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Parkinson's Disease affects more than 1 million people in the United States with 60,000 new cases being diagnosed each year. Currently, there is no cure for Parkinson's Disease, but there are several treatment options available. Currently the most popular surgical option is Deep Brain Stimulation. Microelectrode recording helps identify nuclei as the microelectrode passes through them. While the firing frequencies of the target nuclei are well defined, other nuclei are not. This study will attempt to characterize the Zona Incerta, which is the structure directly above the Subthalamic Nucleus, a target nucleus. Characterization of the firing frequency of the Zona Incerta will help aid Deep Brain Stimulation procedures. Looking at the Interspike Intervals for 25 files showed that the average firing frequency is 11.6Hz. A file recorded in the STN was used for comparison and to validate the methods used. This yielded an average firing frequency of 37.5Hz.

L'hypothalamus latéral (LHA) est impliqué dans un grand nombre de fonctions dont les principales sont la régulation du métabolisme énergétique et des états de vigilance. L'objectif de ce travail est de caractériser les grandes divisions du LHA et d'analyser leur implication dans le cycle veille / sommeil et la prise alimentaire. Une comparaison de la distribution de différents marqueurs hypothalamiques révélés par immunohistochimie ou hybridation in situ a permis de mettre en évidence cinq domaines dans le LHA. L'implication de chacun des domaines dans des conditions expérimentales liées aux états d'éveil ou à la prise alimentaire a été définie à partir de l'expression d'un marqueur d'activation neuronale, la protéine c-Fos. LeLHA antérieur et le LHA tubéral, chacun divisé en deux domaines rostral et caudal, sont composés de neurones localisés de manière diffuse et sont impliqués dans les phénomènes d'activation générale du système nerveux central. Le LHA mamillaire est renommé LHA prémamillaire à partir de l'étude de la distribution des ARNm GAD et préprotachykinine, et est composé de différents noyaux caractérisés par l'expression de marqueurs spécifiques.Parmi eux, les noyaux parasousthalamique (PSTN) et calbindine (CbN) sont activés lors d'exposition à des goûts de valeur hédonique positive. Les analyses hodologiques ont montré que ce complexe nucléaire reçoit des projections CGRP du noyau parabrachial et projette dansle noyau central de l'amygdale. Il est également connecté avec le cortex insulaire. Ces différentes structures sont impliquées dans les circuits de la gustation et de la récompense. Le PSTN et le CbN sont donc intégrés dans différentes voies de régulation du comportement de prise alimentaire. Enfin, les données morpho fonctionnelles obtenues pour le LHA sont mises en relation avec des réseaux impliquant diverses structures cérébrales telles que le télencéphale basal, le thalamus ou le mésencéphale. / The lateral hypothalamic area (LHA) is involved in many functions, but mainly in food intakeor sleep / wake cycle regulation. The aim of this study is to characterize the main regions inthe LHA and to analyze their involvement in the sleep / wake cycle and food intake. Acomparison of the distribution of different hypothalamic markers labeled byimmunohistochemistry or in situ hybridization highlights five domains in the LHA. Theimplication of each domain in different experimental conditions linked to arousal or foodintake is analyzed by studying the expression of the c-Fos protein as a neuronal activationmarker. Neurons in the anterior and tuberal LHA, both divided into rostral and caudaldomains, are distributed in a diffuse way and are activated under arousal conditions. Themammillary LHA, renamed the premammillary LHA on the basis of GAD andpreprotachykinin mRNA expression, is composed of several nuclei characterized by specificmarker expression. Among them, the parasubthalamic nucleus (PSTN) and the calbindinnucleus (CbN) are activated by ingestion of compounds with a positive taste. Theconnectional analysis showed that these two structures receive CGRP projections from theparabrachial nucleus and projects into the central nucleus of the amygdala. The PSTN / CbNcomplex is also connected with the insular cortex. These different structures are known to beinvolved in gustatory and reward circuitries; the PSTN and the CbN are thus integrated innetworks controlling the food intake behavior. Finally, the morphofunctional data obtainedfor the LHA demonstrate that this region is connected to other networks involving variouscerebral structures such as the basal telencephalon, the thalamus or the mesencephalon.

Obsessive compulsive disorder (OCD) is one of the most disabling psychiatric disorder. About 10% of patients with OCD do not respond to pharmacological treatment. However, deep brain stimulation (DBS) has advanced as an alternative treatment. In 2002, two patients who suffered from co-morbidity of Parkinson’s disease (PD) and OCD were treated with DBS for their PD, with DBS-electrodes placed in the subthalamic nucleus (STN). Surprisingly, not only PD symptoms but also OCD symptoms were improved. This was the first time that patients with OCD were treated with DBS in STN and it was found to markedly improve their symptoms. When performing DBS in patients with OCD, as well as for treating PD, several side-effectshave been observed. The side-effects can be both physical and psychological. In this project,the aim is to investigate the efficiency and side-effects of DBS in OCD, correlated with the position of the electrode in, or near, the STN. To address the aim, 10 published reports were analysed. It was found that all electrode positions reported resulted in great improvement of OCD symptoms. In fact, 88% of patients had significant improvement. There was no clear correlation between position of the electrode and number or type of side-effect. However, there was a trend that patients with the electrode placed in associative/limbic STN suffered from more side-effects. In conclusion, this project demonstrates that there might be a correlation between target for electrode stimulation and side-effects. It would be interesting analyse this closer, including additional electrode target areas, but also consider other possible explanations for the variety of side-effects caused by DBS for OCD.

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[pt] Apesar de existir na literatura modelos propostos para gestão de estoques, as premissas consideradas por tais modelos podem inviabilizar suas aplicações. Este trabalho propõe uma metodologia de programação estocástica para reposição e controle de estoques de produto único numa rede logística de duas camadas. O enfoque revisão periódica proposto pode considerar tanto atendimentos à demanda em atraso (backorders) como vendas perdidas (lost sales) sem restrição de pedidos pendentes. Além disso, a fim de alcançar um melhor nível de serviço para o cliente, é introduzida uma regra de rateio proporcional a quantidade faltante do item em estoque no centro de distribuição para atender simultaneamente a demanda de todos os varejistas, a qual é capaz de lidar com as alocações negativas da falta. A periodicidade e o nível alvo da posição dos estoques são determinados através de modelos de programação estocástica de dois estágios e de uma técnica baseada em simulação de Monte Carlo, conhecida como Sample Average Approximation, que levam em conta a natureza incerta dos níveis de demanda pelo item por meio da geração de conjuntos finitos de cenários. Os equivalentes determinísticos são apresentados como modelos de programação não-linear inteira mista e em seguida linearizados. Experimentos numéricos com a metodologia proposta para instâncias do problema geradas aleatoriamente demonstram seu potencial ao obter resultados com erros de aproximadamente 1 por cento. / [en] Although several methods for inventory management are proposed in the literature, the required assumptions can hinder their application in practice. This work proposes a methodology for stock replenishment in two-echelon logistic networks through stochastic programming, considering a single item, periodic review and uncertain demands. The proposed approach is flexible enough to consider backlogs and lost sales cases without limitations on the number of outstanding orders. Also, in order to achieve better customer service, we introduce a variable rationing rule for quantities of the item in short at the distribution center to meet simultaneously all the demands of the retailers, dealing with imbalances or negative allocations of quantities of the item in short. The optimal review periodicity and the target level for inventory position are determined through two-stage stochastic programming models and a Monte Carlo simulation based-technique, known as Sample Average Approximation, which takes into account the uncertain nature of the item demand levels through the generation of finite sets of scenarios. The deterministic equivalent models are presented as mixed-integer non-linear programming models, which are then linearized. Numerical experiments with the proposed approach for instances of the problem randomly generated shows its potential, as the errors of the obtained results are around 1 percent.

[pt] Este trabalho apresenta uma proposta de aceleração da decomposição de Benders aplicada a uma versão mais geral e compacta (menos restrições e variáveis) do modelo de gestão de estoques, otimizado via programação estocástica de dois estágios que considera uma camada, um item, demanda incerta e política de controle (R, S). De maneira a ser possível considerar problemas de grande porte, foram aplicados os métodos L-Shaped tradicional com corte único e a sua forma estendida com múltiplos cortes. Resultados computacionais preliminares mostraram um substancial melhor desempenho computacional do método L-Shaped tradicional em relação à sua forma multi-cut L-Shaped, mesmo o primeiro necessitando de mais iterações para convergir na solução ótima. Tal observação motivou o desenvolvimento de uma nova técnica de aceleração da decomposição de Benders e de um conjunto de desigualdades válidas. Experimentos numéricos mostram que a abordagem proposta de combinar a técnica de aceleração elaborada com as desigualdades válidas desenvolvidas provê significativa redução do tempo computacional necessário para a solução de instâncias de grande porte. / [en] This dissertation presents a speed up proposal for the Benders decomposition applied to a more general and compact version (less constraints and variables) of inventory management model, optimized via two-stage stochastic programming, which considers one layer, one item, uncertain demand and control policy (R, S). In order to be possible to consider large scale problems, the L-Shaped traditional method with single cuts and its extended form with multiple cuts were applied. Preliminary computational results showed a substantially better computational performance of the traditional L-Shaped method in comparison to the multi-cut L-Shaped method, even with the first requiring more iterations to converge on optimum solutions. This observation led to the development of a new technique to accelerate the decomposition of Benders and a set of valid inequalities. Numerical experiments show that the proposed approach of combining the elaborate acceleration technique with the developed valid inequalities, provide significant reduction in the computational time required to solve large scale instances.

Made available in DSpace on 2016-06-02T20:23:15Z (GMT). No. of bitstreams: 1 5832.pdf: 2261692 bytes, checksum: ede99af3ddeae2cf732575bcfea3aea3 (MD5) Previous issue date: 2013-12-18 / Financiadora de Estudos e Projetos / The main goal of this dissertation is to introduce the alternate reality game as a new narrative for multiplatform. By new narratives are understood the forms of storytelling arising from the current development of digital technology; and for multiplatform the variety of means by which the contents of these stories can travel. For this main objective is reached, two main hypotheses are formulated: 1) ARGs are stories for multiple platforms using code-breaking with playful and narrative functions; and 2) they are developed from an intense transtextuality guided by pop mythology that flourished during the twentieth century. Based on this starting point, this thesis will examine two ARGs, Uncertain Zone and Why So Serious?, in a way that it contributes to the hypothesis that Alternate Reality Games are a native narrative form of convergence culture founded on an extensive base of pop culture references. In the chapter dedicated to Uncertain Zone will be listed the various media used during the performance of the ARG, that together with interviews with the developers and testimonials from participants will weave a more descriptive overview of how alternate reality games are composed as multiplatform narratives. In addition, a brief discussion on the playful and narrative functions of the code-breaking in ARGs will be outlined. With Why So Serious? the analysis will focus on the intense transtextuality that alternate reality games establish to what will be called pop mythology in this dissertation and in the relationship between ARGs and market. Incidentally issues related to participatory culture will be raised throughout the text, but without further reflection, since, worth reiterating, the main goal of this thesis is the demonstration of a contemporary narrative form from some elements previously submitted, this form is the alternate reality game. / O principal objetivo da presente dissertação é apresentar o ARG (Alternate Reality Game) como uma nova narrativa para multiplataformas. Por nova narrativa, entendemse as formas de contar histórias decorrentes do desenvolvimento atual da tecnologia digital; e por multiplataforma os variados meios através dos quais os conteúdos dessas histórias podem trafegar. Para que esse objetivo principal seja atingido, duas hipóteses principais serão formuladas: 1) os ARGs são narrativas para múltiplas plataformas que utilizam a quebra de código com função lúdica e narrativa; e 2) são desenvolvidos a partir de uma intensa transtextualidade pautada pela mitologia pop que floresceu durante o século XX. Partindo desse ponto de partida, esta dissertação analisará dois ARGs, Zona Incerta e Why So Serious?, de modo a apresentar as características que corroboram a hipótese de que os Jogos de Realidade Alternada são uma forma narrativa nativa da cultura de convergência fundamentada sobre uma extensa base de referências à cultura pop. No capítulo dedicado ao Zona Incerta serão elencadas as diversas mídias utilizadas durante a realização do ARG, que em conjunto com entrevistas com os realizadores e depoimentos de participantes tecerão um panorama mais descritivo de como os Jogos de Realidade Alternada se compõem enquanto narrativas multiplataformas. Além disso, uma breve discussão sobre o caráter lúdico e narrativo da quebra de código nos ARGs será esboçada. Já com Why So Serious? as análises irão se focar na intensa transtextualidade que os Jogos de Realidade Alternada estabelecem com aquilo que nesta dissertação será chamada de mitologia pop e nas relações que os objetos mantêm com o mercado. Incidentalmente questões relacionadas à cultura participativa serão levantadas por todo o texto, porém sem um maior aprofundamento, uma vez que, vale reiterar, o objetivo principal desta dissertação será a demonstração de uma forma narrativa contemporânea a partir de alguns elementos previamente apresentados, essa forma são os Jogos de Realidade Alternada.