gebhart/patrepeval huggingface dataset:
A Knowledge-Based Approach in Designing Combinatorial or Medicinal Chemistry Libraries for Drug Discovery. 1. A Qualitative and Quantitative Characterization of Known Drug Databases (1998)

The discovery of various protein/receptor targets from genomic research is expanding rapidly. Along with the automation of organic synthesis and biochemical screening, this is bringing a major change in the whole field of drug discovery research. In the traditional drug discovery process, the industry tests compounds in the thousands. With automated synthesis, the number of compounds to be tested could be in the millions. This two-dimensional expansion will lead to a major demand for resources, unless the chemical libraries are made wisely. The objective of this work is to provide both quantitative and qualitative characterization of known drugs which will help to generate "drug-like" libraries. In this work we analyzed the Comprehensive Medicinal Chemistry (CMC) database and seven different subsets belonging to different classes of drug molecules. These include some central nervous system active drugs and cardiovascular, cancer, inflammation, and infection disease states. A quantitative characterization based on computed physicochemical property profiles such as log P, molar refractivity, molecular weight, and number of atoms as well as a qualitative characterization based on the occurrence of functional groups and important substructures are developed here. For the CMC database, the qualifying range (covering more than 80% of the compounds) of the calculated log P is between -0.4 and 5.6, with an average value of 2.52. For molecular weight, the qualifying range is between 160 and 480, with an average value of 357. For molar refractivity, the qualifying range is between 40 and 130, with an average value of 97. For the total number of atoms, the qualifying range is between 20 and 70, with an average value of 48. Benzene is by far the most abundant substructure in this drug database, slightly more abundant than all the heterocyclic rings combined. Nonaromatic heterocyclic rings are twice as abundant as the aromatic heterocycles. Tertiary aliphatic amines, alcoholic OH and carboxamides are the most abundant functional groups in the drug database. The effective range of physicochemical properties presented here can be used in the design of drug-like combinatorial libraries as well as in developing a more efficient corporate medicinal chemistry library.
Intestinal glucose sensing and regulation of intestinal glucose absorption (2007)

SGLT1 (Na(+)/glucose co-transporter 1) transports the dietary sugars, D-glucose and D-galactose, from the lumen of the intestine into enterocytes. SGLT1 regulation has important consequences for the provision of glucose to the respiring tissues and is therefore essential for maintaining glucose homoeostasis. SGLT1 expression is directly regulated in response to changes in the sugar content of the diet. To monitor these variations, there is a requirement for a glucose-sensing system located on the luminal membrane of gut cells. This short review focuses on recent findings on intestinal sugar sensing and the downstream mechanisms responsible for enhancement in SGLT1 expression.
Electrochemical DNA Hybridization Biosensors (2002)

The many different approaches in which electrochemical methods are used to detect DNA hybridization, as the basis of a DNA biosensors, are reviewed. Transduction of the hybridization event can be divided into two broad classes, approaches where a redox active species is used as a label and those where changes in the DNA interface are monitored electrochemically without the use of any labels. Important criteria in fabricating the DNA recognition interface on an electrode and future challenges are also discussed.
Mass Resolution Improvement by Incorporation of Pulsed Ion Extraction in a Matrix-Assisted Laser Desorption/Ionization Linear Time-of-Flight Mass Spectrometer (1995)

A linear time-of-flight mass spectrometer has been modified to incorporate pulsed ion extraction of matrix-assisted laser desorption/ionization (MALDI) generated ions. A unique aspect of the experiments presented is the combination of pulsed extraction with very high source potentials (up to 25 kV) which allows improved mass resolution while maintaining excellent sensitivity for the large m/z ions generated by the MALDI technique. Mass resolution in excess of 1000 (fwhm) is demonstrated for cytochrome c (12,361.1 Da) with the pulsed ion extraction linear time-of-flight mass spectrometer described. The influence on obtainable mass resolution of experimental variables such as delay time between laser ionization and ion extraction, amplitude of the pulsed voltage employed, and the source bias voltage are presented. It is shown that, for any given source potential, the optimum pulsed extraction voltage is a linear function of the mass of the analyte. This is consistent with the observation that the initial ion velocity distribution for MALDI-generated ions is independent of mass.
A Complete U-V-Disparity Study for Stereovision Based 3D Driving Environment Analysis (2005)

Reliable understanding of the 3D driving environment is vital for obstacle detection and adaptive cruise control (ACC) applications. Laser or millimeter wave radars have shown good performance in measuring relative speed and distance in a highway driving environment. However the accuracy of these systems decreases in an urban traffic environment as more confusion occurs due to factors such as parked vehicles, guardrails, poles and motorcycles. A stereovision based sensing system provides an effective supplement to radar-based road scene analysis with its much wider field of view and more accurate lateral information. This paper presents an efficient solution using a stereovision based road scene analysis algorithm which employs the "U-V-disparity" concept. This concept is used to classify a 3D road scene into relative surface planes and characterize the features of road pavement surfaces, roadside structures and obstacles. Real-time implementation of the disparity map calculation and the "U-V-disparity" classification is also presented.
Antibodies against the major brain isofbrms of 14‐3‐3 protein (1993)

14-3-3 proteins are apparently ubiquitous eukaryotic proteins that comprise a large number of isoforms. They have been implicated in the regulation of a wide range of biological processes [reviewed in Aitken et al. (1992) Trends Biochem. Sci. 17, 498-501]. We have raised specific antibodies against each mammalian brain isoform of 14-3-3 employing peptides synthesised from the amino-terminal regions. The peptides were, like the proteins from mammalian brain, N-acetylated. The antiserum specific for the epsilon isoform did not recognise the recombinant form of this protein (lacking the N-acetyl co-translational modification) expressed in E. coli until it was chemically acetylated.
Dietary Intake, Food Composition and Nutrient Intake in Wild and Captive Populations of Daubentonia madagascariensis (1994)

Data are presented on dietary and nutrient intake in a wild population of aye-ayes. Study animals ate 4 main food types: seeds, nectar, fungus and insect larvae. Calculated calorie intake was slightly lower during the cold season than during the hot, wet and the hot, dry seasons. Total intakes almost doubled to compensate for the lower energy content of the diet during the cold season. Comparison of natural and captive diets suggests that maintenance and even growth requirements of aye-ayes can be met by relatively low-fat, low-protein diets. Daily energy requirements were estimated to average about 280 kcal metabolizable energy/day. Animals in the wild were estimated to eat between 260 and 342 kcal, while captive animals consumed 260 kcal/day.
The calcineurin/NFAT signaling pathway: A NOVEL therapeutic target in leukemia and solid tumors (2008)

The calcineurin/NFAT signaling pathway is unique to vertebrates and clear genetic evidences show that it plays critical roles in orchestrating the intricate cellular interactions that characterize vertebrate development and morphogenesis. In this setting, the transcriptional regulators of the NFAT family function as molecular integrators of specific calcium signals with other signaling pathways, including MAPkinase, WNT or NOTCH. Deregulation of calcineurin/NFAT signaling and/or abnormal expression of its components have recently been reported in solid tumors of epithelial origin, lymphoma and lymphoid leukemia. Our studies in mouse models of human T-ALL/lymphoma shows that persistent activation of calcineurin/NFAT signaling is pro-oncogenic in vivo and can be efficiently targeted by well-characterized calcineurin inhibitors. We further discuss facts and hypotheses concerning the molecular events that may act upstream and downstream of calcineurin and/or NFAT activation in different type of cancer cells.
Synthesis and Characterization of Two Novel Lanthanide Coordination Polymers with an Open Framework Based on an Unprecedented [Ln7(μ3-OH)8]13+ Cluster (2004)

Two novel heptanuclear lanthanide clusters of the dicubane-like type [Ln(7)(micro(3)-OH)(8)](13+) (Ln = Ho (1), Yb (2)) were obtained via hydrothermal reaction, and as building blocks, they were formally assembled into porous three-dimensional networks through the linkage of 1,4-naphthalenedicarboxylate (1,4-NDA), forming first examples of porous lanthanide polymers with 1,4-NDA, [Ln(7)(micro(3)-OH)(8)(1,4-NDA)(6)(OH)(0.5)(Ac)(0.5)(H(2)O)(7)].4H(2)O (Ln = Ho, Yb). The coordinating water molecules and lattice water molecules are enclathrated in the cavities.
Cutting Edge: DC-SIGN; a Related Gene, DC-SIGNR; and CD23 Form a Cluster on 19p13 (2000)

DC-SIGN is a C-type lectin, expressed on a dendritic cell subset. It is able to bind ICAM3 and HIV gp120 in a calcium-dependent manner. Here we report the genomic organization of DC-SIGN and map it to chromosome 19p13 adjacent to the C-type lectin CD23 (FcepsilonRII). We also report a novel, closely linked gene, DC-SIGNR, which shows 73% identity to DC-SIGN at the nucleic acid level and a similar genomic organization. Proteins encoded by both genes have tracts of repeats of 23 aa, predicted to form a coiled coil neck region. They also possess motifs that are known to bind mannose in a calcium-dependent fashion. We show concomitant expression of the two genes in endometrium, placenta, and stimulated KG1 cells (phenotypically similar to monocyte-derived dendritic cells). The existence of a DC-SIGN-related gene calls for reinterpretation of the HIV data to consider possible DC-SIGN/DC-SIGNR hetero-oligomerization.
Identification of a Site on Mannan-binding Lectin Critical for Enhancement of Phagocytosis (2001)

Mannan-binding lectin (MBL) constitutes an important part of the human innate immune defense system. It has been shown to mediate the activation of complement upon binding to specific microbial carbohydrate motifs, to directly opsonize organisms, and to enhance the phagocytosis of targets suboptimally opsonized with IgG or complement components C3b or C4b. This enhancement of phagocytic activity induced by MBL and other molecules that contain a collagen-like region contiguous with a pattern recognition domain is mediated by a 126,000 M(r) surface glycoprotein, designated C1qR(P). Although it has been known that the collagen-like domain of these "defense collagens" contains the interaction site(s) that triggers this enhancement of uptake, the specific interaction site has not been identified. To address this issue, wild type and mutant MBL constructs were generated, inserted into baculovirus, expressed in Sf9 cells, and the recombinant MBL (rMBL) proteins purified by mannan affinity chromatography. The effect of wild type and mutant rMBL on the phagocytosis of targets suboptimally opsonized with IgG or with IgM and C4b by human peripheral blood monocytes was then assessed. Two mutants, one of which has five GXY triplets deleted below the kink region of MBL and the other one having only two of the GXY triplets deleted below the kink, failed to enhance phagocytosis, suggesting the importance of the specific sequence GEKGEP in stimulating phagocytic activity. Similar sequences were detected in other defense collagens, implicating the consensus motif GE(K/Q/R)GEP as critical in mediating the enhancement of phagocytosis through C1qR(P.) Clarification of specific ligand-C1qR(P) interactions should facilitate the investigation of the signal transduction processes involved in the cell activation, as well as provide the basis for the design of specific modulators of the functions mediated by this receptor.
RENAL CELL CARCINOMA 2005: NEW FRONTIERS IN STAGING, PROGNOSTICATION AND TARGETED MOLECULAR THERAPY (2005)

Staging systems for RCC serve as a valuable prognostic tool. Several new patient and tumor characteristics have been reported to be important prognostic factors and they have been integrated into current staging systems. In addition, the field of RCC is rapidly undergoing a revolution led by molecular markers and targeted therapies. With this information urologists will be updated with the most current and comprehensive staging strategies, and be provided with a glimpse of the molecular and patient specific staging and treatment paradigms that will in our opinion transform the future management of this malignancy.
Immunohistochemical Characterization of the Cellular Infiltration in Asthmatic Bronchi (1992)

Bronchial biopsies obtained from 16 asthmatic patients and six normal subjects were analyzed by immunohistochemistry. In the asthmatic patients, the total numbers of macrophages infiltrating the airway mucosa were increased. Many of the macrophages had the phenotypic characteristics of blood monocytes. HLA Class II antigen was expressed on infiltrating cells and airway epithelial cells. In biopsies from the asthmatics there was a significant increase in activated eosinophils, but not in neutrophils. There was also a significant increase in the numbers of T-lymphocytes in the asthmatics, but very few B-lymphocytes were detected. These results suggest that lung macrophages may have a central role to play in the mechanisms of the chronic immune-mediated inflammatory response seen in the airway mucosa of asthmatic patients.
Dopamine differentiation factors increase striatal dopaminergic function in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐lesioned mice (1996)

We have previously shown that muscle-derived differentiation factors (MDF) and human recombinant acidic fibroblast growth factor (aFGF) have beneficial behavioral and neurochemical effects on the nigrostriatal dopaminergic neurons of 6-hydroxy-dopamine (6-OHDA)-lesioned rats (Jin and Iacovitti: Neurobiol Dis 2:1–12, 1995). In the present study, we determined the effects of similar treatments on mice treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Five days after unilateral striatal infusion of MDF or aFGF into MPTP-lesioned mice, striatal tyrosine hydroxylase (TH) activity and dihydroxyphenylacetic acid (DOPAC) levels were bilaterally increased (20–35%) compared to untreated (lesion only) or control (phosphate buffered saline + bovine serum albumin) mice. These increases, however, were not accompanied by change in dopamine (DA) levels, indicating an elevation of DA synthesis (TH/DA) and turnover (DOPAC/DA). The present findings that MDF and aFGF may have neurochemical effects in vivo on the lesioned nigrostriatal dopaminergic system suggest their potential pharmacological role in the treatment of Parkinson's disease. © 1996 Wiley-Liss, Inc.
Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects (2005)

Obesity is associated with low-grade inflammation, insulin resistance, type 2 diabetes, and cardiovascular disease. This study investigated the effect of a 15-wk lifestyle intervention (hypocaloric diet and daily exercise) on inflammatory markers in plasma, adipose tissue (AT), and skeletal muscle (SM) in 27 severely obese subjects (mean body mass index: 45.8 kg/m2). Plasma samples, subcutaneous abdominal AT biopsies, and vastus lateralis SM biopsies were obtained before and after the intervention and analyzed by ELISA and RT-PCR. The intervention reduced body weight (P < 0.001) and increased insulin sensitivity (homeostasis model assessment; P < 0.05). Plasma adiponectin (P < 0.001) increased, and C-reactive protein (P < 0.05), IL-6 (P < 0.01), IL-8 (P < 0.05), and monocyte chemoattractant protein-1 (P < 0.01) decreased. AT inflammation was reduced, determined from an increased mRNA expression of adiponectin (P < 0.001) and a decreased expression of macrophage-specific markers (CD14, CD68), IL-6, IL-8, and tumor necrosis factor-alpha (P < 0.01). After adjusting for macrophage infiltration in AT, only IL-6 mRNA was decreased (P < 0.05). Only very low levels of inflammatory markers were found in SM. The intervention had no effect on adiponectin receptor 1 and 2 mRNA in AT or SM. Thus hypocaloric diet and increased physical activity improved insulin sensitivity and reduced low-grade inflammation. Markers of inflammation were particularly reduced in AT, whereas SM does not contribute to this attenuation of whole body inflammation.
Potential for a novel manganese porphyrin compound as adjuvant canine lymphoma therapy (2017)

We obtained critical information regarding the PK and toxicity of MnBuOE in dogs. The acute drug reaction and tachycardia post-injection have not been described in other species and may be specific to canines. The high tissue drug levels in lymph nodes have not been previously reported. MnBuOE accumulation in lymph nodes has important implications for the utility of adjuvant MnBuOE to treat lymphoma. With MnBuOE lymph node accumulation, reduction in the dose and/or administration frequency could be possible, leading to reduced toxicity.
The YEASTRACT database: an upgraded information system for the analysis of gene and genomic transcription regulation inSaccharomyces cerevisiae (2013)

The YEASTRACT (http://www.yeastract.com) information system is a tool for the analysis and prediction of transcription regulatory associations in Saccharomyces cerevisiae. Last updated in June 2013, this database contains over 200,000 regulatory associations between transcription factors (TFs) and target genes, including 326 DNA binding sites for 113 TFs. All regulatory associations stored in YEASTRACT were revisited and new information was added on the experimental conditions in which those associations take place and on whether the TF is acting on its target genes as activator or repressor. Based on this information, new queries were developed allowing the selection of specific environmental conditions, experimental evidence or positive/negative regulatory effect. This release further offers tools to rank the TFs controlling a gene or genome-wide response by their relative importance, based on (i) the percentage of target genes in the data set; (ii) the enrichment of the TF regulon in the data set when compared with the genome; or (iii) the score computed using the TFRank system, which selects and prioritizes the relevant TFs by walking through the yeast regulatory network. We expect that with the new data and services made available, the system will continue to be instrumental for yeast biologists and systems biology researchers.
A second-generation system for unbiased reading frame selection (2004)

Reading frame selection of nucleic acids has important implications for protein engineering and genomics. Current methods are limited because selection of the gene of interest inevitably depends on the solubility of its translated product. Here we report the construction of the pInSALect vector, which provides strict reading frame selection without concomitant selection for protein solubility or folding. This plasmid incorporates the cis-splicing VMA intein sequence from Saccharomyces cerevisiae to facilitate the post-translational self-excision of the protein of interest, thereby eliminating potential aggregation problems. Results from two libraries of chimeric glycinamide ribonucleotide formyltransferases confirm the superior performance of pInSALect over existing reading frame selection systems.
Emerging trends in the WWW user population (1996)

AST amounts of attention and resources have recently been devoted toward the World-Wide Web (WWW) With the goals of understanding the Web user population and promoting the Web as a viable surveying medium, the WWW User Surveys were initially conducted by Georgia Institute of Technology's Graphics, Visualization, and Usability Center during January 1994. Subsequent surveys have been administered approximately every six months thereafter. Each survey is conducted for one month using the limited interactivity of the Web, where users point and click on responses within their Web browsers and submit results to a centralized server for processing.
The Soluble α Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer (2008)

Interleukin (IL)-15 is a proinflammatory cytokine, as it induces the production of inflammatory cytokines [IL-6, tumor necrosis factor alpha (TNFalpha), IL-17, etc.]. A correlation between high intratumoral IL-15 concentrations and poor clinical outcome in lung and head and neck cancer patients has been recently reported. The purpose of this study was to investigate the role of the soluble alpha chain of IL-15 receptor (sIL-15Ralpha), a natural regulator of IL-15, in head and neck cancer. Fifty-three newly diagnosed untreated head and neck cancer patients were included in this study. Quantification of sIL-15Ralpha was performed with a newly developed RIA. Increased serum sIL-15Ralpha concentrations were found in head and neck cancer patients and were closely correlated with poor clinical outcome both in terms of locoregional control and survival even on multivariate analysis. sIL-15Ralpha was mainly produced by tumor cells via proteolytic cleavage of IL-15Ralpha mediated by ADAM-17. A correlation was observed between ADAM-17 expression in tumor cells and serum sIL-15Ralpha concentrations. Surprisingly, sIL-15Ralpha did not act in vitro as an IL-15 antagonist but rather as an enhancer of IL-15-induced proinflammatory cytokines (IL-6, TNFalpha, and IL-17) that may promote tumor progression. This new tumor evasion mechanism based on amplification of the intratumoral inflammatory reaction is probably not restricted to head and neck cancer, as other tumors have been shown to release sIL-15Ralpha. Overall, these results support for the first time an original protumor role of sIL-15Ralpha in cancer.
WebLogic event server (2008)

This paper describes WebLogic Event Server (WL EvS), an application server designed for hosting event-driven applications that require low latency and deterministic behavior. WL EvS is based on a modular architecture in which both server components and applications are represented as modules. The application programming model supports applications that are a mixture of reusable Java components and EPL (Event Processing Language), a query language that extends SQL with stream processing capabilities. WL EvS applications are meta-data driven, in that application behavior can be changed without recompilation or redeploying an application. The paper also presents the results of a benchmark performance study. The results show that the approach used by WL EvS can handle extremely high volumes of events while providing deterministic latency.