gebhart/patrepeval huggingface dataset:
N-Alkyl Urea Hydroxamic Acids as a New Class of Peptide Deformylase Inhibitors with Antibacterial Activity (2002)

Peptide deformylase (PDF) is a prokaryotic metalloenzyme that is essential for bacterial growth and is a new target for the development of antibacterial agents. All previously reported PDF inhibitors with sufficient antibacterial activity share the structural feature of a 2-substituted alkanoyl at the P(1)' site. Using a combination of iterative parallel synthesis and traditional medicinal chemistry, we have identified a new class of PDF inhibitors with N-alkyl urea at the P(1)' site. Compounds with MICs of <or=4 micro g/ml against gram-positive and gram-negative pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae, have been identified. The concentrations needed to inhibit 50% of enzyme activity (IC(50)s) for Escherichia coli Ni-PDF were <or=0.1 micro M, demonstrating the specificity of the inhibitors. In addition, these compounds were very selective for PDF, with IC(50)s of consistently >200 micro M for matrilysin and other mammalian metalloproteases. Structure-activity relationship analysis identified preferred substitutions resulting in improved potency and decreased cytotoxity. One of the compounds (VRC4307) was cocrystallized with PDF, and the enzyme-inhibitor structure was determined at a resolution of 1.7 A. This structural information indicated that the urea compounds adopt a binding position similar to that previously determined for succinate hydroxamates. Two compounds, VRC4232 and VRC4307, displayed in vivo efficacy in a mouse protection assay, with 50% protective doses of 30.8 and 17.9 mg/kg of body weight, respectively. These N-alkyl urea hydroxamic acids provide a starting point for identifying new PDF inhibitors that can serve as antimicrobial agents.
In vitro H2 utilization by a ruminal acetogenic bacterium cultivated alone or in association with an archaea methanogen is stimulated by a probiotic strain of Saccharomyces cerevisiae (1995)

The effects of a live strain of Saccharomyces cerevisiae on hydrogen utilization and acetate and methane production by two hydrogenotrophic ruminal microorganisms, an acetogenic bacterial strain and an archaea methanogen, were investigated. The addition of yeast cells enhanced by more than fivefold the hydrogenotrophic metabolism of the acetogenic strain and its acetate production. In the absence of yeasts, and in a coculture of the acetogen and the methanogen, hydrogen was principally used for methane synthesis, but the presence of live yeast cells stimulated the utilization of hydrogen by the acetogenic strain and enhanced acetogenesis.
Enzyme replacement therapy in mucopolysaccharidosis type I: Progress and emerging difficulties (2001)

Mucopolysaccharidosis type I is due to a deficiency of the lysosomal enzyme alpha-L-iduronidase (EC 3.2.1.76) and is associated with a defect in the catabolism of the glycosaminoglycans heparan and dermatan sulphate. The clinical picture produced by this abnormal storage is diverse and ranges from a disorder that is fatal in the early months of life, due to cardiomyopathy, to a condition compatible with a normal life-span. It has become usual to describe the phenotypes associated with this spectrum of disorders after their eponymous names, Hurler (MPS IH, severe), Scheie (MPS IS, mild) and Hurler/Scheie (MPS IH/S, intermediate). Severely affected patients have progressive learning difficulties, facial and skeletal deformities, cardiac disease, corneal clouding, respiratory compromise and joint stiffness. Patients with MPS IH typically die in the first decade of life. MPS IH/S usually have normal intelligence and die in their twenties of cardiorespiratory disease. Patients with MPS IS may have joint stiffness, aortic valve disease and corneal clouding, but are often able to live a normal life-span. Enzyme replacement therapy has been developed as a potential therapy for some patients with MPS I. This process has been helped by the study of a naturally occurring canine model of the disease, which produces a phenotype similar to MPS IH/S in the human. This review details the progress that has been made in this area and also highlights some potential problems with the introduction of therapy.
A Deep Learning Approach for Automotive Radar Interference Mitigation (2018)

In automotive systems, a radar is a key component of autonomous driving. Using transmit and reflected radar signal by a target, we can capture the target range and velocity. However, when interference signals exist, noise floor increases and it severely affects the detectability of target object. For these reasons, previous studies have been proposed to cancel interference or reconstruct original signals. However, the conventional signal processing methods for canceling the interference or reconstructing the transmits signal are difficult tasks, and also have many restrictions. In this work, we propose a novel approach to mitigate interference using deep learning. The proposed method provides high performance in various interference conditions and has low processing time. Moreover, we show that our proposed method achieves better performance compared to existing signal processing methods.
Comparison of Test Statistics for the Sequential Parallel Design (2010)

AbstractThe sequential parallel design has been proposed to improve the efficiency of clinical trials in psychiatry. The design randomizes patients into three treatment groups. Each group has two phases. The three groups are (1) placebo in the first phase followed by placebo in the second phase, (2) placebo in the first phase followed by drug in the second phase, and (3) drug in the first phase followed by drug in the second phase. We consider the case of binary response data. The analysis of data in the second phase of the trial is restricted to placebo patients who failed to respond in the first phase of the trial. A crucial element in the choice of test statistics is the underlying assumptions of treatment effect in the two phases of the trial. We develop various likelihood-based statistics when the treatment effect is different in the two phases and for the special case in which the treatment effect is equal in the two phases. These statistics are compared in simulation studies to determine their underlying null and nonnull behavior. The score test under the assumption of equal treatment effects is seen to have advantages in terms of Type I error and robustness to assumptions.Keywords: : Binary dataPlacebo responsePowerScore test
Role of non-compatible osmolytes in the stabilization of proteins during heat stress (1998)

This study is a systematic attempt to understand the roles of non-compatible osmolytes, i.e. solutes that have inhibitory effects on enzymes, in the stabilization of proteins against denaturing stress. Thermal denaturation of RNase A, holo-alpha-lactalbumin, apo-alpha-lactalbumin, lysozyme and metmyoglobin in the absence and presence of various concentrations of free basic amino acids was studied by observing changes in the absorption coefficients of these proteins. It has been observed that arginine and histidine destabilize all proteins in terms of the midpoint of the transition curve and Gibbs energy change on denaturation. Study of the heat-induced denaturation of the proteins in the presence of various concentrations of arginine at different pH values demonstrated that arginine binds to the denatured molecules. In contrast with the effect of arginine and histidine on protein stability, it was observed that the effect of lysine on proteins stability is unpredictable, i.e. it may have a stabilizing effect, no effect or a destabilizing effect on proteins during denaturing stress. The results of this study are considered from an evolutionary perspective.
Transposable Element Insertion and Epigenetic Modification Cause the Multiallelic Variation in the Expression of FAE1 in Sinapis alba (2014)

Naturally occurring heritable variation provides a fundamental resource to reveal the genetic and molecular bases of traits in forward genetic studies. Here, we report the molecular basis of the differences in the four alleles E<sup>1</sup>, E<sup>2</sup>, E<sup>3</sup>, and e of the FATTY ACID ELONGATION1 (FAE1) gene controlling high, medium, low, and zero erucic content in yellow mustard (Sinapis alba). E<sup>1</sup> represents a fully functional allele with a coding DNA sequence (CDS) of 1521 bp and a promoter adjacent to the CDS. The null allele e resulted from an insertional disruption in the CDS by Sal-PIF, a 3100-bp PIF/Harbinger-like DNA transposon, whereas E<sup>2</sup> and E<sup>3</sup> originated from the insertion of Sal-T1, a 4863-bp Copia-like retrotransposon, in the 5' untranslated region. E<sup>3</sup> was identical to E<sup>2</sup> but showed cytosine methylation in the promoter region and was thus an epiallele having a further reduction in expression. The coding regions of E<sup>2</sup> and E<sup>3</sup> also contained five single-nucleotide polymorphisms (SNPs) not present in E<sup>1</sup>, but expression studies in Saccharomyces cerevisiae indicated that these SNPs did not affect enzyme functionality. These results demonstrate a comprehensive molecular framework for the interplay of transposon insertion, SNP/indel mutation, and epigenetic modification influencing the broad range of natural genetic variation in plants.
A PLANE-SWEEP STRATEGY FOR THE 3D RECONSTRUCTION OF BUILDINGS FROM MULTIPLE IMAGES (2000)

A new method is described for automatically reconstructing a 3D piecewise planar model from multiple images of a scene. The novelty of the approach lies in the use of inter-image homographies to validate and best estimate planar facets, and in the minimal initialization requirements --- only a single 3D line with a textured neighbourhood is required to generate a plane hypothesis. The planar facets enable line grouping and also the construction of parts of the wireframe which were missed due to the inevitable shortcomings of feature detection and matching. The method allows a piecewise planar model of a scene to be built completely automatically, with no user intervention at any stage, given only the images and camera projection matrices as input. The robustness and reliability of the method are illustrated on several examples, from both aerial and interior views. 1 INTRODUCTION Automating reconstruction from images is one of the continuing goals in photogrammetry and computer vision...
Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family. (1995)

We have developed a PCR approach to clone new apoptotic Ced-3/Ice-like cysteine protease genes. This approach uses degenerate oligonucleotides encoding the highly conserved pentapeptides QACRG and GSWFI that are present in all known apoptotic cysteine proteases. Using this approach, we have cloned a novel apoptotic gene from human Jurkat T lymphocytes. The new gene encodes a approximately 34-kilodalton protein that is highly homologous to human CPP32, Caenorhabditis elegans cell death protein CED-3, mammalian Ich-1 (Nedd2), and mammalian interleukin-1 beta converting enzyme. Because of its high homology to the C. elegans Ced-3 gene, we named the new gene mammalian Ced-3 homologue Mch2. Two Mch2 transcripts (Mch2 alpha, 1.7 kb; Mch2 beta, 1.4 kb) were detected in Jurkat T lymphocytes and other cell lines. We believe that the Mch2 alpha transcript encodes the full-length Mch2, whereas the Mch2 beta transcript encodes a shorter Mch2 isoform, probably as a result of alternative splicing. Like interleukin-1 beta converting enzyme and CPP32, recombinant Mch2 alpha, but not Mch2 beta, possesses protease activity, as determined by its ability to cleave the fluorogenic peptide DEVD-AMC. CPP32 and Mch2 alpha can also cleave poly(ADP-ribose) polymerase in vitro, suggesting that these enzymes participate in poly(ADP-ribose) polymerase cleavage observed during cellular apoptosis. In addition, overexpression of recombinant Mch2 alpha, but not Mch2 beta, induces apoptosis in Sf9 insect cells. Our data suggest that Mch2 is a Ced-3/interleukin-1 beta converting enzyme-like cysteine protease and could be another important mediator of apoptosis in mammalian cells.
MUC5B is the prominent mucin in human gallbladder and is also expressed in a subset of colonic goblet cells (1998)

To elucidate the roles of human gallbladder mucin (HGBM), such as in gallstone formation and cytoprotection, it is essential to identify HGBM and study its expression. This was performed by metabolic labeling, Western blotting, immunohistochemistry, and RT-PCR. In a large number of individuals, antibodies against purified HGBM and against MUC5B detected a mucin precursor (approximately 470 kDa) in the gallbladder and colon, but not in the small intestine. In the gallbladder, Western blotting using specific anti-MUC5B antibodies showed that this mucin precursor represented an identical mucin, MUC5B. RT-PCR experiments demonstrated a similar tissue distribution pattern of MUC5B mRNA. Immunohistochemistry with anti-HGBM and anti-MUC5B showed staining in gallbladder epithelial cells and colonic goblet cells in the crypt base, but not in the small intestine; double labeling showed that HGBM was located in small granules within goblet cells, colocalizing to MUC2-containing goblet cells. Metabolic labeling demonstrated the secretion of mature MUC5B in the colon. Conclusively, MUC5B is identified as the prominent HGBM and is also expressed and secreted in the colon.
Siderophore-Mediated Iron Transport: Crystal Structure of FhuA with Bound Lipopolysaccharide (1998)

FhuA, the receptor for ferrichrome-iron in Escherichia coli, is a member of a family of integral outer membrane proteins, which, together with the energy-transducing protein TonB, mediate the active transport of ferric siderophores across the outer membrane of Gram-negative bacteria. The three-dimensional structure of FhuA is presented here in two conformations: with and without ferrichrome-iron at resolutions of 2.7 and 2.5 angstroms, respectively. FhuA is a beta barrel composed of 22 antiparallel beta strands. In contrast to the typical trimeric arrangement found in porins, FhuA is monomeric. Located within the beta barrel is a structurally distinct domain, the "cork," which mainly consists of a four-stranded beta sheet and four short alpha helices. A single lipopolysaccharide molecule is noncovalently associated with the membrane-embedded region of the protein. Upon binding of ferrichrome-iron, conformational changes are transduced to the periplasmic pocket of FhuA, signaling the ligand-loaded status of the receptor. Sequence homologies and mutagenesis data are used to propose a structural mechanism for TonB-dependent siderophore-mediated transport across the outer membrane.
Design and Development of Water-Soluble Curcumin Conjugates as Potential Anticancer Agents (2007)

Conjugates of curcumin to two differently sized poly(ethylene glycol) molecules were synthesized in an attempt to overcome the low aqueous solubility of this natural product with cytotoxic activity against some human cancer cell lines. The soluble conjugates exhibited enhanced cytotoxicity as compared to that of the parent drug. Synthesis, analyses of the rate of drug release, and cytotoxicity studies are herein reported. The water-soluble conjugates may provide information useful for the development of injectable curcumin conjugates.
Surface size, curvature analysis, and assessment of knee joint incongruity with MRI in vivo (2002)

Abstract The purpose of this study was to develop an MR‐based technique for quantitative analysis of joint surface size, surface curvature, and joint incongruity and to assess its reproducibility under in vivo imaging conditions. The surface areas were determined after 3D reconstruction of the joint by triangulation and the incongruity by Gaussian curvature analysis. The precision was tested by analyzing four replicated MRI datasets of human knees in 14 individuals. The algorithms were shown to produce accurate data in geometric test objects. The interscan precision was &lt;4% (CV%) for surface area, 2.9–5.7 m −1 (SD) for the mean principal curvature, and 4.1–7.4 m −1 for congruence indices. Incongruity was highest in the femoropatellar joint (79.7 m −1 ) and lowest in the medial femorotibial joint (28.6 m −1 ). This technique will permit identification of the specific role of surface size, curvature, and incongruity as potential risk factors for osteoarthritis. Magn Reson Med 47:554–561, 2002. © 2002 Wiley‐Liss, Inc.
Cell filtration‐laser scanning cytometry for the characterisation of circulating breast cancer cells (2003)

Cell filtration-LSC is a viable technique for detecting and studying breast carcinoma cells in peripheral blood.
Discovery of Indoles as Potent and Selective Inhibitors of the Deacetylase SIRT1 (2005)

High-throughput screening against the human sirtuin SIRT1 led to the discovery of a series of indoles as potent inhibitors that are selective for SIRT1 over other deacetylases and NAD-processing enzymes. The most potent compounds described herein inhibit SIRT1 with IC50 values of 60-100 nM, representing a 500-fold improvement over previously reported SIRT inhibitors. Preparation of enantiomerically pure indole derivatives allowed for their characterization in vitro and in vivo. Kinetic analyses suggest that these inhibitors bind after the release of nicotinamide from the enzyme and prevent the release of deacetylated peptide and O-acetyl-ADP-ribose, the products of enzyme-catalyzed deacetylation. These SIRT1 inhibitors are low molecular weight, cell-permeable, orally bioavailable, and metabolically stable. These compounds provide chemical tools to study the biology of SIRT1 and to explore therapeutic uses for SIRT1 inhibitors.
Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. Diabetic Ulcer Study Group. (1996)

Wound debridement is a vital adjunct in the care of patients with chronic diabetic foot ulcers.
CYANOBACTERIA AND CYANOLICHENS: CAN THEY ENHANCE AVAILABILITY OF ESSENTIAL MINERALS FOR HIGHER PLANTS? (1993)

(Uploaded by Plazi from the Biodiversity Heritage Library) No abstract provided.
Treating Poly(3-hexylthiophene) with Dimethylsulfate Improves Its Photoelectrical Properties (2008)

Poly(3-hexylthiophene) is reacted with the methylating agent dimethylsulfate. This increases the hole mobility, almost doubles the exciton diffusion length, and substantially enhances the photochemical stability of the polymer in air. The reaction may involve neutralization of anionic defects via addition of a methyl cation to the polymer backbone.
NF-κB Activation in Airways Modulates Allergic Inflammation but Not Hyperresponsiveness (2004)

Airways display robust NF-kappaB activation and represent targets for anti-inflammatory asthma therapies, but the functional importance of NF-kappaB activation in airway epithelium remains enigmatic. Therefore, transgenic mice were created in which NF-kappaB activation is repressed specifically in airways (CC10-IkappaBalpha(SR) mice). In response to inhaled Ag, transgenic mice demonstrated significantly ameliorated inflammation, reduced levels of chemokines, T cell cytokines, mucus cell metaplasia, and circulating IgE compared with littermate controls. Despite these findings, Ag-driven airways hyperresponsiveness was not attenuated in CC10-IkappaBalpha(SR) mice. This study clearly demonstrates that airway epithelial NF-kappaB activation orchestrates Ag-induced inflammation and subsequent adaptive immune responses, but does not contribute to airways hyperresponsiveness, the cardinal feature that underlies asthma.
Solubility Advantage of Pharmaceutical Cocrystals (2009)

Pharmaceutical cocrystals can improve solubility, dissolution, and bioavailability of poorly water soluble drugs. However, true cocrystal solubility is not readily measured for highly soluble cocrystals because they can transform to the most stable drug form in solution. The objectives of this study are to develop a method to estimate the cocrystal solubility in pure solvent and establish the influence of constituent drug and ligand (i.e., coformer) properties. Cocrystal solubility and solubility product were derived from transition concentration measurements where a solution is in equilibrium with solid drug and cocrystal. Transition concentrations and solubilities are reported for carbamazepine cocrystals in water, ethanol, isopropanol, and ethyl acetate. The aqueous solubility for seven carbamazepine cocrystals was estimated to be 2−152 times greater than the solubility of the stable carbamazepine dihydrate form. Cocrystal solubility is shown to be directly proportional to the solubility of constituent reactants for carbamazepine, caffeine, and theophylline cocrystals. The ligand transition concentration is also correlated with ligand solubility. Transition concentration measurements reveal drug solubilization by ligand for several of the cocrystals studied. The correlation established between constituent and cocrystal solubility was not effectively predicted by fusion properties of the various crystal forms considered.
Neural Network Analysis of Serial Cardiac Enzyme Data A Clinical Application of Artificial Machine Intelligence (1991)

There has been a recent resurgence of interest in the study and application of computerized neural networks within the broad field of artificial intelligence. These “intelligent machines” are modeled after biological nervous systems and are fundamentally different from the many computerized expert systems that previously have been introduced as clinical decision-making aids. The authors describe a neural network designed and trained to predict the probability of acute myocardial infarction (AMI) based on the analysis of paired sets of cardiac enzymes. The neural network predicted 24 of 24 (100%) AMIs and 27 of 29 (93%) No-AMIs when compared with a pathologist's interpretation of the patient's laboratory data (P < 0.000001). The authors attempted to validate the network's diagnoses b two independent methods. When compared with echocardiogram and EKG for diagnosis of AMI, theneural network agreed with the cardiologist's interpretation in 12 of 14 (86%) AMIs and 1 of 3 (33%) No-AMIs, but the correlation was not statistically significant. Using autopsy outcome for validation, the neural network agreed with the anatomic evidence in 24 of 26 (92%) AMIs and 4 of 6 (67%) No-AMIs (P = 0.001). The authors conclude that neural networks can be successfully applied to the analysis of cardiac enzyme data and suggest that broader applications exist within the domain of clinical decision support.
Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility (1997)

(MRSA) with reduced suscept-ibility to vancomycin (MIC 8 mg/L). The strain was isolated from a surgical wound infection which was refrac -tory to vancomycin therapy.In May 1996, a 4 month-old male infant underwent heartsurgery for pulmonary atresia. Two weeks followingsurgery, the infant became febrile and developed a purulent discharge from the sternal surgical incision site;culture of the purulent material yielded MRSA. The patientwas treated with vancomycin (45 mg/kg daily) for 29 days,but fever and discharge of pus continued, and the C-reactive protein (CRP) remained elevated (40 mg/L). Thetreatment was changed to a combination of vancomycin andarbekacin (an aminoglycoside approved for MRSA infec-tion in Japan). After 12 days of this regimen, the purulentdischarge subsided, the wound began to heal, and the CRPdeclined from 40 to 9 mg/L. The antimicrobial therapy wasdiscontinued. However, 12 days later the surgical siteappeared inﬂamed with the development of a subcutaneousabscess accompanied by a sudden onset of fever and a raised CRP level of 35 mg/L. Therapy was resumed with the com -bination of arbekacin and ampicillin/sulbactam which hasbeen shown to have synergic activity against MRSA.