939 resultados para Kirk, David


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17th President 1996-2005

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Estudo sobre as construções simbólicas e identitárias da mulher presentes na narrativa e na estrutura das personagens femininas do filme Malévola (2014) – produção dos estúdios Disney (EUA). A narrativa é inspirada no conto de fadas “A Bela Adormecida do Bosque” e distingue-se pela perspectiva feminina, modificando as possibilidades de interpretação, além de possibilitar a quebra do paradigma dicotômico relacionado ao Bem e ao Mal. A pesquisa tem por objetivo estudar a evolução das construções imaginárias da mulher no cinema e traçar paralelos entre as características arquetípicas das personagens de Malévola em relação à identidade da mulher na contemporaneidade. Para tal, será tomado como referencial teórico os estudos do imaginário social, com as obras de Gilbert Durand, Edgar Morin e, em especial, Michel Maffesoli; conceitos da psicanálise a partir dos trabalhos de C.G. Jung, Erich Neumann, Marie-Louise Von Franz e Clarissa Pinkola Estés; as teorias de Stuart Hall, Laura Mulvey e Gilles Lipovetsky relacionadas aos estudos culturais com ênfase em gênero; e também o ecofeminismo através dos trabalhos de autoras como Vandana Shiva e Maria Mies. Nosso referencial teórico-metodológico é a Hermenêutica de Profundidade (HP) visando à interpretação da estrutura simbólica de nosso objeto. Resultam desta pesquisa a verificação de um processo de saturação de padrões identitários e simbólicos provindos da modernidade e a evolução de novas dinâmicas nas narrativas presentes nas mídias e na comunicação

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Selective inhibition of T cell costimulation using the B7-specific fusion protein CTLA4-Ig has been shown to induce long-term allograft survival in rodents. Antibodies preventing the interaction between CD40 and its T cell-based ligand CD154 (CD40L) have been shown in rodents to act synergistically with CTLA4-Ig. It has thus been hypothesized that these agents might be capable of inducing long-term acceptance of allografted tissues in primates. To test this hypothesis in a relevant preclinical model, CTLA4-Ig and the CD40L-specific monoclonal antibody 5C8 were tested in rhesus monkeys. Both agents effectively inhibited rhesus mixed lymphocyte reactions, but the combination was 100 times more effective than either drug alone. Renal allografts were transplanted into nephectomized rhesus monkeys shown to be disparate at major histocompatibility complex class I and class II loci. Control animals rejected in 5–8 days. Brief induction doses of CTLA4-Ig or 5C8 alone significantly prolonged rejection-free survival (20–98 days). Two of four animals treated with both agents experienced extended (>150 days) rejection-free allograft survival. Two animals treated with 5C8 alone and one animal treated with both 5C8 and CTLA4-Ig experienced late, biopsy-proven rejection, but a repeat course of their induction regimen successfully restored normal graft function. Neither drug affected peripheral T cell or B cell counts. There were no clinically evident side effects or rejections during treatment. We conclude that CTLA4-Ig and 5C8 can both prevent and reverse acute allograft rejection, significantly prolonging the survival of major histocompatibility complex-mismatched renal allografts in primates without the need for chronic immunosuppression.

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We sought to create a comprehensive catalog of yeast genes whose transcript levels vary periodically within the cell cycle. To this end, we used DNA microarrays and samples from yeast cultures synchronized by three independent methods: α factor arrest, elutriation, and arrest of a cdc15 temperature-sensitive mutant. Using periodicity and correlation algorithms, we identified 800 genes that meet an objective minimum criterion for cell cycle regulation. In separate experiments, designed to examine the effects of inducing either the G1 cyclin Cln3p or the B-type cyclin Clb2p, we found that the mRNA levels of more than half of these 800 genes respond to one or both of these cyclins. Furthermore, we analyzed our set of cell cycle–regulated genes for known and new promoter elements and show that several known elements (or variations thereof) contain information predictive of cell cycle regulation. A full description and complete data sets are available at http://cellcycle-www.stanford.edu

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Inclui notas bibliográficas.

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Inclui bibliografia.

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Potent and selective inhibitors of inducible nitric oxide synthase (iNOS) (EC 1.14.13.39) were identified in an encoded combinatorial chemical library that blocked human iNOS dimerization, and thereby NO production. In a cell-based iNOS assay (A-172 astrocytoma cells) the inhibitors had low-nanomolar IC50 values and thus were >1,000-fold more potent than the substrate-based direct iNOS inhibitors 1400W and N-methyl-l-arginine. Biochemical studies confirmed that inhibitors caused accumulation of iNOS monomers in mouse macrophage RAW 264.7 cells. High affinity (Kd ≈ 3 nM) of inhibitors for isolated iNOS monomers was confirmed by using a radioligand binding assay. Inhibitors were >1,000-fold selective for iNOS versus endothelial NOS dimerization in a cell-based assay. The crystal structure of inhibitor bound to the monomeric iNOS oxygenase domain revealed inhibitor–heme coordination and substantial perturbation of the substrate binding site and the dimerization interface, indicating that this small molecule acts by allosterically disrupting protein–protein interactions at the dimer interface. These results provide a mechanism-based approach to highly selective iNOS inhibition. Inhibitors were active in vivo, with ED50 values of <2 mg/kg in a rat model of endotoxin-induced systemic iNOS induction. Thus, this class of dimerization inhibitors has broad therapeutic potential in iNOS-mediated pathologies.

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