Purification of complex biopharmaceuticals with new processes, advanced analytics and computer-aided process design tools

Dissertação para obtenção do Grau de Mestre em Biotecnologia

Microbiology of membrane bioreactors for wastewater treatment: a molecular approach

Dissertation presented to obtain the Ph.D degree in Engineering and Technology Sciences, Biotechnology.

Jacob de Castro Sarmento e o conhecimento médico e científico do século XVIII

Henrique, ou Jacob, de Castro Sarmento (1691-1762), médico judeu, nascido em Bragança e exilado em Inglaterra a partir de 1721, devido às perseguições da Inquisição aos cristãos-novos, é considerado como o introdutor das ideias de Isaac Newton (1662-1727) em Portugal e um dos principais responsáveis pela disseminação da iatroquímica entre os médicos portugueses, contribuindo para o desenvolvimento da medicina e ciência portuguesas do século XVIII. Eleito para sócio da Royal Society em 1730, o médico português tornou-se o principal interlocutor científico entre Portugal e Inglaterra, sendo a sua actividade exemplar do modo como ocorreram as trocas de conhecimento entre o centro da Europa e a sua periferia. Autor de diversas obras médicas, Sarmento abordou algumas das temáticas médicas mais relevantes do século das luzes, como a inoculação das bexigas ou a utilização terapêutica das águas minerais, veiculando uma nova forma de encarar a prática médica. A sua obra Theorica Verdadeira das Mares, editada em 1737, foi a primeira publicada em Portugal onde as ideias de Newton são consideradas com o devido detalhe. Paradoxalmente, Sarmento foi também produtor de medicamentos de segredo, tendo a sua Água de Inglaterra alcançado um sucesso significativo em Portugal. Figura polémica e multifacetada, Sarmento dedicou uma parte considerável da sua vida à divulgação e disseminação das ideias dos autores modernos, dos quais se destacam Boyle, Newton e Boerhaave. O presente trabalho tem como principal objectivo elucidar os principais aspectos da sua vida e obra, procurando enquadrar as suas actividades no contexto da medicina e ciência europeias de setecentos.

EFFECT – Efficient finite element code

The theme of this dissertation is the finite element method applied to mechanical structures. A new finite element program is developed that, besides executing different types of structural analysis, also allows the calculation of the derivatives of structural performances using the continuum method of design sensitivities analysis, with the purpose of allowing, in combination with the mathematical programming algorithms found in the commercial software MATLAB, to solve structural optimization problems. The program is called EFFECT – Efficient Finite Element Code. The object-oriented programming paradigm and specifically the C ++ programming language are used for program development. The main objective of this dissertation is to design EFFECT so that it can constitute, in this stage of development, the foundation for a program with analysis capacities similar to other open source finite element programs. In this first stage, 6 elements are implemented for linear analysis: 2-dimensional truss (Truss2D), 3-dimensional truss (Truss3D), 2-dimensional beam (Beam2D), 3-dimensional beam (Beam3D), triangular shell element (Shell3Node) and quadrilateral shell element (Shell4Node). The shell elements combine two distinct elements, one for simulating the membrane behavior and the other to simulate the plate bending behavior. The non-linear analysis capability is also developed, combining the corotational formulation with the Newton-Raphson iterative method, but at this stage is only avaiable to solve problems modeled with Beam2D elements subject to large displacements and rotations, called nonlinear geometric problems. The design sensitivity analysis capability is implemented in two elements, Truss2D and Beam2D, where are included the procedures and the analytic expressions for calculating derivatives of displacements, stress and volume performances with respect to 5 different design variables types. Finally, a set of test examples were created to validate the accuracy and consistency of the result obtained from EFFECT, by comparing them with results published in the literature or obtained with the ANSYS commercial finite element code.

Implementation of membrane processes for improvement of the detection of food contaminants

The EM3E Master is an Education Programme supported by the European Commission, the European Membrane Society (EMS), the European Membrane House (EMH), and a large international network of industrial companies, research centres and universities (http://www.em3e.eu)

Usefulness of zebrafish model to assess glomerular and tubular alterations induced by tenofovir

Tenofovir (TFV) is one of the most used antiretroviral drugs. However, it is associated with tubular damage with mitochondria as a possible target. Tubulopathy precedes glomerular dysfunction, thus classic markers of renal function like the glomerular filtration rate (GFR) do not detect early TFV damage. Prediction and management of drug induced renal injury (DIRI) rely on the mechanisms of the drug insult and in optimal animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI, since the pronephros is structurally very similar to its human counterpart and is fully developed at 3.5 days postfertilization. The main aim of the present work was to evaluate the effects of TFV, as well as its pro-drug, tenofovir disoproxil fumarate (TDF), on the GFR and in mitochondria morphology in tubular cells of zebrafish larvae. Lethality curves were performed to understand the relationship between drug concentration and lethality. LC10 was selected to explore the renal function using the FITC-inulin assay and to analyze the mitochondrial toxicity by electron microscopy on larvae exposed to TDF, TFV, paracetamol and gentamicin (positive controls) or water (negative control). Lethality curves showed that gentamicin was the most lethal drug, followed by TDF, TFV and paracetamol. Gentamicin and paracetamol decreased the GFR, but no differences were found for either TDF or TFV, when compared to controls (%FITC Control = 33±8; %FITC TDF = 35±10; %FITC TFV = 30±10; %FITC Gentamicin = 46±17; %FITC Paracetamol = 83±14). Tubular mitochondria from treated larvae were notably different from non-treated larvae, showing swelling, irregular shapes, decreased mitochondria network, cristae disruption and loss of matrix granules. These results are in agreement with the effects of these drugs in humans and thus, demonstrate that zebrafish larvae can be a good model to assess the functional and structural damage associated with DIRI.