gebhart/patrepeval huggingface dataset:
A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia (2013)

A Long-term, Phase 2, Multicenter, Randomized, Open-label, Comparative Safety Study of LY2140023 Versus Atypical Antipsychotic Standard of Care in Patients with DSM-IV-TR Schizophrenia.
Real-time hybrid pose estimation from vision and inertial data (2004)

The output signals of inertial sensors and a camera are used to realise a pen-like human-computer interface with six degrees of freedom. The pen-like interface works over planar, structured surfaces. The pose estimation with a monocular camera has a high uncertainty on the rotation if the surface is unknown and no pre-known markers are used. A hybrid pose estimation method is used to improve accuracy. From output signals of three orthogonally placed accelerometers the absolute 2D tilt of the pen-like interface with respect to the gravitational field is calculated. This 2D rotation information is used to improve the robustness of the pose estimation using a modified homography calculation. Utilising three-dimensional detection of the pen’s pose several applications are possible, e.g. ergonomic humancomputer interfaces in 6D, image mosaicing applications or devices for handwriting input.
New polymer syntheses, 3. Binding of nucleosides to basic polypeptides via isocyanato‐isothiocyanates (1980)

Abstract New aliphatic α‐isocyanato‐ω‐isothiocyanates of various chain lengths were synthesized from ω‐isothiocyanatocarboxylic acid chlorides and trimethylsilyl azide. The 5′‐OH group of 2′‐ O ,3′‐ O ‐isopropylideneuridine and of N 6 ‐benzoyl‐2′‐ O ,3′‐ O ‐isopropylideneadenosine was added selectively onto the isocyanate group of aromatic and aliphatic α‐isocyanato‐ω‐isothiocyanates. The isothiocyanate group of the resulting nucleoside derivatives was then reacted with the free amino groups of polylysine, isopolylysine, polyornithine and isopolyornithine. The resulting polypeptides with pending nucleosides were characterized by elemental analyses and 360 MHz 1 H NMR spectra. A new “one‐pot‐procedure” was developed to protect the primary amino group ( N 6 ) of 2′‐ O ,3′‐ O ‐isopropylideneadenosine.
Insulin Signal Transduction and the IRS Proteins (1996)

Insulin controls organismal and cellular physiology by initiating numerous intracellular signals. Insulin first binds the extracellular domain of the insulin receptor, which activates the receptor's intracellular tyrosine kinase. Receptor-mediated phosphorylation of the IRS proteins is required for the propagation of signals for mitogenesis, glucose transport, and numerous other biological and biochemical events during insulin signaling. IRS proteins also mediate signaling by a subset of other growth factor and cytokine receptors; recognition and phosphorylation by specific receptors appears to be mediated by the PH and PTB domains of the IRS proteins. The best understood mechanism of IRS-protein-mediated signaling is the binding of SH2 domain-containing signaling molecules (such as PI 3'-kinase) by tyrosine phosphorylation sites on IRS proteins. Other paradigms of IRS-protein signaling are beginning to emerge, however, and these exciting molecules promise to teach us much in the next few years.
From active towards InterActive learning (2009)

Active learning methods have been proposed to reduce the labeling effort of human experts: based on the initially available labeled instances and information about the unlabeled data those algorithms choose only the most informative instances for labeling. They have been shown to significantly reduce the size of the required labeled dataset to generate a precise model [17]. However, active learning framework assumes "perfect" labelers, which is not true in practice (e.g., [22, 23]). In particular, an empirical study for hand-written digit recognition [5] has shown that active learning works poorly when a human labeler is used. Thus, as active learning enters the realm of practical applications, it will need to confront the practicalities and inaccuracies of human expert decision-making. Specifically, active learning approaches will have to deal with the problem that human experts are likely to make mistakes when labeling the selected instances.
Phase I Trial Of Intravenous Peptide-Pulsed Dendritic Cells in Patients With Metastatic Melanoma (2001)

Sixteen patients with metastatic stage IV melanoma were treated with use of intravenous infusions of dendritic cells (DC) derived by incubation of plastic-adherent peripheral blood mononuclear cells (PBMC) with IL-4 and GM-CSF for 8 days in serumless AIM-V medium, followed by overnight pulsing with peptides. The tyrosinase368-376 (370D) and gp100(209-217 (210M)) peptides restricted to HLA class I A*0201 each differed from wild type by one amino acid modified to increase HLA binding. Median age was 49, with nine men and seven women. All patients, except one, had visceral disease. Patients received escalating doses of peptide-pulsed DCs at 10e7, 3 x 10e7, and 10e8 cells/dose twice at 2 weeks apart, with toxicity and clinical and immune responses as the principal endpoints. The first infusion of DCs was fresh, and frozen DCs were given for the second infusion of each cycle. Mean DC purity by flow cytometry was 49%, with a mean HLA-DR level of 57%, CD86 of 41%, CD58 of 46%, and mean CD14 cells of 0.9%. Toxicity was minimal, with two patients having transient grade III DC-related toxicity. Ten patients received one cycle of treatment and six patients received two cycles of treatment. One patient had a complete remission (CR) of lung and pleural disease after two cycles of DC therapy. Two additional patients had stable disease and two patients had mixed responses. Overall immunity was assessed by recall skin testing with peptides, gamma interferon ELISA assays of peptide specific cytolytic T cell (CTL) stimulated twice with peptide, IL-2, and IL-7 over 24 days, and peptide-specific tetramer assays performed before and after vaccination. Five of 16 patients had an immune response to gp100 or tyrosinase by gamma interferon ELISA assay; four of five were clinically stable or had tumor regression. These data suggest that melanoma antigen peptide-pulsed DC given intravenously are not toxic, and regression or stability of tumor appeared to correlate with the detection of a peptide-specific immune response in the peripheral blood.
Robust decentralized control for multimachine power systems (1998)

In this paper, a new robust linear decentralized controller is proposed to enhance the transient stability of nonlinear multimachine power systems. Only local measurements are required in the proposed controller. The feedback gain of each generator is obtained by solving an algebraic Riccati equation based on the bounds of the machine parameters. The stability analysis shows that the decentralized controller can guarantee the system stability over the whole operating region and regardless of fault locations or parameter uncertainties of the transmission network. Compared with nonlinear controllers, linear controllers are of simpler structure and easier to be implemented. A three-machine power system is considered as an application example. Simulation results show that despite the interconnections between different generators, nonlinearities in the system, different operating points, and different fault locations, the proposed robust decentralized controller can greatly enhance power system transient stability.
Shape and Composition-Controlled Platinum Alloy Nanocrystals Using Carbon Monoxide as Reducing Agent (2011)

The shape of metal alloy nanocrystals plays an important role in catalytic performances. Many methods developed so far in controlling the morphologies of nanocrystals are however limited by the synthesis that is often material and shape specific. Here we show using a gas reducing agent in liquid solution (GRAILS) method, different Pt alloy (Pt-M, M = Co, Fe, Ni, Pd) nanocrystals with cubic and octahedral morphologies can be prepared under the same kind of reducing reaction condition. A broad range of compositions can also be obtained for these Pt alloy nanocrystals. Thus, this GRAILS method is a general approach to the preparation of uniform shape and composition-controlled Pt alloy nanocrystals. The area-specific oxygen reduction reaction (ORR) activities of Pt(3)Ni catalysts at 0.9 V are 0.85 mA/cm(2)(Pt) for the nanocubes, and 1.26 mA/cm(2)(Pt) for the nanooctahedra. The ORR mass activity of the octahedral Pt(3)Ni catalyst reaches 0.44 A/mg(Pt).
Identification of Active Site Residues Essential to 4-Chlorobenzoyl−Coenzyme A Dehalogenase Catalysis by Chemical Modification and Site Directed Mutagenesis (1996)

4-Chlorobenzoyl-coenzyme A (4-CBA-CoA) dehalogenase catalyzes the hydrolysis of 4-CBA-CoA to 4-hydroxybenzoyl-coenzyme A (4-HBA-CoA) via a nucleophilic aromatic substitution pathway involving the participation of an active site carboxylate side chain in covalent catalysis. In this paper we report on the identification of conserved aspartate, histidine, and tryptophan residues essential to 4-CBA-CoA catalysis using chemical modification and site-directed mutagenesis techniques. Treatment of the dehalogenase with diethyl pyrocarbonate resulted in complete loss of catalytic activity (Kinact = 0.17 mM-1 min-1 at pH 6.5, 25 degrees C) that was fully regained by subsequent treatment with hydroxylamine. The protection from inactivation afforded by enzyme bound 4-HBA-CoA indicated that the essential histidine residues are located at the active site. Replacement of conserved histidine residues 81, 90, 94, and 208 with glutamine residues resulted in a significant loss of catalytic activity only in the cases of the histidine 81 and 90 mutants. Substrate and product ligand binding studies showed that binding is not significantly inhibited in these mutants. Site directed mutagenesis of a selection of conserved aspartate and glutamate residues, identified aspartate 145 as being essential to dehalogenase catalysis. Ligand binding studies showed that this residue is not required for tight substrate/product binding. Chemical modification of the dehalogenase with N-bromosuccinimide resulted in full loss of catalytic activity that was prevented by saturation of the active site with product ligand, providing evidence favoring an essential active site tryptophan. Phenylalanine replacement of conserved tryptophan residues 179 and 137 reduced catalytic activity only in the latter (Kcat = 0.03% of wild-type dehalogenase). On the basis of these results and the recently determined X-ray crystal structure of the complex of 4-CBA-CoA dehalogenase and 4-HBA-CoA [Benning, M. M., Taylor, K.L., Liu, R.-Q., Yang, G., Xiang, H., Wesenberg, G., Dunaway-Mariano, D., Holden, H.M. (1996) Biochemistry 35,8103-8109] we propose that aspartate 145 functions as the active site nucleophile, that tryptophan 137 serves as a hydrogen bond donor to the aspartate 145 C = O, and that histidine 90 serves to deprotonate the bound H2O molecule.
Breast Carcinoma and the Role of Iron Metabolism (1993)

Transferrin receptors on proliferating and malignant cells are well documented. Iron is an essential micronutrient for cell growth that plays an important role in energy metabolism and DNA synthesis. Malignant cells requiring more iron modulate a transferrin receptor. Iron-bound transferrin interacts with this receptor, facilitating the transport of iron across the cell membrane. Transferrin is a glycoprotein and is the chief iron transport protein in mammalian blood. The more aggressive the tumor, the higher the transferrin receptor levels and the greater the proliferative index. We have found by cytochemical and ultrastructural studies that ferritin, an iron storage protein, is increased in breast cancer tissue. Anaplastic tumors have higher tissue ferritin levels. Tissue ferritin concentration may be an indirect method of measuring transferrin receptors and thus might be an index of proliferation and a prognostic indicator. Transferrin may be used as a carrier to target toxic therapy selectively to tumor tissue. A platinum transferrin complex (MPTC-63) has been developed and shown to be cytostatic in tissue culture, animal, and human studies. It also sensitizes tissue to agents that produce free radicals, such as adriamycin, and thus is synergistic with other drugs and radiation. Other transferrin complexes and conjugates of gallium, indium, and daunorubicin have also shown growth inhibition in tissue culture and animals. Human studies are in progress. By studying iron metabolism in breast cancer, we may be able to selectively inhibit tumor growth without toxic effects, and with other tumor biologic data be better able to select the stage I patient for adjuvant therapy.
Milestones in camptothecin research (2002)

The discovery of the natural product camptothecin in the early 1960s provided the lead structure for a novel, highly promising class of antitumor agents, Significant progress involving the understanding of the mechanism of action, the drug metabolism, chemistry driven analoging programs and clinical research for dose and schedule optimization led to major breakthroughs in the field. Today, with two successful compounds In clinical practice (irinotecen and topotecan) and more than to clinical development programs, the campothecins have reached a very high clinical relevance.
Optimizing the match in weakly inverted MOSFET's by gated lateral bipolar action (1996)

The on-chip n-type MOSFET current mirror circuit with different drawn gate widths and lengths has been fabricated, and has been characterized across the wafer with back gate slightly forward biased. The weakly inverted MOSFET device with a small back-gate forward bias represents equivalently the high-gain gated lateral bipolar transistor in low-level injection. Experimental results have exhibited a substantial improvement in the match of the drain current in weak inversion due to action of the gated lateral bipolar transistor, especially for the small size devices. The extensively measured mismatch of the weak inversion drain current has been successfully reproduced by an analytic statistical model with back-gate forward bias and device size both as input parameters. The experimentally extracted variations in process parameters such as the flat-band voltage and the body effect coefficient each have been found to follow the inverse square root of the device area. The mismatch model thus can serve as a quantitative design tool, and has been used to optimize the trade-off between the device area and the match with the forward back-gate bias as a parameter.
Determination of the allergenic activity of birch pollen and apple prick test solutions by measurement of β‐hexosaminidase release from RBL‐2H3 cells. Comparison with classical methods in allergen standardization (1999)

This murine model might be a useful tool in the quality control of allergenic extracts. It combines properties of assays based on standardized antisera and of assays that consider IgE cross-linking properties.
Anti- Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role (1998)

ASCA and pANCA are strongly associated with Crohn's disease and ulcerative colitis, respectively. Combination of both tests could help the diagnosis of inflammatory bowel disease.
Cellular and Molecular Mechanisms of Drug Dependence (1988)

The molecular and cellular actions of three classes of abused drugs--opiates, psychostimulants, and ethanol--are reviewed in the context of behavioral studies of drug dependence. The immediate effects of drugs are compared to those observed after long-term exposure. A neurobiological basis for drug dependence is proposed from the linkage between the cellular and behavioral effects of these drugs.
Rapid Differentiation and In Situ Detection of 16 Sourdough Lactobacillus Species by Multiplex PCR (2005)

A two-step multiplex PCR-based method was designed for the rapid detection of 16 species of lactobacilli known to be commonly present in sourdough. The first step of multiplex PCR was developed with a mixture of group-specific primers, while the second step included three multiplex PCR assays with a mixture of species-specific primers. Primers were derived from sequences that specify the 16S rRNA, the 16S-23S rRNA intergenic spacer region, and part of the 23S rRNA gene. The primer pairs designed were shown to exclusively amplify the targeted rrn operon fragment of the corresponding species. Due to the reliability of simultaneously identifying Lactobacillus plantarum, Lactobacillus pentosus, and Lactobacillus paraplantarum, a previously described multiplex PCR method employing recA gene-derived primers was included in the multiplex PCR system. The combination of a newly developed, quick bacterial DNA extraction method from sourdough and this multiplex PCR assay allows the rapid in situ detection of several sourdough-associated lactobacilli, including the recently described species Lactobacillus rossii, and thus represents a very useful alternative to culture-based methodologies.
DNA Methylation Predicts Survival and Response to Therapy in Patients With Myelodysplastic Syndromes (2009)

DNA methylation predicts overall and progression-free survival in MDS.
Ostreolysin induces browning of adipocytes and ameliorates hepatic steatosis (2018)

This study provides first evidence of rOly's prevention of HFD-induced NAFLD by stimulating liver and adipose muscle tissue functionality and oxidative potential, improving glucose tolerance, and ameliorating the metabolic profile of diet-induced obese mice.
An oral SARS-CoV-2 M pro inhibitor clinical candidate for the treatment of COVID-19 (2021)

The worldwide outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to countering the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human coronavirus antiviral activity and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro antiviral cell potency in a phase 1 clinical trial in healthy human participants.
BCG: A throwback from the stone age of vaccines opened the path for bladder cancer immunotherapy. (2017)

After 4 decades of use, BCG remains the most effective agent against high risk NMIBC, but it still holds substantial drawbacks. The enduring use of immunotherapy for NMIBC has created a propitious environment to search for better alternatives. There are an increasing number of promising in vitro, animal and early human clinical trials to anticipate a significant therapeutic alternative in the foreseeable future.
Removal of tetrachloromethane by granular methanogenic sludge. (1995)

Granular sludge grown on sucrose, methanol, or a volatile fatty acid mixture was found to readily degrade tetrachloromethane without any prior adaptation to this compound. Preliminary experiments showed that degradation rates were comparable for the three different sludges. Tetrachloromethane was degraded by granular sludge grown on methanol, forming chloroform as a transient intermediate which was rapidly degraded to dichloromethane and methyl chloride. Degradation by autoclaved controls indicated the involvement of biologically generated abiotic cofactors such as vitamin B{sub 12} and cofactor F{sub 430}. The dechlorination by the autoclaved sludge was inhibited by addition of 1-iodopropane, a selective inhibitor of vitamin B{sub 12}. Degradation by autoclaved granular sludge was also severely inhibited by addition of H{sub 2}O{sub 2} to the medium, which oxidized all reducing equivalents.
Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand (2004)

AMG 531 was well tolerated in this study and was effective at raising platelet counts in healthy volunteers after single intravenous or subcutaneous administration.
Pteroic Acid Derivatives. II. Pteroyl-γ-glutamylglutamic Acid and Pteroyl-γ-glutamyl-γ-glutamylglutamic Acid (1948)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPteroic Acid Derivatives. II. Pteroyl-γ-glutamylglutamic Acid and Pteroyl-γ-glutamyl-γ-glutamylglutamic AcidJ. H. Boothe, J. H. Mowat, B. L. Hutchings, R. B. Angier, C. W. Waller, E. L. R. Stokstad, J. Semb, A. L. Gazzola, and Y. Subba RowCite this: J. Am. Chem. Soc. 1948, 70, 3, 1099–1102Publication Date (Print):March 1, 1948Publication History Published online1 May 2002Published inissue 1 March 1948https://pubs.acs.org/doi/10.1021/ja01183a068https://doi.org/10.1021/ja01183a068research-articleACS PublicationsRequest reuse permissionsArticle Views86Altmetric-Citations26LEARN 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
Acidic epinephrine analogs derived from 1H,3H-2,1,3-benzothiadiazole 2,2-dioxide and from trifluoromethanesulfonanilide. New synthesis of 1H,3H-2,1,3-benzothiadiazole 2,2-dioxide (1981)

Treatment of N,N'-dibenzyl-1,2-diaminobenzene (2) successively with thionyl chloride and then m-chloroperbenzoic acid gave N,N'-dibenzyl-1H,3H-2,1,3-benzothiadiazole 2,2-dioxide (4), which gave (via routes analogous to standard epinephrine syntheses) four bicyclic catecholamine analogues 7a-d. Hydrogenolysis of 4 yielded the parent heterocycle 5 in the first practicable synthesis avoiding expensive sulfamide (Scheme I). The trifluoromethanesulfonamidoacetophenones 8m and 8p on similar elaboration gave triflanilide catecholamine analogues 14m, 14p,17m, and 17p (Scheme II). 4,4'Dimethoxybenzhydrylamine (15) is recommended for the regiospecific synthesis of primary amines from epoxides (Scheme II). Series 7,14, and 17 were inactive in animal cardiovascular screens. Selected compounds were also screened in bronchodilator and in in vitro dopamine-, clonidine-, and prazosin-receptor binding assays as appropriate; again no activity was observed. Steric lipophilicity, and acidity factors are discussed, and the inactivity is ascribed to the high acidity of both systems (pKa approximately equal to 4).