The Visual Culture of Human Rights. Observations on Amnesty International

Trabalho de project de Mestrado em Antropologia de Direitos Humanos e Movimentos Sociais

The optimum size of the portuguese public hospital

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

The human side of change: Qualitative research on a public sector hospital merger

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

DNA damage induced by acrylamide: roe of genetic polymorphisms in DNA damage levels

RESUMO:Em 1994 a acrilamida (AA) foi classificada pela IARC como um provável cancerígeno para o homem. Para além da utilização de AA em numerosas aplicações industriais, a AA está também presente numa grande variedade de alimentos ricos em amido e processados a temperaturas elevadas. Esta exposição através da ingestão de produtos alimentares despoletou elevadas preocupações ao nível do risco para a saúde pública e poderá implicar um risco adicional para o aparecimento de cancro. A glicidamida (GA), o metabolito epóxido formado a partir da oxidação da AA provavelmente através do citocromo P450 2E1, é considerada por vários estudos, o principal responsável pela carcinogenicidade da AA. Actualmente existe uma escassez de resultados relativamente aos mecanismos de genotoxicidade da AA e GA em células de mamífero. Por este motivo, o objectivo deste estudo centra-se na avaliação das consequências genéticas da exposição à AA e GA, recorrendo-se para tal ao uso de células de mamífero como modelo. Tendo como base este objectivo avaliou-se a citotoxicidade da AA e GA, através do ensaio do MTT, e realizaram-se dois testes citogenéticos, o teste das aberrações cromossómicas (CAs) e o teste da troca de cromátides irmãs (SCEs), de modo a avaliar as lesões de DNA induzidas por estes compostos em células de hamster Chinês V79. Os resultados globalmente mostraram que a GA é mais citotóxica e clastogénica do que a AA. No âmbito deste trabalho, foi também efectuada a quantificação de aductos específicos de DNA, nomeadamente N7-(2-carbamoil-2-hidroxietil)guanina (N7-GA-Gua) e N3-(2-carbamoil-2-hidroxietil)adenina (N3-GA-Ade). Os resultados obtidos permitem afirmar que os níveis de N7-GA-Gua e a concentração de GA apresentam uma relação linear dose-resposta. Foi também identificada uma óptima correlação entre os níveis de N7-GA-Gua e a frequência de troca de cromátides irmãs. Adicionalmente, e de forma a compreender os mecanismos de toxicidade da AA, estudaram-se os mecanismos dependentes da modulação do glutationo reduzido (GSH), nomeadamente da butionina sulfoximina (BSO), um inibidor da síntese de GSH, do GSH-monoetil estér (GSH-EE), um composto permeável nas células e que é intra-celularmente hidrolisado a GSH e ainda do GSH adicionado exogenamente ao meio de cultura, em células V79. Os resultados obtidos reforçaram o papel da modulação do GSH nos efeitos de citotoxicidade e clastogenicidade da AA. Para além dos estudos efetuados com células V79, procedeu-se também à determinação da frequência de SCEs, à quantificação de aductos específicos de DNA, bem como ao ensaio do cometa alcalino em amostras de dadores saudáveis expostos à AA e GA. Tanto os resultados obtidos através do ensaio das SCE, como pela quantificação de aductos específicos de DNA, ambos efectuados em linfócitos estimulados, originaram resultados comparáveis aos obtidos anteriormente para as células V79, reforçando a ideia de que a GA é bastante mais genotóxica do que a AA. Por outro lado, os resultados obtidos pelo ensaio do cometa para exposição à AA e GA mostraram que apenas esta última aumenta o nível das lesões de DNA. Outro objectivo deste trabalho, foi a identificação de possíveis associações existentes entre as lesões de DNA, quantificadas através do ensaio das SCEs e do cometa, e biomarcadores de susceptibilidade, tendo em conta os polimorfismos genéticos individuais envolvidos na destoxificação e nas vias de reparação do DNA (BER, NER, HRR e NHEJ) em linfócitos expostos à GA. Tal permitiu identificar associações entre os níveis de lesão de DNA determinados através do ensaio das SCEs, e os polimorfismos genéticos estudados, apontando para uma possível associação entre o GSTP1 (Ile105Val) e GSTA2 (Glu210Ala) e a frequência de SCEs. Por outro lado, os resultados obtidos através do ensaio do cometa sugerem uma associação entre as lesões de DNA e polimorfismos da via BER (MUTYH Gln335His e XRCC1 Gln39Arg) e da via NER (XPC Ala499val e Lys939Gln), considerando os genes isoladamente ou combinados. Estes estudos contribuem para um melhor entendimento da genotoxicidade e carcinogenicidade da AA e GA em células de mamífero, bem como da variabilidade da susceptibilidade individual na destoxificação e reparação de lesões de DNA provocadas pela exposição a estes xenobióticos alimentares. ----------- ABSTRACT:Acrylamide (AA) has been classified as a probable human carcinogen by IARC. Besides being used in numerous industrial applications, AA is also present in a variety of starchy cooked foods. This AA exposure scenario raised concerns about risk in human health and suggests that the oral consumption of AA is an additional risk factor for cancer. A considerable number of findings strongly suggest that the reactive metabolite glycidamide (GA), an epoxide generated presumably by cytochrome P450 2E1, plays a central role in AA carcinogenesis. Until now there are a scarcity of results concerning the mechanisms of genotoxicity of AA and GA in mammalian cells. In view of that, the study described in this thesis aims to unveil the genetic consequences of AA and GA exposure using mammalian cells as a model system. With this aim we evaluated the cytotoxicity of AA and GA using the MTT assay and subsequently performed two cytogenetic end-points: chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs), in order to evaluate DNA damage induced by these compounds in V79 Chinese hamster cell line. The results showed that GA was more cytotoxic and clastogenic than AA. Within the scope of this thesis the quantification of specific DNA adducts were also performed, namely N7-(2-carbamoyl-2-hydroxyethyl)guanine (N7-GA-Gua) and N3-(2-carbamoyl-2-hydroxyethyl)adenine (N3-GA-Ade). Interestingly, the GA concentration and the levels of N7-GA-Gua presented a linear dose-response relationship. Further, a very good correlation between the levels of N7-GA-Gua and the extent of SCEs were observed. In order to understand the mechanisms of AA-induced toxicity, the modulation of reduced glutathione (GSH)-dependent mechanisms were studied, namely the evaluation of the effect of buthionine sulfoximine (BSO), an effective inhibitor of GSH synthesis, of GSH-monoethyl ester (GSH-EE), a cell permeable compound that is intracellularly hydrolysed to GSH and also of GSH endogenously added to culture medium,z in V79 cell line. The overall results reinforced the role of GSH in the modulation of the cytotoxic and clastogenic effects induced by AA.Complementary to the studies performed in V79 cells, SCEs, specific DNA-adducts and alkaline comet assay in lymphocytes from healthy donors exposed to AA and GA were also evaluated. Both, the frequency of SCE and the quantification of specific GA DNA adducts, produced comparable results with those obtained in V79 cell line, reinforcing the idea that GA is far more genotoxic than AA. Further, the DNA damaging potential of AA and GA in whole blood leukocytes evaluated by the alkaline comet assay, showed that GA, but not AA, increases DNA damage. Additionally, this study aimed to identify associations between DNA damage and biomarkers of susceptibility, concerning individual genetic polymorphisms involved in detoxification and DNA repair pathways (BER, NER, HRR and NHEJ) on the GA-induced genotoxicity assessed by the SCE assay and by the alkaline comet assay. The extent of DNA damage determined by the levels of SCEs induced by GA seems to be modulated by GSTP1 (Ile105Val) and GSTA2 (Glu210Ala) genotypes. Moreover, the results obtained from the comet assay suggested associations between DNA damage and polymorphisms of BER (MUTYH Gln335His and XRCC1 Gln399Arg) and NER (XPC Ala499Val and Lys939Gln) genes, either alone or in combination. The overall results from this study contribute to a better understanding of the genotoxicity and carcinogenicity of AA and GA in mammalian cells, as well as the knowledge about the variability in individual susceptibility involved in detoxification and repair of DNA damage due to these dietary xenobiotics.

Calibration, selection and mosaicing of SMART-1 AMIE images

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

Establishing a cell biology platform: isolation and preservation of human blood products

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Maintaining the correctness of transactional memory programs

Dissertação para obtenção do Grau de Doutor em Engenharia Informática

Determinants of export diversification and sophistication in sub-saharan Africa

This paper studies the political and economic factors that determine successful export diversification (ED) and export sophistication (ES) strategies in the Sub-Saharan African (SSA) countries and also the way in which successful ED and sophistication strategies contribute to explain the improving in some of the millennium development goals (MDG). We run separate regressions for the determinants of ES and ED, using disaggregated data of the 48 SSA countries, from 1960 to 2005. The results suggest that better governance is an important determinant for the success of diversification and sophistication strategies in SSA. In particular the level of corruption, transparency and accountability are important factors in limiting or promoting the scope of diversification and the level of sophistication of the exports. The results also suggest that increases in human capital in SSA countries promote both ED and ES, showing that the level of education of the workforce is positively related with ES and ED, with higher levels of education (tertiary) playing a more important role in explaining ES, while lower levels of education (primary) being more important as determinants of ED. In the second part we explore the links between ED and ES and growth presenting evidence that ED and ES are linked to growth stability in SSA. This study also suggests that the Sub-Saharan countries that were more successful in achieving ED and ES tend to be more successful in improving the living conditions of their population. Using different variables of Infant Mortality (one of the MDG) and life expectancy as dependent variables, we present evidence that suggests that in SSA higher ED and ES are associated with lower infant mortality and higher life expectancy. We show that this result is robust, presenting positive and significant results even when a large number of different control variables are introduced, or when fixed effects and instrumental variables are considered. The evidence suggests that ED and ES are part of the solution for a successful development of SSA.

Drivers of China's foreign direct investment into Africa

We assess the determinants of Chinese direct investment in Africa compared with those of global FDI. We find that economic size and macroeconomic stability are positively correlated with Chinese and global FDI in Africa. Institutional variables, such as accountability and rule of law, are not significant in either case and the same can be said about FDI-aid complementarities. The presence of oil is a determinant of Chinese FDI but not of global FDI into Africa. Conversely, the openness of the economy is a determinant for global FDI but not of Chinese FDI, which appears to favour closed economies possibly due to industrial organizational concerns. While these differences accord with intuition, we find no evidence for the claim that Chinese FDI in Africa is related to non-economic governance in a specific way that differs from global practice. More refined governance indicators should be used to verify whether Chinese and global FDI into Africa remain indistinguishable on this score: we plan to do this in future research.

The contribution of Rómulo de Carvalho to Portuguese science education (1934-1974): a humanistic project?

Submitted in accordance with the requirements for the degree of Doctor of Philosophy (Doutoramento em co-tutela)The University of Leeds School of Education

Characterization and surface reconstruction of objects in tomographic images of composite materials

Dissertação para obtenção do Grau de Mestre em Engenharia Informática

Fractionation of hydro-ethanolic extracts from grape pomace through membrane processing: the effect of membrane and extracting media on process performance

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 centers and universities

From Consciousness to Knowledge – The Explanatory Power of Revelation

Epistemology in philosophy of mind is a difficult endeavor. Those who believe that our phenomenal life is different from other domains suggest that self-knowledge about phenomenal properties is certain and therefore privileged. Usually, this so called privileged access is explained by the idea that we have direct access to our phenomenal life. This means, in contrast to perceptual knowledge, self-knowledge is non-inferential. It is widely believed that, this kind of directness involves two different senses: an epistemic sense and a metaphysical sense. Proponents of this view often claim that this is due to the fact that we are acquainted with our current experiences. The acquaintance thesis, therefore, is the backbone in justifying privileged access. Unfortunately the whole approach has a profound flaw. For the thesis to work, acquaintance has to be a genuine explanation. Since it is usually assumed that any knowledge relation between judgments and the corresponding objects are merely causal and contingent (e.g. in perception), the proponent of the privileged access view needs to show that acquaintance can do the job. In this thesis, however, I claim that the latter cannot be done. Based on considerations introduced by Levine, I conclude that this approach involves either the introduction of ontologically independent properties or a rather obscure knowledge relation. A proper explanation, however, cannot employ either of the two options. The acquaintance thesis is, therefore, bound to fail. Since the privileged access intuition seems to be vital to epistemology within the philosophy of mind, I will explore alternative justifications. After discussing a number of options, I will focus on the so called revelation thesis. This approach states that by simply having an experience with phenomenal properties, one is in the position to know the essence of those phenomenal properties. I will argue that, after finding a solution for the controversial essence claim, this thesis is a successful replacement explanation which maintains all the virtues of the acquaintance account without necessarily introducing ontologically independent properties or an obscure knowledge relation. The overall solution consists in qualifying the essence claim in the relevant sense, leaving us with an appropriate ontology for phenomenal properties. On the one hand, this avoids employing mysterious independent properties, since this ontological view is physicalist in nature. On the other hand, this approach has the right kind of structure to explain privileged self-knowledge of our phenomenal life. My final conclusion consists in the claim that the privileged access intuition is in fact veridical. It cannot, however, be justified by the popular acquaintance approach, but rather, is explainable by the controversial revelation thesis.

Semantic enrichment of knowledge sources supported by domain ontologies

This thesis introduces a novel conceptual framework to support the creation of knowledge representations based on enriched Semantic Vectors, using the classical vector space model approach extended with ontological support. One of the primary research challenges addressed here relates to the process of formalization and representation of document contents, where most existing approaches are limited and only take into account the explicit, word-based information in the document. This research explores how traditional knowledge representations can be enriched through incorporation of implicit information derived from the complex relationships (semantic associations) modelled by domain ontologies with the addition of information presented in documents. The relevant achievements pursued by this thesis are the following: (i) conceptualization of a model that enables the semantic enrichment of knowledge sources supported by domain experts; (ii) development of a method for extending the traditional vector space, using domain ontologies; (iii) development of a method to support ontology learning, based on the discovery of new ontological relations expressed in non-structured information sources; (iv) development of a process to evaluate the semantic enrichment; (v) implementation of a proof-of-concept, named SENSE (Semantic Enrichment kNowledge SourcEs), which enables to validate the ideas established under the scope of this thesis; (vi) publication of several scientific articles and the support to 4 master dissertations carried out by the department of Electrical and Computer Engineering from FCT/UNL. It is worth mentioning that the work developed under the semantic referential covered by this thesis has reused relevant achievements within the scope of research European projects, in order to address approaches which are considered scientifically sound and coherent and avoid “reinventing the wheel”.

Portuguese business groups at the beginning of the 21st century: Trends, characteristics and configurations

This study considers the literature on the persistence of business groups in developed economies and analyzes the Portuguese case. The reconstruction of the largest business groups assembles information relevant to define characteristics that enable them to thrive. Increasing internationalization, more specialization in core activities and family control define these types of big businesses. New sectors also emerge as a characteristic of these business groups when compared to the ones existing 40 years ago.