Development of a fuzzy qualitative risk assessment model applied to construction industry

Dissertação para obtenção do Grau de Doutor em Engenharia Industrial

Benchmarking in primary health care: An application of the stochasticd frontier analysis and the grades of membership approach to Portuguese family health units

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

Recursive neuro fuzzy techniques for online identification and control

Dissertação para obtenção do Grau de Mestre em Engenharia Electrotécnica e de Computadores

Novel functions of the cohesin accessory factor dPDS5 uncover a new meiotic checkpoint

Dissertation presented to obtain the Ph.D degree in Biology.

O Conselho de Estado na monarquia constitucional: uma reflexão preliminar

This article summarises the transformations in the State Council’s functions and membership throughout the Portuguese Constitutional Monarchy, and makes a preliminary attempt to scrutinise the political role played by an institution designed since its inception to advise the monarch. In spite of the parsimony of contemporary sources, and even contradictory empirical evidence, it seems indisputable that in several critical occasions the monarch’s political decisions were influenced by the dominant view in the State Council. Finally, the article presents the collective biography of the 73 individuals appointed to the State Council between 1833 and 1910 – who may be defined as the inner circle of the ruling elite - focusing on basic background features (birthplace, age, education, occupation, noble titles and political experience).

Manipulation of host cell functions by Salmonella: the role of the bacterial effector protein SteA

Salmonella enterica serovars are Gram-negative facultative intracellular bacterial pathogens that infect a wide variety of animals. Salmonella infections are common in humans, causing usually typhoid fever and gastrointestinal diseases. Salmonella enterica serovar Typhimurium (S. Typhimurium), which is a leading cause of human gastroenteritis, has been extensively used to study the molecular pathogenesis of Salmonella, because of the availability of sophisticated genetic tools, and of suitable animal and tissue culture models mimicking different aspects of Salmonella infections.(...)

Statistics as a basis for discrimination in the insurance business

The European Court of Justice has held that as from 21 December 2012 insurers may no longer charge men and women differently on the basis of scientific evidence that is statistically linked to their sex, effectively prohibiting the use of sex as a factor in the calculation of premiums and benefits for the purposes of insurance and related financial services throughout the European Union. This ruling marks a sharp turn away from the traditional view that insurers should be allowed to apply just about any risk assessment criterion, so long as it is sustained by the findings of actuarial science. The naïveté behind the assumption that insurers’ recourse to statistical data and probabilistic analysis, given their scientific nature, would suffice to keep them out of harm’s way was exposed. In this article I look at the flaws of this assumption and question whether this judicial decision, whilst constituting a most welcome landmark in the pursuit of equality between men and women, has nonetheless gone too far by saying too little on the million dollar question of what separates admissible criteria of differentiation from inadmissible forms of discrimination.

Grade of membership (GoM) por algoritmos genéticos

Muitas vezes é necessário trabalhar com variáveis categóricas, porem há um número restrito de análisesque as abordam. Uma boa técnica de segmentação é a grade of membership (GoM), muito utilizada na área médica, em psicologia e em sociologia. Essa metodologia possui uma interpretação interessante baseada em perfis extremos (segmentos) e grau de pertencimento. Porém o modelo possui grande complexidade de estimação dos parâmetros pormáxima verossimilhança. Assim, neste trabalho propõe-se o uso de algoritmos genéticos para diminuir a complexidade e o tempo de cálculo, e aumentar a acurácia. A técnica é nomeada de Genetics Algorithms grade of membership (GA-GoM). Para averiguar a efetividade, o modelo foi primeiramente abordado por simulação – foi executado um experimento fatorial levando em conta o número de segmentos e variáveis trabalhadas. Em seguida, foi abordado um caso prático de segmentação de engajamento em redes sociais. Os resultados são superiores para modelos de maior complexidade. Conclui-se, assim, que é útil a abordagem para grandes bases de dados que contenham dados categóricos.

A consumer research project as the basis for the development of a marketing plan for a new spirit brand producing gin in Germany

This work project is about developing a marketing plan for a new gin brand in Germany. It is based on consumer and market research, including Portugal as a trend market for the qualitative research. For the undertaking it is seen as fundamental to understand the industry as well as the consumer needs, attitudes and preferences. Furthermore, it is important to consider the estimation of opinion leaders and trendsetters in the industry. In this context it turned out that barkeepers have a key-influencing role for the stimulation of demand. Based on the insights from this research as well as on the gained market knowledge, the marketing plan was developed. The goal is to convince other brand users to switch brands.

The cellular basis of a congenital heart defect Drosophila

RESUMO: Mutações em genes envolvidos na formação do coração e anomalias em qualquer etapa deste processo causam frequentemente malformações cardíacas, que representam o tipo mais comum de defeitos em neonatais, afetando cerca de 1% dos nascimentos por ano. Assim, estima-se que 20 milhões de pessoas sejam portadoras de um defeito cardíaco congénito. O coração da Drosophila melanogaster (mosca-da-fruta), denominado vaso dorsal, é um órgão relativamente simples que actua como uma bomba muscular, contraindo automaticamente para permitir a circulação da hemolinfa através do corpo. A formação do vaso dorsal na mosca é muito semelhante ao desenvolvimento do coração em vertebrados, representando por isso, um poderoso modelo para estudar a rede de genes e os padrões regulatórios relacionados com o desenvolvimento deste órgão. Anteriormente, nós identificámos um gene em Drosophila, darhgef10, fortemente expresso no coração em desenvolvimento e cuja deleção induz anormalidades cardíacas subtis mas prevalentes. Os mutantes para darhgef10 são viáveis e férteis no ambiente controlado de laboratório. Este trabalho teve como objectivos caracterizar fenotipicamente os mutantes nulos para darhgef10, determinar a localização subcelular da proteína dArhgef10 e investigar a base celular subjacente ao defeito no alinhamento dos cardioblastos observado nos mutantes. Os nossos resultados revelaram que a deleção de darhgef10 provoca uma severa redução da viabilidade, sem no entanto comprometer o tempo de desenvolvimento e a longevidade. Por outro lado, o aumento da expressão de darhgef10 em músculos, glândulas salivares e no disco imaginal do olho afeta drasticamente a integridade destes tecidos. A expressão ectópica de darhgef10 in vitro e in vivo revelou que a proteína está localiza no citoplasma com enriquecimento junto à membrana celular, com associação à actina F. Live imaging de embriões mutantes para darhgef10 revelou que os defeitos observados no coração podem estar associados a um defeito na adesão dos músculos alary e/ou das células pericardiais ao vaso dorsal. O homólogo humano de darhgef10, ARHGEF10, também é expresso no coração e está associação a uma maior susceptibilidade para a ocorrência de acidentes vasculares cerebrais aterotrombóticos, sugerindo que o que aprendemos sobre darhgef10 em Drosophila pode ter implicações do ponto de vista clínico para a saúde humana. ----------------------------- ABSTRACT: Mutations in genes controlling heart development and abnormalities in any of its steps frequently cause cardiac malformations, the most common type of birth defects in humans, affecting nearly 1% of births per year. Hence around 20 million adults are expected to live with a congenital heart defect. The Drosophila melanogaster heart, called dorsal vessel, is a relatively simple organ that acts as a muscular pump contracting automatically to allow the circulation of hemolymph. Drosophila heart formation shares many similarities with heart development in vertebrates providing a powerful system to study gene networks and regulatory pathways involved in heart development. We have previously identified a Drosophila gene, darhgef10, which is strongly expressed in the developing heart and when deleted, leads to flies with highly prevalent yet subtle heart abnormalities, compatible with unchallenged life in the laboratory. Our aims were to phenotypically characterize homozygous null darhgef10 mutants, characterize the subcellular localization of dArhgef10 and to study the cellular basis of the misaligned cardioblasts defect. We found that about half of darhgef10 mutants die during development. However, the survivors surprisingly have a nearly normal developmental time, adult locomotor behavior and total lifespan. Detection of transgene-derived dArhgef10 protein in vitro and in vivo using custom antibodies revealed a cytosolic protein slightly enriched in the cellular membranes and associated with F-actin. Tissue-specific darhgef10 expression disrupts the normal morphology of developing muscles, salivary glands and the eye. Live imaging of darhgef10 mutant embryos revealed that heart defect could be caused by a reduced capacity of attachment of pericardial cells and/or alary muscle to dorsal vessel. The human homolog of darhgef10 is also expressed in the heart and is a susceptibility gene for atherothrombotic stroke, suggesting that what we learn about the function of this gene and its phenotypes in Drosophila could have implications to human health.

Unravelling the role of alpha 2,6 sialic acid on mouse dentritic cells functions

RESUMO: As células dendríticas (CDs) são fundamentais na imunomodulação e iniciação de respostas imunes adaptativas, enquanto os ácidos siálicos (Sias) são potenciais imunomoduladores. Estas células expressam níveis elevados da sialiltransferase ST6Gal-1, que transfere Sias para a posição terminal de oligossacáridos. De facto, a maturação de CDs está associada a uma diminuição da sialilação na sua superfície celular. Apesar de ter função biológica desconhecida, a forma solúvel, extracelular de ST6Gal-1 aumenta em cancros e inflamação. Ainda assim, esta foi recentemente identificada como moduladora da hematopoiese. Considerando o importante papel das CDs na iniciação de respostas anticancerígenas, uma ligação entre a sialilação extrínseca induzida por ST6Gal-1 extracelular e o seu papel na modulação de CDs deve ser identificada. Neste trabalho hipotetizou-se que a sialilação α2,6 extrínseca de CDs diminui o seu perfil de maturação mediante ativação por lipopolissacarídeo (LPS). O objetivo principal foi sialilar extrinsecamente em α2,6 CDs da medula óssea de murganhos, avaliando os seus perfis de maturação e de libertação de citocinas, após estimulação com LPS (por Citometria de Fluxo e ELISA, respetivamente). Ao contrário da hipótese, o perfil celular não foi modulado, usando várias abordagens. Por outro lado, a consequência da falta de α2,6 Sias na maturação de CDs foi avaliada analisando: 1) CDs da medula óssea de murganhos tratadas com sialidase, 2) CDs da medula óssea e 3) CDs das vias aéreas, ambas de murganhos deficientes em ST6Gal-1, comparando com a estirpe selvagem. Estes resultados sugerem que a perta total de α2,6 Sias se relaciona com o aumento da expressão do complexo de histocompatibilidade principal de classe II. Apesar de controverso, é provável existirem mecanismos inerentes à ativação por LPS, reduzindo a eficácia de ST6Gal-1 extracelular. Por outro lado, a modificação no perfil de CDs de murganhos deficientes em ST6Gal-1 poderá relacionar-se com uma predisposição para um estado inflamatório severo. Com isto, o trabalho desenvolvido abriu futuras linhas de investigação, nomeadamente explorar outros fatores envolvidos na (de)sialilação α2,6 de CDs, podendo ter impacto em imunoterapia com uso de CDs.--------------------------ABSTRACT: Dendritic cells (DCs) are vital for immunomodulation and the initiation of adaptive immune responses, whereas sialic acids (Sias) are potential immunomodulators. These cells express high levels of sialyltransferase ST6Gal-1, responsible for transferring Sias to the terminal position of oligosaccharide chains. Indeed, DCs’ maturation is associated with decreased cell surface sialylation. Although its biological significance is unknown, the soluble, extracellular form of ST6Gal-1 increases in cancers and inflammation. However, extracellular ST6Gal-1 was recently identified as modulator of hematopoiesis. Considering that DCs play a crucial role in the initiation of a productive anti-cancer immune response, a link between extrinsic sialylation by the extracellular ST6Gal-1 on DC function needs to be investigated. We hypothesize that extrinsic α2,6 sialylation of DCs diminishes their maturation features upon lipopolysaccharide (LPS) stimulation. The main goal was to extrinsically α2,6 sialylate mice bone marrow derived DCs (BMDCs) and to evaluate their maturation and cytokine profiles upon LPS stimulation (by Flow Cytometry and ELISA, respectively). Unlike the hypothesis, we observed that BMDCs’ profile is not modulated, even using several approaches. In contrast, the consequence of lacking cell surface α2,6 Sias in DC maturation was assessed by analysing: 1) sialidase treated BMDCs, 2) BMDCs from mice lacking ST6Gal-1 and 3) DCs from mice airways, comparing wild type with ST6Gal-1 knockout mice. These results suggest that overall lack in α2,6 Sias is related with increased expression of major histocompatibility class II (MHC-II). Although appearing to be controversial findings, other intracellular mechanisms might be occurring upon LPS-induced BMDC activation, probably reducing extracellular ST6Gal-1 effect. In opposite, the modification observed in DC profile of ST6Gal-1 knockout mice might be related to its predisposition to a more severe inflammatory status. With this, the developed work opened future lines of investigation, namely exploring other factors involved in α2,6 (de)sialylation of DC, which might have influence in immunotherapy using DCs.

Relatório de estágio curricular

The purpose of the current internship report is to share the opportunity I have had to learn during my stay in CMVM as an intern, specifically in relation to the exercise of private equity supervision in Portugal, in order to contribute to the study of private equity legal framework. Private equity is the activity to finance or acquire enterprises with growth potential (normally consider as genuine industry), for a limited period of time, in order to support the enterprise’s development to benefit from future profit sales of participations. By observing and studying the registration procedures, as well as the specific legislation and reality of other jurisdictions, it is concluded that supervision specifically related to private equity is one of the most important aspects in this industry, as it is the best way to know and control it. To improve the performance of supervisory functions, and the very development of private equity, it is essential to have a legislative review in order to simplify the rules enforcement necessary for the proper running of the industry as well as for more efficient supervision and control of this activity, thus developing it and making it more attractive in a national and international basis.

Improving Millennium Bank's personal finance manager

Double Degree