gebhart/patrepeval huggingface dataset:
Stereodivergent Construction of Aminodiols with a CF3 Group (2010)

A stereodivergent synthesis of various 2-amino-1,3-diols and 3-amino-1,2-diols from a single intermediate, 2,3-epoxyketones, is described.
Spiroindolines Identify the Vesicular Acetylcholine Transporter as a Novel Target for Insecticide Action (2012)

The efficacy of all major insecticide classes continues to be eroded by the development of resistance mediated, in part, by selection of alleles encoding insecticide insensitive target proteins. The discovery of new insecticide classes acting at novel protein binding sites is therefore important for the continued protection of the food supply from insect predators, and of human and animal health from insect borne disease. Here we describe a novel class of insecticides (Spiroindolines) encompassing molecules that combine excellent activity against major agricultural pest species with low mammalian toxicity. We confidently assign the vesicular acetylcholine transporter as the molecular target of Spiroindolines through the combination of molecular genetics in model organisms with a pharmacological approach in insect tissues. The vesicular acetylcholine transporter can now be added to the list of validated insecticide targets in the acetylcholine signalling pathway and we anticipate that this will lead to the discovery of novel molecules useful in sustaining agriculture. In addition to their potential as insecticides and nematocides, Spiroindolines represent the only other class of chemical ligands for the vesicular acetylcholine transporter since those based on the discovery of vesamicol over 40 years ago, and as such, have potential to provide more selective tools for PET imaging in the diagnosis of neurodegenerative disease. They also provide novel biochemical tools for studies of the function of this protein family.
Antihyperglycemic Effect of Oolong Tea in Type 2 Diabetes (2003)

Oolong tea may be an effective adjunct to oral hypoglycemic agents in the treatment of type 2 diabetes.
Conjugation of Glycopeptide Thioesters to Expressed Protein Fragments: Semisynthesis of Glycosylated Interleukin-2 (2004)

This method describes the conjugation of a synthetic glycopeptide to the N-terminus of a recombinant human interleukin-2 (IL-2) protein fragment. The IL-2 protein fragment is produced as an affinity-tagged fusion protein in Escherichia coli and then cleaved with the highly selective TEV protease to remove the affinity tag and uncover an N-terminal cysteine. The N-terminal cysteine is then used in native chemical ligation reaction to join the IL-2 protein fragment to a glycosylated tripeptide thioester that had been previously synthesized to produce a glycosylated form of IL-2.
CpG methylation inactivates the promoter activity of the human retinoblastoma tumor-suppressor gene. (1993)

Cytosine methylation of CpG sites in the promoter region of eucaryotic genes is involved in the inactivation of expression of certain genes. Given that methylation can lead to reduced transcription, it is possible that expression of tumor-suppressor genes is also inactivated by hypermethylation, thereby contributing to the etiology of cancer. Recently we found five sporadic retinoblastoma tumors (16% of all unilateral cases) with hypermethylation of the 5' end of the retinoblastoma gene without detecting any structural abnormalities. However, it is unclear whether the promoter of the retinoblastoma gene is actually inactivated by its hypermethylation. Here we show that specific hypermethylation in the promoter region of the retinoblastoma gene reduces its expression to only 8% of the unmethylated control. Furthermore, we have found that two transcription factors important for the promoter activity, an activating transcription factor (ATF)-like factor and the retinoblastoma binding factor 1, do not bind when their recognition sequences are CpG methylated. These results in vitro strongly support the hypothesis that CpG methylation of the human tumor-suppressor gene can result in the inactivation of the gene and thus lead to oncogenesis.
Isolation of a tumor‐associated transplantation antigen (TATA) from an SV40‐induced sarcoma. Resemblance to the TATA of chemically induced neoplasms (1984)

A tumor rejection antigen (TATA), obtained from the cytosol of a BALB/c mKSA sarcoma induced by SV40 virus, has been partially purified. This partially purified antigen is strikingly immunogenic against mKSA, providing more than 90% inhibition of growth at levels of 10-30 micrograms. This antigen preparation does not protect against challenge with another SV40-induced BALB/c sarcoma VLM which, however, shares a group-specific TATA with mKSA. The antigen also does not immunize against challenge with the methylcholanthrene-induced sarcomas of BALB/c mice, Meth A, CI-4, CII-7 and CII-10, each of which has its own unique TATA. Binding assays, using ELISA, failed to detect any SV40 antigen in the antigen preparation despite the fact that the large T antigen of SV40 (or fragments of it) constitutes the immunodominant TATA of mKSA.
Phase III Trial of Vandetanib Compared With Erlotinib in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer (2011)

In patients with previously treated advanced NSCLC, vandetanib showed antitumor activity but did not demonstrate an efficacy advantage compared with erlotinib. There was a higher incidence of some AEs with vandetanib.
Reversible oxygenation and autoxidation of a capped porphyrin iron(II) complex (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReversible oxygenation and autoxidation of a capped porphyrin iron(II) complexJoseph Almog, Jack E. Baldwin, and Joel HuffCite this: J. Am. Chem. Soc. 1975, 97, 1, 227–228Publication Date (Print):January 1, 1975Publication History Published online1 May 2002Published inissue 1 January 1975https://pubs.acs.org/doi/10.1021/ja00834a060https://doi.org/10.1021/ja00834a060research-articleACS PublicationsRequest reuse permissionsArticle Views378Altmetric-Citations98LEARN 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
Graphite: A Mimic for DNA and Other Biomolecules in Scanning Tunneling Microscope Studies (1991)

Highly ordered pyrolytic graphite (HOPG) is the substrate often used in scanning tunneling microscope (STM) studies of biomolecules such as DNA. All of the images presented in this article are of freshly cleaved HOPG surfaces upon which no deposition has occurred. These images illustrate features previously thought to be due to biological molecules, such as periodicity and meandering of "molecules" over steps. These features can no longer be used to distinguish real molecules from features of the native substrate. The feasibility of the continued use of HOPG as a substrate for biological STM studies is discussed.
Quantitative Assessment of Aortic Atherosclerosis in APOE*3 Leiden Transgenic Mice and Its Relationship to Serum Cholesterol Exposure (1996)

Transgenic mice overexpressing the human dysfunctional apolipoprotein E variant, APOE*3 Leiden, develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. In the present study, we investigated the effects of diet composition and feeding period on serum cholesterol exposure and the amount of atherosclerosis in the aortic sinus in these mice, using quantitative image analysis. On each of the three diets tested--a low-fat diet, a high-saturated-fat/cholesterol diet, and a high saturated-fat/high-cholesterol/0.5%-cholate diet--transgenic animals showed a marked hyperlipidemia compared with nontransgenic littermates. Measurement of the atherosclerotic lesion areas in cross sections of the aortic sinus in animals exposed to these three diets for up to 6 months showed a 5 to 10 times greater lesion area in transgenic mice compared with nontransgenic controls. Highly significant positive correlations were found between the log-transformed data on lesion area and serum cholesterol exposure (r = .82 to .85 for the 1-, 2-, and 3-month treatment groups), indicating that the hyperlipidemia is likely to be a major determinant in lesion formation. On the basis of these findings, we suggest that the APOE*3 Leiden mouse represents a promising model for intervention studies with hypolipidemic and antiatherosclerotic drugs.
Ionic Capillary Evaporation in Weakly Charged Nanopores (2010)

Using a variational field theory, we show that an electrolyte confined to a neutral cylindrical nanopore traversing a low dielectric membrane exhibits a first-order ionic liquid-vapor pseudo-phase-transition from an ionic-penetration "liquid" phase to an ionic-exclusion "vapor" phase, controlled by nanopore-modified ionic correlations and dielectric repulsion. For weakly charged nanopores, this pseudotransition survives and may shed light on the mechanism behind the rapid switching of nanopore conductivity observed in experiments.
Fast connection establishment in high speed networks (1990)

Protocols for establishing, maintaining and terminating connections in packet switched networks have been studied in the literature and numerous standards have been developed to address this problem. In this paper, we reexamine connection establishment in the context of a fast packet network with an integrated traffic load, explain why previously proposed solutions are inadequate and develop a protocol for connection establishment/takedown that is appropriate for such a network. The underlying model that we use is the recently developed PARIS network, though our ideas are sufficiently general to cover many other fast packet networking architectures.
Diving up to 60 m depth followed by decompression has no effect on pro-enzyme and total thrombin activatable fibrinolysis inhibitor antigen concentration (2003)

The aim of our study was to investigate the effect of two different hyperbaric exposures followed by decompression on thrombin activatable fibrinolysis inhibitor (TAFI) concentration and activity. The hyperbaric conditions correspond to diving to 30 and 60 m water depth. Thirty-four male divers were tested in decompression habitat LSH-200, with air as a breathing medium. The pro-enzyme and total TAFI antigen concentration were measured. We did not observed significant changes of either pro-enzyme or total TAFI antigen concentration after both series of exposures followed by decompression. The results may suggest that TAFI plays only a marginal role, if any, in the regulation of induced fibrinolysis in divers, which may contribute to bleeding episodes in a course of decompression sickness.
Antibody Mediated Transduction of Therapeutic Proteins into Living Cells (2005)

Protein therapy refers to the direct delivery of therapeutic proteins to cells and tissues with the goal of ameliorating or modifying a disease process. Current techniques for delivering proteins across cell membranes include taking advantage of receptor-mediated endocytosis or using protein transduction domains that penetrate directly into cells. The most commonly used protein transduction domains are small cell-penetrating peptides derived from such proteins as the HIV-1 Tat protein. A novel protein transduction domain developed as the single chain fragment (Fv) of a murine anti-DNA autoantibody, mAb 3E10, has recently been developed and used to deliver biologically active proteins to living cells in vitro. This review will provide a brief overview of the development of the Fv fragment and provide a summary of recent studies using Fv to deliver therapeutic peptides and proteins (such as a C-terminal p53 peptide, C-terminal p53 antibody fragment, full-length p53, and micro-dystrophin) to cells.
Plasma Amino Acid Concentrations Predict Mortality in Patients with End-Stage Liver Disease (2016)

Amino acids in plasma are valuable biomarkers to determine increased risk of mortality in patients with end-stage liver disease. In particular, valine concentrations and constellations composed of branched-chain and aromatic amino acids were strongly associated with prognosis. Due to their pathophysiological importance, the identified amino acids could be used to examine individual dietary recommendations to serve as potential therapeutic targets.
Supporting Dynamic Ad hoc Collaboration Capabilities (2003)

Modern HENP experiments such as CMS and Atlas involve as many as 2000 collaborators around the world. Collaborations this large will be unable to meet often enough to support working closely together. Many of the tools currently available for collaboration focus on heavy-weight applications such as videoconferencing tools. While these are important, there is a more basic need for tools that support connecting physicists to work together on an ad hoc or continuous basis. Tools that support the day-to-day connectivity and underlying needs of a group of collaborators are important for providing light-weight, non-intrusive, and flexible ways to work collaboratively. Some example tools include messaging, file-sharing, and shared plot viewers. An important component of the environment is a scalable underlying communication framework. In this paper we will describe our current progress on building a dynamic and ad hoc collaboration environment and our vision for its evolution into a HENP collaboration environment.
Principles of inner ear sustained release following intratympanic administration (2011)

The inner ear pharmacokinetic profile of drugs administered intratympanically is not only highly dependent upon the nature of the vehicle but also upon the physicochemical properties of the drug delivered.
Synthesis of Thrombin Inhibitor DuP 714 (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Thrombin Inhibitor DuP 714John Wityak, Richard A. Earl, Matthew M. Abelman, Yvonne B. Bethel, Barbara N. Fisher, Goss S. Kauffman, Charles A. Kettner, Philip Ma, Janice L. McMillan, and Cite this: J. Org. Chem. 1995, 60, 12, 3717–3722Publication Date (Print):June 1, 1995Publication History Published online1 May 2002Published inissue 1 June 1995https://pubs.acs.org/doi/10.1021/jo00117a024https://doi.org/10.1021/jo00117a024research-articleACS PublicationsRequest reuse permissionsArticle Views1173Altmetric-Citations61LEARN 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 (2)»Supporting Information Supporting Information Get e-Alerts
Structure-based development of a receptor activator of nuclear factor-κB ligand (RANKL) inhibitor peptide and molecular basis for osteopetrosis (2010)

The receptor activator of nuclear factor-κB (RANK) and its ligand RANKL, which belong to the tumor necrosis factor (TNF) receptor-ligand family, mediate osteoclastogenesis. The crystal structure of the RANKL ectodomain (eRANKL) in complex with the RANK ectodomain (eRANK) combined with biochemical assays of RANK mutants indicated that three RANK loops (Loop1, Loop2, and Loop3) bind to the interface of a trimeric eRANKL. Loop3 is particularly notable in that it is structurally distinctive from other TNF-family receptors and forms extensive contacts with RANKL. The disulfide bond (C125-C127) at the tip of Loop3 is important for determining the unique topology of Loop3, and docking E126 close to RANKL, which was supported by the inability of C127A or E126A mutants of RANK to bind to RANKL. Inhibitory activity of RANK mutants, which contain loops of osteoprotegerin (OPG), a soluble decoy receptor to RANKL, confirmed that OPG shares the similar binding mode with RANK and OPG. Loop3 plays a key role in RANKL binding. Peptide inhibitors designed to mimic Loop3 blocked the RANKL-induced differentiation of osteoclast precursors, suggesting that they could be developed as therapeutic agents for the treatment of osteoporosis and bone-related diseases. Furthermore, some of the RANK mutations associated with autosomal recessive osteopetrosis (ARO) resulted in reduced RANKL-binding activity and failure to induce osteoclastogenesis. These results, together with structural interpretation of eRANK-eRANKL interaction, provided molecular understanding for pathogenesis of ARO.
Regulation of Angiogenic Activity of Human Endometrial Endothelial Cells in Culture by Ovarian Steroids (2004)

Blood vessel growth and regression in human endometrium are regulated throughout the menstrual cycle. We sought a direct role of ovarian steroids on human endometrial endothelial cell (HEEC) proliferation and vascularization. To investigate the HEEC angiogenicity of sex steroids, we developed a reliable method for the isolation of HEEC, which allowed us to investigate the angiogenic effects of sex steroids using immunohistochemistry, immunocytochemistry, Western blot, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt proliferation, and vascular tube formation analyses. We were able to obtain 95-99% pure HEEC with our isolation technique. HEEC expressed predominantly estrogen receptor beta, minimally expressed estrogen receptor alpha, and but did not express progesterone (P(4)) receptors A and B in vivo and in vitro. Estradiol (E(2); 10(-10)-10(-8) m) and P(4) (10(-12)-10(-8) m), alone or in combination, induced HEEC proliferation compared with control values after 48 h of treatment (P < 0.05). Furthermore, after 8 d of treatment, there were significantly more angiogenic patterns in E(2) (10(-8) m), P(4) (10(-10) m), and E(2) plus P(4) (10(-8) and 10(-10) m) treatment groups compared with the control group (angiogenic scores, 2.95 +/- 0.16, 3.26 +/- 0.16, 3.06 +/- 0.17, and 1.93 +/- 0.15, respectively; P < 0.01). In conclusion, our results suggest that there are direct effects of E(2) and P(4) on HEEC and provide a new understanding of the physiological role of sex steroids in the regulation of endometrial events such as angiogenesis.
Oxygen sensing: applications in humans (2004)

Our concepts of oxygen sensing have been transformed over the years. We now appreciate that oxygen sensing is not a unique property limited to "chemoreceptors" but is a common property of tissues and that responses to changes in oxygen levels are not static but can change over time. Respiratory responses initiated at the carotid body are modified by the excitatory and depressant effects of hypoxia at the brain and on the pathways connecting the carotid body to the brain. Equally important is that we are beginning to use our understanding of the cellular and molecular pathways triggered by hypoxia and hyperoxia to identify therapeutic targets to treat diseases such as cancer. We also have a better understanding of the complexities of the human respiratory responses to hypoxia; however, major deficiencies remain in our ability to alter or even measure human ventilatory responses to oxygen deficiency.
Electrophile and oxidant damage of mitochondrial DNA leading to rapid evolution of homoplasmic mutations (2003)

mtDNA mutations occur in a wide variety of degenerative diseases and cancer. mtDNA seems to be more susceptible to DNA damage and consequently sustains higher rates of mutation than does nuclear DNA (nDNA). Many of the somatic mtDNA mutations in human cancers are located in the displacement loop (D-loop) and in particular in a polycytidine stretch (C-tract) termed D310. The D310 region exhibits polymorphic length variation among individuals and has been described as a "hot spot" for somatic mutations in many cancer types. We used real-time quantitative PCR to analyze mtDNA integrity, damage repair, and induced mutations after exposure of human adult retinal pigment epithelial (ARPE)-19 cells to 4-nitroquinoline 1-oxide, a UV-mimetic and adduct-forming carcinogen, and tert-butyl hydroperoxide, an oxidant. The mtDNA-damage profile depended on the region. Thus, the tRNA coding for glycine (tRNA(G)) was the least affected region, whereas the D-loop, and especially its D310 region, were most sensitive to damage. The time course of repair of mutations of the D-loop and especially the D310 region after exposure to DNA-damaging agents was delayed when compared with other regions and gave rise to common D310 C-tract frame-shift mutations. The induced mutations in the D310 region were predominantly homoplasmic only 7 days after exposure to damage. Our results establish that the D-loop (especially its D310 region) is highly susceptible to mutations because of its vulnerability to DNA damage and inefficient repair mechanisms. Our findings may explain the high frequency of homoplasmic D310 somatic mutations in many tumor types.
Lead Optimization of Aryl and Aralkyl Amine-Based Triazolopyrimidine Inhibitors ofPlasmodium falciparumDihydroorotate Dehydrogenase with Antimalarial Activity in Mice (2011)

Malaria is one of the leading causes of severe infectious disease worldwide; yet, our ability to maintain effective therapy to combat the illness is continually challenged by the emergence of drug resistance. We previously reported identification of a new class of triazolopyrimidine-based Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors with antimalarial activity, leading to the discovery of a new lead series and novel target for drug development. Active compounds from the series contained a triazolopyrimidine ring attached to an aromatic group through a bridging nitrogen atom. Herein, we describe systematic efforts to optimize the aromatic functionality with the goal of improving potency and in vivo properties of compounds from the series. These studies led to the identification of two new substituted aniline moieties (4-SF(5)-Ph and 3,5-Di-F-4-CF(3)-Ph), which, when coupled to the triazolopyrimidine ring, showed good plasma exposure and better efficacy in the Plasmodium berghei mouse model of the disease than previously reported compounds from the series.