877 resultados para Global Transcriptional Response


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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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In this paper, the use of differential evolution ( DE), a global search technique inspired by evolutionary theory, to find the parameters that are required to achieve optimum dynamic response of parallel operation of inverters with no interconnection among the controllers is proposed. Basically, in order to reach such a goal, the system is modeled in a certain way that the slopes of P-omega and Q-V curves are the parameters to be tuned. Such parameters, when properly tuned, result in system's eigenvalues located in positions that assure the system's stability and oscillation-free dynamic response with minimum settling time. This paper describes the modeling approach and provides an overview of the motivation for the optimization and a description of the DE technique. Simulation and experimental results are also presented, and they show the viability of the proposed method.

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Mitochondrial inner membrane uncoupling proteins (UCP) catalyze a proton conductance that dissipates the proton electrochemical gradient established by the respiratory chain, thus affecting the yield of ATP synthesis. UCPs are involved in mitochondrial energy flow regulation and have been implicated in oxidative stress tolerance. Based on the global gene expression profiling datasets available for Arabidopsis thaliana, in this review we discuss the regulation of UCP gene expression during development and in response to stress, and provide interesting insights on the possible existence of epigenetic regulation of UCP expression.

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Objective. To use the Pediatric Rheumatology International Trials Organization (PRINTO) core set of outcome measures to develop a validated definition of improvement for the evaluation of response to therapy in juvenile systemic lupus erythematosus (SLE).Methods. Thirty-seven experienced pediatric rheumatologists from 27 countries, each of whom had specific experience in the assessment of juvenile SLE patients, achieved consensus on 128 patient profiles as being clinically improved or not improved. Using the physicians' consensus ratings as the gold standard measure, the chi-square, sensitivity, specificity, false-positive and false-negative rates, area under the receiver operating characteristic curve, and kappa level of agreement for 597 candidate definitions of improvement were calculated. Only definitions with a kappa value greater than 0.7 were retained. The top definitions were selected based on the product of the content validity score multiplied by its kappa statistic.Results. The definition of improvement with the highest final score was at least 50% improvement from baseline in any 2 of the 5 core set measures, with no more than 1 of the remaining worsening by more than 30%.Conclusion. PRINTO proposes a valid and reproducible definition of improvement that reflects well the consensus rating of experienced clinicians and that incorporates clinically meaningful change in core set measures in a composite end point for the evaluation of global response to therapy in patients with juvenile SLE. The definition is now proposed for use in juvenile SLE clinical trials and may help physicians to decide whether a child with SLE responded adequately to therapy.

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Matrix metal loprotease-13 (MMP-13) is induced by pro-inflammatory cytokines and increased expression is associated with a number of pathological conditions such as tumor metastasis, osteoarthritis, rheumatoid arthritis and periodontal diseases. MMP-13 gene regulation and the signal transduction pathways activated in response to bacterial LPS are largely unknown. In these studies, the role of the mitogen-activated protein kinase (MAPK) pathways in the regulation of MMP-13 induced by lipopolysaccharide was investigated. Lipopolysaccharide from Escherichia coli and Actinobacillus actinomycetemcomitans significantly (P < 0.05) increased MMP-13 steady-state mRNA (average of 27% and 46% increase, respectively) in murine periodontal ligament fibroblasts. MMP-13 mRNA induction was significantly reduced by inhibition of p38 MAP kinase. Immunoblot analysis indicated that p38 signaling was required for LPS-induced MMP-13 expression. Lipopolysaccharide induced proximal promoter reporter (-660/+32 mMMP-13) gene activity required p38 signaling. Collectively, these results indicate that lipopolysaccharide-induced murine MMP-13 is regulated by p38 signaling through a transcriptional mechanism.

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Post-transcriptional gene silencing (PTGS) is a conserved surveillance mechanism that identifies and cleaves double-stranded RNA molecules and their cellular cognate transcripts. The RNA silencing response is actually used as a powerful technique (named RNA interference) for potent and specific inhibition of gene expression in several organisms. To identify gene products in Eucalyptus sharing similarities with enzymes involved in the PTGS pathway, we queried the expressed sequence tag database of the Brazilian Eucalyptus Genome Sequence Project Consortium (FORESTs) with the amino acid sequences of known PTGS-related proteins. Among twenty-six prospected genes, our search detected fifteen assembled sequences encoding products presenting high level of similarity (E value < 10 -40) to proteins involved in PTGS in plants and other organisms. We conclude that most of the genes known to be involved in the PTGS pathway are represented in the FORESTs database. Copyright by the Brazilian Society of Genetics.

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Proposicion para la implementacion de un sistema internacional de informacion en poblacion. El marco de referencia esta constituido por 4 principios basicos: servir a los usuarios en el campo de poblacion, aumentar la disponibilidad de informacion, asegurar la distribucion equitativa, transferencia y flujo de la misma y promover la generacion de nueva informacion. Estos propositos descansan en 2 supuestos generales: el sistema de informacion debe ser activo y neutral. La solucion que se propone consiste en el diseno de un sistema: a).global, con verdadero caracter internacional que sirva a todas las regiones y paises; b).descentralizado; c).interdisciplinario ("mission-oriented"), estructurado en torno a areas-problema y objetivos globales vis a vis la estructuracion en torno a disciplinas; d).de amplitud tematica, partiendo de las areas-problema y guardando la mayor neutralidad posible en la seleccion de temas relevantes en el campo de poblacion.

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Global economic conditions have been deteriorating sharply since mid- September 2008. Lending has dropped abruptly, credit spreads have widened sharply, stock markets have plunged and economies everywhere are stumbling. Governments around the world have undertaken unprecedented measures, including some coordinated intervention. However, global economic prospects remain troubled, and further policy action is required. In order to better understand the task before policy makers as they chart a new direction, this paper examines how the global economy arrived at its current predicament, looking back at the sequence of events that contributed to create havoc in financial markets, as well as the policy response they produced. In light of these events, we examine the impact on Latin American financial markets in particular. The global nature of the current crisis underscores the need for coordinating the policy response at the global level, as well as advancing towards a new international financial architecture that will make possible a more effective response to the build-up of systemic pressures.

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Over the past two years the global economy has experienced substantial economic turmoil, resulting in severe economic contraction. While there has been a recent return to growth, this situation has impacted all economic sectors worldwide. In the highly tourism-dependent region of the Caribbean, the impact of the global economic crisis has been most notable on the tourism sector, which, from the early 1990s, became the key driver of economic growth for the region. The eventual emergence of this sector reflects an economic development history which was previously underpinned by the export of agricultural commodities, and subsequently by the adoption of the import substitution industrialization model as promulgated by Arthur Lewis. This was further stimulated by spectacular economic contraction in Caribbean economies during the 1980s as a result of changes in the global terms of trade for commodities, generally low levels of competitiveness for manufactured goods, as well as weak institutional and governance frameworks. Ultimately, many economies began to reflect fiscal and balance of payments constraints. By the end of the 1990s, too, evidence of declining competitiveness even in the tourism sector began to become apparent particularly when evaluated under the framework of the Butler Tourism Area Life- Cycle (TALC) model. The recent economic crisis, therefore, provides an opportunity to reflect on the overall approach to economic development in the Caribbean, and to assess the implications of the region’s response to the crisis. This analysis makes the case for the future development of the sector to be based on two broad strategies. The first is to deepen the integration of the tourism sector into the broader economy through the diversification of the regional tourism product, as well as the enhancement of linkages with other sectors, while the second is to expand the tourism sector into a total service economy through the introduction of new services. Considering linkages, the development of clusters and value chains to support the tourism sector is identified with respect to agriculture and food, handicraft, and furnishings. Among the new services identified are education, wellness, yachting and boating, financial services, and information and communications technologies (ICT). This overall strategy is deemed to be better suited to the macroeconomic realities of the Caribbean, where high labour costs and other structural rigidities require a high-valued specialty tourism product in order to sustain the sector’s global competitiveness.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment.

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HLA-G has a relevant role in immune response regulation. The overall structure of the HLA-G coding region has been maintained during the evolution process, in which most of its variable sites are synonymous mutations or coincide with introns, preserving major functional HLA-G properties. The HLA-G promoter region is different from the classical class I promoters, mainly because (i) it lacks regulatory responsive elements for IFN-gamma and NF-kappa B, (ii) the proximal promoter region (within 200 bases from the first translated ATG) does not mediate transactivation by the principal HLA class I transactivation mechanisms, and (iii) the presence of identified alternative regulatory elements (heat shock, progesterone and hypoxia-responsive elements) and unidentified responsive elements for IL-10, glucocorticoids, and other transcription factors is evident. At least three variable sites in the 3' untranslated region have been studied that may influence HLA-G expression by modifying mRNA stability or microRNA binding sites, including the 14-base pair insertion/deletion, +3142C/G and +3187A/G polymorphisms. Other polymorphic sites have been described, but there are no functional studies on them. The HLA-G coding region polymorphisms might influence isoform production and at least two null alleles with premature stop codons have been described. We reviewed the structure of the HLA-G promoter region and its implication in transcriptional gene control, the structure of the HLA-G 3' UTR and the major actors of the posttranscriptional gene control, and, finally, the presence of regulatory elements in the coding region.