gebhart/patrepeval huggingface dataset:
Quinazoline antifolates inhibiting thymidylate synthase: synthesis of four oligo(L-.gamma.-glutamyl) conjugates of N10-propargyl-5,8-dideazafolic acid and their enzyme inhibition (1989)

The synthesis is described of four oligo(gamma-glutamyl) conjugates of N10-propargyl-5,8-dideazafolic acid containing a total of two, three, four, and five L-glutamic acid residues. The tert-butyl group was chosen as the carboxyl protecting group in order to obviate the use of alkali and thus the possibility of gamma----alpha transpeptidation. The starting material, di-tert-butyl glutamate, was coupled to N-(benzyloxycarbonyl)-L-glutamic acid alpha-tert-butyl ester via a mixed anhydride with isobutyl chloroformate. Hydrogenolysis of the benzyloxycarbonyl group in the product gave a carboxyl-protected diglutamate, which either was acylated with 4-[(benzyloxycarbonyl)amino] benzoyl chloride to give a protected aminobenzamide or was cycled further by using the above mixed anhydride/hydrogenolysis sequence into tri-, tetra-, and pentaglutamates. Each of the last named was also acylated, as above, to give a benzamide. The benzyloxycarbonyl group in the benzamides was removed by hydrogenolysis and the amino groups thus exposed were N-alkylated with propargyl bromide. The resulting proparglyamines were further alkylated with 2-amino-6-(bromomethyl)-4-hydroxyquinazoline hydrobromide to give the antifolate poly(t-Bu) esters. Deprotection with trifluoroacetic acid in the final step delivered the desired antifolates as their trifluoroacetate salts. The di- to pentaglutamates were, respectively, 31-, 97-, 171-, and 167-fold more inhibitory to WI-L2 human thymidylate synthase than the parent compound.
Stereocontrol in homogeneous catalytic hydrogenation via hydroxyl group coordination (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereocontrol in homogeneous catalytic hydrogenation via hydroxyl group coordinationGilbert Stork and Daniel E. KahneCite this: J. Am. Chem. Soc. 1983, 105, 4, 1072–1073Publication Date (Print):February 1, 1983Publication History Published online1 May 2002Published inissue 1 February 1983https://pubs.acs.org/doi/10.1021/ja00342a080https://doi.org/10.1021/ja00342a080research-articleACS PublicationsRequest reuse permissionsArticle Views2570Altmetric-Citations170LEARN 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 and anti-HIV-1 activity of 2'-"up"-fluoro analogs of active anti-AIDS nucleosides 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (DDC) (1990)

1-(3-Azido-2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (6, F-AZT) and 1-(2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl)cytosine (12, F-DDC) were synthesized from the potent antiherpes virus nucleosides 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (1, FMAU) and 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) in the hope that introduction of a 2-"up"-fluoro substituent might potentiate the anti-HIV activity of AZT and DDC. FMAU (1) was converted in three steps into 2,3'-anhydro-1-(2-fluoro-2-deoxy-5-O-trityl-beta-D-lyxofuranosyl)thymine (4), which when treated with NaN3 followed by detritylation afforded 6. F-DDC was prepared by two methods. Tritylation of FIAC followed by treatment of the product with thiocarbonyldimidazole afforded the 5'-O-trityl-3'-O-(imidazolyl)thiocarbonyl nucleoside 9. Upon radical reduction of 9 with Bu3SnH and AIBN, 5'-O-trityl-DDC 10 was obtained. Compound 10 was detritylated to give 12, which (when obtained by this procedure) resisted crystallization, but the diacetate 12' was obtained in crystalline form. Alternatively, FAC (14) was converted into N4,O5'-dibenzoyl derivative 15, which was treated with thiocarbonyldiimidazole. Reduction of 16 with Bu3SnH/AIBN followed by debenzoylation afforded 12, which was obtained in crystalline form. F-AZT did not exhibit any significant activity against the human immunodeficiency virus (HIV) in vitro. F-DDC, however, showed activity against HIV-1, but the therapeutic index is much inferior to that of AZT.
Cardiac allograft vasculopathy: current concepts, recent developments, and future directions. (1992)

Survival after heart transplantation has improved steadily over the past decade, with 1-year mortality rates now less than 15% in most centers. Despite a substantial improvement in early survival, late death has not been significantly impacted. The major cause of late death is due to cardiac allograft vasculopathy, an accelerated form of coronary artery disease. The mechanisms responsible for cardiac allograft vasculopathy are thought to be immunologic; however direct confirmation of this is lacking. Because cardiac allograft vasculopathy is not amenable to traditional therapies for coronary atherosclerosis, to date the only treatment is repeat transplantation. This paper reviews the clinical aspects of cardiac allograft vasculopathy, the recent experimental work, and potential future directions for study.
Prothrombin association with phospholipid monolayers (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProthrombin association with phospholipid monolayersLawrence D. Mayer, Gary L. Nelsestuen, and Howard L. BrockmanCite this: Biochemistry 1983, 22, 2, 316–321Publication Date (Print):January 18, 1983Publication History Published online1 May 2002Published inissue 18 January 1983https://pubs.acs.org/doi/10.1021/bi00271a013https://doi.org/10.1021/bi00271a013research-articleACS PublicationsRequest reuse permissionsArticle Views84Altmetric-Citations38LEARN 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
Functional-Genomics-Based Identification and Characterization of Open Reading Frames Encoding α-Glucoside-Processing Enzymes in the Hyperthermophilic Archaeon Pyrococcus furiosus (2007)

Bioinformatics analysis and transcriptional response information for Pyrococcus furiosus grown on alpha-glucans led to the identification of a novel isomaltase (PF0132) representing a new glycoside hydrolase (GH) family, a novel GH57 beta-amylase (PF0870), and an extracellular starch-binding protein (1,141 amino acids; PF1109-PF1110), in addition to several other putative alpha-glucan-processing enzymes.
Nanoparticle Mediated Electron Transfer Across Organic Layers: From Current Understanding to Applications (2013)

In the last few years electrode-organic layer-nanoparticle constructs have attracted considerable research interest for systems where in the absence of the nanoparticles the electrode is passivated. This is because it has been observed that if the organic layer is a good self-assembled monolayer that passivates the electrode, the presence of the nanoparticles "switches on" faradaic electrochemistry and because electron transfer between the electrode and the nanoparticles is apparently independent of the thickness of the organic layer. This review 1) outlines the full extent of the experimental observations regarding this phenomenon, 2) discusses a recent theoretical description to explain the observations that have just been supported with experimental evidences and 3) provides an overview of the application of these systems in sensing and photovoltaics. © 2014 Sociedade Brasileira de Quimica.
Temperature dependences of the acoustic nonlinearity parameter B/A of aqueous solutions of amino acids (1992)

A differential technique for evaluating the molar increments of the nonlinearity parameter B/A has been employed for investigations of aqueous solutions of the amino acids glycine, alanine, norvaline, norleucine, arginine monohydrochloride, and lysine monohydrochloride in the temperature range 18 degrees C-45 degrees C. Some regularities of temperature dependencies of the nonlinearity parameter B/A of hydration shells of charged and aliphatic groups have been found. Contributions of these groups to the value of B/A molar increments of solute versus temperature have been estimated.
评《马克思的 和今日资本主义》一书 (1979)

此书以貌似严谨的方式,研究了马克思的《资本论》理论结构的一些重要方面。但它却用一大堆混乱的词藻来表达它的思想,因此需要绞尽脑汁反复推敲才能了解它的观点,这无疑要使许多读者望而生畏。再者,把这篇评论的结论预先说出来,那就是:把这本书读到底,也是不会发现任何理论上的黄金之国。尽管如此,此书还是间接提出了马克思主义理论在事实上如何能够发展的一些重要问题。马克思主义的经典基础作者们得出的结论是清楚的。他们不满意那些代表马克思主义经典基础的命题,他们希望在新的基础上建立马克思主义理
Production and characterization of interferon induced in chicken leukocytes by concanavalin A. (1986)

Interferon (IFN) was induced in chicken peripheral blood leukocytes by exposure to Concanavalin A (Con A). It has reached a maximum level 96 hr after stimulation with the optimum dose of 10 micrograms/ml. The IFN was partially purified by chromatography on controlled-pore glass adsorbent and was characterized as a fairly acid-stable and heat-resistant, trypsin-sensitive and species-specific substance with Mr of 20,500 Da. Antiviral response by this type of IFN in chick fibroblast culture developed within several hours. This study provides first evidence of the presence of IFN in supernatants of mitogen-stimulated chicken peripheral leukocytes.
1‐Cyano‐4‐dimethylamino pyridinium tetrafluoroborate as a cyanylating agent for the covalent attachment of ligand to polysaccharide resins (1983)

FEBS LettersVolume 154, Issue 1 p. 209-210 Full-length articleFree Access 1-Cyano-4-dimethylamino pyridinium tetrafluoroborate as a cyanylating agent for the covalent attachment of ligand to polysaccharide resins Correction(s) for this article 1-Cyano-4-dimethylamino pyridinium tetrafluoroborate as a cyanylating agent for the covalent attachment of ligand to polysaccharide resins Volume 161Issue 1FEBS Letters pages: 163-163 First Published online: October 25, 2001 Joachim Kohn, Joachim Kohn Department of Biophysics, The Weizmann Institute of Science, Rehovot 76100, IsraelSearch for more papers by this authorMeir Wilchek, Meir Wilchek Department of Biophysics, The Weizmann Institute of Science, Rehovot 76100, IsraelSearch for more papers by this author Joachim Kohn, Joachim Kohn Department of Biophysics, The Weizmann Institute of Science, Rehovot 76100, IsraelSearch for more papers by this authorMeir Wilchek, Meir Wilchek Department of Biophysics, The Weizmann Institute of Science, Rehovot 76100, IsraelSearch for more papers by this author First published: April 05, 1983 https://doi.org/10.1016/0014-5793(83)80905-3Citations: 54AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume154, Issue1April 05, 1983Pages 209-210 ReferencesRelatedInformation
ANTIGENIC DIVERSITY IN MAXADILAN, A SALIVARY PROTEIN FROM THE SAND FLY VECTOR OF AMERICAN VISCERAL LEISHMANIASIS (2004)

The salivary protein maxadilan (MAX) is a vasodilator and immunomodulator from the sand fly vector of the protozoan parasite Leishmania chagasi. Vaccinating BALB/c mice with sand fly salivary gland extracts or with MAX protects the host against L. major infection. Because of the potential use of MAX in an anti-Leishmania vaccine, we characterized the vertebrate host IgG response to MAX in the present study. Our immunochemical analysis indicated that antibodies to MAX were detected in BALB/c mice, as well as in pigs and humans, from a area in Nicaragua endemic for Lutzomyia longipalpis. Previous studies demonstrate that the MAX protein is polymorphic on the amino acid level. Our findings suggested that naturally occurring MAX variants were recognized specifically by the host immune system and antigenicity appeared to be associated with amino-acid sequence variability. Thus, antigenic diversity of MAX and possibly of other arthropod salivary proteins may dictate the development of vector-based vaccines(s).
Genetic aberrations detected by comparative genomic hybridization predict outcome in node-negative breast cancer. (1995)

Breast cancer progression is determined by a complex pattern of multiple genetic aberrations the association of which with patient prognosis is unknown. In this study, we have undertaken a genome-wide screening to detect genetic changes associated with clinical outcome in node-negative breast cancer. Comparative genomic hybridization was used to screen for DNA sequence gains and losses across all human chromosomes in 23 tumors from node-negative breast cancer patients with no disease recurrence after at least 5 years of follow-up and in 25 node-negative patients with recurrence during the first 5 years of follow-up. The total number of genetic aberrations (copy number gains and losses) per tumor was significantly greater in the recurrence group (P = 0.019) and in the subgroup of these patients who died as a result of breast cancer (P = 0.0022). When copy number losses and gains were analyzed separately, only losses were significant (P = 0.013 for recurrence and P = 0.002 for overall survival). Of the individual loci involved, a high level gain of the long arm of chromosome 8 was significantly associated with recurrence (P = 0.01, Fisher's exact test). Furthermore, amplification of DNA sequences at chromosome 20q12-13 was found in 7 cases (15%), 6 of which had early recurrence within 32 months of diagnosis. This genome-wide overview by comparative genomic hybridization suggests that genetically advanced node-negative breast cancers having a high overall number of genetic aberrations may have a poor prognosis and that increased copy number of two specific regions, 8q and 20q13, may confer a more aggressive phenotype. Results of this pilot study suggest that determination of the total number of DNA sequence copy number aberrations may help therapeutic decision making. Specific probes should be developed to test the prognostic value of 8q and 20q12-13 amplifications in large numbers of patients.
Increased Nox2 expression in human cardiomyocytes after acute myocardial infarction (2003)

Nox2 or its homologue(s) is expressed in normal and jeopardised human cardiomyocytes. This expression is increased in patients with AMI, suggesting a role for this ROS producing Nox2 homologue(s) in the human heart after AMI.
New developments in osteoarthritis: Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options (2010)

Joint trauma can lead to a spectrum of acute lesions, including osteochondral fractures, ligament or meniscus tears and damage to the articular cartilage. This is often associated with intraarticular bleeding and causes posttraumatic joint inflammation. Although the acute symptoms resolve and some of the lesions can be surgically repaired, joint injury triggers a chronic remodeling process in cartilage and other joint tissues that ultimately manifests as osteoarthritis in a majority of cases. The objective of the present review is to summarize information on pathogenetic mechanisms involved in the acute and chronic consequences of joint trauma and discuss potential pharmacological interventions. The focus of the review is on the early events that follow joint trauma since therapies for posttraumatic joint inflammation are not available and this represents a unique window of opportunity to limit chronic consequences.
High pressure structural study of SmNiO3 (2005)

The structural changes of SmNiO3 under high pressure have been studied by means of x-ray powder diffraction with synchrotron radiation in a diamond anvil cell. The orthorhombic perovskite structure transforms into the less distorted rhombohedral structure at a pressure of 26 GPa. The volume versus pressure data are well described by a single Murnaghan equation of state, which yields a bulk modulus of 167 GPa. At 2.5 GPa the cell parameter b undergoes a small abrupt contraction that we propose is related to the expected pressure-induced metallization.
Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal Disorders (1994)

Our data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.
Inhibition of GSK3 Promotes Replication and Survival of Pancreatic Beta Cells (2007)

Recent developments indicate that the regeneration of beta cell function and mass in patients with diabetes is possible. A regenerative approach may represent an alternative treatment option relative to current diabetes therapies that fail to provide optimal glycemic control. Here we report that the inactivation of GSK3 by small molecule inhibitors or RNA interference stimulates replication of INS-1E rat insulinoma cells. Specific and potent GSK3 inhibitors also alleviate the toxic effects of high concentrations of glucose and the saturated fatty acid palmitate on INS-1E cells. Furthermore, treatment of isolated rat islets with structurally diverse small molecule GSK3 inhibitors increases the rate beta cell replication by 2-3-fold relative to controls. We propose that GSK3 is a regulator of beta cell replication and survival. Moreover, our results suggest that specific inhibitors of GSK3 may have practical applications in beta cell regenerative therapies.
ChemInform Abstract: SYNTHESIS AND ANTICONVULSIVE ACTIVITY OF 4‐ALKYL (OR ARYL)AMINO‐6,6‐DIMETHYL‐5,6‐DIHYDRO‐8H‐PYRANO (OR THIOPYRANO)(3,4‐B)THIENO(5,4‐D)PYRIMIDINES (1978)

Abstract Durch ′ Reaktion der Ketone (I) mit Malonsäuredinitril und anschlißend Schwefel in Gegenwart von Diethylamin erhält man die Thiophen‐Derivate (V) bzw. (VI), aus denen mit Orthoameisensäureester und nachfolgend Aminen die Amidine (IX) gewonnen werden können.
Intravenous TAT-GDNF Is Protective After Focal Cerebral Ischemia in Mice (2003)

Our results demonstrate that TAT fusion proteins are powerful tools for the treatment of focal ischemia when delivered both before and after an ischemic insult. This approach may be of clinical interest because such fusion proteins can be intravenously applied and reach the ischemic brain regions. This approach may therefore offer new perspectives for future strategies in stroke therapy.
FtsL, an Essential Cytoplasmic Membrane Protein Involved in Cell Division in Escherichia coli (1992)

We have identified a gene involved in bacterial cell division, located immediately upstream of the ftsI gene in the min 2 region of the Escherichia coli chromosome. This gene, which we named ftsL, was detected through characterization of TnphoA insertions in a plasmid containing this chromosomal region. TnphoA topological analysis and fractionation of alkaline phosphatase fusion proteins indicated that the ftsL gene product is a 13.6-kDa cytoplasmic membrane protein with a cytoplasmic amino terminus, a single membrane-spanning segment, and a periplasmic carboxy terminus. The ftsL gene is essential for cell growth and division. A null mutation in ftsL resulted in inhibition of cell division, formation of long, nonseptate filaments, ultimate cessation of growth, and lysis. Under certain growth conditions, depletion of FtsL or expression of the largest ftsL-phoA fusion produced a variety of cell morphologies, including Y-shaped bacteria, indicating a possible general weakening of the cell wall. The FtsL protein is estimated to be present at about 20 to 40 copies per cell. The periplasmic domain of the protein displays a sequence with features characteristic of leucine zippers, which are involved in protein dimerization.
The apoB/apoA‐I ratio: a strong, new risk factor for cardiovascular disease and a target for lipid‐lowering therapy – a review of the evidence (2006)

During the last several years interest has focused on the importance of the lipid-transporting apolipoproteins--apoB transports all potentially atherogenic very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and LDL particles, and apoA-I transports and acts as the major antiatherogenic protein in the HDL particles. The evidence for the apoB/apoA-I ratio being a strong, new risk factor for cardiovascular (CV) disease and a target for lipid-lowering therapy is reviewed. Results from clinical prospective studies and lipid-lowering trials in healthy subjects and in patients with different clinical manifestations of atherosclerosis are reported. Risk of nonfatal and fatal myocardial infarction and stroke, and manifestations of atherosclerosis documented by angiographic, ultrasound and other techniques has been related to conventional lipids and apolipoproteins (apo). The cholesterol balance determined as the apoB/apoA-I ratio has repeatedly been shown to be a better marker than lipids, lipoproteins and lipid ratios. The results indicate that the apoB/apoA-I ratio is a simple, accurate and new risk factor for CV disease--the lower the apoB/apoA-I ratio, the lower is the risk. Guidelines should be developed in order to recognize the important clinical risk information embedded in the apoB/apoA-I ratio.
Recent developments in molecular organic electroluminescent materials (1998)

Abstract A review of recent developments in the design and use of small molecular organic electroluminescent materials for display applications is presented. The material issues pertaining to transport properties, color, emission efficiencies, and operational stability are described.
Copper-free click chemistry for dynamic in vivo imaging (2007)

Dynamic imaging of proteins in live cells is routinely performed by using genetically encoded reporters, an approach that cannot be extended to other classes of biomolecules such as glycans and lipids. Here, we report a Cu-free variant of click chemistry that can label these biomolecules rapidly and selectively in living systems, overcoming the intrinsic toxicity of the canonical Cu-catalyzed reaction. The critical reagent, a substituted cyclooctyne, possesses ring strain and electron-withdrawing fluorine substituents that together promote the [3 + 2] dipolar cycloaddition with azides installed metabolically into biomolecules. This Cu-free click reaction possesses comparable kinetics to the Cu-catalyzed reaction and proceeds within minutes on live cells with no apparent toxicity. With this technique, we studied the dynamics of glycan trafficking and identified a population of sialoglycoconjugates with unexpectedly rapid internalization kinetics.