Reatores de leito fluidizado circulante são caracterizados por escoamentos altamente heterogêneos e instáveis. Devido a isso, operam em regimes pseudo-estacionários ou estatisticamente permanentes, onde os parâmetros do escoamento oscilam em torno de valores médios bem definidos. Neste trabalho estuda-se o comportamento de uma solução numérica para um escoamento típico de reatores de leito fluidizado circulante na região estatisticamente permanente. A simulação numérica foi realizada com o modelo de dois fluidos. A partir dos dados de simulação são estabelecidas médias e auto-correlações para as várias variáveis de interesse, considerando-se diferentes tempos de simulação ou diferentes tempos de observação. A partir destes resultados discute-se a questão do tempo mínimo de simulação necessário para que os resultados temporais médios sejam representativos do processo. Embora os resultados sugiram que 10 segundos de fluidização sejam suficientes para a geração de resultados médios temporais representativos, uma demonstração mais rigorosa permanece por ser executada. / Circulating fluidized bed reactors are characterized by highly heterogenic and instable flow. Due to this flow, the reactors operate under either pseudo-stationary or statistically permanent patterns, where the flowing parameters vary among well defined average values. This paper aims to study the behavior of a numeric solution for a typical flow of circulating fluidized bed reactors in the statistically permanent region. The numeric simulation was performed with the two-fluid model. From the simulation data both average and self-correlations are established for several variables of interest, considering either different simulation time or different observation time. From these results, the minimum simulation time necessary is discussed, so that the average temporal results can be considered representative in the process. Although the results suggest 10 seconds of fluidization are enough to generate the average temporal results, a more rigorous demonstration is supposed to be executed.

La caractérisation exaustive des variations de l'ADN peut aider à progresser dans de nombreux champs liés à la génomique du cancer. Le séquençage nouvelle génération (NGS en anglais pour Next Generation Sequencing) est actuellement la technique la plus efficace pour déterminer une séquence ADN, du aux faibles coûts et durées des expériences comparé à la méthode de séquençage traditionnelle de Sanger. Cependant, la détection de mutations à partir de données NGS reste encore un problème difficile, en particulier pour les mutations somatiques présentes en très faible abondance comme lorsque l'on essaye d'identifier des mutations sous-clonales d'une tumeur, des mutations dérivées de la tumeur dans l'ADN circulant libre, ou des mutations somatiques dans des tissus normaux. La difficulté principale est de précisement distinguer les vraies mutations des artefacts de séquençage du au fait qu'ils atteignent des niveaux similaires. Dans cette thèse nous avons étudié la nature systématique des erreurs dans les données NGS afin de proposer des méthodologies efficaces capables d'identifier des mutations potentiellement en faible abondance. Dans un premier chapitre, nous decrivons needlestack, un nouvel outil d'appel de variants basé sur la modélisation des erreurs systématiques sur plusieurs échantillons pour extraire des mutations candidates. Dans un deuxième chapitre, nous proposons deux méthodes de filtrage des variants basées sur des résumés statistiques et sur de l'apprentissage automatique, dans le but de d'améliorer la précision de la détection des mutations par l'identification des erreurs non-systématiques. Finalement, dans un dernier chapitre nous appliquons ces approches pour développer des biomarqueurs de détection précoce du cancer en utilisant l'ADN circulant tumoral / Comprehensive characterization of DNA variations can help to progress in multiple cancer genomics fields. Next Generation Sequencing (NGS) is currently the most efficient technique to determine a DNA sequence, due to low experiment cost and time compared to the traditional Sanger sequencing. Nevertheless, detection of mutations from NGS data is still a difficult problem, in particular for somatic mutations present in very low abundance like when trying to identify tumor subclonal mutations, tumor-derived mutations in cell free DNA, or somatic mutations from histological normal tissue. The main difficulty is to precisely distinguish between true mutations from sequencing artifacts as they reach similar levels. In this thesis we have studied the systematic nature of errors in NGS data to propose efficient methodologies in order to accurately identify mutations potentially in low proportion. In a first chapter, we describe needlestack, a new variant caller based on the modelling of systematic errors across multiple samples to extract candidate mutations. In a second chapter, we propose two post-calling variant filtering methods based on new summary statistics and on machine learning, with the aim of boosting the precision of mutation detection through the identification of non-systematic errors. Finally, in a last chapter we apply these approaches to develop cancer early detection biomarkers using circulating tumor DNA

Les maladies cardiovasculaires représentent l’une des principales causes de mortalitédans le monde et leur prévention constitue un enjeu majeur de santé publique. Les études épidémiologiques montrent que la consommation de fruits et légumes est associée à un moindre risque cardiovasculaire. Ces effets pourraient être expliqués par leur richesse en micronutriments et plus particulièrement en polyphénols. La consommation de flavanones, une classe de polyphénols présente spécifiquement et en grandes quantités dans les agrumes, a été inversement associée au risque d’accidents coronaires et d’accidents vasculaires cérébraux. Des données expérimentales obtenues in vivo et in vitro suggèrent que les flavanones (hespéridine ou naringine) possèdent des propriétés hypolipémiantes, hypotensives et anti-inflammatoires. Ces effets pourraient notamment être médiés par une modulation de l’expression de gènes par les flavanones. Cependant jusqu’à présent, l’action anti-athérogène des flavanones in vivo n’a été explorée qu’à des doses supra-nutritionnelles et les mécanismes responsables de ces effets sont encore largement méconnus. Par ailleurs, les données mécanistiques in vitro sont peu informatives, car obtenues avec des formes de flavanones non présentes dans l’organisme. Les objectifs de cette thèse ont donc été : (1) d’évaluer l’impact d’une consommation de flavanones (naringine et hespéridine) à dose nutritionnelle sur le développement de la lésion athéromateuse chez différents modèles murins d’hypercholestérolémie et d’appréhender les mécanismes moléculaires mis en jeu par une approche transcriptomique ; (2) de déterminer l’impact des métabolites circulants sur la fonction des cellules endothéliales et d’identifier les mécanismes moléculaires sous-jacents. In vivo, nous avons montré que seule la supplémentation en naringine (0,02%), la flavanone majoritaire du pamplemousse, réduisait la progression des lésions athéromateuses dans un modèle murin d’athérosclérose induite par l’alimentation (souris C57Bl/6J sous régime riche en graisse et en cholestérol). Cet effet était associé à une réduction des concentrations plasmatiques de non HDL-Chol et de biomarqueurs de la dysfonctionendothéliale, mais semblait indépendant d’une modulation du statut anti-oxydant. Une analyse transcriptomique pangénomique de l’aorte de ces animaux, a montré, que la supplémentation en naringine induisait une variation de l’expression de gènes impliqués dans des processus, tels que l’adhésion cellulaire ou l’organisation du cytosquelette, qui sont impliqués dans la migration trans-endothéliale des leucocytes. Ces résultats mettent en évidence de nouvelles cibles moléculaires d’action des flavanones qui ont été plus largement abordées in vitro. Les données obtenues in vitro montrent que l’exposition de cellules endothéliales(HUVEC) à des concentrations physiologiques de métabolites circulants de la naringénine(dérivés glucuronidés) ou de l’hespérétine (dérivés glucuronidés et sulfatés) diminue l’adhésion des monocytes (U937) aux cellules endothéliales, une étape clé de la migrationtrans-endothéliale. En accord avec ces résultats, une analyse TaqMan Low Density Array a montré que l’exposition des cellules endothéliales aux métabolites circulants de flavanones affectait l’expression de gènes impliqués dans l’inflammation, le chimiotactisme, l’adhésion ou encore la migration trans-endothéliale des leucocytes. Pris dans leur ensemble, les résultats de ce travail de thèse montrent que les effets antiathérogènesdes flavanones ne découlent pas exclusivement d’un effet hypolipémiant, mais aussi d’une action directe sur des étapes clés du développement de l’athérosclérose au niveau de l’endothélium, en particulier les processus d’adhésion et migration trans-endothéliale. / Cardiovascular disease is a major cause of mortality worldwide and its prevention is a major public health issue. Epidemiological studies have shown that fruit and vegetables consumption is associated with a lower cardiovascular risk. These effects could be explainedby their richness in micronutrients, especially polyphenols. Consumption of flavanones, a class of polyphenols present specifically and in large amounts in citrus fruits, was inversely associated with risk of coronary events and stroke. Experimental data obtained in vivo and invitro suggest that the flavanones (hesperidin or naringin) have lipid-lowering, hypotensive and anti-inflammatory properties. These effects could be mediated via modulation of gene expression by these bioactives. However, the anti-atherogenic effect of flavanones in vivo has been only explored at supra-nutritional doses and the mechanisms responsible for these effects are largely unknown. Furthermore, in vitro mechanistic data are questionable as they have been obtained using native forms of flavanones which are not present in the body.The objectives of this thesis were: (1) to assess the impact of consumption of flavanones (naringin and hesperidin) at nutritional doses on the development of atherosclerotic lesions indifferent mouse models of hypercholesterolemia and decipher molecular mechanisms brought into play, using a transcriptomic approach, (2) to determine the impact of physiological concentrations of plasma flavanone metabolites on endothelial cell function and theunderlying molecular mechanisms. In vivo, we showed that only naringin supplementation (0.02%), the major flavanonein grapefruit, reduced the progression of atherosclerotic lesions in a mouse model of dietinduced atherosclerosis (C57BL/6J mice fed an enriched diet in fat and cholesterol). Thiseffect was associated with a reduction in plasma non-HDL-Chol and biomarkers ofendothelial dysfunction, but appeared independent of a modulation of antioxidant status. Agenome-wide transcriptome analysis of the aorta of these animals showed that naringin supplementation modulated expression of genes involved in processes such as cell adhesion and cytoskeleton organization; these latter being involved in leukocytes trans-endothelialmigration. These results reveal new molecular targets of action of flavanones that have beenfurther studied in vitro.The in vitro data showed that exposure of endothelial cells (HUVEC) to physiological concentrations of circulating metabolites of naringenin (glucuronides) or hesperetin(glucuronides and sulfate) decreased the adhesion of monocytes (U937) to endothelial cells, a key step in the trans-endothelial migration. Consistent with these results, a TaqMan Low Density Array analysis showed that exposure of endothelial cells to these flavanone metabolites affected the expression of genes involved in inflammation, chemotaxis, adhesionas well as leukocytes trans-endothelial migration. Overall, the results of this work show that the anti-atherogenic effect of flavanones is not exclusively derived from lipid-lowering effect, but also due to a direct action on the endothelium by modulating key processes of atherosclerosis development, particularly adhesion and trans-endothelial migration.

Die Arbeit zeigt wichtige Nutzungswege von fester Biomasse in Form von Holzhackschnitzel (HHS). Einleitend wird das Potenzial und der derzeitige Stand dargestellt. Es werden die physikalischen und chemischen Eigenschaften mit dem Schwerpunkt Wassergehalt in bezug auf die energetische Nutzung der HHS behandelt. Kerne der Nutzungswege bilden dabei die Vergasung im Gleichstromvergaser und die Co-Verbrennung in der Zirkulierenden Wirbelschicht. Mit Hilfe eines Versuchsvergasers werden die Auswirkungen von HHS-Eigenschaften auf den Betrieb untersucht. Der Modellvergaser IGEL bietet durch seine Konstruktion die Möglichkeit, innere Vorgänge zu beleuchten und Messungen in verschiedenen Vergaserebenen durchzuführen. Die Auswirkungen von verschiedenen Brennstoffchargen mit unterschiedlichem Wassergehalt führten zu Änderungen in der Gaszusammensetzung. Eigene Untersuchungen ermittelten einen Grenzwassergehalt, mit dem der Vergaser noch betrieben werden kann. Die Experimente an der Pilotanlage mit zirkulierender atmosphärischer Wirbelschicht befass-ten sich mit der wichtigen Frage, ob und welches NOx-Minderungspotenzial beim Einsatz von Biomasse vorliegt. Die mathematische Modellierung verdeutlicht die Nutzbarkeit von Simulationsprogrammen bei der Untersuchung von Einflüssen der Co-Verbrennung auf die NOx-Bildung. Hier wurden die Gesichtspunkte der Luftzahl, der Luftstufung, des Wassergehaltes, das Mischungsverhältnis und die Brennstoffstufung betrachtet. Eine Wirtschaftlichkeitsbetrachtung führt zu dem Ergebnis, dass Anlagen zur reinen Stromerzeugung mit Biomasse nur nahe der gesetzlichen Höchstleistung von 20 MWel zur Einspeisevergütung von wirtschaftlich betrieben werden können. Die ökologisch und ökonomisch günstigste Variante stellt die Co-Verbrennung in vorhandenen Anlagen dar. Die Kalkulationen zu den in Deutschland benötigten 20-MWel-Anlagen verdeutlichen, dass bei den gegenwärtig geplanten Heizkraftwerken das Potenzial an HHS schnell aufgebraucht ist.

Endometriosis affects 5-10% of women and is characterized by the growth of endometrial tissue outside of the uterus. Treatment for endometriosis primarily focuses on symptom relief, is short term with severe side effects and often leads to recurrence of the condition. Establishing new blood supply is a fundamental requirement for endometriosis lesions growth. This has led to the idea that antiangiogenic therapy may be a successful approach for inhibiting endometriosis. Recent evidence indicates that endothelial progenitor cells (EPCs) contribute to neoangiogenesis of endometriotic lesions. These EPCs are recruited to the lesion site by stromal cell-derived factor-1 (SDF-1). We hypothesize that SDF-1 is central to the neoangiogenesis and survival of endometriotic lesions and that administration of SDF-1 blocking antibody will inhibit lesion growth by inhibiting angiogenesis in a murine model of endometriosis. Immunohistochemistry for SDF-1 and CD34 was performed on human endometriosis and normal endometrial samples. Quantification of SDF-1 and EPCs was performed in the blood of endometriosis patients and controls using ELISA and flow cytometry, respectively. A new mouse model of endometriosis was developed using BALB/c-Rag2-/-/IL2rg-/- mice to investigate role of SDF-1 in neoangiogenesis. Either SDF-1 blocking antibody or an isotype control was administered on a weekly basis for four weeks. Weekly samples of peripheral blood from mice were analyzed for SDF-1, other cytokines of interest and EPCs. Mice were euthanized at seven weeks to observe lesion growth and blood vessel development. Our results indicate overabundance of SDF-1 and CD34+ progenitor cells in human endometriotic lesions compared to eutopic endometrium. In the mouse model, SDF-1 and circulating EPC levels decreased from pre-treatment levels after one week, and remained constant over the course of the treatment in both SDF-1 blocking antibody and isotype control groups. In the SDF-1 blocking group, reduced vascularity of lesions, identified by immunofluorescence staining for CD31, was revealed compared to isotype controls. These findings suggest that SDF-1 may be responsible for CD34+ progenitor cell recruitment to the neoangiogenic sites in endometriosis. Blocking of SDF-1 reduces neovascularization of human endometriotic lesions in a mouse model. Further studies on blocking SDF-1 in combination with other antiangiogenic agents are needed. / Thesis (Master, Anatomy & Cell Biology) -- Queen's University, 2011-12-21 19:34:43.054

Wound healing and carcinogenesis are defined as complex, adaptive processes which are controlled by intricate communications between the host and the tissue microenvironment. A number of phenotypic similarities are shared by wounds and cancers in cellular signaling and gene expression. Radiotherapy is the second most effective modality of cancer treatment after surgery and can be used, either alone or in combination with chemotherapy. Recent findings suggest that radiotherapy apart from tumor cell death also rapidly and persistently modifies the tissue microenvironment. These modifications affect cell phenotype, tissue metabolism, bidirectional exchanges and signaling events between cells. The complex interactions between stromal cells and cancer cells are of immense interest and in The First Part of My Thesis, I tried to explore the crosstalk between stromal and carcinoma cells in response to radiotherapy by genetic modulation of the stroma and irradiation. We found that fibroblasts, irrespective of their RhoB status, do not modulate intrinsic radiosensitivity of TC-1 but produce diffusible factors able to modify tumor cell fate. Then we found that Wt and RhoB deficient fibroblasts stimulated TC-1 migration through distinct mechanisms respectively, TGF-β1 and MMP-mediated. We also found that co-irradiation of fibroblasts and TC-1 abrogated the pro-migratory phenotype by repression of TGF-β and MMP secretion. This result is highly relevant to the clinical situation and suggests that conversely to, the current view; irradiated stroma would not enhance carcinoma migration and could be manipulated to promote anti-tumor immune response. Secondly, our in vivo experiments, tends to confirm the in vitro data showing that irradiated tumor bed does not stimulate tumor growth and escape. Our results also challenges the view that irradiated stroma would promote migration of carcinoma cells as we show that independently from their genotype co-irradiation of fibroblasts and carcinoma cells repressed carcinoma cell migration and confirmations studies are currently performed in vivo. The Third Part of My Project, was dedicated to investigate the effect on CTC release after radiotherapy. Consistently with the results reported after surgery , the number of CTC increases in the blood stream after radiotherapy probably due to radiation-induced vascular injury induced or/and by EMT induction in tumor cells but these cells seemed to be entrapped into the cardiac cavity. The significance of these CTC to metastatic development is still under investigation but there is evidence for a metastasis-promoting effect of RT from animal studies.Thus the microenvironment can exert antagonist stimulatory or inhibitory effects on malignant cells.

Objective: The aim of this study was to develop an immunomagnetic/real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay and assess its clinical value for the molecular detection of circulating tumor cells (CTCs) in peripheral blood of pancreatic cancer patients. Methods: The presence of CTCs was evaluated in 34 pancreatic cancer patients before systemic therapy and in 40 healthy controls, through immunomagnetic enrichment, using the antibodies BM7 and VU1D9 [targeting mucin 1 and epithelial cell adhesion molecule (EpCAM), respectively], followed by real-time RT-PCR analysis of the genes KRT19, MUC1, EPCAM, CEACAM5 and BIRC5. Results: The developed assay showed high specificity, as none of the healthy controls were found to be positive for the multimarker gene panel. CTCs were detected in 47.1% of the pancreatic cancer patients before the beginning of systemic treatment. Shorter median progression-free survival (PFS) was observed for patients who had at least one detectable tumor-associated transcript, compared with patients who were CTC negative. Median PFS time was 66.0 days [95% confidence interval (CI) 44.8–87.2] for patients with baseline CTC positivity and 138.0 days (95% CI 124.1–151.9) for CTC-negative patients (p = 0.01, log-rank test). Conclusion: Our results suggest that in addition to the current prognostic methods, CTC analysis represents a potential complementary tool for prediction of outcome in pancreatic cancer patients. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The still increasing demand of electrical energy and the rising popularity of renewable energy sources in today's world are two important developments that necessitate the need for innovative solutions in the field of power electronics. Parallel operation of converters is one possible method in trying to bridge an increased current demand. The classical two-level converters, which are the standard in low voltage applications, are rarely adopted in medium and high voltage applications due to the voltage limits on power semiconductor devices. That is one reason for the growing popularity of multilevel converter topologies in medium and high-voltage applications. Although an increase in the number of voltage levels of a multilevel converter has its advantages, there are also challenges posed due to the increased number of switching devices. This has resulted in three-level converters being the most popular compared to converters of higher voltage levels. In this dissertation, the unified operation of parallel connected three-level converter units as a multilevel converter of higher voltage levels is proposed. The mathematical basis for operating parallel connected converter units as a single multilevel converter and the governing equations for such systems are derived. The analysis and the understanding of these equations are important for assessing practicality of the system and devising appropriate control structures. Parallel operation of converter units operating as multilevel converter have their own set of challenges, the two foremost being that of load-sharing and the possibility of circulating and cross currents. Developing solutions to address these challenges require a thorough understanding of how these manifest in the proposed system. Algorithms are then developed for tackling these issues. The control structures are designed and the developed algorithms are implemented. The operation of the system is verified experimentally. / Die weiterhin steigende Nachfrage nach elektrischer Energie und die zunehmende Verwendung erneuerbarer Energiequellen in der heutigen Welt sind zwei wichtige Entwicklungen, die die Notwendigkeit innovativer Lösungen im Bereich der Leistungselektronik erfordern. Der Parallelbetrieb von Stromrichtern ist eine mögliche Methode, um einen erhöhten Strombedarf zu decken. Der klassische Zweipunkt-Spanungszwischenkreisstromrichter, der bei Niederspannungsanwendungen weit verbreitet ist, wird aufgrund der Spannungsgrenzen für Leistungshalbleiterbauelemente zunehmend weniger in Mittel- und Hochspannungsanwendungen eingesetzt. Die begrenzte Spannungsbelastbarkeit der Leistungshalbleiterbauelemente ist ein Grund für die wachsende Beliebtheit von Mehrpunkt-Stromrichtertopologien in Mittelund Hochspannungsanwendungen. Obwohl eine Erhöhung der Anzahl der Spannungsstufen eines Mehrpunkt-Stromrichters Vorteile hat, gibt es auch Herausforderungen und Nachteile aufgrund der erhöhten Anzahl von Leistungshalbleitern. Dies hat dazu geführt, dass der Dreipunkt-Stromrichter die verbreiteste Topologie im Vergleich zu anderen Stromrichtern mit einer höheren Anzahl von Spannungsstufen ist. In dieser Dissertation wird der Betrieb von parallel geschalteten Dreipunkt-Stromrichtereinheiten als ein Mehrpunkt-Stromrichter mit erhöhter Anzahl an Spannungsstufen vorgeschlagen. Die mathematische Basis für den Betrieb von parallel geschalteten Stromrichtereinheiten als ein Mehrpunkt-Stromrichter und die beschreibenden Gleichungen eines solchen Systems werden abgeleitet. Die Analyse und das Verständnis dieser Gleichungen sind wichtig für die Beurteilung der Praktikabilität des Systems und die Erarbeitung geeigneter Regelstrukturen. Der parallele Betrieb von Stromrichtereinheiten hat seine eigenen Herausforderungen, wobei die beiden wichtigsten die Lastverteilung und die Möglichkeit von Kreis- und Querströmen sind. Die Entwicklung von Lösungen zur Bewältigung dieser Herausforderungen erfordert ein gründliches Verständnis dafür, wie sich diese Phänomene in dem vorgeschlagenen System manifestieren. Algorithmen zur Lösung dieser Probleme werden anschlieend entwickelt. Die Regelstrukturen werden entworfen und die entworfenen Algorithmen implementiert. Die Funktionsweise des Systems wird experimentell überprüft.

Abstract Energy production in combustion power plants is a significant source of anthropogenic carbon dioxide emissions. The targets of international climate agreements call for utilizing all available technologies to achieve rapid and cost-effective emission reductions. Carbon capture and storage is one of the possible technical solutions applied in combustion power plants. Circulating fluidized bed boilers have gained increasing popularity due to advantages in availability, emission control, fuel flexibility and option for using challenging fuels, and the possibility of using high-efficiency steam cycles. In the novel process of oxy-combustion, combustion air is replaced by a mixture of oxygen and recycled flue gas to facilitate the capture of carbon dioxide from the flue gas flow. Additional degrees of freedom become available for combustion control as the gas flow and composition can be controlled separately for fluidization and combustion purposes. In the research for this thesis, self-optimizing control was applied for the control structure design of a circulating fluidized bed boiler. Self-optimizing control offers a systematic tool for the early phases of control design, in which decisions have traditionally been made based on intuition, heuristics and previous experience. The self-optimizing control approach searches for controlled variables without a need for constant setpoint optimization when the process is affected by disturbances and implementation errors. Results presented in the thesis show that self-optimizing control can be applied in the control structure design of circulating fluidized bed combustion. A range of control structure alternatives were evaluated using steady-state approximations of a validated process model. For the novel oxy-combustion process, promising control structures were identified and could be dynamically demonstrated. / Tiivistelmä Energiantuotanto polttovoimalaitoksissa on merkittävä hiilidioksidipäästöjen lähde. Kansainväliset ilmastotavoitteet edellyttävät kaikkien käytettävissä olevien teknologioiden hyödyntämistä päästövähennysten aikaansaamiseksi nopeasti ja kustannustehokkaasti. Hiilidioksidin talteenotto on yksi mahdollisista teknisistä ratkaisuista polttovoimalaitoksissa. Kiertoleijukattilat ovat saavuttaneet kasvavaa suosiota etuinaan hyvä käytettävyys, tehokas päästöjen hallinta, soveltuvuus erilaisten haastavienkin polttoaineiden hyödyntämiseen ja mahdollisuus tehokkaiden höyrykiertojen käyttöön. Uudessa happipolttoprosessissa palamisilma korvataan hapen ja kierrätetyn savukaasun seoksella, mikä mahdollistaa hiilidioksidin talteenoton savukaasuista. Kiertoleijupolton säädön kannalta vapausasteet lisääntyvät, sillä leijutukseen ja polttamiseen käytettävän kaasun määrää ja koostumusta voidaan säätää erikseen. Väitöstutkimuksessa käytettiin itseoptimoivaa säätöä kiertoleijukattilan säätörakenteiden suunnitteluun. Itseoptimoiva säätö tarjoaa systemaattisen menetelmän säätösuunnittelun alkuvaiheeseen, jossa päätöksenteko on perinteisesti tehty esimerkiksi intuition, heuristiikan ja aiempien ratkaisujen perusteella. Menetelmän tavoitteena on löytää säädettävät muuttujat, joiden asetusarvot eivät vaadi jatkuvaa optimointia, vaikka prosessiin vaikuttavat erilaiset häiriöt ja mittausvirheet. Väitöstutkimuksen tulokset osoittavat, että itseoptimoiva säätö soveltuu kiertoleijupolton säätörakenteiden suunnitteluun. Erilaisten säätörakenteiden toimivuutta arvioitiin käyttäen validoidun prosessimallin tasapainotilan approksimaatioita. Uudelle happipolttoprosessille löydettiin lupaavia säätörakenteita, joiden toimintaa voitiin demonstroida myös dynaamisesti.

Une étude précise des écoulements gaz-particules poly-solides et réactifs rencontrés dans les lits fluidisés circulants (LFC) appliqués au procédé de Chemical Looping Combustion (CLC) est indispensable pour prédire un point de fonctionnement stable et comprendre l'influence de la réaction et de la polydispersion sur l'hydrodynamique des LFC. Dans ce but, des simulations avec le code NEPTUNE_CFD ont été confrontées aux expériences menées à l'Université Technologique de Compiègne par ALSTOM. Cette modélisation a été validée sur des LFC non réactifs mono-solides et poly-solides. L'influence des caractéristiques des particules et de la position des injecteurs sur l'entrainement de solide est étudiée. Un modèle de prise en compte de la production locale de gaz au cours de la réaction est présenté. L'étude locale de l'écoulement a permis de comprendre l'influence des collisions interparticulaire et de la production locale de gaz sur l'écoulement. Finalement, un point de fonctionnement a été proposé pour le pilote CLC en construction à Darmstadt. Ce travail a montré que NEPTUNE_CFD pouvait prédire l'hydrodynamique de LFC poly-solides à l'échelle du pilote industriel et participer au dimensionnement de centrales de types CLC. / This work deals with the development, validation and application of a model of Chemical Looping Combustion (CLC) in a circulating fluidized bed system. Chapter 1 is an introduction on Chemical Looping Combustion. It rst presents the most important utilizations of coal in the energy industry. Then, it shows that because of the CO2 capture policy, new technologies have been developed in the frame of post-combustion, pre-combustion and oxy-combustion. Then, the Chemical Looping Combustion technology is presented. It introduces multiple challenges: the choice of the Metal Oxide or the denition of the operating point for the fuel reactor. Finally, it shows that there are two specicities for CFD modeling: the influence of the collisions between particles of different species and the local production of gas in the reactor due to the gasication of coal particles. Chapter 2 outlines the CFD modeling approach: the Eulerian-Eulerian approach extended to flows involving different types of particles and coupled with the chemical reactions. Chapter 3 consists in the validation of the CFD model on mono-solid (monodisperse and poly-disperse) and poly-solid flows with the experimental results coming from an ALSTOM pilot plant based at the Universite Tchnologique de Compiegne (France). The relevance of modeling the polydispersity of a solid phase is shown and the influence of small particles in a CFB of large particles is characterized. This chapter shows that the pilot plant hydrodynamics can be predicted by an Eulerian-Eulerian approach. Chapter 4 consists in the validation of the CFD model on an extreme bi-solid CFB of particles of same density but whith a large particle diameter ratio. Moreover, the terminal settling velocity of the largest particles are twice bigger than the fluidization velocity: the hydrodynamics of the large particles are given by the hydrodynamics of the smallest. An experiment performed by Fabre (1995) showed that large particles can circulate through the bed in those operating conditions. Our simulations predicted a circulation of large particles, but underestimated it. It is shown that it can be due to mesh size eect. Finally, a simulation in a periodic box of this case was dened and allowed us to show the major influence of collisions between species. Chapter 5 presents the simulation of a hot reactive CLC pilot plant under construction in Darmstadt (Germany). The simulations account for the chemical reactions and describe its eect on the hydrodynamics. Different geometries and operating conditions are tested.