Exit strategies of Pharmaceutical multinational companies from Portugal and the successful implementation of new Portuguese companies

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Synthesis of new enzyme stabilisers inspired by compatible solutes of hyperthermophilic microorganisms

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

Valorization of pumpkin residue by supercritical extraction of added-value compounds

Dissertação para a obtenção do Grau de Mestre em Engenharia Química e Bioquímica

Applications of the indole scaffold in medicinal chemistry: development of new antioxidants, COX inhibitors and antitubercular agents

Dissertação para obtenção do Grau de Doutor em Química, especialidade Química Orgânica

Design of a Continuous-Time (CT) Sigma-Delta modulator for class D audio power amplifiers

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do Grau de Mestre em Engenharia Electrotécnica e de Computadores

Analysis of the interaction of polycyclic aromatic compounds in a model organism: integration of genotoxic and histopathological effects

Due to their toxicity, especially their carcinogenic potential, polycyclic aromatic hydrocarbons (PAHs) became priority pollutants in biomonitoring programmes and environmental policy, such as the European Water Framework Directive. The model substances tested in this study, namely benzo[b]fluoranthene (B[b]F), considered potentially carcinogenic to humans and an effector carcinogenic PAH to wildlife, and phenanthrene (Phe), deemed a non-carcinogenic PAH, are common PAHs in coastal waters, owning distinct properties reflected in different, albeit overlapping, mechanisms of toxicity. Still, as for similar PAHs, their interaction effects remain largely unknown. In order to study the genotoxic effects of caused by the interaction of carcinogenic and non-carcinogenic PAHs, and their relation to histopathological alterations, juvenile sea basses, Dicentrarchus labrax, a highly ecologically- and economically-relevant marine fish, were injected with different doses (5 and 10 μg.g-1 fish ww) of the two PAHs, isolated or in mixture, and incubated for 48 h. Individuals injected with B[b]F and the PAH mixture exhibited higher clastogenic/aneugenic effects and DNA strand breakage in blood cells, determined through the erythrocytic nuclear abnormalities (ENA) and Comet assays, respectively. Also, hepatic histopathological alterations were found in all animals, especially those injected with B[b]F and the PAH mixture, relating especially to inflammation. Still, Phe also exhibited genotoxic effects in sea bass, especially in higher doses, revealing a very significant acute effect that was accordant with the Microtox test performed undergone in parallel. Overall, sea bass was sensitive to B[b]F (a higher molecular weight PAH), likely due to efficient bioactivation of the pollutant (yielding genotoxic metabolites and reactive oxygen species), when compared to Phe, the latter revealing a more significant acute effect. The results indicate no significant additive effect between the substances, under the current experimental conditions. The present study highlights the importance of understanding PAH interactions in aquatic organisms, since they are usually present in the aquatic environment in complex mixtures.

Gold nanoparticulate systems for new anticancer compounds delivery

My master studies have resulted in the following publication: Martins P, Rosa D, Fernandes AR, Baptista PV. 2014. Nanoparticle Drug Delivery Systems: Recent Patents and Applications in Nanomedicine. Recent Patents in Nanomedicine. 3(2):105-118.

Design of a CMOS amplifier for breast cancer detection

A transimpedance amplifier (TIA) is used, in radiation detectors like the positron emission tomography(PET), to transform the current pulse produced by a photo-sensitive device into an output voltage pulse with a desired amplitude and shape. The TIA must have the lowest noise possible to maximize the output. To achieve a low noise, a circuit topology is proposed where an auxiliary path is added to the feedback TIA input, In this auxiliary path a differential transconductance block is used to transform the node voltage in to a current, this current is then converted to a voltage pulse by a second feedback TIA complementary to the first one, with the same amplitude but 180º out of phase with the first feedback TIA. With this circuit the input signal of the TIA appears differential at the output, this is used to try an reduced the circuit noise. The circuit is tested with two different devices, the Avalanche photodiodes (APD) and the Silicon photomultiplier (SIPMs). From the simulations we find that when using s SIPM with Rx=20kΩ and Cx=50fF the signal to noise ratio is increased from 59 when using only one feedback TIA to 68.3 when we use an auxiliary path in conjunction with the feedback TIA. This values where achieved with a total power consumption of 4.82mv. While the signal to noise ratio in the case of the SIPM is increased with some penalty in power consumption.

Identifying the urban communities of New York City using bikeshare data from NYC citibike

This study identifies a measure of the cultural importance of an area within a city. It does so by making use of origindestination trip data and the bike stations of the bike share system in New York City as a proxy to study the city. Rarely is movement in the city studied at such a small scale. The change in strength of the similarity of movement between each station is studied. It is the first study to provide this measure of importance for every point in the system. This measure is then related to the characteristics which make for vibrant city communities, namely highly mixed land use types. It reveals that the spatial pattern of important areas remains constant over differing time periods. Communities are then characterised by the land uses surrounding these stations with high measures of importance. Finally it identifies the areas of global cultural importance alongside the areas of local importance to the city.

Design of a low-voltage CMOS RF receiver for energy harvesting sensor node

In this thesis a CMOS low-power and low-voltage RF receiver front-end is presented. The main objective is to design this RF receiver so that it can be powered by a piezoelectric energy harvesting power source, included in a Wireless Sensor Node application. For this type of applications the major requirements are: the low-power and low-voltage operation, the reduced area and cost and the simplicity of the architecture. The system key blocks are the LNA and the mixer, which are studied and optimized with greater detail, achieving a good linearity, a wideband operation and a reduced introduction of noise. A wideband balun LNA with noise and distortion cancelling is designed to work at a 0.6 V supply voltage, in conjunction with a double-balanced passive mixer and subsequent TIA block. The passive mixer operates in current mode, allowing a minimal introduction of voltage noise and a good linearity. The receiver analog front-end has a total voltage conversion gain of 31.5 dB, a 0.1 - 4.3 GHz bandwidth, an IIP3 value of -1.35 dBm, and a noise figure lower than 9 dB. The total power consumption is 1.9 mW and the die area is 305x134.5 m2, using a standard 130 nm CMOS technology.

Bioprocess design of canine adenovirus vectors for gene therapy applications

The potential of human adenovirus vectors as vehicles for gene transfer with clinical applications in vaccination, cancer treatment and in many monogenic and acquired diseases has been demonstrated in several studies and clinical trials. However, the clinical use of these vectors can be limited by pre-existing humoral and cellular anti-capsid immunity. One way to circumvent this bottleneck while keeping the advantages of using adenovirus vectors is using non-human viruses such as Canine Adenovirus type 2 (CAV-2). Moreover, CAV-2 vectors present attractive features to develop potential treatment of neurodegenerative and ocular disorders. While the interest in CAV-2 vectors increases, scalable and robust production processes are required to meet the need for preclinical and possibly clinical uses.(...)

Spatial analysis of new cases of leprosy in the State of Espírito Santo, Brazil, between 2004 and 2009

INTRODUCTION: Leprosy in Brazil is a public health issue, and there are many regions in the State of Espírito Santo with high endemic incidence levels of leprosy, characterizing this state as a priority for leprosy programs. The aim of this study was to determine the spatial distribution of coefficients of new cases of leprosy in the State of Espírito Santo, Brazil. METHODS: We conducted a descriptive and ecologic study based on the spatial distribution of leprosy in the State of Espírito Santo between 2004 and 2009. Data were gathered from the available records of the Espírito Santo State Health Secretary. The global and local Bayesian empirical methods were used to produce an estimate of leprosy risk, smoothing the fluctuation effects of the detection coefficients. RESULTS: The study resulted in a coefficient adjustment of new cases in 10 towns that changed their classification, among which, 2 went from low to medium, 4 from medium to high, 3 from high to very high, and 1 from very high to hyper-endemic. An average variation of 1.02, fluctuating between 0 and 12.39 cases/100,000 inhabitants, was found in a comparative calculation between the Local Ebest value and the average coefficient of new leprosy cases in the State of Espírito Santo. CONCLUSIONS: The spatial analysis of leprosy favors the establishment of control strategies with a better cost-benefit relationship since it reveals specific and priority regions, thereby enabling the development of actions that can interfere in the transmission chain.

Strategic design of There App’s business model: From product to multi-sided platform

The following work project illustrates the strategic issues There App, a mobile application, faces regarding the opportunity to expand from its current state as a product to a multisided platform. Initially, a market analysis is performed to identify the ideal customer groups to be integrated in the platform. Strategic design issues are then discussed on how to best match its value proposition with the identified market opportunity. Suggestions on how the company should organize its resources and operational processes to best deliver on its value proposition complete the work.

Report of new cases of Trypanosoma caninum in Brazil

INTRODUCTION: Trypanosoma caninum is a protozoan species recently described in dogs, whose occurrence has been reported in areas of overlap with visceral leishmaniasis. METHODS: Trypanosoma sp. were isolated from nine dogs and characterized by molecular methods. RESULTS: PCR and sequencing confirmed the presence of T. caninum in all dogs, revealing two new areas of transmission: Barra Mansa and São João do Piauí. CONCLUSIONS: The nine new cases described, when added to those already published, account for 62 cases of natural infection by T. caninum and show the geographical spread of this species to new areas, where other trypanosomatids circulate.