gebhart/patrepeval huggingface dataset:
A conserved hairpin motif in the R-U5 region of the human immunodeficiency virus type 1 RNA genome is essential for replication (1997)

The untranslated leader region of the human immunodeficiency virus (HIV) RNA genome contains multiple hairpin motifs. The repeat region of the leader, which is reiterated at the 3' end of the RNA molecule, encodes the well-known TAR hairpin and a second hairpin structure with the polyadenylation signal AAUAAA in the single-stranded loop [the poly(A) hairpin]. The fact that this poly(A) stem-loop structure and its thermodynamic stability are well conserved among HIV and simian immunodeficiency virus isolates, despite considerable divergence in sequence, suggests a biological function for this RNA motif in viral replication. Consistent with this idea, we demonstrate that mutations that alter the stability of the stem region or delete the upper part of the hairpin do severely inhibit replication of HIV type 1. Whereas destabilizing mutations in either the left- or right-hand side of the base-paired stem interfere with virus replication, the double mutant, which allows the formation of new base pairs, replicates more rapidly than the two individual virus mutants. Upon prolonged culturing of viruses with an altered hairpin stability, revertant viruses were obtained with additional mutations that restore the thermodynamic stability of the poly(A) hairpin. Transient transfection experiments demonstrated that transcription of the proviral genomes, translation of the viral mRNAs, and reverse transcription of the genomic RNAs are not affected by mutation of the 5' poly(A) hairpin. We show that the genomic RNA content of the virions is reduced by destabilization of this poly(A) hairpin but not by stabilization or truncation of this structure. These results suggest that the formation of the poly(A) hairpin structure at the 5' end of the genomic RNA molecule is necessary for packaging of viral genomes into virions and/or stability of the virion RNA.
Polyfluorenes: Twenty years of progress (2001)

Abstract Polyfluorenes are an important class of electroactive and photoactive materials. In the last three years this research field has literally exploded because of polyfluorenes' exceptional electrooptical properties for applications in light‐emitting diodes. This is the only family of conjugated polymers that emit colors spanning the entire visible range with high efficiency and low operating voltage. Other unusual optical and electrical properties are made possible with polyfluorene derivatives, such as thermochromism and conducting base‐doped polyelectrolytes. © 2001 John Wiley &amp; Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2867–2873, 2001
The Stanford Hydra CMP (2000)

The Hydra chip multiprocessor (CMP) integrates four MIPS-based processors and their primary caches on a single chip together with a shared secondary cache. A standard CMP offers implementation and performance advantages compared to wide-issue superscalar designs. However, it must be programmed with a more complicated parallel programming model to obtain maximum performance. To simplify parallel programming, the Hydra CMP supports thread-level speculation and memory renaming, a paradigm that allows performance similar to a uniprocessor of comparable die area on integer programs. This article motivates the design of a CMP, describes the architecture of the Hydra design with a focus on its speculative thread support, and describes our prototype implementation. Chip multiprocessors offer an economical, scalable architecture for future microprocessors. Thread-level speculation support allows them to speed up past software.
Ornithine Decarboxylase as a Biologic Marker in Familial Colonic Polyposis (1984)

We investigated whether the activity of ornithine decarboxylase might serve as a diagnostic test for detecting the presence of the genotype for familial polyposis. This rate-limiting enzyme in the polyamine biosynthetic pathway is essential for intestinal mucosal proliferation. In colonic mucosa from 16 normal controls, ornithine decarboxylase activity was less than 2.5 nmol per milligram per hour. In contrast, it was higher than 2.5 nmol per milligram per hour in the normal-appearing areas of colonic mucosa from 11 of 13 patients with familial polyposis and in all polyps biopsied from these same subjects (P less than 0.05 for specimens from both sites, as compared with controls). Mucosa from dysplastic polyps showed higher mean ornithine decarboxylase activity than mucosa from polyps that were not dysplastic (P less than 0.05). In colonic mucosa from clinically unaffected, first-degree relatives of patients with familial polyposis, there was a bimodal distribution of ornithine decarboxylase activity, with one peak at the mean for normal controls and the other near the mean for normal-appearing mucosa from affected patients. Our study suggests that ornithine decarboxylase activity in colonic mucosa may reflect the abnormal proliferative state in familial polyposis and identify clinically normal family members who carry the genotype.
Formation of oligopeptides during the synthesis of 9‐fluorenylmethyloxycarbonyl amino acid derivatives (1983)

We wish to report a serious side reaction which occurs during the preparation of 9-fluorenylmethyloxycarbonyl (Fmoc) amino acid derivatives 1.Because of their base lability, Fmoc-amino acids are potentially amongst the most versatile intermediates for peptide synthesis, especially when used in conjunction with acid-labile sidechain protecting groups.lS2 1 However, when these compounds are prepared by standard pro~edures,~.3we have found that the majority of Fmoc-amino acids are contaminated by variable but often substantial amounts of Fmoc-oligopeptides.We have established this by HPLC, amino acid analysis, nmr, and the synthesis of a number of standards.The Fmoc-oligopeptides are likely formed via the intermediacy of relatively stable mixed anhydrides formed during Fmoc-chloride-mediated synthesis of the Fmoc-amino acid derivatives.'T3The oligopeptide contaminants were first noted during routine TLC analyses to assess the homogeneity of commercial samples of Fmoc-amino acids prior to their use.While the literature TLC systems' (e.g.ch1oroform:methanol:acetic acid, 9:l:0.1)did not necessarily separate the contaminants in all cases, we were able to demonstrate reproducible separations using the TLC system to1uene:acetic acid, 10:l.The impurities were invariably slower-moving in this TLC system, were strongly uv-absorbing, chlorine-tolidine4 positive, and also difficult or impossible to remove completely by recrystallization techniques.This suggested that the impurities were both Fmoc-blocked and amino-acid containing.One of the most severely contaminated amino acid derivatives, Fmoc-glycine, was chosen for careful, in-depth study.When Fmoc-glycine was synthesized by the standard literature procedure,'13 using Fmoc-chloride in dioxane/aqueous sodium carbonate, the product was found by TLC to be contaminated by a major (10-20%), slower-moving contaminant.Fractional crystallization using ethyl acetate/hexane provided a sample that was
ViZDoom: A Doom-based AI research platform for visual reinforcement learning (2016)

The recent advances in deep neural networks have led to effective vision-based reinforcement learning methods that have been employed to obtain human-level controllers in Atari 2600 games from pixel data. Atari 2600 games, however, do not resemble real-world tasks since they involve non-realistic 2D environments and the third-person perspective. Here, we propose a novel test-bed platform for reinforcement learning research from raw visual information which employs the first-person perspective in a semi-realistic 3D world. The software, called ViZDoom, is based on the classical first-person shooter video game, Doom. It allows developing bots that play the game using the screen buffer. ViZDoom is lightweight, fast, and highly customizable via a convenient mechanism of user scenarios. In the experimental part, we test the environment by trying to learn bots for two scenarios: a basic move-and-shoot task and a more complex maze-navigation problem. Using convolutional deep neural networks with Q-learning and experience replay, for both scenarios, we were able to train competent bots, which exhibit human-like behaviors. The results confirm the utility of ViZDoom as an AI research platform and imply that visual reinforcement learning in 3D realistic first-person perspective environments is feasible.
Regulation of cyclic AMP metabolism in human platelets. Sequential activation of adenylate cyclase and cyclic AMP phosphodiesterase by prostaglandins. (1981)

Prostacyclin (PGI2) produces a transient elevation in cyclic AMP in washed human platelets. Intracellular cyclic AMP increases rapidly to a maximal level after 1-2 min of incubation and then gradually declines. This temporal pattern appears to involve a sequential activation of adenylate cyclase and cyclic AMP phosphodiesterase. The following three observations support this interpretation: (a) inhibition of endogenous phosphodiesterase activity with 1-methyl-3-isobutylxanthine eliminates the transient elevation pattern and permits accumulation of the cyclic nucleotide, (b) PGI2 indirectly stimulates the activity of a cyclic AMP phosphodiesterase when preincubated with intact platelets, and (c) the gradual decrease in endogenous cyclic AMP coincides with an increase in phosphodiesterase activity. The potency and efficacy of prostaglandins (PGs) as stimulators of phosphodiesterase activity correlate with their capacity to increase intracellular cyclic AMP (PGI2 > PGD2 ≥ PGE1). PGD2 increases cyclic AMP to a higher maximal level than does PGE1 in intact cells, but stimulates adenylate cyclase to a lower maximal velocity in broken-cell preparations. This discrepancy was observed under a variety of assay conditions. When washed platelets were preincubated in a hypotonic buffer containing EDTA prior to the assay, the discrepancy was eliminated. Thus, under appropriate incubation conditions, the potency and efficacy of several naturally occurring PGs as stimulators of adenylate cyclase correspond to their ability to increase the intracellular concentration of cyclic AMP (PGI2 > PGD2 ≥ PGE1 » PGE2 ≥ PGA1 > PGF2α). Similarly, their potency as inhibitors of ADP-induced platelet aggregation corresponds to their capacity to elevate cyclic AMP to a critical, submaximal level. These results lend further support to the concept that cyclic AMP mediates the effect of PGs on platelet function and that activation of adenylate cyclase is the primary biochemical event responsible for the accumulation of cyclic AMP.

ACKNOWLEDGMENTS We gratefully acknowledge the many useful discussions with Dr. John J. Bruno and his support of this project. This study was facilitated by the technical assistance of Ms. Gail Winter. Platelet electron micrographs were provided by Mrs. Friederike M. Freymark.
Excitatory amino acid binding sites in the hippocampal region of Alzheimer's disease and other dementias. (1990)

Quantitative receptor autoradiography was used to measure muscarinic cholinergic, benzodiazepine, kainate, phencyclidine (PCP), N-methyl-D-aspartate (NMDA) (measured in Tris acetate), quisqualate-sensitive, non-quisqualate-sensitive and total glutamate (measured in Tris chloride buffer) binding sites in adjacent sections of the hippocampal region of 10 Alzheimer's disease, nine control, and six demented, non-Alzheimer's disease postmortem human brains. The measurements were compared to the number of neurofibrillary tangles as revealed by Congo red staining of adjacent sections. All assays and measurements were done by observers blinded to the clinical diagnoses. Binding was decreased significantly for all ligands except quisqualate in stratum pyramidale of CA1 of the Alzheimer's disease brains. The binding loss was significantly greater for the non-quisqualate and NMDA sites than for the muscarinic, benzodiazepine and kainate sites with the total glutamate and PCP site losses being intermediate. Only the loss of benzodiazepine binding was significantly correlated with the number of neurofibrillary tangles. Lesser binding losses were seen in adjacent areas. This difference in the degree of binding decrease is consistent with the hypothesis that NMDA receptors are located on more distal dendrites of hippocampal neurons. There they may be relatively more vulnerable than the other receptors to the pathological process.
The Calculus of Reengineering (1996)

Advances in new Information Technologies (IT) and changes in the business environment such as globalization and competitive pressure have prompted organizations to embark on reengineering projects involving significant investments in IT and business process redesign. However, the evidence of payoff from such investments can be classified as mixed as best, a problem we partly attribute to the absence of a strong theoretical foundation to assess and analyze reengineering projects. We seek to apply complementarity theory and a business value modeling approach to address some questions involving what, when, and how much to reengineer. Complementarity theory is based on the notion that the value of having more of one factor increases by having more of another complementary factor. Further, related developments in the optimization of “supermodular” functions provide a useful way to maximize net benefits by exploiting complementary relationships between variables of interest. Combining this theory with a multi-level business value model showing relationships between key performance measures and their drivers, we argue that organizational payoff is maximized when several factors relating to IT, decision authority, business processes and incentives are changed in a coordinated manner in the right directions by the right magnitude to move toward an ideal design configuration. Our analysis further shows that when a complementary reengineering variable is left unchanged either due to myopic vision or self-interest, the organization will not be able to obtain the full benefits of reengineering due to smaller optimal changes in the other variables. We also show that by increasing the cost of changing the levels of design variables, unfavorable pre-existing conditions (e.g., too much heterogeneity in the computing environment) can lead to reengineering changes of smaller magnitude than in a setting with favorable conditions.
DPP IV resistance and insulin releasing activity of a novel di‐substituted analogue of glucose‐dependent insulinotropic polypeptide, (Ser2–Asp13)GIP (2003)

Structure-function studies suggest that preservation of the N-terminus and secondary structure of glucose-dependent insulinotropic polypeptide (GIP) is important for biological activity. Therefore, a novel di-substituted analogue of GIP, (Ser(2)-Asp(13))GIP, containing a negatively charged Asp residue in place of an Ala in position 13, was synthesised and evaluated for in vitro biological activity. Incubation with dipeptidyl peptidase IV (DPP IV) showed the half-lives of GIP and (Ser(2)-Asp(13))GIP to be 2.3 and >4h, respectively. Insulin releasing studies in clonal pancreatic BRIN-BD11 cells demonstrated that (Ser(2)-Asp(13))GIP (10(-12)to 10(-7)mol/l) was significantly less potent (60-90%; P<0.05 to P<0.001) than native GIP. The peptide failed to display antagonistic properties as it did not significantly alter insulin secretion when incubated in the presence of GIP (10(-7)mol/l). These results demonstrate that despite increased resistance to DPP IV, substituting Ala in position 13 with a negatively charged Asp, thus producing the di-substituted analogue (Ser(2)-Asp(13))GIP, significantly reduces biological activity, most likely due to modifications within the secondary structure.
Early events in the stimulation of mammary tumor virus RNA synthesis by glucocorticoids. Novel assays of transcription rates. (1984)

Two procedures were devised to examine initial events in the glucocorticoid-regulated transcription of integrated murine mammary tumor virus (MTV) DNA sequences. First, cells in monolayer culture were exposed for brief periods to dexamethasone and then permeabilized in situ with digitonin to allow entry of 32P-labeled ribonucleoside triphosphates and measurement of transcription rates. The results revealed that the rate of MTV RNA synthesis is stimulated selectively by dexamethasone after an apparent lag of approximately equal to 1 min and is half-maximal by 8-9 min. Second, the time course of transcription elongation was monitored by quantitating in single strand nuclease protection assays the accumulation of RNA sequences from different regions of the 7.8-kilobase MTV transcription unit. These experiments suggested that the rate of MTV RNA elongation in the presence of hormone does not differ substantially from elongation rates calculated for other genes transcribed by RNA polymerase II. Moreover, dexamethasone increased in parallel and to the same extent the levels of RNA from various segments of the transcription unit, implying that transcripts are elongated across the MTV element at a constant rate. We conclude that glucocorticoids stimulate MTV transcription solely via a rapid and selective increase in the efficiency of transcription initiation.
Synthesis of [131-I]-iodinated quercetin (1997)

Two iodination procedures via thallation were applied to quercetin leading to the formation of 2′-iodoquercetin and 2′,6,8-triiodoquercetin; their structures being elucidated by FT-IR and NMR spectral analysis. The preparation of mono- and polyiodinated products is discussed here on the basis of the experimental details and spectral data. This is the first report on the radiolabelling of quercetin, which is here selectively performed with 131-iodine. The radiochemical purity was of 99%. © 1997 John Wiley & Sons, Ltd.
Hashish. 20. Synthesis of (.+-.)-.DELTA.1- and .DELTA.6-3,4-cis-cannabidiols and their isomerization by acid catalysis (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHashish. 20. Synthesis of (.+-.)-.DELTA.1- and .DELTA.6-3,4-cis-cannabidiols and their isomerization by acid catalysisG. Richard Handrick, Raj K. Razdan, David B. Uliss, Haldean C. Dalzell, and Eliahu BogerCite this: J. Org. Chem. 1977, 42, 15, 2563–2568Publication Date (Print):July 1, 1977Publication History Published online1 May 2002Published inissue 1 July 1977https://pubs.acs.org/doi/10.1021/jo00435a007https://doi.org/10.1021/jo00435a007research-articleACS PublicationsRequest reuse permissionsArticle Views502Altmetric-Citations17LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Synthesis of certain nucleoside methylenediphosphonate sugars as potential inhibitors of glycosyltransferases (1987)

The synthesis of alpha-D-glucopyranosyl 1-(methylenediphosphonate) (11), alpha-D-galactopyranosyl 1-(methylenediphosphonate) (14), and alpha-D-mannopyranosyl 1-(methylenediphosphonate) (17) has been accomplished. [(Di-phenoxyphosphinyl)methyl]phosphonic acid (diphenyl-MDP) (5), synthesized by two different procedures, was fused with beta-D-glucopyranose pentaacetate followed by catalytic hydrogenation to give 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl methylenediphosphonate (glucose-MDP) (10). The anomeric configuration of 10 was assigned on the basis of NMR spectral studies. Condensation of 10 with 2',3'-di-O-acetyladenosine was accomplished by using 1-(mesitylene-2-sulfonyl)-3-nitro-1,2,4-triazole (MSNT) as coupling agent, and removal of the blocking groups gave adenosine 5'-[(alpha-D-glucopyranosylhydroxyphosphinyl)methyl]phosphonate (20). Uridine 5'-[(alpha-D-galactopyranosylhydroxyphosphinyl)methyl] phosphonate (23) and guanosine 5'-[(alpha-D-mannopyranosylhydroxyphosphinyl)methyl]phosphonate (26) were similarly prepared. Using a specific glycoprotein galactosyltransferase (EC 2.4.1.38) assay, uridine 5'-[(alpha-D-galactopyranosylhydroxyphosphinyl)methyl]phosphonate (23) demonstrated competitive inhibition with an apparent Ki of 97 microM. The adenosine analogue did not inhibit the enzyme. None of the above compounds show any in vitro antitumor or antiviral activity. Such specific inhibitors of glycosyltransferases may serve as specific probes to study various glycosyltransferases that might be involved in the process of metastasis.
THE PATH OF CARBON IN PHOTOSYNTHESIS. XXIX. GLASS MICROBEADS (2012)

Glass microbeads are introduced as convenient and applicable mechanical supports for hydroponics that can be released from roots to exhibit visually discernible responses. Moreover, glass microbeads refract light, effectively redistributing light toward the phylloplane. The smallest beads, <300 μm diameter, rose from neutral to ∼pH 9 in water and the rise was attributable the raw materials source, sodalime glass. The largest 700 μm diameter beads were relatively stable in buffered nutrients. Photography of unobstructed roots was aided by release of microbeads from ryegrass, coleus, corn, and narcissus. Propagation of ‘Ninsei’ was undertaken in containers constructed with inflow and drainage ports. Photodocumentation of responses to indoxylglucopyranoside exhibited consistent differences as compared to controls when cultured in glass microbeads; and further investigations into increased light intensity by refraction may lead to enhanced photosynthetic efficiency.
Identification of THW, a putative new tumor suppressor gene. (2000)

Differential Display between metastasizing and non-metastasizing human melanoma cell lines NMCL-1 and 530 led to the identification of a putative transmembrane receptor, designated as THW, which is down-regulated in the metastasizing cell line. THW is composed of 193 aa, exhibits four putative transmembrane domains and does not reveal any homology to other proteins. Down-regulation of THW is correlated with metastatic capacity of melanoma cell lines. THW was down-regulated in mammary carcinoma cell lines compared with cell lines derived from non-malignant mammary epithelium, in pancreas cell lines derived from metastases compared with a cell line derived from a primary tumor and in several tumor tissues compared with normal tissues. The function of THW as a tumor suppressor is emphasized by the location of the THW gene on chromosome 6q. LOH for this region has been reported in malignant melanoma and prostate, pancreas, uterine and mammary carcinomas.