Left: F(3,45) = 15.9, p < 0.001; Right: F(3,45) = 18.3, p < 0.001] (Figure 1). A significant quadratic response was detected in both regions [all F>27.6, p < 0.001].
Figure 1. Temporal dynamics of responses to facial expressions yield "U" pattern. Percent signal change in brain activity in response to facial expressions compared to baseline across blocks in A) Amygdala and B) Fusiform Gyrus. L = Left, R = Right. Small bars indicate one standard error of the mean.
Post-hoc tests were conducted using a significance threshold of p < 0.01 to correct for multiple comparisons and demonstrated a "U" pattern of activity. In the amygdala and fusiform, the response in the initial block (block 1) was greater than the other blocks (blocks 2, 3, and 4) [all regions: T>2.8, p < 0.01]. Contrary to the amygdala [both hemispheres: T<1.2, p > 0.2], the responses in the fusiform gyrus tend to progressively decline (block 2> block3) [both hemispheres: T>2.4, p < 0.03]. In addition, a trend towards significant region (amygdala, fusiform) x time (block 2, block 3) interaction was detected in the left [F(1,15)>5.1, p < 0.04] and the right hemispheres [F(1,15)>3.8, p < 0.07]. Responses to block 4 were greater than block 3 significantly in the right amygdala and bilateral fusiform gyrus [all regions: T>2.9, p < 0.01] and at trend-level significance in the left amygdala [T>2.2, p < 0.04].
In the right amygdala, a trend emotion x time effect was significant [F(3, 45) = 0.06]. Because the initial block yielded the largest response and was subsequently followed by a habituated response, the responses in the first time block were investigated further for valence effects. Greater responses were elicited to negative faces compared to neutral faces [F(1,15)>7.8, p < 0.01]. (Figure 2).
Figure 2. Right Amygdala response to emotion in initial block of facial expressions. Percent signal change in amygdala activity in response to facial expressions compared to baseline for first block of each run. Greater responses were elicited to negative faces compared to neutral faces in the right amygdala [F(1,15)>7.8, p < 0.01]. No significant main effect of face type (schematic, human) was noted.
There were no other significant effects (i.e., face type) in the amygdala. No significant valence, face-type main effets or interactions were found in the fusiform gyrus. [all effects: F<1.7, all p > 0.2].
Discussion
Within each run, the amygdala and the fusiform gyrus showed a "U" response pattern with the initial and final blocks eliciting the greatest activation to a repeated facial expression. The amygdala profile may reflect an initial orienting response, then habituation, followed by recovery of activation in the final block. A similar "U" pattern was observed in skin conductance response (SCR) and late-phase SCR-associated left amygdala response to repeated fearful faces [8]. Like fear, anger is highly arousing and may prompt a similar orienting response and skin conductance response. The activation recovery may be due to emotional priming [8]. Alternatively, it may reflect spontaneous recovery or reinstatement. Vigilance maintenance via a system reset, even in the absence of imminent threat, may be an important survival function [9]. Consistent with this notion, primate electrophysiological data demonstrate that neuronal populations within the amygdala respond maximally to novelty, show decreased activation with familiarity (i.e., habituation), and reset (i.e., show activation again) after limited number of repeated stimulus presentations [4].
In this study, fusiform gyrus activation followed this "U" pattern in response as well; however, a trend towards different temporal patterns are observed in the amygdala and fusiform gyrus. In the amygdala, habituation occurs rapidly; whereas, in the fusiform gyrus, habituation occurs more gradually. This delayed recovery may be explained by enhanced modulation of the amygdala or a slower resetting system of the fusiform gyrus.
Negative faces are discriminated from neutral faces in the right amygdala. Our findings replicate previous work showing that the right amygdala, responds to angry relative to neutral faces [10,11]. In this study, the differential amygdala response to facial expressions was present only during the early time period, suggesting that it is related to the amygdala orienting response. Although some studies report fusiform gyrus activation to emotional faces relative to neutral faces, we did not detect such an effect. It may be that differential fusiform gyrus activation to emotional (vs. neutral) faces is task-dependent. The fusiform gyrus responds more non-selectively to facial stimuli in the context of limited-attentional demands (e.g., passive viewing of repeated facial expressions) [12], yet exhibits a selective or differential pattern of activation when increased attention to face emotional content is required [13]. In fact, the existence of projections from the amygdala to the fusiform cortex suggest that the amygdala may modulate the sensory processing stream according to the salience of the target visual stimulus [14].
Interestingly, no significant differences between schematic and human faces were detected in the amygdala and fusiform gyrus. In a recent study, the amygdala response to human and avatar (or computer-generated faces) was similar, yet the fusiform showed a greater response to human faces [15]. For studying the amygdala, it appears that there is some utility to this response similarity between human and face representations (e.g. schematic or avatar faces). Schematic and avatar faces may be useful to study emotion perception because the key facial features that underlie the neural activation are relatively isolated from stimulus features like race/ethnicity and gender, which may increase the variability in responses. It is also important to note that schematic and avatar faces may be useful in answering different questions concerning emotion that take advantage of the static or moveable representations (e.g. brain responses to key facial features and brain responses to social emotional interactions, respectively).
This study has some potential limitations. Evaluating the temporal dynamics of neural responses is dependent on the time scale examined. In this study, within-run habituation effects were investigated; however, other time scales (e.g., between-run, within-block) may show different effects. Only angry faces were used to represent negative faces. Future studies should examine the temporal dynamics of other expressions (e.g., fearful, sad), including positive expressions (e.g. happy). Our findings suggest schematic and human faces elicit generally similar responses in the amygdala and fusiform gyrus; however, replication in a larger sample is needed. Schematic faces reduce expressions to line drawings and a single exemplar was used in this study. While using a single exemplar may be problematic, it does diminish confounds due to variability in human facial expressions. Finally, although using ROI-based analysis is a more powerful approach for detecting differences in specific a priori regions (i.e., amygdala and fusiform gyrus), this approach does not allow the observation of other regions that may also respond to these stimuli.
Conclusion
In summary, it appears that both the amygdala and fusiform gyrus responses to facial expressions do habituate over time; however, the "U" pattern suggests that the responsivity of these structures resets, possibly to allow attentional reengagement with repeatedly presented stimuli. Future studies with larger samples should investigate whether this pattern discriminates between emotions or stimulus type.
Methods
Participants
Sixteen participants were studied (8 females, 8 males; M = 26.7, SD = 4.7, Range = 22–41 years of age). All participants were Caucasian and right-handed determined by the Edinburgh Handedness Inventory [16], free of psychoactive medications and medical, neurological or psychiatric illness. Beck Depression Inventory (BDI) [17] and Beck Anxiety Inventory (BAI) [18] scores were in the normal range (BDI: M = 0.9, SD = 1.8, BAI: M = 2.4, SD = 2.2).
This study was approved and conducted in accordance with guidelines established by the Partners Human Research Committee. Written informed consent was obtained from each participant.
Stimuli
Participants viewed human faces [19] and schematic faces [20] (Figure 3). To match the perceptual stimulus features, the human and schematic faces were presented in black and white and scaled so the face silhouette (excluding hair) was identical between stimuli. The face stimuli were displayed using standardized software (MacStim 2.5.9) and a Sharp XG-2000 V color LCD projector (Osaka, Japan).
Figure 3. Human and Schematic Faces.
Four different human face identities (two male and two female), each displaying both negative (i.e. angry) and neutral expressions, and one neutral and one negative (i.e. angry) schematic face were used throughout the experiment. Since the schematic faces only have a single identity, each participant viewed human faces of a single identity. As the schematic faces do not have an intrinsic gender, the gender of the human faces viewed was counterbalanced across participants.
Procedure
All participants viewed four 5-minute 24-second runs of faces. Two consecutive runs of schematic faces and two consecutive runs of human faces were counterbalanced across participants. Within each run, four blocks of negative and four blocks of neutral were counterbalanced within and across participants. Each 24-second face block was separated by a 12-second low-level fixation. All runs were bracketed by a 24-second low-level fixation. This design improved upon earlier studies and allowed for better assessment of habituation, given that: 1) neutral blocks were included throughout the run, 2) fixation blocks were interleaved and 3) the design was fully counterbalanced. Within the face blocks, participants viewed a single human or schematic face, repeatedly shown for 200 ms with a 300 ms interstimulus interval.
Before each run, participants were instructed to remain awake and alert and look at the faces at eye level. Immediately after scanning, each participant was given a face recognition form, displaying target faces as well as eight distracters: two schematic (happy and scheming expressions) and six human (three different identities, each displaying neutral and negative expressions). Additionally, participants rated the schematic and human faces according to arousal value (low-high: 0–6) and valence (negative-positive: -3 to +3).
Repeated measures analysis of variance (ANOVA) was used to assess for significant differences in subjective ratings. Significant main effects and interaction effects were determined using a p < 0.05 threshold.
Image Acquisition
A Sonata 1.5 Tesla whole-body high-speed imaging device equipped for echo planar imaging (EPI) (Siemens Medical Systems, Iselin NJ) was used with a 3-axis gradient head coil. After acquiring an automated scout image and optimizing field homogeneity via localized shimming procedures, a high resolution 3D MPRAGE sequence (TR/TE/flip angle = 7.25 ms/3 ms/7°, 1.3 mm in-plane resolution, and 1 mm slice thickness) was collected for anatomical registration and normalization. Then, T1-EPI (TR/TE/flip angle = 8 sec/39 ms/90°) and T2-weighted (TR/TE/flip angle = 10 sec/48 ms/120°) sequences were gathered to monitor scanner function and assist with anatomical registration. Functional MRI images (i.e., blood-oxygenation-level-dependent or BOLD images) were acquired using a gradient echo T2*-weighted sequence (TR/TE/flip angle = 2.4 sec/40 ms/90°), discarding the first four acquisitions to allow longitudinal magnetization to reach equilibrium. Twenty-four coronal slices (slice thickness: 7 mm, 1 mm skip, voxel size: 3.125 × 3.125 × 8 mm) were acquired perpendicular to the ac-pc line. The acquisition parameters were used to minimize susceptibility in medial temporal lobe regions [21].
fMRI Data Analyses
Functional MRI data were analyzed using the standard processing stream of the Martinos Center for Biomedical Imaging [22]. The functional runs were motion corrected using an AFNI-based algorithm [23,24]. The average motion vector across all runs after correction was <1 mm and showed no significant difference between schematic and human face runs. The functional data were spatially smoothed (full-width-half-maximum = 7 mm) using a 3D Gaussian filter and intensity normalized to correct for global signal changes. Data processing included 1) 2nd-order polynomial drift correction to account for low-frequency drift and 2) removal of temporal autocorrelation by whitening [25]. The functional images were aligned to the 3D structural image. During registration, the raw functional data from each participant were visualized in anatomical space to determine that the amygdala BOLD signal was not obscured by susceptibility artifact. No subjects were excluded on this basis.
Functional images were averaged across participants according to expression (neutral, negative). For each expression, averages were made for each block (1,2,3,4) to assess temporal aspects. The averages were collapsed across the runs for each face type (schematic, human) separately. Using an anatomically defined region of interest (ROI)-based approach, each participant's left and right amygdala were manually traced on the participant's high resolution 3D MPRAGE sequence by a trained technician of the Massachusetts General Hospital's Center for Morphometric Analysis [26]. The fusiform gyrus was defined using similar methods and used as a comparison region. The anatomical tracings were used to extract functional data from each participant's selectively averaged BOLD images. The percent signal change for each condition versus fixation was calculated for each participant, and this information was entered into repeated measures ANOVA with within-subject factors: face type (human, schematic), expression (neutral, negative), time (block 1, block 2, block 3, block 4). A separate repeated measures ANOVA was used for each anatomic ROI. Main effects and interaction effects were examined. Significance was determined using p < 0.05. Where appropriate, the sources of significant findings were evaluated using post-hoc tests and multiple-comparison correction (i.e. using a reduced p-value threshold).
Authors' contributions
JCB conducted the analysis and drafted the manuscript. LMS, LFB, SLR helped design the study and revise the manuscript. CIW conceived of the study, coordinated its completion, and helped to draft the manuscript.
Acknowledgements
This work has been presented in abstract form at the Society for Biological Psychiatry annual meeting in Toronto, Canada, May 2006.
The authors wish to thank Katherine McMullin, Michelle Wedig and Danielle Williams for helping with data acquisition and Mary Foley and Larry White for technical assistance. This work was supported by The Robert Wood Johnson Foundation (Dr. Wright), as well as resource grants to the Martinos Center for Biomedical Imaging from the NCRR (P41-RR14075), and the Mental Illness and Neuroscience Discovery (MIND) Institute.
References
1. Mather M, Knight MR: Angry faces get noticed quickly: threat detection is not impaired among older adults.
J Gerontol B Psychol Sci Soc Sci 2006, 61(1):P54-7. PubMed Abstract | Publisher Full Text
2. Aronoff J, Barclay AM, Stevenson LA: The recognition of threatening facial stimuli.
J Pers Soc Psychol 1988, 54(4):647-655. PubMed Abstract | Publisher Full Text
3. Wright CI, Martis B, Shin LM, Fischer H, Rauch SL: Enhanced amygdala responses to emotional versus neutral schematic facial expressions.
Neuroreport 2002, 13(6):785-790. PubMed Abstract | Publisher Full Text
4. Wilson FA, Rolls ET: The effects of stimulus novelty and familiarity on neuronal activity in the amygdala of monkeys performing recognition memory tasks.
Exp Brain Res 1993, 93(3):367-382. PubMed Abstract | Publisher Full Text
5. Wright CI, Fischer H, Whalen PJ, McInerney SC, Shin LM, Rauch SL: Differential prefrontal cortex and amygdala habituation to repeatedly presented emotional stimuli.
Neuroreport 2001, 12(2):379-383. PubMed Abstract | Publisher Full Text
6. Wedig MM, Rauch SL, Albert MS, Wright CI: Differential amygdala habituation to neutral faces in young and elderly adults.
Neurosci Lett 2005, 385(2):114-119. PubMed Abstract | Publisher Full Text
7. Straube T, Kolassa IT, Glauer M, Mentzel HJ, Miltner WH: Effect of task conditions on brain responses to threatening faces in social phobics: an event-related functional magnetic resonance imaging study.
Biol Psychiatry 2004, 56(12):921-930. PubMed Abstract | Publisher Full Text
8. Williams LM, Brown KJ, Das P, Boucsein W, Sokolov EN, Brammer MJ, Olivieri G, Peduto A, Gordon E: The dynamics of cortico-amygdala and autonomic activity over the experimental time course of fear perception.
Cogn Brain Res 2004, 21(1):114-123. Publisher Full Text
9. Kesler-West ML, Andersen AH, Smith CD, Avison MJ, Davis CE, Kryscio RJ, Blonder LX: Neural substrates of facial emotion processing using fMRI.
Brain Res Cogn Brain Res 2001, 11(2):213-226. PubMed Abstract | Publisher Full Text
10. Fischer H, Sandblom J, Gavazzeni J, Fransson P, Wright CI, Backman L: Age-differential patterns of brain activation during perception of angry faces.
Neurosci Lett 2005, 386(2):99-104. PubMed Abstract | Publisher Full Text
11. Whalen PJ, Shin LM, McInerney SC, Fischer H, Wright CI, Rauch SL: A functional MRI study of human amygdala responses to facial expressions of fear versus anger.
Emotion 2001, 1(1):70-83. PubMed Abstract | Publisher Full Text
12. Gauthier I, Tarr MJ, Moylan J, Skudlarski P, Gore JC, Anderson AW: The fusiform "face area" is part of a network that processes faces at the individual level.
J Cogn Neurosci 2000, 12(3):495-504. PubMed Abstract | Publisher Full Text
13. Breiter HC, Etcoff NL, Whalen PJ, Kennedy WA, Rauch SL, Buckner RL, Strauss MM, Hyman SE, Rosen BR: Response and habituation of the human amygdala during visual processing of facial expression.
Neuron 1996, 17(5):875-887. PubMed Abstract | Publisher Full Text
14. Amaral DG, Behniea H, Kelly JL: Topographic organization of projections from the amygdala to the visual cortex in the macaque monkey.
Neuroscience 2003, 118(4):1099-1120. PubMed Abstract | Publisher Full Text
15. Moser E, Derntl B, Robinson S, Fink B, Gur RC, Grammer K: Amygdala activation at 3T in response to human and avatar facial expressions of emotions.
J Neurosci Methods 2007, 161(1):126-133. PubMed Abstract | Publisher Full Text
16. Oldfield RC: The assessment and analysis of handedness: The Edinburgh Inventory.
Neuropsychologia 1971, 9:97-113. PubMed Abstract | Publisher Full Text
17. Beck AT, Steer RA: Beck Anxiety Inventory Manual. Edited by Corporation TP. San Antonio, Texas , Harcourt Brace Jovanovich, Inc.; 1990.
18. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J: An inventory for measuring depression.
Arch Gen Psychiatry 1961, 4:561-571. PubMed Abstract
19. Ekman P, Friesen WV: Pictures of Facial Affect. Palo Alto, California , Consulting Psychologists Press; 1976.
20. Ohman A, Lundqvist D, Esteves F: The face in the crowd revisited: a threat advantage with schematic stimuli.
J Pers Soc Psychol 2001, 80(3):381-396. PubMed Abstract | Publisher Full Text
21. Wright CI, Martis B, Schwartz CE, Shin LM, Fischer HH, McMullin K, Rauch SL: Novelty responses and differential effects of order in the amygdala, substantia innominata, and inferior temporal cortex.
Neuroimage 2003, 18(3):660-669. PubMed Abstract | Publisher Full Text
22. Freesurfer software [http://surfer.nmr.mgh.harvard.edu] webcite
23. AFNI software [http://afni.nimh.nih.gov/] webcite
24. Cox RW: AFNI: software for analysis and visualization of functional magnetic resonance neuroimages.
Comput Biomed Res 1996, 29(3):162-173. PubMed Abstract | Publisher Full Text
25. Burock MA, Dale AM: Estimation and detection of event-related fMRI signals with temporally correlated noise: a statistically efficient and unbiased approach.
Hum Brain Mapp 2000, 11(4):249-260. PubMed Abstract | Publisher Full Text
26. Caviness VS Jr., Kennedy DN, Richelme C, Rademacher J, Filipek PA: The human brain age 7-11 years: a volumetric analysis based on magnetic resonance images.
Cereb Cortex 1996, 6(5):726-736. PubMed Abstract | Publisher Full Text
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Research article
A prospective study of monitoring practices for metabolic disease in antipsychotic-treated community psychiatric patients
Paul Mackin*, David R Bishop and Helen MO Watkinson
Author Affiliations
School of Neurology, Neurobiology and Psychiatry Newcastle University Newcastle upon Tyne UK
For all author emails, please log on.
BMC Psychiatry 2007, 7:28 doi:10.1186/1471-244X-7-28
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-244X/7/28
Received:7 February 2007
Accepted:25 June 2007
Published:25 June 2007
© 2007 Mackin et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
Patients with severe mental illness are at increased risk for metabolic and cardiovascular disease. A number of recent guidelines and consensus statements recommend stringent monitoring of metabolic function in individuals receiving antipsychotic drugs.
Methods
We conducted a prospective cohort study of 106 community-treated psychiatric patients from across the diagnostic spectrum from the Northeast of England to investigate changes in metabolic status and monitoring practices for metabolic and cardiovascular disease. We undertook detailed anthropometric and metabolic assessment at baseline and follow-up, and examined clinical notes and hospital laboratory records to ascertain monitoring practices.
Results
A high prevalence of undiagnosed and untreated metabolic disease was present at baseline assessment. Mean follow-up time was 599.3 (SD ± 235.4) days. Body mass index (p < 0.005) and waist circumference (p < 0.05) had significantly increased at follow-up, as had the number of individuals who were either overweight or obese. Fifty-three per cent of individuals had hypertriglyceridemia, and 31% had hypercholesterolemia, but only 7% were receiving lipid-lowering therapy. Monitoring practices were poor. Recording of measures of adiposity occurred in 0% of individuals, and > 50% of subjects had neither blood glucose nor lipids monitored during the follow-up period.
Conclusion
This cohort has a high prevalence of metabolic disease and heightened cardiovascular risk. Despite the publication of a number of recommendations regarding physical health screening in this population, monitoring rates are poor, and physical health worsened during the follow-up period.
Background
Severe mental illness (SMI) is associated with a significant excess of physical co-morbidity and mortality [1,2], and as such represents a major public health concern. Previous studies have reported a high prevalence of undiagnosed and untreated metabolic disorders and cardiovascular risk factors in patients with SMI [3-7]. Consensus statements from the US [8] and UK [9] have recommended stringent monitoring of metabolic status and cardiovascular risk factors in psychiatric patients receiving antipsychotic drugs, and recently published UK guidelines from the National Institute for Health and Clinical Excellence (NICE) on the management of schizophrenia [10] and bipolar disorder [11] recognise the impact of physical co-morbidity in these mental disorders, as well as the paucity of high-quality research in this field. Currently available evidence suggests that effective screening and intervention for metabolic and cardiovascular disease is lacking [3,4,9,12].
The role of antipsychotic drugs, particularly the second generation (or atypical) agents, in the pathogenesis of metabolic dysfunction and CVD in SMI is controversial. There is a burgeoning literature examining this association, and current evidence suggests that some atypical agents (e.g. clozapine and olanzapine) may have a more deleterious profile with regard to metabolic dysfunction than others (e.g. quetiapine and risperidone) [8,9,13]. Notwithstanding the reported association between antipsychotic drugs and metabolic dysfunction, prospective, longitudinal studies investigating the evolution of metabolic disease in this population are sparse. A number of recent guidelines recommend switching an antipsychotic drug to an agent with a less deleterious effect on metabolic function in patients who develop hyperglycaemia or experience significant weigh gain [8,9,14], but in the absence of longitudinal data, such strategies lack a firm evidence base.
We prospectively studied metabolic function in a cohort of antipsychotic-treated community psychiatric patients from across the diagnostic spectrum, and investigated rates of monitoring and intervention for metabolic and cardiovascular risk.
Methods
We recruited 106 patients from psychiatric out-patient clinics in the Northeast of England between January 2002 and March 2004. Exclusion criteria and baseline characteristics of this cohort have previously been described [4]. Briefly, the only entry criteria were that the patient was prescribed an antipsychotic drug (typical, atypical or combination) and was clinically stable. Patients who had anorexia nervosa or bulimia, those who were actively misusing substances or alcohol, and those with known malignant disease were excluded. All the secondary care consultant psychiatrists and primary care physicians responsible for the mental and physical healthcare of these patients were sent a detailed summary of the metabolic parameters obtained following the baseline visit, and any abnormal findings were highlighted. All patients were invited to participate in this prospective study between June 2005 and December 2005 as part of a planned 18-month follow-up assessment. Subjects gave written informed consent to participate in this study which was approved by the Newcastle Local Research Ethics Committee.
Participants were given written instructions to fast overnight on the day before assessment, and subjects were asked to confirm their fasting status by a member of the research team on the morning of study. All assessments were performed between 8.30 am and 10.00 am on the study day. Demographic and illness characteristics were recorded, together with family history of type 2 diabetes and cardiovascular disease. Current medication (including non-psychotropic drugs) and dosage was recorded and confirmed, where necessary, by reference to case notes and general practitioner records.
Height, weight, and waist and hip circumference were recorded using standardised anatomical landmarks. A single venous blood sample was withdrawn and analysed for glucose, HbA1c, insulin and lipid profile (total cholesterol, high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol and triglycerides). Insulin was measured by ELISA. The homeostatic model assessment [15] was used to assess glucose handling and values calculated using the HOMA calculator, version 2.2 (© Diabetes Trial Unit, University of Oxford). Impaired fasting glucose (IFG) was defined as fasting blood glucose between 6.1 and 7.0 mmol/l, and diabetes mellitus as fasting blood glucose > 7.0 mmol/l [16].
All patients' notes were screened for evidence of monitoring of metabolic function and recommendations regarding lifestyle and referrals to other healthcare professionals during the follow-up period. Hospital biochemistry laboratory records were checked to confirm whether blood glucose or lipid analyses had been requested by the psychiatrist or a primary care physician, but had not been recorded in the case-notes.
Data analysis was conducted using the Statistical Package for the Social Sciences, version 11, [17]. Comparisons between baseline and follow-up characteristics were examined by t-test, chi-squared or McNemar tests where appropriate. All reported p values are two-tailed. Statistical significance is defined as p < 0.05.
Results
Patient characteristics
Of the original 106 patients in the baseline cohort, 90 (85%) consented to participate in the current study. Six (5.7%) did not reply to the invitation, 6 (5.7%) refused to consent, 2 (1.9%) were too unwell to participate, and 1 patient (1%) denied having participated in the original study. Baseline and follow-up characteristics of the 90 patients are given in table 1. Forty-four (49%) of subjects were male and 46 (51%) were female. Eighty-eight (98%) were Caucasian. With regard to diagnosis, 32 (35.6%) had bipolar disorder, 27 (30.0%) had schizophrenia, 9 (10.0%) had schizo-affective disorder, and 22 (24.4%) had other mood and anxiety disorders. Mean duration between the baseline and follow-up visits was 599.3 days (SD ± 235.4; Range 328–1175). Of note is the high prevalence of family history of both cardiovascular disease and diabetes mellitus in the first-degree relatives of subjects.
Table 1. Characteristics of 90 patients at baseline and follow-up assessment.
Medication
Of the 90 patients prescribed antipsychotic medication at baseline, 83 (92%) were still taking an antipsychotic drug at follow-up. Sixty-eight (82%) patients were prescribed the same antipsychotic regimen as at baseline assessment. Details of individual drugs are given in table 2.
Table 2. Antipsychotic, and non-antipsychotic medication taken by patients with SMI
Metabolic parameters
Comparisons between baseline and follow-up metabolic parameters are given in table 3. Both BMI and waist circumference were significantly increased at follow-up, and a greater proportion of subjects were classified as overweight (BMI ≥ 25 kg/m2) compared with follow-up. In the whole cohort, pancreatic β-cell function and insulin resistance estimated by HOMA were significantly lower at follow-up compared with baseline, but these parameters were not significantly different when those subjects no longer prescribed antipsychotic drugs (n = 7) were removed from the analysis. A high proportion of patients had dyslipidaemias at baseline (hypercholesterolemia = 27.8%; hypertriglyceridemia = 53.3%), and continued to do so at follow-up (hypercholesterolemia = 28.9%; hypertriglyceridemia = 51.1%). At follow-up, 30 patients (33.3%) met criteria for the metabolic syndrome as defined by the International Diabetes Federation [18]. A comparison between rates of metabolic syndrome at baseline and follow-up was not possible as blood pressure readings were not available from the baseline assessment.
Table 3. Comparison of baseline and follow-up metabolic parameters.
Prescribing rates of lipid-lowering therapies were low (4.4% and 7.8% at baseline and follow-up, respectively).
Monitoring
Details of records in the case notes of BMI, identified weight problems and referrals to other health care professionals for lifestyle or medical intervention are given in table 4, along with the proportion of subjects who received blood glucose and/or lipid monitoring during the follow-up period. Monitoring of metabolic status was poor across all domains, the majority of patients receiving no assessment of metabolic function (BMI, waist circumference, blood glucose or lipid measurement) during the follow-up period.
Table 4. Monitoring of metabolic parameters in 90 patients over an 18-month follow-up period.
Discussion
At baseline there was a high prevalence of overweight, obesity and dyslipidaemias in this population; a significant proportion of patients also had undiagnosed disorders of glucose homeostasis, and treatment rates for these metabolic disorders was low [4]. Despite informing individual primary and secondary care physicians of these baseline results, after a mean follow-up period of 19.2 months, the metabolic parameters of this cohort had either worsened or remained unchanged.
Mean BMI had significantly increased during the follow-up period, as had the number of individuals who were in the overweight or obese categories. Waist circumference, a measure of visceral adiposity closely associated with Type 2 diabetes [19] and cardiovascular risk [20], had also significantly increased compared with baseline values. A high proportion of patients had elevated total cholesterol and/or triglycerides at baseline assessment, and a similar proportion had dyslipidaemias at follow-up assessment. More than 50% of individuals had raised triglycerides, and almost 30% had elevated total cholesterol at follow-up, but only 7% were prescribed lipid-lowering therapy, which was marginally increased from 4% at baseline. Taken together, these data suggest that the metabolic status of this cohort of patients, all of whom are in contact with mental health services, is worsening over time, and appropriate intervention appears to be lacking. Given the established increased risk of cardiovascular morbidity and mortality in individuals with severe mental illness [21], this is a worrying and ominous trend.
The metabolic health of these patients and poor rates of intervention may be explained, at least in part, by inadequate monitoring practices. A number of recent guidelines and consensus documents have highlighted the need for close monitoring of metabolic function in this population in order to minimise cardiovascular risk [9-11]. Regular monitoring of measures of adiposity and serum glucose and lipid estimation is recommended by all these documents.
Our data reveal an alarmingly poor rate of monitoring of metabolic parameters; BMI or waist circumference was not recorded in the psychiatric case notes of any patient. Although the presence of a weight-problem was identified in 21% of patients there was documented evidence of lifestyle advice in less than 10%, and only 7% were referred to another healthcare professional for further intervention. Monitoring of blood glucose and lipid levels was also poor. The majority of patients (51%) had not received blood glucose or lipid monitoring during the follow-up period; only 27% of individuals had received both glucose and lipid monitoring. Where glucose and lipid monitoring had been performed, for the majority of patients this had not taken place within the preceding 12 months. Although we were able to establish the proportion of patients who had undergone blood monitoring during the follow-up period from hospital laboratory databases, the vast majority of these results (> 90%) were not recorded in the psychiatric case notes indicating that psychiatrists were unaware of the metabolic status of these individuals.
Another observation of interest is the high reported prevalence of a positive family history of both type 2 diabetes (34%) and cardiovascular disease (61%) in the first degree relatives of subjects. The high prevalence of type 2 diabetes (18–30%) in mentally well first-degree relatives of individuals with schizophrenia has previously been reported [22], leading to speculation that there may be common susceptibility regions within the genome for both schizophrenia and type 2 diabetes [23]. Shared exposure to environmental influences known to be involved in the pathogenesis of diabetes may also partly explain this relationship. We are not aware of any previous data reporting a high prevalence of cardiovascular disease in first degree relatives of patients with severe mental illness. The prevalence of type 2 diabetes in relatives together with other shared genetic and environmental influences may explain this association, but this is an area of investigation which warrants further research.
This study has a number of limitations. Subjects were recruited from secondary and tertiary care mental health outpatient clinics, and all volunteered to participate. This cohort is, therefore, likely to comprise a group of relatively well motivated individuals who may take a more active interest in their physical (and mental) well-being than those individuals who were not in contact with mental health services or who refused to participate in this study. The physical health of this cohort may, therefore, not be representative of all psychiatric out-patients. In fact, it is probable that the physical health of those individuals who are not in contact with mental health services or who refuse to participate in physical health screening studies is less closely monitored, and therefore this population will have an even greater burden of physical co-morbidity and cardiovascular risk. The fact that subjects were recruited from a single well-defined geographical region within the UK may raise questions about extrapolating these data to other populations. However, primary and secondary care health service configurations within this geographical region are typical for the UK, and subjects were recruited from a number of community mental health centres representing a diverse socioeconomic population. A further limitation of this study is the lack of data on specific drug-effects on metabolic function. This study was not designed, nor indeed powered, to investigate the effects of individual antipsychotic drugs, or classes of drugs, on the evolution of metabolic dysfunction; our aim was to investigate monitoring practices for metabolic and cardiovascular risk and to describe the change over time of metabolic function in a diagnostically diverse cohort of patients treated with any antipsychotic drug.
Conclusion
In summary, we have presented data from a prospective study on monitoring practices for metabolic function in a cohort of antipsychotic-treated outpatients with severe mental illness from across the diagnostic spectrum. At baseline assessment there was a high prevalence of overweight, obesity and dyslipidaemias. Despite notifying relevant healthcare professionals about the extent of physical morbidity in this population, and the existence of a number of recently published guidelines and recommendations on physical health monitoring in patients receiving antipsychotic drugs, metabolic parameters were either unchanged or, in some cases, significantly worse, at follow-up assessment. Rates of monitoring of measures of adiposity, blood glucose and lipid levels, referrals to other healthcare professionals for medical or lifestyle intervention, and treatment for metabolic diseases is poor, and in many cases non-existent. There is a clear and urgent need to develop integrated models of care which specifically target the physical health of this population which already suffers an excess burden of physical morbidity and mortality.
Abbreviations
SMI Severe mental illness
NICE National Institute for health and Clinical Excellence
CVD Cardiovascular disease
HbA1c Glycosylated haemoglobin
HDL-C High-density lipoprotein cholesterol
LDL-C Low-density lipoprotein cholesterol
ELISA Enzyme-linked immunosorbent assay
HOMA Homeostatic Model Assessment
IFG Impaired fasting glucose
Competing interests
PM has received honoraria for educational meetings from AstraZeneca, BristolMyers Squibb, Eli Lilly and Jannsen-UK. The other authors have no competing interests.
Authors' contributions
PM designed the protocol, assisted in data collection, analysed the data and prepared this manuscript. DRB assisted in data collection, analysis of the results and preparation of the manuscript. HMOW assisted in developing the experimental protocol, data collection and preparation of the manuscript. All authors have seen and approved the final version of the manuscript.
Acknowledgements
PM is the recipient of a Department of Health Clinician Scientist Fellowship. We are grateful to the Newcastle, North Tyneside and Northumberland Mental Health NHS Trust which provided salary support for HMOW during this study.
References
1. Brown S: Excess mortality of schizophrenia. A meta-analysis.
Br J Psychiatry 1997, 171:502-508. PubMed Abstract
2. Phelan M, Stradins L, Morrison S: Physical health of people with severe mental illness.
BMJ 2001, 322(7284):443-444. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
3. Taylor D, Young C, Esop R, Paton C, Walwyn R: Testing for diabetes in hospitalised patients prescribed antipsychotic drugs.
Br J Psychiatry 2004, 185:152-156. PubMed Abstract | Publisher Full Text
4. Mackin P, Watkinson HM, Young AH: Prevalence of obesity, glucose homeostasis disorders and metabolic syndrome in psychiatric patients taking typical or atypical antipsychotic drugs: a cross-sectional study.
Diabetologia 2005, 48(2):215-221. PubMed Abstract | Publisher Full Text
5. Cohen D, Stolk RP, Grobbee DE, Gispen-de Wied CC: Hyperglycemia and diabetes in patients with schizophrenia or schizoaffective disorders.
Diabetes Care 2006, 29(4):786-791. PubMed Abstract | Publisher Full Text
6. Nasrallah HA, Meyer JM, Goff DC, McEvoy JP, Davis SM, Stroup TS, Lieberman JA: Low rates of treatment for hypertension, dyslipidemia and diabetes in schizophrenia: Data from the CATIE schizophrenia trial sample at baseline.
Schizophr Res 2006. PubMed Abstract | Publisher Full Text
7. De Hert M, van Winkel R, Van Eyck D, Hanssens L, Wampers M, Scheen A, Peuskens J: Prevalence of diabetes, metabolic syndrome and metabolic abnormalities in schizophrenia over the course of the illness: a cross-sectional study.
Clin Pract Epidemol Ment Health 2006, 2:14. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
8. Consensus development conference on antipsychotic drugs and obesity and diabetes
J Clin Psychiatry 2004, 65(2):267-272. PubMed Abstract
9. Barnett AH, Mackin P, Chaudhry I, Farooqi A, Gadsby R, Heald A, Hill J, Millar H, Peveler R, Rees A, Singh V, Taylor D, Vora J, Jones P: Minimising metabolic and cardiovascular risk in schizophrenia: diabetes, obesity and dyslipidaemia.
J Psychopharmacol 2007. PubMed Abstract | Publisher Full Text
10. Schizophrenia: Core Interventions in the Treatment and Management of Schizophrenia in Primary and Secondary Care National Institute for Clinical Excellence; 2002.
11. Bipolar disorder: The Management of bipolar disorder in adults, children and adolescents, in primary and secondary care National Institute for Clinical Excellence; 2006.
12. Cohn TA, Sernyak MJ: Metabolic monitoring for patients treated with antipsychotic medications.
Canadian journal of psychiatry 2006, 51(8):492-501.
13. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK: Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.
N Engl J Med 2005, 353(12):1209-1223. PubMed Abstract | Publisher Full Text
14. De Hert M, van Eyck D, De Nayer A: Metabolic abnormalities associated with second generation antipsychotics: fact or fiction? Development of guidelines for screening and monitoring.
Int Clin Psychopharmacol 2006, 21 Suppl 2:S11-5. PubMed Abstract | Publisher Full Text
15. Levy JC, Matthews DR, Hermans MP: Correct homeostasis model assessment (HOMA) evaluation uses the computer program.
Diabetes Care 1998, 21(12):2191-2192. PubMed Abstract | Publisher Full Text
16. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. National Diabetes Data Group
Diabetes 1979, 28(12):1039-1057. PubMed Abstract
17. SPSS: SPSS for Windows, version 11. Chicago, IL , SPSS inc.; 2001.
18. Alberti KG, Zimmet P, Shaw J: Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation.
Diabet Med 2006, 23(5):469-480. PubMed Abstract | Publisher Full Text
19. Ohlson LO, Larsson B, Svardsudd K, Welin L, Eriksson H, Wilhelmsen L, Bjorntorp P, Tibblin G: The influence of body fat distribution on the incidence of diabetes mellitus. 13.5 years of follow-up of the participants in the study of men born in 1913.
Diabetes 1985, 34(10):1055-1058. PubMed Abstract | Publisher Full Text
20. Rexrode KM, Carey VJ, Hennekens CH, Walters EE, Colditz GA, Stampfer MJ, Willett WC, Manson JE: Abdominal adiposity and coronary heart disease in women.
Jama 1998, 280(21):1843-1848. PubMed Abstract | Publisher Full Text
21. Brown S, Inskip H, Barraclough B: Causes of the excess mortality of schizophrenia.
Br J Psychiatry 2000, 177:212-217. PubMed Abstract | Publisher Full Text
22. Mukherjee S, Schnur DB, Reddy R: Family history of type 2 diabetes in schizophrenic patients.
Lancet 1989, 1(8636):495. PubMed Abstract | Publisher Full Text
23. Gough SC, O'Donovan M C: Clustering of metabolic comorbidity in schizophrenia: a genetic contribution?
J Psychopharmacol 2005, 19(6 Suppl):47-55. PubMed Abstract | Publisher Full Text
Pre-publication history
The pre-publication history for this paper can be accessed here:
http://www.biomedcentral.com/1471-244X/7/28/prepub
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Mexico, Campeche State, Catholic Church Records (FamilySearch Historical Records)Edit This Page
From FamilySearch Wiki
This article describes a collection of historical records available at FamilySearch.org.
Contents
Foreign Language Title
Registros Paroquiales de la Iglesia Católica del Estado de Campeche, México.
Record Description
This collection of the Campeche state parish records includes baptism, confirmation, marriage and death records from the years 1638 to 1944.
For additional details about the history of these records and help using them, see the wiki article Mexico Catholic Church Records (FamilySearch Historical Records).
For a list of records by localities, document type and dates currently published in this collection, select the Browse link from the collection landing page.
Citation for This Collection
The following citation refers to the original source of the information published in FamilySearch.org Historical Record collections. Sources include the author, custodian, publisher and archive for the original records.
Parishes in Campeche. Mexico, Campeche, Catholic Church Records. Archivo Diocesano de Campeche, Mexico.
Suggested citation format for a record in this collection.
Record Content
The key genealogical facts found in most baptism records are:
• Date of baptism
• Place of the event and usually the parish saint name
• Name of the person being baptized
• Names of the parents
• Age of the person being baptized or the person’s birth date
• Gender
• Legitimacy
• Before 1820, social class of the parents
• Sometimes the person’s race
The key genealogical facts found in most marriage records are:
• Date of marriage
• Place of the event and usually the parish saint name
• Names of the betrothed
• Names of the parents
• Names of the witnesses
• Ages and marital statuses of the betrothed
• Places of origin and residence of the betrothed and sometimes that of the parents
• Legitimacy of the betrothed
• Sometimes the race of the betrothed
The key genealogical facts found in most burial or death records are:
• Date of death or burial
• Place of burial or death
• Name of the deceased person
• Sometimes the names of the parents or the spouse, if the deceased was married
• Age of the deceased person at time of death
• Place of residence or origin of the deceased person
• Sometimes the race of the deceased
How to Use the Records
To search the collection you will need to follow this series of links:
⇒ Select the "Browse" link in the initial search page
⇒ Select the "Ciudad o pueblo" category
⇒ Select the "Parroquia" category
⇒ Select the "Tipo de registro y años" category which takes you to the images.
Look at the images one by one comparing the information with what you already know about your ancestors to determine which one is your ancestor. You may need to compare the information about more than one person to make this determination.
In most cases, Mexican Catholic parish registers are the only records before 1859 that identify individuals, parents, and spouses. After this date, civil authorities began registering vital statistics (nacimientos, matrimonies, y defunciones) that by law include people of all religions. The information in civil sources confirms and supplements the information in church records. Be sure to search both the parish and civil records after 1860.
Related Web Sites
Related Wiki Articles
Contributions to This Article
We welcome user additions to FamilySearch Historical Records wiki articles. Guidelines are available to help you make changes. Thank you for any contributions you may provide. If you would like to get more involved join the WikiProject FamilySearch Records.
Citing FamilySearch Historical Collections
When you copy information from a record, you should list where you found the information. This will help you or others to find the record again. It is also good to keep track of records where you did not find information, including the names of the people you looked for in the records.
A suggested format for keeping track of records that you have searched is found in the wiki article Help:How to Cite FamilySearch Collections.
Citation Example for a Record Found in This Collection
“Argentina, Buenos Aires, Catholic Church Records, 1635-1981,” images, FamilySearch (https://familysearch.org: accessed 28 February, 2012), La Plata > San Ponciano > Matrimonios 1884-1886 > image 71 of 389 images, Artemio Avendano and Clementina Peralta, 1884; citing Parroquia de San Ponciano en la Plata, Buenos Aires, Argentina, Matrimonios. San Ponciano, La Plata, Buenos Aires.
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• This page has been accessed 463 times.
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What is Vulnerability? (Basics) - Publications
See all Geoscience Australia Publications
Title ↑ Authors Published Released
Community Vulnerability to Natural Hazards: Contributing to total risk assessment Jones, T. 2003 09/Dec/2009
Disaster Data Collection Jones, T. 2003 10/Aug/2010
Floods: Hazards, modelling and risk assessment Geoscience Australia 2003 09/Dec/2009
GIS and Risk-GIS: Decision Support Tools Geoscience Australia 2003 09/Dec/2009
Quantifying social vulnerability: a methodology for identifying those at risk to natural hazards Dwyer, A.Zoppou, C.Nielsen, O.Day, S.Roberts, S. 2004 04/Aug/2005
(5 products total)
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About this Journal Submit a Manuscript Table of Contents
Journal of Biomedicine and Biotechnology
Volume 2010 (2010), Article ID 943254, 4 pages
doi:10.1155/2010/943254
Review Article
IL-17 in Systemic Lupus Erythematosus
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02130, USA
Received 5 February 2010; Accepted 7 February 2010
Academic Editor: Brian Poole
Copyright © 2010 José C. Crispín and George C. Tsokos. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
IL-17 is a cytokine with powerful proinflammatory activity. Production of IL-17 is abnormally increased in patients with systemic lupus erythematosus (SLE), a multiorgan chronic autoimmune disease. In patients with SLE, (double negative) T cells are an important source of IL-17. IL-17 produced by double negative and CD4 T cells participates in the pathogenesis of the disease. IL-17-producing T cells are present in the kidneys of patients with lupus nephritis. IL-17 increased production in patients with SLE can amplify the immune response by increasing target organ inflammation and damage and by augmenting the production of antibodies by B cells.
1. Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disorder that appears in genetically prone individuals triggered by ill-defined environmental factors [1]. Patients with SLE develop an immune response against numerous, mostly intracellular self-antigens. This chronic response alters the function of the immune system and releases self-antigens that along with autoantibodies form immune complexes that deposit in susceptible vascular beds, mostly in skin, joints, and renal glomeruli. Immune complex deposition causes local inflammation and tissue damage that probably amplify the autoimmune response creating thus a vicious cycle.
Cytokines are intimately involved in SLE pathogenesis. They contribute to the underlying immune dysfunction and to immune-mediated events that damage target organs. IL-17 is a cytokine with powerful inflammatory properties. Recent evidence suggests that it is involved in the pathogenesis of SLE. In this paper, we discuss the evidence that links IL-17 to SLE in both human and animal models. Data indicates that IL-17-driven inflammation amplifies SLE-induced tissue damage and contributes to tolerance breakdown in SLE patients.
2. Interleukin-17
Interleukin (IL)-17 is an ancient cytokine intimately related with epithelia—particularly with the intestinal mucosa [2, 3]. Its main receptor, IL-17RA, is broadly expressed on epithelial and endothelial cells as well as on immune cells [46]. It is produced by several cell types including activated T cell subsets (CD4+, CD8+, and TCR- CD4 CD8, TCR-), natural killer cells, and neutrophils [7]. IL-17 plays an essential role in the immune response against bacteria and fungi [8].
IL-17 has pro-inflammatory capacities exerted through its ability to induce secretion of chemokines such as IL-8, monocyte chemoattractant protein-1 (MCP-1), and growth-related oncogene protein-, which recruit monocytes and neutrophils [912]. IL-17 also facilitates T cell activation and infiltration into tissues by upregulating the expression of intercellular adhesion molecule-1 (ICAM-1) and amplifies the immune response by inducing the production of IL-6, prostaglandin E2, granulocyte-macrophage colony stimulating factor (GM-CSF), and granulocyte colony stimulating factor [1315]. Additionally, IL-17 acts synergistically with other cytokines, particularly IL-1, tumor necrosis factor (TNF)-, and interferon (IFN)- [13, 16].
IL-17-producing cells have been recently implicated in the pathogenesis of a wide range of inflammatory and autoimmune diseases including psoriasis, rheumatoid arthritis (RA) [17, 18], inflammatory bowel disease (IBD) [19], systemic sclerosis [20], and systemic lupus erythematosus (SLE) [21, 22].
3. IL-17 Production in SLE
Evidence indicates that production of IL-17 is abnormally high in patients with SLE. Its levels are increased in SLE sera [23] and correlate with SLE disease activity [22, 24]. Moreover, the frequency of IL-17-producing T cells is increased in the peripheral blood of patients with SLE [21, 22, 25].
A significant fraction of the IL-17 produced in SLE patients derives from double negative (DN) TCR-CD4CD8 T cells [21]. DN T cells represent a small T cell subset in healthy individuals. These cells are expanded in peripheral blood of SLE patients and produce pro-inflammatory chemokines and cytokines including IL-17, IFN-, and IL-1 [26]. Support for their pathogenic role derives from the fact that IL-17-producing T cells have been observed in kidneys of patients with lupus nephritis [21, 27], among infiltrates rich in DN T cells [21].
Apart from its direct pro-inflammatory activity, the effects of IL-17 in other cell types may contribute to SLE pathogenesis. Increased production of total IgG, anti-dsDNA IgG, and IL-6 by peripheral blood mononuclear cells of patients with lupus nephritis was observed when they were cultured in the presence of IL-17 [28]. These findings suggest that IL-17 may participate in the activation of B cells in patients with SLE.
IL-17 production is also high in mice affected by lupus-like diseases [29]. An abnormally high fraction of T cells from MRL/lpr mice produce IL-17 [29]. In these mice, as in patients with SLE, DN T cells are an important source of IL-17. Interestingly, lymph node cells derived from MRL/lpr mice were able to cause glomerulonephritis when transferred into lymphocyte-deficient Rag-/- mice. The effect depended on their prestimulation with IL-23, a cytokine known to stimulate IL-17 production in humans and mice [29]. IL-17, along with IL-13 and IFN-, is the main cytokine produced by infiltrating T cells in nephritic kidneys of MRL/lpr mice [29, 30].
In SNF1 mice (New Zealand Black x SWR F1), spleen cells produce significantly higher amounts of IL-17 than spleen cells from control mice when cultured in the presence of nucleosomes, a known lupus autoantigen [31]. In these mice as in the MRL/lpr, IL-17-producing T cells are detected in kidneys affected by nephritis. Interestingly, clinical disease improved along with decreased IL-17 production in mice treated with a tolerating regime induced with a histone-derived peptide [31], or with nasal administration of anti-CD3 [32].
The BXD2 mouse, a model that spontaneously develops arthritis, glomerulonephritis, and autoantibodies [33], has high IL-17 levels in serum as well as increased numbers of IL-17+ cells in the spleen [34]. Accordingly, upon stimulation an increased fraction of BXD2 T cells produce IL-17. Humoral responses are strongly augmented in these mice [35]. They spontaneously develop germinal centers (GC) in the spleen where IL-17+ T cells colocalize with IL-17R+ B cells [34]. The importance of IL-17 in this process was demonstrated when B6 and predisease BXD2 mice were infected with an IL-17-coding adenovirus that increased IL-17 levels and induced the formation of germinal centers in both mouse strains. Concordantly, formation of GC diminished and production of anti-DNA and anti-histone antibodies was abrogated in BXD2 IL-17R deficient mice [34]. This supports the concept that IL-17 can provide help to B cells.
4. Amplification of the IL-17 Response in SLE
IL-17 is the prototypical cytokine of a CD4 T cell effector subset known as cells [7]. cells are generated when naïve CD4 T cells are primed in the presence of TGF- and certain inflammatory cytokines (i.e., IL-21, IL-6, and IL-23) [3638]. Patients with SLE have a higher frequency of IL-17-producing T cells [21, 22, 25]. It is thus assumed that the generation of cells is favored in SLE patients. Nevertheless, this has not been directly addressed in any study. Moreover, cells different than CD4 T cells are important sources of IL-17 and particularly in SLE, DN T cells are important producers of this cytokine [21].
From a theoretical point of view, the SLE environment is ideal for the generation of cells. T cells from patients with SLE produce abnormally low levels of IL-2 [39], a cytokine able to prevent the generation of cells and favor that of regulatory T cells [40, 41]. Moreover, production of the inflammatory cytokines IL-6 and IL-21 is enhanced in cells derived from patients with SLE [42, 43]. Plasmacytoid dendritic cells can induce the conversion of CD4 T cells into cells after stimulation through TLR7 [44]. In patients with SLE, who have circulating immune complexes that contain nucleic acids, this could represent an important mechanism for the amplification of the response (Figure 1).
Figure 1: The IL-17 response is amplified in SLE. Nucleic acid-containing immune complexes and other inflammatory stimuli (e.g., cytokines) induce the production of pro-inflammatory cytokines by dendritic cells. These factors, along with others not yet identified, favor the generation of pro-inflammatory IL-17-producing T cell subsets (i.e., and DN T cells) able to migrate to target organs and inflict damage. Produced IL-17 amplifies the inflammatory response and stimulates other cell types (e.g., B cells).
In summary, IL-17 production is increased in patients with SLE. Elevated IL-17 levels probably contribute to the recruitment and activation of immune cells (e.g., neutrophils and T cells) to target organs and thus amplify an ensuing immune response. The immune environment in patients with SLE is ideally suited for the generation of IL-17-producing T cells. Produced IL-17 probably has broad effects on the immune system that include B cell stimulation [24]. The precise pathways through which IL-17 contributes to SLE pathology will need to be identified in future work.
References
1. J. C. Crispín, S.-N. C. Liossis, K. Kis-Toth, et al., “Pathogenesis of human systemic lupus erythematosus: recent advances,” Trends in Molecular Medicine, vol. 16, no. 2, pp. 47–57, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
2. E. Rouvier, M.-F. Luciani, M.-G. Mattei, F. Denizot, and P. Golstein, “CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus Saimiri gene,” The Journal of Immunology, vol. 150, no. 12, pp. 5445–5456, 1993. View at Scopus
3. C. T. Weaver and R. D. Hatton, “Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective,” Nature Reviews Immunology, vol. 9, no. 12, pp. 883–889, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
4. S. Aggarwal and A. L. Gurney, “IL-17: prototype member of an emerging cytokine family,” Journal of Leukocyte Biology, vol. 71, no. 1, pp. 1–8, 2002. View at Scopus
5. C. T. Weaver, R. D. Hatton, P. R. Mangan, and L. E. Harrington, “IL-17 family cytokines and the expanding diversity of effector T cell lineages,” Annual Review of Immunology, vol. 25, pp. 821–852, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
6. D. Toy, D. Kugler, M. Wolfson, et al., “Cutting edge: interleukin 17 signals through a heteromeric receptor complex,” The Journal of Immunology, vol. 177, no. 1, pp. 36–39, 2006. View at Scopus
7. T. Korn, E. Bettelli, M. Oukka, and V. K. Kuchroo, “IL-17 and Th17 cells,” Annual Review of Immunology, vol. 27, pp. 485–517, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
8. A. Peck and E. D. Mellins, “Precarious balance: Th17 cells in host defense,” Infection and Immunity, vol. 78, no. 1, pp. 32–38, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
9. A. M. Woltman, S. de Haij, J. G. Boonstra, S. J. P. Gobin, M. R. Daha, and C. van Kooten, “Interleukin-17 and CD40-Ligand synergistically enhance cytokine and chemokine production by renal epithelial cells,” Journal of the American Society of Nephrology, vol. 11, no. 11, pp. 2044–2055, 2000. View at Scopus
10. J. Witowski, K. Pawlaczyk, A. Breborowicz, et al., “IL-17 stimulates intraperitoneal neutrophil infiltration through the release of GROα chemokine from mesothelial cells,” The Journal of Immunology, vol. 165, no. 10, pp. 5814–5821, 2000. View at Scopus
11. M. J. Ruddy, F. Shen, J. B. Smith, A. Sharma, and S. L. Gaffen, “Interleukin-17 regulates expression of the CXC chemokine LIX/CXCL5 in osteoblasts: implications for inflammation and neutrophil recruitment,” Journal of Leukocyte Biology, vol. 76, no. 1, pp. 135–144, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
12. M. Laan, Z.-H. Cui, H. Hoshino, et al., “Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways,” The Journal of Immunology, vol. 162, no. 4, pp. 2347–2352, 1999. View at Scopus
13. C. Albanesi, A. Cavani, and G. Girolomoni, “IL-17 is produced by nickel-specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN-γ and TNF-α,” The Journal of Immunology, vol. 162, no. 1, pp. 494–502, 1999. View at Scopus
14. P. Schwarzenberger, W. Huang, P. Ye, et al., “Requirement of endogenous stem cell factor and granulocyte-colony-stimulating factor for IL-17-mediated granulopoiesis,” The Journal of Immunology, vol. 164, no. 9, pp. 4783–4789, 2000. View at Scopus
15. X.-Y. Cai, C. P. Gommoll Jr., L. Justice, S. K. Narula, and J. S. Fine, “Regulation of granulocyte colony-stimulating factor gene expression by interleukin-17,” Immunology Letters, vol. 62, no. 1, pp. 51–58, 1998. View at Publisher · View at Google Scholar · View at Scopus
16. M. J. Ruddy, G. C. Wong, X. K. Liu, et al., “Functional cooperation between interleukin-17 and tumor necrosis factor-α is mediated by CCAAT/enhancer-binding protein family members,” Journal of Biological Chemistry, vol. 279, no. 4, pp. 2559–2567, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
17. P. Miossec, “Interleukin-17 in rheumatoid arthritis: if T cells were to contribute to inflammation and destruction through synergy,” Arthritis and Rheumatism, vol. 48, no. 3, pp. 594–601, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
18. R. L. Van Bezooijen, H. C. M. Farih-Sips, S. E. Papapoulos, and C. W. Lowik, “Interleukin-17: a new bone acting cytokine in vitro,” Journal of Bone and Mineral Research, vol. 14, no. 9, pp. 1513–1521, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
19. D. Q. Shih, S. R. Targan, and D. McGovern, “Recent advances in IBD pathogenesis: genetics and immunobiology,” Current Gastroenterology Reports, vol. 10, no. 6, pp. 568–575, 2008. View at Publisher · View at Google Scholar · View at Scopus
20. K. Kurasawa, K. Hirose, H. Sano, et al., “Increased interleukin-17 production in patients with systemic sclerosis,” Arthritis and Rheumatism, vol. 43, no. 11, pp. 2455–2463, 2000. View at Publisher · View at Google Scholar · View at Scopus
21. J. C. Crispin, M. Oukka, G. Bayliss, et al., “Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys,” The Journal of Immunology, vol. 181, no. 12, pp. 8761–8766, 2008. View at Scopus
22. C. K. Wong, L. C. W. Lit, L. S. Tam, E. K. M. Li, P. T. Y. Wong, and C. W. K. Lam, “Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity,” Clinical Immunology, vol. 127, no. 3, pp. 385–393, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
23. C. K. Wong, C. Y. Ho, E. K. Li, and C. W. K. Lam, “Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus,” Lupus, vol. 9, no. 8, pp. 589–593, 2000. View at Scopus
24. A. Doreau, A. Belot, J. Bastid, et al., “Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus,” Nature Immunology, vol. 10, no. 7, pp. 778–785, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
25. J. Yang, Y. Chu, X. Yang, et al., “Th17 and natural treg cell population dynamics in systemic lupus erythematosus,” Arthritis and Rheumatism, vol. 60, no. 5, pp. 1472–1483, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
26. J. C. Crispin and G. C. Tsokos, “Human TCR-αβ+CD4CD8 T cells can derive from CD8+ T cells and display an inflammatory effector phenotype,” The Journal of Immunology, vol. 183, no. 7, pp. 4675–4681, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
27. Y. Wang, S. Ito, Y. Chino, et al., “Laser microdissection-based analysis of cytokine balance in the kidneys of patients with lupus nephritis,” Clinical and Experimental Immunology, vol. 159, no. 1, pp. 1–10, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
28. G. Dong, R. Ye, W. Shi, et al., “IL-17 induces autoantibody overproduction and peripheral blood mononuclear cell overexpression of IL-6 in lupus nephritis patients,” Chinese Medical Journal, vol. 116, no. 4, pp. 543–548, 2003. View at Scopus
29. Z. Zhang, V. C. Kyttaris, and G. C. Tsokos, “The role of IL-23/IL-17 axis in lupus nephritis,” The Journal of Immunology, vol. 183, no. 5, pp. 3160–3169, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
30. Y. Wang, S. Ito, Y. Chino, et al., “Use of laser microdissection in the analysis of renal-infiltrating T cells in MRL/lpr mice,” Modern Rheumatology, vol. 18, no. 4, pp. 385–393, 2008. View at Publisher · View at Google Scholar · View at PubMed
31. H.-K. Kang, M. Liu, and S. K. Datta, “Low-dose peptide tolerance therapy of lupus generates plasmacytoid dendritic cells that cause expansion of autoantigen-specific regulatory T cells and contraction of inflammatory Th17 cells,” The Journal of Immunology, vol. 178, no. 12, pp. 7849–7858, 2007.
32. H. Y. Wu, F. J. Quintana, and H. L. Weiner, “Nasal anti-CD3 antibody ameliorates lupus by inducing an IL-10-secreting CD4+,” The Journal of Immunology, vol. 181, pp. 6038–6050, 2008.
33. H.-C. Hsu, T. Zhou, H. Kim, et al., “Production of a novel class of polyreactive pathogenic autoantibodies in BXD2 mice causes glomerulonephritis and arthritis,” Arthritis and Rheumatism, vol. 54, no. 1, pp. 343–355, 2006. View at Publisher · View at Google Scholar · View at PubMed
34. H.-C. Hsu, P. A. Yang, J. Wang, et al., “Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice,” Nature Immunology, vol. 9, no. 2, pp. 166–175, 2008. View at Publisher · View at Google Scholar · View at PubMed
35. H.-C. Hsu, Y. Wu, P. Yang, et al., “Overexpression of activation-induced cytidine deaminase in B cells is associated with production of highly pathogenic autoantibodies,” The Journal of Immunology, vol. 178, no. 8, pp. 5357–5365, 2007.
36. M. Veldhoen, R. J. Hocking, C. J. Atkins, R. M. Locksley, and B. Stockinger, “TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells,” Immunity, vol. 24, pp. 179–189, 2006.
37. L. Yang, D. E. Anderson, C. Baecher-Allan, et al., “IL-21 and TGF-β are required for differentiation of human TH17 cells,” Nature, vol. 454, pp. 350–352, 2008. View at Publisher · View at Google Scholar · View at PubMed
38. P. R. Mangan, L. E. Harrington, D. B. O'Quinn, et al., “Transforming growth factor-β induces development of the TH17 lineage,” Nature, vol. 441, pp. 231–234, 2006. View at Publisher · View at Google Scholar · View at PubMed
39. J. Alcocer-Varela and D. Alarcon-Segovia, “Decreased production of and response to interleukin-2 by cultured lymphocytes from patients with systemic lupus erythematosus,” Journal of Clinical Investigation, vol. 69, no. 6, pp. 1388–1392, 1982.
40. B. Stockinger, “Good for goose, but not for gander: IL-2 interferes with Th17 differentiation,” Immunity, vol. 26, no. 3, pp. 278–279, 2007. View at Publisher · View at Google Scholar · View at PubMed
41. E. Bettelli, Y. Carrier, W. Gao, et al., “Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells,” Nature, vol. 441, no. 7090, pp. 235–238, 2006. View at Publisher · View at Google Scholar · View at PubMed
42. M. Linker-Israeli, R. J. Deans, D. J. Wallace, J. Prehn, T. Ozeri-Chen, and J. R. Klinenberg, “Elevated levels of endogenous IL-6 in systemic lupus erythematosus: a putative role in pathogenesis,” The Journal of Immunology, vol. 147, no. 1, pp. 117–123, 1991.
43. C. K. Wong, P. T. Y. Wong, L. S. Tam, E. K. Li, D. P. Chen, and C. W. K. Lam, “Elevated production of B cell chemokine CXCL13 is correlated with systemic lupus erythematosus disease activity,” Journal of Clinical Immunology, vol. 30, no. 1, pp. 45–52, 2010. View at Publisher · View at Google Scholar · View at PubMed
44. C. F. Yu, W. M. Peng, J. Oldenburg, et al., “Human plasmacytoid dendritic cells support Th17 cell effector function in response to TLR7 ligation,” The Journal of Immunology, vol. 184, no. 3, pp. 1159–1167, 2010. View at Publisher · View at Google Scholar · View at PubMed
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About this Journal Submit a Manuscript Table of Contents
International Journal of Distributed Sensor Networks
Volume 2012 (2012), Article ID 820716, 13 pages
doi:10.1155/2012/820716
Research Article
A Wireless Sensor Network for Precise Volatile Organic Compound Monitoring
1University of Florence and The MIDRA Consortium, 50139 Florence, Italy
2Health, Safety, Environment and Quality Department, Eni S.p.A., 00144 Rome, Italy
3Netsens s.r.l, Sesto Fiorentino, 50019 Florence, Italy
Received 24 November 2011; Accepted 8 February 2012
Academic Editor: Carlos Ramos
Copyright © 2012 Gianfranco Manes et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
A variety of methods have been developed to monitor VOC concentration in hazardous sites. The methods range from calculation to measurement, point measuring to remote sensing. Some are suited for leak detection, others for estimation of the annual emission or both. None of the following available methods comes close to the ideal method. A distributed instrument providing precise monitoring of Volatile Organic Compound (VOC) concentration in a petrochemical plant is described; it consists of a Wireless Sensor Network (WSN) platform whose nodes are equipped with meteorological/climatic sensors and VOC detectors. Internet connectivity is provided in real time at a one-minute sampling rate, thus providing environmental authorities and plant management with an unprecedented tool for immediate warning in case of critical events. The paper describes the WSN platform, detailing various units (gateways, nodes, detectors) and shows the features of scalability and reconfigurability, with minimal intrusiveness or obtrusiveness. Environmental and process data are forwarded to a remote server and made available to the authenticated users through a rich user interface that provides data rendering in various formats and worldwide access to data. A survey of the VOC detector technologies involved is also provided.
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Bibliography: Prayers
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Title: Prayers
Author: Nina Kiriki Hoffman
Year: 1995
Type: SHORTFICTION
Storylen: shortstory
Series: Chapel Hollow
Language: English
ISFDB Record Number: 1400022
User Rating: This title has fewer than 5 votes. VOTE
Current Tags: None Add Tags
Publications:
Copyright (c) 1995-2011 Al von Ruff.
ISFDB Engine - Version 4.00 (04/24/06)
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Peter Schiff: The Irish Should Default On Their Debt, Not Become Slaves To Bankers
November 25, 2010
By
Austrian economist and investor Peter Schiff slams criminal governments for bailing out their crony banker buddies. Peter explains that the Irish people are now going to suffer paying heavy taxes to pay back private banker debts.
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Nano Express
Catalytic ozone oxidation of benzene at low temperature over MnOx/Al-SBA-16 catalyst
Jong Hwa Park1, Ji Man Kim2, Mingshi Jin2, Jong-Ki Jeon3, Seung-Soo Kim4, Sung Hoon Park5, Sang Chai Kim6 and Young-Kwon Park1,7*
Author Affiliations
1 Graduate School of Energy and Environmental System Engineering, University of Seoul, Seoul 130-743, South Korea
2 Department of Chemistry, BK21 School of Chemical Materials Science and Department of Energy Science, Sungkyunkwan University, Suwon 440-746, South Korea
3 Department of Chemical Engineering, Kongju National University, Cheonan 330-717, South Korea
4 Department of Chemical Engineering, Kangwon National University, Samcheok 245-711, South Korea
5 Department of Environmental Engineering, Sunchon National University, Suncheon 540-742, South Korea
6 Department of Environmental Education, Mokpo National University, Muan 534-729, South Korea
7 School of Environmental Engineering, University of Seoul, Seoul 130-743, South Korea
For all author emails, please log on.
Nanoscale Research Letters 2012, 7:14 doi:10.1186/1556-276X-7-14
Published: 5 January 2012
Abstract
The low-temperature catalytic ozone oxidation of benzene was investigated. In this study, Al-SBA-16 (Si/Al = 20) that has a three-dimensional cubic Im3m structure and a high specific surface area was used for catalytic ozone oxidation for the first time. Two different Mn precursors, i.e., Mn acetate and Mn nitrate, were used to synthesize Mn-impregnated Al-SBA-16 catalysts. The characteristics of these two catalysts were investigated by instrumental analyses using the Brunauer-Emmett-Teller method, X-ray diffraction, X-ray photoelectron spectroscopy, and temperature-programmed reduction. A higher catalytic activity was exhibited when Mn acetate was used as the Mn precursor, which is attributed to high Mn dispersion and a high degree of reduction of Mn oxides formed by Mn acetate than those formed by Mn nitrate.
Keywords:
Al-SBA-16; Mn precursors; benzene; ozone; catalytic oxidation
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Activity Not Available
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Grierson Lab:Back Door
From OpenWetWare
Revision as of 13:13, 29 November 2010 by CGrierson (Talk | contribs)
Jump to: navigation, search
Grierson Lab frontpage
Claire Grierson
claire.grierson@bris.ac.uk
http://www.bristol.ac.uk/biology/person/index.html?personKey=claire.grierson
Amy Chen
The role of ROP small GTPases in root hair development
Oliver Purcell
Modelling Synthetic Gene Networks
co-supervised by Prof Mario Di Bernardo
Tom Gorochowski
Network dynamics and evolution
co-supervised by Prof Mario Di Bernardo
Ken Groom
Root hair development in cereals
co-supervised by Prof Keith Edwards
Alumnus: Angharad Jones
Regulation of root hair development by auxin
Harry worked in the Friml lab before becoming a post doc in Jim Murray's lab in Cardiff
Alumnus: Gordon Breen
Identifying genes and molecular machines that drive root hair tip growth
Gordon became a post doc in Kerry Franklin's lab. at the University of Bristol
Alumnus: Laura Bevan nee Taylor
Characterisation of the TIP1 S-acyltransferase and the function of S-acylation within the cell.
Laura moved to the Department of Oral and Dental Science at the University of Bristol
Alumnus: Piers Hemsley
Characterisation of the TIP1 S-acyltransferase and the function of S-acylation within the cell.
Piers moved to a post doc position in Heather Knight's lab in Durham
Alumnus: Matt Smallman
Defining the network of ROP GTPase signalling and its regulation in root hair development.
Matt moved to run a lab at a hops company
Alumnus: Eric Lalanne
SCN1/ROPGDI1.
Eric became a research leader for a company in Barcelona
Alumnus: Sarah Usher
Rapid identification of root hair genes, and characterisation of OXI1.
Sarah left to study for a PhD with Graham King
Alumnus: Donal O'Sullivan
Rapid molecular identification of root hair genes, and characterisation of SCN1/ROPGDI1.
Donal left to run a lab at NIAB
Alumnus: Mark Jones
Role of ROP small GTPases in root hair growth.
Mark moved on to post doctoral research with Nick Smirnoff at the University of Exeter before taking on a new career in youth work
Alumnus: Alison Kemp
Molecular identification and genetics of TIP1.
Ali left to take a career break to be a full time Mum.
Alumnus: Jill Parker
Root hair genetics.
Jill is enjoying a well-earned retirement
Grierson Lab frontpage
Personal tools
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IGEM:American University/2009/Notebook/Advanced Experimental Chemistry: Fun Times in Beeghly/2013/02/04
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iGEM Project name 1 Main project page
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Welcome to Advanced Experimental Chemistry
Today's Procedure
1) Crosslinking the 5 isopropanol, pvoh, glutaraldehyde films made on Friday done by the same procedure previously used to crosslink.
2) Making more glutaraldehyde fixant: 1L distilled water + 2 mL H2SO4 + 20 g sodium sulfate stirred on stir plate to dissolution (stored in 4 250mL plastic bottles).
3) Beginning the Synthesis of the Quaternary Amine: 10 mL acetonitrile + 1.148 mL chlorobutanol + 0.753 mL triethylamine in a round bottom flask. Flask was placed on a heating mantle (set to 50 of 100V) and a sand bath and was attached to a redox condenser apparatus [nitrogen gas was allowed to flow through the redox condenser such that the reaction occurs under nitrogenous conditions]. Reaction is run for 3 days.
Notes
After the crosslinking, most of the films were flimsy and breaking. This could be because the films were too thin or bc the isopropanol evaporate before crosslinking. The experiment will be redone with phenol instead of isopropanol and 1g PVOH instead of 0.5g.
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OpenWetWare steering committee/SC retreat
From OpenWetWare
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(Draft OWW Goals & Mission)
(Draft OWW Goals & Mission)
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The goals of OWW are to support open research, education, publication, and discussion in biology and biological engineering.
The goals of OWW are to support open research, education, publication, and discussion in biology and biological engineering.
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The mission of OWW is to promote and support an community of researchers, students, and others who are working towards these goals.
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The mission of OWW is to promote and support a community of researchers, students, and others who are working towards these goals.
Revision as of 15:51, 25 July 2006
The OWW retreat is a relaxed opportunity to reevalute the mission and future directions of OpenWetWare.
Location: 68-121
Time: 1pm - 6pm
Contents
Location Suggestions
Location should be able to handle teleconferencing. Fast internet connection would probably be sufficient - we could use skype.
68-121 is now reserved from 1pm to 8pm --Sri Kosuri 14:54, 18 July 2006 (EDT)
Agenda (1pm-6pm)
Welcome/Introducion (1:00-1:30pm)
• Why we're having this meeting:
• Survival of OWW (technical infrastructure)
• Decisions are currently made ad-hoc, would like to have a mission statement for OWW to use to evaluate options more systematically.
• Decide on an organizational structure to make decisions and carry them out.
• This meeting is not a discussion of how we might specifically implement new technologies on the site (e.g. we should focus on bigger issues, rather than technical implementation details.)
• 5 min introductions:
• Who you are, what you currently use OWW for and your vision for OWW in the future.
Technical infrastructure
• What would it take to keep the site operating indefinitely in its current incarnation.
Mission (1:30-3:00)
To help specify a mission statement, we have listed the current mission statement as well as outlined some of the current issues in each of the major areas of use on OWW. We hope that thinking about these issues will help to crystalize the contentious components of the mission statement.
Current mission statement
OpenWetWare is an effort to promote the sharing of information, know-how, and wisdom among researchers and groups who are working in biology & biological engineering. OWW provides a place for labs, individuals, and groups to organize their own information and collaborate with others easily and efficiently. In the process, we hope that OWW will not only lead to greater collaboration between member groups, but also provide a useful information portal to our colleagues, and ultimately the rest of the world.
Research Laboratory Communities
• Users have requested private pages on the wiki, for sharing sensitive information amongst collaborators.
• Usually we can enable both collaboration and open sharing, but in this case they butt heads - what is the priority for OWW in this case?
• Users have requested a distribution of OWW to run locally in their labs with easy mechanisms to post content to the main OWW site.
• Is it worth our time to develop tools that are useful to biological researchers independent of the OWW site?
• Labs use OWW as their lab/collaboration (syntheticbiology.org) homepage
• How actively do we encourage this (vs. contributing to the shared information resources)?
• Is there a way to let these "specialized" collaborations occur while encouraging/requiring some contribution to shared resources? Should we be more explicit with rules? i.e. some of your content must contribute to the OWW community as a whole if you are going to host your site on OWW; you can't be an independent unit that doesn't "interact" with the rest of the community.
• Doesn't having content in the OWW domain make the interaction with the rest of the community automatic?
• Labs unaffialited with biology have requested to be on OWW, up till now we have rejected their requests.
• Should we remain solely a biology resource? If so, where is the line between biology and the rest of science/engineering?
• Need to have a clear "definition" of biology to do this. May need a more formal mechanism (by committee?) to decide who can join. How is this decided now?
• What are the worries about other sciences joining? Is it because of a scientific culture clash, or is it more pragmatic (like handling more data than we can)? At the moment, biology is welcoming fresh eyes from a variety of traditional fields like physics and applied mathematics, so it seems like limiting participation to biology only will be a fuzzy endeavor.
• Are ethicists, policy-makers, science reporters, etc, included in our community?
• There are currently some non-biology groups and users on the site. Do we reevaluate the eligibility of all current users on the site to ensure everyone fits into our community guidelines and remove those who don't?
Shared information resources
• Users have developed shared information resources pages - such as protocols, materials, equipment, strains, etc.
• Users also put up their own versions of protocols, materials, etc, should we encourage either approach over the other?
Education
• There have been a couple courses taught using OWW. OWW was useful for course development, increasing student involvement, reusing materials, and course improvements. Research communities have used some of the course materials as well.
• Do we have any restrictions on the type of course that can be hosted on OWW? Should it be limited to lab courses, biology courses, etc?
• There are HS Biology Olympiad pages on OWW, should we allow that to continue?
• Should we have non-researcher students on the site?
• Is OWW only a resource for current researchers or is it also a vehicle to encourage new people to explore/participate in research?
Publishing
• John is using OWW to allow for feedback on submitted abstracts, others have posted lab notebooks, preliminary results, drafts of papers for publication, etc.
• Do we want to encourage the development of OWW as an alternative publishing platform?
• Does OWW want to serve as a tool/resource to aid in the traditional publication process (i.e. post preliminary results, drafts, etc. with the aim that they will eventually lead to a publication in a journal), or does OWW want to promote a new publication model? The latter could mean that results and 'articles' posted and developed on OWW could serve as the end publication - one that can be read and commented, and ever perhaps edited by the whole community. Or maybe OWW is the apropriate place to discuss and figure out what an alternative publishing model is.
• If we do this, are we responsible for figuring out how this may or may not impact publication of similar material in more traditional formats? i.e. Does OWW have a responsibility to its users to inform them of what publication/ownership rights they may be giving up by posting things on the site?
Meta
• Are we restricting ourselves by defining a mission itself. Currently, we allow almost everything that has to do with biology on the site. This has allowed us to take advantage of opportunities that individuals have started, and usurp them into the larger mission of OWW. However, it also puts us in a dillemma when we have to consider where to pool our resources to make improvements. What do people think?
Others
• ???
BREAK - cookies! (3:00-3:30pm)
Organizational Structure (3:30-5:00pm)
Current approach
• Steering committee discusses topics seeking consensus.
• Membership is voluntary.
• Secretary/Coordinator to run meetings, take notes
• Volunteer sub-comittee chairs (Education, Info Management, Publicity, etc)
• Admin list deciding on new user approvals and are the point of contact for people emailing OWW.
• This list is volunteers from the SC: Sri, Jason, Austin, Ilya, Reshma, Barry, Ty, Jeff
• Technical team: Sri, Austin, Ilya
• Have access to write to the server and interface with Tech Square, Inc.
• No formal mechanism was used to choose these members.
• Spokespeople to press, etc: Sri, Jason, Drew in practice
• No formal mechanism was used to choose these members.
• Other opportunities are addressed by adhoc groups
• OCW, NSF grant, Nature
Problems
• No agreed upon mechanism for making official decisions
• No clear spokesperson to interact with press, 3rd parties, etc.
• How best to involve new (non-local) people in leadership of the site.
Options
• How do people feel about setting in place an organizational structure for next 6 months based on the current adhoc leadership. This will give them explicit authority, rather than the current implicit approach. Secondly, all major decisions not directly related to the sub-positions will be made by majority vote of the steering committee. TO be clear the sub-positions are:
1. SC Coordinator - organizes SC meetings
2. SC Secretary - takes meeting notes, organizes the SC wiki area
3. Site administration team (may need leader) - keeps site infrastructure functioning and updated
4. Spokesperson - talks to cold calling 3rd parties - individuals would still be able to setup new interactions independent of the spokesperson, e.g. reshma talking to OCW
• During the next 6 months a group will be responsible for defining the long-term organizational structure and it would be voted on by the SC in December. or if we have time we can figure all this out today :).
Break (5:00-5:15)
Conclusions & Other topics(5:15-6:00pm)
• Things we missed.
• Wrap-up
Previous Discussions
OpenWetWare steering committee/SC retreat/Previous discussion
Draft OWW Goals & Mission
The goals of OWW are to support open research, education, publication, and discussion in biology and biological engineering.
The mission of OWW is to promote and support a community of researchers, students, and others who are working towards these goals.
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Communicating With Customers
Aug 7, 2006 • 6:24 pm | (0) by | Filed Under Search Engine Strategies 2006 San Jose
Communicating With Customers
Moderated by ClickZ Editor Rebecca Lieb. Welcomes everyone. Will be taking a broad view from a variety of perspectives on new ways to communicate with customers. These ways transcend email, such as RSS, feeds, podcasts, syndication. Looking from perspective of an Ad Agency (Organic), a PR agency(SEO-PR), and client-side look of things (TerraPass).
Rick Corteville from Organic They look to create empathy with target audience that leads to a customer’s delight. “Always give people more than what they expect to get” – Nelson Boswell. People often do not take this into account when communicating with customers. Some guideposts for customer communication: Be Organized, be relevant, and be flexible. Being relevant: uses tackle-box analogy: there are many types of customers (fish) need the right lure to draw them. Finding the right lure includes examining dbase and establishing a high level of relevancy.
Showcase a connection to the customer needs. Message targeting via SIC code, geography, or zip codes. Look at registrants: newspapers and portals. Look at events and target RSS feeds through particular events. Position self as a resource: social community such as 20th Century Fox’s X-Men 3 community. What they built in conjunction with myspace.com was a custom profile for fans of X-Men to visit. They can download IM skins, screensavers, etc. Obtained approximately 1.7 million friends prior to movie launch. After launch, skyrocketed to over 3 million! The largest myspace site at that point. This also relates to search. In the case of someone who is searching for product/brand name plus “broken,” the ads should be targeted to them instead of simply broad matching an ad with a description of the company as if they are a new customer.
“Bend like the reed.” Testing is the key to find out what are the types of media vehicles that are the best fit for a particular client. Start small, “you are not behind!” People feel tat they are somehow behind, when in fact there aren’t even a large amount of companies doing email marketing, for example. Do not expect results, but be happy if they come. Tells of an example where the person pitched a test to their superior and promised no returns. If you are holding something like an RSS feed to a high pedestal, you may be disappointed. All or nothing: don’t just do a blog for one-way communication, encourage responses/comments, etc and the customers will appreciate it more.
Types of things to do: frequency caps such as click to call pop-ups every fifth page. Is this a positive experience for the user? If you are utilizing video or another more engaging rich media unit, are you pushing it too far? RSS feeds within banner ads, HTML emails. Mobile: SMS for support information (like the ability to add a support Number to their address book) or ideas such as IPSH, which does mobile marketing campaigns. Social networking, desktop applications and other “widgets” to get feedback on products from the community.
Jamie O'Donnell of SEO-PR Discussing a “panoply of offerings and options” for communicating with customers. Set’s up an example by describing how in the early 20th century countries pushed-for adoption of telephone networks. Russia, instead, pushed for loud speakers. So do people look at RSS feeds as telephones or loudspeakers? RSS technology allows you to ID content that interest you and have it delivered directly. Average Blogline user tracks about 20 feeds, one example he has seen is someone that tracks 1440 feeds! (That may be Barry?)
So they tested creating 6 RSS feeds and optimized titles and descriptions for Consumer Reports. News, ratings/reviews, cars, press releases, tips and buying advice, and health guide. He wishes that we could find out the volume of searches taking place across all the aggregators. Difficult to do this. They mapped what categories where in the top ten popular. “They added the feeds to their site and we submitted them to 80 directories.” They use press-feed.com and RSS Submit product. They then monitor to ensure content is being correctly pulled into searches. The key to the Consumer Reports RSS feeds success was “can we provide the potential reader with news that they can’t get anywhere else?” According to research in March 2005, 73% of people read blogs for this purpose (sorry missed the source).
Results: daily blog citation and LinkRank (Pubsub.com free tool, sounds cool - keeps track of your link building efforts as explained by Greg Jarboe) jumped when RSS feeds launched. By putting out really valuable content, they saw great increases in citation, and grew search rankings for the core domains. Second analogy is that there is a tendency for some organizations to want to lecture while others want to hold conversations. Provided Wharton School MBA example: testing a blog in 2005. Did potential MBA students want to hear lectures or hold conversations? Asked: who is the target? Let’s try a model for trying to create a conversation with the audience. Created “student2student” discussion board where students can blog about the experience of getting the MBA, and thereby attract others to want to do so. They actually created an “optimization guide” for the students that were participating. (great idea!) This was critical for that group in helping them to create the conversations they wanted. In order to get traffic, one recommendation is to “think about terms users would type to find your post and actually use it in your post.” One and a half years later, the blog ranks #2 for “mba admissions.” Building on this, they can further track results to data like 94% of students seeking full time employment received offers.
Adam Stein from TerraPass Will present a case study. He feels that there are some great tools out there to help communicate with customers that are “very cheap.” TerraPass is a web retailer that sells an environmental “product,” that is, they ask for donations to help create more sources of alternative power to counteract pollution. They are a small start up, and face the same challenges as any young “pre-profitable” retailers has – they have no money. (laughs) The problem: size, no money, no technical team, no awareness, selling an intangible product to a skeptical audience. Goal is to figure out a cost-effective way to reach their audience using SEO and PR. They need to engage (trying rich content) with the potential client and develop an ongoing relationship (trying social media). Type of audience is difficult to reach in a low-cost way.
Their main marketing outreach tool is their blog: terrablog, with an RSS feed. The content is good. Also has a newsletter and uses email marketing. “Email is king” 16,258 subscribers to email, and only 233 RSS subscribers. He does note that only about one third of emails are opened. They strive in their email newsletter to have the tone of a blog. They promote reader comments from the blog into the email newsletter. Certain advantages to communicating via email: you get very granular statistics, such as links clicked-on, etc. They have incorporated Google Analytics and use them for good details on high-converting blog posts. They can see in a tangible way what effect each post has versus another in terms of converting customers. They are basically spending nothing on the whole email and newsletter package ($100/month).
Some other things they did included emailing other related blogs with an introduction to Terrablog. This led to some nice posts, including one at “Green Car Congress” which was read by an LA Times writer (Dan Neil?) who wrote an article (a flop in terms of conversions), but then led to an article which was written at Wired magazine which actually led to sales. Also, Ford contacted them from the LA Times article which led to a huge business development deal with them. All thanks to the one blog post at Green Car Congress that they had written after receiving an email about the TerraPass product. Also shows some examples of top page Google searches, thanks to G “loving blogs.” Even though the terms are obscure, they lead to some relevant traffic. For example, “TV standby mode” is actually #4 at Google, and this term is becoming more popular. Apparently, leaving TV’s in standby mode is a big waste of energy, and England is even thinking about outlawing them.
They are also very interested in myspace to reach the college market in particular. Will also look at Youtube and eBay “widg-it” and developing interactive games.
QA Rebecca asks “what should marketers be looking to invest?” (On a larger scale.) Rick: depends on the goals and objectives of the particular company. Overall, he sees 5-15% of marketing budgets used for these types of consumer-reaching efforts. Jamie: the biggest cost is the front end design of the feed and feed landing pages. Once design, optimization, and registration is done, it can be “turned over.” We have clients that spend between 5 and 10 thousand dollars over the first few months, but then are pretty much on their own adding new content etc.
How do you see optimizing podcasts as an actual enhancement to blogs? Jamie: finds that if they are helping client leverage all emerging trends, then they will be ready when they hit the main stream. Recommends spending an extra few dollars to optimize the podcast content as well as the feeds and blogs. Adam says that they don’t podcast yet, but are planning to eventually.
Previous story: Social Search: Up Close With Google (Google Co-op)
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Person:George McDonald (13)
Watchers
George McDonald
b.26 January 1845 Pennsylvania, United States
Facts and Events
Name George McDonald
Gender Male
Birth[3] 26 January 1845 Pennsylvania, United States
Death[2][3] 20 JAN 1925 Coalton, Jackson, Ohio, United States
Burial[3][4] Ridgewood Cemetery, Wellston, Jackson, Ohio, United States
Civil War Service
Source: S1
Pension
Source: S2
• Application 412995; Certificate 525072
• Widow's Pension: Application 1228935, Certificate - none listed (an indication that the application was not approved)
References
1. Foraker, J.B; H.A. Axline; and J.S. Robinson. Official roster of the soldiers of the state of Ohio in the War of the Rebellion, 1861-1866. (Akron [Ohio]: Werner Co., 1886-1895).
2. United States. Veterans Administration. Organization index to pension files of veterans who served between 1861 and 1900- [1917]. (Washington, District of Columbia: The National Archives, 1949).
3. 3.0 3.1 3.2 Ohio, United States. Death Certificate. (Ohio, United States).
cert. 3310 (1925)
4. Hixon, Mary J, and Frances Welch Hixon. Cemetery inscriptions of Jackson County, Ohio. (Baltimore [Maryland]: Gateway Press, c1982), II:1014.
Death certificate lists "Wellston Cemetery." However, there is no cemetery by that name. Ridgewood is the largest cemetery in Wellston. Further, the date of death in the cemetery book matchs the death certificate.
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Place:Pleasantville, Atlantic, New Jersey, United States
Watchers
NamePleasantville
TypeCity
Coordinates39.396°N 74.523°W
Located inAtlantic, New Jersey, United States
source: Getty Thesaurus of Geographic Names
source: Family History Library Catalog
the text in this section is copied from an article in Wikipedia
Pleasantville is a city in Atlantic County, New Jersey, United States. As of the 2010 United States Census, the city's population was 20,249,[1][2][3] reflecting an increase of 1,237 (+6.5%) from the 19,012 counted in the 2000 Census, which had in turn increased by 2,985 (+18.6%) from the 16,027 counted in the 1990 Census.
Pleasantville was originally incorporated as a borough by an Act of the New Jersey Legislature on January 10, 1889, from portions of Egg Harbor Township, based on the results of a referendum held on December 15, 1888. Pleasantville was incorporated as a city on April 14, 1914, replacing Pleasantville borough, based on the results of a referendum held that same day.
Research Tips
This page uses content from the English Wikipedia. The original content was at Pleasantville, New Jersey. The list of authors can be seen in the page history. As with WeRelate, the content of Wikipedia is available under the Creative Commons Attribution/Share-Alike License.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
1105.0 - Release Advice, 24 Nov 2000
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 24/11/2000
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• About this Release
ABOUT THIS RELEASE
Previously: Publications Advice (ISSN: 0156-4722)
Lists products released by all ABS offices on the day of issue of the Release Advice and those expected to be released on the following four working days.
Copies are available free of charge on Tuesdays and Fridays over the counter from ABS bookshops, or by subscription. A daily Release Advice is also available from the ABS Statsite on the Internet (www.abs.gov.au).
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
1300.5 - Western Australian Year Book, 1917-1918
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 03/12/1918
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• About this Release
The older versions have a mixture of names between Year Book Western Australia and Statistical Register of Western Australia.
The Statistical Register series started in 1900 and went through to 1959 -60.
There was an overalp with the new series of Year Books starting with the 1957 issue.
From the 1960 issue onwards, the title has been Year Book Western Australia.
The Western Australian Year Book is a contemporary reference book with many subjects that either changed in the later series after 1957.
This publication has been scanned from the paper version using character recognition software. This provides a full-text searching capability once downloaded.
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Catalogue Number
5232.0.55.001 - Assets and Liabilities of Australian Securitisers, Dec 2012
Latest ISSUE Released at 11:30 AM (CANBERRA TIME) 27/02/2013
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NOTES
FORTHCOMING ISSUES
ISSUE (QUARTER) Release Date
March 2013 29 May 2013
June 2013 22 August 2013
REVISIONS
No revisions were made during the December quarter 2012.
INQUIRIES
For further information about these and related statistics, contact the National Information and Referral Service on 1300 135 070 or Stanley Ho on Sydney (02) 9268 4535.
SUMMARY COMMENTARY
KEY FIGURES
Securitisers, Australia - Assets and Liabilities(a)
Sep Qtr 2012
Dec Qtr 2012
Sep Qtr 2011 to Dec Qtr 2012
$m
$m
%
Total assets at end of qtr
124 803
125 221
0.3
of which
Mortgages
Residential
103 653
102 819
-0.8
Non-residential
1 636
1 862
13.8
Total liabilities at end of qtr
124 803
125 221
0.3
of which
Asset backed Securities
Issued domestically
93 393
93 807
0.4
Issued off shore
16 163
15 755
-2.5
(a) See paragraph 7 of the Explanatory Notes for details of the coverage of these statistics.
Assets of Securitisers
As at 31 December 2012, total assets of Australian securitisers were $125.2b, up $0.4b (0.3%) on 30 September 2012.
PERCENTAGE CHANGE IN TOTAL ASSETS, from previous quarter
During the December quarter 2012, the rise in total assets was due primarily to rises in other loans (up $1.0b, 7.8%), non-residential mortgage loans (up $0.2b, 13.8%) and credit card loans and trade receivables (up $0.1b, 42.2%). This was partially offset by the falls in residential mortgage loans (down $0.8b, 0.8%) and cash and deposits (down $0.1b, 2.0%).
Mortgage assets, which accounted for 83.6% of total assets, were $104.7b as at 31 December 2012, a fall of $0.6b (0.6%) during the quarter.
NET ACQUISITION OF MORTGAGES DURING QUARTER
Liabilities of Securitisers
As at 31 December 2012, total liabilities of Australian securitisers were $125.2b, up $0.4b (0.3%) on 30 September 2012. The rise in total liabilities was due primarily to rises in long-term asset backed securities issued in Australia (up $1.4b, 1.6%) and loans and placements (up $0.8b, 8.5%). These were partially offset by the falls in short-term asset backed securities issued in Australia (down $1.0b, 12.0%) and asset backed securities issued overseas (down $0.4b, 2.5%).
CHANGE IN LEVEL OF ASSET BACKED SECURITIES, from previous quarter
As at 31 December 2012, asset backed securities issued overseas as a proportion of total liabilities fell to 12.6%, down 0.4 percentage point on the September quarter 2012 percentage of 13.0%, while asset backed securities issued domestically as a proportion of total liabilities rose to 74.9%, up 0.1 percentage point on the September quarter 2012 percentage of 74.8%.
ASSET BACKED SECURITIES, (percentage of total liabilities)
© Commonwealth of Australia 2013
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Tell me more ×
Answers OnStartups is a question and answer site for entrepreneurs looking to start or run a new business. It's 100% free, no registration required.
Joined together to create a new venture with my ex-boss, we shared a great work dynamics and gelled well together, had complimentary skills & liked the idea and hence I decided to start together.
From day 1, I wanted to be very clear on structure and equity but due to evolving nature of the venture, agreed to wait for 6 months.
I started working full time whereas the founder worked part time. Its 6 months and we have achieved good things and its time to go full on. But, its hard time we have clarity (probably its already late) over structure and equity and hence would like your opinion on the same.
Key Points:
He brings the original idea. I am being paid around 50% market salary and not investing any money(although i offered going without salary for few months and put some money which he said was not needed). He has the core domain expertise and around 10 years of experience whereas I have around 3 years of experience around online mktg, tech and product development and I am good at getting things done so can add good value to operations which is a complimentary skill to his skills. I *worked full time for six months whereas he worked part time during this time.*He is investing little personal savings and we plan to bootstrap and pay the bills via some workshops etc. and grow organically and later go for funding. Have been here from Day 1 while the idea was on paper.
The term core team member was always used to describe my association but I still don't have an answer to what that means: Should I be treated as a Co-Founder or First Employee ? What would be a fair Equity distribution ?
Also I didn't get clear answer to these questions over last 6 months as they were always abstract like "Core Team Member", "Fair Equity" etc and I had certain expectations in mind and seems difficult to be able to accept sth drastically different from my expectations.
share|improve this question
2 Answers
6 months is too long. I always advise to wait no longer than 1 month before having that discussion.
However, it looks like you have been paid for 6 months, so your situation is not so bad. It wasn't a complete rip-off.
The question always goes back to how critical you are: could you be replaced easily, and the founder could just pay someone else with the same cash you are getting right now? Then your situation is not good, and you should be treated like a first employee, with 0.5% to 5% of equity. If you are the heart and soul of the company, and you can't imagine it continuing without you, then you sound like a 50/50 shareholder.
share|improve this answer
Roby, it is time you sat down with your ex-boss and had a heart to heart talk. The outcome of this should be everything laid out in writing in a fashion you can clearly understand. If he is unwilling to do this, then you should definitely think twice about proceeding as you are.
As for titles and labels, they are pretty much meaningless. It is the money that counts. As they say:
"You can call me anything you'd like, just don't call me late to dinner."
If you were going for a job interview would you accept a lower salary just because it came with a better title? I hope not!
It is extremely hard to know what any particular start-up is worth, or even if it will be successful. Everyone wants to be the next Facebook and many experimenters think their new ventures are worth millions before they even make the first sale. You will need to decide for yourself what kind of deal is acceptable to you. Keep in mind that experience and learning can be valuable even if you end up moving on to something else.
What you should not accept is vague promises and hand waving. Everyone has the right to be treated in an honest and straightforward manner.
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Wednesday, May 02, 2012
How Video Apps are Driving SP Network Investment
Infonetics Research released excerpts from two recently published video equipment market share and forecast reports. These latest market studies demonstrate how video entertainment applications demand is impacting broadband service provider (SP) infrastructure investment decisions. That being said, most of the growth will come from online video streaming apps, not traditional pay-TV.
The first report, Video-on-Demand (VOD) and Encoder Equipment and Video Subscribers -- which tracks video equipment sold to telco IPTV, cable video, and satellite video providers. And the second report, Set-Top Boxes and Subscribers -- which tracks IP, cable, satellite hybrid, DVR, and high definition (HD) STBs, as well as over-the-top (OTT) media servers.
"Two of the most interesting trends in the video equipment and set-top box markets are 1) across the board, pay-TV operators continue to increase their investments in MPEG-4 encoders to reduce bandwidth requirements for their broadcast channels and VOD streams, and 2) despite healthy STB unit growth in 2011, revenue was nearly flat, reflecting the growth of lower-cost STBs in emerging markets, particularly China, combined with the increased competition we're seeing in the more mature markets," notes Jeff Heynen, directing analyst for broadband access and video at Infonetics Research.
VOD and Video Encoder Market Highlights
• Following annual declines in 2009 and 2010 during the global recession, the video infrastructure market (VOD and streaming content servers and video encoders) grew 6 percent in 2011 to $803 million, as all major world regions except EMEA increased spending.
• Sequentially (from the third to the fourth quarters), the overall market is up 4 percent and from the year-ago fourth quarter, the market is up 6 percent.
• Infonetics forecasts double-digit percent revenue increases in the global video infrastructure market in 2012.
• A cumulative $1.9 billion will be spent on standard and high definition (SD and HD) MPEG-4 video encoders over the next 5 years, from 2012 to 2016.
• Huawei leads the global VOD server market in both 4Q11 and for the overall year 2011; Motorola and ZTE are neck-and-neck for global VOD revenue in 4Q11
Video Set-Top Box Market Highlights
• In 2011, worldwide set-top box unit shipments grew 13.7 percent compared to the previous year, while revenue was nearly flat, up less than 1 percent, to $13.3 billion.
• Similarly, global set-top box unit shipments grew faster (+6.0 percent) than revenue (+3.8 percent) between the third and fourth quarters of 2011.
• Decent growth in high definition (HD) and DVR STB sales helped keep average selling prices (ASPs) from declining too quickly.
• In the tight race for overall global STB revenue share, Motorola, Echostar, Pace and Cisco lead, all separated by only a few market share percentage points in 4Q11.
• IP STB and hybrid IP/DTT STB unit shipments are forecast to grow the strongest among the various types of set-top boxes over the next 5 years, increasing their share of the total market.
• Demand continues to accelerate for online video streaming devices -- such as those made by Apple, Boxee, Roku, Popcorn Hour, D-Link, NETGEAR, Western Digital and TiVo -- with global over-the-top (OTT) media server revenue jumping 38 percent and unit shipments up 68 percent in 2011 as more service providers offer streaming video to their subscribers.
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IDE Host Controller
From NAS-Central Buffalo - The Linkstation Wiki
(Difference between revisions)
Jump to: navigation, search
m (3 revision(s))
m
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[[Category:Hardware]]
[[Category:Hardware]]
+
[[Category:Kurobox]]
Latest revision as of 23:59, 12 July 2007
Kurobox (HG) IDE Host Controller
The Kurobox and the Kurobox HG both use a Silicon Image SiI 0680A IDE Host Controller which can support one or more IDE hard drives.
Features
• ATA/133
• 48-bit sector addressing
• Dual independent DMA channels with 256K FIFO per channel
• Virtual DMA
• Read ahead
• Command buffering
• Supports external Flash
• Supports external BIOS
• 80-pin cable detect
See Also
Personal tools
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Type Title
Communication Systems Projects with LabVIEW
Control Systems Laboratory
Musical Signal Processing with LabVIEW -- Additive Synthesis
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Musical Signal Processing with LabVIEW -- Introduction to Audio and Musical Signals
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Musical Signal Processing with LabVIEW -- Modulation Synthesis
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SubVI Specifications for "Communication Systems Projects with LabVIEW"
Analyses of Circuit Simulations
Collocated / Noncollocated Control of 2DOF Rectilinear System
Control Lab Setup: Using LabVIEW to Control ECP Plants
Control Systems Lab Introduction, Hardware, Software, and Safety
Creating Circuits in Multisim
Introduction to Lab Hardware and LabVIEW Implementation
Inverted Pendulum on a Translating Base
IR Remote Control Lab
LED Thermometer Lab
Microphone FFT Lab
Musical Signal Processing with LabVIEW
Phase-Lead Compensation of a Rotational Rigid-Body System
Rigid Body PD and PID Control
Self-Erecting Inverted Pendulum on a Rotating Base
State Feedback Compensation of a 2DOF Rectilinear System
Student Scope Using NI USB Data Acquisition
System Identification for the Rectilinear Plant
System Identification for the Torsional Plant
Viewing Embedded LabVIEW Content
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