Made available in DSpace on 2016-06-02T19:06:01Z (GMT). No. of bitstreams: 1 4845.pdf: 2916613 bytes, checksum: aa64366fdbe9befa8f14547fa4545763 (MD5) Previous issue date: 2012-08-18 / Multi-Electrode Array, MEA, was developed more than thirty years ago. This planar device of multiple microelectrodes has been used to detect local electric potential variations created by the ion movement through the protein channels that traverses the cell membranes in the near neighborhood. MEA offers the possibility of non invasive registering of the cell and their network s activities, allowing to know how the neurons start to connect through the synapses forming a network and generating spontaneous electrophysiological activities. In order to understand the neural network dynamics in face of the spontaneous activities and its evolution in dissociated hippocampal cell cultures, important properties in the synaptic plasticity, in this work it is proposed the analysis of the evolution and modeling of the hippocampal cell cultures in MEA using the theory of Partial Directed Coherence and Complex Networks. There were used the electrophysiological records obtained using MEA60 System, of the dissociated neurons of 18 days old Wistar rat embyo, in an experiment denoted as 371, realized at the University of Genoa, Italy. As the results obtained using the Partial Directed Coherence approach, it was verified that the method is capable to detect neuronal connectivity in the neuron cultures using MEA, even with the noisy signals. It was also verified that different time delays between signals during application of the PDC method do not affect directly on the results of the causality. PDC allowed to show that in MEA the amount of direct connections resulted is less than the amount of indirect connections, through the microelectrodes. This can indicate that the neurons prefer to communicate through existing connections than creating new connections. It was also observed that it is easier to lose direct connections than indirect connections between microelectrodes through the time. Through the experiments it can be observed that the culture in 25 DIV (Days In Vitro) developed more amount of connections between neighboring electrodes, with less overall connections than the culture in 46 DIV, that had more overall connections with less neighborhood connections. Since one of the PDC features is the directionality detection between connections, it was observed direction changes through the connections through the time, even though we do not know the physiological meaning of these changes in the cognitive process. It was also observed that the established connections do not follow random patterns, showing an indicative of a free scale network, although we used small statistical measures to characterize the networks. / Há mais de 30 anos a Matriz de microeletrodos (Multi-Electrode Array,MEA) foi desenvolvida. Este dispositivo planar de múltiplos microeletrodos tem permitido detectar as variações do potencial elétrico local que são criadas pelo movimento de íons através dos canais de proteínas que atravessam as membranas das células neuronais em sua vizinhança imediata. A MEA oferece a possibilidade de gravação não-invasiva da atividade das células e de redes de células, permitindo-nos conhecer como os neurônios se comunicam através de sinapses formando uma rede e disparando atividades eletrofisiológicas espontâneas evocadas. No sentido de poder entender melhor a dinâmica das redes neurais em termos de atividades espontâneas e sua evolução em culturas de células hipocampais dissociadas, que são as propriedades mais importantes na plasticidade sináptica, neste trabalho é proposta a análise da evolução e o modelamento de culturas de células hipocampais na MEA usando a teoria de Coerência Parcial Direcionada (PDC) e de Redes Complexas. Foram usados os registros eletrofisiológicos obtidos usando o sistema MEA60, de neurônios dissociados de embrião de rato Wistar, de 18 dias de vida em um experimento denotado como 371, realizado na Universidade de Gênova, Itália. Como resultados obtidos ao utilizar o método de Coerência Parcial Direcionada, verificou-se que o método é capaz de detectar conectividade neuronal nas culturas de neurônios da MEA, mesmo com sinais com presença de ruído. Também verificou-se que tempos de atraso diferentes na aplicação do PDC não tem uma influência direta nos resultados de causalidade. O PDC permitiu mostrar que na MEA a quantidade de conexões diretas estabelecidas foram sempre em menor quantidade do que as conexões indiretas, através de caminhos. Isso pode ser um indicativo de que os neurônios preferem estabelecer comunicações usando caminhos ja existentes do que criando novas conexões. Também observou-se que com o passar do tempo é mais fácil se perderem conexões diretas do que conexões intermediárias entre neurônios. Através dos experimentos realizados pode se obervar que a cultura no 25 DIV (dias in vitro) desenvolveu maior quantidade de conexões com nós vizinhos, possuindo menos conexões em total, do que a rede no 46 DIV que teve maior quantidade de conexões total mas menor quantidade de conexões com nós vizinhos. Como uma das características do PDC é a deteção da direcionalidade nas conexões, observouse mudanças no sentido das conexões ao longo do registro, embora não saibamos ainda o significado fisiológico dessas mudanças em processos cognoscitivos. Também observou-se que as conexões estabelecidas não seguiam um padrão aleatório, encontrando-se um indicativo de um comportamento de redes livres de escala, embora não possamos afirmar isso por ter utilizado poucas medidas estatísticas para caracterizar as redes.

Les épilepsies acquises se déclarent après un processus graduel appelé épileptogenèse. Bien que cliniquement silencieux, ce processus implique des modifications fonctionnelles observables notamment par électroencéphalographie. Cette thèse vise i) à identifier des marqueurs électrophysiologiques apparaissant au cours de l’épileptogenèse, et ii) à comprendre les modifications physiopathologiques sous-jacentes responsables de ces marqueurs et de leur évolution temporelle. Dans un premier temps, nous avons, dans un modèle d’épilepsie partielle chez la souris, monitoré des signaux électrophysiologiques intracérébraux pendant la mise en place de la maladie. Nous avons observé dans ces signaux expérimentaux, l’émergence d’événements transitoires pathologiques appelés pointes épileptiques. Nous avons développé des méthodes de traitement du signal pour détecter et caractériser automatiquement ces événements. Ainsi, nous avons pu mettre en évidence certains changements dans la forme des pointes épileptiques au cours de l’épileptogenèse ; en particulier l’apparition et l’augmentation d’une onde qui suit la pointe épileptique. Une hypothèse défendue dans ces travaux est que ces changements morphologiques peuvent constituer des marqueurs de l’épileptogenèse dans ce modèle animal. Dans un second temps, afin d’interpréter ces modifications électrophysiologiques en termes de processus neurophysiologiques sous-jacents, nous avons implémenté un modèle biomathématique, physiologiquement argumenté, capable de simuler des pointes épileptiques. Formellement, ce modèle est un système dynamique non linéaire qui reproduit les interactions synaptiques (excitatrices et inhibitrices) dans une population de neurones. Une analyse de sensibilité de ce modèle a permis de mettre en évidence le rôle critique de certains paramètres de connectivité dans la morphologie des pointes. Nos résultats montrent en effet, qu’une diminution de l’inhibition GABAergique entraîne un accroissement de l’onde dans les pointes épileptiques. À partir du modèle théorique, nous avons pu ainsi émettre des hypothèses sur les modifications opérant au cours du processus d’épileptogenèse. Ces hypothèses ont pu être en partie vérifiées expérimentalement en bloquant artificiellement l’inhibition GABAergique, dans le modèle in vivo chez la souris, et dans un modèle in vitro chez le rat. En conclusion, ce travail de thèse fournit, dans un modèle animal, un biomarqueur électrophysiologique de l’épileptogenèse et tente d’expliquer, grâce à une modélisation biomathématique, les processus neurophysiologiques sous-jacents qu’il reflète. / Acquired epilepsies occur after a process called epileptogenesis. Although clinically silent, this process involves some functional modifications which can be observed by electroencephalography. The objectives of this thesis are i) to identify electrophysiological markers occurring during epileptogenesis, and ii) to understand which underlying pathophysiological modifications are responsible for these markers and their evolution. Firstly, using an in vivo experimental mouse model of partial epilepsy, we have monitored intracranial electrophysiological signals during epileptogenesis. We observed the emergence of pathological transient events called epileptic spikes. We have developed signal processing methods in order to automatically detect and characterize these events. Hence, we observed and quantified morphological changes of epileptic spikes during epileptogenesis. In particular, we noticed the emergence and the increase of a wave which directly follows the spike component. In this work, we defend the hypothesis that these morphological modifications can constitute markers of the epileptogenesis process in this animal model of epilepsy. Secondly, in order to interpret these electrophysiological modifications in terms of underlying pathophysiological processes, we have implemented a computational model able to simulate epileptic spikes. This neural mass model is a neurophysiologically-plausible mesoscopic representation of synaptic interactions (excitation and inhibition) in the hippocampus. Based on a sensitivity analysis of model parameters, we were able to determine some connectivity parameters that play a key role in the morphology of simulated epileptic spikes. In particular, our results show that a diminution of GABAergic inhibition leads to an increase of the aforementioned wave. Thus, using this theoretical model, we defined some hypotheses about pathophysiological modifications occurring during the epileptogenesis process. One of these hypotheses has been confirmed in blocking GABAa receptors in the in vivo mouse model, as well as in an in vitro model (rat, organotypic slices). In summary, based on the shape features of epileptic spikes, we devised an electrophysiological biomarker of epileptogenesis observed in a mouse model but useful in Human studies as well. Moreover, a computational modeling approach has permitted to suggest which pathophysiological processes might underlie this biomarker.

No description available.

This thesis deals with DC motor control. Main goal was design and realization of DC motor controler module with feedback. The first part dwells on methods for DC motor control and HW design of control module. The second part describes development of software for the module, testing and sums up results.

Much of the impetus for this research can be attributed to Kenneth W. Hinchcliff, who has studied exercise-induced pulmonary haemorrhage (EIPH) extensively. This thesis focused on EIPH in Thoroughbred racehorses competing in South Africa. Using tracheobronchoscopy, the prevalence and severity of EIPH and the association with racing performance was determined. Thereafter, the prevalence of other respiratory tract disorders and their association with racing performance is reported. This is followed by a study assessing interobserver variability using grading systems in the detection of respiratory tract disorders. Finally, there is a report on the immunopathogenesis of EIPH. Using tracheobronchoscopy after racing, the prevalence and severity of EIPH was assessed in 1,005 racehorses competing at high altitude (> 1,400 meters above sea level) and at sea level in a racing jurisdiction that does not allow the use of furosemide and nasal dilator strips. The prevalence and severity of EIPH was affected by altitude as racing at sea level was associated with a higher prevalence and greater severity of EIPH. Results also suggested that EIPH was associated with superior performance in South African Thoroughbred racehorses. Upper and lower respiratory tract disorders identified following tracheobronchoscopic examination included left arytenoid asymmetry, left laryngeal hemiplegia, epiglottic deformity, epiglottic entrapment, subepiglottic cysts, dorsal displacement of the soft palate, pharyngeal lymphoid hyperplasia (PLH), laryngeal and tracheal dirt, tracheal mucous (TM), tracheal stenosis and tracheal cartilage ring spikes in Thoroughbred racehorses after racing. Overall, there was a low prevalence of grade 2 and 3 arytenoid cartilage asymmetry, left laryngeal hemiplegia, epiglottic entrapment, subepiglottic cysts and epiglottic deformity, while more severe grades of PLH, laryngeal debris, tracheal debris, TM and tracheal cartilage ring spikes had a higher prevalence. An association with sex was identified as tracheal cartilage ring spikes occurred more often in male racehorses. Superior racing performance was identified in racehorses with grade 3 tracheal mucous and tracheal cartilage ring spikes. Endoscopic grading of EIPH, PLH, arytenoid cartilage movement (ACM), and TM was performed by 3 observers that were blinded to each racehorse’s identity and race day performance using previously established grading criteria. Excellent interobserver reliability was seen using the EIPH grading system, while the weighted kappa for PLH, ACM and TM was lower. The study demonstrated sufficient reliability for the use of the EIPH, PLH, ACM and TM grading systems in racehorses competing in South Africa. The study concluded that tracheobronchoscopy seemed to be a practical screening technique that may have prognosticative validity and clinical dependability and that would allow safe and quick assessment of the respiratory tract of a large number of racehorses in field conditions. Venous blood was collected from 10 horses in each EIPH grade classification (grade 0 to 4) following tracheobronchoscopic examinations for the determination of the presence and severity of EIPH. Following RNA isolation and cDNA synthesis, real-time PCR was used to detect equine cytokine-specific mRNA for interleukin (IL) -1, -6, -10, interferon (INF) -ã, and tumor necrosis factor (TNF) -á. Results of this study indicated that increased IL-6, and -10 mRNA production was associated with more severe forms of EIPH. Also, there was greater expression of IL-6 mRNA at sea level and TNF-á mRNA at high altitude. This study concluded that although it was unclear whether the inflammatory response observed in the study was due to pre-existing pulmonary inflammation or as a direct consequence of pulmonary bleeding, the study demonstrated a systemic correlation to pulmonary inflammation. The research reported in this thesis has contributed substantially to the determination of the prevalence, severity and affect on racing performance of respiratory tract disorders in Thoroughbred racehorses competing in South Africa. Also, determination of an association between EIPH and inflammation at a molecular level may assist future researchers in anti-cytokine therapies which may help reduce the prevalence and severity of EIPH. / Thesis (PHD)--University of Pretoria, 2007. / Companion Animal Clinical Studies / unrestricted

Cette thèse traite de problèmes de dépendance entre processus stochastiques en temps continu. Ces résultats sont appliqués à la modélisation et à la gestion des risques des marchés de l'électricité.Dans une première partie, de nouvelles copules sont établies pour modéliser la dépendance entre deux mouvements Browniens et contrôler la distribution de leur différence. On montre que la classe des copules admissibles pour les Browniens contient des copules asymétriques. Avec ces copules, la fonction de survie de la différence des deux Browniens est plus élevée dans sa partie positive qu'avec une dépendance gaussienne. Les résultats sont appliqués à la modélisation jointe des prix de l'électricité et d'autres commodités énergétiques. Dans une seconde partie, nous considérons un processus stochastique observé de manière discrète et défini par la somme d'une semi-martingale continue et d'un processus de Poisson composé avec retour à la moyenne. Une procédure d'estimation pour le paramètre de retour à la moyenne est proposée lorsque celui-ci est élevé dans un cadre de statistique haute fréquence en horizon fini. Ces résultats sont utilisés pour la modélisation des pics dans les prix de l'électricité.Dans une troisième partie, on considère un processus de Poisson doublement stochastique dont l'intensité stochastique est une fonction d'une semi-martingale continue. Pour estimer cette fonction, un estimateur à polynômes locaux est utilisé et une méthode de sélection de la fenêtre est proposée menant à une inégalité oracle. Un test est proposé pour déterminer si la fonction d'intensité appartient à une certaine famille paramétrique. Grâce à ces résultats, on modélise la dépendance entre l'intensité des pics de prix de l'électricité et de facteurs exogènes tels que la production éolienne. / In this thesis, we study some dependence modeling problems between continuous time stochastic processes. These results are applied to the modeling and risk management of electricity markets. In a first part, we propose new copulae to model the dependence between two Brownian motions and to control the distribution of their difference. We show that the class of admissible copulae for the Brownian motions contains asymmetric copulae. These copulae allow for the survival function of the difference between two Brownian motions to have higher value in the right tail than in the Gaussian copula case. Results are applied to the joint modeling of electricity and other energy commodity prices. In a second part, we consider a stochastic process which is a sum of a continuous semimartingale and a mean reverting compound Poisson process and which is discretely observed. An estimation procedure is proposed for the mean reversion parameter of the Poisson process in a high frequency framework with finite time horizon, assuming this parameter is large. Results are applied to the modeling of the spikes in electricity prices time series. In a third part, we consider a doubly stochastic Poisson process with stochastic intensity function of a continuous semimartingale. A local polynomial estimator is considered in order to infer the intensity function and a method is given to select the optimal bandwidth. An oracle inequality is derived. Furthermore, a test is proposed in order to determine if the intensity function belongs to some parametrical family. Using these results, we model the dependence between the intensity of electricity spikes and exogenous factors such as the wind production.