gebhart/patrepeval huggingface dataset:
Thermal effects on an enzymatically latent conformation of coagulation factor VIIa (1999)

Activation of the zymogen factor VII yields an enzyme form, factor VIIa, with only modest activity. The thermal effect on this low activity of factor VIIa and its enhancement by the cofactor tissue factor was investigated. Factor VIIa activity measured with a chromogenic peptide substrate is characterized by an unusual temperature dependency which indicates that the activated protease exists in an equilibrium between a latent (enzymatically inactive) and an active conformation. As shown by calorimetry and activity measurements the thermal effects on factor VIIa are fully reversible below the denaturation temperature of 58.1 degrees C. A model for factor VIIa has been proposed [Higashi, S., Nishimura, H., Aita, K. & Iwanaga, S. (1994) J. Biol. Chem. 269, 18891-18898] in which the protease is supposed to exist primarily as a latent enzyme form because of the poor incorporation into the protease structure of the N-terminal Ile153 released by proteolytic cleavage during activation of factor VII. Binding of tissue factor to factor VIIa is assumed to shift the equilibrium towards an active conformation in which the N-terminal Ile153 forms a salt bridge with Asp343. We corroborate the validity of this model by: (a) chemical modification of factor VIIa; this suggests that the thermal effect on the equilibrium between the active and inactive conformation is reflected in the relative accessibility of the active site and the N-terminal Ile153; (b) measurements of factor VIIa binding to tissue factor indicating that complex formation is favoured by stabilization of the active conformation; and (c) activity measurements of a cross-linked factor VIIa-tissue factor complex; this showed that cross-linking stabilized the active conformation of factor VIIa and essentially prevented its thermally-induced transformation into the inactive state.
The Central and Peripheral Influences of Opioids on Gastrointestinal Propulsion (1985)

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic ...Read More
Androgen Receptor Antagonist versus Agonist Activities of the Fungicide Vinclozolin Relative to Hydroxyflutamide (1995)

The mechanism of antiandrogenic activity of vinclozolin (3-(3,5-dichlorophenyl)-5-methyl-5-vinyloxazolidine-2,4-dione), a dicarboximide fungicide under investigation for its potential adverse effects on human male reproduction, was investigated using recombinant human androgen receptor (AR). The two primary metabolites of vinclozolin in plants and mammals are M1 (2-[[3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid) and M2 (3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide). Both metabolites, in a dose-dependent manner, target AR to the nucleus and inhibit androgen-induced transactivation mediated by the mouse mammary tumor virus promoter. M2 is a 50-fold more potent inhibitor than M1 and only 2-fold less than hydroxyflutamide. In the presence of dihydrotestosterone (50 nM), M2 (0.2-10 microM) inhibits androgen-induced AR binding to androgen response element DNA. In the absence of dihydrotestosterone, concentrations of 10 microM M2 or hydroxyflutamide promote AR binding to androgen response element DNA and activation of transcription. Agonist activities of M2 and hydroxyflutamide occur at 10-fold lower concentrations with the mutant AR (Thr877 to Ala) endogenous to LNCaP human prostate cancer cells. The results indicate that androgen antagonists can act as agonists, depending on ligand binding affinity, concentration, and the presence of competing natural ligands.
[N-aryl pyrrole derivatives with analgesic and anti-inflammatory activity 2. Pharmacologic modulation of the 1-arylpyrrole model]. (1984)

In order to increase the pharmacological activities of the molecules described in the first part of the paper, an acetic or a 2-propionic group was introduced in to the fundamental structure, either on the aromatic ring, on the pyrrole nitrogen or on carbon 3 of the heterocycle. Moreover, a 4-chlorobenzoyl group was fixed on carbon 3 of the pyrrole via condensation of 4-chloroaniline with 4-chlorobenzoyl triketones. The structure of the adducts was demonstrated both by N.M.R. spectra and by using another unambiguous synthetic route. Finally, derivatives with the salicylic substructure on the nitrogen of the pyrrole are described. Their analgesic and anti-inflammatory properties are reported as well as some effects on the central nervous system.
Quantum clustering algorithms (2007)

By the term "quantization", we refer to the process of using quantum mechanics in order to improve a classical algorithm, usually by making it go faster. In this paper, we initiate the idea of quantizing clustering algorithms by using variations on a celebrated quantum algorithm due to Grover. After having introduced this novel approach to unsupervised learning, we illustrate it with a quantized version of three standard algorithms: divisive clustering, k-medians and an algorithm for the construction of a neighbourhood graph. We obtain a significant speedup compared to the classical approach.
Effects of Trans-10, Cis-12 Conjugated Linoleic Acid on Ovine Milk Fat Synthesis and Cheese Properties (2007)

Trans-10, cis-12 conjugated linoleic acid (CLA) reduces milk fat synthesis in sheep in a manner similar to that seen in dairy cows, but its effects on cheese yield and flavor are unknown. Additionally, when dietary energy supply is restricted, CLA can increase milk and milk protein yield, which may alter cheese yield and eating quality. The objectives of the study were to examine the effects of supplementing ewe diets with a rumen-protected source of CLA at a high and low dietary energy intake on milk fat and protein synthesis and on cheese yield and eating quality. Sixteen multiparous ewes were randomly allocated to 1 of 4 dietary treatments: a high (6.7 Mcal of metabolizable energy/d) or low (5.0 Mcal of metabolizable energy/d) feeding level that was either unsupplemented or supplemented with 25 g/d of a lipid-encapsulated CLA (to provide 2.4 g/d of CLA) in each of 4 periods of 21 d duration in a 4 x 4 Latin square design. There was no effect of treatment on milk yield (g/d), but milk fat percentage and milk fat yield were reduced by 23 and 20%, respectively, in ewes supplemented with CLA. Milk fatty acid concentration (g/100 g) of chain length < C16 was decreased and > C16 was increased in milk and cheese following CLA supplementation, whereas decreasing the feeding level increased fatty acids > or = C16. Milk fat contents of CLA were 0.01 and 0.12 g/100 g of fatty acids for the unsupplemented and CLA-supplemented treatments, respectively, whereas cis-9, trans-11 CLA was unaffected by CLA supplementation. There was no main effect of treatment on cheese yield, which was 0.11 +/- 0.001 kg of cheese/kg of milk, but cheese yield was highest, at 0.12 +/- 0.001 kg/kg, when made from milk of ewes fed the high feeding level + unsupplemented treatment. Cheese made from the milk of ewes supplemented with CLA, compared with the unsupplemented diet, was rated (scale 0 to 10) higher in the creaminess (2.1 vs. 1.4; SEM 0.15) and less oily (0.8 vs. 1.3; SEM 0.17) attributes, and was preferred overall (4.5 vs. 3.9; SEM 0.21). Cheese produced from sheep on the high vs. low feed level was rated less yellow (2.8 vs. 4.2; SEM 0.11), less salty (1.9 vs. 2.3; SEM 0.15), and more sour (1.5 vs. 1.1; SEM 0.13). We concluded that the effect of feeding level on animal performance and cheese characteristics was small, whereas supplementing the diets of ewes with a ruminally protected CLA source reduced milk fat yield, did not affect cheese yield, and beneficially altered the flavor characteristics of the cheese.
Ribonuclease S-peptide. A model for molecular recognition. (1976)

The relationship of structure to function in the recognition of ribonuclease S-peptide by S-protein was studied by several methods. Liquid phase peptide synthesis was employed to generate analogs of S-peptide in which from 1 to 8 residues were deleted from the NH2-terminal end of the S-peptide. Additional derivatives were made by substitutions in the NH2-terminal three amino acids or by modifying the S-peptide analogs by trifluoroacetylation. The analogs were generated in the following way. S-Peptide was cleaved with chymotrypsin. The fragment obtained, RNase(9-20), was purified and lengthened step by step using liquid phase peptide synthesis. A second set of analogs were prepared by cleavage of CF3CO-S-peptide with elastase and the resulting CF3CO-RNase(7-20), similarly lengthened. The various analogs of S-peptide were tested in their capacity to combine with S-protein and regenerate biological activity as measured by Vmax and Kb. This work shows a positive contribution of every one of the first 8 NH2-terminal residues of S-peptide to the molecular recognition of S-protein in the presence of RNA substrate. Substitution of the first 3 residues by alanine or blocking of the free amino groups decreases recognition, indicating that the original primary structure is the most favorable one.
ON THE ORIGIN AND TRANSFER OF AMMONIA IN THE HUMAN GASTROINTESTINAL TRACT1 (1966)

2 From the Mayo Clinic and Mayo Foundation: Gastrointestinal Research Unit, Rochester, Minnesota 55901.
The Role of Homogentisate Phytyltransferase and Other Tocopherol Pathway Enzymes in the Regulation of Tocopherol Synthesis during Abiotic Stress (2003)

Tocopherols are amphipathic antioxidants synthesized exclusively by photosynthetic organisms. Tocopherol levels change significantly during plant growth and development and in response to stress, likely as a consequence of the altered expression of pathway-related genes. Homogentisate phytyltransferase (HPT) is a key enzyme limiting tocopherol biosynthesis in unstressed Arabidopsis leaves (E. Collakova, D. DellaPenna [2003] Plant Physiol 131: 632-642). Wild-type and transgenic Arabidopsis plants constitutively overexpressing HPT (35S::HPT1) were subjected to a combination of abiotic stresses for up to 15 d and tocopherol levels, composition, and expression of several tocopherol pathway-related genes were determined. Abiotic stress resulted in an 18- and 8-fold increase in total tocopherol content in wild-type and 35S::HPT1 leaves, respectively, with tocopherol levels in 35S::HPT1 being 2- to 4-fold higher than wild type at all experimental time points. Increased total tocopherol levels correlated with elevated HPT mRNA levels and HPT specific activity in 35S::HPT1 and wild-type leaves, suggesting that HPT activity limits total tocopherol synthesis during abiotic stress. In addition, substrate availability and expression of pathway enzymes before HPT also contribute to increased tocopherol synthesis during stress. The accumulation of high levels of beta-, gamma-, and delta-tocopherols in stressed tissues suggested that the methylation of phytylquinol and tocopherol intermediates limit alpha-tocopherol synthesis. Overexpression of gamma-tocopherol methyltransferase in the 35S::HPT1 background resulted in nearly complete conversion of gamma- and delta-tocopherols to alpha- and beta-tocopherols, respectively, indicating that gamma-tocopherol methyltransferase activity limits alpha-tocopherol synthesis in stressed leaves.
Natural Products from Endophytic Microorganisms (2004)

Endophytic microorganisms are to be found in virtually every plant on earth. These organisms reside in the living tissues of the host plant and do so in a variety of relationships ranging from symbiotic to pathogenic. Endophytes may contribute to their host plant by producing a plethora of substances that provide protection and ultimately survival value to the plant. Ultimately, these compounds, once isolated and characterized, may also have potential for use in modern medicine, agriculture, and industry. Novel antibiotics, antimycotics, immunosuppressants, and anticancer compounds are only a few examples of what has been found after the isolation and culturing of individual endophytes followed by purification and characterization of some of their natural products. The prospects of finding new drugs that may be effective candidates for treating newly developing diseases in humans, plants, and animals are great. Other applications in industry and agriculture may also be discovered among the novel products produced by endophytic microbes.
Label Free Detection of CD4+ and CD8+ T Cells Using the Optofluidic Ring Resonator (2010)

We have demonstrated label free detection of CD4+ and CD8+ T-Lymphocyte whole cells and CD4+ T-Lymphocyte cell lysis using the optofluidic ring resonator (OFRR) sensor. The OFRR sensing platform incorporates microfluidics and photonics in a setup that utilizes small sample volume and achieves a fast detection time. In this work, white blood cells were isolated from healthy blood and the concentrations were adjusted to match T-Lymphocyte levels of individuals infected with HIV. Detection was accomplished by immobilizing CD4 and CD8 antibodies on the inner surface of the OFRR. Sensing results show excellent detection of CD4+ and CD8+ T-Lymphocyte cells at medically significant concentrations with a detection time of approximately 30 minutes. This work will lead to a rapid and low-cost sensing device that can provide a CD4 and CD8 count as a measure of HIV progression.
Road Weather Information System Environmental Sensor Station Siting Guidelines, Version 2.0 (2008)

FHWA initiated an effort in 2007 to evaluate and update, as necessary the ESS Guidelines first published in 2004 (FHWA-HOP-05-026). This effort is summarized in a companion report “Implementation and Evaluation of RWIS ESS Siting Guidelines”. The consensus of the project was that the original Guidelines covered most of the major issues in the siting of ESS and provided the necessary information in a concise manner. The major change made to this version of the Guidelines involved an update to the metadata table that was included in the original report. Since the original Guidelines were developed a major effort was conducted as part of the Clarus project to define a standard set of metadata for ESS. An expanded metadata table was thus included in the Guidelines showing Clarus metadata in three categories; required, recommended and optional. Other than the modification to the metadata table, most of the additions were limited, and designed to highlight areas of concern noted by DOT’s with ESS experience. The feedback from most of the DOT’s interviewed was positive and they expressed an interest in using the document for future deployments. Several noted that they would require their contractors to use it.
Antivascular and antitumor evaluation of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromenes, a novel series of anticancer agents (2004)

A novel series of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromenes was identified as potent apoptosis inducers through a cell-based high throughput screening assay. Six compounds from this series, MX-58151, MX-58276, MX-76747, MX-116214, MX-116407, and MX-126303, were further profiled and shown to have potent in vitro cytotoxic activity toward proliferating cells only and to interact with tubulin at the colchicine-binding site, thereby inhibiting tubulin polymerization and leading to cell cycle arrest and apoptosis. Furthermore, these compounds were shown to disrupt newly formed capillary tubes in vitro at low nanomolar concentrations. These data suggested that the compounds might have vascular targeting activity. In this study, we have evaluated the ability of these compounds to disrupt tumor vasculature and to induce tumor necrosis. We investigated the pharmacokinetic and toxicity profiles of all six compounds and examined their ability to induce tumor necrosis. We next examined the antitumor efficacy of a subset of compounds in three different human solid tumor xenografts. In the human lung tumor xenograft (Calu-6), MX-116407 was highly active, producing tumor regressions in all 10 animals. Moreover, MX-116407 significantly enhanced the antitumor activity of cisplatin, resulting in 40% tumor-free animals at time of sacrifice. Our results identify MX-116407 as the lead candidate and strongly support its continued development as a novel anticancer agent for human use.
High-throughput development and characterization of a genomewide collection of gene-based single nucleotide polymorphism markers by chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (2001)

We describe here a system for the rapid identification, assay development, and characterization of gene-based single nucleotide polymorphisms (SNPs). This system couples informatics tools that mine candidate SNPs from public expressed sequence tag resources and automatically designs assay reagents with detection by a chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. As a proof of concept of this system, a genomewide collection of reagents for 9,115 gene-based SNP genetic markers was rapidly developed and validated. These data provide preliminary insights into patterns of polymorphism in a genomewide collection of gene-based polymorphisms.
Stochastic Neural Networks for Hierarchical Reinforcement Learning (2017)

Deep reinforcement learning has achieved many impressive results in recent years. However, tasks with sparse rewards or long horizons continue to pose significant challenges. To tackle these important problems, we propose a general framework that first learns useful skills in a pre-training environment, and then leverages the acquired skills for learning faster in downstream tasks. Our approach brings together some of the strengths of intrinsic motivation and hierarchical methods: the learning of useful skill is guided by a single proxy reward, the design of which requires very minimal domain knowledge about the downstream tasks. Then a high-level policy is trained on top of these skills, providing a significant improvement of the exploration and allowing to tackle sparse rewards in the downstream tasks. To efficiently pre-train a large span of skills, we use Stochastic Neural Networks combined with an information-theoretic regularizer. Our experiments show that this combination is effective in learning a wide span of interpretable skills in a sample-efficient way, and can significantly boost the learning performance uniformly across a wide range of downstream tasks.
Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor (2016)

Contractility is reduced via the EP3 receptor but increased via EP4. These effects may be mediated through changes in phospholamban phosphorylation and has relevance to detrimental effects of inflammation.
Effectiveness and safety of ferric carboxymaltose compared to iron sucrose in women with iron deficiency anemia: phase IV clinical trials (2018)

ISRCTN14484575 Dated: 15-12-2017 retrospectively registered. https://doi.org/10.1186/ISRCTN14484575.
The devil is in the details: an evaluation of recent feature encoding methods (2011)

A large number of novel encodings for bag of visual words models have been proposed in the past two years to improve on the standard histogram of quantized local features. Examples include locality-constrained linear encoding [23], improved Fisher encoding [17], super vector encoding [27], and kernel codebook encoding [20]. While several authors have reported very good results on the challenging PASCAL VOC classification data by means of these new techniques, differences in the feature computation and learning algorithms, missing details in the description of the methods, and different tuning of the various components, make it impossible to compare directly these methods and hard to reproduce the results reported. This paper addresses these shortcomings by carrying out a rigorous evaluation of these new techniques by: (1) fixing the other elements of the pipeline (features, learning, tuning); (2) disclosing all the implementation details, and (3) identifying both those aspects of each method which are particularly important to achieve good performance, and those aspects which are less critical. This allows a consistent comparative analysis of these encoding methods. Several conclusions drawn from our analysis cannot be inferred from the original publications.
Prognostic Model of Pulmonary Adenocarcinoma by Expression Profiling of Eight Genes As Determined by Quantitative Real-Time Reverse Transcriptase Polymerase Chain Reaction (2004)

By analyzing a reasonably small number of genes, patients with adenocarcinoma could be stratified according to their prognosis. The prognostic model could be applicable to future decisions concerning treatment.
Multivalent Ligand-Receptor Binding Interactions in the Fibroblast Growth Factor System Produce a Cooperative Growth Factor and Heparin Mechanism for Receptor Dimerization (1994)

The binding interactions for the three primary reactants of the fibroblast growth factor (FGF) system, basic FGF (bFGF), an FGF receptor, FGFR1, and the cofactor heparin/heparan sulfate (HS), were explored by isothermal titrating calorimetry, ultracentrifugation, and molecular modeling. The binding reactions were first dissected into three binary reactions: (1) FGFR1 + bFGF<==>FGFR1/bFGF, K1 = 41 (+/- 12) nM; (2) FGFR1 + HS<==>FGFR1/HS, K2 = 104 (+/- 17) microM; and (3) bFGF + HS<==>bFGF/HS, K3 = 470 (+/- 20) nM, where HS = low MW heparin, approximately 3 kDa. The first, binding of bFGF to FGFR1 in the absence of HS, was found to be a simple binary binding reaction that is enthalpy dominated and characterized by a single equilibrium constant, K1. The conditional reactions of bFGF and FGFR1 in the presence of heparin were then examined under conditions that saturate only the bFGF heparin site (1.5 equiv of HS/bFGF) or saturate the HS binding sites of both bFGF and FGFR1 (1.0 mM HS). Both 3-and 5-kDa low MW heparins increased the affinity for FGFR1 binding to bFGF by approximately 10-fold (Kd = 4.9 +/- 2.0 nM), relative to the reaction with no HS. In addition, HS, at a minimum of 1.5 equiv/bFGF, induced a second FGFR1 molecule to bind to another lower affinity secondary site on bFGF (K4 = 1.9 +/- 0.7 microM) in an entropy-dominated reaction to yield a quaternary complex containing two FGFR1, one bFGF, and at least one HS. Molecular weight estimates by analytical ultracentrifugation of such fully bound complexes were consistent with this proposed composition. To understand these binding reactions in terms of structural components of FGFR1, a three-dimensional model of FGFR1 was constructed using segment match modeling. Electrostatic potential calculations confirmed that an elongated cluster, approximately 15 x 35 A, of nine cationic residues focused positive potential (+2kBT) to the solvent-exposed beta-sheet A, B, E, C' surface of the D(II) domain model, strongly implicating this locus as the HS binding region of FGFR1. Structural models for HS binding to FGFR1, and HS binding to bFGF, were built individually and then assembled to juxtapose adjacent binding sites for receptor and HS on bFGF, against matching proposed growth factor and HS binding sites on FGFR1. The calorimetric binding results and the molecular modeling exercises suggest that bFGF and HS participate in a concerted bridge mechanism for the dimerization of FGFR1 in vitro and presumably for mitogenic signal transduction in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)