Le cervelet est indispensable à la coordination motrice ainsi qu’au maintien de la posture. Le traitement de l’information dans le cortex cérébelleux repose sur une organisation modulaire : chaque module est impliqué dans le contrôle de muscles spécifiques. Des lésions focales du cervelet entrainent des troubles moteurs dans une région précise du corps, conduisant à des pathologies telles que l’ataxie. Ce travail vise à comprendre comment les modules cérébelleux traitent l’information sensorimotrice, communiquent entre eux et leur implication dans la coordination motrice chez la souris. Des approches optiques et électrophysiologiques ont permis d’établir les cartes de connexions synaptiques entre différents modules. L’étude du développement de ces cartes a démontré que la mise en place des synapses entre des modules distants coïncide avec l’émergence de la locomotion. L’emploi de modèles de perturbation de la locomotion a démontré que les cartes synaptiques sont réorganisées suite à l’adaptation de la coordination motrice. Ce projet apporte de nouvelles hypothèses quant au contrôle de la coordination motrice en conditions normales et pathologiques. / The cerebellum is essential for motor coordination and to learn new motor skills. In the cerebellar cortex, information processing is based on a modular organization: each module is involved in the control of specific motor units. Localized lesions of the cerebellum impair coordinated movements in only one part of the body and lead to movement disorders like ataxia. This project aims to understand how cerebellar modules communicate, process incoming information and how they relate to coordinated movements in mice. We combine optical and electrophysiological approaches in vitro in order to determine the functional synaptic maps between different modules. The development of these maps revealed that the establishment of connections between distant modules coincide with the appearance of motor coordination in mice. Using models of motor alteration, we showed that synaptic maps are reorganized following motor adaptation. The results bring new hypotheses about the control of motor coordination in normal and pathological conditions. Future directions will be to assess how a specific activation of identified modules may compensate for motor impairments.

Noncommutative geometry has over the past four of decades grown into a rich field of study. Novel ideas and concepts are rapidly being developed, and a notable application of the theory outside of pure mathematics is quantum theory. This thesis will focus on a derivation-based approach to noncommutative geometry using the framework of real calculi, which is a rather direct approach to the subject. Due to their direct nature, real calculi are useful when studying classical concepts in Riemannian geometry and how they may be generalized to a noncommutative setting. This thesis aims to shed light on algebraic aspects of real calculi by introducing a concept of morphisms of real calculi, which enables the study of real calculi on a structural level. In particular, real calculi over matrix algebras are discussed both from an algebraic and a geometric perspective.Morphisms are also interpreted geometrically, giving a way to develop a noncommutative theory of embeddings. As an example, the noncommutative torus is minimally embedded into the noncommutative 3-sphere. / Ickekommutativ geometri har under de senaste fyra decennierna blivit ett etablerat forskningsområde inom matematiken. Nya idéer och koncept utvecklas i snabb takt, och en viktig fysikalisk tillämpning av teorin är inom kvantteorin. Denna avhandling kommer att fokusera på ett derivationsbaserat tillvägagångssätt inom ickekommutativ geometri där ramverket real calculi används, vilket är ett relativt direkt sätt att studera ämnet på. Eftersom analogin mellan real calculi och klassisk Riemanngeometri är intuitivt klar så är real calculi användbara när man undersöker hur klassiska koncept inom Riemanngeometri kan generaliseras till en ickekommutativ kontext. Denna avhandling ämnar att klargöra vissa algebraiska aspekter av real calculi genom att introducera morfismer för dessa, vilket möjliggör studiet av real calculi på en strukturell nivå. I synnerhet diskuteras real calculi över matrisalgebror från både ett algebraiskt och ett geometriskt perspektiv. Morfismer tolkas även geometriskt, vilket leder till en ickekommutativ teori för inbäddningar. Som ett exempel blir den ickekommutativa torusen minimalt inbäddad i den ickekommutativa 3-sfären.

No description available.

The work reported in this dissertation is intended to propose, analyze and demonstrate a technology for a high temperature integrated power electronics module, for high temperature (e.g those over 200oC) applications involving high density and low stress. To achieve this goal, this study has examined some existing packaging approaches, such as wire-bond interconnects and solder die-attach, flip-chip and pressure contacts. Based on the survey, a high temperature, multilayer 3-D packaging technology in the form of an Embedded Chip Module (ECM) is proposed to realize a lower stress distribution in a mechanically balanced structure with double-sided metallization layers and material CTE match in the structure. Thermal and thermo-mechanical analysis on an ECM is then used to demonstrate the benefits on the cooling system, and to study the material and structure for reducing the thermally induced mechanical stress. In the thermal analysis, the high temperature ECM shows the ability to handle a power density up to 284 W/in3 with a heat spreader only 2.1x2.1x0.2cm under forced convection. The study proves that the cooling system can be reduced by 76% by using a high temperature module in a room temperature environment. Furthermore, six proposed structures are compared using thermo-mechanical analysis, in order to obtain an optimal structure with a uniform low stress distribution. Since pure Mo cannot be electroplated, the low CTE metal Cr is proposed as the stress buffering material to be used in the flat metallization layers for a fully symmetrical ECM structure. Therefore, a chip area stress as low as 126MPa is attained. In the fabrication process, the high temperature material glass and a ceramic adhesive are applied as the insulating and sealing layers. Particularly, the Cr stress buffering layer is successfully electroplated in the high temperature ECM by means of the hard chrome plating process. The flat metallization layer is accomplished by using a combined structure with Cr and Cu metallization layers. The experimental evaluations, including the electrical and thermal characteristics of the ECM, have been part of in the study. The forward and reverse characteristics of the ECM are presented up to 250oC, indicating proper device functionality. The study on the reverse characteristics of the ECM indicates that the large leakage current at high temperature is not due to the package surrounding the chip, but chiefly caused by the Schottky junction and the chip passivation layer. Finally, steady-state and transient measurements are conducted in terms of the thermal measurements. The steady-state thermal measurement is used to demonstrate the cooling system reduction. To obtain the thermal parameters of the different layers in the high temperature ECM, the transient thermal measurement is applied to a single chip ECM based on the temperature cooling-down curve measurement. / Ph. D.

This thesis concerns two topics. The first topic, that is related to the Dedekind-Mertens Lemma, the notion of the so-called content algebra, is discussed in chapter 2. Let $R$ be a commutative ring with identity and $M$ be a unitary $R$-module and $c$ the function from $M$ to the ideals of $R$ defined by $c(x) = \cap \lbrace I \colon I \text{~is an ideal of~} R \text{~and~} x \in IM \rbrace $. $M$ is said to be a \textit{content} $R$-module if $x \in c(x)M $, for all $x \in M$. The $R$-algebra $B$ is called a \textit{content} $R$-algebra, if it is a faithfully flat and content $R$-module and it satisfies the Dedekind-Mertens content formula. In chapter 2, it is proved that in content extensions, minimal primes extend to minimal primes, and zero-divisors of a content algebra over a ring which has Property (A) or whose set of zero-divisors is a finite union of prime ideals are discussed. The preservation of diameter of zero-divisor graph under content extensions is also examined. Gaussian and Armendariz algebras and localization of content algebras at the multiplicatively closed set $S^ \prime = \lbrace f \in B \colon c(f) = R \rbrace$ are considered as well. In chapter 3, the second topic of the thesis, that is about the grade of the zero-divisor modules, is discussed. Let $R$ be a commutative ring, $I$ a finitely generated ideal of $R$, and $M$ a zero-divisor $R$-module. It is shown that the $M$-grade of $I$ defined by the Koszul complex is consistent with the definition of $M$-grade of $I$ defined by the length of maximal $M$-sequences in I$. Chapter 1 is a preliminarily chapter and dedicated to the introduction of content modules and also locally Nakayama modules.

The dissertation thesis deals with the design of the concept and implementation of models of electrical power system elements with regard to the potential of the use of computer programs – simulations. The solution of the thesis focuses on the compliance simulations of power-generating modules according to RfG (Requirements for Generators), as a document which setting out the requirements for the connection of power-generating facilities and also focuses on the issue of smart grids and MAS (Multi-Agent Systems) respectively. The framework of the thesis is thus defined by the area of requirements for power-generating modules according to legislative requirements (not only RfG, but also related standards incl. DSC (Distribution System Code), CSN EN 50438 and CSN EN 50549), requirements for agent functionalities and power-generating module abilities to operate in synchronous and island operation, including transitions between them, the process of synchronization (phasing) and communication between the individual elements of the power system.

Modularization is a strategy used by many companies, to help them provide their customers with a high variety of customized products efficiently. This is done through the customization of different independent modules, which are connected by standardized interfaces that are shared throughoutthe entire module variety. Scania, being one of the large companies that provide modular products, has been successfully improving their modularization concepts for many years, and is one of the most iconic companies when it comes to modularization of buses, trucks and engines. But with the increasing need ofelectronics integrated in the vehicles, it is becoming more and more important to modularize the electrical system. There is currently an existing, modularized, product architecture for the electrical system, and Scania wants to know how well modularized it is, as there is no unified way that indicates what is considered to be the better solution.To analyze the current state of the electrical system, a systematic method of modularization was used, which would help answer three important questions: Are the modules well defined? Is there a way to systematically compare alternative solutions? What criteria are more important to focus on? Since there is no unified way of modularization, many modularization methods have been created, and each one has been optimized for a certain purpose. This project compares three different modularization methods and then uses one of the methods which is deemed to be the preferred method to help provide the answers that the company seeks when investigating the modularity of the electrical system. As the electrical system is very complex, and the project has limited amount of resources, it was decided to choose one of the control units as an example, which was the APS (air processing system). The literature study showed that the most rewarding method to use was the MFD (Module Function Deployment), as it provides more information about the product and what criteria the company should focus on. It was then decided to use the relevant steps in MFD to analyze the state of the APS as an example of how this method works. / Modularisering är en strategi som används av många företag, för att hjälpa dem att erbjuda sina kunder en mängd olika anpassade produkter på ett effektivt sätt. Detta görs genom anpassning av olika oberoende moduler, som är kopplade med standardiserade gränssnitt som utnyttjas av alla modulvarianterna. Scania, som är ett av de stora företagen som erbjuder modulariserade produkter, har framgångsrikt förbättrat sina modulariseringskoncept under många år och är ett av de mest ikoniska företagen närdet gäller modularisering av bussar, lastbilar och motorer. Men med det ökande behovet av elektronik integrerad i fordonen blir det allt viktigare att modularisera det elektriska systemet. Det finns för närvarande en befintlig, modulär produktarkitektur för det elektriska systemet, och Scania vill veta hur väl modulariserat det är, eftersom det inte finns något enat sätt som anger vad som anses vara den bättre lösningen. För att analysera det elektriska systemets nuvarande tillstånd, måste en systematisk metod förmodularisering användas, vilket skulle hjälpa till att svara på tre viktiga frågor: Är modulerna väldefinierade? Finns det ett sätt att systematiskt jämföra alternativa lösningar? Vilka kriterier är viktigare att fokusera på? Eftersom det inte finns något enhetligt sätt att modularisera har många modulariseringsmetoder skapats, och var och en har optimerats för ett visst ändamål. I projektet jämförs tre olika modulariseringsmetoder och använder sedan en av de metoder som anses vara den föredragna metoden för att hjälpa till att ge svaren som företaget söker när man undersöker modulariteten hos det elektriska systemet. Eftersom det elektriska systemet är väldigt komplext och projektet har begränsat antal resurser beslutades det att välja en av kontrollenheterna som ett exempel, vilket var APS (luftbehandlingssystem). Litteraturstudien visade att den mest givande metoden att använda var MFD (Module FunctionDeployment), eftersom det ger mer information om produkten och vilka kriterier företaget ska fokusera på. Det bestämdes sedan att använda de relevanta stegen i MFD för att analysera APS tillståndet som ett exempel på hur den här metoden fungerar.

L’excès des particules de LDL dans le sang constitue un facteur de risque majeur dans le développement des maladies cardiovasculaires. Dans ce contexte, nous étudions la protéine PCSK9 qui favorise directement ce facteur de risque. Cette protéine est sécrétée en majorité au niveau du foie par les hépatocytes et possède la capacité de reconnaître et de lier le récepteur LDLR. Le rôle premier de ce dernier est d’éliminer les particules de LDL circulant dans le plasma. Ainsi, lorsque la PCSK9 forme un complexe avec le LDLR et l’amène à la dégradation, la conséquence directe de la diminution des ces récepteurs est une accumulation malsaine des particules LDL dans le plasma. L’importante implication de la PCSK9 dans le métabolisme des lipides nous a menés vers des recherches de caractérisation de cette protéine ainsi que dans l’étude de son mode d’action. La PCSK9 est composée de trois domaines et notre intérêt s’est porté sur l’étude structure-fonction des deux domaines dont la fonction était inconnue, soit le domaine en N-terminal : le prodomaine et de son domaine en C-terminal : CHRD. Le premier article présenté dans cette thèse révèle l’importance d’une région acide (acide aminés 33-58) régulatrice de l’activité de la PCSK9 localisée en N-terminal du prodomaine ainsi que l’effet du pH acide, équivalent à celui des endosomes tardifs, qui accroît la capacité de la PCSK9 à induire la dégradation du LDLR. Le deuxième article dissèque davantage la structure de la PCSK9 et met en lumière la différence des prérequis structurels de la région ‘’Hinge’’ ainsi que du module M2, composant du domaine CHRD, dans la voie intracellulaire et la voie extracellulaire d’activité de la PCSK9. La mutation R434W localisée dans la région ‘’Hinge’’ résulte dans une inhibition totale de l’activité intracellulaire de la PCSK9 tandis que son activité extracellulaire est réduite à ~70%. Contrairement, la perte du module M2 du domaine CHRD est bien tolérée par la PCSK9 lors de son activité intracellulaire mais totalement inhibitrice pour son activité extracellulaire. Le troisième article se distingue en présentant une nouvelle stratégie d’inhibition de l’activité de la PCSK9 en utilisant une chimère composée de la fraction Fc de l’immunoglobuline IgG1 humaine couplée avec le prodomaine de la PCSK9. La protéine fusion Fcpro lie directement la PCSK9, crée un encombrement structurel qui résulte dans une régulation négative l’activité de la PCSK9. En résumé, nous présentons dans cette thèse, trois manuscrits qui apportent une contribution à la connaissance des composantes structurelles de la PCSK9 et leur implication dans le rôle de la protéine en tant que régulateur négatif du LDLR. / Hypercholesterolemia is one of the major risk factors leading to cardiovascular disease. In this context, we focused our study on a protein that directly influences hypercholesterolemia: PCSK9. Since 2003, the coding gene for PCSK9 has been identified as the third locus responsible for familial hypercholesterolemia (FH3). PCSK9 is a protein secreted mostly from the liver by hepatocytes and has the capacity to recognize, bind and direct to degradation the LDLR receptor. The latter is responsible for the elimination the LDL particles from the plasma. The direct consequence of the LDLR degradation induced by PCSK9 is the harmful accumulation of the bad cholesterol in the blood. Since PCSK9 activity has undesirable consequences on lipid metabolism homeostasis, we directed our research to characterize this protein to better understand its mechanism of action. Three domains compose PCSK9 structure and we focused on the ‘’structure-function study’’ of two domains, of which roles were still unknown: the prodomain located at the N-terminal extremity and the CHRD domain at the C-terminus of PCSK9. The first manuscript presented in this thesis brings to light the importance of the acidic N-terminal sequence of the prosegment (amino acids 33-58) and its effect on the activity of PCSK9. It also presents a novel mechanism for fine-tuning the activity of PCSK9, which is enhanced at acidic pHs close to those of late endosomes. The second manuscript dissects further the PCSK9 structure, revealing that the structural requirements of the hinge and the M2 module located in the CHRD domain are not the same for the intracellular and extracellular pathways of PCSK9-induced LDLR degradation. Although the R434W natural mutation in the hinge region is absolutely deleterious for the intracellular activity of PCSK9, it reduces by ~70% the extracellular one. In contrast, the loss of M2 module of the CHRD domain is tolerated for the intracellular activity of PCSK9 but not for the extracellular one. The third manuscript demonstrates for the first time that a chimera containing the prosegment (Fcpro) directly binds PCSK9 and effectively acts as a negative regulator (inhibitor) of its ability to induce LDLR degradation. Our work presents a new strategy to develop such inhibitors by interfering with the structure of PCSK9 and exploiting the properties of the PCSK9 prosegment and the advantage of its fusion to a humanized Fc of IgG1. In summary, the present research data sheds new light on the functional contribution of the prodomain and the CHRD domain of PCSK9.

L’excès des particules de LDL dans le sang constitue un facteur de risque majeur dans le développement des maladies cardiovasculaires. Dans ce contexte, nous étudions la protéine PCSK9 qui favorise directement ce facteur de risque. Cette protéine est sécrétée en majorité au niveau du foie par les hépatocytes et possède la capacité de reconnaître et de lier le récepteur LDLR. Le rôle premier de ce dernier est d’éliminer les particules de LDL circulant dans le plasma. Ainsi, lorsque la PCSK9 forme un complexe avec le LDLR et l’amène à la dégradation, la conséquence directe de la diminution des ces récepteurs est une accumulation malsaine des particules LDL dans le plasma. L’importante implication de la PCSK9 dans le métabolisme des lipides nous a menés vers des recherches de caractérisation de cette protéine ainsi que dans l’étude de son mode d’action. La PCSK9 est composée de trois domaines et notre intérêt s’est porté sur l’étude structure-fonction des deux domaines dont la fonction était inconnue, soit le domaine en N-terminal : le prodomaine et de son domaine en C-terminal : CHRD. Le premier article présenté dans cette thèse révèle l’importance d’une région acide (acide aminés 33-58) régulatrice de l’activité de la PCSK9 localisée en N-terminal du prodomaine ainsi que l’effet du pH acide, équivalent à celui des endosomes tardifs, qui accroît la capacité de la PCSK9 à induire la dégradation du LDLR. Le deuxième article dissèque davantage la structure de la PCSK9 et met en lumière la différence des prérequis structurels de la région ‘’Hinge’’ ainsi que du module M2, composant du domaine CHRD, dans la voie intracellulaire et la voie extracellulaire d’activité de la PCSK9. La mutation R434W localisée dans la région ‘’Hinge’’ résulte dans une inhibition totale de l’activité intracellulaire de la PCSK9 tandis que son activité extracellulaire est réduite à ~70%. Contrairement, la perte du module M2 du domaine CHRD est bien tolérée par la PCSK9 lors de son activité intracellulaire mais totalement inhibitrice pour son activité extracellulaire. Le troisième article se distingue en présentant une nouvelle stratégie d’inhibition de l’activité de la PCSK9 en utilisant une chimère composée de la fraction Fc de l’immunoglobuline IgG1 humaine couplée avec le prodomaine de la PCSK9. La protéine fusion Fcpro lie directement la PCSK9, crée un encombrement structurel qui résulte dans une régulation négative l’activité de la PCSK9. En résumé, nous présentons dans cette thèse, trois manuscrits qui apportent une contribution à la connaissance des composantes structurelles de la PCSK9 et leur implication dans le rôle de la protéine en tant que régulateur négatif du LDLR. / Hypercholesterolemia is one of the major risk factors leading to cardiovascular disease. In this context, we focused our study on a protein that directly influences hypercholesterolemia: PCSK9. Since 2003, the coding gene for PCSK9 has been identified as the third locus responsible for familial hypercholesterolemia (FH3). PCSK9 is a protein secreted mostly from the liver by hepatocytes and has the capacity to recognize, bind and direct to degradation the LDLR receptor. The latter is responsible for the elimination the LDL particles from the plasma. The direct consequence of the LDLR degradation induced by PCSK9 is the harmful accumulation of the bad cholesterol in the blood. Since PCSK9 activity has undesirable consequences on lipid metabolism homeostasis, we directed our research to characterize this protein to better understand its mechanism of action. Three domains compose PCSK9 structure and we focused on the ‘’structure-function study’’ of two domains, of which roles were still unknown: the prodomain located at the N-terminal extremity and the CHRD domain at the C-terminus of PCSK9. The first manuscript presented in this thesis brings to light the importance of the acidic N-terminal sequence of the prosegment (amino acids 33-58) and its effect on the activity of PCSK9. It also presents a novel mechanism for fine-tuning the activity of PCSK9, which is enhanced at acidic pHs close to those of late endosomes. The second manuscript dissects further the PCSK9 structure, revealing that the structural requirements of the hinge and the M2 module located in the CHRD domain are not the same for the intracellular and extracellular pathways of PCSK9-induced LDLR degradation. Although the R434W natural mutation in the hinge region is absolutely deleterious for the intracellular activity of PCSK9, it reduces by ~70% the extracellular one. In contrast, the loss of M2 module of the CHRD domain is tolerated for the intracellular activity of PCSK9 but not for the extracellular one. The third manuscript demonstrates for the first time that a chimera containing the prosegment (Fcpro) directly binds PCSK9 and effectively acts as a negative regulator (inhibitor) of its ability to induce LDLR degradation. Our work presents a new strategy to develop such inhibitors by interfering with the structure of PCSK9 and exploiting the properties of the PCSK9 prosegment and the advantage of its fusion to a humanized Fc of IgG1. In summary, the present research data sheds new light on the functional contribution of the prodomain and the CHRD domain of PCSK9.

L’avion plus électrique demande des modules de puissances de plus en plus performants dans les domaines de la fiabilité et de la maîtrise de la durée de vie restante. Le remplacement des systèmes hydrauliques et pneumatiques par des actionneurs électriques et leurs convertisseurs associés est, aujourd’hui, un moyen efficace de réduire les coûts de maintenance et la consommation de carburant. L’ajout de composantes électriques est également un bon moyen d’augmenter la fiabilité des systèmes. La fiabilité est toujours étudiée à partir de contraintes cycliques accélérées. La tendance actuelle est d’embarquer des fonctions de suivi de l’état de santé dans les modules de puissance pour permettre la prédiction de la durée de vie restante. Cette approche implique des modifications du circuit afin de mettre en place des capteurs et est souvent dédiée à un mode de défaillance en particulier. Cette thèse propose une approche par apprentissage du suivi de l’état de santé de modules de puissance à base de MOSFET en carbure de silicium. Une large étude bibliographique a permis de créer et de réaliser un banc de test instrumenté permettant de mettre en œuvre des défaillances attendues dans les modules de puissance mais aussi d’enregistrer un grand nombre de paramètres électriques au cours de la vie du module. Ces paramètres montrent une évolution au cours du vieillissement du module en fonction des modes de défaillances. Un modèle de réseaux neuronaux s’appuie sur la dérive de ces paramètres pour établir le pronostic de durée de vie restante d’un module de puissance à chaque instant de son utilisation normale / More electrical aircraft requires power modules of higher performances, especially in terms of reliability with a control of lifetime. The replacement of hydraulic and pneumatic systems by electric actuators and their associated converters is the present trend to reduce maintenance cost and fuel consumption. Adding more electric components is also thought as a good way to increase reliability in systems. Reliability is still analysed from accelerated stress cycles. A large volume of data must be obtained in various conditions to assert a pertinent extrapolation of remaining lifetime during operation. A trend is to embed some condition monitoring functions in power modules to help predict the remaining lifetime. This approach is the field of hardware developments with respect to sensors and decorrelation methods but mainly dedicated to one particular failure. This thesis presents a learning approach of silicon carbide MOSFET based power modules condition monitoring. A large literature study has led to the elaboration of a test plan and an instrumented test bench. This test bench allows an accelerated lifespan of power module and an on-line recording of several electrical parameters. These parameters shows a drift according to the power module ageing. A neural network model based on these parameters drifts has been constructed to estimate the remaining useful lifetime of a power module in normal operation