500 resultados para 4E-BP1


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Breast cancer remains one of the leading causes of cancer morbidity and mortality. Despite significant advances in treatment of breast cancer a substantial proportion of women affected by this disease succumb to it. Survival of patients with advanced disease, chemoresistant tumors or a suboptimal response to endocrine therapy is significantly shortened. Hence, further understanding of disease pathogenesis is required to enhance the arsenal of approaches to cure this deadly ailment. Recent advances in biochemistry, molecular cell biology and cancer research highlighted the importance of dysregulation of protein synthesis, translation, in the development and progression of tumors. This dysregulation appears to take place at an early stage of translation, called translation initiation, that is a highly controlled and rate-limiting step of the protein synthesis. In this chapter we summarize decades of knowledge accumulated in regards to the role of translation and its regulation in the development and progression of breast cancer. We then extensively discuss applications of this knowledge in diagnosis and treatment of breast cancer.

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Os antigos Egípcios acreditavam que o touro poderoso representava a personalidade do próprio faraó. O touro estava, de facto, intimamente associado ao Estado faraónico, estando presente ao nível dos regalia (cauda taurina) e significativamente nos próprios epítetos reais (ka nakht). Na mitologia egípcia, de todos os touros sagrados o que maior projecção alcançou, como deus agrário da fecundidade, da vegetação renascida e da ressurreição, foi, seguramente, o touro Ápis, associado em Mênfis aos deuses Ptah e Osíris. Na sua condição de touro ágil, vigoroso e viril, Ápis era um intermediário consistente entre o mundo dos vivos e o dos mortos, além de ser um propiciador de fertilidade e renascimento quando associado ao deus-Sol. A sua participação, literalmente ao lado do faraó, na «corrida ritual», importante cerimónia no âmbito da concepção ideológica do poder real, reforçou ainda mais a sua importância no seio do panteão egípcio.

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Les conseillers d’orientation (c.o.) en milieu scolaire ont plusieurs rôles à remplir auprès des élèves, entre autres la réponse aux demandes des élèves, le maintien de l’accès à une documentation pertinente et l’accompagnement dans une meilleure connaissance de soi et du monde du travail (Dupont, Gingras et Marceau, 2002a). Pour ce faire, plusieurs moyens sont à leur disposition, dont l’évaluation psychométrique (OCCOQ, 2013). Un concept qui pourrait utile de mesurer auprès des adolescents est la maturité vocationnelle (Jordaan et Heyde, 1979). Des instruments de mesure évaluant la maturité vocationnelle existent déjà, mais aucun d’entre eux ne semble convenir parfaitement à la réalité du Québec, emmenant la création d’un nouvel outil, le Questionnaire de maturité vocationnelle (QMV). L’objectif de ce mémoire est de vérifier les propriétés psychométriques de l’échelle affective du QMV. Les participants de l’étude sont 1 164 adolescents québécois âgés entre 14 et 18 ans (moyenne : 15,30 ans), provenant de 14 écoles secondaires. Pour ce qui est du niveau scolaire des participants, 511 (43,9 %) sont en 3e secondaire, 303 (26 %) sont en 4e secondaire et 350 (30,1 %) sont en 5e secondaire. Les résultats obtenus appuient la fidélité et la validité de l’instrument de mesure.

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Catalysis plays a vital role in modern synthetic chemistry. However, even if conventional catalysis (organo-catalysis, metal-catalysis and enzyme-catalysis) has provided outstanding results, various unconventional ways to make chemical reactions more effective appear now very promising. Computational methods can be of great help to reach a deeper comprehension of these chemical processes. The methodologies employed in this thesis are Quantum-Mechanical (QM), Molecular Mechanics (MM) and hybrid Quantum-Mechanical/Molecular Mechanics (QM/MM) methods. In this abstract the results are briefly summarised. The first unconventional catalysis investigated consists in the application of Oriented External Electric Fields (OEEFs) to SN2 and 4e-electrocyclic reactions. SN2 reactions with back-side mechanism can be catalysed or inhibited by the presence of an OEEF. Moreover, OEEFs can inhibit back-side mechanism (Walden inversion of configuration) and promote the naturally unfavoured front-side mechanism (retention of configuration). Electrocyclic ring opening reaction of 3-substituted cyclobutene molecules can occur with inward or outward mechanisms depending on the nature of substituent groups on the cyclobutene structure (torquoselectivity principle). OEEFs can catalyse the naturally favoured pathway or circumvent the torquoselectivity principle leading to different stereoisomers. The second case study is based on Carbon Nanotubes (CNTs) working as nano-reactors: the reaction of ethyl chloride with chloride anion inside CNTs was investigated. In addition to the SN2 mechanism, syn and anti-E2 reactions are possible. These reactions inside CNTs of different radii were examined with hybrid QM/MM methods, finding that these processes can be both catalysed and inhibited by the CNT diameter. The results suggest that electrostatic effects govern the activation energy variations inside CNTs. Finally, a new biochemical approach, based on the use of DNA catalyst was investigated at QM level. Deoxyribozyme 9DB1 catalyses the RNA ligation allowing the regioselective formation of the 3'-5' bond, following an addition-elimination two-step mechanism.

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Depoimento do médico de Família e Comunidade João Henrique Kolling, da unidade básica de saúde Santa Cecília, do Hospital de Clínicas de Porto Alegre, sobre a ocorrência, em 2013, de uma microepidemia de dengue na vila Sossego, pequena comunidade da capital gaúcha. O médico fala sobre a identificação dos casos, os fatores determinantes – como o acúmulo de lixo a céu aberto – e a realização de um intenso trabalho de conscientização dos moradores. Conforme o médico, a integração da equipe de Atenção Primária e os laços estabelecidos com a comunidade contribuíram para solução do problema de saúde pública. O vídeo integra o curso de Atualização no combate Vetorial ao Aedes aegypti desenvolvido pelo TelessaúdeRS/UFRGS em parceria com o Ministério da Saúde.