992 resultados para enhancement factor
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The chicken represents the best-characterized animal model for B cell development in the so-called gut-associated lymphoid tissue (GALT) and the molecular processes leading to B cell receptor diversification in this species are well investigated. However, the mechanisms regulating B cell development and homeostasis in GALT species are largely unknown. Here we investigate the role played by the avian homologue of B cell-activating factor of the tumor necrosis factor family (BAFF). Flow cytometric analysis showed that the receptor for chicken B cell-activating factor of the tumor necrosis factor family (chBAFF) is expressed by mature and immature B cells. Unlike murine and human BAFF, chBAFF is primarily produced by B cells both in peripheral lymphoid organs and in the bursa of Fabricius, the chicken's unique primary lymphoid organ. In vitro and in vivo studies revealed that chBAFF is required for mature B cell survival. In addition, in vivo neutralization with a decoy receptor led to a reduction of the size and number of B cell follicles in the bursa, demonstrating that, in contrast to humans and mice, in chickens BAFF is also required for the development of immature B cells. Collectively, we show that chBAFF has phylogenetically conserved functions in mature B cell homeostasis but displays unique and thus far unknown properties in the regulation of B cell development in birds.
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SUMMARYThe incidence of type 2 diabetes (T2D) is increasing worldwide and is linked to the enhancement of obesity. The principal cause of T2D development is insulin resistance, which lead to the increase of insulin production by the pancreatic beta-cells. In a pathological environment, namely dyslipidaemia, hyperglycaemia and inflammation, beta-cell compensation will fail in more vulnerable cells and diabetes will occur. High Density Lipoproteins (HDLs), commonly named "good cholesterol" are known to be atheroprotective. Low levels of HDLs are associated with increased prevalence of cardiovascular disease but are also an independent risk factor for the development of T2D. HDLs were demonstrated to protect pancreatic beta-cells against several stresses. However the molecular mechanisms of the protection are unknown and the objectives of this work were to try to elucidate the way how HDLs protect. The first approach was a broad screening of genes regulated by the stress and HDLs. A microarray analysis was performed on beta-cells stressed by serum deprivation and rescued by HDLs. Among the genes regulated, we focused on 4E-BP1, a cap-dependent translational inhibitor. In addition, HDLs were also found to protect against several other stresses.Endoplasmic reticulum (ER) stress is a mechanism that may play a role in the onset of T2D. The unfolded protein response (UPR) is a physiological process that aims at maintaining ER homeostasis in conditions where the protein folding and secretion is perturbed. Specific signalling pathways are involved in the increase of folding, export and degradation capacity of the ER. However, in case where the stress is prolonged, this mechanism turns to be pathological, by inducing cell death effector pathways, leading to beta-cell apoptosis. In our study, we discovered that HDLs were protective against ER stress induced by drugs and physiological stresses such as saturated free fatty acids. HDLs protected beta-cells by promoting ER homeostasis via the improvement of the folding and trafficking od proteins from the ER to the Golgi apparatus.Altogether our results suggest that HDLs are important for beta-cell function and survival, by protecting them from several stresses and acting on ER homeostasis. This suggests that attempt in keeping normal HDLs levels or function in patients is crucial to lessen the development of T2D.RÉSUMÉL'incidence du diabète de type 2 est en constante augmentation et est fortement liée à l'accroissement du taux d'obésité. La cause principale du diabète de type 2 est la résistance à l'insuline, qui entraîne une surproduction d'insuline par les cellules bêta pancréatiques. Dans un environnement pathologique associé à l'obésité (dyslipidémie, hyperglycémie et inflammation), les cellules bêta les plus vulnérables ne sont plus capables de compenser en augmentant leur production d'insuline, dysfonctionnent, ce qui conduit à leur mort par apoptose. Les lipoprotéines de hautes densités (HDLs), communément appelées (( bon cholestérol », sont connues pour leurs propriétés protectrices contre l'athérosclérose. Des niveaux bas de HDLs sanguins sont associés au risque de développer un diabète de type 2. Les HDLs ont également montré des propriétés protectrices contre divers stresses dans la cellule bêta. Cependant, les mécanismes de protection restent encore inconnus et l'objectif de ce travail a été d'investiguer les mécanismes moléculaires de protection des HDLs. La première approche choisie a été une étude du profil d'expression génique par puce à ADN afin d'identifier les gènes régulés par le stress et les HDLs. Parmi les gènes régulés, notre intérêt s'est porté sur 4E-BP1, un inhibiteur de la traduction coiffe- dépendante, dont l'induction par le stress était corrélée avec une augmentation de l'apoptose. Suite à cette étude, les HDLs ont également montrés un rôle protecteur contre d'autres stresses. Il s'agit particulièrement du stress du réticulum endoplasmique (RE), qui est un mécanisme qui semble jouer un rôle clé dans le développement du diabète. L'UPR (« Unfolded Protein Response ») est un processus physiologique tendant à maintenir l'homéostasie du réticulum endoplasmique, organelle prépondérante pour la fonction des cellules sécrétrices, notamment lorsqu'elle est soumise à des conditions extrêmes telles que des perturbations de la conformation tertiaire des protéines ou de la sécrétion. Dans ces cas, des voies de signalisation moléculaires sont activées, ce qui mène à l'exportation des protéines mal repliées, à leur dégradation et à l'augmentation de l'expression de chaperonnes capables d'améliorer le repliement des protéines mal formées. Toutefois, en cas de stress persistant, ce mécanisme de protection s'avère être pathologique. En induisant des voies de signalisation effectrices de l'apoptose, il conduit finalement au développement du diabète. Dans cette étude, nous avons démontré que les HDLs étaient capables de protéger la cellule bêta contre le stress du RE induits par des inhibiteurs (thapsigargine, tunicamycine) ou des stresses physiologiques tels que les acides gras libres. Les HDLs ont la capacité d'améliorer l'homéostasie du RE, notamment en favorisant le repliement et le transfert des protéines du RE à l'appareil de Golgi.En résumé, ces données suggèrent que les HDLs sont bénéfiques pour la survie des cellules bêta soumises à des stresses impliqués dans le développement du diabète, notamment en restaurant l'homéostasie du RE. Ces résultats conduisent à soutenir que le maintien des taux de cholestérol joue un rôle important dans la limitation de l'incidence du diabète.
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Macrophages play a critical role in intestinal wound repair. However, the mechanisms of macrophage-assisted wound repair remain poorly understood. We aimed to characterize more clearly the repair activities of murine and human macrophages. Murine macrophages were differentiated from bone marrow cells and human macrophages from monocytes isolated from peripheral blood mononuclear cells of healthy donors (HD) or Crohn's disease (CD) patients or isolated from the intestinal mucosa of HD. In-vitro models were used to study the repair activities of macrophages. We found that murine and human macrophages were both able to promote epithelial repair in vitro. This function was mainly cell contact-independent and relied upon the production of soluble factors such as the hepatocyte growth factor (HGF). Indeed, HGF-silenced macrophages were less capable of promoting epithelial repair than control macrophages. Remarkably, macrophages from CD patients produced less HGF than their HD counterparts (HGF level: 84âeuro0/00±âeuro0/0027âeuro0/00pg/mg of protein and 45âeuro0/00±âeuro0/0034âeuro0/00pg/mg of protein, respectively, for HD and CD macrophages, Pâeuro0/00<âeuro0/000·009) and were deficient in promoting epithelial repair (repairing activity: 90·1âeuro0/00±âeuro0/004·6 and 75·8âeuro0/00±âeuro0/008·3, respectively, for HD and CD macrophages, Pâeuro0/00<âeuro0/000·0005). In conclusion, we provide evidence that macrophages act on wounded epithelial cells to promote epithelial repair through the secretion of HGF. The deficiency of CD macrophages to secrete HGF and to promote epithelial repair might contribute to the impaired intestinal mucosal healing in CD patients.
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O trabalho agora concluído pretende apresentar uma proposta de desenvolvimento do turismo rural para São Tomé. Baseado na análise de estudo de caso de outros países, com objectivo de propor actividades turísticas envolvendo a comunidade local e os representantes do turismo, o estudo tenciona contribuir para a construção de uma imagem positiva da roça de Monte Café e suas dependências, visando o seu desenvolvimento. A referida Roça, enquanto um património arquitectónico, histórico, cultural, agroeconómico e natural, oferece as condições necessárias para a prática de turismo, relacionadas com a aventura, o espaço rural e a ecologia. Tais aspectos, aliados a uma infra-estrutura e a um planeamento adequado, tornam-se um excelente produto turístico. Com aplicação do inquérito por questionário para os residentes, comprova-se a possibilidade de implementação do projecto do ponto de vista social, desde que seja planeado de forma a prever impactos negativos e positivos futuros, e garantir um turismo sustentável.
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En un total de 28,265 individuos de Sardina se estudiaron el factor de condición, el coeficiente alimentario y los ítems alimentarios entre 1975 y 1986. Los cambios observados comparados a la situación “normal” en 1980. Durante El Niño 1976-77 la sardina ingirió más fitoplancton que zooplancton, aumentando el coeficiente alimentario pero decreciendo el factor condición.
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We show how, in general equilibrium models featuring increasing returns, imperfectcompetition and endogenous markups, changes in the scale of economic activity affectincome distribution across factors. Whenever final goods are gross-substitutes (gross-complements), a scale expansion raises (lowers) the relative reward of the scarce factoror the factor used intensively in the sector characterized by a higher degree of product differentiation and higher fixed costs. Under very reasonable hypothesis, our theory suggests that scale is skill-biased. This result provides a microfoundation for the secular increase in the relative demand for skilled labor. Moreover, it constitutes an important link among major explanations for the rise in wage inequality: skill-biased technical change, capital-skill complementarities and international trade. We provide new evidence on the mechanism underlying the skill bias of scale.
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A presente monografia aborda o tema do planeamento estratégico como fator de sucesso das empresas, enquanto instrumento de avaliação da situação das empresas em São Vicente, e tem como objetivo “demonstrar a importância do planeamento para as empresas”. Para a sua elaboração utilizou-se a amostra pelo método não probabilistico, ou seja, o de amostra por conveniência e optou-se por uma abordagem quantitativa pela técnica de recolha de dados através da aplicação de questionários dirigidos às empresas atuantes na ilha de São Vicente. Dadas as incertezas do mundo atual, a sobrevivência e o desenvolvimento das empresas dependem, cada vez mais, da sua capacidade de definição de uma estratégia coerente, potencializando oportunidades e ultrapassando obstáculos. No percurso da investigação tentaremos responder à seguinte pergunta: “Poderá o Planeamento Estratégico ser considerado uma ferramenta de competitividade e sucesso das empresas?” Esta monografia e sua fundamentação teórica têm por finalidade demonstrar os procedimentos do Planeamento estratégico nas diversas áreas das empresas e avaliar a adoção desta ferramenta como incremento de competitividade à medida que a utilização desta proporciona reflexões e diretrizes para as atividades da organização, como também possibilita a adaptação e capacidade de resposta às mudanças do mercado.
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This paper presents a two--factor model of the term structure ofinterest rates. We assume that default free discount bond prices aredetermined by the time to maturity and two factors, the long--term interestrate and the spread (difference between the long--term rate and theshort--term (instantaneous) riskless rate). Assuming that both factorsfollow a joint Ornstein--Uhlenbeck process, a general bond pricing equationis derived. We obtain a closed--form expression for bond prices andexamine its implications for the term structure of interest rates. We alsoderive a closed--form solution for interest rate derivatives prices. Thisexpression is applied to price European options on discount bonds andmore complex types of options. Finally, empirical evidence of the model'sperformance is presented.
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The mechanisms of vascular calcifications in chronic renal failure are complex. Apart for clotting factors, vitamin K-dependent proteins include matrix Gla protein. Glutamic acid residues in matrix Gla protein are carboxylated by vitamin K-dependent gamma-carboxylase, which enables it to inhibit calcification. The purpose of this review is to discuss available evidence implicating vitamin K as a modifiable risk factor in the pathogenesis of vascular calcification in renal diseases.
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O presente trabalho tem como objectivo mostrar a importância que a Gestão económica de Stock tem no processo de redução de custo, por via da implementação de um modelo. E para isso far-se-á um estudo de caso numa empresa inserida no ramo de transformação de pescado – FRESCOMAR. A metodologia adoptada para alcançar os objectivos propostos passou pela pesquisa bibliográfica, recolha de dados e de informação relevante junto da empresa e tratamento dos dados numa folha de Excel. O modelo de gestão de Stock a ser implementado depende essencialmente da componente procura, onde que para uma empresa com procura constante utiliza-se os modelos determinísticos e para uma com procura aleatória utiliza-se os modelos estocásticos (Nível de Encomenda e Revisão Cíclica). Nos modelos determinísticos temos 4 modelos diferenciados pela forma de reposição e a admissibilidade da procura. Com as informações recolhidas junto da empresa em estudo escolhemos implementar o modelo de reposição não instantânea com ruptura não permitida e obtivemos a optimização do Stock com níveis reduzidos de produção e consequentemente houve uma diminuição do custo. Com resultados obtiveram-se ainda valores da Quantidade Óptima a ser Produzida, do Stock Máximo e do Custo Total Óptimo por unidade de tempo. Devido a diversidade de produtos propomos à empresa a utilização da análise ABC para classificar os produtos reagrupando-os em classes A, B e C, conforme o peso no consumo de Stock.
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Leaf-litter amount as a factor in the structure of a ponerine ants community (Hymenoptera, Formicidae, Ponerinae) in an eastern Amazonian rainforest, Brazil. Leaf-litter may be an important factor in structuring ponerine ant communities (Hymenoptera, Formicidae, Ponerinae) in tropical rainforests. We specifically examined how leaf-litter affects the structure of a ponerine ant community in primary Amazonian rainforest sites at the Ferreira Penna Scientific Station, Pará, Brazil. A total of 53 species belonging to eight genera of three ponerine tribes were collected with mini-Winkler extractors. The amount of leaf-litter positively affected the abundance and richness of the ponerine ant community, and also influenced species composition. Nearby samples often had low species similarity, especially when adjacent samples differed in the amount of leaf-litter. Leaf-litter availability in Amazonian primary forests is a key factor for distribution of ground-dwelling ponerine species, even at small scales.
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In cost-effectiveness analysis (CEA) it is usually assumed that a QALY is of equal value to everybody, irrespective of the patient's age. However, it is possible that society assigns different social values to a QALY according to who gets it. In this paper we discuss the possibility of weighting health benefits for age in CEA. We also examinethe possibility that age-related preferences depend on the size of the health gain. An experiment was performedto test these hypotheses. The results assessing suggest that the patient's age is a relevant factor when assessing health gains.
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Analiza el balance de oxigeno consumido en las profundidades de las aguas continentales del norte del Perú
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O desempenho da empresa é influenciado pelas competências dos seus funcionários. A competência humana aliada a outros recursos empresariais dá origem e sustentação à competência empresarial. A participação dos funcionários no processo de gestão de competências expondo as suas expectativas, motivações e também, percepções a respeito do seu superior e da estratégia de negócios da empresa é fundamental para o sucesso empresarial.