Pharmacogenetic analysis of the pregnane x receptor in breast cancer. Case-control study

Dissertação de Mestrado, Mestrado em Qualidade em Análises, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Regulatory interactions between the metabolic sensors SIRT1 and AMPK in modulating PPARα linked functions, in obesity-dependent type 2 diabetes mellitus

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

Interference of mycobacterium tuberculosis with the endocytic/ antigen presentation pathways on macrophages and dendritic cells

Tese de doutoramento, Farmácia (Biologia Celular e Molecular), Universidade de Lisboa, Faculdade de Farmácia, 2014

How does developmental plasticity differ between diverse types of nutrition regimes?

Tese de mestrado em Biologia Evolutiva e do Desenvolvimento, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2016

Transgender Freedom and the Law: A Liberal-Poststructural Discussion on McNally

In R v McNally, gender deception is found capable of leading to the vitiation of consent to sexual intercourse and, in so doing, places restriction on the freedom of transgendered individuals in favour of cisgendered freedom. This paper seeks to challenge the standing of this decision by adopting a combined methodological approach between Deleuzian post-structuralism and Gewirthian legal idealism. In so doing, we attempt to show that the combination offers a novel and productive approach to contentious decisions, such as that in McNally. Our approach brings together post-structuralist corporeality which conceives of the body as material and productive, and Gewirth’s ‘agent’ to conceptualise the legal body as an entity which can, and should, shape judicial reasoning. It does this by employing the criterion of categorically necessary freedom on institutionalised practical reasoning. These ‘bodies of agents’ can be conceived as the underpinning and justificatory basis for the authority of the law subject to the morally rational Principle of Generic Consistency. This egalitarian condition precedent requires individualisation and the ability to accept self-differentiation in order to return to a status, which can be validly described as “law”. Ultimately, we argue that this theoretical combination responds to a call to problematise the connection made between gender discourse and judicial reasoning, whilst offering the opportunity to further our conceptions of law and broaden the theoretical armoury with which to challenge judicial reasoning in McNally. That is, a ‘good faith’ attempt to further and guarantee transgender freedoms.

Next-generation sequencing is highly sensitive for the detection of beta-catenin mutations in desmoid-type fibromatoses

Desmoid-type fibromatoses are locally aggressive and frequently recurrent tumours, and an accurate diagnosis is essential for patient management. The majority of sporadic lesions harbour beta-catenin (CTNNB1) mutations. We used next-generation sequencing to detect CTNNB1 mutations and to compare the sensitivity and specificity of next-generation sequencing with currently employed mutation detection techniques: mutation-specific restriction enzyme digestion and polymerase chain reaction amplification. DNA was extracted from formalin-fixed paraffin-embedded needle biopsy or resection tissue sections from 144 patients with sporadic desmoid-type fibromatoses, four patients with syndrome-related desmoid-type fibromatoses and 11 morphological mimics. Two primer pairs were designed for CTNNB1 mutation hotspots. Using ≥10 ng of DNA, libraries were generated by Fluidigm and sequenced on the Ion Torrent Personal Genome Machine. Next-generation sequencing had a sensitivity of 92.36 % (133/144, 95 % CIs: 86.74 to 96.12 %) and a specificity of 100 % for the detection of CTNNB1 mutations in desmoid-type fibromatoses-like spindle cell lesions. All mutations detected by mutation-specific restriction enzyme digestion were identified by next-generation sequencing. Next-generation sequencing identified additional mutations in 11 tumours that were not detected by mutation-specific restriction enzyme digestion, two of which have not been previously described. Next-generation sequencing is highly sensitive for the detection of CTNNB1 mutations. This multiplex assay has the advantage of detecting additional mutations compared to those detected by mutation-specific restriction enzyme digestion (sensitivity 82.41 %). The technology requires minimal DNA and is time- and cost-efficient.

Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology

Objective: Individuals with obesity and type 2 diabetes differ from lean and healthy individuals in their abundance of certain gut microbial species and microbial gene richness. Abundance of Akkermansia muciniphila, a mucin-degrading bacterium, has been inversely associated with bodyfat mass and glucose intolerance in mice, but more evidence is needed in humans. The impact of diet and weight loss on this bacterial species is unknown. Our objective was to evaluate the association between fecal A. muciniphila abundance, fecal microbiome gene richness, diet, host characteristics, and their changes after calorie restriction (CR). Design: The intervention consisted of a 6-week CR period followed by a 6-week weight stabilization (WS) diet in overweight and obese adults (N=49, including 41 women). Fecal A. muciniphila abundance, fecal microbial gene richness, diet and bioclinical parameters were measured at baseline and after CR and WS. Results: At baseline A. muciniphila was inversely related to fasting glucose, waist-to-hip ratio, and subcutaneous adipocyte diameter. Subjects with higher gene richness and A. muciniphila abundance exhibited the healthiest metabolic status, particularly in fasting plasma glucose, plasma triglycerides and body fat distribution. Individuals with higher baseline A. muciniphila displayed greater improvement in insulin sensitivity markers and other clinical parameters after CR. A. muciniphila was associated with microbial species known to be related to health. Conclusion: A. muciniphila is associated with a healthier metabolic status and better clinicaloutcomes after CR in overweight/obese adults, however the interaction between gut microbiota ecology and A. muciniphila has to be taken into account.

Ajustes posturais para o alcance funcional dos membros superiores - migração do centro de pressão na posição de sentado

Objetivos: Pretende-se verificar as modificações neuromotoras após uma intervenção baseada no conceito de Bobath ao nível dos ajustes posturais durante o alcance funcional dos membros superiores, em três crianças com paralisia cerebral. Pretende-se também, verificar o efeito desta abordagem nas atividades e participação, bem como destacar os aspetos individuais das mesmas crianças com a capacidade de mudança após a intervenção. Metodologia: A avaliação foi realizada antes e três meses após a intervenção em fisioterapia segundo o conceito de Bobath. Optou-se por um registo observacional com uma Máquina Fotográfica Digital, um sistemas de Câmaras de Vídeo, uma Plataforma de Forças e, utilizaram-se ainda instrumentos como o Gross Motor Functional Measure– versão 88 itens, o Gross Motor Function Classification System, o Teste de Alcance Funcional Modificado e a ferramenta, Classificação Internacional de Funcionalidade, Incapacidade e Saúde – crianças e jovens. Resultados: Verificou-se um progresso nos ajustes posturais e na funcionalidade em geral, o que se repercutiu na restrição da participação e na limitação da actividade. A postura na posição de sentado, o deslocamento do centro de pressão, a capacidade de deslocamento no sentido anterior, bem como as capacidades motoras grosseiras modificaram-se em todas as crianças, tendo a criança B apresentado a maior e a criança A a menor capacidade de mudança após a intervenção. Conclusão: A intervenção segundo o Conceito de Bobath promoveu modificações neuromotoras, o que levaram a uma melhoria da funcionalidade geral, da mobilidade e do controlo postural da criança, refletindo-se nos ajustes posturais durante o alcance funcional dos membros superiores na posição de sentado. Verificou-se ainda, uma melhoria na restrição da participação e na limitação da actividade diária.

A questão da língua na União Europeia – implicações sobre a liberdade de circulação de mercadorias

Dissertação apresentada ao Instituto Superior de Contabilidade e Administração do Porto para a obtenção do Grau de Mestre em Empreendedorismo e Internacionalização Orientada pela Mestre Maria Luísa Verdelho Alves

Prática de ensino supervisionado no 1.º e 2.º ciclo do ensino básico: desenvolver competências de recolha e tratamento da informação na aprendizagem da História e Geografia no 1.º e 2.º CEB

Relatório de investigação apresentado à Escola Superior de Educação de Lisboa para obtenção de grau de mestre no Mestrado em Ensino do 1.º e 2.º Ciclo do Ensino Básico

Task assignment algorithms for two-type heterogeneous multiprocessors

Consider the problem of assigning real-time tasks on a heterogeneous multiprocessor platform comprising two different types of processors — such a platform is referred to as two-type platform. We present two linearithmic timecomplexity algorithms, SA and SA-P, each providing the follow- ing guarantee. For a given two-type platform and a given task set, if there exists a feasible task-to-processor-type assignment such that tasks can be scheduled to meet deadlines by allowing them to migrate only between processors of the same type, then (i) using SA, it is guaranteed to find such a feasible task-to- processor-type assignment where the same restriction on task migration applies but given a platform in which processors are 1+α/2 times faster and (ii) SA-P succeeds in finding 2 a feasible task-to-processor assignment where tasks are not allowed to migrate between processors but given a platform in which processors are 1+α/times faster, where 0<α≤1. The parameter α is a property of the task set — it is the maximum utilization of any task which is less than or equal to 1.

Buckling strength of adhesively-bonded single and double-strap repairs on carbon-epoxy structures

This work reports on an experimental and finite element method (FEM) parametric study of adhesively-bonded single and double-strap repairs on carbon-epoxy structures under buckling unrestrained compression. The influence of the overlap length and patch thickness was evaluated. This loading gains a particular significance from the additional characteristic mechanisms of structures under compression, such as fibres microbuckling, for buckling restrained structures, or global buckling of the assembly, if no transverse restriction exists. The FEM analysis is based on the use of cohesive elements including mixed-mode criteria to simulate a cohesive fracture of the adhesive layer. Trapezoidal laws in pure modes I and II were used to account for the ductility of most structural adhesives. These laws were estimated for the adhesive used from double cantilever beam (DCB) and end-notched flexure (ENF) tests, respectively, using an inverse technique. The pure mode III cohesive law was equalled to the pure mode II one. Compression failure in the laminates was predicted using a stress-based criterion. The accurate FEM predictions open a good prospect for the reduction of the extensive experimentation in the design of carbon-epoxy repairs. Design principles were also established for these repairs under buckling.

Strength prediction of single- and double-lap joints by standard and extended finite element modelling

The structural integrity of multi-component structures is usually determined by the strength and durability of their unions. Adhesive bonding is often chosen over welding, riveting and bolting, due to the reduction of stress concentrations, reduced weight penalty and easy manufacturing, amongst other issues. In the past decades, the Finite Element Method (FEM) has been used for the simulation and strength prediction of bonded structures, by strength of materials or fracture mechanics-based criteria. Cohesive-zone models (CZMs) have already proved to be an effective tool in modelling damage growth, surpassing a few limitations of the aforementioned techniques. Despite this fact, they still suffer from the restriction of damage growth only at predefined growth paths. The eXtended Finite Element Method (XFEM) is a recent improvement of the FEM, developed to allow the growth of discontinuities within bulk solids along an arbitrary path, by enriching degrees of freedom with special displacement functions, thus overcoming the main restriction of CZMs. These two techniques were tested to simulate adhesively bonded single- and double-lap joints. The comparative evaluation of the two methods showed their capabilities and/or limitations for this specific purpose.

Perturbações da voz profissional: da prevalência ao impacto económico

Dissertação apresentada à Associação de Politécnicos do Norte para obtenção do Grau de Mestre em Gestão das Organizações, Ramo de Gestão de Empresas Orientação: Prof. Doutor Jorge Ferreira Dias de Figueiredo Co-Orientação: Mestre Luís Francisco de Oliveira Marques Metello

Task assignment algorithms for two-type heterogeneous multiprocessors

Consider the problem of assigning implicit-deadline sporadic tasks on a heterogeneous multiprocessor platform comprising two different types of processors—such a platform is referred to as two-type platform. We present two low degree polynomial time-complexity algorithms, SA and SA-P, each providing the following guarantee. For a given two-type platform and a task set, if there exists a task assignment such that tasks can be scheduled to meet deadlines by allowing them to migrate only between processors of the same type (intra-migrative), then (i) using SA, it is guaranteed to find such an assignment where the same restriction on task migration applies but given a platform in which processors are 1+α/2 times faster and (ii) SA-P succeeds in finding a task assignment where tasks are not allowed to migrate between processors (non-migrative) but given a platform in which processors are 1+α times faster. The parameter 0<α≤1 is a property of the task set; it is the maximum of all the task utilizations that are no greater than 1. We evaluate average-case performance of both the algorithms by generating task sets randomly and measuring how much faster processors the algorithms need (which is upper bounded by 1+α/2 for SA and 1+α for SA-P) in order to output a feasible task assignment (intra-migrative for SA and non-migrative for SA-P). In our evaluations, for the vast majority of task sets, these algorithms require significantly smaller processor speedup than indicated by their theoretical bounds. Finally, we consider a special case where no task utilization in the given task set can exceed one and for this case, we (re-)prove the performance guarantees of SA and SA-P. We show, for both of the algorithms, that changing the adversary from intra-migrative to a more powerful one, namely fully-migrative, in which tasks can migrate between processors of any type, does not deteriorate the performance guarantees. For this special case, we compare the average-case performance of SA-P and a state-of-the-art algorithm by generating task sets randomly. In our evaluations, SA-P outperforms the state-of-the-art by requiring much smaller processor speedup and by running orders of magnitude faster.