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

The determinants of Foreign Direct Investments attraction in Portugal and Spain: A comparative analysis

Double Degree. A Work Project presented as part of the requirements for the Award of a Master Degree in Management from the NOVA – School of Business and Economics and a Master Degree in Business Engineering from Louvain School of Management

Essays in entrepreneurship among foreign individuals

We study how countries of origin affect foreign individuals’ choice between salaried work and entrepreneurship upon arrival to the host country. Using a change in the Portuguese immigration law we evaluate the impact of reducing regulations on entrepreneurship upon the probability of foreign individuals choose entrepreneurship upon arrival. We find that foreigners from countries more dissimilar to the host country and those from wealthier countries are more likely engage in entrepreneurship upon arrival than those from similar countries. Foreigners from countries outside the European Economic Area, who have to fulfil requirements that are not required to those from countries within this area, are less likely to enter the labor market as entrepreneurs than those from countries within this area. According to our findings reducing legal requirements to foreign entrepreneurship may encourage foreigners to engage in entrepreneurship upon arrival, although such impact is not considerable.

Phage display as a tool for generation of bio-therapeutic agents for breast cancer

Notch is a conserved signalling pathway, which plays a crucial role in a multiple cellular processes such as stem cell self-renewal, cell division, proliferation and apoptosis. In mammalian, four Notch receptors and five ligands are described, where interaction is achieved through their extracellular domains, leading to a transcription activation of different target genes. Increased expression of Notch ligands has been detected in several types of cancer, including breast cancer suggesting that these proteins represent possible therapeutic targets. The goal of this work was to generate quality protein targets and, by phage display technology, select function-blocking antibodies specific for Notch ligands. Phage display is a powerful technique that allows the generation of highly specific antibodies to be used for therapeutics, and it has also proved to be a reliable approach in identifying and validating new cancer-related targets. Also, we aimed at solving the tri-dimensional structure of the Notch ligands alone and in complex with selected antibodies. In this work, the initial phase focused on the optimization of the expression and purification of a human Delta-like 1 ligand mutant construct (hDLL1-DE3), by refolding from E. coli inclusion bodies. To confirm the biological activity of the produced recombinant protein cellular functional studies were performed, revealing that treatment with hDLL1-DE3 protein led to a modulation of Notch target genes. In a second stage of this study, Antibody fragments (Fabs) specific for hDLL1-DE3 were generated by phage display, using the produced protein as target, in which one good Fab candidate was selected to determine the best expression conditions. In parallel, multiple crystallization conditions were tested with hDLL1-DE3, but so far none led to positive results.

Raptos, sequestros e tomada de reféns

In this thesis we address the paradigms and inconsistencies involving crisis kidnappings and hostage-taking. This work particularly focuses on foreign hostages seized by terrorists and guerrilla movements. It highlights major global events that have contributed to the collective awareness of the phenomenon and the evolution of international agreements and protocols. We focus on the episodes involving Portugal or Portuguese abroad, particularly on the kidnapping of Portuguese in the Cabinda enclave. It also deals with the problems associated with the payment of ransoms, the increasing involvement of private agents in addressing these crises, and incongruities in the motivations of the kidnappers.

A new credit monitoring framework for agents' networks

The purpose of this work is to develop a practicable approach for Telecom firms to manage the credit risk exposition to their commercial agents’ network. Particularly it will try to approach the problem of credit concession to clients’ from a corporation perspective and explore the particular scenario of agents that are part of the commercial chain of the corporation and therefore are not end-users. The agents’ network that served as a model for the presented study is composed by companies that, at the same time, are both clients and suppliers of the Telecommunication Company. In that sense the credit exposition analysis must took into consideration all financial fluxes, both inbound and outbound. The current strain on the Financial Sector in Portugal, and other peripheral European economies, combined with the high leverage situation of most companies, generates an environment prone to credit default risk. Due to these circumstances managing credit risk exposure is becoming increasingly a critical function for every company Financial Department. The approach designed in the current study combined two traditional risk monitoring tools: credit risk scoring and credit limitation policies. The objective was to design a new credit monitoring framework that is more flexible, uses both external and internal relationship history to assess risk and takes into consideration commercial objectives inside the agents’ network. Although not explored at length, the blueprint of a Credit Governance model was created for implementing the new credit monitoring framework inside the telecom firm. The Telecom Company that served as a model for the present work decided to implement the new Credit Monitoring framework after this was presented to its Executive Commission.