gebhart/patrepeval huggingface dataset:
Preventive effect of an oral prostacyclin analog, beraprost sodium, on digital necrosis in systemic sclerosis. French Microcirculation Society Multicenter Group for the Study of Vascular Acrosyndromes. (1999)

Our study suggests that oral beraprost sodium may benefit patients with SSc. Such patients, especially those with distal SSc, tend to have fewer recurrent ischemic digital ulcerations in winter, and the onset of their ulceration is delayed.
Antagonistic effect of insulin-like growth factor I on protein kinase inhibitor—mediated apoptosis in human glioblastoma cells in association with bcl-2 and bcl-x-L (1998)

Because many gliomas secrete large amounts of IGF-I in autocrine/paracrine growth pathways, these data may, in part, explain the failure of TAM to achieve clinical results as dramatic as those in vitro.
Identification of allosteric inhibitors of the ecto-5'-nucleotidase (CD73) targeting the dimer interface (2018)

The ecto-5'-nucleotidase CD73 plays an important role in the production of immune-suppressive adenosine in tumor micro-environment, and has become a validated drug target in oncology. Indeed, the anticancer immune response involves extracellular ATP to block cell proliferation through T-cell activation. However, in the tumor micro-environment, two extracellular membrane-bound enzymes (CD39 and CD73) are overexpressed and hydrolyze efficiently ATP into AMP then further into immune-suppressive adenosine. To circumvent the impact of CD73-generated adenosine, we applied an original bioinformatics approach to identify new allosteric inhibitors targeting the dimerization interface of CD73, which should impair the large dynamic motions required for its enzymatic function. Several hit compounds issued from virtual screening campaigns showed a potent inhibition of recombinant CD73 with inhibition constants in the low micromolar range and exhibited a non-competitive inhibition mode. The structure-activity relationships studies indicated that several amino acid residues (D366, H456, K471, Y484 and E543 for polar interactions and G453-454, I455, H456, L475, V542 and G544 for hydrophobic contacts) located at the dimerization interface are involved in the tight binding of hit compounds and likely contributed for their inhibitory activity. Overall, the gathered information will guide the upcoming lead optimization phase that may lead to potent and selective CD73 inhibitors, able to restore the anticancer immune response.
Evaluation of the efficacy of 3% citronella candles and 5% citronella incense for protection against field populations of Aedes mosquitoes. (1996)

We assessed the efficacy of 3% citronella candles and 5% citronella incense in protecting subjects from bites of Aedes spp. under field conditions. The study was conducted in a deciduous woodlot in Guelph, Ontario, Canada from July 26 to August 10, 1995. Eight subjects, dressed identically, were assigned to one of 8 positions on a grid within the study area. Two citronella candles, 2 citronella incense, 2 plain unscented candles, or no candles (i.e., nontreated controls) were assigned to 2 positions on the grid each evening. Subjects conducted 5-min biting counts at each position and performed 16 biting counts per evening. On average, subjects received 6.2 +/- 0.4, 8.2 +/- 0.5, 8.2 +/- 0.4, and 10.8 +/- 0.5 bites/ 5 min at positions with citronella candles, citronella incense, plain candles, and no candles, respectively. Although significantly fewer bites were received by subjects at positions with citronella candles and incense than at nontreated locations, the overall reduction in bites provided by the citronella candles and incense was only 42.3 and 24.2%, respectively.
ChemInform Abstract: SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF HIGH ALKYL BARBITURIC ACIDS (1981)

Abstract Cyclopropylmethylbromid (I) wird mit dem Decylmalonsäureester (II) zum disubstituierten Diester (III) substituiert.
Genome sequence of the lignocellulose-bioconverting and xylose-fermenting yeast Pichia stipitis (2007)

Xylose is a major constituent of plant lignocellulose, and its fermentation is important for the bioconversion of plant biomass to fuels and chemicals. Pichia stipitis is a well-studied, native xylose-fermenting yeast. The mechanism and regulation of xylose metabolism in P. stipitis have been characterized and genes from P. stipitis have been used to engineer xylose metabolism in Saccharomyces cerevisiae. We have sequenced and assembled the complete genome of P. stipitis. The sequence data have revealed unusual aspects of genome organization, numerous genes for bioconversion, a preliminary insight into regulation of central metabolic pathways and several examples of colocalized genes with related functions. The genome sequence provides insight into how P. stipitis regulates its redox balance while very efficiently fermenting xylose under microaerobic conditions.
CD1d Ligands: The Good, the Bad, and the Ugly (2006)

The MHC class I-like CD1d glycoprotein is a member of the CD1 family of Ag-presenting molecules and is responsible for the selection of NKT cells. A number of ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells have been identified. These include glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules. The presentation of many of these molecules can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer or can be deleterious. This review will highlight these ligands in a discussion of their potential use against (and role in the pathogenesis of) these diseases.
THEORY AND PRACTICE OF NUCLEAR SPIN RELAXATION IN PROTEINS (1996)

NMR relaxation experiments can provide information on overall and internal motions in proteins. This review consists of a concise report on the evolution of the theories for nuclear relaxation followed by an overview of mathematical models for internal motions in proteins. Next, the method of spectral density mapping with recent developments is reviewed. This is followed by a discussion of pulse sequences for relaxation experiments. Finally, we review recent studies correlating relaxation parameters, in particular spectral density functions, with structural features of proteins and with results of molecular dynamics simulations.
Clinical Data on the CGRP Antagonist BIBN4096BS for Treatment of Migraine Attacks (2006)

Basal studies have shown that calcitonin gene-related peptide (CGRP) is a major sensory neuronal messenger in the trigeminovascular system, the pathway conveying intracranial pain. In migraine and cluster headache attacks, CGRP is released in parallel with the pain and successful treatment of the attacks abort both the associated pain and the CGRP release. The search for a potent small molecule CGRP antagonist has been successful and such an agent has been tested in preclinical and clinical studies. The aim of the present study was to examine current knowledge on the clinical pharmacology of systemic BIBN4096BS, which has been shown in man to abort acute migraine attacks as well or better than oral sumatriptan. BIBN4096BS is a specific and potent CGRP receptor antagonist in humans. In safety and tolerability studies the substance is well tolerated with no or only mild side effects. In acute migraine attacks the overall response was 66% with the drug and 27% with placebo. A difference as compared to placebo was seen at 30 min; the response was still rising at 4 h suggesting a long duration of action. At 24 h the pain-free rate was better than that with triptans, suggesting a lower grade of rebound and perhaps even a prophylactic possibility.
Purification and Characterization of Hypoxia-inducible Factor 1 (1995)

Hypoxia-inducible factor 1 (HIF-1) is a DNA-binding protein that activates erythropoietin (Epo) gene transcription in Hep3B cells subjected to hypoxia or cobalt chloride treatment. HIF-1 DNA binding activity is also induced by hypoxia or cobalt in non-Epo-producing cells, suggesting a general role for HIF-1 in hypoxia signal transduction and transcriptional regulation. Here we report the biochemical purification of HIF-1 from Epo-producing Hep3B cells and non-Epo-producing HeLa S3 cells. HIF-1 protein was purified 11,250-fold by DEAE ion-exchange and DNA affinity chromatography. Analysis of HIF-1 isolated from a preparative gel shift assay revealed four polypeptides. Peptide mapping of these HIF-1 components demonstrated that 91-, 93-, and 94-kDa polypeptides had similar tryptic maps, whereas the 120-kDa polypeptide had a distinct profile. Glycerol gradient sedimentation analysis suggested that HIF-1 exists predominantly in a heterodimeric form and to a lesser extent as a heterotetramer. Partially purified HIF-1 bound specifically to the wild-type HIF-1 binding site from the EPO enhancer but not to a mutant sequence that lacks hypoxia-inducible enhancer activity. UV cross-linking analysis with purified HIF-1 indicated that both subunits of HIF-1 contact DNA directly. We conclude that in both cobalt chloride-treated HeLa cells and hypoxic Hep3B cells HIF-1 is composed of two different subunits: 120-kDa HIF-1 alpha and 91-94-kDa HIF-1 beta.
Identification of platelet-activating factor receptors in P388D1 murine macrophages. (1988)

Platelet-activating factor (PAF) binding and metabolism by eight murine and human cell lines was analyzed. Only the murine P388D1 macrophage line had specific, high affinity PAF binding sites. PAF binding reached saturation within 10 min at room temperature and was irreversible. Minimal PAF metabolism was observed at the time binding saturation was achieved. Scatchard analysis of PAF binding revealed a single class of PAF receptors (7872 +/- 1310/cell) which had a dissociation constant of 0.08 +/- 0.01 nM (mean +/- SEM, eta = 6). The dissociation constant was confirmed independently by quantifying the kinetics of initial specific PAF binding. PAF binding was stereospecific, required an sn-2 acetyl substituent, and was inhibited by structurally diverse PAF antagonists including kadsurenone, BN 52021, triazolam, and CV3988. The fact that the receptors are functionally active was shown by the observation that 1 to 100 pM PAF increased free intracellular calcium in P388D1 cells in a dose-related manner. These studies demonstrate that P388D1 macrophages have functional PAF receptors whose affinity and structural specificities are similar to PAF receptors in other cells. The availability of a stable cell line that binds but does not metabolize PAF will greatly facilitate studies of the PAF receptor.
Endogenous Antioxidant Activities in Relation to Concurrent Vitamins A, C, and E Intake in Dementia (2002)

Previous reports on the activities of essential endogenous antioxidants such as superoxide dismutase, catalase, and glutathione in dementia patients have not included a simultaneous quantitative assessment of dietary antioxidant intake. This is important because the reported differences in endogenous antioxidant levels among dementia patients may have reflected variations in the total antioxidants' intake. In this study we measured the levels of antioxidant vitamins A, C, and E in the diet of 81 dementia patients and controls at the same time as assessing blood levels of three endogenous antioxidants. Results showed a significant decrease in the intake of vitamins C (p < .001) and E (p < .01) in patients with severe Alzheimer's disease (AD) when compared to controls. Patients with mild/moderate AD differed from controls only in the intake of vitamin C (p < .01). The blood levels of catalase but not superoxide dismutase and glutathione were significantly decreased in the patients with severe AD when compared to controls (p < .01), patients with mild/moderate AD (p < .0 1), and patients with dementia with Lewy bodies (p < .05). The blood catalase levels of dementia patients, as a whole, were significantly and positively associated with the intake of vitamins A (p < .05), C (p < .01), and E (p < .05). The results indicated that dietary intake of vitamins A, C, and E may influence blood levels of catalase possibly through their antioxidant effects on free radicals. The data underscore the importance of concurrent quantitative assessment of nutritional intake when measuring endogenous antioxidant activities and support a role for antioxidant supplementation in the treatment of dementia disorders.
IES3: a fast integral equation solver for efficient 3-dimensional extraction (1997)

Integral equation techniques are often used to extract models of integrated circuit structures. This extraction involves solving a dense system of linear equations, and using direct solution methods is prohibitive for large problems. In this paper, we present IES/sup 3/ (pronounced ice cube), a fast Integral Equation Solver for three-dimensional problems with arbitrary kernels. Extraction methods based on IES/sup 3/ are substantially more efficient than existing multipole-based approaches.
Overexpression ofmarA, soxS, oracrABproduces resistance to triclosan in laboratory and clinical strains ofEscherichia coli (1998)

Triclosan (Irgasan) is a broad spectrum antimicrobial agent used in handsoaps, toothpastes, fabrics, and plastics. It inhibits lipid biosynthesis in Escherichia coli, probably by action upon enoyl reductase (FabI) (McMurry, L.M., Oethinger, M. and Levy, S.B. (1988) Nature 394, 531-532). We report here that overexpression of the multidrug efflux pump locus acrAB, or of marA or soxS, both encoding positive regulators of acrAB, decreased susceptibility to triclosan 2-fold. Deletion of the acrAB locus increased the susceptibility to triclosan approximately 10-fold. Four of five clinical E. coli strains which overexpressed marA or soxS also showed enhanced triclosan resistance. The acrAB locus was involved in the effects of triclosan upon both cell growth rate and cell lysis.
Mutations of Chromosome 5q21 Genes in FAP and Colorectal Cancer Patients (1991)

Previous studies suggested that one or more genes on chromosome 5q21 are responsible for the inheritance of familial adenomatous polyposis (FAP) and Gardner's syndrome (GS), and contribute to tumor development in patients with noninherited forms of colorectal cancer. Two genes on 5q21 that are tightly linked to FAP (MCC and APC) were found to be somatically altered in tumors from sporadic colorectal cancer patients. One of the genes (APC) was also found to be altered by point mutation in the germ line of FAP and GS patients. These data suggest that more than one gene on chromosome 5q21 may contribute to colorectal neoplasia, and that mutations of the APC gene can cause both FAP and GS. The identification of these genes should aid in understanding the pathogenesis of colorectal neoplasia and in the diagnosis and counseling of patients with inherited predispositions to colorectal cancer.
Atherosclerosis in APOE*3-Leiden Transgenic Mice (1999)

This study shows that in APOE*3-Leiden mice, duration of an HFC diet is associated with (1) a craniocaudal progression of lesion development and (2) an increased complexity of atherosclerotic lesions. Furthermore, DNA synthesis is predominant in early lesions, whereas apoptosis is present mainly in more advanced lesions. Both parameters of cell turnover are confined primarily to the macrophage-derived foam cell.
Multiple Distinct Sets of Stereotyped Antigen Receptors Indicate a Role for Antigen in Promoting Chronic Lymphocytic Leukemia (2004)

Previous studies suggest that the diversity of the expressed variable (V) region repertoire of the immunoglobulin (Ig)H chain of B-CLL cells is restricted. Although limited examples of marked constraint in the primary structure of the H and L chain V regions exist, the possibility that this level of restriction is a general principle in this disease has not been accepted. This report describes five sets of patients, mostly with unmutated or minimally mutated IgV genes, with strikingly similar B cell antigen receptors (BCRs) arising from the use of common H and L chain V region gene segments that share CDR3 structural features such as length, amino acid composition, and unique amino acid residues at recombination junctions. Thus, a much more striking degree of structural restriction of the entire BCR and a much higher frequency of receptor sharing exists among patients than appreciated previously. The data imply that either a significant fraction of B-CLL cells was selected by a limited set of antigenic epitopes at some point in their development and/or that they derive from a distinct B cell subpopulation with limited Ig V region diversity. These shared, stereotyped Ig molecules may be valuable probes for antigen identification and important targets for cross-reactive idiotypic therapy.
MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B (2007)

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate expression of many genes. Recent studies suggest roles of miRNAs in carcinogenesis. We and others have shown that expression profiles of miRNAs are different in lung cancer vs. normal lung, although the significance of this aberrant expression is poorly understood. Among the reported down-regulated miRNAs in lung cancer, the miRNA (miR)-29 family (29a, 29b, and 29c) has intriguing complementarities to the 3'-UTRs of DNA methyltransferase (DNMT)3A and -3B (de novo methyltransferases), two key enzymes involved in DNA methylation, that are frequently up-regulated in lung cancer and associated with poor prognosis. We investigated whether miR-29s could target DNMT3A and -B and whether restoration of miR-29s could normalize aberrant patterns of methylation in non-small-cell lung cancer. Here we show that expression of miR-29s is inversely correlated to DNMT3A and -3B in lung cancer tissues, and that miR-29s directly target both DNMT3A and -3B. The enforced expression of miR-29s in lung cancer cell lines restores normal patterns of DNA methylation, induces reexpression of methylation-silenced tumor suppressor genes, such as FHIT and WWOX, and inhibits tumorigenicity in vitro and in vivo. These findings support a role of miR-29s in epigenetic normalization of NSCLC, providing a rationale for the development of miRNA-based strategies for the treatment of lung cancer.
A BGP-based mechanism for lowest-cost routing (2002)

The routing of traffic between Internet domains or Autonomous Systems (ASs), a task known as interdomain routing, is currently handled by the Border Gateway Protocol (BGP). In this paper, we address the problem of interdomain routing from a mechanism-design point of view. The application of mechanism-design principles to the study of routing is the subject of earlier work by Nisan and Ronen [14] and Hershberger and Suri [10]. In this paper, we formulate and solve a version of the routing-mechanism design problem that is different from the previously studied version in three ways that make it more accurately reflective of real-world interdomain routing: (1) we treat the nodes as strategic agents, rather than the links; (2) our mechanism computes lowest-cost routes for all source-destination pairs and payments for transit nodes on all of the routes (rather than computing routes and payments for only one source-destination pair at a time, as is done in [14, 10]); (3) we show how to compute our mechanism with a distributed algorithm that is a straightforward extension to BGP and causes only modest increases in routing-table size and convergence time (in contrast with the centralized algorithms used in [14, 10]). This approach of using an existing protocol as a substrate for distributed computation may prove useful in future development of Internet algorithms generally, not only for routing or pricing problems. Our design and analysis of a strategyproof, BGP-based routing mechanism provides a new, promising direction in distributed algorithmic mechanism design, which has heretofore been focused mainly on multicast cost sharing.
Reference Intervals of the Dilute Tissue Thromboplastin Inhibition and Dilute Russell's Viper Venom Tests Revisited (2002)

Reference intervals for two well-recognized tests for the lupus anticoagulant were determined using 98 healthy subjects. The purpose of the study was to compare the reference intervals for the dilute tissue thromboplastin inhibition test on this group of healthy subjects calculated by parametric and nonparametric statistical methods, and to compare these results with results obtained on subsets of 20 and 40 randomly selected individuals from the group of 98. The same procedures were followed for the dilute Russell's viper venom test. Results were recorded in seconds of clotting times and in ratios (subject/mean of that set or subset). Statistical analysis revealed Gaussian distribution of the results in the large group as well as in each subset for both tests. The results showed more variation between sets of the dilute tissue thromboplastin inhibition test than of the dilute Russell's viper venom test. Nonparametrically calculated reference intervals were wider than those determined by the parametric method, especially if confidence intervals are provided for both reference limits in a group of 94 controls or in a subset of 40 subjects. The nonparametric technique uses all data for the calculation of reference interval of such sample sizes no matter how widely spread the results are. There was no significant difference between the reference intervals of subsets and the whole group (p > 0.05) calculated by both statistical techniques. Very few outliers were observed among these subjects in both tests.
Aldehyde dehydrogenase 1A1 in stem cells and cancer (2016)

The human genome contains 19 putatively functional aldehyde dehydrogenase (ALDH) genes, which encode enzymes critical for detoxification of endogenous and exogenous aldehyde substrates through NAD(P)+-dependent oxidation. ALDH1 has three main isotypes, ALDH1A1, ALDH1A2, and ALDH1A3, and is a marker of normal tissue stem cells (SC) and cancer stem cells (CSC), where it is involved in self-renewal, differentiation and self-protection. Experiments with murine and human cells indicate that ALDH1 activity, predominantly attributed to isotype ALDH1A1, is tissue- and cancer-specific. High ALDH1 activity and ALDH1A1 overexpression are associated with poor cancer prognosis, though high ALDH1 and ALDH1A1 levels do not always correlate with highly malignant phenotypes and poor clinical outcome. In cancer therapy, ALDH1A1 provides a useful therapeutic CSC target in tissue types that normally do not express high levels of ALDH1A1, including breast, lung, esophagus, colon and stomach. Here we review the functions and mechanisms of ALDH1A1, the key ALDH isozyme linked to SC populations and an important contributor to CSC function in cancers, and we outline its potential in future anticancer strategies.
Serial compressed sensing communication system for UWB impulse radio in bursty applications (2011)

A digital pre-coding based serial compressed sensing (CS) ultra-wideband (UWB) communication system is proposed. By establishing a mathematical model, signal detection is studied based on the CS theory. Simulation results in the IEEE 802.15.3a channel model show that with a low sampling rate, the proposed system can operate in a regime of heavy intersymbol interference.