衡量投資組合的稀有事件時，即使稀有事件違約的機率極低，但是卻隱含著高額資產違約時所帶來的重大損失，所以我們必須要精準地評估稀有事件的信用風險。本研究係在估計信用損失分配的尾端機率，模擬的模型包含同質模型與異質模型；然而蒙地卡羅法雖然在風險管理的計算上相當實用，但是估計機率極小的尾端機率時模擬不夠穩定，因此為增進模擬的效率，我們利用Glasserman and Li (Management Science, 51(11),2005)提出的重點取樣法，以及根據Chiang et al. (Joural of Derivatives, 15(2),2007)重點取樣法為基礎做延伸的改良式重點取樣法，兩種方法來對不同的投資組合做模擬，更是將改良式重點取樣法推廣至異質模型做討論，本文亦透過變異數縮減效果來衡量兩種方法的模擬效率。數值結果顯示，比起傳統的蒙地卡羅法，此兩種方法皆能達到變異數縮減，其中在同質模型下的改良式重點取樣法有很好的表現，模擬時間相當省時，而異質模型下的重點取樣法也具有良好的估計效率及模擬的穩定性。 / When measuring portfolio credit risk of rare-event, even though its default probabilities are low, it causes significant losses resulting from a large number of default. Therefore, we have to measure portfolio credit risk of rare-event accurately. In particular, our goal is estimating the tail of loss distribution. Models we simulate are including homogeneous models and heterogeneous models. However, Monte Carlo simulation is useful and widely used computational tool in risk management, but it is unstable especially estimating small tail probabilities. Hence, in order to improve the efficiency of simulation, we use importance sampling proposed by Glasserman and Li (Management Science, 51(11),2005) and modified importance sampling based on importance sampling which proposed by Chiang et al. (2007 Joural of Derivatives, 15(2),). Simulate different portfolios by these two of simulations. On top of that, we extend and discuss the modified importance sampling simulation to heterogeneous model. In this article, we measure efficiency of two simulations by variance reduction. Numerical results show that proposed methods are better than Monte Carlo and achieve variance reduction. In homogeneous model, modified importance sampling has excellent efficiency of estimating and saves time. In heterogeneous model, importance sampling also has great efficiency of estimating and stability.

Diploma thesis named Theme of the city in a contemporary Czech fairy tale story aims to examine various styles of constructions of space and shaping it in a Czech literature for children and youth of last decade. This thesis chooses a theme that is popularized by Pavel Šrut and his novel Lichožrouti - city space. In the first part of this thesis are briefly characterized children proses which were chosen for analysing. Mainly because of showing on which aspects of space are these proses focused and because in the theoretical section are mentioned some of the findings connected to chosen books. The last part of this thesis is focused on analysing the interpretations of different text sections from space point of view. Parts related to each individual proses are organized and divided by locations, in which the books are placed. Taking into account that authors are operating with the space differently based on their intentions and audience, this thesis points out differences and similarities in how the city space and through it its inhabitant and their worries are formed. The thesis indicates how contemporary literature for children and youth is not avoiding serious issues of modern society. Powered by TCPDF (www.tcpdf.org)

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Portfolio selection has a long tradition in financial economics and plays an integral role in investment management. Portfolio selection provides the framework to determine optimal portfolio choice from a universe of available investments. However, the asset weightings from portfolio selection are optimal only if the empirical characteristics of asset returns do not violate the portfolio selection model assumptions. This thesis explores the empirical characteristics of traditional assets and hedge fund returns and examines their effects on the assumptions of linearity-in-the-mean testing and portfolio selection. The encompassing theme of this thesis is the empirical interplay between traditional assets and hedge fund returns. Despite the paucity of hedge fund research, pension funds continue to increase their portfolio allocations to global hedge funds in an effort to pursue higher risk-adjusted returns. This thesis presents three empirical studies which provide positive insights into the relationships between traditional assets and hedge fund returns. The first two empirical studies examine an emerging body of literature which suggests that the relationship between traditional assets and hedge fund returns is non-linear. For mean-variance investors, non-linear asset returns are problematic as they do not satisfy the assumption of linearity required for the covariance matrix in portfolio selection. To examine the linearity assumption as it relates to a mean-variance investor, a hypothesis test approach is employed which investigates the linearity-in-the-mean of traditional assets and hedge funds. The findings from the first two empirical studies reveal that conventional linearity-in-the-mean tests incorrectly conclude that asset returns are nonlinear. We demonstrate that the empirical characteristics of heteroscedasticity and autocorrelation in asset returns are the primary sources of test mis-specification in these linearity-in-the-mean hypothesis tests. To address this problem, an innovative approach is proposed to control heteroscedasticity and autocorrelation in the underlying tests and it is shown that traditional assets and hedge funds are indeed linear-in-the-mean. The third and final study of this thesis explores traditional assets and hedge funds in a portfolio selection framework. Following the theme of the previous two studies, the effects of heteroscedasticity and autocorrelation are examined in the portfolio selection context. The characteristics of serial correlation in bond and hedge fund returns are shown to cause a downward bias in the second sample moment. This thesis proposes two methods to control for this effect and it is shown that autocorrelation induces an overallocation to bonds and hedge funds. Whilst heteroscedasticity cannot be directly examined in portfolio selection, empirical evidence suggests that heteroscedastic events (such as those that occurred in August 1998) translate into the empirical feature known as tail-risk. The effects of tail-risk are examined by comparing the portfolio decisions of mean-variance analysis (MVA) versus mean-conditional value at risk (M-CVaR) investors. The findings reveal that the volatility of returns in a MVA portfolio decreases when hedge funds are included in the investment opportunity set. However, the reduction in the volatility of portfolio returns comes at a cost of undesirable third and fourth moments. Furthermore, it is shown that investors with M-CVaR preferences exhibit a decreasing demand for hedge funds as their aversion for tail-risk increases. The results of the thesis highlight the sensitivities of linearity tests and portfolio selection to the empirical features of heteroscedasticity, autocorrelation and tail-risk. This thesis contributes to the literature by providing refinements to these frameworks which allow improved inferences to be made when hedge funds are examined in linearity and portfolio selection settings.

This thesis is divided into three main parts. In the first, we discuss that, although permutation tests can provide exact control of false positives under the reasonable assumption of exchangeability, there are common examples in which global exchangeability does not hold, such as in experiments with repeated measurements or tests in which subjects are related to each other. To allow permutation inference in such cases, we propose an extension of the well known concept of exchangeability blocks, allowing these to be nested in a hierarchical, multi-level definition. This definition allows permutations that retain the original joint distribution unaltered, thus preserving exchangeability. The null hypothesis is tested using only a subset of all otherwise possible permutations. We do not need to explicitly model the degree of dependence between observations; rather the use of such permutation scheme leaves any dependence intact. The strategy is compatible with heteroscedasticity and can be used with permutations, sign flippings, or both combined. In the second part, we exploit properties of test statistics to obtain accelerations irrespective of generic software or hardware improvements. We compare six different approaches using synthetic and real data, assessing the methods in terms of their error rates, power, agreement with a reference result, and the risk of taking a different decision regarding the rejection of the null hypotheses (known as the resampling risk). In the third part, we investigate and compare the different methods for assessment of cortical volume and area from magnetic resonance images using surface-based methods. Using data from young adults born with very low birth weight and coetaneous controls, we show that instead of volume, the permutation-based non-parametric combination (NPC) of thickness and area is a more sensitive option for studying joint effects on these two quantities, giving equal weight to variation in both, and allowing a better characterisation of biological processes that can affect brain morphology.

Made available in DSpace on 2016-06-02T19:22:05Z (GMT). No. of bitstreams: 1 3116.pdf: 11974848 bytes, checksum: d69698c04f669985473e9e441c532444 (MD5) Previous issue date: 2009-12-11 / Universidade Federal de Sao Carlos / In innate or learned threatening situations, animals display a set of defensive behaviors specie-specific such as autonomic alterations, flight, fight and antinociception. Exposure of mice to open elevated plus-maze (oEPM: four open arms), an aversive situation, elicits antinociception of high magnitude. However, mechanisms involved in this kind of antinociception are not clear yet. This study investigated whether antinociception induced by exposure to an oEPM shows cross-tolerance with morphine (Exp. I and II); is attenuated by repetead exposure to the oEPM (Exp. III); is blocked by systemic treatment with naltrexone (Exp. IV); is prevented by adrenalectomy (Exp. V); persists after animal removal from the oEPM and if there are sex-related differences in this factor (Exp. VI); is mediated by CB1 cannabinoid receptor (Exp. VII). Rats were daily treated with morphine (M, 5 mg/kg, i.p.) or distilled water (DW) for 5 consecutive days (antinociceptive tolerance assessed by the tailflick test). Next day, rats received formalin 2.5% injection (50 μL) into the right hind paw and, after first phase of formalin test, they were treated with M or DW. 25 minutes after formalin injection into the paw, time spent licking the injected paw was recorded for 10 minutes (Exp. 1). Similar procedure was followed in the Experiment II, except that time spent licking the paw was recorded during exposure to the oEPM or enclosed EPM (eEPM: four arms enclosed) in undrugged rats. In Experiment III, nociception was evaluated in rats submitted to 1, 2, 3, 4 or 6 exposures to either eEPM or oEPM (formalin was injected only during the last exposure). Experiment IV investigated the effects of naltrexone (0 and 2.5 mg/kg; s.c.) on nociception during eEPM or oEPM exposure. Nociception was also assessed during the eEPM or oEPM exposure in sham and adrenalectomized rats (exp. V). In experiment VII, rats were treated with vehicle (DMSO 60%) or AM251 (1 mg/kg, i.p., CB1 receptor antagonist). Fifteen minutes later, animals received formalin injection into the paw and, 25 minutes after, they were exposed to the eEPM or oEPM. In experiment VI, male and female rats were exposed to eEPM or oEPM (with no noxious stimulus during exposure) and imediately after they were tested on the hot plate test (52.4 °C). Results showed that antinociception induced by oEPM does not display cross-tolerance to morphine; was not altered for at least 6 exposures to the maze; failed to be reversed by naltrexone; was not prevented by adrenalectomy and was not blocked by AM251. In addition, this antinociception does not persist after animal removal of the apparatus, by contrast, it occurs a hyperalgesia (as assessed by hot plate test), a response that does not depend on sex-related differences. Results suggest that antinociception induced by oEPM: is not mediated by opioid system or CB1 cannabinoid receptors and it is not sensitive to corticosterone. Furthermore, animal removal of aversive environment alters nociceptive response from antinociception to hyperalgesia, a phenomenon that is independent of the gender. / Em situações ameaçadoras de natureza inata ou aprendida, animais exibem um conjunto de comportamentos defensivos espécie-específicos, tais como alterações autonômicas, fuga, luta e antinocicepção. A exposição de camundongos ao labirinto em cruz elevado aberto (LCEa: quatro braços abertos), uma situação aversiva, induz antinocicepção de alta magnitude. Todavia, os mecansimos envolvidos em tal antinocicepção ainda não estão elucidados. O presente estudo investigou se a antinocicepção induzida por exposição ao LCEa: mostra tolerância cruzada a morfina (experimentos I e II); é atenuada por exposição repetida ao LCEa (experimento III); é revertida por tratamento sistêmico com naltrexona (experimento IV); é impedida por adrenalectomia (experimento V); persiste após remoção do animal do LCEa e se há diferenças relacionadas ao sexo neste fator (experimento VI); é mediada pelo receptor canabinóide, CB1 (experimento VII). Ratos foram diariamente tratados com morfina (M, 5 mg/Kg, i.p.) ou água destilada (AD) por 5 dias consecutivos (tolerância antinociceptiva avaliada pelo teste de retirada da cauda). No dia seguinte, os ratos receberam injeção de formalina 2,5% (50L) na pata traseira direita e, após a primeira fase do teste de formalina, foram tratados com M ou AD. Vinte e cinco minutos após injeção de formalina na pata, o tempo de lambidas na pata foi registrado por 10 minutos (experimento I). Procedimento semelhante foi utilizado no experimento II, exceto que o tempo de lambidas na pata foi registrado durante exposição ao LCEa ou LCE fechado (LCEf: quatro braços fechados). No experimento III, nocicepção foi avaliada em ratos submetidos a 1, 2, 3, 4 ou 6 exposições ao LCEf ou LCEa (formalina injetada somente durante a última exposição). O experimento IV investigou os efeitos de naltrexona (2,5 mg/kg; s.c.) sobre a nocicepção durante exposição ao LCEf ou LCEa. A nocicepção também foi avaliada durante exposição ao LCEf ou LCEa em ratos sham operados e adrenalectomizados (experimento V). No experimento VII, os ratos foram tratados com veículo (DMSO 60%) ou AM251 (1 mg/kg, i.p., antagonista CB1). Quinze minutos após, os animais receberam formalina na pata e, após 25 minutos, foram expostos ao LCEf ou LCEa. Já no experimento VI, ratos machos e fêmeas foram expostos ao LCEf ou LCEa, sem nenhum estímulo nociceptivo aplicado durante exposição e, imediatamente após, foram testados no teste da placa quente (52,4 °C). Os resultados mostraram que a antinocicepção induzida pelo LCEa não exibe tolerância cruzada a morfina; não foi alterada por ao menos 6 exposições ao labirinto; mostrou-se insensível à naltrexona; não foi impedida por adrenalectomia e não foi bloqueada por AM251. Ainda, tal antinocicepção não perdura após remoção dos animais do aparelho, pelo contrário, ocorre uma hiperalgesia (conforme avaliado pelo teste de placa quente), uma resposta que independe de diferenças relacionadas ao sexo. Os resultados sugerem que a antinocicepção induzida pelo LCEa: não é mediada por sistema opióide ou receptores canabinóides CB1 e não é sensível a corticosterona. Além disso, a retirada dos animais do ambiente aversivo altera a resposta nociceptiva de antinocicepção para hiperalgesia, um fenômeno que independe do gênero.

Der Mensch erfasst die Umwelt mithilfe seiner Sinnessysteme. Licht macht die physikalische Welt sichtbar und liefert dem visuellen System dadurch wichtige Informationen über unsere Umgebung. Im Straßenverkehr wird die visuelle Wahrnehmung durch die Fahrzeugbeleuchtung unterstützt. Dabei erfüllen Heckleuchten zwei zentrale Funktionen: Zum einen wird die Sichtbarkeit des Fahrzeugs bei Dunkelheit und schlechter Sicht für andere Verkehrsteilnehmer erhöht. Das Schlusslicht übermittelt Informationen über die Anwesenheit eines Fahrzeugs, über den Fahrzeugtyp und über die Fahrzeugbreite. Diese Informationen sind notwendig, um während der Fahrt einen angemessenen Abstand zu einem vorausfahrenden Fahrzeug einschätzen und einhalten zu können. Die zweite zentrale Funktion von Heckleuchten ist die Kommunikation und Interaktion mit dem rückwärtigen Verkehr. Mithilfe von Lichtsignalen der Bremsleuchte und des Fahrtrichtungsanzeigers wird die Aufmerksamkeit auf das vorausfahrende Fahrzeug gelenkt und es werden gezielt Informationen an andere Verkehrsteilnehmer übertragen. So werden Verzögerungen in Längsrichtung, Fahrtrichtungsänderungen und der Hinweis auf eine mögliche Gefahrenquelle durch die Heckleuchte kommuniziert. Für alle Lichtfunktionen gilt, dass die ausgesendeten Signale in jeder Situation gut wahrnehmbar und intuitiv verständlich sein müssen. In dieser Arbeit wurde der mögliche Einfluss verschiedener Heckleuchtenattribute auf den Straßenverkehr untersucht. Eine Unfallanalyse ergab, dass der Großteil der Auffahrunfälle durch ein angemessenes Geschwindigkeits- und Abstandsverhalten sowie eine adäquate Aufmerksamkeitsverteilung vermieden werden könnte. Adaptive Schlusslichtfunktionen weisen das Potenzial auf, bei schlechter Sicht die Erkennbarkeit des Fahrzeugs zu erhöhen, ohne dabei den Hinterherfahrenden zu blenden. In der Literatur finden sich Hinweise darauf, dass die Anbauhöhe und Position von Heckleuchten sowie die Helligkeit des Schlusslichts die Entfernungsschätzung zwischen zwei Fahrzeugen beeinflussen können. Im Rahmen von verkehrspsychologischen Untersuchungen wurde der Einfluss einer adaptiven Helligkeitssteuerung im Schlusslicht auf die Wahrnehmung untersucht. Es zeigte sich, dass eine kontinuierliche Helligkeitsanpassung des Schlusslichts an den Abstand zum Hinterherfahrenden die Entfernungsschätzung nicht beeinflusste. Um die Bedeutung der Gestaltungsform einer Heckleuchte für die Güte der Entfernungsschätzung beurteilen zu können, wurden zwei psychophysikalische Experimente durchgeführt. Diese Experimente zeigten, dass der Abstand zwischen zwei Elementen durch das Hinzufügen einer Verbindungslinie minimal verändert wahrgenommen wurde. Auf Heckleuchten übertragen könnte man daher von einer leichten Überschätzung der Breite des Fahrzeughecks bei verbundenen Schlussleuchten ausgehen. Dies könnte das Abstandsverhalten eines Hinterherfahrenden tendenziell positiv beeinflussen, indem der Fahrer durch diese Wahrnehmungstäuschung den Abstand zum Fahrzeug minimal unterschätzen würde. Da Licht und Bewegung durch ihre Salienz ein großes Potenzial zur Aufmerksamkeitslenkung aufweisen, beschäftigte sich eine weitere Versuchsreihe mit der Wirkung dynamischer Lichtfunktionen. Die Reaktionszeiten auf die Deaktivierung eines Bremslichts konnten durch eine Dynamik im Bremslicht nicht weiter verbessert werden. Die Untersuchung von Dynamiken im Schlusslicht zeigte jedoch, dass in Abhängigkeit bestimmter Umgebungsbedingungen, der Bewegungsart und -geschwindigkeit unterschiedliche Reaktionen hervorgerufen werden können. Durch die Entwicklung salienter und intuitiv verständlicher Lichtfunktionen könnten somit die Kommunikationsmöglichkeiten im Straßenverkehr erweitert und differenziert werden. Die gezielte Steuerung der Aufmerksamkeit durch Heckleuchtenfunktionen in kritischen Situationen kann zur Erhöhung der Verkehrssicherheit führen. Ziel der automobilen Lichtentwicklung ist eine innovative, allgemein akzeptierte und sicherheitsfördernde Heckleuchtengestaltung. Die Arbeit zeigte im Rahmen einer Unfallanalyse und verschiedenen wahrnehmungspsychologischen Experimenten die sicherheitsrelevanten Anforderungen an Heckleuchten auf. Dabei weisen verschiedene Heckleuchtenattribute und -funktionen das Potenzial auf, positiven Einfluss auf die Verkehrssicherheit nehmen zu können. / Humans perceive the world through their senses. Light makes the world visible and provides the visual system with important information about our environment. On the road, visual perception is supported by automotive lighting. Tail lights have two main functions: firstly, they improve the visibility of the vehicle for other road users at night time and in bad weather conditions. The tail light gives information about the presence of a car and the type and width of the vehicle. This information is necessary to assess and keep the appropriate distance to a vehicle in front. The second important function of tail lights is the communication and interaction with the following traffic. The lighting signals of the brake light and the turn signal draw attention to the car in front and specific information can be transmitted to other road users. In this manner, the tail light communicates decelerations in the longitudinal direction, changes in the driving direction and the indication of a possible source of danger. It is essential for every lighting signal that it is detectable in all situations and that it is highly intuitive at any time. This doctoral thesis studied the potential influence of distinct attributes of tail lights on the road traffic. Accident analysis showed that the majority of rear end crashes could be prevented by an appropriate speed and distance behavior as well as an adequate allocation of attention. Adaptive rear lighting shows potential to improve the perceptibility of the vehicle in poor visibility conditions without excessive glare for the following driver. Evidence from literature shows that the distance estimation between two vehicles could be influenced by the mounting height and the position of tail lights as well as by the brightness of the rear position lamp. Psychological experiments showed the influence of adaptive brightness control in the rear position lamp on the human perception. There was no effect on the distance perception by continuous adjustment of the brightness of the rear position lamp to the distance of the following vehicle. To evaluate the importance of the design of a tail light, two psychophysical experiments were conducted. These experiments showed a minimal influence on the perceived distance between two elements by adding a connection line. Transferred to tail lights, this effect implies a small overestimation of the width of the vehicle rear with connected rear position lamps. This could have a small positive effect on the distance behavior of the following driver due to the sensory illusion of slightly underestimating the distance. Because of the high potential for attention control by light and movement, another series of experiments was conducted, to assess the effect of dynamic light functions. Reaction times were not further improved through the use of dynamic functions in the brake light deactivation. However, the use of dynamics in the rear position lamp produced different responses as a function of distinct environment variables, the type of movement and the speed of animation. The development of salient and intuitive understandable light functions points out various communication possibilities for use within road traffic. Capturing the attention of other road users in critical situations through tail light functions could lead to an improvement in road safety. The aim of automotive lighting development is an innovative, universally accepted and safety enhancing tail light design. The dissertation demonstrated the safety requirements for tail lights through accident analysis and different perception experiments. Different attributes and functions of the tail light show the potential to have a positive influence on road safety.

Depuis 1973, l’un des objectifs principaux de la France est la diminution de la consommation des énergies de chauffage des bâtiments du résidentiel et du tertiaire qui représentent plus de 40% de la consommation énergétique totale du pays. Le développement des isolants thermiques a été par conséquent un sujet de recherche qui a abouti à de nouveaux matériaux : les super-isolants thermiques de conductivité thermique inférieure à 25 mW.m-1.K-1. Les aérogels organiques de faible densité de Z-Phe-NH-Napht étudiés au LCPM présentent une structure fibrillaire qui leur confère des propriétés thermiques intéressantes malgré une résistance mécanique faible. Une étude fondamentale de l’organisation supramoléculaire nous a permis d’une part de démontrer l’existence de deux modes d’empilement des molécules organogélatrices : tête-à-tête (monocristaux) et tête-à-queue (gels), caractérisées par une signature infrarouge propre à des pseudo-cycles respectivement en C12 et C10/C14. D’autre part, nous avons étudié le mécanisme de formation séquentiel de ces gels et abouti à un modèle complet d’organisation de la molécule isolée à la fibre basé sur une symétrie hexagonale. En vue d’une commercialisation d’un isolant à base d’aérogel organique, nous avons tout d’abord optimisé le protocole d’obtention des aérogels pour ensuite travailler à l’amélioration des propriétés thermiques et mécaniques. Nous sommes parvenus à un nouvel isolant hydrophobe présentant une conductivité thermique de l’ordre de celles des super-isolants et de bonnes propriétés mécaniques compatibles avec les pré-requis industriels pour une application dans le bâtiment / Since 1973, France's main objective in this domain has been to reduce the consumption of energy in heating residential and industrial buildings, which represents more than 40% of the national consumption. Consequently, the development of heat insulators has been the subject of research which has resulted in new materials: super thermal insulators with a thermal conductivity of less than 25 mW.m-1.K-1. Organic aerogels with a low density of Z-Phe-NH-Napht have been studied at LCPM for the past 10 years. Despite their very weak mechanical resistance they present a fibrillar structure which gives them very interesting thermal properties. A fundamental study of the supermolecular self-assembly allowed us to demonstrate the existence of two stacking methods of gelling molecules: head-to-head (monocrystals) and head-to-tail (gels) which are characterized by a specific infrared signature to the pseudo-cycles respectively on C12 and C10/C14. In addition, we also studied the sequential formation mechanism of these gels which resulted in a full model of their molecular organization from the single molecule to the fiber and based on a hexagonal packing symmetry. In aim of commercializing an insulator made from organic aerogels, we firstly optimized the protocol for obtaining aerogels to then work on improving their thermal and mechanical properties. We created a new hydrophobic insulator which has both a thermal conductivity in the range of the super heat insulators' and good mechanical properties that are compatible with industrial prerequisites for the construction of buildings

Les neurones dopaminergiques (DA) de l’aire tegmentale ventrale (VTA) sont influencés par différents stimuli comme des récompenses naturelles et d’autres stimuli moins physiologiques tels que les drogues d’abus. Ces drogues agissent en détournant les mécanismes d’apprentissage qui sous-tendent normalement la motivation pour des renforçateurs naturels. Les neurones DA, en conditions physiologiques, sont subtilement régulés par une balance entre tonus GABA et glutamatergique. Ils sont soumis à de multiples sources inhibitrices dont le noyau accumbens, les interneurones locaux ou les neurones GABA de la queue de la VTA (tVTA). Le glutamate est également important dans leur modulation. Il contrôle leur activité en bursts, qui est le mode de décharge le plus efficace pour libérer de la dopamine et coder des informations associées à la récompense. Il permet des adaptations synaptiques à long terme qui se sont révélées importantes dans la prise de drogue. La connaissance des facteurs endogènes qui contrôlent l’excitabilité des cellules DA de la VTA est essentielle à la compréhension des processus physiologiques (recherche de plaisir…) mais aussi pathologiques (addiction…). L’objectif de mon travail a été de comprendre les circuits de régulation des neurones DA en conditions physiologiques et lors de l’exposition à la morphine. Dans un premier temps, nous avons étudié les mécanismes de régulation des neurones DA par la formation hippocampique ventrale incluant le subiculum ventral et l’aire CA1 ventrale (vSUB/CA1). Grâce à l’utilisation d’approches d’électrophysiologie in vivo chez le rat anesthésié, nous avons montré que le vSUB/CA1 exerce un contrôle excitateur glutamatergique des neurones DA. Nous avons mis en évidence que cette voie vSUB/CA1-VTA est polysynaptique, faisant intervenir le BNST comme relais. J’ai aussi pu confirmer le rôle fonctionnel de la tVTA en tant que nouvelle structure GABA modulant l’activité des neurones DA, renforçant ainsi l’idée d’une balance entre tonus GABA et glutamatergique régulant les neurones DA in vivo.La deuxième partie de ma thèse a consisté en l’étude des circuits neuronaux à l’origine des effets excitateurs de la morphine sur les neurones DA de la VTA in vivo. L’hypothèse actuelle est que la morphine excite les neurones DA par un mécanisme de désinhibition en inhibant les neurones GABA de la VTA. Grâce à l’utilisation d’approches multiples, nous avons proposé un nouveau circuit expliquant les effets de la morphine. Ces effets sont la conséquence d’une modification de la balance GABA/glutamate par la morphine. Elle se traduit par une diminution du tonus GABA et d’une augmentation du tonus glutamatergique. Enfin, nous avons pu démontrer qu’une seule exposition à la cocaïne augmente l’activité de base des neurones DA. Chez ces animaux, les effets excitateurs de la morphine sont potentialisés confirmant ainsi l’hypothèse que l’amplitude de l’activation des neurones DA par la morphine dépend de leur état d’excitabilité. / Dopaminergic (DA) neurons of the ventral tegmental area (VTA) are influenced by several stimuli such as natural rewards or drugs of abuse. Drugs shunt learning mechanisms which underlie motivation for natural reinforcers. Under physiological conditions, DA neurons are regulated by a balance between GABA and glutamatergic inputs. They receive several inhibitory inputs especially from the nucleus accumbens, VTA local interneurons and GABA neurons of the tail of the VTA (tVTA). Glutamate is also important in modulating DA neuron activity. It controls their bursting activity which is the most efficient way to release dopamine and to encode reward-associated informations. It allows long term synaptic adaptations important for addiction. Knowing how these endogenous factors control VTA DA neuron excitability is essential to understand physiological (search for pleasure…) and pathological (drug addiction…) processes.In the first part of my thesis, we studied the regulation of the VTA by the hippocampal formation including the ventral subiculum and the ventral CA1 area (vSUB/CA1). Using electrophysiological approaches in anesthetized animal, we showed that the vSUB/CA1 controls VTA DA neurons and that this input is glutamatergic. We also demonstrated that the vSUB/CA1-VTA pathway is polysynaptic implicating the BNST as a relay. I also confirmed the inhibitory control of the VTA by tVTA, new GABA input to DA neurons. Thus, in vivo, DA neurons are regulated by a balance between GABA and glutamatergic inputs. The second part of my research consisted in studying the neuronal circuits underlying excitatory effects of morphine on VTA DA neurons in vivo. The actual hypothesis is that morphine excites DA neurons by a disinhibition mechanism inhibiting VTA GABA neurons. Using several approaches (electrophysiological approaches in anesthetized animal, tract-tracing methods), we proposed a new circuitry explaining morphine effects. These excitatory effects result from a modification of the balance between GABA and glutamatergic inputs with a decrease of the GABA tone and an increase of the glutamatergic tone. Finally, we demonstrated that an acute cocaine exposure increases DA neuron activity. In animals exposed to cocaine, morphine excitatory effects are potentiated. This last experiment confirms the hypothesis that the amplitude of morphine-induced activation of VTA DA neurons depends on their excitability state.

The diploma thesis involves the design of certification static strength tests for the newly developed aircraft of the TL-Ultralight company. At the beginning of the work, the theory of aircraft testing is generally discussed with emphasis on static strength tests. Furthermore, an analysis of the requirements of the Czech regulation UL 2 and the German LTF-UL, which represent the certification basis for this aircraft, is performed. The requirements of regulations on the construction of the aircraft (or its individual parts) and the requirements for strength tests are discussed in detail. Based on the regulation and the provided calculation protocols, individual test cases and test plans of the wing, tail surfaces, engine bed, and chassis are calculated and prepared. In the end, the calculation of the rocker system and the basic design of jigs are performed.