Este trabalho de mestrado apresenta um estudo de Grades Computacionais e Simulações Distribuídas sobre a técnica MRIP. A partir deste estudo foi possível propor e implementar o protótipo de uma ferramenta para Gerenciamento de Experimento em Ambiente de Grade, denominada Grid Experiments Manager - GEM, organizada de forma modular podendo ser usada como um programa ou integrada com outro software, podendo ser expansível para vários middlewares de Grades Computacionais. Com a implementação também foi possível avaliar o desempenho de simulações sequenciais com aquelas executadas em cluster e em uma Grade Computacional de teste, sendo construído um benchmark que possibilitou repetir a mesma carga de trabalho para os sistemas sobre avaliação. Com os testes foi possível verificar um ganho alto no tempo de execução, quando comparadas as execuções sequenciais e em cluster, obteve-se eficiência em torno de 197% para simulações com tempo de execução baixo e 239% para aquelas com tempo de execução maior; na comparação das execuções em cluster e em grade, obteve-se os valores para eficiência de 98% e 105%, para simulações pequenas e grandes, respectivamente / This master\'s thesis presents a study of Grid Computing and Distributed Simulations using the MRIP approach. From this study was possible to design and implement the prototype of a tool for Management of Experiments in Grid Environment, called Grid Experiments Manager - GEM, which is organized in a modular way and can be used as a program or be integrated with another piece of software, being expansible to varius middlewares of Computational Grids. With its implementation was also possible to evaluate the performance of sequencial simulations executed in clusters and a Computational testbed Grid, also being implemented a benchmark which allowed repeat the same workload at the systems in evaluation. A high gain turnaround of the executions was infered with those results. When compared Sequential and Cluster executions, the eficiency was about of 197% for thin time of execution and 239% for those bigger in execution; when compared Cluster and Grid executions, the eficiency was about of 98% and 105% for thin and bigger simulations, repectivelly

Les ganglions de la base (GB) sont un ensemble de noyaux sous-corticaux impliqués dans les fonctions motrices, mnésiques et cognitives. Le globus pallidus externe (GPe) est un noyau GABAergique, qui tient la place de structure relais entre le striatum et le noyau sous-thalamique au sein du réseau des GB. Les changements de mode et de fréquence de décharge des neurones du GPe sont connus pour être les signatures électro-physiologiques des maladies de Parkinson (MP) et de Huntington (MH). Dans la MP, où les concentrations de GABA extracellulaires sont anormalement élevées dans le GPe, il est admis que la voie striato-pallidale (STR-GPe) est hyperactive, ce qui contribue à l’hypoactivité des neurones pallidaux. A l’inverse dans la MH, il est admis que l’hyperactivité des neurones du GPe est due à la dégénérescence de la voie STR-GPe levant la principale influence inhibitrice du GPe. Cependant, les mécanismes moléculaires impliqués dans ces changements d’activité pallidale sont encore peu connus. Nous avons donc entrepris des expériences de biologie moléculaire, d’immunohistochimie et d’électrophysiologie sur tranches, afin de mieux caractériser l’origine des modifications de transmission GABAergique conduisant aux changements d’activité électro-physiologique des neurones du GPe dans ces deux pathologies à l’aide de modèles animaux. Mes principaux résultats montrent l’apparition d’une inhibition tonique dans les neurones du GPe due à un déficit de recapture du GABA dans la MP et une réduction précoce de la transmission synaptique GABAergique dans la MH. Ces résultats suggèrent que les altérations de la transmission GABAergique contribuent à la physiopathologie de la MP et la MH. / The basal ganglia (BG) are a group of sub-cortical nuclei involved in motor, memory and cognitive functions. In the BG, the GABAergic external globus pallidus (GPe) holds a position of relay nucleus between the striatum (STR) and the sub thalamic nucleus within the indirect pathway of the BG. Modifications of rate and pattern of activity of this nucleus are known to be the electrophysiological signatures of Parkinson’s (PD) and Huntington’s diseases (HD). In PD, hyperactivity of the striato-pallidal (STR-GPe) pathway is thought to be responsible for the increase of the extracellular GABAergic concentrations in the GPe and participate to the hypoactivity of pallidal neurons observed in experimental Parkinsonism. In contrast, during HD, it is recognized that the hyperactivity of GPe neurons is due to the degeneration of striato-pallidal neurons and thus to the reduction of the main source of pallidal GABAergic inhibition. However, the molecular mechanisms involved in these modifications of pallidal activity are not well characterized. Therefore, using PD and HD animal models, the 6-OHDA rodents and the R6-1 transgenic mice respectively, we have performed molecular biology, immunohistochemistry and electrophysiological in vitro experiments in order to better understand the origin of GABAergic transmission alterations leading to changes in electrophysiological activity of GPe neurons into these two pathologies. My main results show the apparition of a tonic GABAergic inhibition due to a deficit of GABA uptake in PD and a early stage reduction of GABAergic synaptic transmission in HD. Altogether, these results suggest that alterations of GABAergic transmission contribute to the pathophysiology of PD and HD.

Les ganglions de la base (GB) forment une boucle complexe avec le cortex et le thalamus qui est impliquée dans la sélection de l’action et le contrôle du mouvement. Les activités oscillatoires synchronisées dans le réseau des GB ont été proposées comme pouvant jouer un rôle essentiel dans la coordination du flux de l’information au sein de ces circuits neuronaux. Ainsi, leur dérégulation dans le temps et l’espace pourrait devenir pathologique. Dans la maladie de Parkinson (MP), l’expression anormalement élevée d’oscillations neuronales comprises dans les gammes de fréquences beta (β, 10-30 Hz) serait la cause des déficits moteurs (akinétique et bradykinétique) de cette maladie. Cependant, les réseaux neuronaux à l’origine des oscillations β et l’implication physiopathologique de celles-ci restent encore inconnus. Le noyau sous-thalamique (NST) est un carrefour anatomique des GB situé au centre de réseaux potentiellement impliqués dans l’émergence de ces états hyper-synchronisés. L’objectif de cette thèse était de déterminer le rôle causal des principales entrées du NST (i.e. le cortex moteur, le globus pallidus, et le noyau parafasciculaire du thalamus) dans le maintien et la propagation des oscillations β. Pour cela, nous avons développé des approches de manipulation optogénétique combinées à des enregistrements électrophysiologiques in vivo dans un modèle rongeur de la MP. L’ensemble de nos travaux démontre la contribution respective des différents circuits neuronaux interrogés et souligne l’importance du globus pallidus dans le contrôle de la propagation et du maintien des oscillations β dans l’ensemble de la boucle des GB. / The basal-ganglia (BG) form a complex loop with the cortex and the thalamus that is involved in action selection and movement control. Synchronized oscillatory activities in basal-ganglia neuronal circuits have been proposed to play a key role in coordinating information flow within this neuronal network. If synchronized oscillatory activities are important for normal motor function, their dysregulation in space and time could be pathological. Indeed, in Parkinson’s disease (PD), many studies have reported an abnormal increase in the expression level of neuronal oscillations contain in the beta (β) frequency range (15-30 Hz). These abnormal β oscillations have been correlated with two mains symptoms of PD: akinesia/bradykinesia. However, which BG neuronal circuits generate those abnormal β oscillations, and whether they play a causal role in PD motor dysfunction is not known. The subthalamic nucleus (STN) is a key nucleus in BG that receives converging inputs from the motor cortex, the parafascicular thalamic nucleus and the globus pallidus. Here, we used a rat model of PD combined with in vivo electrophysiological recordings and optogenetic silencing to investigate how selective manipulation of STN inputs causally influence BG network dynamic. Our data highlight the causal role of the globus pallidus in the generation and propagation mechanisms of abnormal β-oscillations.

Este trabalho de mestrado apresenta um estudo de Grades Computacionais e Simulações Distribuídas sobre a técnica MRIP. A partir deste estudo foi possível propor e implementar o protótipo de uma ferramenta para Gerenciamento de Experimento em Ambiente de Grade, denominada Grid Experiments Manager - GEM, organizada de forma modular podendo ser usada como um programa ou integrada com outro software, podendo ser expansível para vários middlewares de Grades Computacionais. Com a implementação também foi possível avaliar o desempenho de simulações sequenciais com aquelas executadas em cluster e em uma Grade Computacional de teste, sendo construído um benchmark que possibilitou repetir a mesma carga de trabalho para os sistemas sobre avaliação. Com os testes foi possível verificar um ganho alto no tempo de execução, quando comparadas as execuções sequenciais e em cluster, obteve-se eficiência em torno de 197% para simulações com tempo de execução baixo e 239% para aquelas com tempo de execução maior; na comparação das execuções em cluster e em grade, obteve-se os valores para eficiência de 98% e 105%, para simulações pequenas e grandes, respectivamente / This master\'s thesis presents a study of Grid Computing and Distributed Simulations using the MRIP approach. From this study was possible to design and implement the prototype of a tool for Management of Experiments in Grid Environment, called Grid Experiments Manager - GEM, which is organized in a modular way and can be used as a program or be integrated with another piece of software, being expansible to varius middlewares of Computational Grids. With its implementation was also possible to evaluate the performance of sequencial simulations executed in clusters and a Computational testbed Grid, also being implemented a benchmark which allowed repeat the same workload at the systems in evaluation. A high gain turnaround of the executions was infered with those results. When compared Sequential and Cluster executions, the eficiency was about of 197% for thin time of execution and 239% for those bigger in execution; when compared Cluster and Grid executions, the eficiency was about of 98% and 105% for thin and bigger simulations, repectivelly

Quantification of blood fraction (fblood), blood oxygenation (S<img src="http://onlinelibrary.wiley.com/store/10.1002/jbio.201200055/asset/equation/tex2gif-inf-2.gif?v=1&amp;t=h70man4a&amp;s=4a6d004ec608a2a6ec8e8597f73bdb6be30286e8" />), melanin, lipofuscin and oxidised and reduced Cytochrome aa 3 and c was done from diffuse reflectance spectra captured in cortex, white matter, globus pallidus internus (GPi) and subthalamus during stereotactic implantations of 29 deep brain stimulation (DBS) electrodes with the aim of investigating whether the chromophores can give physiological information about the targets for DBS. Double-sided Mann-Whitney U -tests showed more lipofuscin in GPi compared to white matter and subthalamus (p &lt; 0.05). Compared to the other structures, fbloodwas significantly higher in cortex (p &lt; 0.05) and S<img src="http://onlinelibrary.wiley.com/store/10.1002/jbio.201200055/asset/equation/tex2gif-inf-4.gif?v=1&amp;t=h70man4c&amp;s=855c70105e88a292de25618487573dfc7d30e08a" /> lower in GPi (p &lt; 0.05). Median values and range for fblood were 1.0 [0.2–6.0]% in the cortex, 0.3 [0.1–8.2]% in white matter, 0.2 [0.1–0.8]% in the GPi and 0.2 [0.1–11.7]% in the subthalamus. Corresponding values for S<img src="http://onlinelibrary.wiley.com/store/10.1002/jbio.201200055/asset/equation/tex2gif-inf-6.gif?v=1&amp;t=h70man4e&amp;s=151ec25bee7270bcfc2292e70d6f4aea18348dbc" /> was 20 [0–81]% in the cortex, 29 [0–78]% in white matter, 0 [0–0]% in the GPi and 0 [0–92]% in the subthalamus. In conclusion, the measurements indicate very low oxygenation and blood volume for DBS patients, especially in the GPi. It would be of great interest to investigate whether this is due to the disease, the normal situation or an artefact of doing invasive measurements.

No description available.

This diploma thesis elaborates on the customer behavior on the Czech grocery market. The emphasis is particularly put on the customers' reaction to the special offer flyers. This research paper describes the real special offer price campaigns of the retailer Globus and analyses the customer behavior that is caused by these special offer prices. Furthermore this thesis also develops the concept of better reaction to such a customer behavior. By applying this concept, better and more effective realization of special offer price campaigns could be generated.

No description available.

La stimulation cérébrale profonde (SCP) du globus pallidus interne (GPi) est une technique neurochirurgicale établie pour le traitement des mouvements anormaux. Malgré l'effet bénéfique de la SCP du GPi chez les patients porteurs d'un syndrome dystono-dyskinétique (SDD) primaire généralisé, le degré d'amélioration varie d'un patient à l'autre. Nous proposons un modèle anatomique computationnel basé sur l'IRM stéréotaxique mis en concordance avec un modèle de la distribution électrique du système de SCP qui peut être appliqué en pré- et postopératoire sur des patients déjà implantés. Le but de ce modèle est d'optimiser la localisation de la cible au moment de la planification chirurgicale, permettant une localisation des contacts de l'électrode après la chirurgie et d'ajuster les paramètres électriques en routine clinique et pour chaque patient. Nous avons appliqué le modèle à des données cliniques enregistrées de patients avec un SDD primaire généralisé qui ont été traités par l'implantation bilatérale d'électrode dans le GPi. Cette thèse discute les effets des variables liniques, anatomiques (volume du GPi) et électriques (volume stimulé) sur le score moteur postopératoire de l'échelle Burke-Fahn-Marden Dystonia rating scale (BFMDRS) afin d'identifier les facteurs pouvant prédire le degré d'amélioration. En utilisant ces résultats, nous avons modélisé une nouvelle électrode théorique pour optimiser la délivrance du courant, améliorer le bénéfice thérapeutique, minimiser les effets de bord de la SCP et obtenir une distribution du champ électrique plus homogène.

Gamma oscillations of local field potentials (LFP) in the basal ganglia and thalamus had not been studied during saccades. Eleven patients were studied during deep brain stimulation (DBS); 6 were in the subthalamic nucleus (STN); 3 in the globus pallidus interna (GPi); and 2 in the thalamic ventralis intermedius nucleus (Vim). Patients performed horizontal saccades to visual targets while LFPs from DBS electrodes, scalp electroencephalogram (EEG), and electrooculogram (EOG) were recorded. Wavelet spectrograms were generated and saccade onset and event-related gamma synchronizations (ERS) were compared to baseline without eye motion. ERS were recorded at and after saccade onset in the STN, GPi and Vim, EEGs and EOGs; but were absent during target light illumination without saccades. ERS were symmetric in all DBS contacts and appeared identical in DBS LFPs, frontal EEGs and EOGs. These findings indicate their origin from extraocular muscle spike potentials rather than brain neural activity.