Biomaterials are designed to improve impaired healing of injured tissue. To accomplish better cell integration, we suggest to coat biomaterial surfaces with bio-functional proteins. Here, a mussel-derived surface-binding peptide is used and coupled to CXCL12 (stromal cell-derived factor 1α), a chemokine that activates CXCR4 and consequently recruits tissue-specific stem and progenitor cells. CXCL12 variants with either non-releasable or protease-mediated-release properties were designed and compared. Whereas CXCL12 was stabilized at the N-terminus for protease resistance, a C-terminal linker was designed that allowed for specific cleavage-mediated release by matrix metalloproteinase 9 and 2, since both enzymes are frequently found in wound fluid. These surface adhesive CXCL12 derivatives were produced by expressed protein ligation. Functionality of the modified chemokines was assessed by inositol phosphate accumulation and cell migration assays. Increased migration of keratinocytes and primary mesenchymal stem cells was demonstrated. Immobilization and release were studied for bioresorbable PCL-co-LC scaffolds, and accelerated wound closure was demonstrated in an ex vivo wound healing assay on porcine skin grafts. After 24 h, a significantly improved CXCL12-specific growth stimulation of the epithelial tips was already observed. The presented data display a successful application of protein-coated biomaterials for skin regeneration.

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Tesis por compendio / [EN] This thesis addresses to the current status of lightning protection, focusing on the external protection with emphasis on the process of interception. Under this approach, three pillars are studied due to their obvious interest in the evaluation and practical application of lightning protection during the first phase, the lightning interception. Those pillars are: Laboratory Tests Field Tests Lightning Protection Models. These three points can be treated individually; nevertheless, they are interrelated, not only for the technical field they belong to, all together pose an evolution in the magnitude of the electric discharge, starting by the study of the electric discharge in laboratory in order to understand the processes that involves its behavior. It is no possible reproduce the whole event of lightning in laboratory, so field tests are essential to characterize empirically the most important parameters of lightning in natural conditions. The measurements made in natural conditions, are employed to fundament some protection models, furthermore with the statistics, it is possible the definition of the lightning protection levels which determines the practical application of the lightning protection. The fact of encompassing different points in a technical field is imposed because this thesis has been made in a company specialized in lightning protection, which implies a need of knowledge applied to all the points concerning its scope. The main contributions of the thesis are collected in each of the chapters and in the proposals made in them, opening new lines of work on which to base a set of techniques and practices that could complement the ones currently applied. After an introductory chapter, it is treated the main core of the Thesis, composed by the chapters 3, 4 and 5 where the contributions, published by the author are exposed. In the chapter 3 it is made a revision of the laboratory tests studying the physical processes associated to the electric discharge. At this point and after the review, the author focuses on the U50 parameter (amplitude of a pulse voltage in a determined configuration whose application involves a 50% of probability to get a disruptive discharge) using a tool based on neural networks with a configuration of multilayer perceptron (MLP) with which the level of predictability of an individual pulse is evaluated with different configurations, data input and time windows, as indicative of the influence of a variable in the process of generation and interception of the electric arc. Regarding the field tests, its application typically involves monitoring high-rise structures, the use of rockets for artificial lightning triggering or lightning detection networks. At this point the different measurement strategies are evaluated and a new point of view that could be used to obtain reliable statistics in a short period of time is introduced, which resulted in a paper. The dissertation also introduces a methodology for continuous evaluation of lightning protection systems, comparing the performance of the installed systems and considering also the protection model used for the design of the installation. About protection models, in a brief introduction the author discusses the different models of protection by extending information about those standardized which, despite their lacks, remain widely used today. After evaluating the current context under standardized lightning protection, it is indicated that one way to complement physically the protection models is the inclusion of methods whose application is consistent with standardized lightning protection models. In this line the author presents a contribution embodied in an article. / [ES] En esta Tesis se aborda el estado actual de la protección contra el rayo centrándose en la protección externa y concretamente en el proceso de intercepción. Bajo este planteamiento, se estudian tres pilares fundamentales que presentan un evidente interés para la evaluación y aplicación de la protección contra el rayo en la fase de intercepción: Los ensayos de laboratorio Los estudios en campo Los modelos de protección Estos tres puntos pueden tratarse de forma individual, no obstante están relacionados entre sí, no sólo por el campo de la técnica al que pertenecen, sino también porque juntos plantean una evolución en la magnitud de la descarga eléctrica, comenzando con la descarga eléctrica en laboratorio para comprender los procesos que gobiernan su comportamiento. Al no ser posible la completa reproducción del fenómeno del rayo en laboratorio, los estudios de campo resultan necesarios para poder caracterizar empíricamente los parámetros característicos de los rayos en la naturaleza. Con las medidas en la naturaleza, además de fundamentar algunos modelos de protección, también se realizan estadísticas que son empleadas en la definición de los niveles de protección que determinan la aplicación práctica de la protección contra el rayo. El hecho de abarcar diferentes puntos de un campo de la técnica viene impuesto porque esta Tesis se ha realizado dentro del marco de una empresa especializada en la protección contra el rayo, lo que implica una necesidad de conocimiento aplicado a todos los puntos que conciernen a su campo de aplicación. Las principales contribuciones de la Tesis quedan recogidas en cada uno de los capítulos y las propuestas que se hacen en ellos, abriendo nuevas líneas de trabajo sobre las que fundamentar un conjunto de técnicas y prácticas que podrían complementar a las aplicadas actualmente. Tras un capítulo introductorio, se trata el núcleo principal de la Tesis, formado por los capítulos 3, 4 y 5 donde se presentan las contribuciones del autor en forma de publicación. En el capítulo 3 se revisan los ensayos en laboratorio, donde se pueden estudiar los procesos físicos asociados a los arcos eléctricos. En este punto y, tras una revisión, el autor se centra en el parámetro U50 (amplitud de un pulso de tensión en una configuración determinada cuya aplicación implica un 50% de probabilidad de obtener una descarga disruptiva) empleando una herramienta basada en redes neuronales en la configuración de perceptrón multicapa (MLP) con la que se analiza el nivel de predicción del resultado de un impulso individual con diferentes configuraciones, datos de entrada y ventanas temporales, como indicativo de la influencia de una variable en el proceso de generación e intercepción del arco eléctrico. Sobre los ensayos en campo, su aplicación implica normalmente la monitorización de estructuras de gran altura, el empleo de cohetes para el cebado artificial de rayos, o las redes de detección de rayos. En este punto se evalúan las diferentes estrategias de medida y se introduce un nuevo punto de vista que podría utilizarse para la obtención de estadísticas fiables en un tiempo reducido y que ha dado lugar a un artículo. También se menciona una metodología para la evaluación continua de los sistemas de protección contra el rayo con la que se podría comparar el rendimiento de los sistemas instalados, con el modelo de protección empleado para realizar el diseño de la instalación. Sobre los modelos de protección, tras una revisión de varios modelos de protección, la Tesis se centra en los modelos normalizados los cuales, pese a sus carencias son los más utilizados. Tras evaluar el contexto actual bajo las normativas de protección contra el rayo se indica que una vía para complementar físicamente los modelos de protección es la inclusión de métodos con fundamentación física cuya aplicación sea compatible con los modelos de protección normalizad / [CA] A aquesta Tesi s'aborda l'estudi del estat actual de la protecció contra el llamp centrant l'objectiu en la protecció externa i amb èmfasi en el procés de intercepció. Baix aquest plantejament, s'estudien tres pilars fonamentals que presenten un evident interès par la avaluació y aplicació pràctica de la protecció contra el raig a la seua primera fase, la intercepció del llamp: Els assajos de laboratori Els estudis de camp Els models de protecció Aquests tres punts poden tractar-se de forma individual, però estan relacionats entre si, no només pel camp de la tècnica al que pertanyen, sino també perquè junts plantegen una evolució en la magnitud de la descàrrega elèctrica, començant amb l'estudi de la descàrrega elèctrica al laboratori per a comprendre el processos que governen el seu comportament. Al no ser possible la completa reproducció del fenomen del raig al laboratori, els estudis de camp resulten imprescindibles per a poder caracteritzar empíricament els paràmetres característics dels rajos a la naturalesa. Amb les mesures realitzades a la naturalesa, amés de fonamentar alguns models de protecció, també es realitzen estadístiques que son emprades a la definició dels nivells de protecció que determinen la aplicació pràctica de la protecció contra el raig. El fet de comprendre diferents punts d'un camp de la tècnica ve impost per el fet de que aquesta Tesi ha sigut realitzada dins del marc d'una empresa especialitzada en la protecció contra el llamp, i açò implica la necessitat de coneixement aplicat a tots els punts que concerneixen al seu camp d'aplicació. Les principals contribucions de la Tesi queden arreplegades en cada un dels capítols i les propostes que se fan en ells, obrint noves línies de treball sobre les que fonamentar un conjunt de tècniques i practiques que podrien complementar a les aplicades actualment. Després d'un capítol introductori, es tracta el nucli principal de la Tesi, format per els capítols 3, 4 y 5 on es presenten les contribucions de l'autor en forma de publicació. Al capítol 3, es revisen els assajos en laboratori, a on es poden estudiar els processos físics associats als arcs elèctrics. En aquest punt i, desprès de una revisió, l'autor es centra en el paràmetre U50 (amplitut d'un impuls de tensió a una configuració determinada que implica un 50% de probabilitat de obtenir una descarrega disruptiva) emprant una ferramenta basada en xarxes neuronals amb configuració de perceptró multicapa (MLP) en la que s'analitza el nivell de predicció del resultat d'un impuls individual amb diferents configuracions, senyals d'entrada i finestres temporals, com indicatiu de l'influencia d'un variable en el procés de generació i intercepció de l'arc elèctric. Referent als assajos en camp, la seua aplicació implica normalment la monitorització d'estructures de gran alçada, la utilització de coets per al encebat artificial de rajos, o les xarxes de detecció de llamps. En aquest punt s'avaluen les diferents estratègies de mesura i s'introdueix un nou punt de vista que es podria utilitzar per a l'obtenció d'estadístiques fiables en un temps reduït, del que també ha sorgit un article. També es menciona una metodologia per a l'avaluació continua dels sistemes de protecció contra el raig en la que se podria comparar el rendiment dels sistemes instal¿lats, amb el model de protecció empleat per a realitzar el disseny de la instal.lació. Sobre els models de protecció, tres una revisió dels diferents models de protecció existents, la Tesi es centra en els models normalitzats, el quals, a pesar de les seues carències segueix sent els mes utilitzats en l'actualitat. Desprès de avaluar el context actual baix les normatives de protecció contra el raig s'indica que una via per a complementar físicament els models de protecció es la inclusió de mètodes amb fonamentació física que continuen sent compatibles amb els models de protecció / Ruiz Muñoz, D. (2015). Contribuciones a los sistemas de protección contra el rayo [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/59440 / Compendio

<p dir="ltr">A recent emphasis of distributed learning research has been on federated learning (FL), in which model training is conducted by the data-collecting devices. In traditional FL algorithms, trained models at the edge are periodically sent to a central server for aggregation, utilizing a star topology as the underlying communication graph. However, assuming access to a central coordinator is not always practical, e.g., in ad hoc wireless network settings, motivating efforts to fully decentralize FL. Consequently, Decentralized federated learning (DFL) captures FL settings where both (i) model updates and (ii) model aggregations are exclusively carried out by the clients without a central server. Inherent challenges due to distributed nature of FL training, i.e., data heterogeneity and resource heterogeneity, become even more prevalent in DFL since it lacks a central server as a coordinator. In this thesis, we present two algorithms for resource-aware DFL, which result in achieving an overall desired performance across the clients in shorter amount of time compared to existing conventional DFL algorithms which do not factor in the resource availability of clients in their approaches.</p><p dir="ltr"><br></p><p dir="ltr">In the first project, we propose EF-HC, a novel methodology for distributed model aggregations via asynchronous, event-triggered consensus iterations over the network graph topology. We consider personalized/heterogeneous communication event thresholds at each device that weigh the change in local model parameters against the available local resources in deciding whether an aggregation would be beneficial enough to incur a communication delay on the system. In the second project, we propose Decentralized Sporadic Federated Learning (DSpodFL), a DFL methodology built on a generalized notion of sporadicity in both local gradient and aggregation processes. DSpodFL subsumes many existing decentralized optimization methods under a unified algorithmic framework by modeling the per-iteration (i) occurrence of gradient descent at each client and (ii) exchange of models between client pairs as arbitrary indicator random variables, thus capturing heterogeneous and time-varying computation/communication scenarios. We analytically characterize the convergence behavior of both algorithms for strongly convex models using both a constant and a diminishing learning rate, under mild assumptions on the communication graph connectivity, data heterogeneity across clients, and gradient noises. In DSpodFL, we do the same for non-convex models as well. Our numerical experiments demonstrate that both EF-HC and DSpodFL consistently achieve improved training speeds compared with baselines under various system settings.</p>

Networked control over wireless networks is of growing importance in many application domains such as industrial control, building automation and transportation systems. Wide deployment however, requires systematic design tools to enable efficient resource usage while guaranteeing close-loop control performance. The control system may be greatly affected by the inherent imperfections and limitations of the wireless medium and malfunction of system components. In this thesis, we make five important contributions that address these issues.  In the first contribution, we consider event- and self-triggered control and investigate how to efficiently tune and execute these paradigms for appropriate control performance. Communication strategies for aperiodic control are devised, where we jointly address the selection of medium-access control and scheduling policies. Experimental results show that the best trade-off is obtained by a hybrid scheme, combining event- and self-triggered control together with contention-based and contention-free medium access control. The second contribution proposes an event-based method to select between fast and slow periodic sampling rates. The approach is based on linear quadratic control and the event condition is a quadratic function of the system state. Numerical and experimental results show that this hybrid controller is able to reduce the average sampling rate in comparison to a traditional periodic controller, while achieving the same closed-loop control performance. In the third contribution, we develop compensation methods for out-of-order communications and time-varying delays using a game-theoretic minimax control framework. We devise a linear temporal coding strategy where the sensor combines the current and previous measurements into a single packet to be transmitted. An experimental evaluation is performed in a multi-hop networked control scenario with a routing layer vulnerability exploited by a malicious application. The experimental and numerical results show the advantages of the proposed compensation schemes. The fourth contribution proposes a distributed reconfiguration method for sensor and actuator networks. We consider systems where sensors and actuators cooperate to recover from faults. Reconfiguration is performed to achieve model-matching, while minimizing the steady-state estimation error covariance and a linear quadratic control cost. The reconfiguration scheme is implemented in a room heating testbed, and experimental results demonstrate the method's ability to automatically reconfigure the faulty system in a distributed and fast manner. The final contribution is a co-simulator, which combines the control system simulator Simulink with the wireless network simulator COOJA. The co-simulator integrates physical plant dynamics with realistic wireless network models and the actual embedded software running on the networked devices. Hence, it allows for the validation of the complete wireless networked control system, including the study of the interactions between software and hardware components. / <p>QC 20140929</p>

The Electric/Electronic architecture of vehicle becomes more complex and costly, self-adaption can reduce the system, enhance the adaptive meanwhile reduce energy consumption and costs. The self-adaption needs the cooperation of both hardware and software reconfigurations, such that after the software is reconfigured the automotive network continues to fulfill the time constraints for time-critical applications. The thesis focuses on the real-time network reconfiguration. It uses EAST-ADL to model a real-time automotive system with timing events and constraints, which conforms to AUTOSAR timing extensions. The network media access is analyzed based on the model and a scheduling algorithm is developed. Then the concept is implemented by a use case, which is transformed from an EAST-ADL model to an executable simulation.

Cette thèse est dédiée à l'analyse de stabilité des systèmes à pas d'échantillonnage variable et à la commande dynamique de l'échantillonnage. L'objectif est de concevoir des lois d'échantillonnage permettant de réduire la fréquence d'actualisation de la commande par retour d'état, tout en garantissant la stabilité du système.Tout d'abord, un aperçu des récents défis et axes de recherche sur les systèmes échantillonnés est présenté. Ensuite, une nouvelle approche de contrôle dynamique de l'échantillonnage, "échantillonnage dépendant de l'état", est proposée. Elle permet de concevoir hors-ligne un échantillonnage maximal dépendant de l'état défini sur des régions coniques de l'espace d'état, grâce à des LMIs.Plusieurs types de systèmes sont étudiés. Tout d'abord, le cas de système LTI idéal est considéré. La fonction d'échantillonnage est construite au moyen de polytopes convexes et de conditions de stabilité exponentielle de type Lyapunov-Razumikhin. Ensuite, la robustesse vis-à-vis des perturbations est incluse. Plusieurs applications sont proposées: analyse de stabilité robuste vis-à-vis des variations du pas d'échantillonnage, contrôles event-triggered et self-triggered, et échantillonnage dépendant de l'état. Enfin, le cas de système LTI perturbé à retard est traité. La construction de la fonction d'échantillonnage est basée sur des conditions de stabilité L2 et sur un nouveau type de fonctionnelles de Lyapunov-Krasovskii avec des matrices dépendant de l'état. Pour finir, le problème de stabilisation est traité, avec un nouveau contrôleur dont les gains commutent en fonction de l'état du système. Un co-design contrôleur/fonction d'échantillonnage est alors proposé / This PhD thesis is dedicated to the stability analysis of sampled-data systems with time-varying sampling, and to the dynamic control of the sampling instants. The main objective is to design sampling laws that allow for reducing the sampling frequency of state-feedback control for linear systems while ensuring the system's stability.First, an overview of the recent problems, challenges, and research directions regarding sampled-data systems is presented. Then, a novel dynamic sampling control approach, "state-dependent sampling", is proposed. It allows for designing offline a maximal state-dependent sampling map over conic regions of the state space, thanks to LMIs.Various classes of systems are considered throughout the thesis. First, we consider the case of ideal LTI systems, and propose a sampling map design based on the use of polytopic embeddings and Lyapunov-Razumikhin exponential stability conditions. Then, the robustness with respect to exogenous perturbations is included. Different applications are proposed: robust stability analysis with respect to time-varying sampling, as well as event-triggered, self-triggered, and state-dependent sampling control schemes. Finally, a sampling map design is proposed in the case of perturbed LTI systems with delay in the feedback control loop. It is based on L2-stability conditions and a novel type of Lyapunov-Krasovskii functionals with state-dependent matrices. Here, the stabilization issue is considered, and a new controller with gains that switch according to the system's state is presented. A co-design controller gains/sampling map is then proposed

The Electric/Electronic architecture of vehicle becomes more complex and costly, self-adaption can reduce the system, enhance the adaptive meanwhile reduce energy consumption and costs. The self-adaption needs the cooperation of both hardware and software reconfigurations, such that after the software is reconfigured the automotive network continues to fulfill the time constraints for time-critical applications. The thesis focuses on the real-time network reconfiguration. It uses EAST-ADL to model a real-time automotive system with timing events and constraints, which conforms to AUTOSAR timing extensions. The network media access is analyzed based on the model and a scheduling algorithm is developed. Then the concept is implemented by a use case, which is transformed from an EAST-ADL model to an executable simulation.:1. Introduction 2. Research Fundamentals 2.1. AUTOSAR Specifications for Modeling Function Communication 2.2. Media Access Control in Real-time Network 3. Function Communication Model and Determination of Network Configuration 3.1. Function Communication Model 3.2. Scheduling Algorithm for Media Access 4. Implementation of Communication Model and Plugin for Model Transformation 4.1. EAST-ADL Modeling Language 4.2. Implementation of Function Communication Model in EAST-ADL 4.3. Model Transformation Plugin and Simulation Tool Integration 5. Evaluation of the Function Communication Model 5.1. Use-Case Model for Evaluation 5.2. Time Values of Use-Case Model 5.3. Analysis and Evaluation of Simulation Result 6. Conclusion and Outlook 6.1. Conclusion of the Work 6.2. Outlook of the Future Work A. OMNeT++ Simulation Log B. EAST-ADL Model to Artop Model Mapping Bibliography Nomenclature

This research is aimed at exploding a wire via electromagnetic induction, with a preference for obtaining restrike of the exploding wire in a ring shape or otherwise. Literature on both exploding wire and electromagnetic induction are introduced together. A mathematical framework to describe the wire explosion by induction is formulated from first principles using the idea of magnetic flux linkages. The environment in which the experiments took place is described, with reference to matters of laboratory safety and also measurement of transient electrical current and voltage in the wire explosion by induction. The results describe the approaches taken to explode a wire by induction to obtain a plasma conductor. Voltage and current data are displayed and described. Throughout this work, there are long-exposure digital photographic images of the experiments taking place. These contribute to determining the outcome of experiments, and support the conclusions. Wires were exploded by induction in an air-cored mutually coupled coils system, and restrike of those wires was achieved. Electrical characteristics of wire explosion by electromagnetic induction are displayed and discussed based on what is known about straight exploding wires. Future works involving creation of plasma rings, electromagnetic thrust and exploding wires in vacuum are discussed.

La maladie de Parkinson (MP) est la deuxième maladie neurodégénérative la plus commune. Les symptômes principalement observés chez les patients atteints de la MP sont la rigidité, les tremblements, la bradykinésie et une instabilité posturale. Leur sévérité est souvent asymétrique. La cause principale de ces symptômes moteurs est la dégénérescence du circuit dopaminergique nigro-striatal qui mène à un débalancement d’activité du circuit cortico-striatal. Ce débalancement de circuits est le point essentiel de cette thèse. Dans les protocoles de recherche décrits ici, des patients atteints de la MP (avant et après une dose de levodopa) et des participants contrôles sains ont effectué des mouvements auto-initiés ou en réponse à des stimulis externes pendant que l’on mesurait leur activité cérébrale en imagerie par résonance magnétique fonctionnelle (IRMf). Dans cette thèse, nous abordons et mettons en évidence quatre (4) points principaux. En première partie (chapitre 2), nous présentons un recensement de la littérature sur les cicruits cortico-striataux et cortico-cérébelleux dans la MP. En utilisant des méthodes de neuroimagerie, des changements d’activité cérébrale et cérébelleuse ont été observés chez les patients atteints de la MP comparés aux participants sains. Même si les augmentations d’activité du cervelet ont souvent été attribuées à des mécanismes compensatoires, nos résultats suggèrent qu’elles sont plus probablement liées aux changements pathophysiologiques de la MP et à la perturbation du circuit cortico-cérébelleux. En général, nous suggérons (1) que le circuit cortico-cérébelleux est perturbé chez les patients atteints de la MP, et que les changements d’activité du cervelet sont liés à la pathophysiologie de la MP plutôt qu’à des mécanismes compensatoires. En deuxième partie (chapitre 3), nous discutons des effets de la levodopa sur les hausses et baisses d’activité observés chez les patients atteints de la MP, ainsi que sur l’activité du putamen pendant les mouvements d’origine interne et externe. De nombreuses études en neuroimagerie ont montré une baisse d’activité (hypo-activité) préfrontale liée à la déplétion de dopamine. En revanche, l’utilisation de tâches cognitives a montré des augmentations d’activité (hyper-activité) corticale chez les patients atteints de la MP comparés aux participants sains. Nous avons suggéré précédemment que ces hypo- et hyper-activités des régions préfrontales dépendent de l’implication du striatum. Dans cette thèse nous suggérons de plus (2) que la levodopa ne rétablit pas ces hyper-activations, mais plutôt qu’elles sont liées à la perturbation du circuit méso-cortical, et aussi possiblement associées à l’administration de médication dopaminergique à long terme. Nous montrons aussi (3) que la levodopa a un effet non-spécifique à la tâche sur l’activité du circuit cortico-striatal moteur, et qu’elle n’a pas d’effet sur l’activité du circuit cortico-striatal cognitif. Nous montrons enfin (chapitre 4) que la levodopa a un effet asymétrique sur les mouvements de la main droite et gauche. À peu près 50% des patients atteints de la MP démontrent une asymétrie des symptômes moteurs, et ceci persiste à travers la durée de la maladie. Nos résultats suggèrent (4) que la levodopa pourrait avoir un plus grand effet sur les patrons d’activations des mouvements de la main la plus affectée. / Parkinson’s disease (PD) is the second most common neurodegenerative disease, mainly manifested by tremor, rigidity, bradykinesia and postural instability, and often an asymmetry of symptom severity of the left and right sides of the body. The depletion of dopamine of the nigrostriatal pathway is the primary cause of the motor symptoms observed in patients with PD, leading to an imbalance in basal-ganglia prefrontal circuits. In the protocols described here, patients with PD before and after levodopa administration and healthy participants performed self-initiated (SI) and externally triggered (ET) movements with the left and right hand during functional magnetic resonance imaging (fMRI). In the chapters of this thesis, we argue and provide evidence for four main points. The first portion (chapter 2) provides a literature review on cortico-striatal and cortico-cerebellar circuit disruption in PD. Using neuroimaging techniques, changes in cerebral and cerebellar activity have been observed in patients with PD compared with healthy participants. Although increases in activity in the cerebellum have often been interpreted as compensatory mechanisms, we provide evidence that they are more likely to be related to pathophysiological changes of the disease, and the disruption of the cortico- cerebellar circuit. In general, we argue (1) is that activity in the cerebellum is linked to the pathophysiology of PD. In the second section (chapter 3) we discuss the effect of levodopa on the patterns of cortical hypo- and hyper-activity in PD, as well as the activity of the putamen in SI and ET movements. Many studies have shown cortical hypo-activity in relation to nigrostriatal dopamine depletion. In contrast, some cognitive studies have also identified increases in cortical activity in patients with PD as compared with healthy control participants. We have previously suggested that cortical hypo- and hyper-activations depend on striatal recruitment. In this thesis, we further show that hyper-activations in the prefrontal cortex are not reestablished with levodopa administration. We suggest (2) that they are rather associated with mesocortical dopamine circuit dysfunction, and perhaps linked with long- term dopaminergic medication administration. Furthermore, we show (3) that levodopa has a non-task specific effect on the motor cortico-striatal loop, but does not affect the cognitive cortico-striatal circuit. Finally (chapter 4), we show that the effect of levodopa on movements of the left and right hands is not symmetrical. Previous studies have shown that in about 50% of patients, one side of the body is more severely affected, and this asymmetry persists throughout the duration of the disease. Our results suggest (4) that levodopa may have stronger effects on the cerebral hemodynamic patterns related to the movements of the more affected hand than on those of the less affected hand.