Étude des mécanismes de localisation auditive et de leur plasticité dans le cortex auditif humain

Pouvoir déterminer la provenance des sons est fondamental pour bien interagir avec notre environnement. La localisation auditive est une faculté importante et complexe du système auditif humain. Le cerveau doit décoder le signal acoustique pour en extraire les indices qui lui permettent de localiser une source sonore. Ces indices de localisation auditive dépendent en partie de propriétés morphologiques et environnementales qui ne peuvent être anticipées par l'encodage génétique. Le traitement de ces indices doit donc être ajusté par l'expérience durant la période de développement. À l’âge adulte, la plasticité en localisation auditive existe encore. Cette plasticité a été étudiée au niveau comportemental, mais on ne connaît que très peu ses corrélats et mécanismes neuronaux. La présente recherche avait pour objectif d'examiner cette plasticité, ainsi que les mécanismes d'encodage des indices de localisation auditive, tant sur le plan comportemental, qu'à travers les corrélats neuronaux du comportement observé. Dans les deux premières études, nous avons imposé un décalage perceptif de l’espace auditif horizontal à l’aide de bouchons d’oreille numériques. Nous avons montré que de jeunes adultes peuvent rapidement s’adapter à un décalage perceptif important. Au moyen de l’IRM fonctionnelle haute résolution, nous avons observé des changements de l’activité corticale auditive accompagnant cette adaptation, en termes de latéralisation hémisphérique. Nous avons également pu confirmer l’hypothèse de codage par hémichamp comme représentation de l'espace auditif horizontal. Dans une troisième étude, nous avons modifié l’indice auditif le plus important pour la perception de l’espace vertical à l’aide de moulages en silicone. Nous avons montré que l’adaptation à cette modification n’était suivie d’aucun effet consécutif au retrait des moulages, même lors de la toute première présentation d’un stimulus sonore. Ce résultat concorde avec l’hypothèse d’un mécanisme dit de many-to-one mapping, à travers lequel plusieurs profils spectraux peuvent être associés à une même position spatiale. Dans une quatrième étude, au moyen de l’IRM fonctionnelle et en tirant profit de l’adaptation aux moulages de silicone, nous avons révélé l’encodage de l’élévation sonore dans le cortex auditif humain.

An investigation into the folding and assembly of engineered antibodies and novel antibody formats

Monoclonal antibodies and novel antibody formats are currently one of the principal therapeutic in the biopharmaceutical industry worldwide and are widely used in the treatment of autoimmune diseases and cancer. It is for this reason that the productivity and quality of antibody production requires improvement; specifically investigations into the engineering of antibodies and any issues that may arise from the production of these therapeutics. The work presented in this thesis describes an investigation into the folding and assembly of seven antibodies plus the novel antibody format FabFv. IgG is comprised of two identical HCs and two identical LCs. The folding process of immunoglobulin is controlled by the CH1 domain within the HC. The CH1 domain remains in a disordered state and is sequestered by BiP in the endoplasmic reticulum. Upon the addition of a folded CL domain, BiP is displaced, the CH1 domain is able to fold and the complete IgG protein can then be secreted from the cell. The results presented in this thesis however, have outlined an additional mechanism for the folding of the CH1 domain. We have shown that the CH1 domain is able to fold in the absence of LC resulting in the secretion of HC dimers in a VH dependent manner. The proposed mechanism for the secretion of HC dimers suggests that some VH domains can interact with each other in order to bring the CH1 domains in close proximity to enable folding to occur. As HC dimer secretion is a hindrance in antibody production, this result has highlighted an engineering target to improve antibody yield. Examination of the folding of IgG4 with the variable region A33 has revealed the inability to secrete LC dimers, cleavage of the HC during expression and secretion of HC dimers in the Fab, FabFv and full length forms. The attributes described have also been shown to be variable region dependent. This has introduced a new concept that the variable domain is important in determining the expression and secretion of antibodies and their individual chains. Pulse chase and 2D gel electrophoresis analysis of the novel antibody format FabFv has revealed that the folding and expression of the LC and HC causes multimeric species of FabFv to be secreted, as opposed to the monomeric form which is the desired therapeutic. Our hypothesis is that this process occurs via a LC dependent mechanism. The proposed hypothesis suggests that further engineering to the LC could diminish the formation and secretion of FabFv multimers. The results from these investigations can be applied to increase the productivity of therapeutics and increase the biological understanding of the domain interactions of IgG during folding, assembly and secretion.

Re-conceituando estratégia de marketing sob uma perspectiva luso-brasileira

Estratégias de marketing têm sido importantes para empresas, consumidores e mercados por serem capazes de contornar a histórica dificuldade enfrentada pelo âmbito da estratégia corporativa e pela alta hierarquia em reconhecer diferenças e especificidades dos mercados e consumidores. Apesar disso a literatura dominante argumenta que o advento da era da globalização tornou obsoleto o âmbito da estratégia de marketing por causa do processo de convergência das economias nacionais em torno do modelo de economia liberal de mercado. O principal objetivo deste ensaio é argumentar que acadêmicos do contexto luso-brasileiro – com especial ênfase para pesquisadores do Brasil e de Portugal – devem desafiar a literatura dominante e promover a construção de uma perspectiva lusobrasileira para reconceituar a estratégia de marketing tanto em termos domésticos quanto em termos internacionais. O ensaio mostra que dimensões institucionais e históricas do contexto luso-brasileiro e o boom recente de investimentos estrangeiros feitos por organizações portuguesas no Brasil e por organizações brasileiras em Portugal contrariando o argumento de que o âmbito da estratégia de marketing está obsoleto e que este é importante demais para ser desprezado na era da globalização.

A Visual Analytics Approach to Comparing Cohorts of Event Sequences

Sequences of timestamped events are currently being generated across nearly every domain of data analytics, from e-commerce web logging to electronic health records used by doctors and medical researchers. Every day, this data type is reviewed by humans who apply statistical tests, hoping to learn everything they can about how these processes work, why they break, and how they can be improved upon. To further uncover how these processes work the way they do, researchers often compare two groups, or cohorts, of event sequences to find the differences and similarities between outcomes and processes. With temporal event sequence data, this task is complex because of the variety of ways single events and sequences of events can differ between the two cohorts of records: the structure of the event sequences (e.g., event order, co-occurring events, or frequencies of events), the attributes about the events and records (e.g., gender of a patient), or metrics about the timestamps themselves (e.g., duration of an event). Running statistical tests to cover all these cases and determining which results are significant becomes cumbersome. Current visual analytics tools for comparing groups of event sequences emphasize a purely statistical or purely visual approach for comparison. Visual analytics tools leverage humans' ability to easily see patterns and anomalies that they were not expecting, but is limited by uncertainty in findings. Statistical tools emphasize finding significant differences in the data, but often requires researchers have a concrete question and doesn't facilitate more general exploration of the data. Combining visual analytics tools with statistical methods leverages the benefits of both approaches for quicker and easier insight discovery. Integrating statistics into a visualization tool presents many challenges on the frontend (e.g., displaying the results of many different metrics concisely) and in the backend (e.g., scalability challenges with running various metrics on multi-dimensional data at once). I begin by exploring the problem of comparing cohorts of event sequences and understanding the questions that analysts commonly ask in this task. From there, I demonstrate that combining automated statistics with an interactive user interface amplifies the benefits of both types of tools, thereby enabling analysts to conduct quicker and easier data exploration, hypothesis generation, and insight discovery. The direct contributions of this dissertation are: (1) a taxonomy of metrics for comparing cohorts of temporal event sequences, (2) a statistical framework for exploratory data analysis with a method I refer to as high-volume hypothesis testing (HVHT), (3) a family of visualizations and guidelines for interaction techniques that are useful for understanding and parsing the results, and (4) a user study, five long-term case studies, and five short-term case studies which demonstrate the utility and impact of these methods in various domains: four in the medical domain, one in web log analysis, two in education, and one each in social networks, sports analytics, and security. My dissertation contributes an understanding of how cohorts of temporal event sequences are commonly compared and the difficulties associated with applying and parsing the results of these metrics. It also contributes a set of visualizations, algorithms, and design guidelines for balancing automated statistics with user-driven analysis to guide users to significant, distinguishing features between cohorts. This work opens avenues for future research in comparing two or more groups of temporal event sequences, opening traditional machine learning and data mining techniques to user interaction, and extending the principles found in this dissertation to data types beyond temporal event sequences.

Vidas à margem : relações de gênero, etnia e espaço na narrativa afro-brasileira contemporânea

Dissertação (mestrado)—Universidade de Brasília, Instituto de Letras, Programa de Pós-Graduação em Literatura, 2016.

Política e planeamento linguístico da língua portuguesa na Namíbia : perspetivas de futuro

A importância da língua portuguesa, idioma representado nos cinco continentes, é uma realidade incontornável. Este prestígio linguístico é visível no aumento do número de falantes ao longo das últimas décadas. Hoje em dia, o português é usado como língua de comunicação de aproximadamente 250 milhões de pessoas. Para além da representatividade cultural, técnica, tecnológica e económica que possui nos países de língua oficial portuguesa, esta ocorrência é impulsionada também por países pertencentes a outros espaços linguísticos que se sentem atraídos economicamente por economias de países de língua portuguesa. Nesta dissertação apresenta-se o caso da Namíbia, país situado na África subsaarina que mantém relações político-económicas com países de língua portuguesa e que, por isso mesmo, integrou o português como língua curricular estrangeira no sistema de ensino. Questiona-se os motivos pelos quais o ensino formal de português tem cada vez mais aprendentes, isto é, pretende saber-se se a motivação dos alunos adultos está de facto relacionada com razões estritamente económicas ou não. Para o caso foi elaborado um questionário, aplicado em todos os locais onde o português é aprendido como PLE. Seguindo a mesma linha de dúvidas, pretendia-se também aferir se a política linguística que estava a ser implementada na Namíbia se estava a consolidar ou, se pelo contrário, não se estava a solidificar, e, assim sendo, deixar pistas no sentido de encaminhar o planeamento linguístico para as reais necessidades comunicativas dos informantes e potenciais falantes de português.

An expert model approach to assess the potential of non-wood forest products for forest owners

Mestrado em Engenharia Florestal e dos Recursos Naturais - Instituto Superior de Agronomia - UL

(N)um lugar ao sol: contributos do turismo para as dinâmicas criativas e para a atração da classe criativa no Algarve

Tese de Doutoramento, Turismo, Faculdade de Economia, Universidade do Algarve, 2016

Traitement de la transidentité dans "Laurence Anyways"

Notre travail s'articule autour du film Laurence Anyways (2012), de Xavier Dolan. Nous y explorons la représentation du personnage de femme transgenre. Dans un premier temps, nous procédons à une analyse filmique axée sur la transidentité, puis à une analyse de réception à deux volets : celle dans la presse, mais aussi celle des personnes trans. Enfin, nous précisons la démarche de recherche-création ayant mené à la réalisation d'un documentaire où figurent deux personnes trans qui témoignent de leurs rapports à la représentation des personnes trans dans les médias audiovisuels contemporains.

DIFFUSE-INTERFACE FIELD APPROACH TO MODELING SELF-ASSEMBLY OF HETEROGENEOUS COLLOIDAL SYSTEMS AND RELATED DIPOLE-DIPOLE INTERACTION PHENOMENA

Colloid self-assembly under external control is a new route to fabrication of advanced materials with novel microstructures and appealing functionalities. The kinetic processes of colloidal self-assembly have attracted great interests also because they are similar to many atomic level kinetic processes of materials. In the past decades, rapid technological progresses have been achieved on producing shape-anisotropic, patchy, core-shell structured particles and particles with electric/magnetic charges/dipoles, which greatly enriched the self-assembled structures. Multi-phase carrier liquids offer new route to controlling colloidal self-assembly. Therefore, heterogeneity is the essential characteristics of colloid system, while so far there still lacks a model that is able to efficiently incorporate these possible heterogeneities. This thesis is mainly devoted to development of a model and computational study on the complex colloid system through a diffuse-interface field approach (DIFA), recently developed by Wang et al. This meso-scale model is able to describe arbitrary particle shape and arbitrary charge/dipole distribution on the surface or body of particles. Within the framework of DIFA, a Gibbs-Duhem-type formula is introduced to treat Laplace pressure in multi-liquid-phase colloidal system and it obeys Young-Laplace equation. The model is thus capable to quantitatively study important capillarity related phenomena. Extensive computer simulations are performed to study the fundamental behavior of heterogeneous colloidal system. The role of Laplace pressure is revealed in determining the mechanical equilibrium of shape-anisotropic particles at fluid interfaces. In particular, it is found that the Laplace pressure plays a critical role in maintaining the stability of capillary bridges between close particles, which sheds light on a novel route to in situ firming compact but fragile colloidal microstructures via capillary bridges. Simulation results also show that competition between like-charge repulsion, dipole-dipole interaction and Brownian motion dictates the degree of aggregation of heterogeneously charged particles. Assembly and alignment of particles with magnetic dipoles under external field is studied. Finally, extended studies on the role of dipole-dipole interaction are performed for ferromagnetic and ferroelectric domain phenomena. The results reveal that the internal field generated by dipoles competes with external field to determine the dipole-domain evolution in ferroic materials.

Traitement de la transidentité dans "Laurence Anyways"

Notre travail s'articule autour du film Laurence Anyways (2012), de Xavier Dolan. Nous y explorons la représentation du personnage de femme transgenre. Dans un premier temps, nous procédons à une analyse filmique axée sur la transidentité, puis à une analyse de réception à deux volets : celle dans la presse, mais aussi celle des personnes trans. Enfin, nous précisons la démarche de recherche-création ayant mené à la réalisation d'un documentaire où figurent deux personnes trans qui témoignent de leurs rapports à la représentation des personnes trans dans les médias audiovisuels contemporains.