Numerical analysis of complex failure mechanisms in composite panels

A three-dimensional continuum damage mechanics-based material model has been implemented in an implicit Finite Element code to simulate the progressive degradation of advanced composite materials. The damage model uses seven damage variables assigned to tensile, compressive and non-linear shear damage at a laminae level. The objectivity of the numerical discretization is assured using a smeared formulation. The material model was benchmarked against experimental uniaxial coupon tests and it is shown to reproduce key aspects observable during failure, such as the inclined fracture plane in matrix compression and the shear band in a ±45° tension specimen.

Gene regulatory mechanisms underpinning prostate cancer susceptibility

Molecular characterization of genome-wide association study (GWAS) loci can uncover key genes and biological mechanisms underpinning complex traits and diseases. Here we present deep, high-throughput characterization of gene regulatory mechanisms underlying prostate cancer risk loci. Our methodology integrates data from 295 prostate cancer chromatin immunoprecipitation and sequencing experiments with genotype and gene expression data from 602 prostate tumor samples. The analysis identifies new gene regulatory mechanisms affected by risk locus SNPs, including widespread disruption of ternary androgen receptor (AR)-FOXA1 and AR-HOXB13 complexes and competitive binding mechanisms. We identify 57 expression quantitative trait loci at 35 risk loci, which we validate through analysis of allele-specific expression. We further validate predicted regulatory SNPs and target genes in prostate cancer cell line models. Finally, our integrated analysis can be accessed through an interactive visualization tool. This analysis elucidates how genome sequence variation affects disease predisposition via gene regulatory mechanisms and identifies relevant genes for downstream biomarker and drug development.

Molecular mechanisms mediating the beneficial metabolic effects of [Arg4]tigerinin-1R in mice with diet-induced obesity and insulin resistance

The frog skin host-defense peptide tigerinin-1R stimulates insulin release in vitro and improves glucose tolerance and insulin sensitivity in animal models of type 2 diabetes. This study extends these observation by investigating the molecular mechanisms of action underlying the beneficial metabolic effects of the analogue [Arg4]tigerinin-1R in mice with diet induced obesity, glucose intolerance and insulin resistance. The study also investigates the electrophysiological effects of the peptide on KATP and L-type Ca2+ channels in BRINBD11 clonal β cells. Non-fasting plasma glucose and glucagon concentrations were significantly (P<0.05) decreased and plasma insulin increased by twice daily treatment with [Arg4]tigerinin-1R (75 nmol.kg-1 body weight) for 28 days. Oral and intraperitoneal glucose tolerance were significantly (P < 0.05) improved accompanied by enhanced secretion and action of insulin. The peptide blocked KATP channels and, consistent with this, improved beta cell responses of isolated islets to a range of secretagogues. Peptide administration resulted in up-regulation of key functional genes in islets involved insulin secretion (Abcc8, Kcnj11, Cacna1c and Slc2a2) and in skeletal muscle involved with insulin action (Insr, Irs1, Pdk1, Pik3ca, and Slc2a4). These observations encourage further development of tigerinin-1R analogues for the treatment of patients with type 2 diabetes.

The duration compression effect is mediated by adaptation of both retinotopic and spatiotopic mechanisms

The duration compression effect is a phenomenon in which prior adaptation to a spatially circumscribed dynamic stimulus results in the duration of subsequent subsecond stimuli presented in the adapted region being underestimated. There is disagreement over the frame of reference within which the duration compression phenomenon occurs. One view holds that the effect is driven by retinotopic-tuned mechanisms located at early stages of visual processing, and an alternate position is that the mechanisms are spatiotopic and occur at later stages of visual processing (MT+). We addressed the retinotopic-spatiotopic question by using adapting stimuli – drifting plaids - that are known to activate global-motion mechanisms in area MT. If spatiotopic mechanisms contribute to the duration compression effect, drifting plaid adaptors should be well suited to revealing them. Following adaptation participants were tasked with estimating the duration of a 600ms random dot stimulus, whose direction was identical to the pattern direction of the adapting plaid, presented at either the same retinotopic or the same spatiotopic location as the adaptor. Our results reveal significant duration compression in both conditions, pointing to the involvement of both retinotopic-tuned and spatiotopic-tuned mechanisms in the duration compression effect.

Gene expression in understanding mechanisms of toxicity in amphibians

De uma forma geral os anfíbios são conhecidos como organismos que apresentam uma grande sensibilidade a vários tipos de contaminantes. Contudo existem casos, como o de Pelophylax perezi (rã-verde), em que estes organismos habitam áreas extremamente contaminadas. Este facto verifica-se na mina de urânio desactivada, da Cunha Baixa (Viseu, centro de Portugal), em que uma população destas rãs habita na lagoa de efluente ácido mineiro (M). Estudos ecotoxicológicos anteriores com estes organismos revelaram apenas efeitos de toxicidade ténues levantando algumas questões. Com o objectivo de elucidar quais os mecanismos que permitem a P. perezi permanecer neste local, sem sofrer aparentemente efeitos perniciosos, encetamos este trabalho. Numa primeira abordagem, avaliámos o sistema de defesa antioxidante de rãs adultas, bem como o conteúdo em metais de alguns órgãos. Desta forma verificámos alterações enzimáticas, principalmente no pulmão e acumulação de metais nos vários órgãos. Posteriormente foi realizado um estudo de expressão genética diferencial, também em organismos adultos e desta feita foram sugeridos alguns mecanismos de protecção basal que estarão por detrás da capacidade de suportar este ambiente extremamente contaminado. Numa etapa seguinte abordámos os efeitos em fases larvares, fazendo inicialmente uma exposição in situ, a vários efluentes, caracteristicamente diferentes, do complexo mineiro. Avaliámos o crescimento, a acumulação de metais e a actividade de alguns biomarcadores de stress oxidativo. Como resultado pudemos constatar que nas fases larvares para além de alguma mortalidade existe acumulação de metais bem como algumas alterações a nível de biomarcadores de stress oxidativo. Numa última abordagem realizamos uma exposição crónica dos girinos a efluente da mina com diversos níveis de pH para distinguir os efeitos da toxicidade do pH, dos efeitos da toxicidade pelo conteúdo de metais. Para tal avaliámos novamente biomarcadores de stress oxidativo, crescimento, acumulação de metais e efectuamos ainda um estudo de expressão genética diferencial. Esta última aproximação permitiu verificar que a toxicidade do efluente resulta primariamente do pH ácido, assumindo a contaminação por metais um papel secundário. Contudo o crescimento dos girinos de P. perezi apresenta-se estimulado por pHs mais baixos. São apontados ainda alguns mecanismos, em girinos, para lidar com o stress causado pela contaminação por metais.De uma forma geral pôde-se constatar que quer anfíbios adultos quer girinos expostos ao efluente apresentam valores altos de metais acumulados. Os biomarcadores de stress oxidativo na sua maioria não apresentaram respostas coerentes mediante as várias exposições. Este trabalho apresentase como um contributo importante para a ecotoxicologia de anfíbios, aumentando os níveis actuais de conhecimento sobre o efeito de contaminação proveniente de efluentes mineiros, sugerindo ainda mecanismos de resistência quer em larvas, quer para adultos.

UV-induced stress in bacterioneuston : mechanisms and ecological implications

As bactérias desempenham um papel chave na reciclagem de energia e matéria nas teias tróficas aquáticas. No entanto, as suas pequenas dimensões, curto tempo de geração e o facto de os seus genomas constituírem uma grande porção do seu volume celular, tornam as bactérias mais suscetíveis às alterações ambientais que os organismos superiores. O aumento dos níveis de radiação UVB (280-320 nm) constitui uma ameaça particularmente importante para as comunidades bacterianas dos sistemas aquáticos, uma vez que a radiação consegue penetrar até profundidades consideráveis. No entanto, os mecanismos através dos quais a radiação causa danos nas bactérias ainda não são claros, o que impede a modelação precisa dos efeitos da radiação UV nas comunidades bacterianas naturais. O bacterioneuston habita a microcamada superficial (primeiro milímetro da coluna de água), estando naturalmente exposto a níveis de radiação UV superiores aos que o bacterioplâncton está exposto. Deste modo, a microcamada superficial pode ser vista como um nicho ecológico modelo para estudar as interações entre as bactérias e a radiação UV. Os objetivos deste trabalho foram (i) avaliar a influência do nível de exposição natural à radiação das comunidades bacterianas na sua sensibilidade à radiação UV, através da comparação das respostas fotobiológicas do bacterioneuston e bacterioplâncton; (ii) aprofundar o conhecimento acerca dos mecanismos através dos quais a radiação UV causa danos, bem como dos fatores que afetam a interação entre a radiação UV e as bactérias; e (iii) avaliar o potencial da proteína RecA, que medeia a resposta SOS das bactérias, para ser usada como marcador de danos induzidos por UV nas comunidades bacterianas. Verificou-se que o bacterioneuston é mais resistente à radiação UVB que o bacterioplâncton e recupera de modo mais eficiente dos danos induzidos por UV, particularmente em condições de escassez de nutrientes, indicando assim que o nível de exposição natural das comunidades bacterianas à radiação afeta a sua sensibilidade à radiação UV. Os resultados das análises independentes do cultivo revelaram o potencial da radiação UV para afetar a estrutura das comunidades bacterianas ao selecionar bactérias resistentes. A análise do perfil de utilização de fontes de carbono usando o sistema de Ecoplacas Biolog ® e a determinação das taxas de incorporação de leucina e timidina permitiu também verificar que a radiação UV modifica o funcionamento das comunidades bacterianas. Os resultados obtidos indicam a possibilidade do bacterioneuston conter um conjunto de estirpes resistentes a UV que, mediante as condições meteorológicas apropriadas, podem ser selecionadas aquando da exposição à radiação.

DACA: architecture to implement dynamic access control mechanisms on business tier components

Access control is a software engineering challenge in database applications. Currently, there is no satisfactory solution to dynamically implement evolving fine-grained access control mechanisms (FGACM) on business tiers of relational database applications. To tackle this access control gap, we propose an architecture, herein referred to as Dynamic Access Control Architecture (DACA). DACA allows FGACM to be dynamically built and updated at runtime in accordance with the established fine-grained access control policies (FGACP). DACA explores and makes use of Call Level Interfaces (CLI) features to implement FGACM on business tiers. Among the features, we emphasize their performance and their multiple access modes to data residing on relational databases. The different access modes of CLI are wrapped by typed objects driven by FGACM, which are built and updated at runtime. Programmers prescind of traditional access modes of CLI and start using the ones dynamically implemented and updated. DACA comprises three main components: Policy Server (repository of metadata for FGACM), Dynamic Access Control Component (DACC) (business tier component responsible for implementing FGACM) and Policy Manager (broker between DACC and Policy Server). Unlike current approaches, DACA is not dependent on any particular access control model or on any access control policy, this way promoting its applicability to a wide range of different situations. In order to validate DACA, a solution based on Java, Java Database Connectivity (JDBC) and SQL Server was devised and implemented. Two evaluations were carried out. The first one evaluates DACA capability to implement and update FGACM dynamically, at runtime, and, the second one assesses DACA performance against a standard use of JDBC without any FGACM. The collected results show that DACA is an effective approach for implementing evolving FGACM on business tiers based on Call Level Interfaces, in this case JDBC.

Life after Stroke: Coping mechanisms among African Caribbean Women

In the UK stroke is the third most common cause of death for women and the incidence in African Caribbean women is higher than the general population. Stroke burden has major consequences for the physical, mental and social health of African Caribbean women. In order to adjust to life after stroke individuals affected employ a range of strategies which may include personal, religious (church) or spiritual support (i.e. prayer), individual motivation, or resignation to life with a disability. This study explored these areas through the coping mechanisms that African Caribbean women utilised post stroke in the context of stroke recovery and lifestyle modification efforts needed to promote healthy living post stroke. A qualitative approach using Interpretative Phenomenological Analysis was adopted. Eight women were recruited into the study. Semi structured in-depth interviews were audio recorded and were transcribed verbatim. Data were analysed using a four-stage framework: familiarisation, sense making, developing themes and data refinement and analysis. Three main themes on coping emerged: the need to follow medical rules to manage stroke, strength and determination, and the use of religion and faith to cope with life after stroke. These findings illustrate both a tension between religious beliefs and the medical approach to stroke and highlight the potential benefits that religion and the church can play in stroke recovery. Implications for practice include acknowledgement and inclusion of religion and church based health promotion in post stroke recovery.

Study of Perkinsus olseni infection mechanisms: identification and regulation of parasite genes differentially expressed in response to host and environmental stress

Tese dout., Biologia, Universidade do Algarve, 2008

Role of insulin and insulin-like peptides in bone formation: identification of bone-specific target genes and regulatory mechanisms, and characterization of the insulin-mimetic effect of vanadium

Tese de Doutoramento em Biologia, Especialidade em Biologia Molecular, Universidade do Algarve, 2008

Effects of vitamin K deficiency and its mechanisms in vertebrate's early development: zebrafish as a model

Disertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015

Epigenetic mechanisms of effector y&T cell differentiation : focus on histone modifications and microRNAs

Tese de doutoramento, Ciências Biomédicas (Imunologia), Universidade de Lisboa, Faculdade de Medicina, 2014