gebhart/patrepeval huggingface dataset:
Synthesis and biological properties of pyrimidine 4′-fluoronucleosides and 4′-fluorouridine 5′-O-triphosphate (2010)

4'- Fluoro-2',3'-O-isopropylidenecytidine was synthesized via interaction of 5'-O-acetyl-4'-fluoro-2',3'-O-isopropylideneuridine with triazole and 4-chlorophenyl dichlorophosphate followed by ammonolysis. Treatment of 5'-O-acetyl-4'-fluoro-2',3'-O-isopropylidenecytidine with hydroxylamine resulted in 5'-O-acetyl-4'-fluoro-2',3'-O-isopropylidene-N(4)-hydroxycytidine. Subsequent removal of 2',3'-O-isopropylidene groups gave 5'-O-acetyl derivatives of 4'-fluorouridine, 4'-fluorocytidine and 4'-fluoro-N(4)-hydroxycytidine. 5'-O-Triphosphate of 4'-fluorouridine was obtained in three steps starting from 4'-fluoro-2',3'-O-isopropylideneuridine. The 4'-fluoro uridine 5'-O-triphospate was found to be an effective inhibitor of HCV RNA-dependent RNA polymerase, substrate for NTPase reaction, catalyzed by protein NS3 HCV (a rate of the analogue hydrolysis was similar to that of ATP) and an activator for helicase reaction (with an efficacy only three fold lower than that of ATP).
Clinical Female Sexual Outcome after Sacral Neuromodulation Implant for Lower Urinary Tract Symptom (LUTS) (2008)

The positive effects regarding sexuality may be due either to enhancement of LUTS or to the direct stimulation of the sacral roots (S3).
Time Series Prediction Using Support Vector Machines: A Survey (2009)

Time series prediction techniques have been used in many real-world applications such as financial market prediction, electric utility load forecasting , weather and environmental state prediction, and reliability forecasting. The underlying system models and time series data generating processes are generally complex for these applications and the models for these systems are usually not known a priori. Accurate and unbiased estimation of the time series data produced by these systems cannot always be achieved using well known linear techniques, and thus the estimation process requires more advanced time series prediction algorithms. This paper provides a survey of time series prediction applications using a novel machine learning approach: support vector machines (SVM). The underlying motivation for using SVMs is the ability of this methodology to accurately forecast time series data when the underlying system processes are typically nonlinear, non-stationary and not defined a-priori. SVMs have also been proven to outperform other non-linear techniques including neural-network based non-linear prediction techniques such as multi-layer perceptrons.The ultimate goal is to provide the reader with insight into the applications using SVM for time series prediction, to give a brief tutorial on SVMs for time series prediction, to outline some of the advantages and challenges in using SVMs for time series prediction, and to provide a source for the reader to locate books, technical journals, and other online SVM research resources.
The SNF1 Kinase Ubiquitin-associated Domain Restrains Its Activation, Activity, and the Yeast Life Span (2015)

The enzyme family of heterotrimeric AMP-dependent protein kinases is activated upon low energy states, conferring a switch toward energy-conserving metabolic pathways through immediate kinase actions on enzyme targets and delayed alterations in gene expression through its nuclear relocalization. This family is evolutionarily conserved, including the presence of a ubiquitin-associated (UBA) motif in most catalytic subunits. The potential for the UBA domain to promote protein associations or direct subcellular location, as seen in other UBA-containing proteins, led us to query whether the UBA domain within the yeast AMP-dependent protein kinase ortholog, SNF1 kinase, was important in these aspects of its regulation. Here, we demonstrate that conserved UBA motif mutations significantly alter SNF1 kinase activation and biological activity, including enhanced allosteric subunit associations and increased oxidative stress resistance and life span. Significantly, the enhanced UBA-dependent longevity and oxidative stress response are at least partially dependent on the Fkh1 and Fkh2 stress response transcription factors, which in turn are shown to influence Snf1 gene expression.
Specific Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Integration in Cell Culture: Putative Inhibitors of HIV-1 Integrase (2001)

To study the effect of potential human immunodeficiency virus type 1 (HIV-1) integrase inhibitors during virus replication in cell culture, we used a modified nested Alu-PCR assay to quantify integrated HIV DNA in combination with the quantitative analysis of extrachromosomal HIV DNA. The two diketo acid integrase inhibitors (L-708,906 and L-731,988) blocked the accumulation of integrated HIV-1 DNA in T cells following infection but did not alter levels of newly synthesized extrachromosomal HIV DNA. In contrast, we demonstrated that L17 (a member of the bisaroyl hydrazine family of integrase inhibitors) and AR177 (an oligonucleotide inhibitor) blocked the HIV replication cycle at, or prior to, reverse transcription, although both drugs inhibited integrase activity in cell-free assays. Quercetin dihydrate (a flavone) was shown to not have any antiviral activity in our system despite reported anti-integration properties in cell-free assays. This refined Alu-PCR assay for HIV provirus is a useful tool for screening anti-integration compounds identified in biochemical assays for their ability to inhibit the accumulation of integrated HIV DNA in cell culture, and it may be useful for studying the effects of these inhibitors in clinical trials.
Deletion of transfected oncogenes from NIH 3T3 transformants by inhibitors of poly(ADP-ribose) polymerase. (1988)

a1-1 cells, a transformant line obtained by transfection of NIH 3T3 cells with human c-Ha-rasT24 (hc-Ha-rasT24), were converted to morphologically normal flat cells following a 2-week culture in the presence of benzamide (BA), an inhibitor of poly(ADP-ribose) polymerase [ADP-ribosyltransferase (polymerizing); EC 2.4.2.30]. Concomitant with these morphological changes was the loss of the exogenous hc-Ha-rasT24 sequence. When cells were cultured without transfer, multiple clusters of flat revertant cells surrounded by transformed cells within single colonies of a1-1 cells were observed. This, together with the slow growth rate of flat cells in the presence of BA, indicated that flat revertants were induced rather than selected by BA. Flat cells isolated from mixed colonies completely lost the exogenous and amplified hc-Ha-rasT24 gene. In contrast, the endogenous mouse c-Ha-ras in flat revertant cells was not lost during culture with BA. Similarly, the endogenous hc-Ha-rasT24 in human bladder carcinoma T24 cells was not affected by BA. By using various chemicals, it was suggested that inhibition of poly(ADP-ribose) polymerase induces an efficient and specific loss of the exogenous transforming genes including Ki-ras, N-ras, c-raf, and ret-II.
Fractional Langevin equation (2001)

We investigate fractional Brownian motion with a microscopic random-matrix model and introduce a fractional Langevin equation. We use the latter to study both subdiffusion and superdiffusion of a free particle coupled to a fractal heat bath. We further compare fractional Brownian motion with the fractal time process. The respective mean-square displacements of these two forms of anomalous diffusion exhibit the same power-law behavior. Here we show that their lowest moments are actually all identical, except the second moment of the velocity. This provides a simple criterion that enable us to distinguish these two non-Markovian processes.
Predictable Flight Management System Implementation on a Multicore Processor (2014)

International audience
Ferulic Acid: Therapeutic Potential Through Its Antioxidant Property (2007)

There has been considerable public and scientific interest in the use of phytochemicals derived from dietary components to combat human diseases. They are naturally occurring substances found in plants. Ferulic acid (FA) is a phytochemical commonly found in fruits and vegetables such as tomatoes, sweet corn and rice bran. It arises from metabolism of phenylalanine and tyrosine by Shikimate pathway in plants. It exhibits a wide range of therapeutic effects against various diseases like cancer, diabetes, cardiovascular and neurodegenerative. A wide spectrum of beneficial activity for human health has been advocated for this phenolic compound, at least in part, because of its strong antioxidant activity. FA, a phenolic compound is a strong membrane antioxidant and known to positively affect human health. FA is an effective scavenger of free radicals and it has been approved in certain countries as food additive to prevent lipid peroxidation. It effectively scavenges superoxide anion radical and inhibits the lipid peroxidation. It possesses antioxidant property by virtue of its phenolic hydroxyl group in its structure. The hydroxy and phenoxy groups of FA donate electrons to quench the free radicals. The phenolic radical in turn forms a quinone methide intermediate, which is excreted via the bile. The past few decades have been devoted to intense research on antioxidant property of FA. So, the present review deals with the mechanism of antioxidant property of FA and its possible role in therapeutic usage against various diseases.
Equine Herpesvirus Type 1 Unique Short Fragment Encodes Glycoproteins with Homology to Herpes Simplex Virus Type 1 gD, gI and gE (1990)

The nucleotide sequence of a 6.4 kbp portion of the 10.6 kbp BamHI fragment D contained in the unique short region of the equine herpesvirus type 1 (EHV-1) genome has been determined. Analysis of this sequence revealed five open reading frames (ORFs), four complete and one incomplete, which were encoded by the same sense strand. Comparison of the EHV-1 DNA sequence with that encoding glycoproteins of other alphaherpesviruses has revealed no significant homologies. Comparison at the amino acid level, however, has demonstrated regions of significant sequence similarity between the three complete EHV-1 ORFs 2, 3 and 4, and the herpes simplex virus type 1 (HSV-1) glycoprotein gD encoded by the US6 gene, the HSV-1 glycoprotein gI encoded by the US7 gene and the HSV-1 glycoprotein gE encoded by the US8 gene, respectively. The interrupted ORF 5 was found to display partial homology with the HSV-1 US9-encoded protein, but no homology was found between the protein encoded by ORF 1 and other proteins. The three collinear EHV-1 ORFs encoding putative glycoproteins with homology to the HSV-1 glycoproteins were therefore designated EHV-1 gD, gI and gE, respectively. Moreover, further similarities were found between EHV-1 gD and pseudorabies virus (PRV) gp50, between EHV-1 gI and PRV gp63 and varicellazoster virus (VZV) gpIV, and between EHV-1 gE and PRV gI and VZV gpI. It is concluded that EHV-1, PRV, HSV-1 and VZV encode homologous glycoprotein genes in the small unique components of their genomes and that the genetic organization of these regions is conserved.
Hydrogen bond-directed cocrystallization and molecular recognition properties of diarylureas (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydrogen bond-directed cocrystallization and molecular recognition properties of diarylureasMargaret C. Etter, Zofia Urbanczyk-Lipkowska, Mohammad Zia-Ebrahimi, and Thomas W. PanuntoCite this: J. Am. Chem. Soc. 1990, 112, 23, 8415–8426Publication Date (Print):November 1, 1990Publication History Published online1 May 2002Published inissue 1 November 1990https://pubs.acs.org/doi/10.1021/ja00179a028https://doi.org/10.1021/ja00179a028research-articleACS PublicationsRequest reuse permissionsArticle Views3171Altmetric-Citations447LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
ACTR-31. PHASE 1 STUDY OF AG-881, AN INHIBITOR OF MUTANT IDH1 AND IDH2: RESULTS FROM THE RECURRENT/PROGRESSIVE GLIOMA POPULATION (2018)

INTRODUCTION: Isocitrate dehydrogenase 1 and 2 mutations (mIDH1/2) occur in >70% of low-grade gliomas and secondary glioblastomas, and lead to genetic and epigenetic dysregulation, promoting tumorigenesis. AG-881 is an oral, potent, brain-penetrant inhibitor of mIDH1/2 under phase 1 clinical evaluation in gliomas and other solid tumors. Here we present clinical data from the glioma population. Patients with recurrent/progressive mIDH1/2 glioma received AG-881 daily in continuous 28-day cycles. A Bayesian model was used for dose escalation. Dose-limiting toxicity (DLT) definition: Grade 3 AG-881-related adverse event (AE) in Cycle 1 or by sponsor designation. Blood samples were collected for pharmacokinetic (PK)/pharmacodynamic (PD) evaluations. MRI response every 8 weeks by RANO and RANO-LGG criteria. As of 28Mar2018, 52 patients with glioma had received AG-881 and 17 (32.7%) remained on treatment. Grade 2/3 = 90.4%; median age = 42.5 years; IDH1/2: 48/3; median no. prior therapies = 2 (range 1–6). Five initial dose levels tested: 25mg (n=6), 50mg (n=5), 100mg (n=10), 200mg (n=14), and 300mg (n=5). To confirm safety and PK, a 10mg dose level was tested (n=6) and 6 additional patients enrolled in the 50mg cohort. Common (>20%) AEs across glioma patients regardless of attribution: ALT increased (44.2%), AST increased (38.5%), headache (34.6%), fatigue (30.8%), nausea (26.9%), seizure (21.2%). Five patients experienced DLTs at 100mg: Grade 2 ALT/AST that resolved to Grade 1 with dose modification (n=4) or discontinuation (n=1). Among the evaluable glioma population: 2% minor response, 75% stable disease, 21% progressive disease, and 2% missing as best overall response. CONCLUSION: Maximum tolerated dose/recommended phase 2 dose was not reached by Bayesian model; clinical team recommendation was to proceed with doses <100mg in patients with glioma. The 10mg and 50mg doses are being explored in an ongoing perioperative glioma study. Updated safety, PK, and imaging response analyses will be presented.
Lack of Effect of Intrathecally Administered N-methyl-D-aspartate Receptor Antagonists in a Rat Model for Postoperative Pain (1998)

Unlike intrathecal and systemic morphine, intrathecal NMDA receptor antagonists did not modify pain behaviors in this rat model of postoperative pain. These data suggest that NMDA receptors do not play an important role in the maintenance of postoperative pain behaviors and that NMDA receptor antagonists, administered spinally by themselves during the postoperative period, will not be useful for the treatment of postoperative pain in humans.
Recruitment of activated microglia cells in the spinal cord of mice by ALS IgG (2001)

Mice were injected i.p. with IgG samples of different patients to test whether IgG from amyotrophic lateral sclerosis (ALS) can initiate an immune/inflammatory reaction targeting motor neurons. All IgG samples of five ALS patients and none of the disease controls recruited activated microglia cells in the ventral horn of the spinal cord. CD3 lymphocytes were not accumulated in the same tissue. Similar reaction was evoked by injection of IgG from guinea pigs with experimental autoimmune gray matter disease (EAGMD) induced by immunization with the homogenate of the ventral horn of bovine spinal cord. The results indicate that ALS IgG and anti-motoneuron IgG induce microglia reaction targeting motor neurons without initiating T cell response in the recipient mice.
Progressive inactivation of the expression of an erythroid transcriptional factor in GM- and G-CSF-dependent myeloid cell lines (1990)

The transcriptional binding protein NFE-1 (also called GF-1 and Ery-f1) is thought to play a necessary, but not sufficient, role in the regulation of differentiation-related gene expression in a subset of hematopoietic lineages (erythroid, megakaryocytic, and basophil-mast cell). In order to clarify the mechanism which underlies the lineage-specificity of the NFE-1 expression, as well as the relationship between the expression of this factor and growth factor responsiveness, we have evaluated the capacity of erythropoietin (Epo)-, granulomonocytic (GM)-colony stimulating factor (CSF)-, and granulocyte (G)-CSF-dependent subclones derived from the interleukin 3 (IL-3)-dependent cell line 32D, to express 1) NFE-1 mRNA, 2) NFE-1-related nuclear proteins, and 3) chloramphenicol acetyl transferase (CAT) activity when transfected with a CAT gene under the control of NFE-1 cognate sequences. NFE-1 mRNA was found to be expressed not only in cells with mast cell (IL-3-dependent 32D) and erythroid (Epo-dependent 32D Epo1) phenotypes, but also in cells with predominantly granulocyte/macrophage properties, such as the GM-CSF- (early myelomonocytic) and G-CSF- (myelocytic) dependent subclones of 32D. However, a gradient of expression, correlating with the lineage, the stage of differentiation, and the growth factor responsiveness of the cell lines, was found among the different subclones: Epo greater than or equal to IL-3 greater than GM-CSF greater than G-CSF. Binding experiments demonstrated NFE-1 activity in all cell lines except the G-CSF-dependent line. Function of the NFE-1 protein was assessed by the expression of the CAT gene linked to the SV40 promoter and a mutant (-175 T----C) HPFH gamma-globin promoter. High level CAT expression was seen only in the Epo1 cells although low level expression was also seen in the parent 32D. These results demonstrate that the specificity of the expression of NFE-1 for the erythroid--megakaryocytic--mast cell lineages is obtained by progressive inactivation of its expression in alternative lineages.
Nanoplasmonics for chemistry (2014)

Noble metal nanoparticles supporting plasmonic resonances behave as efficient nanosources of light, heat and energetic electrons. Owing to these properties, they offer a unique playground to trigger chemical reactions on the nanoscale. In this tutorial review, we discuss how nanoplasmonics can benefit chemistry and review the most recent developments in this new and fast growing field of research.
Identification on receptors for leukotriene B4 expressed on guinea-pig peritoneal eosinophils. (1992)

We have recently reported that guinea-pig eosinophil chemotactic factor of anaphylaxis (ECF-A), an activity present in diffusates from antigen-challenged sensitized lung, is largely accounted for by leukotriene B4 (LTB4) and to a lesser extent 8(S)15(S)-dihydroxy 5,9,11,13 (Z,E,Z,E) eicosatetraenoic acid. We characterized cell surface receptors for LTB4 on guinea-pig eosinophils in order to demonstrate an association between receptor occupancy and eosinophiliotactic activity of guinea-pig ECF-A. Equilibrium binding studies showed that peritoneal eosinophils bound [3H]LTB4 in a cell concentration and time-dependent fashion. The binding was saturable and specific for LTB4 as other eosinophil chemoattractants, i.e. platelet-activating factor (PAF) and 8(S)15(S)-diHETE, were unable to displace significant amounts of [3H]LTB4. In addition the binding was readily reversed by the LTB4 receptor antagonist LY 255283 (Ki 4.30 nM). Scatchard plot analysis revealed two discrete populations of binding sites, high affinity (Kd1 = 0.30 nM; Bmax = 900 sites/cell) and low-affinity sites (Kd2 = 140 nM; Bmax = 60,000 sites/cell). The major migratory component of LTB4-stimulated eosinophil locomotion was chemotaxis, optimal at 1 x 10(-7) M (P < 0.01) with EC50 value of 3 x 10(-9) M. A comparison of the profile of arachidonic acid metabolism by RP-HPLC analysis showed that following stimulation with calcium ionophore (A23187) guinea-pig eosinophils preferentially synthesized LTB4 (10 ng/10(6) cells) while in contrast human eosinophils synthesized LTC4 (10 ng/10(6) cells). Therefore our data show that guinea-pig eosinophils express both high- and low-affinity receptors for LTB4 and that the chemotactic response to this mediator may be mediated by ligation of the high-affinity binding site. Furthermore guinea-pig peritoneal eosinophils can synthesize LTB4, a mediator which constitutes > 60% of guinea-pig ECF-A.
Ray Casting Deformable Models on the GPU (2008)

The GPUs pack high computation power and a restricted architecture into easily available hardware today. They are now used as computation co-processors and come with programming models that treat them as standard parallel architectures. We explore the problem of realtime ray casting of large deformable models (over a million triangles) on large displays (a million pixels) on an off-the-shelf GPU in this paper. Ray casting is an inherently parallel and highly compute intensive operation. We build a GPU-efficient three-dimensional data structure for this purpose and a corresponding algorithm that uses it for fast ray casting. We also present fast methods to build the data structure on the SIMD GPUs, including a fast multi-split operation. We achieve real-time ray-casting of a million triangle model onto a million pixels on current Nvidia GPUs using the CUDA model. Results are presented on the data structure building and ray casting on a number of models. The ideas presented here are likely to extend to later models and architectures of the GPU as well as to other multi-core architectures.
Adenovirus-Mediated Heme Oxygenase-1 Gene Transfer Inhibits the Development of Atherosclerosis in Apolipoprotein E–Deficient Mice (2001)

Overexpression of HO-1 in vascular cells facilitates iron metabolism and attenuates development of atherosclerosis in apoE-deficient mice.
The Enigma of Non-A, Non-B Hepatitis (1982)

Journal Article The Enigma of Non-A, Non-B Hepatitis Get access William S. Robinson William S. Robinson Department of Medicine Stanford University School of Medicine, Stanford, California Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 145, Issue 3, March 1982, Pages 387–395, https://doi.org/10.1093/infdis/145.3.387 Published: 01 March 1982
Allopregnanolone Analogs That Positively Modulate GABAA Receptors Protect against Partial Seizures Induced by 6‐Hz Electrical Stimulation in Mice (2004)

Neuroactive steroids have comparable potencies in the 6-Hz and PTZ models. Their structural specificity in both models corresponds with their activities as positive allosteric modulators of GABAA receptors, although ganaxolone is more potent than expected, probably because it has greater bioavailability. The 6-Hz model may be a valuable tool in drug development for the identification of GABAergic AEDs.
Biopterin derivatives in normal and phenylketonuric patients after oral loads of L-phenylalanine, L-tyrosine, and L-tryptophan. (1976)

Plasma biopterin derivatives studied in 10 normal and 21 phenylketonuric children showed a significantly high concentration in the latter group. Biopterin derivatives correlated with plasma phenylalanine concentration, but in normal adults given an oral phenylalanine load the rate of increase with phenylalanine differed from that in phenylketonuric patients. A patient with hyperphenylalaninaemia, not due to phenylketonuria, had an abnormal biopterin derivatives response to phenylalanine distinct from that of patients with classical phenylketonuria. This may be a useful investigation to differentiate some variants of phenylketonuria.