gebhart/patrepeval huggingface dataset:
Inhibition of Ileal Na+/Bile Acid Cotransporter by S-8921 Reduces Serum Cholesterol and Prevents Atherosclerosis in Rabbits (1998)

The ileal Na+/bile acid cotransporter (IBAT) plays an important role in the enterohepatic circulation of bile acids. We investigated the effects of IBAT inhibition on the maintenance of serum cholesterol level by using a novel IBAT inhibitor, S-8921, in rabbits. Administration of S-8921 by its incorporation into the diet (0.01% to 0.1%) for 1 to 2 weeks in heterozygous Watanabe heritable hyperlipidemic rabbits decreased serum cholesterol by 29% to 37% and increased fecal excretion of measured bile acids by 60% to 180% compared with control rabbits. Liver microsomal cholesterol 7alpha-hydroxylase and 3-hydroxy-3-methylglutaryl coenzyme A reductase activities were increased by 75% to 84% and 84% to 89%, respectively, with S-8921 treatment. S-8921 administration (0.1% in the diet) to normal New Zealand White rabbits for 2 weeks resulted in increased hepatic low density lipoprotein receptor expression, which was assessed by Northern blot analysis. In cholesterol-fed New Zealand White rabbits, S-8921 treatment (0.003% to 0.1% in the diet) for 10 weeks dose-dependently inhibited the development of hypercholesterolemia. It also inhibited the accumulation of cholesterol in the aortic arch and reduced the severity of coronary atherosclerosis. These results indicate that IBAT inhibition by S-8921 affects serum cholesterol, liver enzymes, low density lipoprotein receptor activity, and atherosclerosis in the same manner as bile acid sequestrants. We suggest that an IBAT inhibitor such as S-8921 could be useful in the treatment of hypercholesterolemia.
Use of Murine CXCR-4 as a Second Receptor by Some T-Cell-Tropic Human Immunodeficiency Viruses (1998)

The human CXCR-4 molecule serves as a second receptor for primary, T-cell-tropic, and laboratory-adapted human immunodeficiency virus type 1 (HIV-1) isolates. Here we show that murine CXCR-4 can support the entry of some of these HIV-1 isolates. Differences between mouse and human CXCR-4 in the ability to function as an HIV-1 receptor are determined by sequences in the second extracellular loop of the CXCR-4 protein.
Differential distribution of the adenovirus E1A proteins and colocalization of E1A with the 70-kilodalton cellular heat shock protein in infected cells (1988)

Five distinct localization patterns were observed for the adenovirus E1A proteins in the nuclei of infected HeLa cells: diffuse, reticular, nucleolar, punctate, and peripheral. The variable distribution of E1A was correlated with the time postinfection and the cell cycle stage of the host cell at the time of infection. All staining patterns, with the exception of peripheral E1A localization, were associated with the early phase of infection since only the diffuse, reticular, nucleolar, and punctate staining patterns were observed in the presence of hydroxyurea. Because the E1A proteins (12S and 13S) stimulate the expression of the cellular heat shock 70-kilodalton protein (hsp70), we examined the intracellular distribution of hsp70 in the adenovirus-infected cells. Whereas hsp70 was predominantly cytoplasmic in the cells before infection, after adenovirus infection most of the protein was now found within the nucleus. Specifically, hsp70 was found within the nucleoli as well as exhibiting reticular, diffuse, and punctate nuclear staining patterns, analogous to those observed for the E1A proteins. Double-label indirect immunofluorescence of E1A and hsp70 in infected cells demonstrated a colocalization of these proteins in the nucleus. Translocation of hsp70 to the nucleus was dependent upon both adenovirus infection and expression of the E1A proteins. The localization of hsp70 was unaltered by infection with an E1A 9S cDNA virus which does not synthesize a functional E1A gene product. Moreover, the discrete nuclear localization patterns of E1A and the colocalization of E1A with hsp70 were not observed in adenovirus-transformed 293 cells which constitutively express E1A and E1B. E1A displayed exclusively diffuse nuclear staining in 293 cells; however, localization of E1A into the discrete nuclear patterns occurred after adenovirus infection of 293 cells. Immunoprecipitation of labeled infected-cell extracts with a monoclonal antibody directed against the E1A proteins resulted in precipitation of small amounts of hsp70 along with E1A. These data indicate that the adenovirus E1A proteins colocalize with, and possibly form a physical complex with, cellular hsp70 in infected cells. The relevance of this association, with respect to the function of these proteins during infection and the association of other oncoproteins with hsp70, is discussed.
Isolation and Characterization of a Glucosamine-Requiring Mutant of Escherichia coli K-12 Defective in Glucosamine-6-Phosphate Synthetase (1971)

A mutant was isolated from Escherichia coli K-12 which requires glucosamine or N-acetylglucosamine for growth. Depriving the mutant of glucosamine resulted in a rapid loss of viability of the cells, followed by a decrease in the turbidity of the culture. When the mutant cells were resuspended in broth media containing 10% sucrose, the rod-shaped cells became spheroplasts. However, the presence of sucrose in the media did not prevent the cells from losing their viability. This mutant was shown to be deficient in the activity of l-glutamine:d-fructose-6-phosphate aminotransferase (EC 2.6.1.16). The activity of the deaminating enzyme, 2-amino-2-deoxy-d-glucose-6-phosphate ketol-isomerase (EC 5.3.1.10), appeared to be normal in this mutant. The position of the mutation has been determined to be at the 74th min of the Taylor and Trotter map, as shown by cotransduction with phoS (90%) and ilv (25%) by using bacteriophage P1.
Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia (2006)

The present study was designed to assess the effects of dietary leucine supplementation on muscle protein synthesis and whole body protein kinetics in elderly individuals. Twenty healthy male subjects (70 +/- 1 years) were studied before and after continuous ingestion of a complete balanced diet supplemented or not with leucine. A primed (3.6 micromol kg(-1)) constant infusion (0.06 micromol kg(-1) min(-1)) of L-[1-13C]phenylalanine was used to determine whole body phenylalanine kinetics as well as fractional synthesis rate (FSR) in the myofibrillar fraction of muscle proteins from vastus lateralis biopsies. Whole body protein kinetics were not affected by leucine supplementation. In contrast, muscle FSR, measured over the 5-h period of feeding, was significantly greater in the volunteers given the leucine-supplemented meals compared with the control group (0.083 +/- 0.008 versus 0.053 +/- 0.009% h(-1), respectively, P < 0.05). This effect was due only to increased leucine availability because only plasma free leucine concentration significantly differed between the control and leucine-supplemented groups. We conclude that leucine supplementation during feeding improves muscle protein synthesis in the elderly independently of an overall increase of other amino acids. Whether increasing leucine intake in old people may limit muscle protein loss during ageing remains to be determined.
Tailored Living Block Copolymerization: Multiblock Poly(cyclohexene carbonate)s with Sequence Control (2011)

ADVERTISEMENT RETURN TO ISSUEPREVCommunication to the...Communication to the EditorNEXTTailored Living Block Copolymerization: Multiblock Poly(cyclohexene carbonate)s with Sequence ControlJeung Gon Kim†, Christina D. Cowman†, Anne M. LaPointe†, Ulrich Wiesner‡, and Geoffrey W. Coates*†View Author Information† Department of Chemistry and Chemical Biology‡ Department of Materials Science and Engineering Cornell University, Ithaca, New York 14853, United States*Corresponding author. E-mail: [email protected]Cite this: Macromolecules 2011, 44, 5, 1110–1113Publication Date (Web):February 3, 2011Publication History Received12 November 2010Revised14 January 2011Published online3 February 2011Published inissue 8 March 2011https://doi.org/10.1021/ma102585aCopyright © 2011 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views3845Altmetric-Citations100LEARN 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 (1 MB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Catalysts,Copolymerization,Copolymers,Monomers,Polymers Get e-Alerts
Cell cycle-specific effects of tumor necrosis factor. (1984)

The immediate effect of tumor necrosis factor (TNF) added to cultures of L-cells is cytostasis, manifested as cell arrest in G2. This effect prevails during the initial 4 hr when the number of G2 cells increases markedly in the absence of any significant cell death in the culture. Shortly thereafter, the cytolytic effect becomes apparent; extensive cell lysis can be detected after 7 hr of exposure to TNF. After 24 hr nearly all cells are lysed. Results of experiments in which the effects of TNF on the kinetics of cell progression through various phases of the cell cycle were studied indicate that in the presence of TNF cells do progress through G2, although with considerable delay, and reach mitosis. Most cells die (undergo lysis) specifically at late stages of mitosis (telophase) or soon after cytokinesis. Sensitivity of cells to the lytic effect of TNF is increased by cell arrest in mitosis with Colcemid or vinblastine. TNF exerts little effect on rates of cell progression through G1 or S phases of the cell cycle, although few cells die during S phase. Nonlysed cells from cultures treated with TNF do not show any changes in nuclear chromatin, suggesting that neither DNA nor nuclear proteins are the primary targets of the TNF. The present data implicate metabolic changes which occur during mitosis (cytokinesis), perhaps associated with synthesis or assembly of cell membrane components, as being responsible for increased cell sensitivity towards the cytolytic effect of TNF. The mechanism of the early cytostatic effect of the factor is unknown.
Lymphocyte receptors. II. Receptors for rabbit IgM on human T lymphocytes. (1976)

Lipoprotein metabolism is governed by a highly complex network of metabolic pathways involved in lipid and protein synthesis and degradation. Understanding the dynamics of network regulation is impossible without the help of computational modeling. We present a new modeling approach to analyze the long term effects of a dietary or pharmacological intervention in lipoprotein metabolism. A concept of time-dependent evolution of model parameters is introduced to study the dynamics of metabolic network adaptations. The progression of these adaptations is predicted by identifying necessary dynamic changes in the model parameters to describe the transition of steady states during different stages of the dietary or pharmacological treatment. The trajectories provide insight into the affected underlying biological systems and provide targeted direction to the molecular events that should be studied in more detail to unravel the mechanistic basis of treatment outcome. Modulating effects on pathways caused by interactions with the proteome and transcriptome levels can be captured by the time-dependent descriptions of the parameters. The approach was employed to identify metabolic adaptations induced upon a 3-week activation of the liver X receptor (LXR) in C57BL/6J wild-type mice. The metabolic trajectories were modeled to analyze the metabolic adaptations in time. This provided a number of sometimes counterintuitive insights into the underlying mechanisms inducing hepatic steatosis, dynamic changes in plasma triglycerides, and plasma HDL content. The model predicted for instance decreased activity of the scavenger receptor class B1 (SR-B1) despite an increased flux mediated via the receptor. This prediction was validated experimentally by immunoblotting measurements of SR-B1 in hepatic membranes. We also show that this procedure can be used quite simply to select optimal therapeutic targets successfully.
Combined radiation and hyperthermia in superficial human tumors (1980)

Hyperthermia (42--43 C) appears to potentiate the effects of radiation therapy in experimental tumor models. In addition, some studies indicate that tumors may be sensitized to a greater extent than normal tissue. This study was designed to test whether the effectiveness of irradiating human tumors was enchanced significantly by concomitant heating. We also examined skin to see if heating enhanced the response to radiation of normal tissues. Nineteen patients with multiple metastatic superficial tumor masses of various histologies were studied. All were considered incurable and an independent clinical decision had been made to irradiate for palliation. Two or more masses in the same patient were matched for size and location, so that one of the patient's own tumors was a control to monitor the effect of irradiation alone. On each patient the tumors were treated with identical fractions and to the same total dose of radiation. One of the matched nodules was given hyperthermia (43 C) for 15 minutes before and 30 minutes after each radiation fraction. The response of the tumor that received radiation alone was compared with that of the tumor receiving hyperthermia and radiation. In seven of 15 evaluable patients the tumor that received heat in addition to radiation had a greater objective response than the tumor receiving radiation alone (P < .065). Of the remaining eight patients, four had complete tumor regression in both areas without later regrowth, two failed to respond in either area, and two partially responded in both areas. Two patients had increased cutaneous reaction to radiation in the heated area; one of these was a severe desquamative reaction, which conformed to the size and shape of the ultrasound field. These results suggest that hyperthermia improves the objective response to radiation in some human tumors; in two cases it appeared to sensitize skin as well.
The electrode–skin interface and optimal detection of bioelectric signals (2010)

Despite many years of research and a few review articles (McAdams et al 1996, Franks et al 2005), the problem of detecting bioelectric signals (ECG, EMG, EEG, etc) from the skin of human subjects has still not been solved in a fully satisfactory way, especially for the case of EMG where signals may be acquired during motion and with large arrays of small and close contacts, making the requirements more challenging. The classical approach involves a small metal surface (10–200 mm2) applied to the skin using conductive gel or glue as an interface (McAdams et al 1996). Capacitive electrodes, dry electrodes, and electrodes with rough surfaces, porous or covered by biolayers or tiny pins (0.2–0.4 mm long) penetrating the 'stratum corneum' are being investigated in many research laboratories (Oehler et al 2008).
Structural Consensus among Antibodies Defines the Antigen Binding Site (2012)

The Complementarity Determining Regions (CDRs) of antibodies are assumed to account for the antigen recognition and binding and thus to contain also the antigen binding site. CDRs are typically discerned by searching for regions that are most different, in sequence or in structure, between different antibodies. Here, we show that ~20% of the antibody residues that actually bind the antigen fall outside the CDRs. However, virtually all antigen binding residues lie in regions of structural consensus across antibodies. Furthermore, we show that these regions of structural consensus which cover the antigen binding site are identifiable from the sequence of the antibody. Analyzing the predicted contribution of antigen binding residues to the stability of the antibody-antigen complex, we show that residues that fall outside of the traditionally defined CDRs are at least as important to antigen binding as residues within the CDRs, and in some cases, they are even more important energetically. Furthermore, antigen binding residues that fall outside of the structural consensus regions but within traditionally defined CDRs show a marginal energetic contribution to antigen binding. These findings allow for systematic and comprehensive identification of antigen binding sites, which can improve the understanding of antigenic interactions and may be useful in antibody engineering and B-cell epitope identification.
In Vitro Antimicrobial Susceptibility Testing of Bacterial Enteropathogens Causing Traveler's Diarrhea in Four Geographic Regions (2001)

The emergence of resistant enteropathogens has been reported worldwide. Few data are available on the contemporary in vitro activities of commonly used antimicrobial agents against enteropathogens causing traveler's diarrhea (TD). The susceptibility patterns of antimicrobial agents currently available or under evaluation against pathogens causing TD in four different areas of the world were evaluated. Pathogens were identified in stool samples from U.S., Canadian, or European adults (18 years of age or older) with TD during 1997, visiting India, Mexico, Jamaica, or Kenya. MICs of 11different antimicrobials were determined against 284 bacterial enteropathogens by the agar dilution method. Ciprofloxacin, levofloxacin, ceftriaxone, and azithromycin were highly active in vitro against the enteropathogens, while traditional antimicrobials such as ampicillin, trimethoprim, and trimethoprim/sulfamethoxazole showed high levels and high frequencies of resistance. Rifaximin, a promising and poorly absorbable drug, had an MIC at which 90% of the strains tested were inhibited of 32 microg/ml, 250 times lower than the concentration of this drug in the stools. Amdinocillin, nalidixic acid, and doxycycline showed moderate activity. Fluoroquinolones are still the drugs of choice for TD in most regions of the world, although our study has a limitation due to the lack of Escherichia coli samples from Kenya and possible bias in selection of the patients for evaluation. Azithromycin and rifaximin should be considered as promising new agents. The widespread in vitro resistance of the traditional antimicrobial agents reported since the 1980s and the new finding of resistance to fluoroquinolones in Southeast Asia are the main reasons for monitoring carefully the antimicrobial susceptibility patterns worldwide and for developing and evaluating new antimicrobial agents for the treatment of TD.
FTIR fiber optics and FT-Raman spectroscopic studies for the diagnosis of cancer. (2000)

The authors' preliminary investigation has shown that FTIR spectroscopy in conjunction with fiber optics can reflect differences between normal and malignant tissues. Further studies are being conducted to determine the applicability of the technique to cancer diagnosis.
Copula-based Kernel Dependency Measures (2012)

The paper presents a new copula based method for measuring dependence between random variables. Our approach extends the Maximum Mean Discrepancy to the copula of the joint distribution. We prove that this approach has several advantageous properties. Similarly to Shannon mutual information, the proposed dependence measure is invariant to any strictly increasing transformation of the marginal variables. This is important in many applications, for example in feature selection. The estimator is consistent, robust to outliers, and uses rank statistics only. We derive upper bounds on the convergence rate and propose independence tests too. We illustrate the theoretical contributions through a series of experiments in feature selection and low-dimensional embedding of distributions.
Baculovirus-Mediated Expression of Human 65 kDa and 67 kDa Glutamic Acid Decarboxylases in SF9 Insect Cells and Their Relevance in Diagnosis of Insulin-Dependent Diabetes Mellitus11 (1993)

cDNAs coding for the full-length human 65 and 67 kDa glutamic acid decarboxylases (GAD65 and GAD67) were amplified from pancreas and hippocampus cDNA libraries by polymerase chain reaction, respectively. Both cDNAs were inserted into a baculovirus vector which mediated highly efficient expression of the human GAD65 and GAD67 with histidine-hexapeptides as affinity ligands at their C-termini in Spodoptera frugiperda (Sf9) cells. The recombinant GAD proteins were purified to homogeneity by affinity chromatography using a metal-chelating matrix. The infected Sf9 insect cells expressed the recombinant human GAD65 and GAD67 with natural-like conformations, as confirmed by measurement of their enzyme activities as well as their fully restored autoantigenicities. Immunoprecipitation of metabolically labeled infected Sf9 cells demonstrated the autoantigenic potential of the recombinant GAD proteins. The practicability of using recombinant GAD65 and GAD67 derived from the baculovirus expression system for the development of an immunoassay for the diagnosis of insulin-dependent diabetes mellitus is discussed.
Disulfide stabilization of antibody Fv: computer predictions and experimental evaluation (1995)

Using molecular modeling technology we have recently identified positions in conserved framework regions of Fvs which can be used to stabilize antibody Fvs by an interchain disulfide bond engineered in between the structurally conserved framework positions of the variable domains of heavy (VH) and light (VL) immunoglobulin chains (disulfide-stabilized Fv; dsFv). The computer model indicated the existence of other potential sites in the framework regions that might be suitable for disulfide bond formation between VH and VL. The possibility of obtaining dsFvs using these positions is evaluated here experimentally by constructing dsFv immunotoxins in which the Fv moiety is fused to a truncated form of Pseudomonas exotoxin. We analyzed the extent of dsFv formation and the activity of the resulting dsFv immunotoxins, and compared various dsFv molecules with the scFv immunotoxin. Our results demonstrate that position H44-L105 is the only one which gives high production yields of active dsFv. All other positions gave either low yields and activity or completely failed to produce active dsFv. With one exception, the formation and activities of the dsFvs corresponded to the C alpha-C alpha distance between the VH and VL positions, with an optimal distance of 5.7 A producing the best dsFv. Distances of 6.0-6.9 A resulted in a low yield of protein that was still capable of binding antigen, whereas distances > 7.0 A resulted in molecules in which dsFv formation was not obtained.
Signalling in a component based world (2002)

To provide ubiquitous access to applications, the QoS and computing requirements of the various components of the application must adapt.,The authors argue that the appropriate techniques for providing adaptive interfaces is through open implementation, in which the abstractions to control behaviour are couched in the language of the component, not some generic QoS definition language. They describe how open implementation techniques can be applied to determining QoS configuration, and report on their experiences in implementing such an architecture for low bandwidth access to networked multimedia.