Hybrid time dependent/independent solution for the He i line ratio temperature and density diagnostic for a thermal helium beam with applications in the scrape-off layer-edge regions in tokamaks

Spectroscopic studies of line emission intensities and ratios offer an attractive option in the\r\ndevelopment of non-invasive plasma diagnostics. Evaluating ratios of selected He I line\r\nemission profiles from the singlet and triplet neutral helium spin systems allows for simultaneous\r\nmeasurement of electron density (ne) and temperature (Te) profiles. Typically, this powerful\r\ndiagnostic tool is limited by the relatively long relaxation times of the 3S metastable term of helium\r\nthat populates the triplet spin system, and on which electron temperature sensitive lines are based.\r\nBy developing a time dependent analytical solution, we model the time evolution of the two spin\r\nsystems. We present a hybrid time dependent/independent line ratio solution that improves the\r\nrange of application of this diagnostic technique in the scrape-off layer (SOL) and edge plasma\r\nregions when comparing it against the current equilibrium line ratio helium model used at\r\nTEXTOR.

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

Les pratiques de gouvernance de commissions scolaires du Québec

Le système d'éducation public québécois actuel est marqué par la complexité de son fonctionnement multijoueurs amplifiée par un accroissement des prescriptions législatives en matière de gouvernance et de procédures participatives. Devant ce constat, l'objectif de cette thèse est de décrire et de comprendre, à partir de l'analyse de pratiques d'acteurs, le fonctionnement réel de la gouvernance de deux commissions scolaires (CS) québécoises en regard de ce qui est prescrit par la Loi. Utilisant une approche qualitative, notre recherche repose sur une étude de cas dans laquelle trois dossiers sont étudiés pour chacune des organisations. L' analyse est menée à partir des concepts propres aux approches théoriques de l'analyse stratégique et du néoinstitutionnalisme. Nous concluons de cette étude de pratiques de gouvernance que les dossiers étudiés sont menés conformément aux prescriptions législatives, voire que ces pratiques vont souvent au-delà des exigences législatives, notamment quant aux procédures de participation. Dans les CS étudiés, les processus de gouvernance mis en oeuvre s'appuient généralement sur un porteur de dossier et des comités de travail regroupant des représentants-relais de plusieurs acteurs concernés. Ce fonctionnement est observé au sein des deux organisations, et ce, même si les modes de coopération présentent des différences notables. Au niveau des acteurs, dans les deux cas étudiés, les cadres de la CS et le Conseil des commissaires sont perçus comme étant très influents sur le déroulement des dossiers. L'influence des autres acteurs, tels que les parents, les représentants de la communauté et les acteurs associés aux établissements, est perçue comme étant variable selon les organisations et selon les dossiers. Les perceptions quant à la marge de manoeuvre et aux capacités d'influence des acteurs, l'intérêt porté au dossier et la personnalité des individus impliqués s'avèrent des facteurs marquants quant à cette inégalité.

Study of influence of regulatory polymorphisms of expression in development of breast cancer

The human genome has millions of genetics variants that can affect gene expression. These variants are known as cis-regulatory variants and are responsible for intra-species phenotypic differences and individual susceptibility to disease. One of the diseases affected by cis-regulatory variants is breast cancer. Breast cancer is one of the most common cancers, with approximately 4500 new cases each year in Portugal. Breast cancer has many genes mutated and TP53 has been shown to be relevant for this disease. TP53 is one of the most commonly mutated genes in human cancer and it is involved in cell cycle regulation and apoptosis. Previous work by Maia et al has shown that TP53 has differential allelic expression (DAE), which suggests that this gene may be under the influence of cis-regulatory variants. Also, its DAE pattern is totally altered in breast tumours with normal copy number. We hypothesized that cis-regulatory variants affecting TP53 may have a role in breast cancer development and treatment. The present work aims to identify the cis-regulatory variants playing a role in TP53 expression, using in silico, in vitro and in vivo approaches. By bioinformatic tools we have identified candidate cis-regulatory variants and predicted the possible transcription factor binding sites that they affect. By EMSA we studied DNA-protein interactions in this region of TP53. The in silico analysis allowed us to identified three candidate cis-regulatory SNPs which may affect the binding of seven transcription factors. However, the EMSA experiments have not been conclusive and we have not yet confirmed whether any of the identified SNPs are associated with gene expression control of TP53. We will carry out further experiments to validate our findings.

The activity of mouse Cerberus like 2 during cardiogenesis - genetic and morphogenetic studies

Cardiogenesis is a delicate and complex process that requires the coordination of an intricate network of pathways and the different cell types. Therefore, understanding heart development at the morphogenetic level is an essential requirement to uncover the causes of congenital heart disease and to provide insight for disease therapies. Mouse Cerberus like 2 (Cerl2) has been defined as a Nodal antagonist in the node with an important role in the Left-Right (L/R) axis establishment, at the early embryonic development. As expected, Cerl2 knockout mice (Cerl2-/-) showed multiple laterality defects with associated cardiac failure. In order to identify the endogenous role of Cerl2 during heart formation independent of its described functions in the node, we accurately analyzed animals where laterality defects were not present. We thereby unravel the consequences of Cerl2 lossof- function in the heart, namely increased left ventricular thickness due to hyperplasia of cardiomyocytes and de-regulated expression of cardiac genes. Furthermore, the Cerl2 mutant neonates present impaired cardiac function. Once that the cardiac expression of Cerl2 is mostly observed in the left ventricle until around midgestration, this result suggest a specific regulatory role of Cerl2 during the formation of the left ventricular myoarchitecture. Here, we present two possible molecular mechanisms underlying the cardiac Cerl2 function, the regulation of Cerl2 antagonist in activation of the TGFßs/Nodal/Activin/Smad2 signaling identified by increased Smad2 phosphorilation in Cerl2-/- hearts and the negative feedback between Cerl2 and Wnt/ß-catenin signaling in heart formation. In this work and since embryonic stem cells derived from 129 mice strain is extensively used to produce targeted mutants, we also present echocardiographic reference values to progressive use of juveniles and young adult 129/Sv strain in cardiac studies. In addition, we investigate the cardiac physiology of the surviving Cerl2 mutants in 129/Sv background over time through a follow-up study using echocardiographic analysis. Our results revealed that Cerl2-/- mice are able to improve and maintain the diastolic and most of systolic cardiac physiologic parameters as analyzed until young adult age. Since Cerl2 is no longer expressed in the postnatal heart, we suggest that an intrinsic and compensatory mechanism of adaptation may be active for recovering the decreased cardiac function found in Cerl2 mutant neonates. Altogether, these data highlight the role of Cerl2 during embryonic heart development in mice. Furthermore, we also suggest that Cerl2-/- may be an interesting model to uncover the molecular, cellular and physiological mechanisms behind the improvement of the cardiac function, contributing to the development of therapeutic approaches to treat heart failures.

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

Cystathionine beta-synthase variants : identification, characterization and modulation by thiol compounds

Tese de doutoramento, Farmácia (Bioquímica), Universidade de Lisboa, Faculdade de Farmácia, 2014

Towards the therapeutic use of regulatory T cells for the treatment of human autoimmune diseases

Tese de doutoramento, Medicina (Imunologia Clínica), Universidade de Lisboa, Faculdade de Medicina, 2016

The BBC's role in the changing production ecology of pre-school television in Britain

This paper examines the changing production ecology of British pre-school television in light of developments since the mid-1990s and the specific role played by the BBC. Underpinning the research is the perception that pre-school television is characterised by a complex set of industry relationships and dependencies that demands content which needs to satisfy a wide range of international circumstances and commercial prerogatives. For the BBC this has created tension between its public service goals and commercial priorities. Pre-school programming began in Britain in 1950, but it was not until the mid-1990s that Britain emerged as a leading producer of pre-school programming worldwide with government/industry reports regularly identifying the children’s production sector as an important contributor to exports. The rise of pre-school niche channels (CBeebies, Nick Junior, Playhouse Disney), audience fragmentation and the internationalisation and commercialisation of markets have radically altered the funding base of children’s television and the relationships that the BBC enjoys with key players. The international success of much of its pre-school programming is based on the relationships it enjoys with independent producers who generate significant revenues from programme-related consumer products. This paper focuses on the complex and changing relationships between the BBC, independent producers, and financiers, that constitute the production ecology of pre-school television and shape its output. Within the broader setting of cultural production and global trends the paper investigates the following questions: 1) In the light of changes to the sector since the mid-1990s, what makes pre-school television significant both generally and as an ideal public service project? 2) What is the nature of the current funding crisis in British children’s television and what implications does this crisis have for the BBC’s involvement in pre-school television? 3) How is the Corporation reacting to and managing the wider commercial, cultural, regulatory and technological forces that are likely to affect its strategies for the commissioning, production and acquisition of pre-school content?

A Benefit-Risk Assessment Framework for Development of Clinical Guidelines in Diagnostic Radiology

Thesis (Ph.D.)--University of Washington, 2015-12

Acute hypoxia reduces plasma myostatin independent of hypoxic dose

Background: Muscle atrophy is seen ~ 25 % of patients with cardiopulmonary disorders, such as chronic obstructive pulmonary disorder and chronic heart failure. Multiple hypotheses exist for this loss, including inactivity, inflammation, malnutrition and hypoxia. Healthy individuals exposed to chronic hypobaric hypoxia also show wasting, suggesting hypoxia alone is sufficient to induce atrophy. Myostatin regulates muscle mass and may underlie hypoxic-induced atrophy. Our previous work suggests a decrease in plasma myostatin and increase in muscle myostatin following 10 hours of exposure to 12 % O2. Aims: To establish the effect of hypoxic dose on plasma myostatin concentration. Concentration of plasma myostatin following two doses of normobaric hypoxia (10.7 % and 12.3 % O2) in a randomised, single-blinded crossover design (n = 8 lowlanders, n = 1 Sherpa), with plasma collected pre (0 hours), post (2 hours) and 2 hours following (4 hours) exposure. Results: An effect of time was noted, plasma myostatin decreased at 4 hours but not 2 hours relative to 0 hours (p = 0.01; 0 hours = 3.26 [0.408] ng.mL-1, 2 hours = 3.33, [0.426] ng.mL-1, 4 hours = 2.92, [0.342] ng.mL-1). No difference in plasma myostatin response was seen between hypoxic conditions (10.7 % vs. 12.3 % O2). Myostatin reduction in the Sherpa case study was similar to the lowlander cohort. Conclusions: Decreased myostatin peptide expression suggests hypoxia in isolation is sufficient to challenge muscle homeostasis, independent of confounding factors seen in chronic cardiopulmonary disorders, in a manner consistent with our previous work. Decreased myostatin peptide may represent flux towards peripheral muscle, or a reduction to protect muscle mass. Chronic adaption to hypoxia does not appear to protect against this response, however larger cohorts are needed to confirm this. Future work will examine tissue changes in parallel with systemic effects.

A regulatory framework for short-term stochastic maintenance outage scheduling in smart grids

The current regulatory framework for maintenance outage scheduling in distribution systems needs revision to face the challenges of future smart grids. In the smart grid context, generation units and the system operator perform new roles with different objectives, and an efficient coordination between them becomes necessary. In this paper, the distribution system operator (DSO) of a microgrid receives the proposals for shortterm (ST) planned outages from the generation and transmission side, and has to decide the final outage plans, which is mandatory for the members to follow. The framework is based on a coordination procedure between the DSO and other market players. This paper undertakes the challenge of optimization problem in a smart grid where the operator faces with uncertainty. The results show the effectiveness and applicability of the proposed regulatory framework in the modified IEEE 34- bus test system.