Downstream processing development of enveloped viruses for clinical applications: innovative tools for rational process optimization

Dissertation presented to obtain a Ph.D. degree in Engineering and Technology Sciences, Biotechnology at the Instituto de Tecnologia Química e Biológica, Universidade Nova de LisboaViral vectors and virus-like particles hold a tremendous potential in various clinical applications in the areas of gene therapy and/or vaccination, drawing the attention of biotechnology and pharmaceutical companies. The majority of these products are manufactured in animal cell cultures, inherently making the process costly. A great deal of effort is taking place to generate optimized biological and engineering strategies to find scalable and cost-effective processes, easily transferable to cGMP facilities. However, the implementation of robust downstream processes generating this type of biopharmaceuticals in the amounts required for pre-clinical and clinical trials is still lacking and lagging. By including a labile lipid membrane layer harboring glycoproteins (often critical for infection) over the viral capsid, enveloped viruses bring extra challenges in terms of their bioprocessing particularly downstream. The work developed during this thesis aimed at improving the state-of-the-art purification processes for these types of viral particles. The rationale was to integrate process understanding with product characterization, still scarce in such biological systems.(...

Seismic vulnerability assessment of existing reinforced concrete buildings in urban centers

Despite the recent advances in the analysis of the seismic performance of reinforced concrete structures, the assessment of large building inventories aimed at defining and prioritizing structural retrofitting strategies is still a technically challenging task. This paper aims to contribute to bridging this gap by presenting a simplified methodology for assessing the seismic vulnerability of reinforced concrete buildings, which is then applied to a group of 91 buildings affected by recent earthquakes with different macroseismic intensities. The presented methodology is based on the evaluation of eight parameters associated with different factors that affect the seismic response of the building, namely its structural features, foundation conditions, and position within the urban mesh. The formulation of each parameter and the relative weight attributed to each one of them were defined on the basis of post-earthquake damage observation and expert opinion. After defined, the proposed methodology is applied to Faro city center. Based on the results obtained, a cost benefit analysis is made considering a strengthening solution to the buildings with soft-story irregularity

Direito à Educação como Mínimo Existencial e os Desafios de sua Concretização diante da Escassez de Recursos Públicos

The objective of this study is to demonstrate the compulsory provision of the right to basic education, guaranteed by the 1988 Constitution. Based on knowledge of Constitutional, Financial, part of the legal and constitutional provision, passing through the characterization as fundamental right and existential minimum. Then there are cited forms provided in the Constitution of enforceability of the right to education, such as the use of lawsuits. The budgetary and financial challenges for realizing the right to education are analyzed. Finally, the importance of responsible action of the Public Power for the effectiveness of the Right to Education is emphasized.O presente trabalho tem como objetivo demonstrar a obrigatoriedade da prestação do direito à educação básica, garantido pela Constituição de 1988. Com base em conhecimentos de Direito Constitucional, Financeiro e Teoria dos Direitos Fundamentais, parte-se da previsão legal e constitucional, passando pela caracterização como direito fundamental e mínimo existencial. Depois citam-se formas previstas na Constituição de exigibilidade do direito à educação, como o uso de ações judiciais. Analisam-se os desafios de natureza orçamentária e financeira para a concretização do direito à educação. Por fim, ressalta-se a importância da atuação responsável do Poder Público para a efetividade do Direito à Educação

Otimização das rotas para operadores de coleta da EMEL

Mestrado em Decisão Económica e EmpresarialAtravés da parceria entre o ISEG e a EMEL - Empresa Municipal de Mobilidade e Estacionamento de Lisboa, foi realizado um estágio profissional, tendo como objetivo otimizar as rotas dos operadores de coleta da EMEL. Foi assim definido o objetivo de identificar, de forma automática, rotas que permitam coletar mais dinheiro no fim de cada turno, reduzindo e homogeneizando os montantes de dinheiro que ficam na rua e, por consequência, o risco de roubo. O problema enquadrado no Vehicle Routing Problem with Profits, identifica rotas que, partindo e regressando de/a um ponto fixo (a base), visitam um certo conjunto de nodos (parquímetros), compatíveis com a capacidade do veículo e com a duração dos turnos dos operadores de coleta. Não se exige que todos os nodos sejam visitados diariamente, sendo apenas visitados os que garantem maior retorno. Foi construída uma função para estimar o valor depositado em cada parquímetro, por hora, sendo assim possível estimar o seu valor no momento da coleta. De seguida, desenvolveu-se e programou-se (em VBA) uma heurística construtiva para a geração de rotas.Through the partnership between ISEG and EMEL - Empresa Municipal de Mobilidade e Estacionamento de Lisboa, the traineeship has been proposed aiming to optimize the routes made by the EMEL's coin collection operators. The scope is to automatically identify routes that allow the coin collection of more parking meters at the end of each working shift, reducing the amount of money left on the street. The problem was interpreted as a Vehicle Routing Problem with Profits. The routes start and end at a fixed point (the base), and the vehicles must visit a certain set of nodes (metered), within the crew time limit. In this problem there is no need to visit every node daily but to visit those that guarantee a higher return, provided that both the vehicles' capacity and the time limits are satisfied. A valuation function was built to estimate the value deposited in each parking meter per hour. Then, a constructive heuristic was developed and programmed (VBA) to generate routes.info:eu-repo/semantics/publishedVersio

Ligações especiais entre estruturas metálicas e de betão: projecto baseado em modelos de escoras e tirantes

Este trabalho reflecte sobre a capacidade resistente do betão, no que diz respeito à utilização do espaço provido pelo recobrimento das estruturas de betão armado, para proporcionar a transmissão de esforços nas pós-instalações de uma maneira mais eficiente e com um menor número de condicionantes. Nas ligações onde existe um binário de esforços nas interfaces, podemos estabelecer que se for provida uma indentação adequada na zona de compressão, o betão tem a capacidade de transmitir esforços elevados com um ângulo relativamente baixo face à sua superfície. Neste documento é analisada uma solução utilizando a formulação com base nos modelos de escoras e tirantes, de forma a retratar de forma simplificada e coerente como essa introdução de esforços se redistribui para o interior do corpo sólido de betão. No caso apresentado resolveu contabilizar-se o efeito favorável da compressão triaxial junto a cargas concentradas que levou a um modelo tridimensional. Através da análise são apresentados os procedimentos para caracterizar a zona nodal nas imediações da ligação. Com base na simplificação dos campos de tensão, foram adaptadas as formulações com vista a encontrar o valor máximo de resistência dessa ligação.This work reflects on concrete capacity design of a connection that uses concrete cover to establish a way to transmit forces in post-installations with efficiency and less construction site problems. In connections where there is a set of forces between interfaces, if a keyed joint where created on the correspondent compression area, concrete is able to transmit that force even in a lower angle of application regarding to concrete’s surface. In this paper an analysis has been conducted to a specific case with a strut and tie formulation, in a way to comprehend with a simple yet clarifying perspective the flow of forces, from where they’re applied into the interior of the solid body. In this case, the favorable effect of confining stresses in the periphery of a concentrated load has been taken into account, which has lead into a tri-dimensional model. Through the analysis, procedures had been carried out in order to characterize the nodal zone in the vicinity of the connection. With simplified stress fields the recommendations and formulations had been adapted to each case in order to establish a maximum value that connection could support

Dermatite das almofadas plantares em frangos de engorda em explorações da região oeste de Portugal

A dermatite das almofadas plantares consiste numa lesão cutânea localizada nas almofadas plantares dos frangos, que se forma devido ao contacto com cama húmida. Esta lesão pode ter diversas origens como fatores genéticos, ambientais, nutricionais e de maneio. É um importante indicador de bem-estar animal, uma vez que permite estimar a qualidade do ar, da cama e de saúde animal que existiram no ciclo produtivo, além de terem impacto fundamental a nível económico para os criadores. Ao longo do tempo de vigência deste estudo, realizado na região oeste de Portugal, o objetivo que o norteou passou por avaliar a incidência e a gravidade de dermatite das almofadas plantares ante mortem, nas explorações avícolas (em diferentes zonas do pavilhão, entre os 8 e os 12 dias, e os 20 e os 28 dias de vida) e post mortem, no matadouro. Pretendeu-se avaliar a relação da humidade da cama, da humidade relativa do ambiente, da ventilação, da taxa de mortalidade, do índice de conversão, do tipo de material utilizado nas camas das explorações e o tipo de maneio utilizado pelo criador, no desenvolvimento de dermatites das almofadas plantares. Na exploração, foram avaliados 50 frangos, num total de 58 bandos de 22 explorações. A sua classificação foi feita com base no guia interpretativo "Avaliação dos parâmetros de bem estar dos frangos no matadouro", da Direção Geral de Alimentação e Veterinária. No final do ciclo produtivo, o bando foi classificado segundo o grau de dermatite que obteve no matadouro. Foram ainda analisados dados produtivos de alguns bandos, onde foi possível verificar que os que apresentaram dermatite das almofadas plantares tiveram menor peso e um índice de conversão maior comparado com bandos que não sofreram desta patologia. Em bandos onde não foi realizado o maneio de camas, a dermatite foi mais frequente.Contudo, também foi identificada em bandos onde esse maneio era realizado, tendo sido verificados, neste caso, problemas de controlo da ventilação nos pavilhões. Foram diagnosticadas coccidiose e enterite necrótica o que pode ter favorecido a dermatite, uma vez que estas doenças provocam uma alteração na flora intestinal, levando à elevada humidade nas camas, o que foi, por si só, suficiente para conduzir a dermatites. A leitura dos diversos estudos que foram mencionados ao longo da elaboração deste possibilitou a comparação com os resultados obtidos, e verificaram-se na generalidade as mesmas situações já descritas na literatura.Foot pad dermatitis is a skin lesion located on the pads of the chickens, which is formed due to contact with wet litter. This lesion may have several factors such as genetic, environmental, nutritional and management factors. It is an important animal welfare indicator since it allows to estimate air quality, bedding and animal health that existed in the production cycle, and have fundamental economic impact for the breeders. During this study in the Oeste region of Portugal, the objective was to evaluated the incidence and severity of foot pad dermatitis ante mortem in poultry farms (in different areas of the shed, between 8 and 12 days, and 20 and 28 days of life) and post mortem, in the slaughterhouse. The aim to evaluate the relationship of the litter humidity, ambient relative humidity, ventilation, mortality rate, feed conversion rate, the type of material used in the litters of farms and the type of management used by the breeder, on development of foot pad dermatitis. Fifty chickens per flock were evaluated on a farm resulting in a total of 58 flocks from 22 farms, the classification was based on the interpretative guide "Avaliação dos parâmetros de bem estar dos frangos no matadouro" done by Direção Geral de Alimentação e Veterinária. At the end of the productive cycle, the flock was classified according to the degree of dermatitis it obtained at the slaughterhouse, and productive data from some flocks were analyzed, where it was possible to verify that those who presented foot pad dermatitis had lower weight and higher feed conversion rate compared with flocks that didn`t suffer from this pathology.In flocks where litter weren`t managed the dermatitis was more frequent, however it also identified in flocks where this management was performed, being found in this case, ventilation control problems in the shed. Cocidiosis and necrotic enteritis were diagnosed, which may have favored dermatitis, since these diseases cause a change in the intestinal flora leading to the high humidity in the litters, which factor alone is sufficient to lead to dermatitis. The reading of the several studies that were mentioned throughout this one made possible the comparison with the obtained results, in that it was able to understand the same assumptions of the literature

Implementing open-source information systems for assessing and managing the seismic vulnerability of historical constructions

Reducing the uncertainty about the structural vulnerability of historical constructions comprises the selection of reasonably generalised approaches in a context of a significant typological variability; the difficulty of performing large-scale assessments with reasonable reliability; and the lack of dedicated infrastructures for efficiently storing, sharing, managing, and updating data – an issue that is even more relevant for small (and often isolated) settlements. This work presents a proposal to set up a geographic database for surveying, calculating and storing the seismic vulnerability index of masonry constructions using an adapted version of the GNDT-II approach. Some critical steps for setting up Geographical Information System (GIS) databases for storing and managing the fields of a parameter-based vulnerability assessment are presented. Then, some alternatives for distributing the database are introduced, including cloud-based distribution and Transactional Web Feature Service (WFS-T) protocols, even using virtual servers. Additionally, an alternative front-end for accessing data and calculating the vulnerability index of constructions and levels of damage is presented. The main objective is to offer a replicable and feasible workflow to be performed even with reduced infrastructure and computational resources but can be easily connected and associated to a progressively enlarged system based on free and open-source software

Seismic vulnerability assessment of Portuguese adobe buildings

Adobe construction represents 5.3% of the total Portuguese building stock according to the latest National Housing Census. The distribution of these adobe buildings is scattered across the country, with higher density in the central region and in Algarve in the south, where the seismic hazard is highest. A large proportion of these buildings are still in use for residential and commercial purposes and are of historical significance, contributing to the cultural heritage of the country. Adobe buildings are known to exhibit low seismic resistance due to their brittle behavior, thus making them vulnerable to ground shaking and more prone to structural damage that can potentially cause human fatalities. Three buildings with one-story, two-stories, and two-stories plus an attic were numerically modeled using solid and contact elements. Calibration and validation of material properties were carried out following experimental results. A set of 30 ground motion records with bi-directional components were selected, and non-linear time-history analyses were performed until complete collapse occurred. Two novel engineering demand parameters (EDPs) were used, and damage thresholds were proposed. Finally, fragility and fatality vulnerability functions were derived. These functions can be used directly in seismic risk assessment studies.This work was funded by the Foundation for Science and Technology (FCT)—Aveiro Research Centre for Risks and Sustainability in Construction (RISCO), Universidade de Aveiro, Portugal in the framework of research project PTDC/ECI-EST/31865/2017 MitRisk—Framework for seismic risk reduction resorting to cost-effective retrofitting solutions