Cette thèse est dédiée à l’analyse et la modélisation d'expériences où la position d'un traceur dans le milieu cellulaire est enregistrée au cours du temps. Il s’agit de pouvoir de retirer le maximum d’information à partir d’une seule trajectoire observée expérimentalement. L’enjeu principal consiste à identifier les mécanismes de transport sous-jacents au mouvement observé. La difficulté de cette tâche réside dans l’analyse de trajectoires individuelles, qui requiert de développer de nouveaux outils d’analyse statistique. Dans le premier chapitre, un aperçu est donné de la grande variété des dynamiques observables dans le milieu cellulaire. Notamment, une revue de différents modèles de diffusion anormale et non-Gaussienne est réalisée. Dans le second chapitre, un test est proposé afin de révéler la rupture d'ergodicité faible à partir d’une trajectoire unique. C’est une généralisation de l’approche de M. Magdziarz et A. Weron basée sur la fonction caractéristique du processus moyennée au cours du temps. Ce nouvel estimateur est capable d’identifier la rupture d’ergodicité de la marche aléatoire à temps continu où les temps d'attente sont distribués selon une loi puissance. Par le calcul de la moyenne de l’estimateur pour plusieurs modèles typiques de sous diffusion, l’applicabilité de la méthode est démontrée. Dans le troisième chapitre, un algorithme est proposé afin reconnaître à partir d’une seule trajectoire les différentes phases d'un processus intermittent (e.g. le transport actif/passif à l'intérieur des cellules, etc.). Ce test suppose que le processus alterne entre deux phases distinctes mais ne nécessite aucune hypothèse sur la dynamique propre dans chacune des phases. Les changements de phase sont capturés par le calcul de quantités associées à l’enveloppe convexe locale (volume, diamètre) évaluées au long de la trajectoire. Il est montré que cet algorithme est efficace pour distinguer les états d’une large classe de processus intermittents (6 modèles testés). De plus, cet algorithme est robuste à de forts niveaux de bruit en raison de la nature intégrale de l’enveloppe convexe. Dans le quatrième chapitre, un modèle de diffusion dans un milieu hétérogène où le coefficient de diffusion évolue aléatoirement est introduit et résolu analytiquement. La densité de probabilité des déplacements présente des queues exponentielles et converge vers une Gaussienne au temps long. Ce modèle généralise les approches précédentes et permet ainsi d’étudier en détail les hétérogénéités dynamiques. En particulier, il est montré que ces hétérogénéités peuvent affecter de manière drastique la précision de mesures effectuées sur une trajectoire par des moyennes temporelles. Dans le dernier chapitre, les méthodes d’analyses de trajectoires individuelles sont utilisées pour étudier deux expériences. La première analyse effectuée révèle que les traceurs explorant le cytoplasme montrent que la densité de probabilité des déplacements présente des queues exponentielles sur des temps plus longs que la seconde. Ce comportement est indépendant de la présence de microtubules ou du réseau d’actine dans la cellule. Les trajectoires observées présentent donc des fluctuations de diffusivité témoignant pour la première fois de la présence d’hétérogénéités dynamiques au sein du cytoplasme. La seconde analyse traite une expérience dans laquelle un ensemble de disques de 4mm de diamètre a été vibré verticalement sur une plaque, induisant un mouvement aléatoire des disques. Par une analyse statistique approfondie, il est démontré que cette expérience est proche d'une réalisation macroscopique d'un mouvement Brownien. Cependant les densités de probabilité des déplacements des disques présentent des déviations par rapport à la Gaussienne qui sont interprétées comme le résultat des chocs inter-disque. Dans la conclusion, les limites des approches adoptées ainsi que les futures pistes de recherches ouvertes par ces travaux sont discutées en détail. / This thesis is dedicated to the analysis and modeling of experiments where the position of a tracer in the cellular medium is recorded over time. The goal is to be able to extract as much information as possible from a single experimentally observed trajectory. The main challenge is to identify the transport mechanisms underlying the observed movement. The difficulty of this task lies in the analysis of individual trajectories, which requires the development of new statistical analysis tools. In the first chapter, an overview is given of the wide variety of dynamics that can be observed in the cellular medium. In particular, a review of different models of anomalous and non-Gaussian diffusion is carried out. In the second chapter, a test is proposed to reveal weak ergodicity breaking from a single trajectory. This is a generalization of the approach of M. Magdziarz and A. Weron based on the time-averaged characteristic function of the process. This new estimator is able to identify the ergodicity breaking of continuous random walking where waiting times are power law distributed. By calculating the average of the estimator for several subdiffusion models, the applicability of the method is demonstrated. In the third chapter, an algorithm is proposed to recognize the different phases of an intermittent process from a single trajectory (e.g. active/passive transport within cells, etc.).This test assumes that the process alternates between two distinct phases but does not require any hypothesis on the dynamics of each phase. Phase changes are captured by calculating quantities associated with the local convex hull (volume, diameter) evaluated along the trajectory. It is shown that this algorithm is effective in distinguishing states from a large class of intermittent processes (6 models tested). In addition, this algorithm is robust at high noise levels due to the integral nature of the convex hull. In the fourth chapter, a diffusion model in a heterogeneous medium where the diffusion coefficient evolves randomly is introduced and solved analytically. The probability density function of the displacements presents exponential tails and converges towards a Gaussian one at long time. This model generalizes previous approaches and thus makes it possible to study dynamic heterogeneities in detail. In particular, it is shown that these heterogeneities can drastically affect the accuracy of measurements made by time averages along a trajectory. In the last chapter, single-trajectory based methods are used for the analysis of two experiments. The first analysis carried out shows that the tracers exploring the cytoplasm show that the probability density of displacements has exponential tails over periods of time longer than the second. This behavior is independent of the presence of both microtubules and the actin network in the cell. The trajectories observed therefore show fluctuations in diffusivity, indicating for the first time the presence of dynamic heterogeneities within the cytoplasm. The second analysis deals with an experiment in which a set of 4mm diameter discs was vibrated vertically on a plate, inducing random motion of the disks. Through an in-depth statistical analysis, it is demonstrated that this experiment is close to a macroscopic realization of a Brownian movement. However, the probability densities of disks’ displacements show deviations from Gaussian which are interpreted as the result of inter-disk shocks. In the conclusion, the limits of the approaches adopted as well as the future research orientation opened by this thesis are discussed in detail.

Le syndrome d’apnées obstructives du sommeil (SAOS) est un problème de santé publique majeur qui est considéré comme un facteur indépendant de risque de survenue d’un infarctus du myocarde (IM). Les altérations cardiovasculaires associées au SAOS sont principalement dues à l’hypoxie intermittente (HI) chronique. En particulier, l’HI induit l’activation du facteur de transcription hypoxia-inducible factor-1 (HIF-1), susceptible d’être impliqué dans la vulnérabilité accrue du myocarde à l’ischémie-reperfusion. L’objectif de cette thèse était d’étudier le rôle de HIF-1 dans les mécanismes induits par l’HI et impliqués dans l’augmentation de la taille de l’infarctus suite à une ischémie-reperfusion. Ces travaux ont mis en évidence deux nouveaux effets délétères de l’HI, à savoir l’induction d’un stress du réticulum endoplasmique (RE) et d’altérations mitochondriales. A travers, l’inhibition génétique et/ou pharmacologique de HIF-1, nous avons montré que HIF-1 apparaît comme un acteur primordial dans l’ensemble des mécanismes délétères de l’HI, incluant ceux découverts lors de cette thèse. De plus, HIF-1 joue un rôle majeur dans l’augmentation de la taille de l’IM induite par l’HI chronique. Parallèlement, son activation myocardique est corrélée à l’index d’apnées-hypopnées chez des patients apnéiques atteints d’une maladie coronarienne (comparativement aux non-apnéiques). Par conséquent, l’activation de HIF-1 pourrait être utilisée comme marqueur diagnostic du SAOS chez les patients à risque cardiovasculaire. HIF-1 pourrait également représenter une cible pour le développement de nouvelles thérapies complémentaires ou substitutives aux traitements actuels. / Obstructive sleep apnea syndrome (OSAS) is a major public health problem that is considered an independent risk factor for the occurrence of myocardial infarction (MI). The cardiovascular alterations associated with OSA are mainly due to the chronic intermittent hypoxia (IH). In particular, activation by IH, the hypoxia-inducible factor-1 (HIF-1) transcription factor likely contributes to enhance myocardial vulnerability to ischemia-reperfusion injury. The aim of this thesis was to study the role of HIF-1 in the mechanisms involved in the increase in MI induced by chronic IH. This work has highlighted two new deleterious consequences of IH exposure, namely endoplasmic reticulum (ER) stress and mitochondrial alterations. Through genetic and/or pharmacological inhibition of HIF-1, we have shown that HIF-1 appears to be a primordial actor in all the deleterious mechanisms of IH, including those discovered during this thesis. HIF-1 also appears to play a major role in the IH-induced increase in MI size. In parallel, its myocardial activation is correlated with the apnea-hypopnea index in apnoeic, compared to non-apnoeic, patients with coronary heart disease. Therefore, HIF-1 activation could serve as a diagnostic marker of OSA in patients with cardiovascular risk. HIF 1 could also be a target for new therapeutic approaches, in complement or replacement of standard treatments.

Intermitted Water Supply strategy is implemented commonly in some developing countries nowadays in order to minimize the water scarcity problems. Unstable hydraulic conditions in the distribution system, low pressure, high risk of water contamination, wasting water, rising costs paid by consumers and water providers, failures and problems with consumption metering and inconvenience to consumers are some of the consequences. Risk Analysis Methodology is developed to handle with intermittent water supply systems in developing countries conditions that include undesired events identification; risk estimation and risk evaluation and reduction plan, the catalogue list of potential undesired events (UE) which may occur in these types of systems have been also developed using the HAZard and OPerability technique (HAZOP). The developed methodology is implemented and tested in this research on one of the potential undesired events UE _ Low operational pressure

Inledning: Övervikt och fetma är förknippat med flera ämnesomsättningssjukdomar. Kostens betydelse har blivit central i det förebyggande arbetet av övervikt och fetma. Periodisk fasta har under de senaste åren blivit ett populärt verktyg för viktnedgång och förbättring av den allmänna hälsan. Tidsbegränsat ätande (TRF) är en form av periodisk fasta där fastandet sker mellan 14–16 timmar per dygn och resterande timmarna är s.k ätfönster. Preliminära data från studier antyder att TRF som kosthållning för med sig en rad hälsofördelar såsom att förbättra den metabola hälsan och kan därmed förebygga en rad ämnesomsättningssjukdomar. Syfte: Syfte med detta litteraturarbete var att analysera ifall tidsbegränsat ätande (TRF) kan främja viktminskning och förbättra de metabola parametrarna hos människor som har övervikt eller lider av fetma. Metod: Sex experimentella studier analyserades. Studierna söktes i databasen PubMed med sökorden: ”time restricted feeding” OR ”time restricted eating”. De inkluderade studierna valdes på basis av fastställda inklusions- och exklusionskriterier. Resultat: Största delen av de inkluderade studierna visade att TRF har en positiv påverkan på viktminskning. De flesta studierna förbättrade inte fasteglukos hos TRF-gruppen i jämförelse med kontrollgruppen. Två studier visade en signifikant förbättring av några av glukosparametrarna. Två av studierna visade att fasteinsulin och HOMA-IR minskade signifikant. Endast en studie visade att faste-triglyceridvärdet minskade.  Diskussion: Sammanfattningsvis visar de flesta studierna att TRF ger viktminskning utan kaloribegränsning och därmed skulle TRF kunna fungera som ett bra verktyg för viktnedgång. Vidare verkar längden på ätfönstret (4-12 timmar) och tiden på dagen (morgon och förmiddag) när matintaget sker viktigt både för att ge viktminskning och för att förändra de metabola parametrarna. TRF skulle därför kunna användas som ett möjligt redskap för att förebygga fetma och därmed förbättra olika metabola parametrar som i sin tur kanske kan förhindra/skjuta upp insjuknande i metabola syndromet, diabetes typ 2 samt hjärt- och kärlsjukdomar. / Introduction: Overweight and obesity are associated with several metabolic diseases. The importance of diet has become central in the preventive work of overweight and obesity. Periodic fasting has in recent years become a popular tool for weight loss and improvement of general health. Time-restricted eating (TRF) is a form of periodic fasting where the fasting window is between 14–16 hours per day and the remaining hours are so-called eating windows. Preliminary data from studies suggest that TRF contributes to a number of health benefits, improves metabolic health, and thus can prevent a number of metabolic diseases. Aim: The aim of this review was to analyze whether time-restricted eating (TRF) can promote weight loss and improve the metabolic parameters of overweight and obese people. Method: Six experimental studies were analyzed. The studies were searched in the PubMed database; the keywords were: "time restricted feeding" OR "time restricted eating". The included studies were selected on the basis of established inclusion and exclusion criteria. Results: Most of the included studies showed that TRF has a positive effect on weight loss. Most studies showed no significant improvement in fasting glucose in the TRF group compared to the control group. Two studies showed a significant improvement in some of the glucose parameters. Two of the studies showed a significant reduction in fasting insulin and HOMA-IR. Only one study showed a significant reduction in the fasting triglyceride value. Discussion: In summary, most studies showed that TRF provides weight loss without calorie restriction, and thereby TRF could work as a good tool for weight loss. Furthermore, the length of the eating window (4-8 hours) and the time of day (morning and before noon) when food intake takes place are important both to provide weight loss and to change the metabolic parameters. TRF could therefore be used as a possible tool to prevent obesity and thereby improve various metabolic parameters that may prevent / delay the onset of metabolic syndrome, type 2 diabetes, and cardiovascular disease.

[pt] Demanda intermitente é definida por períodos de vendas nulas intercaladas com vendas positivas e de quantidade altamente variável. A maior parte das unidades de manutenção de estoque (stock keeping units, em inglês) ao nível loja pode ser caracterizada como contendo demanda desse tipo. Assim, modelos acurados para prever séries com demanda intermitente trazem grandes impactos em relação à gestão de estoque. Nesta dissertação nós propomos o uso do framework GAS com as distribuições adequadas para dados de contagem, além de suas versões com excesso de zeros, e aplicamos os modelos derivados a dados reais obtidos com uma grande rede varejista brasileira. Nós demonstramos que os modelos com excesso de zeros propostos são estimados de forma consistente por máxima verossimilhança e a distribuição dos estimadores é assintóticamente normal. A performance dos modelos propostos é comparada com benchmarks adequados das literaturas de séries temporais para dados de contagem e previsão de demanda intermitente. A avaliação das previsões é feita com base tanto na precisão da distribuição preditiva quanto na precisão das previsões pontuais. Nossos resultados mostram que os modelos propostos, em especial o modelo derivado sob distribuição hurdle Poisson, performam melhor do que os benchmarks analisados. / [en] Intermittent demand is defined by periods of zero sales interleaved with positive sales with highly variable quantities. Most stock keeping units at the store level can be characterized as containing such demand. Thus, accurate models for predicting series with intermittent demand have major impacts in relation to inventory management. In this dissertation we propose the use of the GAS framework with the appropriate distributions for count data, in addition to their versions with excess of zeroes, and apply the derived models to real data obtained from a large Brazilian retail chain. We demonstrate that the proposed models with excess of zeros are consistently estimated via maximum likelihood and the distribution of the estimator is asymptotically normal. The performance of the proposed models is compared to adequate benchmarks from the time series literature for count data and intermittent demand forecast. Forecasting is evaluated based on the accuracy of both the entire predictive distribution and point forecasts. Our results show that the proposed models, specially the one derived from hurdle Poisson distribution, perform better than the analyzed benchmarks.

In an electrical system there needs to be a constant balance between supply and demand ofelectricity and this is measured by the frequency in the grid. Due to the increasing awarenessof climate change, more renewable energy resources have been introduced in the Swedishelectricity system. This is, however, not solely positive since renewable energy sources areoften of intermittent character which entails more imbalances between supply and demand. Inaddition, statistics and data show that the deviation in the frequency in the Nordic system hasincreased during the latest years. Thus, in this thesis, the issues regarding the frequency havebeen addressed by examining the demand for frequency control in the Swedish electricitysystem and what balancing efforts that can be carried out on a local level to contribute to abetter balanced system. This thesis has been conducted at KTH Royal Institute of Technologywith collaboration with the commissioner Mälarenergi AB. A case study of the Swedish electricity system has been carried out to gather empiricalmaterial and this material has been analyzed using Geels theory on technical transitions, themulti-level perspective. The results indicates that it is likely the demand for frequency controlwill increase, and this is due to factors as more intermittent energy, current market design fortrading electricity, overseas transmission connections, decommissioning of nuclear powerand limited internal transmission capacity. Three other developments have been identified,which could have a large impact on the demand in the future, as an increasing use of electricvehicles, prosumers and the deployment of IoT in the energy sector. These developmentshave not been integrated to a large extent yet in the energy sector and thus have a moreuncertain impact. In terms of resources, the thesis has identified that it is likely that hydropower will continueto be the main resource for frequency regulation. Another source that could be used morefrequently than today and possibly compete with hydropower is combined heat and powerplants. Furthermore, the study has found that local actors can contribute by advertisingsmaller local resources on a market for trading regulating power called“reglerkraftmarknaden”, that balance providing companies collaborate, that the load iscontrolled in the local grids or that smaller local production facilities are operated in standalonemode during extreme situations. / För att uppnå ett välfungerande elektrisk system så måste det vara en konstant balans mellan produktion och konsumtion av el i systemet. Den här balansen mäts genom att mäta frekvensen i elnätet. Eftersom allt fler har blivit mer medvetna om de klimatförändringar vår planet står inför har det successivt införts mer och mer förnybara energikällor i det svenska elsystemet. Den här utvecklingen har inte enbart varit positivt, eftersom förnybara energikällor ofta är av intermittent karaktär, vilket har medfört att balansen mellan produktion och konsumtion av el har försämrats. Flertalet undersökningar har påvisat att det förekommer mer frekvensavvikelser i det nordiska elsystemet idag än tidigare. Denna rapport har således undersökt dessa problem genom att analysera efterfrågan på frekvensreglering i det svenska elsystemet och vilka initiativ som kan tas på lokal nivå för att förbättra balansen i elsystemet. Rapporten har genomförts på Kungliga Tekniska Högskolan i samarbete med uppdragsgivaren Mälarenergi AB. Rapporten har genomfört en fallstudie av det svenska elsystemet för att samla in empiriskt material, och detta material har i sin tur analyserats genom Geels flernivåsansats. De resultat som har framkommit i undersökningen visar på att det är troligt att efterfrågan av frekvensreglering kommer att öka. Denna ökning beror på faktorer som att mer intermittent energi integreras i elnätet, hur marknaden för att handla elektricitet är utformad, fler utländska överföringsförbindelser, nedrustning av kärnkraft och begränsad överföringskapacitet inom det nationella elnätet. Tre andra utvecklingar har identifierats som möjligen kan ha en stor påverkan på behovet av frekvensreglering. Dessa är ett ökat antal elektriska fordon, prosumenter och att energisektorn integreras av IoT och smarta objekt i större utsträckning än idag. Dessa faktorer har inte integrerats i det svenska elsystemet nämnvärt ännu och deras påverkan är därmed mer osäker. Denna studie har också kommit fram till att vattenkraft troligtvis kommer fortsätta att vara den resurs som används mest för frekvensreglering, men även att kraftvärmeverk har potential att användas mer för reglering än idag. Vidare har rapporten även identifierat att lokala aktörer kan bidra till en bättre balans i systemet genom att antingen annonsera mindre lokala resurser på reglerkraftmarknaden, öka samarbetet mellan balansansvariga företag, kontrollera lasten i lokala elnät eller att mindre lokala produktionsanläggningar drivs i ö-drift under extrema situationer.

Wireless sensor networks (WSNs) have become pivotal in precision agriculture, environmental monitoring, and smart healthcare applications. However, the challenges of energy consumption and security, particularly concerning the reliance on large battery-operated nodes, pose significant hurdles for these networks. Energy-harvesting wireless sensor networks (EH-WSNs) emerged as a solution, enabling nodes to replenish energy from the environment remotely. Yet, the transition to EH-WSNs brought forth new obstacles in ensuring reliable and secure data transmission. In our initial study, we tackled the intermittent connectivity issue prevalent in EH-WSNs due to the dynamic behavior of energy harvesting nodes. Rapid shifts between ON and OFF states led to frequent changes in network topology, causing reduced link stability. To counter this, we introduced the hybrid routing method (HRM), amalgamating grid-based and opportunistic-based routing. HRM incorporated a packet fragmentation mechanism and cooperative localization for both static and mobile networks. Simulation results demonstrated HRM's superior performance, enhancing key metrics such as throughput, packet delivery ratio, and energy consumption in comparison to existing energy-aware adaptive opportunistic routing approaches. Our second research focused on countering emerging threats, particularly the malicious energy attack (MEA), which remotely powers specific nodes to manipulate routing paths. We developed intelligent energy attack methods utilizing Q-learning and Policy Gradient techniques. These methods enhanced attacking capabilities across diverse network settings without requiring internal network information. Simulation results showcased the efficacy of our intelligent methods in diverting traffic loads through compromised nodes, highlighting their superiority over traditional approaches. In our third study, we developed a deep learning-based two-stage framework to detect MEAs. Utilizing a stacked residual network (SR-Net) for global classification and a stacked LSTM network (SL-Net) to pinpoint specific compromised nodes, our approach demonstrated high detection accuracy. By deploying trained models as defenses, our method outperformed traditional threshold filtering techniques, emphasizing its accuracy in detecting MEAs and securing EH-WSNs. In summary, our research significantly advances the reliability and security of EH-WSN, particularly focusing on enhancing the network layer. These findings offer promising avenues for securing the future of wireless sensor technologies.

[pt] A demanda global por soluções sustentáveis para geração de energia elétrica cresceu rapidamente nas últimas décadas, sendo impulsionada por incentivos fiscais dos governos e investimentos em pesquisa e desenvolvimento de tecnologias. Isso provocou uma crescente inserção de fontes renováveis nas redes elétricas ao redor do mundo, criando novos desafios críticos para as avaliações de desempenho dos sistemas que são potencializados pela intermitência desses recursos energéticos combinada às falhas dos equipamentos de rede. Motivado por esse cenário, esta dissertação aborda a estimativa de risco de inadequação de grandezas elétricas, como ocorrências de sobrecarga em ramos elétricos ou subtensão em barramentos, através do uso do fluxo de potência probabilístico, baseado na simulação Monte Carlo e no método de entropia cruzada. O objetivo é determinar o risco do sistema não atender a critérios operativos, de forma precisa e com eficiência computacional, considerando as incertezas de carga, geração e transmissão. O método é aplicado aos sistemas testes IEEE RTS 79 e IEEE 118 barras, considerando também versões modificadas com a inclusão de uma usina eólica, e os resultados são amplamente discutidos. / [en] The global demand for sustainable solutions for electricity generation has grown rapidly in recent decades, driven by government tax incentives and investments in technology research and development. This caused a growing insertion of renewable sources in power networks around the world, creating new critical challenges for systems performance assessments that are enhanced by the intermittency of these energy resources combined with the failures of network equipment. Motivated by this scenario, this dissertation addresses the estimation of risk of inadequacy of electrical quantities, such as overload occurrences in electrical branches or undervoltage in buses, through the use of probabilistic power flow, based on Monte Carlo simulation and the cross-entropy method. The objective is to determine the risk of the system not meeting operational criteria, precisely and with computational efficiency, considering load, generation and transmission uncertainties. The method is applied to IEEE RTS 79 and IEEE 118 bus test systems, also considering modified versions with the inclusion of a wind power plant, and the results are widely discussed.

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