gebhart/patrepeval huggingface dataset:
Enantioselective Synthesis of α-Amino Nitriles from N-Benzhydryl Imines and HCN with a Chiral Bicyclic Guanidine as Catalyst (1999)

A novel catalytic enantioselective Strecker synthesis of chiral α-amino nitriles and α-amino acids is described and analyzed with regard to the possible mechanistic basis for stereoselectivity. Key features of the enantioselective process include (1) the use of the chiral bicyclic guanidine 1 as catalyst and (2) the use of the N-benzhydryl substituent on the imine substrate.
Effect of induced metabolic acidosis on human skeletal muscle metabolism during exercise (1999)

The roles of pyruvate dehydrogenase (PDH), glycogen phosphorylase (Phos), and their regulators in lactate (Lac(-)) metabolism were examined during incremental exercise after ingestion of 0.3 g/kg of either NH(4)Cl [metabolic acidosis (ACID)] or CaCO(3) [control (CON)]. Subjects were studied at rest, at rest postingestion, and during continuous steady-state cycling at three stages (15 min each): 30, 60, and 75% of maximal oxygen uptake. Radial artery and femoral venous blood samples, leg blood flow, and biopsies of the vastus lateralis were obtained during each power output. ACID resulted in significantly lower intramuscular concentration of [Lac(-)] (ACID 40.8 vs. CON 56.9 mmol/kg dry wt), arterial whole blood [Lac(-)] (ACID 4.7 vs. CON 6.5 mmol/l), and leg Lac(-) efflux (ACID 3.05 vs. CON 6.98 mmol. l(-1). min(-1)). The reduced intramuscular [Lac(-)] resulted from decreases in pyruvate production due to inhibition of glycogenolysis, at the level of Phos a, and phosphofructokinase, together with an increase in the amount of pyruvate oxidized relative to the total produced. The reduction in Phos a activity was mediated through decreases in transformation, decreases in free inorganic phosphate concentration, and decreases in the posttransformational allosteric regulator free AMP. Reduced PDH activity occurred with ACID and may have resulted from alterations in the concentrations of acetyl-CoA, free ADP, pyruvate, NADH, and H(+), leading to greater relative activity of the kinase. The results demonstrate that imposed metabolic acidosis in skeletal muscle results in decreased Lac(-) production due to inhibition of glycogenolysis at the level of Phos and increased pyruvate oxidation at PDH.
Design of Organic Structures in the Solid State: Molecular Tapes Based on the Network of Hydrogen Bonds Present in the Cyanuric Acid.cntdot.Melamine Complex (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign of Organic Structures in the Solid State: Molecular Tapes Based on the Network of Hydrogen Bonds Present in the Cyanuric Acid.cntdot.Melamine ComplexJonathan A. Zerkowski, John C. MacDonald, Christopher T. Seto, Derk A. Wierda, and George M. WhitesidesCite this: J. Am. Chem. Soc. 1994, 116, 6, 2382–2391Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/ja00085a018https://doi.org/10.1021/ja00085a018research-articleACS PublicationsRequest reuse permissionsArticle Views1106Altmetric-Citations160LEARN 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 (8)»Supporting Information Supporting Information Get e-Alerts
Porphyrin molecules boost the sensitivity of epitaxial graphene for NH3detection (2016)

The sensitivity of quasi-free standing epitaxial graphene for NH<sub>3</sub> detection is strongly enhanced by chemical functionalization with cobalt porphyrins resulting in a detection limit well below 100 ppb. Hybridization between NH<sub>3</sub> and cobalt porphyrins induces a charge transfer to graphene and results in a shift of the graphene Fermi-level as detected by Hall measurements and theoretically explained by electronic structure calculations.
Forebrain astroglial plasticity is induced following withdrawal from repeated cocaine administration (2003)

Astrocytes actively participate in synaptic plasticity and respond to insult or metabotropic glutamate receptor activation with increased expression of the intermediate filament glial fibrillary acidic protein (GFAP). Extended withdrawal from repeated cocaine administration induces many forms of neuroplasticity. The present study with rats utilized a 3-week withdrawal period from daily cocaine administration (i.p.; 7 days) to investigate whether astrocytes participate in cocaine-mediated plasticity observed in brain nuclei associated with addiction. Following the 3-week withdrawal period, immunoblotting revealed increased GFAP expression in the prefrontal cortex (PFC) and in the shell and core compartments of the nucleus accumbens (NAshell and NAcore). Upregulation of GFAP did not occur in the striatum or in any brain region tested following shorter withdrawal times from repeated cocaine (24 h or 1 week) or following 2-h withdrawal from an acute cocaine injection (30 mg/kg i.p.). However, GFAP expression increased following a 3-week withdrawal from a single cocaine injection selectively in the NAshell. Cell counts revealed that astrocyte cell number increased only in the NAcore while immunoblots of a marker for immature or reactive astrocytes, vimentin, showed an increase only in the PFC following the 3-week withdrawal. Taken together, these results suggest that altered intermediate filament expression within forebrain astrocytes may be a significant part of the plasticity occurring during withdrawal from repeated cocaine. Furthermore, the increase in GFAP may arise from regionally distinct mechanisms, with the NAcore relying more on cell proliferation while the PFC relies on a larger reactive astrocyte population.
Detection and clinical significance of occult tumour cells in colorectal cancer (2001)

Standardization of terminology and techniques used, combined with large prospective clinical studies, is required if detection of occult residual disease is to become a prognostic marker for recurrence in colorectal cancer.
Role of quinones in the branch of the Escherichia coli respiratory chain that terminates in cytochrome o (1984)

The role of quinones in the cytochrome o branch of the Escherichia coli respiratory chain was investigated by using mutant strains lacking the cytochrome d terminal oxidase complex. The only cytochromes present were cytochrome b556 and the cytochrome o complex, consisting of cytochrome b555-b562. Mutant strains missing ubiquinone, menaquinone, or both were constructed in the cytochrome d-minus (cyd) background. The steady-state levels of cytochrome b reduction were examined and compared in these strains to assess the effects of the quinone deficiencies. The data clearly show that a ubiquinone deficiency results in a lower level of cytochrome b reduction in the steady state. The data are consistent with a simple model in which ubiquinone is placed on the dehydrogenase side of all the cytochromes in this branch of the respiratory chain. There is no evidence from these experiments for a role of quinones in the respiratory chain at any site besides this one.
Antigenic Sites on the CVS Rabies Virus Glycoprotein: Analysis with Monoclonal Antibodies (1983)

Antigenic variation in the glycoprotein of rabies (CVS-11) virus was studied. Neutralization-resistant variant viruses were isolated in vitro at high frequency (10(-4) to 10(-5)) in the presence of anti-glycoprotein monoclonal antibody. Analysis of these variants identified at least three functionally independent antigenic sites, based on the grouping of variants that were no longer neutralized by one or more of a panel of 24 monoclonal antibodies. Competition radioimmunoassay suggested that one of these three antigenic sites was topologically distinct, with the other two in close proximity. In addition, it was shown that most (but not all) neutralization-resistant variants failed to bind the relevant monoclonal antibody. Viruses with altered antigenicity were shown to accumulate in virus stocks following several passages in vitro in the absence of antibody. In addition, variants were isolated in vivo following treatment of mice with monoclonal antibody.
Interleukin-2–Receptor Blockade with Daclizumab to Prevent Acute Rejection in Renal Transplantation (1998)

Daclizumab reduces the frequency of acute rejection in kidney-transplant recipients.
In VivoStimulation of Bone Formation by Transforming Growth Factor-β (1989)

The effect of transforming growth factor-beta (TGF beta) on bone in vivo was examined. Twelve daily injections of 1 microgram TGF beta directly onto the periostea of parietal bones of neonatal rats stimulated the formation of periosteal woven bone. The thickness of the treated parietal bones increased at least 2-fold in a dose-dependent manner. This TGF beta effect was localized at the sites of injection, and no change was observed in contralateral parietal bones and tibiae. The body weight in these growing rats was not affected by TGF beta 1. TGF beta 2 had effects similar to those of TGF beta 1 on the parietal bones in vivo. These results reveal for the first time that TGF beta stimulates bone formation in vivo and indicate its anabolic role in local bone metabolism.
A positive inotropic effect of ATP in the human cardiac atrium (2008)

We studied contractile effects in isolated electrically driven (1 Hz) atrial preparations from patients undergoing cardiac bypass surgery. ATP concentration dependently (10, 30, and 100 microM) and rapidly decreased force of contraction (negative inotropic effect, NIE) and thereafter more slowly increased force of contraction. The maximum positive inotropic effect (PIE) at 100 microM ATP amounted to 152% of the predrug value (n = 9) and was stable and could be washed out fast and completely. The PIE did not affect time parameters of contraction (time to peak tension and time of relaxation). Moreover, a similar NIE and PIE were noted with adenosine 5'-O-(2-thiotriphosphate) (100 microM). In contrast 2-methyl-thio-ATP did not exert a NIE but only a PIE. In a second set of experiments, preparations were first incubated for 30 min with purinoreceptor antagonists and, in their continuous presence, 100 microM ATP was applied. However, the PIE and NIE of ATP could neither be blocked with suramin (100 and 500 microM), pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (50 microM), nor reactive blue 2 (30, 100, and 500 microM), which are known blockers for subtypes of P(2) receptors, or 1,3-dipropyl-cyclopentvl-xanthine (1 and 10 microM), a subtype (A(1) adenosine) P(1) receptor blocker. Likewise, the inhibitor of phospholipase C (PLC) activity (U-73122) and the inhibitor of adenylate cyclase activity (SQ-022563) (10 microM each) failed to affect the NIE and the PIE of ATP. We tentatively suggest that the PIE of ATP might be mediated via P(2X4)-like receptors. In summary, we describe a novel biphasic effect of ATP on force contraction in the isolated human atrium. It is conceivable that ATP plays a physiological role in the human heart, for instance, after cardiac injury to sustain contractility.
Inhibition of experimental asthma by indoleamine 2,3-dioxygenase (2004)

Epidemiological evidence points to the inverse relationship between microbial exposure and the prevalence of allergic asthma and autoimmune diseases in Westernized countries. The molecular basis for this observation has not yet been completely delineated. Here we report that the administration of certain toll-like receptor (TLR) ligands, via the activation of innate immunity, induces high levels of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of tryptophan catabolism in various organs. TLR9 ligand-induced pulmonary IDO activity inhibits Th2-driven experimental asthma. IDO activity expressed by resident lung cells rather than by pulmonary DCs suppressed lung inflammation and airway hyperreactivity. Our results provide a mechanistic insight into the various formulations of the hygiene hypothesis and underscore the notion that activation of innate immunity can inhibit adaptive Th cell responses.
Mutational Analysis of Glycosylation, Membrane Translocation, and Cell Surface Expression of the Hepatitis E Virus ORF2 Protein (1999)

Hepatitis E virus (HEV) is the etiological agent for viral hepatitis type E, which is a major problem in the developing world. Because HEV cannot be cultured in vitro, very little information exists on the mechanisms of HEV gene expression and genome replication. HEV is a positive-strand RNA virus with three potential open reading frames (ORFs), one of which (ORF2) is postulated to encode the major viral capsid protein (pORF2). We earlier showed (S. Jameel, M. Zafrullah, M. H. Ozdener, and S. K. Panda, J. Virol. 70:207-216, 1996) pORF2 to be a approximately 88-kDa glycoprotein, carrying N-linked glycans and a potential endoplasmic reticulum (ER)-directing signal at its N terminus. Treatment with the drugs brefeldin A and monensin suggest that the protein may accumulate within the ER. Based on mutational analysis, we demonstrate Asn-310 to be the major site of N-glycan addition. In COS-1 cell expression and in vitro translation experiments, we confirm the ER-translocating nature of the pORF2 N-terminal hydrophobic sequence and show that the protein is cotranslationally, but not posttranslationally, translocated across the ER membrane. Earlier, we had also demonstrated cell surface localization of a fraction of the COS-1 cell-expressed pORF2. Using glycosylation- and translocation-defective mutants of pORF2, we now show that while transit of pORF2 into the ER is necessary for its cell surface expression, glycosylation of the protein is not required for such localization. These results may offer clues to the mechanisms of gene expression and capsid assembly in HEV.
Identification of regulatory oxysterols, 24(S),25-epoxycholesterol and 25-hydroxycholesterol, in cultured fibroblasts. (1985)

Biosynthetically tritiated sterols from Chinese hamster lung (Dede) cells were fractionated by high performance liquid chromatography, and fractions were assayed for their ability to repress 3-hydroxy-3-methylglutaryl-CoA reductase in L cell cultures. Most of the activity found was associated with two oxysterols, 24(S),25-epoxycholesterol and 25-hydroxycholesterol. The identities of the two sterols were established by co-chromatography with authentic samples and by isotopic dilution and recrystallization. Only low levels of repressor activity were found in other fractions of the sterol extract. The endogenous concentrations of 24(S),25-epoxycholesterol (7.2 fg/cell) and 25-hydroxycholesterol (1.5 fg/cell) appear to be within the ranges required for the regulation of HMG-CoA reductase.
Sequence-dependent termination of in vitro DNA synthesis by cis- and trans-diamminedichloroplatinum (II). (1985)

Inhibition of DNA replication by the antitumor drug cis-diamminedichloroplatinum (II) (cis-DDP) has been proposed to be responsible for its cytotoxicity. Treatment of primed phage M13 mp8 viral DNA templates with the drug followed by second-strand synthesis using large fragment DNA polymerase I reveals that cis-DDP forms an adduct with DNA that inhibits DNA synthesis in vitro. This inhibition occurs at all (dG)n (n greater than or equal to 2) sequences in the template strand, confirming that these regions are the major cis-DDP binding sites on DNA. trans-Diamminedichloroplatinum (II), which is inactive as a drug, also forms adducts that inhibit DNA synthesis. Although considerably lower specificity is observed with the trans isomer, there appears to be a preference for d(GpNpG) sequences, where N is any intervening nucleotide. The monofunctional adduct formed between chlorodiethylenetriamineplatinum(II) chloride and DNA does not inhibit DNA synthesis in this system.
Association of MicroRNA Expression in Hepatocellular Carcinomas with Hepatitis Infection, Cirrhosis, and Patient Survival (2008)

We show that a global increase in the transcription of miRNA genes occurs in cirrhotic and hepatitis-positive livers and that miRNA expression may prognosticate disease outcome in HCC.
Intrathymic implants of genetically modified fibroblasts (1992)

Implantation of autologous rodent fibroblasts genetically altered to express human growth hormone has recently been shown to be a feasible approach to the delivery of new gene products in somatic gene therapy. However, the novel gene product elicited in its recipients an intense antibody response that would have curtailed the effectiveness of such therapy. The possibility of inducing tolerance to foreign gene product was explored by implanting allogeneic fibroblasts transfected with the human growth hormone gene into rat thymus, a site recently shown to be immunologically privileged and able to induce donor-specific tolerance to transplanted tissues. In the circulation of the implanted rats, human growth hormone was detected at 4-15 ng/ml serum within the first day and subsided to 0.6-9 ng/ml within the first wk in all animals implanted either thymically or intraperitoneally. Within 2-3 wk, high titers of anti-human growth hormone were detected in all animals regardless of the site of implantation. The failure of the thymus to offer immune protection for the foreign antigen was further confirmed when the animals were subsequently challenged with purified human growth hormone. An immediate twofold increase in titer within the first week of challenge was detected in animals previously implanted thymically. In contrast, animals implanted intraperitoneally but treated with short-term daily injection of cyclosporine A (28-41 days) did not mount any significant antibody response to human growth hormone throughout the experiment or even when challenged subsequently at weeks 8-10 with purified growth hormone. In conclusion, implantation of genetically modified fibroblasts in the thymus does not lead to tolerization toward soluble novel gene product secreted by these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Combinatorial Strategies for Targeting Protein Families: Application to the Proteases (2002)

Tens of thousands of proteins have been identified as a result of recent large scale genomic and proteomic efforts. With this large influx of new proteins, the formidable task of elucidating their function begins. However, this task becomes more manageable if proteins are divided into families based upon sequence homology, thereby allowing tools for their systematic study to be developed based upon their common structural and mechanistic characteristics. Combinatorial chemistry is ideally suited for the systematic study of protein families because a large amount of diversity can be readily displayed about a common scaffold designed to target a given protein family. Targeted combinatorial libraries have been particularly effective for the study of a ubiquitous family of proteins, the proteases. Substrate-specificity profiles of many proteases have been determined by using combinatorial libraries of appropriately labeled peptides. This specificity information been utilized to identify the physiological protein substrates of these enzymes and has facilitated inhibitor design efforts. Furthermore, combinatorial libraries of small molecules prepared with mechanism-based scaffolds have resulted in the identification of potent, small-molecule inhibitors of numerous proteases. Cell-permeable small-molecule inhibitors identified by these methods have served as powerful chemical tools to study protease function in vitro and in vivo and have served as leads for the development of therapeutic agents.
Combined Promoter Methylation Analysis of CADM1 and MAL: An Objective Triage Tool for High-Risk Human Papillomavirus DNA–Positive Women (2011)

We developed an objective methylation marker panel that was equally discriminatory for CIN3(+) as cytology or cytology with HPV16/18 genotyping in hrHPV-positive women. This opens the possibility for complete cervical screening by objective, nonmorphological molecular methods.
Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men (2012)

Feeding stimulates robust increases in muscle protein synthesis (MPS); however, ageing may alter the anabolic response to protein ingestion and the subsequent aminoacidaemia. With this as background, we aimed to determine in the present study the dose-response of MPS with the ingestion of isolated whey protein, with and without prior resistance exercise, in the elderly. For the purpose of this study, thirty-seven elderly men (age 71 (sd 4) years) completed a bout of unilateral leg-based resistance exercise before ingesting 0, 10, 20 or 40 g of whey protein isolate (W0-W40, respectively). Infusion of l-[1-13C]leucine and l-[ring-13C6]phenylalanine with bilateral vastus lateralis muscle biopsies were used to ascertain whole-body leucine oxidation and 4 h post-protein consumption of MPS in the fed-state of non-exercised and exercised leg muscles. It was determined that whole-body leucine oxidation increased in a stepwise, dose-dependent manner. MPS increased above basal, fasting values by approximately 65 and 90 % for W20 and W40, respectively (P < 0·05), but not with lower doses of whey. While resistance exercise was generally effective at stimulating MPS, W20 and W40 ingestion post-exercise increased MPS above W0 and W10 exercised values (P < 0·05) and W40 was greater than W20 (P < 0·05). Based on the study, the following conclusions were drawn. At rest, the optimal whey protein dose for non-frail older adults to consume, to increase myofibrillar MPS above fasting rates, was 20 g. Resistance exercise increases MPS in the elderly at all protein doses, but to a greater extent with 40 g of whey ingestion. These data suggest that, in contrast to younger adults, in whom post-exercise rates of MPS are saturated with 20 g of protein, exercised muscles of older adults respond to higher protein doses.