gebhart/patrepeval huggingface dataset:
The Effects of Recombinant Human Growth Hormone on Body Composition and Glucose Metabolism in HIV-Infected Patients with Fat Accumulation (2001)

GH has been proposed as a therapy for patients with HIVassociated fat accumulation, but the pharmacological doses (6 mg/d) used have been associated with impaired fasting glucose and hyperglycemia. In contrast, physiologic doses of GH ( 1 mg/d) in HIV-negative men reduced visceral adiposity and eventually improved insulin sensitivity, despite initially causing insulin resistance. We conducted an open-label study to evaluate the effects of a lower pharmacologic dose of GH (3 mg/d) in eight men with HIV-associated fat accumulation. Oral glucose tolerance, insulin sensitivity, and body composition were measured at baseline, and 1 and 6 months. Six patients completed 1 month and 5, 6 months of GH therapy. IGF-I levels increased 4-fold within 1 month of GH treatment. Over 6 months, GH reduced buffalo hump size and excess visceral adipose tissue. Total body fat decreased (17.9 10.9 to 13.5 8.4 kg, P 0.05), primarily in the trunk region. Lean body mass increased (62.9 6.4 to 68.3 9.1 kg, P 0.03). Insulin-mediated glucose disposal, measured by a euglycemic hyperinsulinemic clamp, declined at month 1 (49.7 27.5 to 25.6 6.6 nmol/kg LBM min/pmol INSULIN /liter, P 0.04); values improved at month 6 (49.2 22.6, P 0.03, compared with month 1) and did not differ significantly from baseline. Similarly, the integrated response to an oral glucose load worsened at month 1 (glucose area under the curve 20.1 2.3 to 24.6 3.7 mmolh/liter, P < 0.01), whereas values improved at month 6 (22.1 1.5, P 0.02, compared with month 1) and did not differ significantly from baseline. One patient developed symptomatic hyperglycemia within 2 wk of GH initiation; baseline oral glucose tolerance testing revealed preexisting diabetes despite normal fasting glucose. In conclusion, GH at 3 mg/d resulted in a decrease in total body fat and an increase in lean body mass in this open-label trial. While insulin sensitivity and glucose tolerance initially worsened, they subsequently improved toward baseline. However, the dose of GH used in this trial was supraphysiologic and led to an increase in IGF-I levels up to three times the upper normal range. Because there are known adverse effects of long-term GH excess, the effectiveness of lower doses of GH should be studied. We also recommend a screening oral glucose tolerance test be performed to exclude subjects at risk for GH-induced hyperglycemia. (
CloudGenius: Decision Support for Web Server Cloud Migration (2012)

Cloud computing is the latest computing paradigm that delivers hardware and software resources as virtualized services in which users are free from the burden of worrying about the low-level system administration details. Migrating Web applications to Cloud services and integrating Cloud services into existing computing infrastructures is non-trivial. It leads to new challenges that often require innovation of paradigms and practices at all levels: technical, cultural, legal, regulatory, and social. The key problem in mapping Web applications to virtualized Cloud services is selecting the best and compatible mix of software images (e.g., Web server image) and infrastructure services to ensure that Quality of Service (QoS) targets of an application are achieved. The fact that, when selecting Cloud services, engineers must consider heterogeneous sets of criteria and complex dependencies between infrastructure services and software images, which are impossible to resolve manually, is a critical issue. To overcome these challenges, we present a framework (called CloudGenius) which automates the decision-making process based on a model and factors specifically for Web server migration to the Cloud. CloudGenius leverages a well known multi-criteria decision making technique, called Analytic Hierarchy Process, to automate the selection process based on a model, factors, and QoS parameters related to an application. An example application demonstrates the applicability of the theoretical CloudGenius approach. Moreover, we present an implementation of CloudGenius that has been validated through experiments.
Ibrutinib antagonizes rituximab-dependent NK cell–mediated cytotoxicity (2014)

To the editor:

Ibrutinib is an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) with promising activity in CD20+ B-cell malignancies including recent US Food and Drug Administration approval in mantle cell lymphoma.[1][1] Given the homology between BTK and interleukin-2 inducible tyrosine
Anti-apoptotic and growth-stimulatory functions of CK1 delta and epsilon in ductal adenocarcinoma of the pancreas are inhibited by IC261 in vitro and in vivo (2008)

Targeting CK1 isoforms by IC261 influences both pancreatic tumour cell growth and apoptosis sensitivity in vitro and the growth of induced tumours in vivo, thus providing a promising new strategy for the treatment of pancreatic tumours.
Directed evolution of novel polymerase activities: Mutation of a DNA polymerase into an efficient RNA polymerase (2002)

The creation of novel enzymatic function is of great interest, but remains a challenge because of the large sequence space of proteins. We have developed an activity-based selection method to evolve DNA polymerases with RNA polymerase activity. The Stoffel fragment (SF) of Thermus aquaticus DNA polymerase I is displayed on a filamentous phage by fusing it to a pIII coat protein, and the substrate DNA template/primer duplexes are attached to other adjacent pIII coat proteins. Phage particles displaying SF polymerases, which are able to extend the attached oligonucleotide primer by incorporating ribonucleoside triphosphates and biotinylated UTP, are immobilized to streptavidin-coated magnetic beads and subsequently recovered. After four rounds of screening an SF library, three SF mutants were isolated and shown to incorporate ribonucleoside triphosphates virtually as efficiently as the wild-type enzyme incorporates dNTP substrates.
Vaccinia DNA Topoisomerase I: Kinetic Evidence for General Acid-Base Catalysis and a Conformational Step (1994)

The pH dependences of the internal equilibrium (Kcl) and rate constants for site-specific DNA strand cleavage (kcl) and resealing (kr) catalyzed by Vaccinia DNA topoisomerase I have been investigated using single-turnover conditions in the pH range 4.6-9.8 at 20 degrees C. The pH dependence of the rate constant for strand cleavage (kcl) shows a bell-shaped profile with apparent pKa values of 6.3 +/- 0.2 and 8.4 +/- 0.2, suggesting base catalysis of the attack of the active site Tyr-274 on the phosphodiester phosphorus, and acid catalysis of the expulsion of the 5'-deoxyribose oxygen. A low pKa (i.e., 6.3) for Tyr-274 in the free enzyme is ruled out by NMR titration from pH 5.1 to 8.8 monitoring the C-zeta chemical shift of [zeta-13C]-tyrosine-enriched topoisomerase. The dependence of the internal equilibrium constant (Kcl) on pH reveals very similar pKa values as kcl (5.8 +/- 0.2 and 8.6 +/- 0.2). However, kr is found to be independent of pH. The differing response of kcl and kr to pH rules out a simple two-state internal cleavage equilibrium and suggests that a conformational change occurs following formation of the covalent complex which retains the correct protonation state for strand religation. A conformation step is further indicated by a 4.6-fold "thio effect" on kcl upon substitution of the nonbridging oxygen atom of the attacked phosphoryl group by sulfur [Stivers, J. T., Shuman, S., & Mildvan, A. S. (1994) Biochemistry 33, 327], and the absence of such an effect on kr, (krphos/krthio = 0.9 +/- 0.2), indicating the rates of cleavage and religation to be limited by covalent chemistry and a conformational step, respectively. The rate constant of this conformational change in the direction of religation agrees with the average rate constant for supercoil release from plasmid substrates, suggesting this conformational change to be a part of the topoisomerization step. Although the general acid and general base catalysts have not yet been identified, the quantitative roles of these and other residues in catalysis are discussed.
Bayesian Poisson Tucker Decomposition for Learning the Structure of International Relations (2016)

We introduce Bayesian Poisson Tucker decomposition (BPTD) for modeling country--country interaction event data. These data consist of interaction events of the form "country $i$ took action $a$ toward country $j$ at time $t$." BPTD discovers overlapping country--community memberships, including the number of latent communities. In addition, it discovers directed community--community interaction networks that are specific to "topics" of action types and temporal "regimes." We show that BPTD yields an efficient MCMC inference algorithm and achieves better predictive performance than related models. We also demonstrate that it discovers interpretable latent structure that agrees with our knowledge of international relations.
Prevalence and Clinical Importance of Aortic Valve Calcification Detected Incidentally on CT Scans: Comparison with Echocardiography (2006)

Aortic valve calcification was an incidental finding on 18% of multi-detector row CT scans. The grade of aortic valve calcification is correlated with the hemodynamic severity of aortic valve disease as determined with echocardiography.
Carcinoma cell lines become sensitive to DNA-damaging agents by the expression of the adenovirus E1A gene. (1996)

Squamous cell carcinomas can show different oncogenic alterations, histological patterns, and an unpredictable clinical behavior. We previously reported that the adenovirus E1a gene may induce sensitivity to DNA-damaging agents in mouse keratinocytes. In order to study whether E1a expression could be used as a therapeutic agent in different malignant cell lines carrying mutations on the p53 gene and other oncogenic alterations, we transfected and infected several murine and human carcinoma cell lines (HaCa4; MSC11A5; HeLa) with vectors containing the 13S or 12S E1a region. We evaluated the sensitivity to cisplatin (CDDP), doxorubicin (DOX) and gamma irradiation (RX) by the crystal violet method. The induction of apoptosis was assessed by flow cytometry and presence of DNA ladders in agarose gels. The expression of E1a and the tumor suppressor p53 protein was analysed by Western blotting. The carcinoma cell lines expressing E1a were about four- to tenfold more sensitive to CDDP and RX, respectively, than the control cells. Moreover, the reduction in cell viability and cell growth after exposure to CDDP or RX was very significant in the carcinoma cells expressing E1a. With these results, we conclude that expression of E1a may confer great sensitivity to DNA-damaging agents on squamous cell carcinoma cells independently of the p53 protein status and other oncogenic alterations.
Morphology of polyanhydride microsphere delivery systems. (1990)

Scanning electron microscopy (SEM) was used to elucidate the mechanism of polymer degradation and drug release in polyanhydride microspheres. Three different fabrication methods--solvent removal, solvent evaporation, and hot melt microencapsulation--were used to prepare polyanhydride microspheres containing a variety of drugs. The morphology of these microspheres releasing drug in vitro and in vivo was studied by SEM and compared with degradation and release data measured by conventional methods. Microspheres prepared by the three techniques were shown to have distinctive morphological characteristics induced by the nature of the fabrication method. In addition, SEM analysis could be used to explain the drug release profiles and polymer degradation behavior seen in vitro as well as the in vivo effects of insulin-loaded microspheres on diabetic rats. This study has shown SEM to be an important and powerful tool for analyzing the effects of microsphere fabrication method on drug release.
Distances between the Paclitaxel, Colchicine, and Exchangeable GTP Binding Sites on Tubulin (1998)

Distances between the paclitaxel, colchicine, and exchangeable GTP binding sites on tubulin polymers have been probed using fluorescence spectroscopy. Techniques for measuring fluorescence resonance energy transfer (FRET) between fluorescent or chromophoric ligands for each binding site were employed. 2-Debenzoyl-2-(m-aminobenzoyl)paclitaxel (2-AB-PT) was the fluorophore ligand for the paclitaxel binding site; thiocolchicine, allocolchicine, and MDL 27048 were probes for the colchicine site, and 2'(or 3')-O-(trinitrophenyl)guanosine 5'-triphosphate (TNP-GTP) was the fluorophore ligand for the exchangeable GTP site. The distance between the colchicine and paclitaxel binding sites was determined with two different acceptor ligands in the colchicine site. An average distance distribution of 17 A was found in both cases. Energy transfer between 2-AB-PT bound to the paclitaxel site and TNP-GTP (acceptor) bound to the exchangeable GTP site was observed in the polymer. The average distance distribution between the fluorophores was 16.0 A, but the half-width of the distribution was large (17.9 A), which indicates that energy transfer between more than one donor-acceptor pair occurred in the system. One interpretation of this result is that 2-AB-PT serves as an energy transfer donor for two GTP sites, one contained on the same subunit and one on an adjacent protofilament. No FRET was observed between ligands bound to the colchicine and exchangeable GTP sites, indicating that the result of colchicine binding on the GTP region of beta-tubulin is a long range, allosteric effect. The results from these experiments are interpreted in terms of known structural features of microtubules.
Fibroblast Response to Gadolinium (2010)

The responses to gadolinium chloride are similar to responses previously seen with chelated Gd3+ in clinically used magnetic resonance imaging contrast agents. Fibroblast responses appear to reflect Gd3+-induced PDGF receptor activation and downstream signaling. Increased dermal fibroblast proliferation in conjunction with effects on matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 could contribute to the fibroplastic/fibrotic changes seen in the lesional skin of individuals with nephrogenic systemic fibrosis.
Molecular cloning of the mouse grb2 gene: differential interaction of the Grb2 adaptor protein with epidermal growth factor and nerve growth factor receptors. (1993)

We report the isolation and molecular characterization of the mouse grb2 gene. The product of this gene, the Grb2 protein, is highly related to the Caenorhabditis elegans sem-5 gene product and the human GRB2 protein and displays the same SH3-SH2-SH3 structural motifs. In situ hybridization studies revealed that the mouse grb2 gene is widely expressed throughout embryonic development (E9.5 to P0). However, grb2 transcripts are not uniformly distributed, and in certain tissues (e.g., thymus) they appear to be regulated during development. Recent genetic and biochemical evidence has implicated the Grb2 protein in the signaling pathways that link cell surface tyrosine kinase receptors with Ras. We have investigated the association of the Grb2 protein with epidermal growth factor (EGF) and nerve growth factor (NGF) receptors in PC12 pheochromocytoma cells. EGF treatment of PC12 cells results in the rapid association of Grb2 with the activated EGF receptors, an interaction mediated by the Grb2 SH2 domain. However, Grb2 does not bind to NGF-activated Trk receptors. Mitogenic signaling of NGF in NIH 3T3 cells ectopically expressing Trk receptors also takes place without detectable association between Grb2 and Trk. These results suggest that whereas EGF and NGF can activate the Ras signaling pathway in PC12 cells, only the EGF receptor is likely to do so through a direct interaction with Grb2. Finally, binding studies with glutathione S-transferase fusion proteins indicate that Grb2 binds two distinct subsets of proteins which are individually recognized by its SH2 and SH3 domains. These observations add further support to the concept that Grb2 is a modular adaptor protein.
Thermal behaviour of graft copolymers of sodium alginate (1996)

Abstract The thermal stability of sodium alginate (SA) and its graft copolymers of acrylonitrile (AN), methyl acrylate (MA), ethyl acrylate (EA) and methyl methacrylate (MMA) has been examined in air atmosphere by means of thermogravimetric analysis. The following order of decreasing stability was found from characteristic decomposition temperatures: SA‐g‐PAN &gt; SA‐g‐PMA &gt; SA‐g‐PEA &gt; SA‐g‐PMMA. The overall thermal stability of the different SA graft copolymers was evaluated by comparing their activation energies of thermal degradation; it agreed with the same order of thermal stability.
Metamaterials and Negative Refractive Index (2004)

Recently, artificially constructed metamaterials have become of considerable interest, because these materials can exhibit electromagnetic characteristics unlike those of any conventional materials. Artificial magnetism and negative refractive index are two specific types of behavior that have been demonstrated over the past few years, illustrating the new physics and new applications possible when we expand our view as to what constitutes a material. In this review, we describe recent advances in metamaterials research and discuss the potential that these materials may hold for realizing new and seemingly exotic electromagnetic phenomena.
Association of a putative regulatory polymorphism in the PD‐1 gene with susceptibility to type 1 diabetes (2003)

The immunoreceptor programmed cell death-1 (PD-1) is reported to play an important role in the regulation of peripheral tolerance in rodents, and it was recently shown that a polymorphism in a regulatory site of the PD-1 gene is associated with susceptibility to the autoimmune disease systemic lupus erythematosus (SLE) in humans. We investigated the existence of single-nucleotide polymorphisms (SNPs) in the PD-1 gene in patients with type 1 diabetes in comparison with healthy control subjects, by analyzing 94 children and adolescents with type 1 diabetes diagnosed before their eighteenth birthday (male : female = 52 : 42) and 155 control subjects. Polymorphisms in the complete PD-1 gene (minus the large intron 1) were detected by sequencing. In total, we identified 14 SNPs, of which six have been previously described, including an intronic 7146G/A SNP. We found this polymorphism to be associated with the development of type 1 diabetes [found in 12.2% of diabetic individuals vs 6.8% in controls; odds ratio (OR) = 1.92]. The associated allele is previously shown to alter a transcription factor-binding site (RUNX1/AML1), and the results of this study suggest that this allele could act as an additional susceptibility allele to type 1 diabetes.
Roles of DegP in Prevention of Protein Misfolding in the Periplasm upon Overexpression of Penicillin Acylase in Escherichia coli (2003)

Enhancement of the production of soluble recombinant penicillin acylase in Escherichia coli via coexpression of a periplasmic protease/chaperone, DegP, was demonstrated. Coexpression of DegP resulted in a shift of in vivo penicillin acylase (PAC) synthesis flux from the nonproductive pathway to the productive one when pac was overexpressed. The number of inclusion bodies, which consist primarily of protein aggregates of PAC precursors in the periplasm, was highly reduced, and the specific PAC activity was highly increased. DegP was a heat shock protein induced in response to pac overexpression, suggesting that the protein could possibly suppress the physiological toxicity caused by pac overexpression. Coexpression of DegP(S210A), a DegP mutant without protease activity but retaining chaperone activity, could not suppress the physiological toxicity, suggesting that DegP protease activity was primarily responsible for the suppression, possibly by degradation of abnormal proteins when pac was overexpressed. However, a shortage of periplasmic protease activity was not the only reason for the deterioration in culture performance upon pac overexpression because coexpression of a DegP-homologous periplasmic protease, DegQ or DegS, could not suppress the physiological toxicity. The chaperone activity of DegP is proposed to be another possible factor contributing to the suppression.
<title>Discrimination gain to optimize detection and classification</title> (1995)

A method for managing agile sensors to optimize detection and classification based on discrimination gain is presented. Expected discrimination gain is used to determine threshold settings and search order for a collection of discrete detection cells. This is applied in a low signal-to-noise environment where target-containing cells must be sampled many times before a target can be detected or classified with high confidence. Bayes rule is used to compute the expected discrimination gain for each sample region using estimated probability that it contains a target. This gain is used to select the optimal cell for the next sample. The effectiveness of this approach was assessed in a simple test case by comparing the result of discrimination optimized search with direct search. For a single 0 dB Gaussian target, the error rate for discrimination optimized search was similar to the direct search result against a 6 dB target.
Ordering in thin films of asymmetric diblock copolymers (2001)

The time evolution of the free surface of asymmetric diblock copolymers of polystyrene and poly(methyl methacrylate) on a strongly interacting surface was studied with atomic force microscopy. The surface morphology underwent morphological transitions to satisfy commensurability conditions. These transformations were consistent with recent self-consistent field arguments predicting the phase transitions of copolymers as a function of thickness (see M. J. Fasolka, P. Banerjee, A. M. Mayes, G. Pickett, & A. C. Balazs, Macromolecules 2000, 33, 5702). © 2001 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 39: 663–668, 2001
Investigation of the Initiation Behavior of a Dendritic 12-Arm Initiator in Atom Transfer Radical Polymerization (2001)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTInvestigation of the Initiation Behavior of a Dendritic 12-Arm Initiator in Atom Transfer Radical PolymerizationAndreas Heise, Steve Diamanti, James L. Hedrick, Curtis W. Frank, and Robert D. MillerView Author Information IBM Research Center, 650 Harry Road, San Jose, California 95120, and Department of Chemical Engineering, Stanford University, Stanford, California 95305 Cite this: Macromolecules 2001, 34, 11, 3798–3801Publication Date (Web):April 18, 2001Publication History Received29 August 2000Published online18 April 2001Published inissue 1 May 2001https://doi.org/10.1021/ma001508pCopyright © 2001 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views416Altmetric-Citations58LEARN 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 (55 KB) Get e-AlertsSUBJECTS:Organic compounds,Polymerization,Polymers,Radical polymerization,Star polymers Get e-Alerts