gebhart/patrepeval huggingface dataset:
New Trends in Cross-Coupling (2014)

Palladium-catalysed cross-coupling reactions constitute a powerful class of chemical methods for the creation of carbon-carbon and carbon-heteroatom bonds used in organic synthesis, famously recognized by the 2010 Nobel Prize awarded to Richard F. Heck, Ei-ichi Negishi and Akira Suzuki ‘for palladium-catalysed cross-couplings in organic synthesis.’ These methods have become ubiquitous in academic and industrial settings alike, as applications span from industrial production of pharmaceuticals, agrochemicals, polymers, and dyes to the synthesis of complex natural products.New Trends in Cross-Coupling provides the reader with the history and basic, concepts of cross-coupling up to the state of the art in modern coupling reactions from both technology and applied perspectives. A wide breadth of topics including selecting prominent ligand types; advances in Pd-phosphine precatalysts and Pd N-heterocyclic carbene complexes; new reactions such as carboiodination; implementation of new technologies such as continuous flow and advanced metal detection methods; greener approaches to cross-coupling; as well as large-scale applications in the syntheses of pharmaceutical materials are covered.Edited by Thomas J. Colacot, an Industrial expert on cross coupling, the book contains contributions from academic and industrial world leaders in the field as well as a Forewords from Professor Barry M. Trost, Gregory C. Fu and 2010 Nobel Laureate in Chemistry Professor Ei-ichi Negishi. New Trends in Cross-Coupling serves as a reference guide for both undergraduate and graduate students as well as those who are experts in the area.'...this compilation, a “Must” for anyone interested in learning and using newer trends in cross-coupling.' Ei-ichi Negishi, 2010 Nobel Laureate in Chemistry'I am very pleased to see such a book concerning cross coupling reactions published.' Professor Akira Suzuki - 2010 Nobel Laureate in Chemistry.'this book is invaluable to anyone involved in synthesis of organic compounds for any purpose.' Professor Barry Trost, Stanford University.
Transcriptional mapping of vesicular stomatitis virus in vivo (1977)

Synthesis of the proteins of vesicular stomatitis virus (Indiana serotype) was studied in mouse L cells infected with virus that had been exposed to UV radiation. The UV target sizes measured during primary transcription indicated that the five genes occupy a single transcriptional unit. Thus, in infected cells, as a cell-free system, transcription of vesicular stomatitis virus RNA initiates at a single point and proceeds in the order N. NS, M, G, and L.
Marfan syndrome--current medical and genetic knowledge: how to treat and when. (1997)

Marfan syndrome (MFS), first described 100 years ago, remains a clinical diagnosis. Two out of 3 major systems (ocular, cardiac, skeletal) must be classically affected, to avoid overdiagnosis. Diagnosis may be confirmed by linkage to the dominantly inherited gene MFS-1 on 15q21, or by discovering the family mutation. Either technique may be used for prenatal diagnosis. Modern medical and surgical management is prolonging life, by on average, 13 years, with postoperative 20 year survival rate 65%. Beta-blocker therapy slows aortic root dilatation, and elective surgery is offered at ascending aorta diameter > or = 5 cm. Known associations with early death include new mutation, family history of dissection < 5 cm, male sex, and emergency surgery where the death rate is 5 times higher than in elective surgery. Pregnancy bears a 1% risk of fatal complication, and this risk rises with increasing aortic root diameter. Caesarean section at 38 weeks gestation should be offered if aortic root diameter is greater than 4.5 cm. Gene mapping reveals almost every mutation to be unique, interfering with multimerization of fibrillin monomers, or interactions with other connective tissue elements. Neonatal MFS is caused by mutations in exons 24-32, in calcium-binding EGF-like sequences. Mutations affecting cysteines or amino acids critical for calcium binding in other EGF-like domains, or deletions of complete EGF-like domains, generally lead to classical MFS phenotypes, as do mutations in TGF receptor-like domains. Heterogeneity has been reported with a second locus (MFS-2) on chromosome 3 in one French pedigree.
Human nidogen: cDNA cloning, cellular expression, and mapping of the gene to chromosome Iq43. (1989)

A human placental lambda gt11 expression cDNA library was screened for nidogen cDNAs by hybridizations with a heterologous mouse nidogen cDNA. A total of four positive overlapping clones were identified, and the sizes of the inserts were shown to vary from 0.8 to 2.8 kb. Nucleotide sequencing of the human cDNAs revealed that the largest clone, cHPN-16, contained both a 5' open reading frame encoding 582 amino acids and a 3' untranslated region of 1,063 nucleotides. Comparison of human cDNA sequences with mouse nidogen sequences revealed 84% identity on the nucleotide level and 88% identity with the deduced amino acid sequence. The deduced amino acid sequence of the human cDNAs revealed the presence of cysteine-rich epidermal growth factor-like repeats and the sequence Arg-Gly-Asp (RGD), a potential cell binding site, two features previously identified in mouse nidogen. The sequence Asn-Pro-Ser, a consensus sequence for N-linked glycosylation, was also noted. The newly isolated human cDNAs were utilized to analyze the expression of the nidogen gene by cultured human cells. Northern hybridizations revealed a single mRNA transcript of approximately 6.0 kb in human skin fibroblast and in HT 1080 fibrosarcoma cell cultures. However, the human choriocarcinoma cell line JEG-3, which expressed laminin genes, did not contain detectable levels of nidogen mRNAs. Quantitation of the relative nidogen mRNA abundance in HT 1080 fibrosarcoma cells indicated that nidogen mRNA levels were approximately the same as those for the laminin B2 chain. Finally, one of the nidogen cDNAs was used to map the nidogen gene onto locus q43 of chromosome 1.
Boolean Programs: A Model and Process for Software Analysis (2000)

A fundamental issue in model checking of software is the choice of a model for software. We present a model called boolean programs that is expressive enough to represent features in common programming languages and is amenable to model checking. We present a model checking algorithm for boolean programs using context-free-language reachability. The model checking algorithm allows procedure calls with unbounded recursion, exploits locality of variable scopes, and gives short error traces. Furthermore, we give a process for incrementally re ning an initial skeletal boolean program B (representing a source program P ) with respect to a particular reachability query in P . The presence of infeasible paths in P may lead to the model checker reporting false positive errors in B. We show how to re ne B by introducing boolean variables to rule out the infeasible paths. The process uses ideas from model checking, symbolic execution, and program slicing.
Virus of Pekin ducks with structural and biological relatedness to human hepatitis B virus (1980)

A virus found in the sera of Pekin ducks appears to be a new member of the human hepatitis B-like family of viruses. This virus had a diameter of 40 nm and an appearance in the electron microscope similar to that of human hepatitis B virus. The DNA genome of the virus was circular and partially single stranded, and an endogenous DNA polymerase associated with the virus was capable of converting the genome to a double-stranded circle with a size of ca. 3,000 base pairs. An analysis for viral DNA in the organs of infected birds indicated preferential localization in the liver, implicating this organ as the site of virus replication. In all of these aspects, the virus bears a striking resemblance to human hepatitis B virus and appears to be a new member of this family, which also includes ground squirrel hepatitis virus and woodchuck hepatitis virus.
Discovery of new acetylcholinesterase and butyrylcholinesterase inhibitors through structure-based virtual screening (2017)

Small molecule cholinesterase (ChE) inhibitors represent one of the most effective therapeutic strategies for the treatment of Alzheimer's disease (AD).
Support vector machine-based short-term wind power forecasting (2011)

This paper proposes a support vector machine (SVM)-based statistical model for wind power forecasting (WPF). Instead of predicting wind power directly, the proposed model first predicts the wind speed, which is then used to predict the wind power by using the power-wind speed characteristics of the wind turbine generators. Simulation studies are carried out to validate the proposed model for very short-term and short-term WPF by using the data obtained from the National Renewable Energy Laboratory (NREL). Results show that the proposed model is accurate for very short-term and short-term WPF and outperforms the persistence model as well as the radial basis function neural network-based model.
Structural basis of hepatocyte growth factor/scatter factor and MET signalling (2006)

The polypeptide growth factor, hepatocyte growth factor/scatter factor (HGF/SF), shares the multidomain structure and proteolytic mechanism of activation of plasminogen and other complex serine proteinases. HGF/SF, however, has no enzymatic activity. Instead, it controls the growth, morphogenesis, or migration of epithelial, endothelial, and muscle progenitor cells through the receptor tyrosine kinase MET. Using small-angle x-ray scattering and cryo-electron microscopy, we show that conversion of pro(single-chain)HGF/SF into the active two-chain form is associated with a major structural transition from a compact, closed conformation to an elongated, open one. We also report the structure of a complex between two-chain HGF/SF and the MET ectodomain (MET928) with 1:1 stoichiometry in which the N-terminal and first kringle domain of HGF/SF contact the face of the seven-blade beta-propeller domain of MET harboring the loops connecting the beta-strands b-c and d-a, whereas the C-terminal serine proteinase homology domain binds the opposite "b" face. Finally, we describe a complex with 2:2 stoichiometry between two-chain HGF/SF and a truncated form of the MET ectodomain (MET567), which is assembled around the dimerization interface seen in the crystal structure of the NK1 fragment of HGF/SF and displays the features of a functional, signaling unit. The study shows how the proteolytic mechanism of activation of the complex proteinases has been adapted to cell signaling in vertebrate organisms, offers a description of monomeric and dimeric ligand-receptor complexes, and provides a foundation to the structural basis of HGF/SF-MET signaling.
Sterols. CXLVIII. Sapogenins. LXII. The Structure of the Side Chain in the Dihydro-pseudosapogenins1 (1942)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSterols. CXLVIII. Sapogenins. LXII. The Structure of the Side Chain in the Dihydro-pseudosapogenins1Russell E. Marker, D. L. Turner, and Paul R. UlshaferCite this: J. Am. Chem. Soc. 1942, 64, 7, 1655–1658Publication Date (Print):July 1, 1942Publication History Published online1 May 2002Published inissue 1 July 1942https://pubs.acs.org/doi/10.1021/ja01259a052https://doi.org/10.1021/ja01259a052research-articleACS PublicationsRequest reuse permissionsArticle Views22Altmetric-Citations6LEARN 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 ß-Thioxoketones: byt-Butyllithium-Promoted Claisen Condensation Reaction of Ketones with Thionoesters (1985)

Condensation entre des alcanones-2, des cyclanones et les thioacetate et thiopropionate de O-ethyle en presence de t-butyl-lithium
Expression of proliferation‐associated nuclear autoantigens, p330d/CENP‐F and PCNA, in differentiation and in drug‐induced growth inhibition using two‐parameter flow cytometry (1996)

Abstract p330 d /CENP‐F is a recently described nuclear autoantigen that was detected in PHA‐stimulated but not in resting peripheral lymphocytes. This protein accumulates in the nucleus during S‐phase and reaches maximum levels during the G 2 and M phases of the cell cycles. We compared the expression of p330 d /CENP‐F and proliferating cell nuclear antigen (PCNA) during the induction of terminal myeloid differentiation of HL‐60 tumour cells. HL‐60 cells were induced to differentiate with retinoic acid (RA), dimethyl sulfoxide (DMSO), and 3‐nitrobenzothiazolo [3,2‐]quinolinium (NBQ), and collected at different intervals. Control and treated cells were analyzed by two‐parameter flow cytometry using propidium iodide and antibodies to p330 d /CENP‐F and PCNA. The percentage of p330 d /CENP‐F and PCNA positive cells was found to be proportional to the percentage of proliferating cells. After two cell cycles (65 h), the percentage of p330 d /CENP‐F and PCNA positive cells was reduced proportionately to the number of cells that had differentiated. Reduction in the expression of both antigens was completed after 120 h when 80% to 85% of the cells were arrested in G 1 and displayed the mature phenotype. The expression of p330 d /CENP‐F and PCNA was also assessed in the growth inhibition of HT‐29 cells induced by various concentrations of camptothecin (CPT), etoposide (VP‐16), and aphidicolin (APH). There was a dose‐dependent displacement of cells to late S‐phase by CPT while VP‐16 induced cells to accumulate in G 2 + M, and as expected these effects caused a strong increase in the cellular levels of both antigens. The arrest of cells in G 1 by APH led to a significant decrease in their expression. The dramatic reduction in p330 d /CENP‐F levels during differentiation, and the correlation of its expression with the cell cycle effects of the cytotoxic drugs are consistent with the behaviour expected for a proliferation marker.
Heparin Binding to Plasma Proteins, an Important Mechanism for Heparin Resistance (1992)

Heparin dosage requirements vary widely among patients with venous thromboembolism. In this study, we measured the proportion of anticoagulantly-active heparin which was reversibly bound and neutralized by plasma proteins (defined as reversible heparin neutralization) in the pre-treatment plasma (in vitro) and in the 6 h post-treatment plasma (ex vivo) of patients with venous thromboembolism treated with a fixed dose of heparin. Reversible heparin neutralization was assessed by comparing the heparin levels measured as anti-factor Xa activity before and after the addition of low affinity heparin which is essentially devoid of anti-factor Xa activity, in order to displace heparin bound to plasma proteins. The results indicate that reversible heparin neutralization due to binding to plasma proteins is a major determinant of the anticoagulant response to a fixed dose of standard heparin 6 h post-treatment and of the eventual heparin dose required to achieve a therapeutic anticoagulant effect on days 3-5 of heparin treatment.
An integrated approach to the discovery of potent agelastatin A analogues for brain tumors: chemical synthesis and biological, physicochemical and CNS pharmacokinetic analyses (2013)

(−)-Agelastatin A (AA), isolated from the coral sea axinellid sponge Agelas dendromorpha, has shown a high antineoplastic activity. We have synthesized eighteen AA analogues and analyzed their cytotoxicities towards three cancer cell lines. By the structure–activity relationship (SAR) study, we identified three novel analogues with higher or comparable cytotoxic activities to AA. They were subjected to chemoinformatic analysis, which revealed physicochemical properties favoring excellent central nervous system (CNS) penetration. CNS pharmacokinetic analysis in murine models validated the chemoinformatic prediction and revealed that these analogues indeed had better CNS penetration than AA. These novel potent AA analogues deserve further evaluation for therapeutic use against cancers, particularly primary and secondary brain tumors.
The Judicial Betrayal of Blacks - Again: The Supreme Court's Destruction of the Hopes Raised by Brown V. Board of Education (2004)

This Article discusses the history of school desegregation beginning with the pivotal decision in Brown v. Board of Education and noting the hopes that the case raised for black americans. The Article notes the resistance that Brown faced, especially from political forces who began to subvert the desegregation process, and examines the Supreme Court's subsequent decisions which aimed to secure Brown's objectives. The Article also examines the desegregation attempts in the North and discusses the difficulties plaintiffs faced in proving racial discrimination in school districts. The Article concludes by stating that the commitment to desegregation is waring and that segregation is retaking American schools.
Direct current insulator‐based dielectrophoretic characterization of erythrocytes: ABO‐Rh human blood typing (2011)

A microfluidic platform developed for quantifying the dependence of erythrocyte (red blood cell, RBC) responses by ABO-Rh blood type via direct current insulator dielectrophoresis (DC-iDEP) is presented. The PDMS DC-iDEP device utilized a 400 x 170 μm² rectangular insulating obstacle embedded in a 1.46-cm long, 200-μm wide inlet channel to create spatial non-uniformities in direct current (DC) electric field density realized by separation into four outlet channels. The DC-iDEP flow behaviors were investigated for all eight blood types (A+, A-, B+, B-, AB+, AB-, O+, O-) in the human ABO-Rh blood typing system. Three independent donors of each blood type, same donor reproducibility, different conductivity buffers (0.52-9.1 mS/cm), and DC electric fields (17.1-68.5 V/cm) were tested to investigate separation dependencies. The data analysis was conducted from image intensity profiles across inlet and outlet channels in the device. Individual channel fractions suggest that the dielectrophoretic force experienced by the cells is dependent on erythrocyte antigen expression. Two different statistical analysis methods were conducted to determine how distinguishable a single blood type was from the others. Results indicate that channel fraction distributions differ by ABO-Rh blood types suggesting that antigens present on the erythrocyte membrane polarize differently in DC-iDEP fields. Under optimized conductivity and field conditions, certain blind blood samples could be sorted with low misclassification rates.
The CXC Chemokine Stromal Cell-Derived Factor Activates a Gi-Coupled Phosphoinositide 3-Kinase in T Lymphocytes (1999)

The cellular effects of stromal cell-derived factor-1 (SDF-1) are mediated primarily by binding to the CXC chemokine receptor-4. We report in this study that SDF-1 and its peptide analogues induce a concentration- and time-dependent accumulation of phosphatidylinositol-(3,4,5)-trisphosphate (PtdIns(3,4,5)P3) in Jurkat cells. This SDF-1-stimulated generation of D-3 phosphoinositide lipids was inhibited by pretreatment of the cells with an SDF-1 peptide antagonist or an anti-CXCR4 Ab. In addition, the phosphoinositide 3 (PI 3)-kinase inhibitors wortmannin and LY294002, as well as the Gi protein inhibitor pertussis toxin, also inhibited the SDF-1-stimulated accumulation of PtdIns(3,4,5)P3. The effects of SDF-1 on D-3 phosphoinositide lipid accumulation correlated well with activation of the known PI 3-kinase effector protein kinase B, which was also inhibited by wortmannin and pertussis toxin. Concentrations of PI 3-kinase inhibitors, sufficient to inhibit PtdIns(3,4,5)P3 accumulation, also inhibited chemotaxis of Jurkat and peripheral blood-derived T lymphocytes in response to SDF-1. In contrast, SDF-1-stimulated actin polymerization was only partially inhibited by PI 3-kinase inhibitors, suggesting that while chemotaxis is fully dependent on PI 3-kinase activation, actin polymerization requires additional biochemical inputs. Finally, SDF-1-stimulated extracellular signal-related kinase (ERK)-1/2 mitogen-activated protein kinase activation was inhibited by PI 3-kinase inhibitors. In addition, the mitogen-activated protein/ERK kinase inhibitor PD098059 partially attenuated chemotaxis in response to SDF-1. Hence, it appears that ERK1/2 activation is dependent on PI 3-kinase activation, and both biochemical events are involved in the regulation of SDF-1-stimulated chemotaxis.
Leukotriene modifiers in the treatment of asthma (1998)

Leukotriene modifiers are an entirely new class of asthma treatment, which have entered clinical practice in 1996-7 in several countries including Britain, Japan, and the United States. Their development is an example of rational drug design following the elucidation of leukotriene structures in 1979-80 and the subsequent confirmation of their pathophysiological role as inflammatory mediators in asthma.1

There are two types of leukotriene modifier: leukotriene synthesis inhibitors and cysteinyl leukotriene receptor antagonists.2 Both are used to block the bronchoconstrictor and pro-inflammatory activity of cysteinyl leukotrienes within the asthmatic airway. Cysteinyl leukotrienes (LTC4, LTD4, and LTE4) were originally identified as long lasting smooth muscle spasmogens and collectively termed “slow reacting substance of anaphylaxis” (SRS-A). They are now known to be metabolites of arachidonic acid formed by the 5-lipoxygenase pathway1 and are produced almost exclusively by inflammatory leucocytes, especially mast cells, basophils, and eosinophils. The leukotriene receptor antagonists block the activity of cysteinyl leukotrienes at their receptors ( CysLT 1 ) on bronchial smooth muscle and elsewhere, while the leukotriene synthesis inhibitors block the synthesis of all leukotrienes by interrupting the 5-lipoxygenase pathway.2

Cysteinyl leukotrienes are among …
Enhanced Cellular Immune Responses Elicited by an Engineered HIV-1 Subtype B Consensus-based Envelope DNA Vaccine (2007)

An important goal for human immunodeficiency virus (HIV) vaccines is to develop immunogens that induce broader and more potent cellular immune responses. In this study of DNA vaccine potency, we constructed a novel subtype B env gene (EY2E1-B) with the goal of increasing vaccine antigen immune potency. The vaccine cassette was designed based on subtype B-specific consensus sequence with several modifications, including codon optimization, RNA optimization, the addition of a Kozak sequence, and a substituted immunoglobulin E leader sequence. The V1 and V2 loops were shortened and the cytoplasmic tail was truncated to prevent envelope recycling. Three different strains of mice (BALB/c, C57BL/6, and HLA-A2 transgenic mice) were immunized three times with pEY2E1-B or the primary DNA immunogen pEK2P-B alone. The analysis of specific antibody responses suggested that EY2E1-B could induce a moderate subtype B-specific antibody response. Moreover, this construct was up to four times more potent at driving cellular immune responses. Epitope mapping results indicated that there is an increase in the breadth and magnitude of cross-reactive cellular responses induced by the EY2E1-B immunogen. These properties suggest that such a synthetic immunogen deserves further examination for its potential to serve as a component antigen in an HIV vaccine cocktail.