1,869 research outputs found

    Thermodynamic analysis of black hole solutions in gravitating nonlinear electrodynamics

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    We perform a general study of the thermodynamic properties of static electrically charged black hole solutions of nonlinear electrodynamics minimally coupled to gravitation in three space dimensions. The Lagrangian densities governing the dynamics of these models in flat space are defined as arbitrary functions of the gauge field invariants, constrained by some requirements for physical admissibility. The exhaustive classification of these theories in flat space, in terms of the behaviour of the Lagrangian densities in vacuum and on the boundary of their domain of definition, defines twelve families of admissible models. When these models are coupled to gravity, the flat space classification leads to a complete characterization of the associated sets of gravitating electrostatic spherically symmetric solutions by their central and asymptotic behaviours. We focus on nine of these families, which support asymptotically Schwarzschild-like black hole configurations, for which the thermodynamic analysis is possible and pertinent. In this way, the thermodynamic laws are extended to the sets of black hole solutions of these families, for which the generic behaviours of the relevant state variables are classified and thoroughly analyzed in terms of the aforementioned boundary properties of the Lagrangians. Moreover, we find universal scaling laws (which hold and are the same for all the black hole solutions of models belonging to any of the nine families) running the thermodynamic variables with the electric charge and the horizon radius. These scale transformations form a one-parameter multiplicative group, leading to universal "renormalization group"-like first-order differential equations. The beams of characteristics of these equations generate the full set of black hole states associated to any of these gravitating nonlinear electrodynamics...Comment: 51 single column pages, 19 postscript figures, 2 tables, GRG tex style; minor corrections added; final version appearing in General Relativity and Gravitatio

    Evolutionary Dynamics of Intratumor Heterogeneity

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    Intraneoplastic diversity in human tumors is a widespread phenomenon of critical importance for tumor progression and the response to therapeutic intervention. Insights into the evolutionary events that control tumor heterogeneity would be a major breakthrough in our comprehension of cancer development and could lead to more effective prevention methods and therapies. In this paper, we design an evolutionary mathematical framework to study the dynamics of heterogeneity over time. We consider specific situations arising during tumorigenesis, such as the emergence of positively selected mutations (“drivers”) and the accumulation of neutral variation (“passengers”). We perform exact computer simulations of the emergence of diverse tumor cell clones over time, and derive analytical estimates for the extent of heterogeneity within a population of cancer cells. Our methods contribute to a quantitative understanding of tumor heterogeneity and the impact of heritable alterations on this tumor trait

    Multi-level modeling of social factors and preterm delivery in Santiago de Chile

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    <p>Abstract</p> <p>Background</p> <p>Birth before the 37th week of gestation (preterm birth) is an important cause of infant and neonatal mortality, but has been little studied outside of wealthy nations. Chile is an urbanized Latin American nation classified as "middle-income" based on its annual income per capita of about $6000.</p> <p>Methods</p> <p>We studied the relations between maternal social status and neighborhood social status on risk of preterm delivery in this setting using multilevel regression analyses of vital statistics data linked to geocoded decennial census data. The analytic data set included 56,970 births from 2004 in the metropolitan region of Santiago, which constitutes about 70% of all births in the study area and about 25% of all births in Chile that year. Dimensionality of census data was reduced using principal components analysis, with regression scoring to create a single index of community socioeconomic advantage. This was modeled along with years of maternal education in order to predict preterm birth and preterm low birthweight.</p> <p>Results</p> <p>Births in Santiago displayed an advantaged pattern of preterm risk, with only 6.4% of births delivering before 37 weeks. Associations were observed between risk of outcomes and individual and neighborhood factors, but the magnitudes of these associations were much more modest than reported in North America.</p> <p>Conclusion</p> <p>While several potential explanations for this relatively flat social gradient might be considered, one possibility is that Chile's egalitarian approach to universal prenatal care may have reduced social inequalities in these reproductive outcomes.</p

    Analyses of an Expressed Sequence Tag Library from Taenia solium, Cysticerca

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    A method used to describe expressed genes at a specific stage in an organism is an EST library. In this method mRNA from a specific organism is isolated, transcribed into cDNA and sequenced. The sequence will derive from the 5â€Č-end of the cDNA. The library will not have sequences from all genes, especially if they are expressed in low amounts or not at all in the studied stage. Also the library will mostly not contain full length sequences from genes, but expression patterns can be established. If EST libraries are made from different stages of the same organisms these libraries can be compared and differently expressed genes can be identified. Described here is an analysis of an EST library from the pig cysticerca which is thought to be similar to the stage giving the human neglected disease neurocysticercosis. Novel genes together with putative drug targets are examples of data presented

    Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria

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    Albuminuria development in hypertensive patients is an indicator of higher cardiovascular (CV) risk and renal damage. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control but it does not prevent from albuminuria development. We pursued the identification of protein indicators in urine behind albuminuria development in hypertensive patients under RAS suppression. Urine was collected from 100 patients classified in three groups according to albuminuria development: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Quantitative analysis was performed in a first discovery cohort by isobaric labeling methodology. Alterations of proteins of interest were confirmed by target mass spectrometry analysis in an independent cohort. A total of 2416 proteins and 1223 functional categories (coordinated protein responses) were identified. Immune response, adhesion of immune and blood cells, and phagocytosis were found significantly altered in patients with albuminuria compared to normoalbuminuric individuals. The complement system C3 increases, while Annexin A1, CD44, S100A8 and S100A9 proteins showed significant diminishment in their urinary levels when albuminuria is present. This study reveals specific links between immune response and controlled hypertension in patients who develop albuminuria, pointing to potential protein targets for novel and future therapeutic interventions.Sin financiaciĂłn4.122 JCR (2017) Q1, 12/64 Multidisciplinary Sciences0.809 SJR (2017) Q2, 4/10 OptometryNo data IDR 2017UE

    Therapeutic Effect of a Poly(ADP-Ribose) Polymerase-1 Inhibitor on Experimental Arthritis by Downregulating Inflammation and Th1 Response

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    Poly(ADP-ribose) polymerase-1 (PARP-1) synthesizes and transfers ADP ribose polymers to target proteins, and regulates DNA repair and genomic integrity maintenance. PARP-1 also plays a crucial role in the progression of the inflammatory response, and its inhibition confers protection in several models of inflammatory disorders. Here, we investigate the impact of a selective PARP-1 inhibitor in experimental arthritis. PARP-1 inhibition with 5-aminoisoquinolinone (AIQ) significantly reduces incidence and severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of AIQ is associated with a striking reduction of the two deleterious components of the disease, i.e. the Th1-driven autoimmune and inflammatory responses. AIQ downregulates the production of various inflammatory cytokines and chemokines, decreases the antigen-specific Th1-cell expansion, and induces the production of the anti-inflammatory cytokine IL-10. Our results provide evidence of the contribution of PARP-1 to the progression of arthritis and identify this protein as a potential therapeutic target for the treatment of rheumatoid arthritis

    Interphase Nucleo-Cytoplasmic Shuttling and Localization of SIRT2 during Mitosis

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    The human NAD+-dependent protein deacetylase SIRT2 resides predominantly in the cytoplasm where it functions as a tubulin deacetylase. Here we report that SIRT2 maintains a largely cytoplasmic localization during interphase by active nuclear export in a Crm1-dependent manner. We identified a functional, leptomycin B-sensitive, nuclear export signal sequence within SIRT2. During the cell cycle, SIRT2 becomes enriched in the nucleus and is associated with mitotic structures, beginning with the centrosome during prophase, the mitotic spindle during metaphase, and the midbody during cytokinesis. Cells overexpressing wild-type or a catalytically inactive SIRT2 exhibit an increase in multinucleated cells. The findings suggest a novel mechanism of regulating SIRT2 function by nucleo-cytoplasmic shuttling, as well as a role for SIRT2 in the nucleus during interphase and throughout mitosis

    Selection Mechanisms Underlying High Impact Biomedical Research - A Qualitative Analysis and Causal Model

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    BACKGROUND: Although scientific innovation has been a long-standing topic of interest for historians, philosophers and cognitive scientists, few studies in biomedical research have examined from researchers' perspectives how high impact publications are developed and why they are consistently produced by a small group of researchers. Our objective was therefore to interview a group of researchers with a track record of high impact publications to explore what mechanism they believe contribute to the generation of high impact publications. METHODOLOGY/PRINCIPAL FINDINGS: Researchers were located in universities all over the globe and interviews were conducted by phone. All interviews were transcribed using standard qualitative methods. A Grounded Theory approach was used to code each transcript, later aggregating concept and categories into overarching explanation model. The model was then translated into a System Dynamics mathematical model to represent its structure and behavior. Five emerging themes were found in our study. First, researchers used heuristics or rules of thumb that came naturally to them. Second, these heuristics were reinforced by positive feedback from their peers and mentors. Third, good communication skills allowed researchers to provide feedback to their peers, thus closing a positive feedback loop. Fourth, researchers exhibited a number of psychological attributes such as curiosity or open-mindedness that constantly motivated them, even when faced with discouraging situations. Fifth, the system is dominated by randomness and serendipity and is far from a linear and predictable environment. Some researchers, however, took advantage of this randomness by incorporating mechanisms that would allow them to benefit from random findings. The aggregation of these themes into a policy model represented the overall expected behavior of publications and their impact achieved by high impact researchers. CONCLUSIONS: The proposed selection mechanism provides insights that can be translated into research coaching programs as well as research policy models to optimize the introduction of high impact research at a broad scale among institutional and governmental agencies

    Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

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    OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

    Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

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    This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}andcorrespondtoanintegratedluminosityof and correspond to an integrated luminosity of 4.6\;{\rm f}{{{\rm b}}^{-1}}.ThemeasurementisperformedbyreconstructingtheboostedWorZbosonsinsinglejets.ThereconstructedjetmassisusedtoidentifytheWandZbosons,andajetsubstructuremethodbasedonenergyclusterinformationinthejetcentre−of−massframeisusedtosuppressthelargemulti−jetbackground.Thecross−sectionforeventswithahadronicallydecayingWorZboson,withtransversemomentum. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum {{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}andpseudorapidity and pseudorapidity |\eta |\lt 1.9,ismeasuredtobe, is measured to be {{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques
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