gebhart/patrepeval huggingface dataset:
Inhibition of RXR and PPARγ ameliorates diet-induced obesity and type 2 diabetes (2001)

PPARgamma is a ligand-activated transcription factor and functions as a heterodimer with a retinoid X receptor (RXR). Supraphysiological activation of PPARgamma by thiazolidinediones can reduce insulin resistance and hyperglycemia in type 2 diabetes, but these drugs can also cause weight gain. Quite unexpectedly, a moderate reduction of PPARgamma activity observed in heterozygous PPARgamma-deficient mice or the Pro12Ala polymorphism in human PPARgamma, has been shown to prevent insulin resistance and obesity induced by a high-fat diet. In this study, we investigated whether functional antagonism toward PPARgamma/RXR could be used to treat obesity and type 2 diabetes. We show herein that an RXR antagonist and a PPARgamma antagonist decrease triglyceride (TG) content in white adipose tissue, skeletal muscle, and liver. These inhibitors potentiated leptin's effects and increased fatty acid combustion and energy dissipation, thereby ameliorating HF diet-induced obesity and insulin resistance. Paradoxically, treatment of heterozygous PPARgamma-deficient mice with an RXR antagonist or a PPARgamma antagonist depletes white adipose tissue and markedly decreases leptin levels and energy dissipation, which increases TG content in skeletal muscle and the liver, thereby leading to the re-emergence of insulin resistance. Our data suggested that appropriate functional antagonism of PPARgamma/RXR may be a logical approach to protection against obesity and related diseases such as type 2 diabetes.
Interaction between the endophytic fungus Epichloë bromicola and the grass Bromus erectus: effects of endophyte infection, fungal concentration and environment on grass growth and flowering (1999)

Epichloe bromicola is an endophytic fungal species that systemically and perennially colonizes intercellular spaces of leaf blades, leaf sheaths and culms of Bromus grass species. E. bromicola causes choke disease in B. erectus, suppressing maturation of most, if not all, host inflorescences. In an investigation of the interaction between fungus and host, we used a quantitative polymerase chain reaction technique to estimate the amount of fungal DNA, and thereby fungal concentration, in host plants. Fungal concentration was directly correlated with vegetative vigour of the plant, as measured by longest leaf length, number of tillers and vegetative above-ground biomass, suggesting that, during vegetative growth, the endophytic fungus is most beneficial for the plant when present in high concentrations. In contrast, the reproduction of the plant, as measured by the number of functional inflorescences, was inversely correlated with fungal concentration: the majority of infected plants, and all that were associated with high concentrations of fungi, were diseased. Thus, the benefit of endophyte infection for the plant is coupled with the disadvantages of infertility. Fungal concentration was shown to be at least in part genetically determined because fungal concentration differed significantly in different plant-endophyte genotype combinations (symbiotum). In a field experiment with normal and CO2-enriched environments, elevated CO2 levels favoured fungal reproductive vigour over host reproductive vigour, suggesting that these plant endophytes would be at a selective advantage in a corresponding environmental-change scenario. We conclude that a dynamic and complex relationship between fungal endophyte infection, fungal concentration, genotype and environment affects growth and fecundity of B. erectus and should contribute to the evolution of these plant-fungal interactions.
Virtual object manipulation on a table-top AR environment (2002)

We address the problems of virtual object interaction and user tracking in a table-top augmented reality (AR) interface. In this setting there is a need for very accurate tracking and registration techniques and an intuitive and useful interface. This is especially true in AR interfaces for supporting face to face collaboration where users need to be able to easily cooperate with each other. We describe an accurate vision-based tracking method for table-top AR environments and tangible user interface (TUI) techniques based on this method that allow users to manipulate virtual objects in a natural and intuitive manner. Our approach is robust, allowing users to cover some of the tracking markers while still returning camera viewpoint information, overcoming one of the limitations of traditional computer vision based systems. After describing this technique we describe its use in prototype AR applications.
Fenton's reagent revisited (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFenton's reagent revisitedCheves WallingCite this: Acc. Chem. Res. 1975, 8, 4, 125–131Publication Date (Print):April 1, 1975Publication History Published online1 May 2002Published inissue 1 April 1975https://pubs.acs.org/doi/10.1021/ar50088a003https://doi.org/10.1021/ar50088a003research-articleACS PublicationsRequest reuse permissionsArticle Views8323Altmetric-Citations2374LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Characterization of a DNA polymerase from the hyperthermophile archaea Thermococcus litoralis. Vent DNA polymerase, steady state kinetics, thermal stability, processivity, strand displacement, and exonuclease activities. (1993)

We have isolated, cloned, and characterized a DNA polymerase from the hyperthermophile archaea Thermococcus litoralis, the Tli DNA polymerase (also referred to as Vent DNA polymerase). The enzyme is extremely thermostable, having a half-life of 8 h at 95 degrees C and about 2 h at 100 degrees C. Pseudo-first-order kinetics at 70 degrees C reveal an extremely low Km for a primed M13mp18 substrate (0.1 nM), coupled with a relatively high Km for dNTPs (50 microM). Accompanying extension rates are on the order of 1000 nucleotides/min. Synthesis by the polymerase is largely distributive, adding an average of 7 nucleotides/initiation event. This distributive synthesis can generate products of at least 10,000 bases. Tli DNA polymerase contains a 3'-->5' exonuclease activity that enhances the fidelity of replication by the enzyme (Mattila, P., Korpela, J., Tenkanen, T. and Pitkanen, K. (1991) Nucleic Acids Res. 19, 4967-4973). A 2-amino acid substitution within the conserved exonuclease domain abolishes both double and single strand-dependent exonuclease activity, without altering kinetic parameters for polymerization on a primed single-stranded template. Strand displacement activity by the mutated and unmutated forms increases with increasing temperature and is enhanced in the exonuclease-deficient form of the enzyme.
Lactate-Utilizing Bacteria, Isolated from Human Feces, That Produce Butyrate as a Major Fermentation Product (2004)

The microbial community of the human colon contains many bacteria that produce lactic acid, but lactate is normally detected only at low concentrations (<5 mM) in feces from healthy individuals. It is not clear, however, which bacteria are mainly responsible for lactate utilization in the human colon. Here, bacteria able to utilize lactate and produce butyrate were identified among isolates obtained from 10(-8) dilutions of fecal samples from five different subjects. Out of nine such strains identified, four were found to be related to Eubacterium hallii and two to Anaerostipes caccae, while the remaining three represent a new species within clostridial cluster XIVa based on their 16S rRNA sequences. Significant ability to utilize lactate was not detected in the butyrate-producing species Roseburia intestinalis, Eubacterium rectale, or Faecalibacterium prausnitzii. Whereas E. hallii and A. caccae strains used both D- and L-lactate, the remaining strains used only the d form. Addition of glucose to batch cultures prevented lactate utilization until the glucose became exhausted. However, when two E. hallii strains and one A. caccae strain were grown in separate cocultures with a starch-utilizing Bifidobacterium adolescentis isolate, with starch as the carbohydrate energy source, the L-lactate produced by B. adolescentis became undetectable and butyrate was formed. Such cross-feeding may help to explain the reported butyrogenic effect of certain dietary substrates, including resistant starch. The abundance of E. hallii in particular in the colonic ecosystem suggests that these bacteria play important roles in preventing lactate accumulation.
Expression and Activation of Signal Regulatory Protein α on Astrocytomas (2004)

Abstract High-grade astrocytomas and glioblastomas are usually unresectable because they extensively invade surrounding brain tissue. Here, we report the expression and function of a receptor on many astrocytomas that may alter both the proliferative and invasive potential of these tumors. Signal regulatory protein (SIRP) α1 is an immunoglobulin superfamily transmembrane glycoprotein that is normally expressed in subsets of myeloid and neuronal cells. Transfection of many cell types with SIRPα1, including glioblastomas, has been shown to inhibit their proliferation in response to a range of growth factors. Furthermore, the expression of a murine SIRPα1 mutant has been shown to enhance cell adhesion and initial cell spreading but to inhibit cell extension and movement. The extracellular portion of SIRPα1 binds CD47 (integrin-associated protein), although this interaction is not required for integrin-mediated activation of SIRPα1. On phosphorylation, SIRPα1 recruits the tyrosine phosphatases SHP-1 and SHP-2, which are important in its functions. Although SHP-1 is uniquely expressed on hematopoietic cells, SHP-2 is ubiquitously expressed, so that SIRPα1 has the potential to function in many cell types, including astrocytomas. Because SIRPα1 regulates cell functions that may contribute to the malignancy of these tumors, we examined the expression of SIRPs in astrocytoma cell lines by flow cytometry using a monoclonal antibody against all SIRPs. Screening of nine cell lines revealed clear cell surface expression of SIRPs on five cell lines, whereas Northern blotting for SIRPα transcripts showed mRNA present in eight of nine cell lines. All nine cell lines expressed the ligand for SIRPα1, CD47. To further examine the expression and function of SIRPs, we studied the SF126 and U373MG astrocytoma cell lines, both of which express SIRPs, in greater detail. SIRP transcripts in these cells are identical in sequence to SIRPα1. The expressed deglycosylated protein is the same size as SIRPα1, but in the astrocytoma cells, it is underglycosylated compared with SIRPα1 produced in transfected Chinese hamster ovary cells. It is nonetheless still capable of binding soluble CD47. Moreover, SIRPα1 in each of the two cell lines recruited SHP-2 on phosphorylation, and SIRPα1 phosphorylation in cultured cells is CD47 dependent. Finally, examination of frozen sections from 10 primary brain tumor biopsies by immunohistochemistry revealed expression of SIRPs on seven of the specimens, some of which expressed high levels of SIRPs. Most of the tumors also expressed CD47. This is the first demonstration that astrocytomas can express SIRPα. Given the known role of SIRPα in regulating cell adhesion and responses to mitogenic growth factors, the expression of SIRPα1 on astrocytomas may be of considerable importance in brain tumor biology, and it offers the potential of a new avenue for therapeutic intervention.
A mutation in the putative Mg(2+)-binding site of Gs alpha prevents its activation by receptors. (1991)

The properties of a Gs alpha mutant with an Asn substituted for Ser at position 54, designated mutant 54Asn alpha s, were studied after expression in S49 alpha s-deficient (cyc-) cells. Ser-54 in alpha s is comparable to Ser-17 in Ras, which is involved in binding Mg2+ associated with bound nucleotide. 54Asn alpha s did not restore either hormone-induced cyclic AMP production in intact cyc- cells or hormone-induced adenylyl cyclase activation in membranes isolated from these cells. The defect was a failure of ligand-bound receptor to activate 54Asn alpha s, since the mutant protein retained the ability to activate adenylyl cyclase in isolated membranes in the presence of GTP or GTP gamma S. Guanine nucleotide regulation of mutant alpha s suggested that it has increased guanine nucleotide exchange rates and an increased preference for diphosphates over triphosphates. Hormone stimulation magnified the preference of 54Asn alpha s for diphosphates, which could account for its inability to be activated by receptor. The properties of this mutant are discussed in terms of similarities to and differences with the analogous RasH mutant, which has been shown to interfere with endogenous Ras function in cells.
Improved Hemodynamics With a Novel Miniaturized Intra-aortic Axial Flow Pump in a Porcine Model of Acute Left Ventricular Dysfunction (2013)

Currently, long-term mechanical circulatory support (MCS) is limited to large, complex devices that require invasive, high-risk surgical implantation. These devices are mainly used in patients with late stage heart failure (HF). We are developing a novel percutaneous intra-aortic micro-axial fluid entrainment pump intended for long-term MCS in patients with earlier stage HF. This study examined the pump's hemodynamic effects in a porcine model of acute HF. In three porcine experiments, the pump was deployed in the thoracic aorta by standard cardiac catheterization techniques and was anchored with self-expanding struts. Acute cardiac dysfunction was induced by infusing esmolol continuously. Pump support increased cardiac output (+10.4%), stroke volume (+8.9%), and ejection fraction (+10.8%) while decreasing cardiac stroke work (-10.8%) and afterload (-22.7%). Furthermore, pump support significantly enhanced renal perfusion through sustained increases in both renal artery flow (+36.4%) and pressure (+73.6%). In a porcine model of acute HF, the catheter-based intra-aortic fluid entrainment pump improved hemodynamics and renal perfusion. These results suggest that the pump could improve HF outcomes and patients' quality of life by resting the heart, promoting reverse remodeling, and augmenting end-organ perfusion. Furthermore, the enhanced renal perfusion may help disrupt the cardiorenal syndrome cycle and improve HF treatment.
Evaluating the reliability cost of computer system interruptions due to power system disturbances (1989)

The authors present a general modeling and simulation approach for estimating the cost of interruptions to a computer center caused by power system disturbances and outages. The major variables (e.g loss of revenue, equipment damage, renewal of lost records, costing data, user profiles, power system reliability characteristics, etc.) were included in the costing method. The simulation model was applied to the University of Alberta's computer center, which does not have an uninterruptable power system. Actual historical databases (i.e. 11 years) were used in the case studies presented. The advantages and limitations of the reliability-costing methodology are discussed in some detail with reference to existing methods. It is concluded that estimating the cost of computer system interruptions is a complex and difficult task requiring large databases.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Small-molecule agonists for the glucagon-like peptide 1 receptor (2007)

The peptide hormone glucagon-like peptide (GLP)-1 has important actions resulting in glucose lowering along with weight loss in patients with type 2 diabetes. As a peptide hormone, GLP-1 has to be administered by injection. Only a few small-molecule agonists to peptide hormone receptors have been described and none in the B family of the G protein coupled receptors to which the GLP-1 receptor belongs. We have discovered a series of small molecules known as ago-allosteric modulators selective for the human GLP-1 receptor. These compounds act as both allosteric activators of the receptor and independent agonists. Potency of GLP-1 was not changed by the allosteric agonists, but affinity of GLP-1 for the receptor was increased. The most potent compound identified stimulates glucose-dependent insulin release from normal mouse islets but, importantly, not from GLP-1 receptor knockout mice. Also, the compound stimulates insulin release from perfused rat pancreas in a manner additive with GLP-1 itself. These compounds may lead to the identification or design of orally active GLP-1 agonists.
Oxidative stress during viral infection: A review (1996)

The purpose of this review is to analyze the role of reactive oxygen species (ROS) in the pathogenesis of viral infections, an area of research that has recently gained momentum given the accumulation of evidence regarding the role of ROS in the pathogenesis of infection with the human immunodeficiency virus (HIV). Attention will be focussed on three classes of viruses: (1) RNA viruses, (2) DNA viruses, and (3) retroviruses, with particular attention to influenza viruses, hepatitis B virus, and HIV as representative examples of these three classes, respectively. For each type of virus, evidence for the following will be analyzed: (1) the effect of the virus on activation of phagocytic cells to release ROS and pro-oxidant cytokines such as tumor necrosis factor; (2) the effect of the virus on the pro-/antioxidant balance in host cells, including virally induced inhibition of antioxidant enzymes such as superoxide dismutase and virally induced increases in pro-oxidants such as nitric oxide; (3) effects of the redox state of the cell on the genetic composition of the virus as well as ROS-mediated release of host cell nuclear transcription factor-kappa-B, resulting in increased viral replication; and (4) efficacy of antioxidants as therapeutic agents in viral diseases of both animal models and patients.
Nationwide Census of Institutional Repositories: Preliminary Findings (2007)

The MIRACLE (Making Institutional Repositories A Collaborative Learning Environment) Project is a multi-phased research project that is investigating the development of institutional repositories (IRs) in American colleges and universities to identify models and best practices in the administration, technical infrastructure, and access to repository collections. This paper features preliminary findings from the project’s first phase, a nationwide census that will reveal the extent of college and university involvement with IRs in the United States. Preliminary findings address the types of investigative activities that institutions are conducting prior to making the decision to implement an IR, perceived benefits of IRs, staffing for IRs, methods of recruiting digital content, characteristics of operational IRs including their costs, and respondents ’ next steps on the road to implementing an IR.
Relationship of plasmids responsible for hairy root and crown gall tumorigenicity (1980)

Three strains of Agrobacterium rhizogenes were examined for plasmids. Strains 15834 and A4 contained essentially identical large plasmids, pAr15834c and pArA4c, respectively (approximately 260 x 10(6) daltons). These plasmids can dissociate to two smaller plasmid species. Strain TR105 contained only a single plasmid, which was homologous with the dissociation product of pAr15834c, pAr15834b. Plasmid pAr15834c shared little overall sequence homology with other Ti plasmids. One region of conserved homology between pAr15834c and a region of the octopine type plasmid pTiB6806 which contains oncogenicity functions was detected. Lower levels of homology were detected with sequences which are distributed throughout 65% of pTiB6806. Homology with the so-called common deoxyribonucleic acid in the integrated plasmid deoxyribonucleic acid region was detected only after lowering the stringency of hybridization (Tm, -41 degrees C). Furthermore, the A. rhizogenes plasmid is compatible with other Ti plasmids. Therefore, the results suggest that the virulence plasmids of A. rhizogenes are functionally similar to other Ti plasmids, yet have diverged sufficiently from an ancestral Ti plasmid that they now represent a distinct plasmid type based on homology, compatibility, and virulence.
Evaluation of acepromazine, diazepam and midazolam as sedatives in buffalo calves. (2010)

The buffalo calves became ataxic at 6.16±1.07 minute of acepromazine administration. There was good sedation. The animals stood up with ataxia at 131.5±17.80 minute and complete recovery took 211.83±6.94 minutes. Significant hypotension and tachycardia were observed after acepromazine administration. Midazolam caused ataxia at 3.33±0.76 minute and animals went into sternal recumbency at 34.0±15.85 minute. There was good muscle relaxation. Complete recovery took 183.5±10.92 minutes. Significant increase in respiratory rate was observed at the its peak effect. A significant reduction in mean arterial pressure (MAP) was also seen at 30 minute of midazolam administration. Diazepam produced ataxia within one minute and animals went into sternal recumbency. It produced quick onset of action and delayed recovery. A significant hypotension was observed at 5 minute of diazepam with decreased pulse pressure. No change was observed in electrocardiograph on administration of acepromazine and diazepam but slight increase in the amplitude of primary T-wave was observed after midazolam administration.
Design of bioactive peptides based on antibody hypervariable region structures. Development of conformationally constrained and dimeric peptides with enhanced affinity. (1991)

The variable regions of antibody molecules bind antigens with high affinity and specificity. This binding is imparted largely by the hypervariable portions of the variable region. Hypervariable regions typically fold into reverse turn or loop structures. Peptides derived from antibody hypervariable region sequences can bind antigens with similar specificity, albeit with markedly lower affinity. In this study, cyclic and dimeric peptide analogs of an anti-idiotypic/antireceptor antibody hypervariable region were developed. This antibody (87.92.6) binds to reovirus type 3 receptors on cells as well as to a neutralizing anti-reovirus type 3 monoclonal antibody (9B.G5). The cyclic peptides were utilized to probe the optimal conformation for binding to both the receptor and 9B.G5. By dimerizing or constraining the conformation of these peptides, higher affinity binding was produced. By utilizing several different cyclic peptides, the optimal conformation for binding was established. The conformationally optimized cyclic peptide possessed greater than 40-fold higher affinity for the receptor and the idiotype than the linear analog. This study suggests that conformationally constrained and dimeric peptides derived from antibody hypervariable loop sequences can bind antigens (including receptors) with reasonable affinity. hypervariable loop sequences can bind antigens (including
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice (2020)

A ribonucleoside analog inhibits SARS-CoV-2 in human airway epithelial cell cultures and SARS-CoV and MERS-CoV in mice.