4 resultados para titrage calorimétrique isotherme (ITC)

em Repositório Científico do Instituto Politécnico de Lisboa - Portugal


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O trabalho consiste na descrição pormenorizada do processo de elaboração dos cursos Portugués para Restauración y Servicio de Bar (A1-A2) e Portugués para Dependiente de Comercio (A1-A2) (2008), cujo objetivo é certificar o nível de conhecimento linguístico dos membros da União Europeia para a realização de ocupações profissionais. Apresentamos os diferentes contextos que a equipa de língua portuguesa teve em conta antes da elaboração dos cursos ─ suportes, níveis de língua, fins ocupacionais, estudantes, região e cultura, línguas de origem dos alunos ─, bem como uma amostra das propostas desenvolvidas a nível de conteúdos culturais, gramaticais, fonéticos, lexicais, de atividades e exercícios e da avaliação.

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Dissertação apresentada à Escola Superior de Educação de Lisboa para obtenção do grau de Mestre em Ensino Especial – ramo de Problemas de Cognição e Multideficiência

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Trabalho de projeto realizado para obtenção do grau de Mestre em Engenharia Informática e de Computadores

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Isoniazid (INH) is still one of the two most effective antitubercular drugs and is included in all recommended multitherapeutic regimens. Because of the increasing resistance of Mycobacterium tuberculosis to INH, mainly associated with mutations in the katG gene, new INH-based compounds have been proposed to circumvent this problem. In this work, we present a detailed comparative study of the molecular determinants of the interactions between wt KatG or its S315T mutant form and either INH or INH-C10, a new acylated INH derivative. MD simulations were used to explore the conformational space of both proteins, and results indicate that the S315T mutation did not have a significant impact on the average size of the access tunnel in the vicinity of these residues. Our simulations also indicate that the steric hindrance role assigned to Asp137 is transient and that electrostatic changes can be important in understanding the enzyme activity data of mutations in KatG. Additionally, molecular docking studies were used to determine the preferred modes of binding of the two substrates. Upon mutation, the apparently less favored docking solution for reaction became the most abundant, suggesting that S315T mutation favors less optimal binding modes. Moreover, the aliphatic tail in INH-C10 seems to bring the hydrazine group closer to the heme, thus favoring the apparent most reactive binding mode, regardless of the enzyme form. The ITC data is in agreement with our interpretation of the C10 alkyl chain role and helped to rationalize the significantly lower experimental MIC value observed for INH-C10. This compound seems to be able to counterbalance most of the conformational restrictions introduced by the mutation, which are thought to be responsible for the decrease in INH activity in the mutated strain. Therefore, INH-C10 appears to be a very promising lead compound for drug development.