gebhart/patrepeval huggingface dataset:
Modeling, design, and development of potential inhibitors of gamma-glutamylamine cyclotransferase and inhibitors of cruzain as therapeutic agents for Chagas' disease (2008)

γ-Glutamylamine cyclotransferase (γ-GACT) catalyzes cyclization of the L-glutamyl moiety in the isolated e-(L-γ-glutamyl)-L-lysine crosslink, thereby releasing lysine. Although implicated in the degradation of the crosslink, the physiological function of γ-GACT has not been established, and purification and characterization of the enzyme is essential for the elucidation of its function. Although much information on the formation of this crosslink, which is essential in blood coagulation, wound healing, and apoptosis, has been reported in the literature, little has been documented about the degradation process. Design, synthesis, and development of potential inhibitors of γ-GACT are based on the previous substrate specificity studies, and the best inhibitor was incorporated into a solid support of a customized affinity column for enzyme purification. Although no X-ray crystal structures of the enzyme exist, molecular modeling of substrates and inhibitors may still provide useful information in the further development of inhibitors. Chagas’ disease, a result of Trypanosoma cruzi infection, is the third largest parasitic disease challenge after malaria and leishmania. It is an emerging concern since globalization brings the disease to the backyard of all countries. A significant percentage of all incidents develop into the chronic stage and lead ultimately to death caused by parasite induced organ failure. Currently, there is no satisfactory cure. Cruzipain, a cysteine protease essential to the T. cruzi organism, is a validated therapeutic target and its inhibition has been shown to achieve an experimental cure in mice. A library of thiosemicarbazone (TSC) and α,β-unsaturated carbonyl derivatives of benzophenone, propiophenone, α- and β-tetralone, 4-chromanone, and 4-thiochromenone was evaluated for inhibition of cruzain, a cloned version of cruzipain. Kinetics studies and molecular modeling was used to gain understanding of enzyme-inhibitor interactions. The best compounds, the TSC derivatives of a dibromobenzophenone and a bromo-α-tetralone were found to be slow, tight binding inhibitors of cruzain. Modeling studies support the kinetic results of a transient, reversible covalent bond formed between the inhibitor and the enzyme. These studies indicate that the best inhibitors from the library place the TSC moiety close to the active site thiolate and aromatic groups in the S2 pocket. Modeling studies also suggest that while the best inhibitors of cathepsin L from the same library have the TSC in the same position as in cruzain, the S1′ pocket, which is larger in cathepsin L than in cruzain, is more important in inhibitor binding. These studies are expected to help in the rational design of more potent inhibitors in the future.
Recent advances in the understanding of bile acid malabsorption (2009)

Further research into the precise mechanism of IBAM is needed. Improvements in the recognition of the condition and optimization of treatment are required.
SPOT5 HRG and HRS first in-flight geometric quality results (2003)

As compared to other SPOT satellites, SPOT5 geometric accuracy is improved : a stellar sensor unit allows absolute location accuracy of 60 meters; geometric resolution is 10 meters for multispectral mode, 5 meters for panchromatic mode and 2,5 meters for THR mode; HRS along track stereoscopic mode leads to 10 meters accuracy digital terrain models. This paper presents the results of in-flight geometric characterization of SPOT5 remote sensing satellite established during the first two months of SPOT5's life in orbit. Calibration of the viewing model has been performed : platform's biases and modelization of mirror positioning are measured thanks to a triangulation process using images acquired on several targets around the world chosen for their referential ground control points. Geometric performances of THR mode was precisely measured thanks to the comparison of the two images of the quincunx mode. Multispectral registration was measured using correlation methods. The viewing model includes a description of the focal plane with each detector viewing angle. This description was improved for HRS and HRG cameras thanks to a reference composed of a set of aerial photographs. Finally, a first evaluation of HRS' DTM accuracy has been done by comparison to a reference DTM over FRANCE.
Hepcidin in iron overload disorders (2005)

Hepcidin is the principal regulator of iron absorption in humans. The peptide inhibits cellular iron efflux by binding to the iron export channel ferroportin and inducing its internalization and degradation. Either hepcidin deficiency or alterations in its target, ferroportin, would be expected to result in dysregulated iron absorption, tissue maldistribution of iron, and iron overload. Indeed, hepcidin deficiency has been reported in hereditary hemochromatosis and attributed to mutations in HFE, transferrin receptor 2, hemojuvelin, and the hepcidin gene itself. We measured urinary hepcidin in patients with other genetic causes of iron overload. Hepcidin was found to be suppressed in patients with thalassemia syndromes and congenital dyserythropoietic anemia type 1 and was undetectable in patients with juvenile hemochromatosis with HAMP mutations. Of interest, urine hepcidin levels were significantly elevated in 2 patients with hemochromatosis type 4. These findings extend the spectrum of iron disorders with hepcidin deficiency and underscore the critical importance of the hepcidin-ferroportin interaction in iron homeostasis.
Engineering multiple-domain forms of the therapeutic antibody CAMPATH-1H: effects on complement lysis. (1994)

Antibody-mediated lysis of cells involves a complex interaction between the cell, the target antigen, the antibody and host effector mechanisms. One such mechanism, complement-mediated cell lysis, requires the interaction of C1q with the antibody heavy chain constant regions, and in particular the CH2 domain. Here we investigate the potential benefit of multiple-domain forms of the therapeutic monoclonal antibody CAMPATH-1H. This antibody is directed against the CDw52 antigen expressed by human lymphocytes and has proven lytic abilities both in vitro and in vivo. Using target cells with either high or low antigen density, engineered antibodies that contained additional domains in tandem (CH2, hinge-CH2 or Fc intramolecular repeats) showed no improvement in complement-mediated lysis when compared with controls. However, a homodimeric form of the antibody that was engineered by mutation of a serine residue to cysteine near the carboxy-terminal of the CH3 domain, exhibited markedly improved lysis using target cells expressing antigen at low density. Interestingly, no improvement was seen using cells expressing antigen at high density. These results suggest that dimeric forms of antibodies could be useful for converting cells with low density antigens into useful targets for therapy.
Upside‐down faces: A review of the effect of inversion upon face recognition (1988)

Several studies have found that face recognition is disproportionately impaired by stimulus inversion when compated to recognition of other classes of visual stimuli. This effect has been interpreted as evidence that face recognition benefits from a 'special' process which is not engaged by an inverted face. This paper reviews studies of the effect of inversion on face recognition in recognition memory tasks, matching tasks and upon cerebral hemisphere asymmetries. Evidence is drawn from developmental studies and from studies of brain-injured and normal adult subjects. It is concluded that the evidence that inverted faces are processed differently from upright faces is far from compelling, and therefore the effect of inversion provides little or no evidence of a unique process in face recognition. The inversion effect is interpreted in terms of expertise in face processing and the highly homogeneous nature of faces as a stimulus class.
Effects of contact shape on the scaling of biological attachments (2004)

Adhesion of biological systems has recently received much research attention: the survival of organisms ranging from single cells and mussels to insects, spiders and geckos relies crucially on their mechanical interaction with their environments. For spiders, lizards and possible other ‘dry’ adhesive systems, explanations for adhesion are based on van der Waals interaction, and the adhesion of single–contact elements has been described by the classical Johnson–Kendall–Roberts (JKR) model derived for spherical contacts. However, real biological contacts display a variety of shapes and only rarely resemble a hemisphere. Here, we theoretically assess the influence of various contact shapes on the pull–off force for single contacts as well as their scaling potential in contact arrays. It is concluded that other shapes, such as a toroidal contact geometry, should lead to better attachment; such geometries are observed in our microscopic investigations of hair–tip shapes in beetles and flies.
WaterSense (2011)

Smart water meters will soon provide real-time access to instantaneous water usage in many homes, and disaggregation is the problem of deciding how much of that usage is due to individual fixtures in the home. Existing disaggregation techniques require additional water sensing infrastructure and/or a manual characterization of each water fixture, which can be expensive and time consuming. In this paper, we describe a novel technique called WaterSense to perform fixture-level disaggregation using only a handful of inexpensive motion sensors. WaterSense automatically infers how many fixtures are in each room, and how much water each fixture uses. We evaluate the system using a 7-day in-situ evaluation in 2 diverse multi-resident homes with a total of 10 different water fixtures and 467 fixture events and observe that our approach achieves 86% classification accuracy in identifying individual water fixture events and 80--90% accuracy in determining the water consumption of individual water fixtures.
Circadian Rhythms in Lizards: Phase Response Curve for Melatonin (1986)

Single biweekly injections of melatonin were administered to lizards (Sceloporus occidentalis) free-running (exhibiting their endogenous circadian activity rhythm) in constant dim illumination. The injections caused phase shifts in the activity rhythm whose magnitude and direction were a function of the time of the melatonin injections, relative to activity onsets. Plotting the direction and amount of phase shift versus the time (phase) at which the injection was given generates a phase-response curve (PRC). The PRC shows that injections administered between midsubjective day and early subjective night (6-15 hr after activity onset) elicit phase advances in the activity rhythm, whereas injections given at other phases of the activity cycle induce phase delays. The existence of a PRC for melatonin suggests that the daily endogenous rhythm of melatonin (i.e., of pineal origin) may be involved in phasing, or entraining, the circadian system of lizards. The shape of the PRC also allows predictions as to the effects of continuous exogenous melatonin administration on the period of free-running activity rhythms as well as on the mechanism of entrainment of activity rhythms to daily melatonin injections.
Chemical composition, antibacterial and antioxidant profile of essential oil from Murraya koenigii (L.) leaves. (2014)

The oil has a maximum zone of inhibition ability against Corynebacterium tuberculosis, Pseudomonas aeruginosa, Streptococcus pyogenes, Klebsiella pneumonia and Enterobacter aerogenes. The antioxidant profile of the sample was determined by different test systems. In all the systems, essential oil showed a strongest activity profile within the concentration range.
Defective Lipolysis and Altered Energy Metabolism in Mice Lacking Adipose Triglyceride Lipase (2006)

Fat tissue is the most important energy depot in vertebrates. The release of free fatty acids (FFAs) from stored fat requires the enzymatic activity of lipases. We showed that genetic inactivation of adipose triglyceride lipase (ATGL) in mice increases adipose mass and leads to triacylglycerol deposition in multiple tissues. ATGL-deficient mice accumulated large amounts of lipid in the heart, causing cardiac dysfunction and premature death. Defective cold adaptation indicated that the enzyme provides FFAs to fuel thermogenesis. The reduced availability of ATGL-derived FFAs leads to increased glucose use, increased glucose tolerance, and increased insulin sensitivity. These results indicate that ATGL is rate limiting in the catabolism of cellular fat depots and plays an important role in energy homeostasis.
Analysis of electrocardiograms during atrial fibrillation (2006)

The research discussed in this article is motivated by the search for an optimal classification of the different types of atrial fibrillation (AF) on the basis of recorded atrial signals. This would facilitate the selection of an optimal therapy. This article focuses on the biophysical models of the genesis of ECG waveforms during AF. The model of the electric activity of the atria was found to have sufficient realism to be used to describe the electric sources during AF. The inclusion of the volume conduction model resulted in electrocardiographic signals that are in all aspects similar to those observed clinically. The model is currently applied to solve various problems related to optimal signal preprocessing and extraction of features in AF signals for the classification of AF abnormalities. The biophysical model of the atrial activity is an essential element in this research, since it is capable of describing the electric source specifications derived from different hypotheses relating to the etiology of AF
Ensembl 2015 (2014)

Ensembl (http://www.ensembl.org) is a genomic interpretation system providing the most up-to-date annotations, querying tools and access methods for chordates and key model organisms. This year we released updated annotation (gene models, comparative genomics, regulatory regions and variation) on the new human assembly, GRCh38, although we continue to support researchers using the GRCh37.p13 assembly through a dedicated site (http://grch37.ensembl.org). Our Regulatory Build has been revamped to identify regulatory regions of interest and to efficiently highlight their activity across disparate epigenetic data sets. A number of new interfaces allow users to perform large-scale comparisons of their data against our annotations. The REST server (http://rest.ensembl.org), which allows programs written in any language to query our databases, has moved to a full service alongside our upgraded website tools. Our online Variant Effect Predictor tool has been updated to process more variants and calculate summary statistics. Lastly, the WiggleTools package enables users to summarize large collections of data sets and view them as single tracks in Ensembl. The Ensembl code base itself is more accessible: it is now hosted on our GitHub organization page (https://github.com/Ensembl) under an Apache 2.0 open source license.
Chemical and Biological Oxidation of Thiophene:  Preparation and Complete Characterization of Thiophene S-Oxide Dimers and Evidence for Thiophene S-Oxide as an Intermediate in Thiophene Metabolism in Vivo and in Vitro (1997)

Direct evidence for the involvement of thiophene S-oxide as a key primary reactive intermediate in the metabolism of thiophene (1) in rats was obtained from the isolation of two diastereoisomeric thiophene S-oxide dimers, 4a and 4b, both in vitro (oxidation of thiophene with rat liver microsomes) and in vivo (isolation of 4a from rat urine). The structure of these dimers was established after an original preparation of identical samples by oxidation of thiophene with H2O2 and CF3COOH. In fact, the H2O2/CF3COOH system appeared to be the best oxidizing agent for the selective transformation of thiophene to its S-oxide. The complete determination of the structures of 4a and 4b was carried out for the first time by X-ray diffraction for the former and by a sequence of chemical reactions for the latter. The reported results indicate two fates for thiophene S-oxide in vivo: (i) its dimerization via a Diels−Alder reaction and (ii) its reaction with nucleophiles such as glutathione leading eventually to mercapturates. These results together with recent literature data on thiophene derivatives suggest that thiophene S-oxides, a class of reactive intermediates whose chemistry is still not well-known, could play a central role in the metabolism and toxic effects of thiophenes in mammals. This situation would be different from that observed in the metabolism of other aromatic compounds, such as benzene or furan, in which arene oxides are predominant intermediates.
Non‐specific host response markers in the differentiation between pneumococcal and viral pneumonia: What is the most accurate combination? (2004)

CRP, PCT, WBC and ESR have only limited value in differentiating pneumococcal or other bacterial pneumonia from viral pneumonia. If there was a high value in at least one of the markers (CRP > 80 mg/L, PCT > 1.8 microg/L, WBC > 22 x 10(9)/L or ESR > 60 mm/h), viral infections were rare. There was no combination of these markers which was sufficiently sensitive and specific to be used in clinical pediatric practice.
A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS (2018)

Erythropoiesis-stimulating agents are first choice for treating anemia in low-risk MDS. This double-blind, placebo-controlled study assessed the efficacy and safety of epoetin-α in IPSS low- or intermediate-1 risk (i.e., low-risk) MDS patients with Hb ≤ 10.0 g/dL, with no or moderate RBC transfusion dependence (≤4 RBC units/8 weeks). Patients were randomized, 2:1, to receive epoetin-α 450 IU/kg/week or placebo for 24 weeks, followed by treatment extension in responders. The primary endpoint was erythroid response (ER) through Week 24. Dose adjustments were driven by weekly Hb-levels and included increases, and dose reductions/discontinuation if Hb > 12 g/dL. An independent Response Review Committee (RRC) blindly reviewed all responses, applying IWG-2006 criteria but also considering dose adjustments, drug interruptions and longer periods of observation.A total of 130 patients were randomized (85 to epoetin-α and 45 to placebo). The ER by IWG-2006 criteria was 31.8% for epoetin-α vs 4.4% for placebo (p < 0.001); after RRC review, the ER was 45.9 vs 4.4% (p < 0.001), respectively. Epoetin-α reduced RBC transfusions and increased the time-to-first-transfusion compared with placebo.Thus, epoetin-α significantly improved anemia outcomes in low-risk MDS. IWG-2006 criteria for ER may require amendments to better apply to clinical studies.
Aspect-ratio and lateral-resolution enhancement in force microscopy by attaching nanoclusters generated by an ion cluster source at the end of a silicon tip (2011)

One of the factors that limit the spatial resolution in atomic force microscopy (AFM) is the physical size of the probe. This limitation is particularly severe when the imaged structures are comparable in size to the tip's apex. The resolution in the AFM is usually enhanced by using sharp tips with high aspect ratios. In the present paper we propose an approach to modify AFM tips that consists of depositing nanoclusters on standard silicon tips. We show that the use of those tips leads to atomic force microscopy images of higher aspect ratios and spatial resolution. The present approach has two major properties. It provides higher aspect-ratio images of nanoscale objects and, at the same time, enables to functionalize the AFM tips by depositing nanoparticles with well-controlled chemical composition.
Novel Hyaluronan‐Based Nanocarriers for Transmucosal Delivery of Macromolecules (2008)

The goal of this work was to design a new nanocarrier composed of the glycosaminoglycan hyaluronan and the polysaccharide chitosan, intended for the transmucosal delivery of macromolecules. The nanoparticles were characterized for their size and superficial charge. The incorporation of hyaluronan was verified by agarose gel electrophoresis and Fourier transform infrared (FT-IR) spectroscopy. The ability of the nanosystems to encapsulate macromolecules was studied taking the hydrophilic protein bovine serum albumin (BSA) and the hydrophobic polypeptide Cyclosporine A (CyA) as models. Results showed that the experimental conditions could be conveniently adjusted in order to modulate the physicochemical properties of the carriers and their composition. Moreover, the nanoparticles provided high association efficiencies of the selected macromolecules.
Alzheimer's disease. A double-labeling immunohistochemical study of senile plaques. (1988)

The senile plaque is one of the histopathologic changes that characterizes Alzheimer's disease and the aging brain. The histopathology of senile plaques was studied using double-labeling immunohistochemistry and lectin histochemistry with thioflavin S fluorescent microscopy in 9 cases of Alzheimer's disease, 2 nondemented elderly individuals, and 3 individuals with non-Alzheimer primary degenerative dementias. Every plaque that was visualized with thioflavin also had amyloid, but not all thioflavin-positive plaques contained neurites that could be recognized with specific monoclonal antibodies to paired helical filament, tau, or neurofilament epitopes. Some neurofilament-positive neurites were not visualized with thioflavin, but almost all tau-positive neurites were colabeled with thioflavin. Microglia were associated with most plaques. Most plaques were also surrounded by fibrous astrocytes. These results suggest that amyloid may be the common feature that defines senile plaques, but that other elements may be more specific for Alzheimer's disease, because extensive neuritic degeneration was seen only in Alzheimer brains and not in either nondemented elderly individuals with senile plaques or in non-Alzheimer dementia cases.