Quand un fluide mouillant visqueux (comme une huile) pénètre un milieu hétérogène tel qu’une fracture, l’interface (entre l’air déplacé et l’huile) développe des corrélations à longue portée menant à une dynamique spatio-temporelle complexe. Dans cette Thèse, nous avons étudié expérimentalement et théoriquement ce processus de transport d’un fluide, appelé imbibition, dans un modèle de fracture ouverte, pertinent dans diverses situations. Notre travail a combiné une étude expérimentale détaillée, avec une analyse précise des données, basées sur des méthodes de physique statistique et non-linéaire. D’abord, la position moyenne de l'interface h(t) est étudiée lors d’expériences de montée capillaire donnant lieu à une nouvelle solution analytique pour h(t). Nous avons ensuite étudié les propriétés d’invariance d’échelle de l’interface et en particulier leur évolution pour des processus d’imbibition forcées, caractérisée par un scénario dit «super-rugueux». Enfin, nous avons étudié et quantifié la dynamique intermittente par avalanches des fronts d’imbibition à partir de l’analyse multi-échelle (spatiales et temporelles) de leurs vitesses. L'ensemble des résultats présentés dans cette Thèse propose une image très générale de la dynamique hors équilibre des fronts d’imbibition se propageant lentement dans des fractures ouvertes. La propagation latérale des fluctuations interfaciales est contrôlée par conservation de la masse locale. L'avancement de l'interface dans la direction de propagation est contrôlé par l’échelle caractéristique du désordre et la vitesse moyenne du front. / The heterogeneous structure of fractured media can lead to complex spatiotemporal fluid invasion dynamics. It thus brings forward challenging fundamental questions in the context of out-of-equilibrium dynamical systems, but also relevant to many processes of interest. The goal of the Thesis is to study the spatio-temporal dynamics of the oil-air interface between displaced air and invading oil, in imbibition through a model open fracture. The research combines exhaustive experimental work with accurate data analysis based on methods of nonlinear statistical physics. The mean postion of the interface h(t) is studied in capillary rise experiments, giving rise to a new analytical solution for h(t). The fluctuations of the interface in forced-flow experiments are analysed in the context of kinetic roughening, characterizing a super-rough scaling scenario. Finally, the burst-like dynamics is studied by analysing the local and global velocities of the front, which are widely distributed and display complex spatio-temporal correlations. We define local and global avalanches whose sizes and durations are also widely distributed, with cutoffs that diverge with the capillary number. Intermittentcy of the global signal is quantified. The ensemble of results presented in this Thesis supports a very general picture of the nonequilibrium dynamics of slowly-driven fronts in open fractures: the lateral propagation of interfacial fluctuations is controlled by local mass conservation, through the lateral correlation length; and the advancement of the interface in the direction of propagation is controlled by the characteristic extent of the disorder d and by the mean front velocity.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study was conducted with the aim of generating information about the tillering process and contribute to the understanding of the defoliation process of Italian ryegrass (Lolium multiflorum Lam) utilized by lambs submitted to different herbage allowances: 6, 8 and 12 kg body weight DM/100 kg. The grazing method was intermittent. Pasture was utilized during 12 days and an accumulated thermal sum of 250 degree-days was the criterion to determine the grazing interval. The experimental design was completely randomized with repeated measures on time, three treatments and two area replication. It was used 35 marked tillers per paddock to determine the intensity and interval of defoliation. Tillering dynamics on the identification and counting of remaining living tiller and new appearance tillers. The intensity of defoliation is greater in 6 and 9% herbage allowances. The interval of defoliation is higher in forage herbage allowance 12%, intermediate in 9% and lower in the 6% offer. The rate appearance, survival and death of tillers, stability index of tillers number are similar for herbage allowances and differ according phenological stages of ryegrass. Different herbage allowances and phenological stages promote variable intensity and interval of defoliation. The advance of phenological stage increases tiller mortality and reduce the interval between defoliation. / Este estudo foi conduzido com o objetivo de gerar informações a respeito do processo de perfilhamento e contribuir com o entendimento do processo de desfolhação do azevém (Lolium multiflorum Lam.) utilizado por cordeiras submetidas a diferentes ofertas de forragem: 6; 8 e 12 kg de MS/100kg de peso corporal. O método de pastejo foi intermitente. O período de ocupação da pastagem foi de 12 dias e o critério para determinar o intervalo entre pastejos foi a soma térmica acumulada de 250 graus-dia. O delineamento experimental foi inteiramente casualizado, com medidas repetidas no tempo, três tratamentos e duas repetições de área. Utilizaram-se 35 perfilhos marcados por parcela para a determinação da intensidade e intervalo de desfolhação. A dinâmica de perfilhamento baseou-se na identificação e na contagem de perfilhos vivos remanescentes e no aparecimento de novos perfilhos. A intensidade de desfolhação foi superior nas ofertas de forragem 6 e 9%. O intervalo de desfolhação foi superior na oferta de forragem 12%, intermediário na oferta 9% e inferior na oferta 6%. As taxas de aparecimento, sobrevivência e mortalidade de perfilhos e o índice de estabilidade da população de perfilhos são similares nas ofertas de forragem e variam em função dos estádios fenológicos do azevém. As diferentes ofertas de forragem e estádios fenológicos promovem intensidade e intervalo de desfolhação variável. O avanço do estádio fenológico aumenta a mortalidade de perfilhos e reduz o intervalo entre desfolhações.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Human activity has been pointed out as the main reason of global warming by effluxes of CO2, N2O and CH4. In the last years, harmful effects of greenhouse gases due to its increase in atmosphere have been arousing interests of scientists into propose mechanisms of mitigation. Flooding rice is responsible for about 12% of CH4 released to atmosphere and therefore, is considerate one of the most important source of this greenhouse gas. There are many factors that control CH4 efflux in irrigated rice fields, which difficult an accurate identification of the responsible mechanisms. However, is known that irrigation regime and selection of rice cultivars affect CH4 efflux and may be managed intending to mitigate it. The objectives of this thesis were: (a) verify the effect of continuous irrigation, intermittent irrigation and intermittent flooding into CH4 efflux of a hapludalf soil cultivated with flooding rice at central region of Rio Grande do Sul State; (b) evaluate CH4 efflux of rice cultivated in greenhouse under different irrigation managements and relate the efflux to agronomic parameters of rice plants; (c) evaluate the irrigation systems over the rice crop and how it affect the electrochemical of soil solution and plant development; (d) evaluate CH4 efflux through cultivars of rice from Rio Grande do Sul and Santa Catarina States and relate it to plant morphological attributes. Intermittent irrigation was efficient to mitigate CH4 efflux in rice cultivations, when the lack of rain did not establish water layers, without having decrease in rice productivity. intermittent flooding management by irrigations, even at saturated soil, decreased the CH4 efflux by 70%. The management of intermittent flooding by irrigations when soil was bellow the field capacity do not cause CH4 efflux, however, this management caused decrease of rice productivity. Irrigation management does affect electrochemical conditions of soil, which are determinant to the CH4 production in soils. The dynamic of efflux of CH4 is similar between cultivars; however, there are differences on potential of CH4 efflux from cultivars of flooding rice. The cultivars Arize 1003, Avaxi Cl, BRS Atalanta, BRS Querência, BRS Taim, Inov Cl, Irga 422 and Irga 424 have showed lower efflux and higher productivities. Morphological characteristics of plants have not explained completely the differences of CH4 effluxes between cultivars. / A atividade antrópica tem sido apontada como a principal causa do aquecimento global pelo efluxo de CO2, N2O e CH4. Nos últimos anos, os efeitos prejudiciais do aumento da concentração atmosférica desses gases têm despertado os cientistas a propor mecanismos de mitigação. A cultura do arroz irrigado por alagamento é responsável por cerca de 12% do efluxo total de CH4 para a atmosfera, sendo considerada uma das principais fontes emissoras desse gás de efeito estufa. Os fatores que controlam o efluxo de CH4 no arroz irrigado são muitos, dificultando identificar com precisão os mecanismos responsáveis pelo seu efluxo. O regime de irrigação e a seleção de cultivares de arroz são fatores que afetam o efluxo de CH4 e podem ser modificados visando mitigar os efluxos para a atmosfera. Os objetivos da tese foram: (a) verificar o efeito do regime de irrigação contínua, intermitente e a banhos no efluxo de CH4 em um Planossolo cultivado com arroz irrigado por alagamento na Depressão Central do Rio Grande do Sul; (b) avaliar o efluxo de CH4 no arroz cultivado em casa de vegetação submetido a diferentes manejos de irrigação e relacionar o efluxo com parâmetros agronômicos da planta de arroz; (c) avaliar os sistemas de manejo de irrigação na cultura do arroz e os efeitos nos atributos eletroquímicos da solução do solo e no desenvolvimento das plantas; (d) avaliar o efluxo de CH4 em cultivares de arroz do RS e SC e relacionar com atributos morfofisiológicos das cultivares; e (e) caracterizar morfologicamente a cultura do arroz e verificar a provável rota de difusão do CH4 do solo até a atmosfera. A prática da irrigação intermitente foi eficiente em mitigar o efluxo de CH4 no cultivo do arroz irrigado quando as condições climáticas permitiram a ausência da lâmina de água durante o cultivo, sem diminuir a produtividade do arroz. O manejo da irrigação intermitente com o realagamento do solo ainda saturado diminuiu a emissão de CH4 em 70%. O manejo intermitente da irrigação com o realagamento do solo abaixo da capacidade de campo não causa efluxo de CH4, porém os efeitos foram negativos sobre a produtividade do arroz. O manejo da irrigação afeta as condições eletroquímicas do solo e são determinantes para a produção de CH4 nos solos. A dinâmica de efluxo de CH4 é semelhante entre as cultivares, porém, existem diferenças no potencial de efluxo de CH4 em cultivares de arroz irrigado por alagamento. As cultivares Arize 1003, Avaxi Cl, BRS Atalanta, BRS Querência, BRS Taim, Inov Cl, Irga 422 e Irga 424 apresentaram menor efluxo de CH4 com a maior produtividade do arroz. As características morfofisiológicas das plantas não explicaram completamente as diferenças de efluxos de CH4 entre as cultivares.

The introduction of artemisinin-based combination therapy (ACT) substantially reduced malaria-related mortality and morbidity during the past decade. Despite the widespread use of ACT, there is still a considerable knowledge gap with regards to safety, efficacy and pharmacokinetic properties of these drugs, particularly in vulnerable populations like children and pregnant women. In addition, there is growing evidence of widespread artemisinin-resistance across the Greater Mekong Subregion. Expedited delivery of novel antimalarial drugs with different mechanisms of action to the clinical setting is still far off; therefore, it is crucial to improve the use of existing antimalarial drugs for optimal outcome in order to prolong their therapeutic life span. This thesis focuses on utilizing pharmacometric tools to support this effort for malaria prevention and treatment. An extensive simulation framework was used to explore alternative malaria chemopreventive dosing regimens of a commonly used ACT, dihydroartemisinin-piperaquine. Different monthly and weekly dosing regimens were evaluated and this allowed an understanding of the interplay between adherence, loading dose and malaria incidence. A weekly dosing regimen substantially improved the prevention effect and was less impacted by poor adherence. This is also expected to reduce selection pressure for development of resistance to piperaquine. Population pharmacokinetics-pharmacodynamic models were developed for artesunate and the active metabolite dihydroartemisinin, effect on parasite clearance, in patients with artemisinin-resistant and -sensitive malaria infections in Southeast Asia. The modeling identified an association between parasite density and drug bioavailability. It predicted the presence of high levels of artemisinin resistant infection among patients in Cambodia and its spread into Myanmar. A nomogram to identify patients with artemisinin resistant infections was developed. Furthermore, the model was used to demonstrate the need for extended treatment duration to treat patients with artemisinin resistant infections. A population pharmacokinetic model developed from data on pregnant women in East Africa allowed further understanding of artemether-lumefantrine exposure in pregnant populations. It also suggested that the lumefantrine exposure in this population is not compromised. In summary, the results presented in this thesis demonstrate the value of pharmacometric approaches for improving antimalarial drug treatment and prevention. This ultimately contributes to overcoming the prevailing challenges to malaria control.

In this paper, a new algorithm for utilizing energy storage is proposed and applied on floating wind turbine economics. The proposed algorithm’s decision making on storing energy or selling electricity onto the grid is based on the electricity price, which makes it unique and different from similar algorithms. From the literature review, it was concluded Ocean Renewable Energy Storage to be most suitable with the Spar-Type and Semi-Submersible floating wind turbine to which the paper is based upon. The objective of this paper is to find the suitable ratio of energy storage versus wind farm, find the product of increase in wholesale, and evaluate whether the proposed method makes the hybrid economically sound. The algorithm was applied on spot-price data from Denmark due to its large share of wind energy with wind data from off the coast of Morro Bay in California, USA. Additionally, a sensitivity analysis is applied to evaluate to energy storage cost impact as well as evaluate the algorithm by lowering the required energy storage size.   Using the algorithm, the wind farm must account for nine days’ worth of energy production with a product of energy storage versus wind farm ratio of 1.42. The wholesale price increased with 11.9-21.5% for the four years studied, however, all financial results favored not utilizing energy storage. By the results derived from the sensitivity analysis, it was concluded that with future cost reductions, the algorithm will still favor no energy storage. However, by fine tuning the algorithm to reduce the need for storage, positive financial result might be achievable. The key to achieve a profitable result seems to rely on minimizing the need for energy storage, to which the proposed algorithm fail to achieve. Conclusively, spot-price decision-based energy storing is not economically sound.

Dans une vision de développement durable et d'indépendance énergétique visant l'intégration massive des énergies renouvelables à moyen terme dans le mix énergétique, les travaux menés au cours de cette thèse se sont axés sur deux thématiques :- d'une part, la comparaison de la production de trois technologies différentes de panneaux solaires (silicium, silicium avec concentration, CdTe) en fonctionnement réel dans une centrale photovoltaïque au sol dotée du suivi deux axes de la course du soleil ;- d'autre part et étant donné la nature intermittente de l'énergie photovoltaïque et son non-synchronisme avec la consommation, le développement et l'intégration de batteries à base de lithium comme moyen de stockage électrochimique de l'énergie photovoltaïque. L'approche est novatrice et a permis l'étude de nouveaux composés d'électrodes étudiés sous contraintes photovoltaïques réelles et utilisant différentes stratégies de restitution de l'énergie en vue du déploiement prochain des réseaux intelligents. Les simulations portent sur des accumulateurs de petites tailles classiquement utilisés dans les laboratoires de recherche mais préfigurant ce qui pourra être construit à plus grande taille. / In a vision of sustainable development and energy independence aiming at the massive integration of the medium-term renewable energies in the energy mix, the research works are centered on two themes:- On one hand, the comparison of the production of three technologies different from solar panels (silicon, silicon with concentration, CdTe) installed into a photovoltaic power plant with 2-axes sun tracking;- On the other hand and given the intermittent nature of the photovoltaic energy and its non-simultaneity with the consumption, the development and the integration of batteries with lithium as means of electrochemical storage of the photovoltaic energy. The approach is innovative and allowed the study of new compounds of electrodes studied under real photovoltaic constraints and using various strategies of return of the energy with the aim of the next deployment of the intelligent networks. The simulations concern batteries of small sizes classically used in research laboratories but prefiguring what can be built in bigger size.

O ácido 5-aminolevulínico (ALA) é o primeiro precursor do grupo heme acumulado, principalmente no fígado, em alguns tipos de porfirias hepáticas hereditárias (porfiria aguda intermitente-AIP e tirosinemia) ou adquiridas (intoxicação por chumbo) devido à diminuição da atividade da enzima porfobilinogênio deaminase. Amostras de biópsias de fígado de pacientes portadores de AIP revelaram alterações estruturais nas mitocôndrias e no retículo endoplasmático, acúmulo de lipofuscina, gordura e corpúsculos de ferritina. Têm sido demonstrado que mutações mitocondriais induzidas por pró-oxidantes também contribuem para o envelhecimento celular e para o desenvolvimento do câncer. Esses dados podem estar relacionados à maior incidência de carcinoma hepatocelular (HCC) em pacientes sintomáticos de AIP. In vitro, ALA produz espécies reativas de oxigênio (ROS), através da oxidação catalisada por metais, e pode ser visto como uma fonte endógena de ROS, iniciando danos oxidativos a estruturas celulares como o DNA, podendo estar envolvido na iniciação e promoção do câncer. Além disso, o produto final de oxidação do ALA, o ácido 4,5-dioxovalérico (DOVA) é capaz de induzir modificações nas bases do DNA como outros derivados carbonílicos reativos. Neste estudo, demonstramos que o ALA é capaz de produzir danos ao DNA como quebras de fita de DNA plasmidial, aumento do nível de 8-oxo-7,8- dihidro-2\'-desoxiguanosina e 5-hidroxi-2´-desoxicitidina em DNA de órgãos de ratos tratados com ALA e aumento da formação de diversas bases modificadas em DNA de timo de bezerro. O DOVA reagiu com 2´-desoxiguanosina e DNA de timo de bezerro isolado produzindo dois adutos diastereoisômeros. O ALA e o DOVA foram capazes de aumentar a mutagenicidade em S. typhimurium TA104 e induzir resposta SOS em E. coli PQ37. Danos ao DNA mitocondrial e nuclear também foram detectados através da técnica de reação quantitativa em cadeia da polimerase em fibroblastos humanos transformados tratados com ALA. Todos esses dados fornecem informações referentes ao potencial genotóxico do ALA e permitem estabelecer uma proposta de bases moleculares para conectar as lesões ao DNA promovidas pelo ALA com a maior incidência de carcinoma hepatocelular em pacientes sintomáticos de AIP. / 5-Aminolevulinic acid (ALA) is a heme precursor accumulated in some inborn (acute intermittent porphyria-AIP and tyrosinosis) or acquired (lead poisoning) types of hepatic porphyria. In AIP patients, ALA is overproduced and accumulated in the liver. Liver biopsy samples of AIP patients revealed mitochondrial and endoplasmic reticulum structural alterations and accumulation of lipofucsin, fat and ferritin bodies. Mitochondrial mutations induced by pro- oxidants were suggested to contribute to cellular aging and cancer. These findings may be connected to the higher frequency of hepatocellular carcinoma (HCC) associated to symptomatic AIP patients. In vitro, ALA produces reactive oxygen species (ROS) upon metal- catalyzed oxidation and can be viewed as a deleterious endogenous source of ROS, triggering oxidative damage to cell structures and organs and being involved in the initiation and promotion of cancer. Besides, the final oxidation product of ALA, the 4,5-dioxovaleric acid (DOVA) is expect to induce DNA base modifications as already shown for other reactive carbonyl derivatives. In this study we demonstrated that ALA is able to produce DNA lesions such as strand breaks in plasmid DNA, increased steady state level of 8-oxo-7,8- dihydro-2\'-deoxyguanosine and 5-hydroxy-2´-deoxycytidine in rat organs DNA of ALA-treated rats and increased formation of several modified DNA bases in calf thymus DNA. 4,5-Dioxovaleric acid was showed to react with 2\'-deoxyguanosine and isolated calf thymus DNA through Schiff?s base formation to produce two diastereisomeric adducts. Aminolevulinic acid and DOVA were able to increase mutagenicity of the S. typhimurim strain TA104 and induce SOS response in E. coli PQ37. The mitochondrial and nuclear DNA damage were also detected by quantitative polymerase chain reaction technique in transformed human fibroblasts treated with ALA. All these data provide additional information on the genotoxic potential of ALA and reinforce the hypothesis that ALA may be involved in the induction of HCC in symptomatic AIP patients.

L’hypoxie désigne une baisse de la biodisponibilité en oxygène au niveau tissulaire. La combinaison de l’hypoxie intermittente et de l’hypercapnie est identifiée dans le cadre de plusieurs maladies respiratoires comme un élément physiopathologique déterminant. Cependant, des travaux de recherche suggèrent qu’une exposition à l’hypoxie hypo- ou normocapnique à l’éveil peut améliorer la santé cardiovasculaire. La combinaison d’une exposition hypoxique et de l’entraînement à l’effort est utilisée par les athlètes pour améliorer la performance sportive aérobie. Des études pilotes récentes y compris chez le malade chronique indiquent que l’exposition à l’hypoxie modérée au repos ou à l’effort chez le patient est susceptible d’induire des gains significatifs en termes de santé cardiovasculaire, de composition corporelle et de statut métabolique.Nous nous sommes intéressés aux effets cardiorespiratoires et tissulaires de l’exposition hypoxique normobarique chez le sujet sain et chez la personne en surpoids ou obèse présentant un risque ou des anomalies cardio-métaboliques. Nous avons étudié l’efficacité de 2 types de conditionnement au repos consistant en une hypoxie continue ou une hypoxie intermittente et un entraînement à l’effort hypoxique par comparaison à la situation normoxique. Nous avons tout d’abord étudié les effets d’une exposition hypoxique à court terme au repos chez 14 sujets sains. Nous avons ensuite étudié les effets cardiorespiratoires, tissulaires, vasculaires et métaboliques d’un programme de conditionnement hypoxique normobarique à moyen terme au repos chez 35 patients en surpoids ou obèse. Nous avons de plus réalisé chez 24 sujets sains une étude préliminaire afin de vérifier la faisabilité et de caractériser les réponses cardio-respiratoires et l’oxygénation tissulaire au cours d’un exercice aigu à charge constante d’intensité modérée ou intermittent intense en hypoxie comparé à une condition placébo normoxique. La dernière étude a consisté à étudier les conséquences cardiorespiratoires, tissulaires, vasculaires et métaboliques d’un programme d’entraînement à l’effort en hypoxie par rapport au même programme en normoxie chez 23 patients en surpoids ou obèses.L’étude réalisée chez le sujet sain met en évidence l’intérêt à court terme d’un conditionnement hypoxique intermittent au repos sur des variables associées aux risques cardiovasculaires (diminution de la pression artérielle systolique en normoxie et augmentation de la variabilité sinusale) et une modulation de l’hypoxie tissulaire. Nous avons montré chez le sujet sain que l’hypoxie combiné à l’exercice aigu provoque une diminution de l’oxygénation musculaire similaire mais une diminution de l’oxygénation du cortex préfrontal plus importante par comparaison à un effort normoxique à même intensité relative. Ensuite, chez le sujet en surpoids ou obèse, nous avons montré que le conditionnement hypoxique passif chronique induit une diminution de la pression artérielle diastolique de repos en normoxie, une augmentation de la réponse ventilatoire hypoxique et une diminution de la variabilité cardiaque (après conditionnement par hypoxie intermittente seulement) et que le conditionnement hypoxique actif chronique améliore l’aptitude maximale aérobie par rapport à une situation placébo normoxique.Les résultats obtenus montrent la faisabilité de plusieurs conditionnements hypoxiques prometteurs au plan vasculaire y compris chez le sujet en surpoids ou obèse limité à l’exercice musculaire. Le conditionnement hypoxique actif montre également des bénéfices accrus sur l’aptitude aérobie. Ces protocoles de conditionnement doivent être affinés en vue d’optimiser leur efficacité en termes de perte de poids et d’amélioration du risque cardio-vasculaire et métabolique dans des populations présentant une obésité associée à une morbidité cardio-métabolique. Ils représentent également une piste thérapeutique innovante dans d’autres pathologies chroniques / Hypoxia refers to a decrease in the oxygen bioavailability at the tissue level. The combination of intermittent hypoxia and hypercapnia is identified in several respiratory diseases as a critical pathophysiological element. However, research suggests that exposure to hypo- or normocapnic hypoxia can improve cardiovascular health. The combination of hypoxic exposure and exercise training has been used by athletes to improve aerobic exercise performance. Recent pilot studies in patients with chronic diseases indicate that exposure to moderate hypoxia at rest or during exercise is likely to induce significant gains in cardiovascular health, body composition and metabolic status.We investigated the effects of normobaric hypoxic exposure on cardiorespiratory and tissue function in healthy subjects, overweight or obese subjects at risk or with cardio-metabolic abnormalities. We assessed the efficacy of 2 types of passive hypoxic conditioning consisting in sustained hypoxia or intermittent hypoxia and hypoxic exercise training in comparison with normoxic condition. First, we assessed the effects of short-term hypoxic exposure at rest in 14 healthy subjects. Then, we evaluated the cardiovascular and metabolic effects of a 8-week normobaric hypoxic conditioning program at rest (intermittent or sustained hypoxia) in 35 overweight or obese patients, compared to placebo normoxic exposure. Next, we conducted a preliminary study in 24 healthy subjects to assess the acute responses to submaximal constant-load and high intensity interval cycling exercise performed in normoxia and in hypoxia. The last study aimed to compare the effect of an 8-week exercise training program performed either in normoxia or hypoxia on maximal aerobic capacity in overweight or obese subjects.In the healthy subject, we emphasized the rapid benefits of intermittent hypoxic conditioning on cardiovascular function (lower baseline systolic blood pressure and increased heart rate variability) and the modulation of tissue deoxygenation in response to hypoxia. We have also shown in healthy subjects that acute exercise (combined with hypoxia causes a similar decrease in muscle oxygenation but a greater prefrontal cortex deoxygenation compared to normoxic condition. Then, in the overweight or obese subject, we have shown that chronic passive hypoxic conditioning induces a decrease in diastolic blood pressure at rest in normoxia, an increase in the hypoxic ventilatory response and a decrease in heart rate variability after intermittent hypoxic conditioning only. In addition, chronic active (exercise training) hypoxic conditioning improves the maximal aerobic capacity compared to placebo normoxic training.Our results show the feasibility of several hypoxic conditioning strategies and their interesting effects on the vascular function in overweight/obese subjects presenting exercise limitations impeding exercise reconditioning. In addition, active hypoxic conditioning showed a greater effect on physical fitness than normoxic exercise training. These hypoxic conditioning strategies must be further optimized to improve their efficacy regarding weight loss and cardiometabolic morbidity in obese. They also represent promising therapeutic opportunities for other chronic diseases

La commande intermittente a pour but principal d'augmenter le rendement de l'ensemble machine-convertisseur par une réduction des pertes. Dans le but de maintenir le couple moyen de la machine requis par la charge, cette commande augmente le couple de référence et éteint quelques phases pendant chaque période électrique ou chaque période mécanique. Par ce fait, elle réduit les pertes du convertisseur et les pertes ferromagnétiques de la machine. Elle dispose également d'une liberté de sélection des phases activées qui influence des fréquences générées du courant, de la force radiale et du couple. Par conséquent, cette stratégie de la commande intermittente, qui est appelée le glissement, peut éviter l'excitation de fréquences naturelles du stator, ou bien celles de la chaine cinématique. Elle a pour but de réduire les effets négatifs de la commande intermittente vis-à-vis de comportements vibratoire du stator et pulsatoire de la chaine cinématique qui sont respectivement à l'origine du bruit acoustique et des à-coups mécaniques. En fin, la commande intermittente est validée sur des cycles de conduite et peut économiser jusqu’à 5,17 % de l’énergie électrique consommée. / The intermittent control aims to increase the efficiency of the machine-converter system by reducing the losses. In the purpose to maintain the average torque of the machine required by the load, this control increases the reference torque and turns off some phases during each electrical period or each mechanical period. By this fact, it reduces the converter losses and the ferromagnetic losses of the machine. It also has a freedom in the selection of the activated phases which influences the generated frequencies of the current, the radial force and the torque. Therefore, this strategy of the intermittent control, which is called sliding strategy, can avoid the excitation of the natural frequencies of the stator, or those of the drivetrain. It aims to reduce the negative effects of the intermittent control vis-à-vis the vibration of the stator and the pulsation of the drivetrain which are respectively at the origins of acoustic noise and mechanical jerks. Finally, the intermittent control is validated on driving cycles and can save up to 5.17 % of the consumed electrical energy.

Dans cette thèse, nous présentons un cadre théorique pour étudier les systèmes de particules actives fonctionnant avec une quantité discrète d'états internes qui contrôlent le comportement externe de ces objets. Les concepts théoriques développés dans cette thèse sont introduits afin de comprendre un grand nombre de systèmes biologiques multi-agents dont les individus présentent différents types de comportements se succédant au cours du temps. Par construction, le modèle théorique suppose que l'observateur extérieur a accès uniquement au comportement visible des individus, et non pas à leurs états internes. C'est seulement après une étude détaillée de la dynamique comportementale que l'existence de ces états internes devient évidente. Cette analyse est cruciale pour pouvoir associer les comportements observés expérimentalement avec un ou plusieurs états internes du modèle. Cette association entre les états et les comportements doit être faite selon les observations et la phénoménologie du système biologique faisant l'objet de l'étude. Les scénarios qui peuvent être observés en utilisant notre modèle théorique sont déterminés par la conception du mécanisme interne des individus (nombre d'états internes, taux de transition, etc…) et seront de nature markovienne par construction. Tous les travaux expérimentaux et théoriques contenus dans cette thèse démontrent que notre modèle est approprié pour décrire des systèmes réels montrant des comportements intermittents individuels ou collectifs. Ce nouveau cadre théorique pour des particules actives avec états internes, introduit ici, est encore en développement et nous sommes convaincus qu'il peut potentiellement ouvrir de nouvelles branches de recherche à l'interface entre la physique, la biologie et les mathématiques. / In this thesis we introduce a theoretical framework to understand collections of active particles that operate with a finite number of discrete internal states that control the external behavior of these entities. The theoretical concepts developed in this thesis are conceived to understand the large number of existing multiagent biological systems where the individuals display distinct behavioral phases that alternate with each other. By construction, the premise of our theoretical model is that an external observer has access only to the external behavior of the individuals, but not to their internal state. It is only after careful examination of the behavioral dynamics that the existence of these internal states becomes evident. This analysis is key to be able to associate the experimentally observed behaviors of individuals with one or many internal states of the model. This association between states and behaviors should be done accordingly to the observations and the phenomenology displayed by the biological system that is being the subject of study. The possible scenarios that can be observed using our theoretical model are determined by the design of the internal mechanism of the individuals (number of internal states, transition rates, etc...) and will be of markovian nature by construction. All the experimental and theoretical work contained in this thesis is evidence that our model is suitable to be used to describe real-life systems showing individual or collective intermittent behaviors. This here-introduced new framework of active particles with internal states is still in development and we are convinced that it can potentially open new branches of research at the interface between physics, biology and mathematics.