762 research outputs found

    Identificação de Danos Empregando um Modelo de Dano Contínuo e o Método de Monte Carlo com Cadeias de Markov

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    RESUMO O presente trabalho apresenta um estudo referente à aplicação da abordagem Bayesiana como técnica de solução do problema de identificação de danos estruturais, onde a integridade da estrutura é continuamente descrita por um parâmetro denominado parâmetro de coesão. A estrutura escolhida para análise é uma viga simplesmente apoiada do tipo Euler-Bernoulli. A identificação de danos é baseada em alterações na resposta impulsiva da estrutura, provocadas pela presença dos mesmos. O problema direto é resolvido através do Método de Elementos Finitos (MEF), que, por sua vez, é parametrizado pelo parâmetro de coesão da estrutura. O problema de identificação de danos é formulado como um problema inverso, cuja solução, do ponto de vista Bayesiano, é uma distribuição de probabilidade a posteriori do parâmetro de coesão, obtida utilizando-se a metodologia de amostragem de Monte Carlo com Cadeias de Markov. As incertezas inerentes aos dados medidos serão contempladas na função de verossimilhança. São apresentadas três estratégias de solução e um conjunto de resultados numéricos, onde considera-se diferentes níveis de ruído para as três estratégias de solução adotadas

    Mutational analysis of human CEACAM1: the potential of receptor polymorphism in increasing host susceptibility to bacterial infection

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    A common overlapping site on the N-terminal IgV-like domain of human carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAMs) is targeted by several important human respiratory pathogens. These include Neisseria meningitidis (Nm) and Haemophilus influenzae (Hi) that can cause disseminated or persistent localized infections. To define the precise structural features that determine the binding of distinct pathogens with CEACAMs, we have undertaken molecular modelling and mutation of the receptor molecules at previously implicated key target residues required for bacterial binding. These include Ser-32, Tyr-34, Val-39, Gln-44 and Gln-89, in addition to Ile-91, the primary docking site for the pathogens. Most, but not all, of these residues located adjacent to each other in a previous N-domain model of human CEACAM1, which was based on REI, CD2 and CD4. In the current studies, we have refined this model based on the mouse CEACAM1 crystal structure, and observe that all of the above residues form an exposed continuous binding region on the N-domain. Examination of the model also suggested that substitution of two of these residues 34 and 89 could affect the accessibility of Ile-91 for ligand binding. By introducing selected mutations at the positions 91, 34 and 89, we confirmed the primary importance of Ile-91 in all bacterial binding to CEACAM1 despite the inter- and intraspecies structural differences between the bacterial CEACAM-binding ligands. The studies further indicated that the efficiency of binding was significantly enhanced for specific strains by mutations such as Y34F and Q89N, which also altered the hierarchy of Nm versus Hi strain binding. These studies imply that distinct polymorphisms in human epithelial CEACAMs have the potential to decrease or increase the risk of infection by the receptor-targeting pathogens

    Apoio Em Rede: A Rede Humaniza Sus Conectando Possibilidades No Ciberespaço

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    This paper presents the HUmanizaSUS Network (Rede HumanizaSUS) as a virtual environment connecting practices and knowledge about SUS (Brazilian National Health System), conveying the support function in a network. Based on the theoretical framework of Collective Intelligence, we present some dimensions of support experienced on Rede HumanizaSUS as a network intervention technology for strengthening the virtual environment of SUS or CiberespaSUS. © 2016, Fundacao UNI Botucatu/UNESP. All rights reserved.205733734

    Inhalation of the prodrug PI3K inhibitor CL27c improves lung function in asthma and fibrosis

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    PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action. In murine models of acute or glucocorticoid-resistant neutrophilic asthma, inhaled CL27c reduces inflammation and improves lung function. Finally, inhaled CL27c administered in a therapeutic setting protects from bleomycin-induced lung fibrosis, ultimately leading to significantly improved survival. Therefore, local delivery of a pan-PI3K inhibitor prodrug reduces systemic on-target side effects but effectively treats asthma and irreversible pulmonary fibrosis

    Identificación del índice de vulnerabilidad territorial a partir de modelos jerárquicos y heurísticos aplicando SOA

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    Auxiliar de InvestigaciónEn el proyecto se realiza el diseño y desarrollo de 4 servicios web implementando los modelos de toma de decisión (AHP, AHP FUZZY, ELECTRE y PROMETHEE), encargados de procesar datos obtenidos en campo en la primera fase del proyecto que se realizó a través de encuestas, formatos de entrevistas, talleres y metodologías de análisis. Los datos se procesaran de acuerdo al modelo de toma de decisión seleccionado, generando como resultado final un indicador de vulnerabilidad territorial.PregradoIngeniero de Sistema

    Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

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    A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
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