gebhart/patrepeval huggingface dataset:
Pharmacokinetics of a novel surface‐active agent, purified poloxamer 188, in rat, rabbit, dog and man (2002)

Purified poloxamer 188 (PP188) is a non-ionic, block copolymer surfactant that is currently being evaluated clinically in sickle cell disease vaso-occlusive crisis and acute chest syndrome and preclinically in spinal cord injury and muscular dystrophy. This paper describes the pharmacokinetics of PP188 in rats, pregnant rats, pregnant rabbits, dogs and humans. Plasma protein binding interaction studies demonstrated no clinically significant effects on narcotic analgesics, hydroxyurea, warfarin, diazepam or digitoxin, but an increase in free fraction for propranolol. The plasma concentrations increased proportionate with increasing dose in all species tested. Renal clearance accounted for 90% of total plasma clearance in man. A single metabolite was detected and quantified in the plasma from dogs and humans that was cleared more slowly than parent drug. Allometric scaling of plasma clearance and volume of distribution at steady-state (Vss) across species provided good predictions of the pharmacokinetic parameters in humans. Based on the comparative pharmacokinetics of PP188 in rat, rabbit, dog and man, all three animal species were appropriate models for evaluating various aspects of PP188's toxicological profile.
Isolation of mutants of Saccharomyces cerevisiae requiring DNA topoisomerase I. (1995)

Despite evidence that DNA topoisomerase I is required to relieve torsional stress during DNA replication and transcription, yeast strains with a top1 null mutation are viable and display no gross defects in DNA or RNA synthesis, possibly because other proteins provide overlapping functions. We isolated mutants whose inviablility or growth defect is relieved when TOP1 is expressed [trf mutants (topoisomerase one-requiring function)]. The TRF genes define at least four complementation groups. TRF3 is allelic to TOP2. TRF1 is allelic to HPR1, previously shown to be homologous to TOP1 over two short regions. TRF4 encodes a novel 584-amino acid protein with homology to the N-terminus of Saccharomyces cerevisiae topo I. Like top1 mutants, trf4 mutants have elevated rDNA recombination and fail to shut off RNA polymerase II transcription in stationary phase. trf4 null mutants are cs for viability, display reduced expression of GAL1 and Cell Cycle Box UAS::LacZ fusions, and are inviable in combination with trfI null mutants, indicating that both proteins may share a common function with DNA topoisomerase I. The existence of multiple TRF complementation groups suggests that not all biological functions of topo I can be carried out by topo II.
Laser cross-linking of proteins to nucleic acids. II. Interactions of the bacteriophage T4 DNA replication polymerase accessory proteins complex with DNA (1993)

In this paper we examine the interactions of the polymerase accessory proteins subassembly of the bacteriophage T4 DNA replication complex, using single-pulse ultraviolet laser excitation to induce protein-nucleic acid cross-links. The laser-induced cross-linking permits effective "freezing" of the instantaneous equilibrium state of the complex and thus provides a mechanism to dissect the individual protein-nucleic acid interactions involved in complex assembly. We find that the binding of the gene 44, 62, and 45 proteins is dependent not only on the presence of each of the other proteins, but also on the presence of adenine nucleotide cofactors. We find that the nonhydrolyzable analogs of ATP often behave more like ADP than ATP in these experiments. Gene 45 protein is able to induce an increase in cross-linking of the gp44/62 complex to nucleic acids, and this increased cross-linking correlates with changes in the apparent Km of the gp44/62 complex for polynucleotides and with changes in Vmax during ATP hydrolysis. Our results suggest that the enhanced DNA binding is predominately through the gene 62 protein and not the ATPase catalytic subunit (gene 44 protein). Thus the gene 62 protein seems to play an integral role in gp45-mediated enhancement of the ATP hydrolytic activity of gp44. These results are summarized and integrated in the form of a model for the multiple interactions of the accessory proteins with DNA and one another in the presence of mononucleotide cofactors and substrates.
Mechanism of Mevalonate Pyrophosphate Decarboxylase: Evidence for a Carbocationic Transition State (1994)

Mevalonate pyrophosphate decarboxylase catalyzes the decarboxylation of mevalonate pyrophosphate to isopentyl pyrophosphate. The mechanism of action of this enzyme was investigated to elucidate the mechanism of inhibition by 3-hydroxy-3-(fluoromethyl)-5-pyrophosphopentanoic acid (II). It was previously found that II is a competitive inhibitor (Ki = 0.01 microM) of the enzyme reaction [Reardon, J.E., & Abeles, R.H. (1987) Biochemistry 26, 4717-4722; Nave, J.F., d'Orchymont, H., Ducep, J.B., Piriou, F., & Jung, M.J. (1985) Biochem. J. 227, 247-254]. We have now observed that II is decarboxylated 2500-fold more slowly than mevalonate pyrophosphate (3-hydroxy-3-methyl-5-pyrophosphopentanoic acid, I). The enzyme was exposed to saturating concentrations of II and ATP and then passed through a Penefsky column to remove excess substrate. The enzyme was denatured immediately upon emerging from the Penefsky column. Nearly 1 equiv of both 3-phospho-3-(fluoromethyl)-5-pyrophosphopentanoic acid and ADP was bound to the enzyme. 3-Hydroxy-5-pyrophosphopentanoic acid (III) is phosphorylated at the secondary hydroxyl group and released from the enzyme without decarboxylation. This reaction is 30-fold slower than the rate of decarboxylation of I. The introduction of the 3-fluoromethyl group as well as the removal of the 3-methyl group results in low rates of decarboxylation. These substrate analogs have decreased electron density relative to the tertiary carbon of the substrate. Therefore, the transition state of the decarboxylation step has considerable carbocationic character. Further support for the carbocationic transition state is provided by the finding that N-methyl-N-carboxymethyl-2-pyrophosphoethanolamine (IV) inhibits the enzyme reaction with Ki = 0.75 microM. IV is probably a transition-state analog in which the positively charged nitrogen atom is analogous to the carbocation.
Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region (1996)

Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.
Identification of a 15-kilodalton surface glycoprotein on sporozoites of Cryptosporidium parvum (1991)

An immunoglobulin A monoclonal antibody (MAb5C3) was developed against a 15-kDa surface glycoprotein (GP15) of Cryptosporidium parvum sporozoites. Indirect immunofluorescence and colloidal gold immunoelectron microscopy revealed that the antibody reacted with both the sporozoite and merozoite surface plasma membranes. On Western immunoblots, MAb5C3 binding was found to be strongly inhibited when 200 mM N-acetylglucosamine was used as a competing sugar. N-Acetylgalactosamine inhibited binding of the antibody only slightly, whereas glucose, mannose, and galactose failed to inhibit binding. MAb5C3 was found to recognize a similar 15-kDa epitope associated with a Cryptosporidium sp. isolated from guinea pigs. However, MAb5C3 failed to react with any proteins or glycoproteins associated with C. baileyi from chickens, Cryptosporidium sp. (= bovine C. muris) from cattle, C. serpentis from a rat snake, bradyzoites of Besnoitia darlingi from an opossum, sporozoite/oocyst extracts of Caryospora bigenetica from an eastern diamondback rattlesnake, sporozoites of Eimeria nieschulzi and E. papillata from rats and mice, or tachyzoites of Toxoplasma gondii (RH strain). When hybridoma supernatants containing MAb5C3 were administered orally to suckling mice experimentally infected with C. parvum, a 75% reduction in developmental stages was seen histologically at 72 h postinfection and a 67.5% reduction in mean oocyst output was found at 6 days postinfection.
Temperature-Dependent Electron Transport through Silver Nanocrystal Superlattices (2001)

Temperature-dependent electron transport was measured through three-dimensional close-packed alkanethiol-stabilized silver nanocrystal arrays using interdigitated array electrodes. Nanocrystals ranging from 35 to 77 Å in diameter with Coulomb blockade energies well above kT were studied. The nanocrystal superlattices exhibit linear current−voltage behavior for temperatures as low as 70 K. Ordered face-centered cubic (fcc) superlattices exhibit a positive temperature coefficient of resistivity (TCR), characteristic of a metal, at temperatures above approximately 225 to 245 K, depending on the particle size. The values of the conductivity, on the order of 10-6 to 10-7 Ω-1 cm-1, however, are characteristic of semiconductors. Below the transition temperature, the TCR for the size-monodisperse nanocrystal arrays becomes negative, characteristic of an insulator and the conductance G, of the ordered arrays scales exponentially with temperature as G ∝ exp[−(To/T)ν]. The exponent ν, ranges from 0.67 to 1.34 for nanocrystals 77 Å to 35 Å in diameter, respectively, characteristic of a gap in the density of states in the overall electronic structure of the superlattice. We believe that electron transport occurs through a polaron hopping mechanism. In contrast to the organized superlattices, disordered close-packed nanocrystals exhibit insulating behavior at all temperatures studied due to (Anderson-type) disorder.
Spiro β-Lactams as β-Turn Mimetics. Design, Synthesis, and NMR Conformational Analysis (2001)

Molecular modeling calculations using high-level ab initio methods (MP2/6-31+G) of a new type of spiro beta-lactams predict that these systems could adopt a beta-turn secondary structure in solution. Strong intramolecular hydrogen bonds stabilize the beta-turn conformation with a geometry that is very close to the ideal type II beta-turns. The synthesis of the spiro beta-lactams is achieved by Staudinger reaction of a cyclic ketene derived from N-bencyloxycarbonyl-L-proline acid chloride with an imine. This reaction allows the formation of the spiranic backbone in a single-step with high diastereoselectivity and good yields. The new spiro beta-lactams obtained are the core for the preparation of different types of peptidomimetics using well-established peptide chemistry. The NMR conformational analysis shows that these compounds adopt beta-turn conformation as predicted by the theoretical studies.
Enhancement in Ethanol Electrooxidation by SnOxNanoislands Grown on Pt(111): Effect of Metal Oxide–Metal Interface Sites (2011)

An integrated surface science and electrochemistry approach has been used to prepare and characterize SnOx/Pt(111) model catalysts and evaluate their electrochemical activity for the ethanol oxidation reaction (EOR). Nanoislands of SnOx are deposited onto the Pt(111) by reactive layer assisted deposition in which Sn metal is vapor deposited onto a Pt(111) surface precovered by NO2. X-ray photoelectron spectroscopy (XPS) shows that the SnOx islands are highly reduced with Sn2+ being the dominant chemical species. After exposing the SnOx/Pt(111) surface to H2O or an electrolyte solution, XPS provides evidence for a significant amount of H2O/OH adsorbed on the reduced SnOx surfaces. Electrochemical testing reveals that the catalytic performance of Pt(111) toward ethanol electrooxidation is significantly enhanced with SnOx islands added onto the surface. The enhanced EOR activity is tentatively attributed to the efficient removal of COads-like poisoning species at Pt sites by oxygen-containing species that are readily formed on the SnOx nanoislands. Moreover, the strong dependence of the EOR activity on SnOx coverage provides experimental evidence for the importance of SnOx–Pt interface sites in the EOR.
Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability (2008)

Pin1 is a novel regulator of erbB2 that modulates the ubiquitin-mediated degradation of erbB2. The overexpression of Pin1 in a majority of Her2-overexpressing breast cancer may contribute to maintain erbB2 levels. Pin1 inhibition alone and in conjunction with mTOR inhibition suppresses the growth of Her2+ breast cancer cells.
Treatment of obesity: need to focus on high risk abdominally obese patients (2001)

Editorial by Little and Byrne 

It is generally accepted that obesity is a health hazard because of its association with numerous metabolic complications such as dyslipidaemia, type 2 diabetes, and cardiovascular diseases.1 On that basis, health agencies 2 3 have proposed that obesity should be defined on the basis of weight in kg expressed over height in m2, the so called body mass index,4 initially described by Quetelet in 1869 (table). Epidemiological studies have reported a progressive increase in the incidence of chronic diseases such as hypertension, diabetes, and coronary heart disease with increasing body mass index.1-3 However, despite this well documented evidence, physicians are, in their daily practice, perplexed by the remarkable heterogeneity found in their obese patients. For instance, some patients show a relatively “normal” profile of metabolic risk factors despite the presence of substantial excess body fat, whereas others who are only moderately overweight can nevertheless be characterised by a whole cluster of metabolic complications, increasing the risk of type 2 diabetes, coronary atherosclerosis, and cardiovascular disease.

View this table:

Classification of obesity based on body mass index (BMI)2 3



#### Summary points

A simple measurement such as waist circumference can indicate accumulation of abdominal fat

Viscerally obese men are characterised by an atherogenic plasma lipoprotein profile

A triad of non-traditional markers for coronary heart disease found in viscerally obese middle aged men (hyperinsulinaemia, raised apolipoprotein B concentration, and small LDL particles) increases the risk of coronary heart disease 20-fold

Four out of five middle aged men with a waist measurement ≥90 cm and triglyceride concentrations ≥2 mmol/l are characterised by this triad

Even in the absence of hypercholesterolaemia, hyperglycaemia, or hypertension, obese patients could be at high risk of coronary heart disease if they have this “hypertriglyceridaemic waist” phenotype

In this regard, epidemiological and metabolic studies …
Cytokine Production (IL-1α, IL-1β, and TNFα) and Endothelial Cell Activation (ELAM-1 and HLA-DR) in Reactive Lymphadenitis, Hodgkin's Disease, and in Non-Hodgkin's Lymphomas: An Immunocytochemical Study (1990)

Cryostat sections of 58 lymph nodes were immunostained with a polyclonal rabbit serum against IL-1α, and with monoclonal antibodies directed to IL-1α (Vmp18), IL-1β (Vhp20 and BRhC3), and tumor necrosis factor α (TNFα) (B154.7). Furthermore the presence of cytokine-containing cells was correlated with the expression of endothelial leukocyte adhesion molecule (ELAM-1; 29F2) and of human leukocyte antigen (HLA-DR) (OKIa-1)by endothelial cells. Cells containing IL-1 and/or TNFα were detected mainly inpathologic conditions characterized by reactive or neoplastic expansion of the lymph node paracortex. Cells positive for IL-1 were detected in 16 of 21 cases of Hodgkin's disease,in 4 of 4 cases of T-NHL, and in 5 cases of diffuse or mixed lymphadenitis. Interleukin-1α was detected in macrophages, interdigitating reticulum cells (IDRCs), endothelial cells, and neoplastic Hodgkin's and Reed-Sternberg (H-RS) cells. Cells positive for IL-1 β were much fewer and consisted mainly of macrophages. Hodgkin's Reed-Sternberg cells were negative for IL-1β even after in vitro stimulation with bacterial endotoxin. Tumor necrosis factor α (TNFα) was present in macrophages and H-RS cells. Endothelial leukocyte adhesion molecule-1 expression by endothelial venules was detected in 17 of 20 cases of Hodgkin's disease, in 2 of 4 cases of T-NHL, and in 5 of 5 cases of diffuse lymphadenitis. In these pathologic conditions, HLADR antigens also were expressed frequently by endothelial cells. Cytokine-containing cells and ELAM-1-positive high endothelial venules (HEV) were extremely rare in lymph nodes involved by follicular lymphadenitis (12 cases) or B-NHL (16 cases). In cases of reactive or neoplastic B-cell proliferations, HLA-DR-positive HEVs still were present often. Our results indicate that IL-1/TNFα production at tissue level is often associated with ELAM-1 expression by HEVs, but is less well correlated with expression of HLA-DR antigens by endothelial cells.
Tryptophan metabolism in chronic inflammatory lung disease. (1995)

Induction of indoleamine 2,3-dioxygenase (IDO), an enzyme expressed by mononuclear phagocytes and some fibroblast cell lines in response to interferon-gamma, leads to enhanced degradation of tryptophan to kynurenine. Because inflammatory lung diseases are generally associated with activation of pulmonary macrophages, we investigated tryptophan metabolism in patients with interstitial lung disease by measuring circulating levels of tryptophan and kynurenine in peripheral blood and by measuring the IDO activity of bronchoalveolar cells. IDO activities were increased for bronchoalveolar lavage (BAL) cells obtained from patients with interstitial lung disease (115.4 +/- 30.4, n = 37) when compared with BAL cells from normal subjects (15.2 +/- 7.4, n = 14; p < 0.05), and messenger RNA for IDO was present in BAL cells from patients with interstitial disease but was not present in BAL cells from normal volunteer subjects. Patients with inflammatory lung disease also had decreased tryptophan and increased kynurenine concentrations in serum. The ratio of serum tryptophan levels to serum kynurenine levels was significantly depressed for patients with idiopathic pulmonary fibrosis (18.4 +/- 1.7, n = 29; p < 0.0001), patients with fibrosing alveolitis associated with collagen vascular disease (13.1 +/- 1.6, n = 18; p < 0.0001), or patients with sarcoidosis (21.0 +/- 1.1, n = 50; p < 0.0001), as compared with the ratio for normal subjects (31.8 +/- 2.3, n = 18). Patients with fibrotic disease had the highest levels of BAL cell IDO activity, and patients with collagen vascular disease associated fibrosing alveolitis had the most depressed levels of serum tryptophan and the greatest elevations in serum kynurenine. Measurement of tryptophan and kynurenine concentrations in serum may provide a useful measure of disease activity in chronic inflammatory parenchymal lung diseases such as sarcoidosis and idiopathic pulmonary fibrosis.
Statistically Robust Approach to Lens Distortion Calibration with Model Selection (2003)

This paper addresses the problem of calibrating camera lens distortion, which can be significant in medium to wide angle lenses. While almost all existing nonmetric distortion calibration methods need user involvement in one form or another,we present an approach to distortion calibration based on the robust the-least-median-of-squares (LMedS) estimator. Our approach is thus able to proceed in a ful ly-automatic manner while being less sensitive to erroneous input data such as image curves that are mistakenly considered as projections of 3D linear segments. Our approach uniquely uses fast, closed-form solutions to the distortion coefficients, which serve as an initial point for a non-linear optimization algorithm to straighten imaged lines. Moreover we propose a method for distortion model selection based on geometrical inference.Successful experiments to evaluate the performance of this approach on synthetic and real data are reported.
The peptide pheromone-inducible conjugation system of Enterococcus faecalis plasmid pCF10: cell–cell signalling, gene transfer, complexity and evolution (2007)

Expression of a large set of gene products required for conjugative transfer of the antibiotic resistance plasmid pCF10 is controlled by cell-cell communication between plasmid-free recipient cells and plasmid-carrying donor cells using a peptide mating pheromone cCF10. Most of the recent experimental analysis of this system has focused on the molecular events involved in initiation of the pheromone response in the donor cells, and on the mechanisms by which the donor cells control self-induction by endogenously produced pheromone. Recently, studies of the molecular machinery of conjugation encoded by the pheromone-inducible genes have been initiated. In addition, the system may serve as a useful bacterial model for addressing the evolution of biological complexity.
Multi-camera spatio-temporal fusion and biased sequence-data learning for security surveillance (2003)

We present a framework for multi-camera video surveillance. The framework consists of three phases: detection, representation, and recognition. The detection phase handles multi-source spatio-temporal data fusion for efficiently and reliably extracting motion trajectories from video. The representation phase summarizes raw trajectory data to construct hierarchical, invariant, and content-rich descriptions of the motion events. Finally, the recognition phase deals with event classification and identification on the data descriptors. Because of space limits, we describe only briefly how we detect and represent events, but we provide in-depth treatment on the third phase: event recognition. For effective recognition, we devise a sequence-alignment kernel function to perform sequence data learning for identifying suspicious events. We show that when the positive training instances (i.e., suspicious events) are significantly outnumbered by the negative training instances (benign events), then SVMs (or any other learning methods) can suffer a high incidence of errors. To remedy this problem, we propose the kernel boundary alignment (KBA) algorithm to work with the sequence-alignment kernel. Through empirical study in a parking-lot surveillance setting, we show that our spatio-temporal fusion scheme and biased sequence-data learning method are highly effective in identifying suspicious events.