gebhart/patrepeval huggingface dataset:
Functional domains of SIR4, a gene required for position effect regulation in Saccharomyces cerevisiae. (1987)

The product of the Saccharomyces cerevisiae SIR4 gene, in conjunction with at least three other gene products, prevents expression of mating-type genes resident at loci at either end of chromosome III, but not of the same genes resident at the MAT locus in the middle of the chromosome. To address the mechanism of this novel position effect regulation, we have conducted a structural and genetic analysis of the SIR4 gene. We have determined the nucleotide sequence of the gene and found that it encodes a lysine-rich, serine-rich protein of 152 kilodaltons. Expression of the carboxy half of the protein complements a chromosomal nonsense mutation of sir4 but not a complete deletion of the gene. These results suggest that SIR4 protein activity resides in two portions of the molecule, but that these domains need not be covalently linked to execute their biological function. We also found that high-level expression of the carboxy domain of the protein yields dominant derepression of the silent loci. This anti-Sir activity can be reversed by increased expression of the SIR3 gene, whose product is normally also required for maintaining repression of the silent loci. These results are consistent with the hypothesis that SIR3 and SIR4 proteins physically associate to form a multicomponent complex required for repression of the silent mating-type loci.
Diels−Alder Reaction for the Selective Immobilization of Protein to Electroactive Self-Assembled Monolayers (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTDiels−Alder Reaction for the Selective Immobilization of Protein to Electroactive Self-Assembled MonolayersMuhammad N. Yousaf and Milan MrksichView Author Information Department of Chemistry, The University of Chicago Chicago, Illinois 60637 Cite this: J. Am. Chem. Soc. 1999, 121, 17, 4286–4287Publication Date (Web):April 14, 1999Publication History Received5 October 1998Published online14 April 1999Published inissue 1 May 1999https://doi.org/10.1021/ja983529tCopyright © 1999 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views1472Altmetric-Citations207LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (106 KB) Get e-AlertsSUBJECTS:Alcohols,Immobilization,Monolayers,Nutrition,Organic compounds Get e-Alerts
Solution-Phase Parallel Synthesis and SAR of Homopiperazinyl Analogs as Positive Allosteric Modulators of mGlu4 (2011)

Using a functional high-throughput screening (HTS) and subsequent solution-phase parallel synthesis approach, we have discovered a novel series of positive allosteric modulators for mGlu₄, a G-protein coupled receptor. This series is comprised of a homopiperazine central core. The solution-phase parallel synthesis and SAR of analogs derived from this series will be presented. This series of positive allosteric modulators of mGlu₄ provide critical research tools to further probe the mGlu₄-mediated effects in Parkinson's disease.
Insertion of the DNA for the 163–171 peptide of IL1β enables a DNA vaccine encoding p185neu to inhibit mammary carcinogenesis in Her-2/neu transgenic BALB/c mice (2001)

An assessment was made of the effectiveness of DNA vaccination in prevention of the mammary adenocarcinomas of BALB/c female mice transgenic for the activated rat Her-2/neu oncogene. Atypical hyperplasia is evident in their mammary glands when they are 6 weeks old and in situ carcinoma by the 13th week. Palpable invasive carcinomas appear around the 17th week and are always evident in all 10 glands by the 33rd week. Intramuscular vaccinations with 100 microg plasmid DNA encoding the extracellular domain of the Her-2/neu p185 (ECD) performed at the 6th, 12th, 18th and 24th week provided no significant protection, whereas those ECD plasmids in which the DNA coding for the immunomodulatory 163-171 (VQGEESNDK) nonapeptide of human IL1beta (ECD-IL1betap) had been inserted both delayed carcinogenesis and reduced tumor multiplicity. This reduction was associated with a marked immune-inflammatory reaction and a conspicuous leukocyte infiltrate located in the stroma surrounding the hyperplastic mammary ductul-alveolar structures. It was also directly correlated with a high anti-p185(neu) antibody production and an immunoglobulin switch to IgG2a and IgA. No anti-p185(neu) cytotoxic response was found. No significant protection was obtained when the DNA coding for the non-active peptide 189-197 of IL1beta was inserted.
Importance of Intrinsic-$Q$ in Microring-Based Optical Filters and Dispersion-Compensation Devices (2007)

We investigate the impact of the intrinsic-Q of the resonant poles on the performance of multiring-based optical filters and dispersion-compensating devices. We highlight the role of quality factor by defining figures-of-merit for some specific filter configurations.
Tcf3 Functions as a Steady-State Limiter of Transcriptional Programs of Mouse Embryonic Stem Cell Self-Renewal (2008)

Elucidating the underlying transcriptional control of pluripotent cells is necessary for the development of new methods of inducing and maintaining pluripotent cells in vitro. Three transcription factors, Nanog, Oct4, and Sox2, have been reported to form a feedforward circuit promoting pluripotent cell self-renewal in embryonic stem cells (ESC). Previously, we found that a transcriptional repressor activity of Tcf3, a DNA-binding effector of Wnt signaling, reduced Nanog promoter activity and Nanog levels in mouse embryonic stem cells (mESC). The objective of this study was to determine the scope of Tcf3 effects on gene expression and self-renewal beyond the regulation of Nanog levels. We show that Tcf3 acts broadly on a genome-wide scale to reduce the levels of several promoters of self-renewal (Nanog, Tcl1, Tbx3, Esrrb) while not affecting other ESC genes (Oct4, Sox2, Fgf4). Comparing effects of Tcf3 ablation with Oct4 or Nanog knockdown revealed that Tcf3 counteracted effects of both Nanog and Oct4. Interestingly, the effects of Tcf3 were more strongly correlated with Oct4 than with Nanog, despite the normal levels of Oct4 in TCF3-/- mESC. The deranged gene expression allowed TCF3-/- mESC self-renewal even in the absence of leukemia inhibitory factor and delayed differentiation in embryoid bodies. These findings identify Tcf3 as a cell-intrinsic inhibitor of pluripotent cell self-renewal that functions by limiting steady-state levels of self-renewal factors. Disclosure of potential conflicts of interest is found at the end of this article.
Antisense Strategy: Biological Utility and Prospects in the Treatment of Hematological Malignancies (1997)

The use of antisense oligonucleotides for the specific control of cellular genes expression has undergone rapid developments recently. Besides the antisense approach, which usually targets translation initiation or splicing sites, it is also possible to interfere specifically with transcription process through triple helix formation (anti-gene strategy) or through the titration of regulatory proteins (sense and aptamer approaches). Progresses in oligonucleotides chemistry have led to the synthesis of analogs with improved pharmacological properties, while their generation from recombinant vectors in situ has improved oligos deliver to their nuclear or cytoplasmic targets. Hematological malignancies provide an ideal paradigm for the development of antisense therapeutic strategies. Many disease-specific molecular lesions have been identified which provide suitable targets for systemic in vivo administration of oligonucleotides as well as for ex vivo bone marrow purging manipulation. However, oligonucleotides have also been shown to bind to unexpected cellular targets and to induce various unpredictable biological responses as well. In addition, the multi-stage nature of carcinogenesis may indicate that even if successful inhibition of a single gene by oligomer is achieved, it may still be insufficient to induce a major impact on a malignant clone. Thus, much more basic information about both the disease and antisense technology is still required before antisense strategy gains the status of an acceptable therapeutical approach.
Plasma Polymerization of Thiophene Derivatives (2003)

To obtain plasma polymerized (PP) layers with a high retention of the conjugated monomer structure, fragmentation during deposition should be minimized. Different methylated and halogenated thiophenes were used as monomers in plasma polymerization, and the influence of the substituent(s) on fragmentation during deposition was investigated. With the use of optical emission spectroscopy (OES) and mass spectroscopy (MS), it was found that methylated thiophenes show a low degree of fragmentation during deposition, whereas for halogenated thiophenes a high degree of fragmentation was observed. For a specific substituent, fragmentation was less for thiophene derivatives with substitution on the 2-position than on the 3-position. Disubstituted thiophenes always showed less fragmentation than their monosubstituted analogues. Due to the lower degree of fragmentation, PP layers from methylated thiophenes contained a higher amount of conjugated structures. Consequently, a higher conductivity was measured for these PP layers after iodine doping.
The Biochemistry of Methane Oxidation (2007)

Methanotrophic bacteria oxidize methane to methanol in the first step of their metabolic pathway. Two forms of methane monooxygenase (MMO) enzymes catalyze this reaction: soluble MMO (sMMO) and membrane-bound or particulate MMO (pMMO). pMMO is expressed when copper is available, and its active site is believed to contain copper. Whereas sMMO is well characterized, most aspects of pMMO biochemistry remain unknown and somewhat controversial. This review emphasizes advances in the past two to three years related to pMMO and to copper uptake and copper-dependent regulation in methanotrophs. The pMMO metal centers have been characterized spectroscopically, and the first pMMO crystal structure has been determined. Significant effort has been devoted to improving in vitro pMMO activity. Proteins involved in sMMO regulation and additional copper-regulated proteins have been identified, and the Methylococcus capsulatus (Bath) genome has been sequenced. Finally, methanobactin (mb), a small copper chelator proposed to facilitate copper uptake, has been characterized.
A new human interferon-gamma mutant harboring EGF receptor-interfering sequence possesses high antiproliferative activity. (1992)

An interferon gamma (IFN-gamma) mutant gene harboring an additional epidermal growth factor (EGF) sequence at its 3' terminal was constructed and highly expressed in E. coli by using pBV220 as a vector. The new fusion protein-IFN-gamma-EGF possesses not only high antiviral activity, but also high antiproliferative effect as demonstrated by 3H-TdR incorporation method using CN II cells which are rich in EGF receptors.
Perflenapent emulsion: a US contrast agent for diagnostic radiology--multicenter, double-blind comparison with a placebo. EchoGen Contrast Ultrasound Study Group. (1998)

Perflenapent emulsion is a safe and effective contrast agent for US of the liver, kidneys, and vasculature.
In vitro studies of ferric carboxymaltose on placental permeability using the dual perfusion model of human placenta (2011)

An in vitro perfusion model of human placenta was used to study the transplacental passage of iron applied in the form of the drug compound ferric carboxymaltose (FCM) which had been radio-labelled with 59Fe. In four placental perfusion experiments, two simulated circuits for the maternal and fetal sides of the placenta were set up with two experimental phases each lasting 3 h. FCM was added to the maternal circuit at the beginning of each phase to a final iron concentration of 11 mM, which is at least 10 times higher than the maximal predicted level in blood after an administration of 200 mg iron as FCM. The effects of adding transferrin at a physiological concentration of 1.67 mg/ ml were also tested. The concentration profiles of 59Fe showed a 10% decrease within the first 30 min of perfusion on the maternal side. Thereafter the radioactivity levels remained unchanged. The addition of transferrin had no effect on the tissue uptake of 59Fe-FCM. No transferred iron radioactivity could be detected in the fetal circuit. Despite a loss of approximately 10% of the radio-labelled iron observed on the maternal side, only 0.5-2% of the radioactivity was detected in the placental tissue after perfusion. No free iron could be detected at the end of perfusion on the maternal side using ultrafiltration or acid precipitation methods. In addition, the production of transferrin receptor remained unchanged, with similar concentrations in placental tissue before and after perfusion. No effects of FCM on placental viability were observed in terms of energy metabolism (glucose consumption and lactate production), hormone release or placental permeability (assessed by the transfer rates of creatinine and antipyrine). However, two additional observations were made: firstly, a significant reduction in the rate of cell death compared to control conditions was observed in the presence of FCM; secondly, the integrity of the fetal capillary system was improved on the fetal side of the perfusion system. It is concluded that the iron compound FCM does not cross the placenta and may increase the integrity of placental tissue (at least under in vitro conditions), but this latter observation needs further investigation.
Identification of Essential Amino Acids in Phenylalanine Ammonia-Lyase by Site-Directed Mutagenesis (1997)

The postulated precursor of the prosthetic dehydroalanine of phenylalanine ammonia-lyase (PAL), serine 202, was changed to cysteine by site-directed mutagenesis. After cloning and heterologous expression in Escherichia coli, the gene product was assayed for PAL activity. Mutant S202C showed full catalytic activity, and its kinetic constants and the amount of thiol groups were identical to those of wild-type PAL. It must be concluded that in a posttranslational modification both water and hydrogen sulfide can be eliminated from the amino acid in position 202 to form dehydroalanine. In an attempt to identify further amino acids essential either for the posttranslational modification or for catalysis, arginine 174, glutamine 425, and lysine 499 were changed to isoleucine. Analysis of the heterologously expressed mutated gene products revealed that only the R174I mutant showed a significantly lower Vmax value (1/450) identifying this arginine as important. This finding was supported by treatment of wild-type PAL and mutant R174I with phenylglyoxal and 2,3-butandione. Both react specifically with the guanidino group of arginine. They irreversibly inhibited wild-type PAL but had no influence of the Vmax value of mutant R174I. Preincubation with l-phenylalanine protected wild-type PAL from inhibition by phenylglyoxal indicating that arginine 174 is close to the active site. Incubation with KCN irreversibly abolished the remaining activity of mutant R174I leading to the conclusion that arginine 174 is important in catalysis.
Delegation of IP6.ARPA (2001)

This document discusses the need for delegation of the IP6.ARPA DNS zone, and specifies a plan for the technical operation thereof.
Thrombosis and embolism after injury. (1970)

is frequent in injured patients. It takes different forms, and at least one of them, deep vein thrombosis in the lower limbs, is a common cause of morbidity and death through embolic detachment. The different kinds may be on July 21,
The Problem of Creating Multi-Tenant Database Clusters (2012)

SaaS (Software as a Service) paradigm brings both lots of benefits to end users and lots of problems to software developers. One of such problems is an implementation of a data storage which is able to satisfy needs of clients of a service provider, at the same time providing easy application interface for software developers and great opportunities for administration and scaling. This paper provides a brief review of existing problems in the field of organizing cloud data storages that are based on the relational data model and proposes the concept of architecture of RDBMS cluster dedicated to serve multi-tenant cloud applications.
Role of IL-18 in Acute Lung Inflammation (2001)

We have examined the role of IL-18 after acute lung inflammation in rats caused by intrapulmonary deposition of IgG immune complexes. Constitutive IL-18 mRNA and protein expression (precursor form, 26 kDa) were found in normal rat lung, whereas in inflamed lungs, IL-18 mRNA was up-regulated; in bronchoalveolar (BAL) fluids, the 26-kDa protein form of IL-18 was increased at 2-4 h in inflamed lungs and remained elevated at 24 h, and the "mature" protein form of IL-18 (18 kDa) appeared in BAL fluids 1-8 h after onset of inflammation. ELISA studies confirmed induction of IL-18 in inflamed lungs (in lung homogenates and in BAL fluids). Prominent immunostaining for IL-18 was found in alveolar macrophages from inflamed lungs. When rat lung macrophages, fibroblasts, type II cells, and endothelial cells were cultured in vitro with LPS, only the first two produced IL-18. Intratracheal administration of rat recombinant IL-18 in the lung model caused significant increases in lung vascular permeability and in BAL content of neutrophils and in BAL content of TNF-alpha, IL-1beta, and cytokine-induced neutrophil chemoattractant, whereas intratracheal instillation of anti-IL-18 greatly reduced these changes and prevented increases in BAL content of IFN-gamma. Intratracheal administration of the natural antagonist of IL-18, IL-18 binding protein, resulted in suppressed lung vascular permeability and decreased BAL content of neutrophils, cytokines, and chemokines. These findings suggest that endogenous IL-18 functions as a proinflammatory cytokine in this model of acute lung inflammation, serving as an autocrine activator to bring about expression of other inflammatory mediators.
Development of radiation-mode filters for WDM (1998)

We present a simple theoretical model to predict the performance of radiation-mode filters written in optical fibres and demonstrate good agreement with experiment. We also present a new fibre structure for use in radiation-mode filters for telecommunications applications, with low insertion loss due to splices and bends and a filter FWHM bandwidth of only 3.4 nm.
IGFBP3 suppresses retinopathy through suppression of oxygen-induced vessel loss and promotion of vascular regrowth (2007)

Vessel loss precipitates many diseases. In particular, vessel loss resulting in hypoxia induces retinal neovascularization in diabetic retinopathy and in retinopathy of prematurity (ROP), major causes of blindness. Here we define insulin-like growth factor binding protein-3 (IGFBP3) as a new modulator of vascular survival and regrowth in oxygen-induced retinopathy. In IGFBP3-deficient mice, there was a dose-dependent increase in oxygen-induced retinal vessel loss. Subsequent to oxygen-induced retinal vessel loss, Igfbp3(-/-) mice had a 31% decrease in retinal vessel regrowth versus controls after returning to room air. No difference in serum insulin-like growth factor 1 (IGF1) levels was observed among groups. Wild-type mice treated with exogenous IGFBP3 had a significant increase in vessel regrowth. This correlated with a 30% increase in endothelial progenitor cells in the retina at postnatal day 15, indicating that IGFBP3 could be serving as a progenitor cell chemoattractant. In a prospective clinical study, we measured IGFBP3 (and IGF1) plasma levels weekly and examined retinas in all premature infants born at gestational ages <32 weeks at high risk for ROP. The mean level of IGFBP3 at 30-35 weeks postmenstrual age (PMA) for infants with proliferative ROP (ROP stages 3>, n = 13) was 802 microg/liter, and for infants with no ROP (ROP stage 0, n = 38) the mean level was 974 microg/liter (P < 0.03). These results suggest that IGFBP3, acting independently of IGF1, helps to prevent oxygen-induced vessel loss and to promote vascular regrowth after vascular destruction in vivo in a dose-dependent manner, resulting in less retinal neovascularization.
Direct Current Stimulation over V5 Enhances Visuomotor Coordination by Improving Motion Perception in Humans (2004)

The primary aim of this study was to determine the extent to which human MT+/V5, an extrastriate visual area known to mediate motion processing, is involved in visuomotor coordination. To pursue this we increased or decreased the excitability of MT+/V5, primary motor, and primary visual cortex by the application of 7 min of anodal and cathodal transcranial direct current stimulation (tDCS) in healthy human subjects while they were performing a visuomotor tracking task involving hand movements. The percentage of correct tracking movements increased specifically during and immediately after cathodal stimulation, which decreases cortical excitability, only when V5 was stimulated. None of the other stimulation conditions affected visuomotor performance. We propose that the improvement in performance caused by cathodal tDCS of V5 is due to a focusing effect on to the complex motion perception conditions involved in this task. This hypothesis was proven by additional experiments: Testing simple and complex motion perception in dot kinetograms, we found that a diminution in excitability induced by cathodal stimulation improved the subject's perception of the direction of the coherent motion only if this was presented among random dots (complex motion perception), and worsened it if only one motion direction was presented (simple movement perception). Our data suggest that area V5 is critically involved in complex motion perception and identification processes important for visuomotor coordination. The results also raise the possibility of the usefulness of tDCS in rehabilitation strategies for neurological patients with visuomotor disorders.
Quantitative Assessment of Human Proteinases as Agents for Chemonucleolysis (1988)

A rabbit model system is described. It allows accurate measurement of the dose-dependent loss of glycosaminoglycan from the nucleus pulposus of lumbar intervertebral discs after injection of a proteinase. At the dose equivalent to that of chymopapain used in human chemonucleolysis, two human serine proteinases, cathepsin G and chymotrypsin, were as effective as chymopapain in removing up to 80% of the glycosaminoglycan from the disc. A cysteine proteinase, cathepsin B released no more than 45% of glycosaminoglycan. X-ray films clearly showed narrowing of the disc space when 30-40% of glycosaminoglycan was removed. The degradation of the nucleus pulposus was seen histologically as loss of toluidine blue metachromasia.