961 resultados para Fernández de Lizardi


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Homenaje a Ignacio Barandiarán Maestu / coord. por Javier Fernández Eraso, Juan Santos Yanguas.

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O estudo desenvolvido nesta Tese de Doutorado trata da análise crítica da estética dos conceitos: forma, tectônica, funcionalidade, semiótica e afetuosidade, no âmbito da arquitetura, no programa de museus de arte contemporânea e centros culturais. Os museus de arte contemporânea e centros culturais, estudos de caso, selecionados para nossa Tese de Doutorado foram inaugurados na década de 1990. Como segue: Centro Cultural Jean-Marie Tijibaou (Nova Caledônia, França), de Renzo Piano; Museu de Arte Contemporânea de Naoshima (Japão), de Tadao Ando; Museu Guggenheim Bilbao (Espanha), de Frank O. Gehry; Museu de Arte Contemporânea Fundação Serralves (Portugal), de Álvaro Siza Vieira; Museu de Arte Contemporânea de Niterói (Brasil), de Oscar Niemeyer; Fundació Museu d'Art Contemporani de Barcelona (Espanha), de Richard Meier; Museu de Arte Contemporânea Carré d'Art de Nimes (França), de Norman Foster; Museu de Arte Contemporânea de Lyon (França), de Renzo Piano; Centro Cultural Consonni (Espanha), ausência de um arquiteto autor do projeto. Tanto os estudos de caso como os arquitetos, autores dos projetos, são considerados de destaque no panorama da arquitetura internacional erudita contemporânea. Os teóricos que forneceram a fundamentação conceitual deste estudo multidisciplinar são, em primeiro lugar, o Professor Catedrático Luiz Felipe Baêta Neves Flores (Transdisciplinaridade) além da Professora Catedrática Maria Luisa Amigo Fernández de Arroyabe (Ócio Estético) e ainda, os também importantes, Manuel Cuenca Cabeza (Ócio Humanista), Charles Jencks e Gonçalo Miguel Furtado Cardoso Lopes (Crítica de Arquitetura), Jesús Pedro Lorente, Chris van Uffelen e Roberto Segre (Museus de Arte Contemporânea).

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O presente trabalho consistiu em realizar uma proposta metodológica de análise quantitativa da sustentabilidade de estabelecimentos agropecuários fluminenses através do emprego do marco metodológico proposto por Sauvenier et al. (2006) e van Cauwenbergh et al. (2007), denominado SAFE (Sustainability Assessment of Farming and the Environment Framework). Conforme a aplicação para sistemas agrários realizada por Sánchez-Fernández (2009) e por sua vez, incorporando a quarta dimensão da sustentabilidade (dimensão institucional), ademais das três dimensões clássicas neste tipo de análise (econômica, social e ambiental), seguindo a sugestão do IBGE (2010), com base nas recomendações do Livro Azul da ONU (1996). Esse procedimento contou com a colaboração e validação de um painel composto por 16 especialistas em agricultura fluminense o que permitiu selecionar 20 indicadores de sustentabilidade, derivados de 17 critérios, 8 princípios e 4 dimensões. Dos resultados alcançados e de seus possíveis desdobramentos, a proposta metodológica sugerida pode ser considerada uma ferramenta potencialmente útil para guiar as políticas públicas que incidem sobre o setor.

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Homenaje a Ignacio Barandiarán Maestu / coord. por Javier Fernández Eraso, Juan Santos Yanguas.

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Homenaje a Ignacio Barandiarán Maestu / coord. por Javier Fernández Eraso, Juan Santos Yanguas.

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Background: Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. Methods: A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. Results: Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: p(M-H) = 0.0005; ORM-H (95% CI) = 1.27 (1.11-1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [p(M-H) = 0.0003, ORM-H (95% CI) = 1.32 (1.14-1.53)]. Conclusion: Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.

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Homenaje a Ignacio Barandiarán Maestu / coord. por Javier Fernández Eraso, Juan Santos Yanguas.

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Homenaje a Ignacio Barandiarán Maestu / coord. por Javier Fernández Eraso, Juan Santos Yanguas

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Homenaje a Ignacio Barandiarán Maestu / coord. por Javier Fernández Eraso, Juan Santos Yanguas.

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Homenaje a Ignacio Barandiarán Maestu / coord. por Javier Fernández Eraso, Juan Santos Yanguas.

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While TRAIL is a promising anticancer agent due to its ability to selectively induce apoptosis in neoplastic cells, many tumors, including pancreatic ductal adenocarcinoma (PDA), display intrinsic resistance, highlighting the need for TRAIL-sensitizing agents. Here we report that TRAIL-induced apoptosis in PDA cell lines is enhanced by pharmacological inhibition of glycogen synthase kinase-3 (GSK-3) or by shRNA-mediated depletion of either GSK-3 alpha or GSK-3 beta. In contrast, depletion of GSK-3 beta, but not GSK-3 alpha, sensitized PDA cell lines to TNF alpha-induced cell death. Further experiments demonstrated that TNF alpha-stimulated I kappa B alpha phosphorylation and degradation as well as p65 nuclear translocation were normal in GSK-3 beta-deficient MEFs. Nonetheless, inhibition of GSK-3 beta function in MEFs or PDA cell lines impaired the expression of the NF-kappa B target genes Bcl-xL and cIAP2, but not I kappa B alpha. Significantly, the expression of Bcl-xL and cIAP2 could be reestablished by expression of GSK-3 beta targeted to the nucleus but not GSK-3 beta targeted to the cytoplasm, suggesting that GSK-3 beta regulates NF-kappa B function within the nucleus. Consistent with this notion, chromatin immunoprecipitation demonstrated that GSK-3 inhibition resulted in either decreased p65 binding to the promoter of BIR3, which encodes cIAP2, or increased p50 binding as well as recruitment of SIRT1 and HDAC3 to the promoter of BCL2L1, which encodes Bcl-xL. Importantly, depletion of Bcl-xL but not cIAP2, mimicked the sensitizing effect of GSK-3 inhibition on TRAIL-induced apoptosis, whereas Bcl-xL overexpression ameliorated the sensitization by GSK-3 inhibition. These results not only suggest that GSK-3 beta overexpression and nuclear localization contribute to TNF alpha and TRAIL resistance via anti-apoptotic NF-kappa B genes such as Bcl-xL, but also provide a rationale for further exploration of GSK-3 inhibitors combined with TRAIL for the treatment of PDA.

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166 p. : il. col.

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Kv7.2 (KCNQ2) is the principal molecular component of the slow voltage gated M-channel, which strongly influences neuronal excitability. Calmodulin (CaM) binds to two intracellular C-terminal segments of Kv7.2 channels, helices A and B, and it is required for exit from the endoplasmic reticulum. However, the molecular mechanisms by which CaM controls channel trafficking are currently unknown. Here we used two complementary approaches to explore the molecular events underlying the association between CaM and Kv7.2 and their regulation by Ca2+. First, we performed a fluorometric assay using dansylated calmodulin (D-CaM) to characterize the interaction of its individual lobes to the Kv7.2 CaM binding site (Q2AB). Second, we explored the association of Q2AB with CaM by NMR spectroscopy, using N-15-labeled CaM as a reporter. The combined data highlight the interdependency of the N- and C-lobes of CaM in the interaction with Q2AB, suggesting that when CaM binds Ca2+ the binding interface pivots between the N-lobe whose interactions are dominated by helix B and the C-lobe where the predominant interaction is with helix A. In addition, Ca2+ makes CaM binding to Q2AB more difficult and, reciprocally, the channel weakens the association of CaM with Ca2+.