Constituição e transcendência: os casos dos regimes comunitários do entre-guerras

Tede de Doutoramento, na especialidade de Ciências Políticas apresentada à FDUNL

Enhancing and implementing a pairs trading strategy

This paper designs a pairs trading model with the intent to identify existing profitable market opportunities to invest, i.e. traditionally strong correlated stocks that have diverged from its historical norm. It comprises a broad literature review on this strategy whose relevant findings (strategy improvements) are contemplated in the model. The authors combine the statistical results of the model with a backtesting analysis in order to provide guidance on the best investment opportunities.

Ensino de Português como Língua Estrangeira a Alunos Adultos: Prática Pedagógica, Manuais e o Papel do Professor

A língua, nas suas diversas vertentes, tem vindo a ser, desde tempos remotos, alvo de investigação, dada a sua importância como meio de comunicação e de transmissão de pensamento. Nas categorias atribuídas por Cook (2010), a língua tem também uma função social, útil à necessária convivência em comunidade. Esta obrigatória convivência entre povos não é um dado do presente, as constantes invasões, de que nos falam os relatos históricos, permitem-nos constatar a importância da língua nas imposições de poder que uns países exerciam sobre outros. O poder económico é, nos dias de hoje, ditado pela comunicação e informação, resultantes do necessário contacto entre diferentes países. Falar de modernidade implica falar em contágio de culturas, imperativo para a relação dos sujeitos com o meio envolvente. Conceitos como interculturalidade, multilinguismo e multiculturalidade ganham espaço e tornam-se fundamentais para a integração desses indivíduos. O convívio entre pessoas oriundas de diversas partes do mundo é responsável pelo aparecimento de novas necessidades de aprendizagem, muito vocacionadas para o conhecimento de línguas, considerado como um bem essencial. O interesse pelo outro e pela sua língua é extensível ao interesse pela sua cultura. Integrado num universo cada vez maior de aprendentes de português como LE, o presente estudo centra-se num público-alvo muito específico, alunos adultos residentes em Portugal que se encontram a trabalhar em empresas multinacionais, fruto da constante mobilidade a que assistimos atualmente. Sendo esta uma realidade com especificidades que não encontram eco nos estudos empíricos, especialmente dedicados à investigação de estratégias de ensino-aprendizagem de PLE, o trabalho apresentado pretende focar alguns aspetos que possam concorrer para o desenvolvimento teórico em torno desta matéria. Num contexto empresarial, é o professor que se desloca ao local de trabalho dos alunos, onde os mesmos pretendem aprender uma língua estrangeira. A adaptação a estes contextos tem início na observação feita aos alunos, às suas necessidades e características e culmina no contexto físico onde o ensinante exerce a sua atividade. Muitos são os fatores que convergem para o sucesso ou insucesso destas aulas, nas quais o professor tem um papel fundamental. São inúmeras as dúvidas levantadas por si sobre os métodos a utilizar e os materiais a preparar, no sentido de poder melhorar, a cada dia, as suas abordagens pedagógicas e contribuir para o aumento de falantes ativos de português. Não pretendendo assumir-se como uma forma de responder a todas essas questões, o presente estudo debruça-se, essencialmente, sobre o papel do professor em contextos designados como empresariais, aludindo a algumas estratégias a adotar em aula e ao tipo de materiais pedagógicos de que o ensinante se deverá munir, cuja análise é suportada nos resultados obtidos com a aplicação prática de exercícios a alunos adultos, numa ótica de ensino individualizado. Tendo em conta o contexto de aula mencionado, começa-se por fazer uma abordagem teórica à realidade atual marcada pela globalização, seguindo-se a referência a algumas estratégias de aprendizagem em língua estrangeira e à aceção de L1, L2 e LE defendidas por diferentes estudiosos.

Evolutionary dynamics of Chlamydia trachomatis genome and identification of molecular patterns of hypothetical protein coding genes

The obligate intracellular bacterium Chlamydia trachomatis is a human pathogen of major public health significance. Strains can be classified into 15 main serovars (A to L3) that preferentially cause ocular infections (A-C), genital infections (D-K) or lymphogranuloma venereum (LGV) (L1-L3), but the molecular basis behind their distinct tropism, ecological success and pathogenicity is not welldefined. Most chlamydial research demands culture in eukaryotic cell lines, but it is not known if stains become laboratory adapted. By essentially using genomics and transcriptomics, we aimed to investigate the evolutionary patterns underlying the adaptation of C. trachomatis to the different human tissues, given emphasis to the identification of molecular patterns of genes encoding hypothetical proteins, and to understand the adaptive process behind the C. trachomatis in vivo to in vitro transition. Our results highlight a positive selection-driven evolution of C. trachomatis towards nichespecific adaptation, essentially targeting host-interacting proteins, namely effectors and inclusion membrane proteins, where some of them also displayed niche-specific expression patterns. We also identified potential "ocular-specific" pseudogenes, and pointed out the major gene targets of adaptive mutations associated with LGV infections. We further observed that the in vivo-derived genetic makeup of C. trachomatis is not significantly compromised by its long-term laboratory propagation. In opposition, its introduction in vitro has the potential to affect the phenotype, likely yielding virulence attenuation. In fact, we observed a "genital-specific" rampant inactivation of the virulence gene CT135, which may impact the interpretation of data derived from studies requiring culture. Globally, the findings presented in this Ph.D. thesis contribute for the understanding of C.trachomatis adaptive evolution and provides new insights into the biological role of C. trachomatishypothetical proteins. They also launch research questions for future functional studies aiming toclarify the determinants of tissue tropism, virulence or pathogenic dissimilarities among C. trachomatisstrains.

Da intercepção de comunicações, acções encobertas e serviços de informações

The Portuguese Intelligence Services have their operational skills limited due to the grievances caused by the Dictatorship and, in particular, by its political police. With the help of historical elements, and by analyzing current legislation, we demonstrate that such grievances are today unjustified and misplaced, mainly taking into account the Risk Society’s multifaceted threats. Also part of our analysis is the impugnment of the Constitutional Court’s decision nº 413/2015, which pronounced unconstitutional the norm contained in Decree nº 426/XII, of the Republic’s Assembly, article nº 78, nº2, which intended to allow Intelligence Services access to the so-called “metadata”, as well as to tax and banking information. It is our understanding, and we demonstrate it in our dissertation, that should be allowed the access of, not only the above mentioned information, but also the means known as communications interception and undercover operations to the Intelligence Services, as long as properly supervised and inspected.

Avaliação do risco de LMEMSLT : aplicação dos métodos RULA e SI / Florentino , António de Sousa Uva

RESUMO - A frequente insuficiência de informação e até, eventualmente, a presença de elementos cientificamente pouco robustos (ou mesmo hipotéticos) no procedimento de obtenção dos resultados finais (scores) com os diversos métodos de avaliação do risco, julga-se determinar a obtenção de distintos resultados no mesmo posto de trabalho e que interessam analisar. O presente estudo foi efectuado numa empresa da indústria automóvel e pretendeu contribuir para a efectividade do processo de avaliação do risco destas lesões em meio industrial. Utilizaram-se como ponto de partida as classificações de risco em postos de trabalho onde a aplicação do método OCRA — base do projecto de norma Europeu prEN 1005-5 para a estimativa do risco de LMEMSLT (Lesões Musculoesqueléticas do Membro Superior Ligadas ao Trabalho) — identificou níveis de risco moderados e/ou elevados (score OCRA ≥ 16,5). Assim nos postos de trabalho (n = 71) registou-se em vídeo a actividade de trabalho. Analisaram-se os principais factores de risco (postura, força, repetitividade e exposição a vibrações) com uma amostragem de segundo em segundo e aplicaram-se dois métodos: 1) RULA (McAtamney; Corlett, 1993); 2) SI (Moore; Garg, 1995). Dos resultados globais da aplicação dos métodos identificam- se discrepâncias evidentes: o método SI classificou 41 postos de risco elevado e o método RULA classificou apenas 26 postos de risco. Destaque para as divergências entre os postos classificados de risco elevado como, por exemplo: de entre os 41 postos com scores de risco da aplicação do método SI apenas se encontram 12 postos classificados de risco pelo método RULA. Os resultados permitem evidenciar validades preditivas diversas para os factores de risco analisados: 1) situações de aplicação de força (SI = 0,80; RULA = 0,66); 2) presença de posturas extremas (SI = 0,68; RULA = 0,48); 3) repetitividade (SI = 0,35; RULA = 0,43). Conclui-se pela divergência de resultados dos métodos SI e RULA aplicados nos mesmos postos de trabalho que tal situação alerta para a pertinência da utilização de um filtro que permita a identificação dos factores de risco presentes em cada posto de trabalho e que, por consequência, oriente a selecção do método mais indicado ou ainda, em oposição, do método contra-indicado. Este trabalho, como um contributo para uma efectiva identificação e avaliação do risco de LMEMSLT, conduz, no limite, à necessidade de elaboração de uma «grelha» das «grelhas» e de informação mais precisa sobre os métodos e sua aplicação, permitindo, desse modo, uma mais efectiva gestão do risco destas lesões.

Prévention des alcoolisations aiguës a l'adolescence: quel rôle pour le médecin de famille [Prevention of binge drinking in adolescents: do family doctors have a role to play?].

Binge drinking has nearly become the norm for young people and is thus worrying. Although alcohol use in males attracts more media attention, females are also frequently affected. A variety of preventive measures can be proposed: at the individual level by parents, peers and family doctors; at the school and community level, particularly to postpone age of first use and first episode of drunkenness; at the structural level through a policy restricting access to alcohol for young people and increasing its price. Family doctors can play an important role in identifying at risk users and individualising preventive messages to which these young people are exposed in other contexts.

Pathfinding of corticothalamic axons relies on a rendezvous with thalamic projections.

Major outputs of the neocortex are conveyed by corticothalamic axons (CTAs), which form reciprocal connections with thalamocortical axons, and corticosubcerebral axons (CSAs) headed to more caudal parts of the nervous system. Previous findings establish that transcriptional programs define cortical neuron identity and suggest that CTAs and thalamic axons may guide each other, but the mechanisms governing CTA versus CSA pathfinding remain elusive. Here, we show that thalamocortical axons are required to guide pioneer CTAs away from a default CSA-like trajectory. This process relies on a hold in the progression of cortical axons, or waiting period, during which thalamic projections navigate toward cortical axons. At the molecular level, Sema3E/PlexinD1 signaling in pioneer cortical neurons mediates a "waiting signal" required to orchestrate the mandatory meeting with reciprocal thalamic axons. Our study reveals that temporal control of axonal progression contributes to spatial pathfinding of cortical projections and opens perspectives on brain wiring.

Creation of an Age-Adjusted, Dual-Energy X-ray Absorptiometry-Derived Trabecular Bone Score Curve for the Lumbar Spine in Non-Hispanic US White Women.

The trabecular bone score (TBS, Med-Imaps, Pessac, France) is an index of bone microarchitecture texture extracted from anteroposterior dual-energy X-ray absorptiometry images of the spine. Previous studies have documented the ability of TBS of the spine to differentiate between women with and without fractures among age- and areal bone mineral density (aBMD)-matched controls, as well as to predict future fractures. In this cross-sectional analysis of data collected from 3 geographically dispersed facilities in the United States, we investigated age-related changes in the microarchitecture of lumbar vertebrae as assessed by TBS in a cohort of non-Hispanic US white American women. All subjects were 30 yr of age and older and had an L1-L4aBMDZ-score within ±2 SD of the population mean. Individuals were excluded if they had fractures, were on any osteoporosis treatment, or had any illness that would be expected to impact bone metabolism. All data were extracted from Prodigy dual-energy X-ray absorptiometry devices (GE-Lunar, Madison, WI). Cross-calibrations between the 3 participating centers were performed for TBS and aBMD. aBMD and TBS were evaluated for spine L1-L4 but also for all other possible vertebral combinations. To validate the cohort, a comparison between the aBMD normative data of our cohort and US non-Hispanic white Lunar data provided by the manufacturer was performed. A database of 619 non-Hispanic US white women, ages 30-90 yr, was created. aBMD normative data obtained from this cohort were not statistically different from the non-Hispanic US white Lunar normative data provided by the manufacturer (p = 0.30). This outcome thereby indirectly validates our cohort. TBS values at L1-L4 were weakly inversely correlated with body mass index (r = -0.17) and weight (r = -0.16) and not correlated with height. TBS values for all lumbar vertebral combinations decreased significantly with age. There was a linear decrease of 16.0% (-2.47 T-score) in TBS at L1-L4 between 45 and 90 yr of age (vs. -2.34 for aBMD). Microarchitectural loss rate increased after age 65 by 50% (-0.004 to -0.006). Similar results were obtained for other combinations of lumbar vertebra. TBS, an index of bone microarchitectural texture, decreases with advancing age in non-Hispanic US white women. Little change in TBS is observed between ages 30 and 45. Thereafter, a progressive decrease is observed with advancing age. The changes we observed in these American women are similar to that previously reported for a French population of white women (r(2) > 0.99). This reference database will facilitate the use of TBS to assess bone microarchitectural deterioration in clinical practice.

PD-1 is a regulator of NY-ESO-1-specific CD8+ T cell expansion in melanoma patients.

The programmed death 1 (PD-1) receptor is a negative regulator of activated T cells and is up-regulated on exhausted virus-specific CD8(+) T cells in chronically infected mice and humans. Programmed death ligand 1 (PD-L1) is expressed by multiple tumors, and its interaction with PD-1 resulted in tumor escape in experimental models. To investigate the role of PD-1 in impairing spontaneous tumor Ag-specific CD8(+) T cells in melanoma patients, we have examined the effect of PD-1 expression on ex vivo detectable CD8(+) T cells specific to the tumor Ag NY-ESO-1. In contrast to EBV, influenza, or Melan-A/MART-1-specific CD8(+) T cells, NY-ESO-1-specific CD8(+) T cells up-regulated PD-1 expression. PD-1 up-regulation on spontaneous NY-ESO-1-specific CD8(+) T cells occurs along with T cell activation and is not directly associated with an inability to produce cytokines. Importantly, blockade of the PD-1/PD-L1 pathway in combination with prolonged Ag stimulation with PD-L1(+) APCs or melanoma cells augmented the number of cytokine-producing, proliferating, and total NY-ESO-1-specific CD8(+) T cells. Collectively, our findings support the role of PD-1 as a regulator of NY-ESO-1-specific CD8(+) T cell expansion in the context of chronic Ag stimulation. They further support the use of PD-1/PD-L1 pathway blockade in cancer patients to partially restore NY-ESO-1-specific CD8(+) T cell numbers and functions, increasing the likelihood of tumor regression.

Pathogen-induced hatching and population-specific life-history response to water-borne cues in brown trout (Salmo trutta)

Hatching is an important niche shift, and embryos in a wide range of taxa can either accelerate or delay this life-history switch in order to avoid stage-specific risks. Such behavior can occur in response to stress itself and to chemical cues that allow anticipation of stress. We studied the genetic organization of this phenotypic plasticity and tested whether there are differences among populations and across environments in order to learn more about the evolutionary potential of stress-induced hatching. As a study species, we chose the brown trout (Salmo trutta; Salmonidae). Gametes were collected from five natural populations (within one river network) and used for full-factorial in vitro fertilizations. The resulting embryos were either directly infected with Pseudomonas fluorescens or were exposed to waterborne cues from P. fluorescens-infected conspecifics. We found that direct inoculation with P. fluorescens increased embryonic mortality and induced hatching in all host populations. Exposure to waterborne cues revealed population-specific responses. We found significant additive genetic variation for hatching time, and genetic variation in trait plasticity. In conclusion, hatching is induced in response to infection and can be affected by waterborne cues of infection, but populations and families differ in their reaction to the latter.

Glycogen synthase 2 is a novel target gene of peroxisome proliferator-activated receptors.

Glycogen synthase 2 (Gys-2) is the ratelimiting enzyme in the storage of glycogen in liver and adipose tissue, yet little is known about regulation of Gys-2 transcription. The peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in the regulation of lipid and glucose metabolism and might be hypothesized to govern glycogen synthesis as well. Here, we show that Gys-2 is a direct target gene of PPARalpha, PPARbeta/delta and PPARgamma. Expression of Gys-2 is significantly reduced in adipose tissue of PPARalpha-/-, PPARbeta/delta-/- and PPARgamma+/- mice. Furthermore, synthetic PPARbeta/delta, and gamma agonists markedly up-regulate Gys-2 mRNA and protein expression in mouse 3T3-L1 adipocytes. In liver, PPARalpha deletion leads to decreased glycogen levels in the refed state, which is paralleled by decreased expression of Gys-2 in fasted and refed state. Two putative PPAR response elements (PPREs) were identified in the mouse Gys-2 gene: one in the upstream promoter (DR-1prom) and one in intron 1 (DR-1int). It is shown that DR-1int is the response element for PPARs, while DR-1prom is the response element for Hepatic Nuclear Factor 4 alpha (HNF4alpha). In adipose tissue, which does not express HNF4alpha, DR-1prom is occupied by PPARbeta/delta and PPARgamma, yet binding does not translate into transcriptional activation of Gys-2. Overall, we conclude that mouse Gys-2 is a novel PPAR target gene and that transactivation by PPARs and HNF4alpha is mediated by two distinct response elements.

The G0/G1 switch gene 2 is a novel PPAR target gene.

PPARs (peroxisome-proliferator-activated receptors) alpha, beta/delta and gamma are a group of transcription factors that are involved in numerous processes, including lipid metabolism and adipogenesis. By comparing liver mRNAs of wild-type and PPARalpha-null mice using microarrays, a novel putative target gene of PPARalpha, G0S2 (G0/G1 switch gene 2), was identified. Hepatic expression of G0S2 was up-regulated by fasting and by the PPARalpha agonist Wy14643 in a PPARalpha-dependent manner. Surprisingly, the G0S2 mRNA level was highest in brown and white adipose tissue and was greatly up-regulated during mouse 3T3-L1 and human SGBS (Simpson-Golabi-Behmel syndrome) adipogenesis. Transactivation, gel shift and chromatin immunoprecipitation assays indicated that G0S2 is a direct PPARgamma and probable PPARalpha target gene with a functional PPRE (PPAR-responsive element) in its promoter. Up-regulation of G0S2 mRNA seemed to be specific for adipogenesis, and was not observed during osteogenesis or myogenesis. In 3T3-L1 fibroblasts, expression of G0S2 was associated with growth arrest, which is required for 3T3-L1 adipogenesis. Together, these data indicate that G0S2 is a novel target gene of PPARs that may be involved in adipocyte differentiation.

Biblia sacra, pars.

Avec prologues. Evang. Matthaei (2), Marci (45v), Lucae (72v), Johannis (116) ; Actus Apost. (148v) ; Apocalypsis (186v) ; VII Epist. canon. (205) ; XIV Epist. Pauli (222). F. 1v Addition : Ezechiel, XXXV, 1-5 et Jeremias, IV, 7. F. 305 Calendrier de Florence, avec des additions (dans le sens dominicain).

Collective learning within nursing clinical groups /

This qualitative study examined collective learning within nursing clinical groups. Specifically, it explored the influence of the individual on the group and the impact of the group on the individual. The study was organized using the concepts from Debbie Kilgore's theory of collective learning (1999). The sample consisted of 1 8 second-year university nursing students and 3 clinical instructors. Data were collected via individual interviews with each participant and researcher's observations during a group conference. The interviews were tape-recorded, transcribed, and analyzed using key concepts from Kilgore's framework. Several interesting findings emerged. Overall, it appeared that individual components and group components contributed to the quality and quantity of collective learning that occurred in the groups. Individually, each person's past group experiences, personality, culture, and gender influenced how that individual acted in the group, their roles, and how much influence they had over group decisions. Moreover, the situation which seemed to cause the greatest sense of helplessness and loss of control was when one of their group members was breaking a norm. They were unable to deal with such situations constructively. Also, the amount of sense of worthiness (respect) and sense of agency (control) the member felt within the group had an impact on the person's role in group decisions. Finally, it seemed that students felt more connected with their peers within the clinical setting when they were close with them on a personal and social level. With respect to the group elements, it seemed that the instructors' values and way of being were instrumental in shaping the group's identity. In group 2, there were clear examples of group consciousness and the students' need to go along with the majority viewpoint, even when it was contrary to their own beliefs. Finally, the common goal of passing clinical and dealing with the fears of being in the clinical setting brought solidarity among the group members, and there seemed to be a high level of positive interdependence among them. From the discussion and analysis of the findings, recommendations were given on how to improve the learning within clinical groups.