Staying under the radar - the multifunctional LANA Protein

Many viruses have developed numerous strategies to recruit and take advantage of cellular protein degradation pathways to evade the cellular viral immune system. One such virus is the Kaposi´s Sarcoma associated herpesvirus (KSHV), first discovered in Kaposi´s Sarcoma lesions found in AIDS patients. Latency-Associated Nuclear Antigen (LANA) is a KSHV multifunctional protein responsible for tethering viral DNA to the chromosome ensuring maintenance and segregation of the viral genome during cell division. Besides its main role of viral maintenance, LANA also physically interacts with several host proteins to modulate cell functions. One such function is to recruit the EC5S ubiquitin-ligase complex by interacting with Elongin BC complex and Cullin 5 protein, which in turn ubiquitinate substrates such as NF-κB and p53 to allow persistent viral infection. Like any other post-translation modifications, ubiquitination is reversible through deubiquitination enzymes (DUBs). LANA also interacts with ubiquitin specific protease 7 (USP7), a deubiquitination enzyme involved in regulation of several proteins including p53. Interaction with USP7 is made through a conserved peptide motif, which is also present in LANA. This work addresses the role of LANA in the recruitment and modulation of the ubiquitination and deubiquitination pathways. Despite the continued efforts in uncovering new LANA interacting partners to form a functional EC5S ubiquitin-ligase complex, only MHV-68 LANA interacted directly with Elongin BC, other interactions were not direct and may require a linker protein. On the other hand, LANA interaction with USP7 was able to be analysed by X-ray structure determination. In addition to a conserved P/AxxS motif, a novel Glutamine (Gln) residue from KSHV LANA was shown to make a specific interaction with USP7. This Gln residue is also present in other herpesvirus protein and hence it might be a conserved motif within herpesviruses.

A GNR e a cooperação entre órgãos da polícia criminal na sociedade do risco. Estudo de caso:

Cooperation between police forces is a topic that is increasingly relevant. The emergence of new threats, as well as looking for new ways to fight crime, require from the, careful monitoring and strict sharing of all relevant information. This Work is entitled “The GNR and cooperation between Criminal Police Bodies in the Risk Society. Case Study: District of Lisbon” and aims to study the cooperation and coordination between police forces in Lisbon district, and verify if there is an parallel between the rule of law and the police procedures. The work is organized in four chapters. The first consists in a theoretical framework to perceive the context and objectives of this work. The second addresses the role of the, the different types of cooperation and instruments that promote cooperation between them. The third presents and analyzes the results. Finally, the fourth and last chapter the conclusions are woven answered the questions derived and starting question, tested hypotheses, and those limitations and future recommendations. In conclusion, the District of Lisbon, there is cooperation, materialized in a constant exchange of information, based on personal and informal relationship between the elements of the various Police Forces.

Specification of a partial replication protocol with TLA+

Nowadays, data available and used by companies is growing very fast creating the need to use and manage this data in the most efficient way. To this end, data is replicated overmultiple datacenters and use different replication protocols, according to their needs, like more availability or stronger consistency level. The costs associated with full data replication can be very high, and most of the times, full replication is not needed since information can be logically partitioned. Another problem, is that by using datacenters to store and process information clients become heavily dependent on them. We propose a partial replication protocol called ParTree, which replicates data to clients, and organizes clients in a hierarchy, using communication between them to propagate information. This solution addresses some of these problems, namely by supporting partial data replication and offline execution mode. Given the complexity of the protocol, the use of formal verification is crucial to ensure the protocol two correctness properties: causal consistency and preservation of data. The use of TLA+ language and tools to formally specificity and verify the proposed protocol are also described.

User-centric product derivation in software product lines

Software Product Line (SPL) engineering aims at achieving efficient development of software products in a specific domain. New products are obtained via a process which entails creating a new configuration specifying the desired product’s features. This configuration must necessarily conform to a variability model, that describes the scope of the SPL, or else it is not viable. To ensure this, configuration tools are used that do not allow invalid configurations to be expressed. A different concern, however, is making sure that a product addresses the stakeholders’ needs as best as possible. The stakeholders may not be experts on the domain, so they may have unrealistic expectations. Also, the scope of the SPL is determined not only by the domain but also by limitations of the development platforms. It is therefore possible that the desired set of features goes beyond what is possible to currently create with the SPL. This means that configuration tools should provide support not only for creating valid products, but also for improving satisfaction of user concerns. We address this goal by providing a user-centric configuration process that offers suggestions during the configuration process, based on the use of soft constraints, and identifying and explaining potential conflicts that may arise. Suggestions help mitigating stakeholder uncertainty and poor domain knowledge, by helping them address well known and desirable domain-related concerns. On the other hand, automated conflict identification and explanation helps the stakeholders to understand the trade-offs required for realizing their vision, allowing informed resolution of conflicts. Additionally, we propose a prototype-based approach to configuration, that addresses the order-dependency issues by allowing the complete (or partial) specification of the features in a single step. A subsequent resolution process will then identify possible repairs, or trade-offs, that may be required for viabilization.

A presunção de inocência nas fases preliminares do processo penal

This study analyses the principle of presumption of innocence in the preliminary stages of the Portuguese criminal process, its procedural aspect related with the principle of in dubio pro reo and its material aspect concerning the treatment of the defendant during the proceedings. The consequences and manifestations of the principle of presumption of innocence are analysed in the decisions of the closing stages of the preliminary criminal procedure and the application of the principle of in dubio pro reo is analysed in the judgement of sufficiency of evidence for the procedure to continue. It addresses the question of circumstantial evidence, its particular relevance in economic and financial crime, highly organized crime, the grounds for the indictment in general and when the sufficiency of evidence criteria is based on that evidence. It analyses the scope of the principle of presumption of innocence in the application of coercive measures, with reference to the arrest, first interrogation of the accused under detention and reasons for the subsequent dispatch about the measures. The asset assurance measures of preventive seizure and the preventive seizure to ensure confiscation are analysed and principle of presumption of innocence is considered non applicable to those measures.

Cell functional enviromics: applications to Pichia pastoris

The present PhD thesis develops the cell functional enviromics (CFE) method to investigate the relationship between environment and cellular physiology. CFE may be defined as the envirome-wide cellular function reconstruction through the collection and systems-level analysis of dynamic envirome data. Throughout the thesis, CFE is illustrated by two main applications to cultures of a constitutive P. pastoris X33 strain expressing a scFv antibody fragment. The first application addresses the challenge of culture media development. A dataset was built from 26 shake flask experiments, with variations in trace elements concentrations and basal medium dilution based on the standard BSM+PTM1. Protein yield showed high sensitivity to culture medium variations, while biomass was essentially determined by BSM dilution. High scFv yield was associated with high overall metabolic fluxes through central carbon pathways concomitantly with a relative shift of carbon flux from biosynthetic towards energy-generating pathways. CFE identified three cellular functions (growth, energy generation and by-product formation) that together described 98.8% of the variance in observed fluxes. Analyses of how medium factors relate to identified cellular functions showed iron and manganese at concentrations close to PTM1 inhibit overall metabolic activity. The second application addresses bioreactor operation. Pilot 50 L fed-batch cultivations, followed by 1H-NMR exometabolite profiling, allowed the acquisition of data for 21 environmental factors over time. CFE identified five major metabolic pathway groups that are frequently activated by the environment. The resulting functional enviromics map may serve as template for future optimization of media composition and feeding strategies for Pichia pastoris. The present PhD thesis is a step forward towards establishing the foundations of CFE that is still at its infancy. The methods developed herein are a contribution for changing the culture media and process development paradigm towards a holistic and systematic discipline in the future.

What do broadband consumers want? Design and execution of a questionnaire on demand for bundled services on the Portuguese telecomunications market

The report addresses the question of what are the preferences of broadband consumers on the Portuguese telecommunication market. A triple play bundle is being investigated. The discrete choice analysis, adopted in the study, base on 110 responses, mainly from NOVA students. The data for the analysis was collected via manually designed on-line survey. The results show that the price attribute is relatively the most important one while the television attribute is being overlooked in the decision making process. Main effects examined in the research are robust. In addition, "extras" components are being tested in terms of users' preferences.

Breaking the Pattern and Creating New Paths – Feminist Mizrahi Women Artists in Israel

This article addresses the work of Mizrahi women artists, i.e., Israeli-Jewish women of Asian or African ethnic origin, using the artist Vered Nissim as a case study. Nissim seeks to affirm the politics of identity and recognition, as well as feminism in order to create a paradigm shift with regards to the local regime of cultural representations in the Israeli art scene. Endeavouring to find ways of undermining the rigid imbalances between different social groups, she calls for a comprehensive reform of the status quo through artistic activism. Nissim employs a style, content, and medium that disrupts the accepted social order, using humour and irony as unique weapons with which she takes liberties with conventional moral, social, and economic values. Placing issues of race, class and gender at the centre of her work, she seeks to undermine and problematize essentialist attitudes, highlighting the political intersections of different identity categories as the critical analysis of intersectionality unfolds.

O direito de exoneração do acionista minoritário

This study specifically addresses the situation of minority shareholders after the transfer of control in an listed company. The various underlying interests and reasons that shareholders have for investing in a company can demonstrate shareholders’ reasoning for taking radically different positions on issues relating to the transfer of control of the referred company. This study analyses the current legal system in Portugal and in the European Union in order to assess whether, in the event of a takeover bid of a listed company where there is a transfer of control, minority shareholders have the same appraisal rights as other shareholders to sell their shares and leave the company. The study then examines the European Court of Justice decision on whether a general principle of equal treatment of minority shareholders exists upon a transfer of control (Audiolux) and the Portuguese Securities Market Commission decision regarding the delisting of Brisa - Autoestradas de Portugal, S.A. based on the principle of investor protection. The study concludes that although the principle of equality amongst shareholders has made progress in the European legal system e.g. it is laid down in Directive 2004/25/EC of 21 April 2004 on takeover bids and the Portuguese Securities Market Code, there is also a need for further improvement, which can be accomplished by allowing minority shareholders to exercise an appraisal right in similar unregulated situations.

Improving practical reasoning and argumentation

This thesis justifies the need for and develops a new integrated model of practical reasoning and argumentation. After framing the work in terms of what is reasonable rather than what is rational (chapter 1), I apply the model for practical argumentation analysis and evaluation provided by Fairclough and Fairclough (2012) to a paradigm case of unreasonable individual practical argumentation provided by mass murderer Anders Behring Breivik (chapter 2). The application shows that by following the model, Breivik is relatively easily able to conclude that his reasoning to mass murder is reasonable – which is understood to be an unacceptable result. Causes for the model to allow such a conclusion are identified as conceptual confusions ingrained in the model, a tension in how values function within the model, and a lack of creativity from Breivik. Distinguishing between dialectical and dialogical, reasoning and argumentation, for individual and multiple participants, chapter 3 addresses these conceptual confusions and helps lay the foundation for the design of a new integrated model for practical reasoning and argumentation (chapter 4). After laying out the theoretical aspects of the new model, it is then used to re-test Breivik’s reasoning in light of a developed discussion regarding the motivation for the new place and role of moral considerations (chapter 5). The application of the new model shows ways that Breivik could have been able to conclude that his practical argumentation was unreasonable and is thus argued to have improved upon the Fairclough and Fairclough model. It is acknowledged, however, that since the model cannot guarantee a reasonable conclusion, improving the critical creative capacity of the individual using it is also of paramount importance (chapter 6). The thesis concludes by discussing the contemporary importance of improving practical reasoning and by pointing to areas for further research (chapter 7).

Learning domain-specific sentiment lexicons with applications to recommender systems

Search is now going beyond looking for factual information, and people wish to search for the opinions of others to help them in their own decision-making. Sentiment expressions or opinion expressions are used by users to express their opinion and embody important pieces of information, particularly in online commerce. The main problem that the present dissertation addresses is how to model text to find meaningful words that express a sentiment. In this context, I investigate the viability of automatically generating a sentiment lexicon for opinion retrieval and sentiment classification applications. For this research objective we propose to capture sentiment words that are derived from online users’ reviews. In this approach, we tackle a major challenge in sentiment analysis which is the detection of words that express subjective preference and domain-specific sentiment words such as jargon. To this aim we present a fully generative method that automatically learns a domain-specific lexicon and is fully independent of external sources. Sentiment lexicons can be applied in a broad set of applications, however popular recommendation algorithms have somehow been disconnected from sentiment analysis. Therefore, we present a study that explores the viability of applying sentiment analysis techniques to infer ratings in a recommendation algorithm. Furthermore, entities’ reputation is intrinsically associated with sentiment words that have a positive or negative relation with those entities. Hence, is provided a study that observes the viability of using a domain-specific lexicon to compute entities reputation. Finally, a recommendation system algorithm is improved with the use of sentiment-based ratings and entities reputation.

Estratégias de classificação dos arquivos familiares e pessoais contemporâneos: o exemplo do arquivo da família Benito Maçãs

A presente dissertação aborda a problemática teórica e metodológica da classificação de arquivos familiares e pessoais. Centrando-se no arquivo da família Benito Maçãs, produzido entre o final do século XVIII e o início do século XXI, são analisadas algumas das tendências recentes da classificação destes arquivos, sobretudo as que demonstram a sobrevalorização do enfoque orgânico e informativo. Através da caraterização das circunstâncias de produção e utilização do referido fundo, do aprofundamento dos principais conceitos operatórios subjacentes à classificação arquivística, bem como da análise de modelos classificativos teóricos e práticos, este estudo procura compreender as metodologias para a contextualização de arquivos familiares e pessoais. Os resultados demonstram a inexequibilidade da aplicação normalizada de modelos teóricos ou de critérios pré-definidos na contextualização de arquivos familiares e pessoais. Revelam, ainda, que as metodologias para a observação dos contextos não devem sobrepor-se à realidade documental, nem às especificidades da entidade produtora.

The relationship between liquidity and profitability in the food & beverage industry evidence from Europe and United States

This Work Project clarifies the relationship between liquidity and profitability based on a sample in the Food & Beverage (F&B) industry, and comparing the largest European and United States companies. The research concludes that liquidity, proxied by current ratio or quick ratio, correlates with return on assets taken as the measure of profitability, and so does the cash conversion cycle and its components. Moreover, company size correlates with liquidity, and indirectly affects ROA. This research contributes and addresses to managers in the F&B industry and recommends how they should act in order to improve profitability in the industry.

Growth hacking model for B2B saas startups

The following project introduces a model of Growth Hacking strategies for business-tobusiness Software-as-a-Service startups that was developed in collaboration with and applied to a Portuguese startup called Liquid. The work addresses digital marketing channels such as content marketing, email marketing, social marketing and selling. Further, the company’s product, pricing strategy, partnerships and website communication are examined. Applying best case practices, competitor benchmarks and interview insights from numerous industry influencers and experts, areas for improvement are deduced and procedures for each of those channels recommended.

Garland, since 1776- a unique ownership structure

The case is based on Garland, a 240 years old Portuguese family business, now owned by the Dawson family. It focuses on a decision made 50 years ago, aligned with what had been the company’s history, about the ownership rules for family members, which influences the ownership structure of the firm. It addresses the main issues about ownership in family businesses, and tackles the problem of succession planning and fair process. It contains a teaching note to support the utilization of the case in a classroom context, with learning objectives, target audience, a teaching plan, questions and proposed answers, and theory that relates to the case. It is also complemented with an epilogue and an overview of the case.