584 research outputs found

    Machado-Joseph Disease / Spinocerebellar Ataxia Type 3

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    Tubagens industriais de alto risco : materiais, fiabilidade e inspecção RBI

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    Mestrado em Engenharia MecânicaEste trabalho, pretende reflectir a actividade do autor no período pós licenciatura, em que prosseguiu a sua actividade profissional na certificação e manutenção de parques industriais. Esta actividade é de indiscutível importância pelo factor de garantir a operacionalidade de equipamentos, e pela minimização do risco de avaria, para que o intervalo entre paragens indesejadas seja o maior possível. Esta área deengenharia, representa um constante desafio, a optimização e actualização das técnicas e estratégias usadas nos programas demanutenção e inspecção. A particularizar este facto, refere-se o uso do critério RBI, como base de análise e classificaçãoestabelecendo níveis de risco que juntamente com aprobabilidade de falha dos equipamentos, estabelecerá níveisde fiabilidade. O autor pôde, consequentementedesenvolver trabalho nesta área com os métodos acima referidos

    Gestão de eventos desportivos : o controlo de multidões e os seus intervenientes na segurança dos estádios

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    Mestrado em Gestão do Desporto - Organizações Desportivas“Security”, que traduzida para português significa “Segurança”, é o ponto principal desta investigação. Pretende-se analisar os vários aspetos ligados á Segurança nos eventos desportivos, em particular nos estádios de Futebol, desde os agentes que neles intervém, os mecanismos que possuem, a legislação pelos quais se regem e como é efetuado a interação entre todos. A metodologia aplicada para esta investigação foi elaborada através da elaboração de Entrevistas aos agentes envolvidos nos eventos desportivos e do levantamento de dados em Jornais, Revistas, Teses e Livros como pode ser observado na Bibliografia. Todas as perguntas efetuadas tinham o fundamento de 5 pontos estratégicos, os Recursos Humanos, Financeiros e Materiais, o Cronograma e a Legislação. O intuito de focar estes pontos foi verificar as diferentes formas de atuação, de coordenação e de relacionamento entre os agentes envolvidos. As conclusões de maior relevo neste estudo são: a segurança em todos os eventos deve fazer parte do planeamento da mesma; a comunicação entre os agentes envolvidos na segurança do evento é de extrema importância; a educação pública bem como as leis precisam de ser revistas e melhoradas, criando mais sinergias entre todos os envolvidos; encontrar novos mecanismo de segurança mais objetivos e modernos

    Liderança dos coordenadores de departamento : estudo realizado num agrupamento da zona centro do país

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    A presente Dissertação de Mestrado incide no estudo sobre a perceção dos professores sobre a liderança praticada pelos Coordenadores de Departamentos Curriculares ao nível de um Agrupamento de Escolas da Zona Centro do País. A questão da liderança é, desde há muito tempo a esta parte, retratada em inúmeros trabalhos contudo, considera-se relevante perceber como lidam os professores com os líderes que lhe são mais próximos. Por isso, o estudo reflecte sobre as lideranças intermédias nas escolas, nomeadamente da competência dos coordenadores de departamentos. O estudo empírico realizado teve assim como principal objetivo: caracterizar a liderança dos Coordenadores de todos os Departamentos Curriculares de um Agrupamento de Escolas da Zona Centro do País, especificamente ao nível da Gestão do Departamento, do Desenvolvimento Curricular, da Gestão de Pessoas e da Resolução de Problemas/Tomadas de Decisões. Tendo em conta este contexto, o presente estudo baseou-se numa amostra constituída por duzentos e sessenta e nove professores de todos os Departamentos Curriculares do Agrupamento em análise e os dados foram obtidos através da aplicação de questionários e submetidos a tratamento estatístico descritivo e inferencial. Da investigação efetuada concluiu-se que os professores do Agrupamento em questão se encontram satisfeitos com a liderança praticada pelos seus Coordenadores devido à sua eficiência na convocatória e presidência de reuniões do Departamento Curricular; pela promoção e partilha de experiências, pela representação dos respetivos professores no Conselho Pedagógico, atuando como elementos de ligação entre este órgão e o Departamento. É de realçar ainda, o facto de assegurarem a articulação entre o Departamento e as restantes estruturas de orientação educativa, estimularem a criação de condições que favoreçam a formação contínua e apoiarem os professores menos experientes, fomentarem a articulação entre a formação inicial e a formação contínua dos professores colaborando com as estruturas de formação contínua. O fato de promoverem a planificação das atividades e assegurem o cumprimento das orientações e decisões do Conselho Pedagógico é um contributo fundamental para a satisfação manifestada pelos seus pares.This Master dissertation focuses on the study of The teachers’ perception of the Department Coordinators’ Styles of Leadership within a « Agrupamento de Escolas» located in the centre area of Portugal. The issue of leadership has already been treated in many papers and studies and we considered it useful to learn how teachers deal with the leaders who are close to them. Thus, our study focuses on the intermediate leaderships embodied by the Department Coordinators. The main objective of this empirical study was to characterize the Department Coordinators’ Leadership from all the teaching levels of a «Agrupamento de Escolas» located in the centre of Portugal, specifically as far as the Department management, curricular development, staff management, problem solving and decision taking are concerned. This paper is based on a sample that includes two hundred and sixty-nine teachers from all the departments of the school we worked with and the Data was obtained through the application of questionnaires which were then treated statistically using a descriptive- inferential method. The results showed that those teachers are satisfied with the leadership shown by their coordinators. They consider that they are more efficient when they schedule and preside at meetings of their curricular department, when they encourage them to share experiences, represent the department teachers in the Pedagogical Council , acting as agents of transmission between this organ and the department, make sure that there is a real articulation between the department and the other structures of educational orientation, stimulate the creation of conditions that would favor the teachers’ training and support the less experienced teachers, promote the articulation between the teachers’ initial formation and their training in cooperation with the training structures, promote activities planning measures and make sure that the decisions and orientations from the Pedagogical Council are followed

    Caffeine and adenosine A 2A receptor inactivation decrease striatal neuropathology in a lentiviral-based model of Machado–Joseph disease

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    Objective: Machado–Joseph disease (MJD) is a neurodegenerative disorder associated with an abnormal CAG expansion, which translates into an expanded polyglutamine tract within ataxin-3. There is no therapy to prevent or modify disease progression. Because caffeine (a nonselective adenosine receptor antagonist) and selective adenosine A2A receptor (A2A R) blockade alleviate neurodegeneration in different brain diseases, namely at early stages of another polyglutamine-related disorder such as Huntington’s disease, we now tested their ability to control MJD-associated neurodegeneration. Methods: MJD was modeled by transducing the striatum of male adult C57Bl/6 mice with lentiviral vectors encoding mutant ataxin-3 in one hemisphere and wild-type ataxin-3 in the other hemisphere (as internal control). Caffeine (1g/L) was applied through the drinking water. Mice were killed at different time points (from 2 to 12 weeks) to probe for the appearance of different morphological changes using immunohistochemical analysis. Results: Mutant ataxin-3 caused an evolving neuronal dysfunction (loss of DARPP-32 staining) leading to neurodegeneration (cresyl violet and neuronal nuclei staining) associated with increased number of mutant ataxin-3 inclusions in the basal ganglia. Notably, mutant ataxin-3 triggered early synaptotoxicity (decreased synaptophysin and microtubule-associated protein-2 staining) and reactive gliosis (glial fibrillary acidic protein and CD11b staining), which predated neuronal dysfunction and damage. Caffeine reduced the appearance of all these morphological modifications, which were also abrogated in mice with a global A2A R inactivation (knockout). Interpretation: Our findings provide a demonstration that synaptotoxicity and gliosis are precocious events in MJD and that caffeine and A2A R inactivation decrease MJD-associated striatal pathology, which paves the way to consider A2A Rs as novel therapeutic targets to manage MJD

    Modelling dissolution of sparingly soluble powders

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    The present work deals with the simulation of the dissolution process of polydisperse powders. Three different size fractions of Ibuprofen were used to develop a model which assumes a diffusion layer thickness proportional to the particle diameter, up to a critical value, beyond which it is considered constant. The application of the resultant integrated equations to each size class of the primary particle size distribution leads to an almost perfect agreement between simulated and experimental dissolution profiles

    Neuropeptide Y Enhances Progerin Clearance and Ameliorates the Senescent Phenotype of Human Hutchinson-Gilford Progeria Syndrome Cells

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    Hutchinson-Gilford progeria syndrome (HGPS, or classical progeria) is a rare genetic disorder, characterized by premature aging, and caused by a de novo point mutation (C608G) within the lamin A/C gene (LMNA), producing an abnormal lamin A protein, termed progerin. Accumulation of progerin causes nuclear abnormalities and cell cycle arrest ultimately leading to cellular senescence. Autophagy impairment is a hallmark of cellular aging, and the rescue of this proteostasis mechanism delays aging progression in HGPS cells. We have previously shown that the endogenous Neuropeptide Y (NPY) increases autophagy in hypothalamus, a brain area already identified as a central regulator of whole-body aging. We also showed that NPY mediates caloric restriction-induced autophagy. These results are in accordance with other studies suggesting that NPY may act as a caloric restriction mimetic and plays a role as a lifespan and aging regulator. The aim of the present study was, therefore, to investigate if NPY could delay HGPS premature aging phenotype. Herein, we report that NPY increases autophagic flux and progerin clearance in primary cultures of human dermal fibroblasts from HGPS patients. NPY also rescues nuclear morphology and decreases the number of dysmorphic nuclei, a hallmark of HGPS cells. In addition, NPY decreases other hallmarks of aging as DNA damage and cellular senescence. Altogether, these results show that NPY rescues several hallmarks of cellular aging in HGPS cells, suggesting that NPY can be considered a promising strategy to delay or block the premature aging of HGPS

    Calpain inhibition reduces ataxin-3 cleavage alleviating neuropathology and motor impairments in mouse models of Machado-Joseph disease

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    Machado–Joseph Disease (MJD) is the most prevalent autosomal dominantly inherited cerebellar ataxia. It is caused by an expanded CAG repeat in the ATXN3 gene, which translates into a polyglutamine tract within the ataxin-3 protein. Present treatments are symptomatic and do not prevent disease progression. As calpain overactivation has been shown to contribute to mutant ataxin-3 proteolysis, translocation to the nucleus, inclusions formation and neurodegeneration, we investigated the potential role of calpain inhibition as a therapeutic strategy to alleviate MJD pathology. For this purpose, we administered orally the calpain inhibitor BDA-410 to a lentiviral mouse model of MJD. Western-blot and immunohistochemical analysis revealed the presence of N- and C-terminal mutant ataxin-3 fragments and the colocalization of large inclusions with cleaved caspase-3 in the mice brain. Oral administration of the calpain inhibitor BDA-410 decreased both fragments formation and full-length ataxin-3 levels, reduced aggregation of mutant ataxin-3 and prevented cell injury and striatal and cerebellar degeneration. Importantly, in correlation with the preserved cerebellar morphology, BDA-410 prevented motor behavioural deficits. In conclusion, BDA-410 alleviates Machado–Joseph neuropathology and may therefore be an effective therapeutic option for MJD

    Trehalose alleviates the phenotype of Machado–Joseph disease mouse models

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    Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is the most common of the dominantly inherited ataxias worldwide and is characterized by mutant ataxin-3 aggregation and neuronal degeneration. There is no treatment available to block or delay disease progression. In this work we investigated whether trehalose, a natural occurring disaccharide widely used in food and cosmetic industry, would rescue biochemical, behavioral and neuropathological features of an in vitro and of a severe MJD transgenic mouse model.This work was funded by BioBlast Pharma, the ERDF through the Regional Operational Program Center 2020, Competitiveness Factors Operational Program (COMPETE 2020) and National Funds through FCT (Foundation for Science and Technology) - SFRH/BD/87404/2012, BrainHealth2020 projects (CENTRO-01-0145-FEDER-000008), ViraVector (CENTRO-01-0145FEDER-022095), CortaCAGs (POCI-01-0145-FEDER-016719), SpreadSilenc‑ing POCI-01-0145-FEDER-029716 and POCI-01-0145-FEDER-007440, as well as the SynSpread, ESMI and ModelPolyQ under the EU Joint ProgramNeurodegenerative Disease Research (JPND), the last two co-funded bythe European Union H2020 program, GA No. 643417; by National Ataxia Foundation (USA), the American Portuguese Biomedical Research Fund (APBRF) and the Richard Chin and Lily Lock Machado–Joseph Disease Research Fund.info:eu-repo/semantics/publishedVersio

    Study On The Optimization Of TheTextile Coloristic Performance Of The Bleaching Process Using Pad-Steam

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    Information concerning the critical variables of the bleaching process (transformation of a raw fabric into bleached) by pad-steam is scarce, since it is considered a recent process in the textile industry. One hundred percent fine cotton fabrics present great difficulties in the standardization of bleaching across different production batches, which is even more complex when the fabric composition provided by the supplier is unknown. Thus, one carried out an evaluation of the variables that influence color yield in the bleaching process by pad-steam. The conditions used consisted of the reintroduction of the process of desizing by pad-batch, as well as washing and bleaching by pad-steam. The other variable changed was the chemical recipes (desizing and bleaching). As result of this research, the variables which most influenced color performance were the degree of whiteness (Berger) and the pH of extraction. Hence, a change in the production process for this type of 100% fine cotton is required. In this work, a statistical control was performed on the characteristics of the product obtained, which compared results before and during the study. The suggestions for improvement, some of which have already been implemented, are also presented. The results were then compared, enabling one to observe a significant improvement.info:eu-repo/semantics/publishedVersio
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