gebhart/patrepeval huggingface dataset:
Acute Effects of Febuxostat, a Nonpurine Selective Inhibitor of Xanthine Oxidase, in Pacing Induced Heart Failure (2006)

We investigated whether xanthine oxidase inhibition with febuxostat enhances left ventricular (LV) function and improves myocardial high energy phosphates (HEP) in dogs with pacing-induced heart failure (CHF). Febuxostat (2.2 mg/kg over 10 minutes followed by 0.06 mg/kg/min) caused no change of LV function or myocardial oxygen consumption (MVO2) at rest or during treadmill exercise in normal dogs. In dogs with CHF, febuxostat increased LV dP/dtmax at rest and during heavy exercise (P < 0.05), indicating improved LV function with no change of MVO2. Myocardial adenosine triphosphate (ATP) and phosphocreatine (PCr) were examined using 31P nuclear magnetic resonance spectroscopy in the open chest state. In normal dogs, febuxostat increased PCr/ATP during basal conditions and during high workload produced by dobutamine + dopamine (P < 0.05). PCr/ATP was decreased in animals with CHF; in these animals, febuxostat (given after completing basal and high workload measurements with vehicle) tended to increase PCr/ATP during basal conditions with no effect during catecholamine stimulation. Thus, febuxostat improved LV performance in awake dogs with CHF, but caused only a trend toward increased PCr/ATP in the open chest state. It is possible that the antecedent high workload condition prior to drug administration blunted the effect of febuxostat on HEP in the CHF animals. Alternatively, beneficial effects of febuxostat on LV performance in the failing heart may not involve HEP.
Synthetic glycoprotein D-related peptides protect mice against herpes simplex virus challenge (1985)

Glycoprotein D (gD) of herpes simplex virus (HSV) protects mice from a lethal challenge by either HSV type 1 (HSV-1; oral) or HSV-2 (genital). We evaluated whether synthetic peptides representing residues 1 through 23 of gD (mature protein) can be used as a potential synthetic herpesvirus vaccine. The immunogenicity of the peptides was demonstrated by the biological reactivity of antipeptide sera in immunoprecipitation and neutralization assays. All sera which immunoprecipitated gD had neutralizing against both HSV-1 and HSV-2. The highest titers were found in animals immunized with the longest peptides. The region of residues 1 through 23 was immunogenic regardless of whether the type 1 or type 2 sequence was presented to the animal. Immunization of mice with gD or synthetic peptides conferred solid protection against a footpad challenge with HSV-2. However, the peptides were not as effective as gD in protection against an intraperitoneal challenge. The results suggested that synthetic vaccines based on gD show promise and should be more rigorously tested in a variety of animal models.
Dim Light at Night Disrupts Molecular Circadian Rhythms and Increases Body Weight (2013)

With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms that are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electric lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however, the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to dim light at night and investigated changes in the circadian system and metabolism. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night altered core circadian clock rhythms in the hypothalamus at both the gene and protein level. Circadian rhythms in clock expression persisted during light at night; however, the amplitude of Per1 and Per2 rhythms was attenuated in the hypothalamus. Circadian oscillations were also altered in peripheral tissues critical for metabolic regulation. Exposure to dimly illuminated, as compared to dark, nights decreased the rhythmic expression in all but one of the core circadian clock genes assessed in the liver. Additionally, mice exposed to dim light at night attenuated Rev-Erb expression in the liver and adipose tissue. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide evidence that mild changes in environmental lighting can alter circadian and metabolic function. Detailed analysis of temporal changes induced by nighttime light exposure may provide insight into the onset and progression of obesity and metabolic syndrome, as well as other disorders involving sleep and circadian rhythm disruption.
Isolation and characterization of cDNA clones specifically expressed in testicular germ cells (1994)

We have cloned cDNAs involved in germ cell-specific expression. For this, a subtracted cDNA library was generated by subtracting cDNAs derived from supporting cells of mutant testis from wild-type testis cDNAs. Detailed analyses of mRNA expression revealed that the genes corresponding to the cloned cDNAs were exclusively expressed in testes and were developmentally controlled.
The Drosophila Toll Gene Functions Zygotically and Is Necessary for Proper Motoneuron and Muscle Development (1995)

Toll is a maternally required Drosophila gene that encodes a transmembrane protein with an important function in embryonic dorsal-ventral patterning. The Toll protein is widely expressed zygotically, but its roles in late embryo-genesis have not been described in detail. We have examined the expression of Toll protein in the late embryonic central nervous system and somatic musculature. Toll is expressed in a dynamic pattern in teh musculature, initially in several muscle fibers in each hemisegment, with a later narrowing of expression to a single muscle fiber pair. Zygotic Toll mutants were used to investigate the development consequences of loss of Toll expression. We found that loss of one or both copies of the Toll gene leads to widespread defects in motoneuron number and muscle patterning. Loss of motoneurons prevents certain muscle fibers from receiving their wild-type innervation. Denervation in the mutants results in collateral sprouting from nearby nerve branches and leads to the appearance of ectopically placed motor endings. The limited expressivity observed suggests that Toll is only one of several genes required for proper motoneuron and muscle specification.
Role of interferon-gamma in interleukin 12-induced pathology in mice. (1995)

Interleukin 12 (IL-12) activates natural killer (NK) and T cells with the secondary synthesis and release of interferon-gamma (IFN-gamma) and other cytokines. IL-12-induced organ alterations are reported for mice and the pathogenetic role of IFN-gamma is investigated by the use of mice deficient in the IFN-gamma receptor (IFN-gamma R-/-). IL-12 caused a rapid infiltration of liver and splenic red pulp with activated macrophages; this and increased NK cells resulted in a fivefold increase of splenic weight in wild-type mice. Splenomegaly was associated with myelosuppression and decreasing peripheral leukocyte counts. IL-12-induced changes in wild-type mice were associated with markedly increased IFN-gamma serum levels and up-regulation of major histocompatibility complex (MHC) class I and II expression in various epithelia. IL-12 induced a qualitatively similar macrophage infiltration in IFN-gamma R-/- mice, less marked splenomegaly (to 2 x normal), and no MHC upregulation. Strikingly increased vascular endothelial intercellular adhesion molecule-1 expression was apparent in both IFN-gamma R-/- and IFN-gamma R+/+ mice. Restricted to mutant mice was a severe, invariably lethal, interstitial, and perivascular pulmonary macrophage infiltration with diffuse pulmonary edema. Extensive quantitative reverse transcriptase polymerase chain reaction analysis revealed an increase of only IL-6 and IL-10 pulmonary gene transcripts in IFN-gamma R-/- mice compared with wild-type mice. IL-12-induced myelosuppression is due to IFN-gamma-release from NK cells and T cells, and is associated with macrophage activation and distinct MHC class I and II antigen upregulation. The pulmonary pathology in IFN-gamma R-/- mice, however, reveals a toxic potential for IL-12 and suggests that endogenous IFN-gamma plays a protective role in preventing fatal pulmonary disease in these mice.
Spatial mapping of the chemical shift in NMR (1984)

Abstract In many biological systems, nuclear magnetic resonance chemical‐shift studies of 31 P, 13 C, and 1 H can be of great value as a means of studying metabolic processes in vivo. This information is likely to be of great clinical value in the diagnosis of disease and in the study and monitoring of the effect of drug treatment. This paper discusses two new techniques, based on the echo‐planar imaging (EPI) method. One is the echo‐planar shift mapping (EPSM) technique and the other is a hybrid projection reconstruction‐echo‐planar (PREP) method. Both methods may be used to obtain complete chemical‐shift spectra at each point of a specified grid in a chosen plane through the subject. A major attraction of the EPSM method is the very high speed at which this information is obtained. The major attraction of the PREP hybrid method is its simplicity. Both techniques have the advantage of speed and efficiency over both the point‐by‐point topical magnetic resonance (TMR) and 3D Fourier transform approaches. The new mapping techniques may also be used to measure magnetic field spatial inhomogeneities, caused by either the presence of magnetic material or simply nonalignment of the magnet.
Animal Cell Dna Polymerases (1986)

The authors present: General Introduction. Multiplicity of DNA Polymerases in Animal Cells. DNA Polymerase-..cap alpha... DNA Polymerase-..beta... DNA Polymerase-..gamma.. and DNA Polymerase-delta. Roles of Animal Cell DNA Polymerases in Replication of Cellular DNA. Roles of Animal Cell DNA Polymerases in DNA Repair Synthesis. Fidelity of DNA Synthesis. Biology of Animal Cell DNA Polymerases. Future Perspectives. Index.
CTLA-4 ligation delivers a unique signal to resting human CD4 T cells that inhibits interleukin-2 secretion but allows Bcl-X(L) induction. (1998)

We have assessed the functional effects of a panel of CTLA-4 mAbs on resting human CD4+ T cells. Our results demonstrate that some CTLA-4 mAbs can inhibit proliferative responses of resting CD4+ cells and cell cycle transition from G0 to G1. The inhibitory effects of CTLA-4 were evident within 4 h, at a time when cell surface CTLA-4 expression remained undetectable. Other CTLA-4 mAbs had no detectable inhibitory effects, indicating that binding of Ab to CTLA-4 alone is not sufficient to mediate down-regulation of T cell responses. Interestingly, while IL-2 production was shut off, inhibitory anti-CTLA-4 mAbs permitted induction and expression of the cell survival gene bcl-X(L). Consistent with this observation, cells remained viable and apoptosis was not detected after CTLA-4 ligation.
The effects of auricular transcutaneous electrical nerve stimulation (TENS) on experimental pain threshold and autonomic function in healthy subjects (1991)

The present study examines the effects of auricular transcutaneous electrical nerve stimulation (TENS) on electrical pain threshold measured at the ipsilateral wrist and autonomic functions including skin temperature, blood pressure and pulse rate in 24 healthy subjects. TENS was administered as low frequency trains of pulses delivered at a 'strong but comfortable' intensity to 1 of 3 auricular points to be examined: (i) autonomic effects (autonomic point), (ii) pain threshold effects (wrist point), and (iii) placebo effects at an unrelated point (face point). A fourth untreated group was designated as a situation control. The main finding of the study was that auricular TENS produced no significant overall effects on experimental pain threshold or autonomic functions recorded under the present conditions. However, pain threshold was found to increase by over 50% of its pretreatment baseline in 4 subjects and by 30% in 6 subjects. This rise was not dependent upon the site of auricular TENS. The possible mechanisms of such changes are discussed.
Task articulation in software maintenance: Integrating source code annotations with an issue tracking system (2008)

Managing and articulating development tasks is an important aspect of software maintenance. Developers already have a variety of specialty tools to support task management, for example, issue tracking and configuration management software, but they also make use of other tools within their software engineering environments to support software task management. An example of one such mechanism is the appropriation of source code comments to document finer grained details of formally specified tasks. In this research, we propose and present a tool that integrates these source code annotations with an issue tracking management system. We describe how this tool addresses deficiencies that occur in task management and propose future research to improve task management.
Retinoid signaling and cardiac anteroposterior segmentation (2001)

Establishment of anterior-posterior polarity is one of the earliest decisions in cardiogenesis. Specification of anterior (outflow) and posterior (inflow) structures ensures proper connections between venous system and inflow tract and between arterial tree and outflow tract. The last few years have witnessed remarkable progress in our understanding of cardiac anteroposterior patterning. Molecular cloning and subsequent studies on RALDH2, the key embryonic retinaldehyde dehydrogenase in retinoic acid (RA) synthesis, provided the missing link between teratogenic studies on RA deficiency and excess and normal chamber morphogenesis. We discuss work establishing the foundations of our current understanding of the mechanisms of cardiac anteroposterior segmentation, the reasons why early evidence pointing to the role of RA in anteroposterior segmentation was overlooked, and the key experiments unraveling the role of RA in cardiac anteroposterior segmentation. We have also integrated recent experiments in a model of cardiac anteroposterior patterning in which RALDH2 expression determines anteroposterior boundaries in the heart field.
The Physiologic Health Care Needs of HIV-Infected Black Men on Admission to an AIDS-Dedicated Nursing Home (2003)

The purpose of this study is to describe the physiologic health care needs of HIV-infected Black men on admission to an AIDS-dedicated nursing home. Participants were 68 Black men aged 26 to 60 years who were admitted to an AIDS-dedicated nursing home in the southern New England area between 1995 and 1999. The participants were very ill and weak on their admission to the nursing home, with most having diagnoses of AIDS (n = 65), an average Karnofsky Performance Scale score of 44 (SD = 14.90), and some degree of mental impairment. The late-stage of disease of the participants was reflected in their multiple symptomatology and functional impairment in activities of daily living. With patients living longer in the chronic disease stages of HIV disease, the results of this study provide support for the further investigation of the most effective long-term care settings for Black men with HIV/AIDS. The results also have implications for the multiple clinical roles nursing can assume within HIV/AIDS long-term care settings.
Introduction:  Combinatorial Chemistry (1997)

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTIntroduction: Combinatorial ChemistryJack W. SzostakView Author Information Department of Molecular Biology Massachusetts General Hospital Guest EditorCite this: Chem. Rev. 1997, 97, 2, 347–348Publication Date (Web):April 1, 1997Publication History Published online1 April 1997Published inissue 1 April 1997https://pubs.acs.org/doi/10.1021/cr9700080https://doi.org/10.1021/cr9700080editorialACS PublicationsCopyright © 1997 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views4875Altmetric-Citations66LEARN 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 PDF (23 KB) Get e-AlertscloseSUBJECTS:Chemical synthesis,Combinatorial chemistry,Nucleic acids,Solid phase synthesis,Viruses Get e-Alerts
Cellular infrared detector appears to be contained in the centrosome (1994)

Previous experiments have suggested that 3T3 cells were able to extend pseudopodia toward latex particles up to 60 microns away from the cell body if the particles were irradiated by an infrared beam in the range of 700-900 nm [Albrecht-Buehler, 1991: J. Cell Biol. 114:493-502]. The present article reports that this response of cells to infrared light can be inhibited if the cell center is simultaneously irradiated with a beam of the same light. In marked contrast, the cells responded normally to the presence of infrared light scattering particles if the second beam irradiated other parts of the cell body. The results imply that the cellular mechanism of infrared detection is located at the cell center. The infrared sensing mechanism remains intact in enucleated cells and in cells which were incubated in monensin to vesiculate their Golgi apparatus and inhibit their Golgi functions. Accordingly, it is proposed that the centrosome which contains the centrioles is the only remaining candidate in the cell center for a cellular detection device for the direction of infrared signal sources. The results support an earlier suggestion that centrioles may be such detection devices [Albrecht-Buehler, 1981: Cell Motil. Cytoskeleton 1:237-245].
Use of Porcine Factor VIII in the Management of Seventeen Patients with Factor VIII Antibodies (1984)

A polyelectrolyte-fractionated porcine factor VIII concentrate was given to 16 hemophiliacs with anti-F VIII antibodies (Ab) and to a woman with post-partum-acquired Ab during 24 courses of treatment including three major surgical procedures. Before treatment, antiporcine F VIII Ab was always lower than anti-human F VIII Ab, with a median cross reactivity of 32%. After treatment, the mean rise in F VIII was 1.5 U/dl/Unit infused/Kg b.w. and in vivo recovery was 50% of the theoretical values. Anamnestic rises in anti-porcine F VIII Ab (3 X the baseline titer) were seen after 9 of 22 courses of treatment with porcine F VIII only; similar rises in anti-human F VIII Ab, after 6 courses of treatment; median cross reactivity did not change significantly. Lower than expected increases in plasma F VIII without marked changes in Ab titers and severe thrombocytopenia occurred during surgery in two patients. Porcine F VIII is a rational and effective therapeutic choice for patients who have anti-human Ab titers above 10 U/ml; it can solve clinical situations that would otherwise be very difficult to manage; anamnesis is perhaps less frequent than after human F VIII; however, the incidence of thrombocytopenia, resistance and other side-effects is still higher than desirable.
The Folk Theorem in Repeated Games with Discounting or with Incomplete Information (1986)

When either there are only two players or a full dimensionality condition holds, any individually rational payoff vector of a one-shot game of complete information can arise in a equilibrium of the infinitely-repeated game if players are sufficiently patient. In contrast to earlier work, mixed strategies are allowed in determining the individually rational payoffs (even when only realized actions are observable). Any individually rational payoffs of a one-shot game can be approximated by sequential equilibrium payoffs of a long but finite game of incomplete information, where players' payoffs are almost certainly as in the one-shot game. THAT STRATEGIC RIVALRY in a long-term relationship may differ from that of a one-shot game is by now quite a familiar idea. Repeated play allows players to respond to each other's actions, and so each player must consider the reactions of his opponents in making his decision. The fear of retaliation may thus lead to outcomes that otherwise would not occur. The most dramatic expression of this phenomenon is the celebrated for repeated games. An outcome that Pareto dominates the minimax point is called individually rational. The Folk Theorem asserts that any individually rational outcome can arise as a equilibrium in infinitely repeated games with sufficiently little discounting. As Aumann and Shapley [3] and Rubinstein [20] have shown, the same result is true when we replace the word Nash by (subgame) perfect and assume no discounting at all. Because the Aumann-Shapley/Rubinstein result supposes literally no discounting, one may wonder whether the exact counterpart of the Folk Theorem holds for equilibrium, i.e., whether as the discount factor tends to one, the set of equilibrium outcomes converges to the individually rational set. After all, agents in most games of economic interest are not completely patient; the no discounting case is of interest as an approximation. It turns out that this counterpart is false. There can be a discontinuity (formally, a failure of lower hemicontinuity) where the discount factor, 8, equals one, as we show in Example 3. Nonetheless the games in which discontinuities occur are quite degenerate, and, in the end, we can give a qualified yes (Theorem 2) to the question of whether the Folk Theorem holds with discounting. In particular, it always holds in two-player games (Theorem 1). This last result contrasts with the recent work of Radner-Myerson-Maskin [18] showing that, even in two-player games, the equilibrium set may not be continuous at 8 = 1 in
Mutational analysis of the carboxyl terminus of the Moloney murine leukemia virus integration protein (1991)

The integration protein (IN) is required for retrovirus DNA integration into the host DNA. The function of the C terminus of the Moloney murine leukemia virus IN protein was examined. The terminal 28 amino acids were found to be nonessential. A linker insertion at position 6025, within a 36-amino-acid insertion not found in any other retrovirus, also produced viable virus.