966 resultados para Structural behaviour
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Dissertação de mestrado em Administração Pública, orientada pelo Professor Doutor J. A. Oliveira Rocha apresentada na Escola de Economia e Gestão da Universidade do Minho, em 2006.
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Dissertation presented to obtain the Ph.D. degree in Chemistry (Physical Chemistry) at the Instituto de Tecnologia Química e Biológica da Universidade Nova de Lisboa
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The S100 proteins are 10-12 kDa EF-hand proteins that act as central regulators in a multitude of cellular processes including cell survival, proliferation, differentiation and motility. Consequently, many S100 proteins are implicated and display marked changes in their expression levels in many types of cancer, neurodegenerative disorders, inflammatory and autoimmune diseases. The structure and function of S100 proteins are modulated by metal ions via Ca2+ binding through EF-hand motifs and binding of Zn2+ and Cu2+ at additional sites, usually at the homodimer interfaces. Ca2+ binding modulates S100 conformational opening and thus promotes and affects the interaction with p53, the receptor for advanced glycation endproducts and Toll-like receptor 4, among many others. Structural plasticity also occurs at the quaternary level, where several S100 proteins self-assemble into multiple oligomeric states, many being functionally relevant. Recently, we have found that the S100A8/A9 proteins are involved in amyloidogenic processes in corpora amylacea of prostate cancer patients, and undergo metal-mediated amyloid oligomerization and fibrillation in vitro. Here we review the unique chemical and structural properties of S100 proteins that underlie the conformational changes resulting in their oligomerization upon metal ion binding and ultimately in functional control. The possibility that S100 proteins have intrinsic amyloid-forming capacity is also addressed, as well as the hypothesis that amyloid self-assemblies may, under particular physiological conditions, affect the S100 functions within the cellular milieu.
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Pharmaceutical spending in many other countries has had a steep increase in the last decade. The Portuguese Government has adopted several measures to reduce pharmaceutical expenditure growth, ranging from increased co-payments to price decreases determined administratively. Promotion of generic consumption has also ranked high in political priorities. We assess the overall impact of the several policy measures on total pharmaceutical spending, using monthly data over the period January 1995 – August 2008. Endogenous structural breaks (time-series) methods were employed. Our findings suggest that policy measures aimed at controlling pharmaceutical expenditure have been, in general, unsuccessful. Two breaks were identified. Both coincide with administratively determined price decreases. Measures aimed at increasing competition in the market had no visible effect on the dynamics of Government spending in pharmaceutical products. In particular, the introduction of reference pricing had only a transitory effect of less than one year, with historical growth resuming quickly. The consequence of it is a transfer of financial burden from the Government to the patients, with no apparent effect on the dynamics of pharmaceutical spending. This strongly suggests that pharmaceutical companies have been able to adjust to policy measures, in order to sustain their sales. It remains a challenge for the future to identify firms’ strategies that supported continued growth of sales, despite the several policy measures adop
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Structure and Infrastructure Engineering, 1-17
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Methamphetamine (METH) is a potent psychostimulant highly used worldwide. Recent studies evidenced the involvement of METH in the breakdown of the blood-brain-barrier (BBB) integrity leading to compromised function. The involvement of the matrix metalloproteinases (MMPs) in the degradation of the neurovascular matrix components and tight junctions (TJs) is one of the most recent findings in METH-induced toxicity. As BBB dysfunction is a pathological feature of many neurological conditions, unveiling new protective agents in this field is of major relevance. AcetylL-carnitine (ALC) has been described to protect the BBB function in different paradigms, but the mechanisms underling its action remain mostly unknown. Here, the immortalized bEnd.3 cell line was used to evaluate the neuroprotective features of ALC in METH-induced damage. Cells were exposed to ranging concentrations of METH, and the protective effect of ALC 1 mM was assessed 24 h after treatment. F-actin rearrangement, TJ expression and distribution, and MMPs activity were evaluated. Integrin-linked kinase (ILK) knockdown cells were used to assess role of ALC in ILK mediated METHtriggered MMPs’ activity. Our results show that METH led to disruption of the actin filaments concomitant with claudin-5 translocation to the cytoplasm. These events were mediated by MMP-9 activation in association with ILK overexpression. Pretreatment with ALC prevented METH-induced activation of MMP-9, preserving claudin-5 location and the structural arrangement of the actin filaments. The present results support the potential of ALC in preserving BBB integrity, highlighting ILK as a new target for the ALC therapeutic use.
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Whereas child care quality has been extensively studied in the U.S., there is much less information about the quality of child care in other countries.With one of the highest maternal employment rates in Europe, it is important to examine child care in Portugal. Thirty toddler classrooms in child care centers were observed. The purpose of this studywas to determine whether structural features account for overall toddler child care quality. Results showed younger and better-paid teachers provided better toddler child care quality. Space available per childwas not a statistically significant predictor of toddler child care quality.Overall quality results suggest some issues to be addressed by early education policy makers and indicate the need to promote quality in Portuguese toddler child care programs.
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Dissertation presented to obtain a Doctoral Degree in Biology by Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa
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Nesta Dissertação ir-se-á avaliar o desempenho de algumas ligações existentes nos veículos pesados de passageiros, através do Regulamento Eurocódigo 3. Nos últimos anos ocorreram diversos acidentes envolvendo este tipos de veículos, em que os mesmos causaram vítimas mortais e feridos graves. Serão testadas por simulação numérica algumas ligações pertencentes a elementos constituintes da superestrutura, em que esta é normalmente afectada com a ocorrência de acidentes. Assim sendo, o estudo de nós de ligação tem uma importância fulcral para que uma superestrutura suporte situações extremas e que resista a solicitações externas aplicadas. Iniciou-se esta Dissertação com o estudo da sinistralidade e de acidentes que envolvem veículos pesados de passageiros. No capítulo 2 abordou-se um programa que promove simulações numéricas de acidentes e estudo do comportamento dos passageiros em caso de acidente, sendo referido o Regulamento que homologa os veículos pesados de passageiros e os seus principais métodos. Abordaram-se os principais constituintes da estrutura de um veículo pesado de passageiros. No capítulo 3, é referido o Eurocódigo 3 em termos do estudo das ligações tubulares usadas neste tipo de veículos. No capítulo 4, fez-se o estudo e selecção de elementos a utilizar para a simulação numérica de casos preconizados pelo Eurocódigo 3 e estudaram-se três tipos de ligações que são usadas na construção da superestrutura deste tipo de veículos, tendo-se retirado conclusões deste estudo.
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Hindawi Publishing Corporation Bioinorganic Chemistry and Applications Volume 2010, Article ID 634597, 8 pages
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The aim of this study was to undertake a comparative analysis of the practices and information behaviour of European information users who visit information units specialising in European information in Portugal and Spain. The study used a quantitative methodology based on a questionnaire containing closed questions and one open question. The questions covered the general sociological profile of the respondents and their use of European Document Centres, in addition to analysing aspects associated with information behaviour relating to European themes. The study therefore examined data on the preferred means and sources for accessing European information, types of documents and the subjects investigated most. The use of European databases and the Internet to access material on Europe was also studied, together with the reasons which users considered made it easy or difficult to access European information, and the aspects they valued most in accessing this information. The questionnaire was administered in European Document Centres in 2008 and 2010.
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One parameter that influences the adhesively bonded joints performance is the adhesive layer thickness. Hence, its effect has to be investigated experimentally and should be taken into consideration in the design of adhesive joints. Most of the results from literature are for typical structural epoxy adhesives which are generally formulated to perform in thin sections. However, polyurethane adhesives are designed to perform in thicker sections and might have a different behavior as a function of adhesive thickness. In this study, the effect of adhesive thickness on the mechanical behavior of a structural polyurethane adhesive was investigated. The mode I fracture toughness of the adhesive was measured using double-cantilever beam (DCB) tests with various thicknesses of the adhesive layer ranging from 0.2 to 2 mm. In addition, single lap joints (SLJs) were fabricated and tested to assess the influence of adhesive thickness on the lap-shear strength of the adhesive. An increasing fracture toughness with increasing adhesive thickness was found. The lap-shear strength decreases as the adhesive layer gets thicker, but in contrast to joints with brittle adhesives the decrease trend was less pronounced.
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Adhesive bonding is an excellent alternative to traditional joining techniques such as welding, mechanical fastening or riveting. However, there are many factors that have to be accounted for during joint design to accurately predict the joint strength. One of these is the adhesive layer thickness (tA). Most of the results are for epoxy structural adhesives, tailored to perform best with small values of tA, and these show that the lap joint strength decreases with increase of tA (the optimum joint strength is usually obtained with tA values between 0.1 and 0.2 mm). Recently, polyurethane adhesives were made available in the market, designed to perform with larger tA values, and whose fracture behaviour is still not studied. In this work, the effect of tA on the tensile fracture toughness (View the MathML source) of a bonded joint is studied, considering a novel high strength and ductile polyurethane adhesive for the automotive industry. This work consists on the fracture characterization of the bond by a conventional and the J-integral techniques, which accurately account for root rotation effects. An optical measurement method is used for the evaluation of crack tip opening (δn) and adherends rotation at the crack tip (θo) during the test, supported by a Matlab® sub-routine for the automated extraction of these parameters. As output of this work, fracture data is provided in traction for the selected adhesive, enabling the subsequent strength prediction of bonded joints.
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Adhesively bonded techniques are an attractive option to repair aluminium structures, compared to more traditional methods. Actually, as a result of the improvement in the mechanical characteristics of adhesives, adhesive bonding has progressively replaced the traditional joining methods. There are several bonded repair configurations, as single-strap, double-strap and scarf. Compared with strap repairs, scarf repairs have the advantages of a higher efficiency and the absence of aerodynamic disturbance. The higher efficiency is caused by the elimination of the significant joint eccentricities of strap repairs. Moreover, stress distributions along the bond length are more uniform, due to tapering of the scarf edges. The main disadvantages of this technique are the difficult machining of the surfaces, associated costs and requirement of specialised labour. This work reports on an experimental and numerical study of the tensile behaviour of two-dimensional (2D) scarf repairs of aluminium structures bonded with the ductile epoxy adhesive Araldite® 2015. The numerical analysis, by Finite Elements (FE), was performed in Abaqus® and used cohesive zone models (CZM) for the simulation of damage onset and growth in the adhesive layer, thus enabling the strength prediction of the repairs. A parametric study was performed on the scarf angle (α) and different configurations of external reinforcement (applied on one or two sides of the repair, and also different reinforcement lengths). The obtained results allowed the establishment of design guidelines for repairing, showing that the use of external reinforcements enables increasing α for equal strength recovery, which makes the repair procedure easier. The numerical technique was accurate in predicting the repairs’ strength, enabling its use for design and optimisation purposes.