Cette thèse développe une réflexion épistémologique autour de la notion de biomarqueurs dans le cas de la maladie d’Alzheimer. Elle est centrée sur le transfert des connaissances du domaine de la biologie à celui de la pratique médicale et clinique, avec une attention particulière aux techniques de diagnostic précoce et aux Big Data. La maladie d’Alzheimer présente une temporalité particulière, son apparition étant insidieuse et sa phase asymptomatique longue. Elle se différencie des cancers en ne se prêtant pas à l’analyse génomique de cellules spécifiques, et permet ainsi d’aborder différemment le statut épistémique des biomarqueurs. Le biomarqueur (que ce soit une molécule, un réseau d’interactions, voire un algorithme), est porteur d’information sans pour autant établir un lien de causalité directe avec la maladie. C’est essentiellement un indice et non la représentation de la condition réelle d’un sujet ; c’est ensuite un objet entouré d’incertitude ; c’est enfin un objet dont la maîtrise n’est pas totale, un objet qui n’est jamais complètement donné. Enfin, les relations entre le biomarqueur et le milieu extérieur font partie intégrante de son fonctionnement. Les biomarqueurs sont essentiels dans la transformation des pratiques médicales vers l’anticipation et le suivi de l’évolution de la condition d’un sujet. En mettant en évidence des éléments transformant des facteurs de risque en une pathologie, les biomarqueurs invitent chacun à se surveiller et permettent un accompagnement des personnes dans une situation où elles n’ont encore aucun signe clinique d’une maladie évolutive. / This dissertation develops epistemological reflections on the notion of biomarkers in the case of Alzheimer’s disease. It focuses on the challenge posed by the transfer of knowledge from the field of biology to medical and clinical practices, with a special attention to the techniques of early diagnosis and especially the role of Big Data. Alzheimer's disease presents a particular temporality, its appearance being insidious with a long asymptomatic phase. It differs from cancer by not being amenable to genomic analysis of specific cells, and thus allows a different approach to the epistemic status of biomarkers. The biomarker whether it be a molecule, network of interactions, or even an algorithm, sheds light on the disease in the absence of any direct causal links between the biomarker and the disease. It is primarily an indicator rather than the representation of a body condition. As a consequence, it is always surrounded by uncertainty and never fully mastered, nor fully given. The biomarker is an object whose relations with the environment are an integral part of its functioning. Biomarkers are essential in transforming medical practices towards anticipating and monitoring the evolution of a subject's health condition. By highlighting elements that transform risk factors into a pathology, biomarkers invite everyone to monitor themselves and make it possible to support people well ahead of the appearance of clinical signs of an evolving disease.

Cette thèse s'intéresse à deux types de systèmes de différents degrés de liberté en interaction, et soumis à des fluctuations quantiques.Dans le premier projet abordé dans le manuscrit, on établit un diagramme de phase d'électrons en interactions dans un cristal bidimensionnel à géométrie kagome. Ce diagramme de phase est dressé en fonction de deux paramètres étant les interactions coulombiennes entre électrons sur un même atome pour le premier, et sur des atomes plus proches voisins pour le second. Les énergies caractéristiques de ces deux interactions sont quantifiées par rapport à une énergie de référence étant celle des fluctuations quantiques. On met alors en évidence quatre phases dont deux sont nouvelles, alors que les deux autres font le lien avec la littérature déjà existante, et sont en accord avec cette dernière. Ces deux nouvelles phases émergent lorsque l'énergie de répulsion coulombienne entre électrons sur un même atome domine devant l’énergie caractéristique des fluctuations quantiques. En présence d’une forte répulsion coulombienne entre électrons sur des atomes plus proches voisins, les charges électroniques ne peuvent se délocaliser pour former des ondes de Bloch et sont soumis à ce que l’on appelle une contrainte locale de charge. Apparaissent alors sous la compétition de ces deux interactions coulombiennes, des modes unidimensionnels collectifs le long des chaines d’atomes antiferromagnétiquement ordonnées. Ces modes ont la particularité d’être stabilisés à la fois par les fluctuations des degrés de liberté de spin, et de charge des électrons. La seconde de ces nouvelles phases émerge lorsque la répulsion coulombienne entre électrons sur des atomes voisins devient faible devant les fluctuations quantiques. La contrainte locale est alors relâchée et les électrons forment des ondes de Bloch le long de ce qui s’apparente à des bulles quantiques unidimensionnelles et polarisées en spin. Ces bulles sont alors piégées dans un cristal d’électrons inversement polarisés, avec lesquels elles sont en interaction antiferromagnétique.Le second projet porte sur l’étude d’un aimant moléculaire de Terbium Double-Decker. Cette molécule peut être modélisée par trois degrés de liberté interagissant en cascade les uns avec les autres. Le premier d’entre eux est un degré de liberté de spin nucléaire porté par le noyau de l’ion terbium de la molécule. Ce spin nucléaire est en interaction d’échange avec un degré de liberté de spin électronique porté par les électrons de l’ion terbium. Enfin, en première approximation, ce spin électronique génère un champ dipolaire auquel sont soumis les deux ligands de l’aimant moléculaire. Ces deux ligands sont couplés à deux électrodes de source et de drain, assurant le transport d’électrons uniques à travers ces deniers. Le tout forme donc un transistor à électron unique dans lequel les ligands servent de boîte quantique. Par mesure de magnéto-conductance, il est donc possible par une lecture en cascade, de remonter à l’état du spin électronique et du spin nucléaire. La première étape du projet a donc consisté à établir un modèle décrivant l’aimant moléculaire couplé à ces deux électrodes, afin de prédire les mesures de conductance réalisées au travers du transistor lors des thèses de Stefen Thiele et Clément Godfrin. Les résultats théoriques et expérimentaux obtenus sont en accord quantitatifs.D’autres part, à l’aide de champs électriques radio-fréquences, il est possible de manipuler expérimentalement et de façon cohérente le spin nucléaire. Cette manipulation cohérente du spin nucléaire se fait par l’intermédiaire du nuage électronique de l’ion, et permet ainsi d’être en mesure de réaliser un algorithme quantique sur le spin nucléaire de l’ion terbium. La réalisation d’un programme de simulation a permis de guider la réalisation expérimentale de l’algorithme de Grover, lequel a été implémenté avec succès au cours de la thèse de Clément Godfrin. / This thesis focuses on two different spin and charge systems, interacting under the effect of quantum fluctuations.The first project highlights the phase diagram of interacting electrons on a kagome lattice. This diagram is driven by two Coulomb repulsions. The first is a on site repulsion, and the second a nearest neighbor one. These two repulsions are in competition with quantum fluctuations of electronic charges. Four phases are depicted, two are unknown and the two other are in agreement with the literature. The two new phases are stabilized in the strong on site repulsion regime. When nearest neighbor repulsions are strong enough to induce a charge local constraint, the system enters in a so called Heisenberg-Loop Phase. These loops are antiferromagnetically arranged and can be described by a Heisenberg-like model in which both charge and spin play surprisingly a role in the exchange interaction. The second new phase is stabilized in the regime where nearest neighbor interactions are too weak to maintain the local constraint. Then, half of the electrons are delocalized in unidimensional Bloch states similar to quantum polarized electronic bubbles. These bubbles are trapped in an inversely polarized electronic cristal formed by the other electrons. This peculiar phase is favored by both quantum charge fluctuations in the bubbles, and antiferromagnetic exchanges between their electrons and the cristal ones.The second project deals with a Terbium Double-Decker molecular magnet. This molecule is modeled by three interacting degrees of freedom. The first is a nuclear spin of the Terbium ion, and the second is the electronic spin of this same ion. The two spins interact via a magnetic exchange.In a first approximation, the effect of the electronic spin is to induce a dipolar field. Finally, the last degree of freedom is carried by two ligands under the influence of the dipolar field. The ligands play the role of a read-out quantum dot, and by conductance measurements through this last one, we can probe the electronic spin and then, the nuclear spin. The first step of this project highlights the modeling of the global system. Then numerical computations are depicted and are in a quantitative agreement with the experimental measurements realized during the thesis of Stefan Thiele and Clément Godfrin.On the other hand, by applying electrical Radio Frequency Fields, we can drive quantum fluctuations on the nuclear spin. This quantum manipulation of the spin is realized by the dynamic deformation of the electron cloud under the effect of the Radio Frequency Field. As a result, we are able to implement a Grover Quantum Algorithm on the nuclear field. This thesis focuses on the realization of a simulation program that was a tool used by Clément Godfrin to successfully implement the Grover Algorithm.

Le travail expérimental développé pendant cette thèse se situe à l'interface de deux champs en physique de la matière condensée, à savoir les verres de spins et la physique mésoscopique. Les verres de spins ont été largement étudié et font partie des problèmes les plus débattus au cours des années tant d'un point de vue expérimental que théorique. Cet état est caractérisé par des propriétés très particulières qui se font jour lors d'une transition de phase magnétique à très basses températures qui est elle-même inhabituelle. En effet, cette transition est due à un mélange de frustration et de désordre dans la structure magnétique du système. Ce faisant, c'est un système modèle pour les verres et les systèmes frustrés en général. Après bien des efforts, des travaux théoriques ont réussi à décrire l'état fondamental du système au moyen de deux approches différentes et apparemment incompatibles. Cependant, la question de la vraie nature de la phase verre de spin reste grandement débattue.La physique mésoscopique, de son côté, traite du transport électronique dans les échantillons pour lesquels les électrons gardent leur cohérence de phase. Si les électrons restent cohérents, il est possible de voir des effets d'interférences qui sont des signes quantiques de ce qu'il se passe au niveau atomique. Dans cette thèse, il est utilisé pour sonder le désordre aussi bien magnétique que statique dans un verre de spins.Nous montrons que, contrairement à ce qui est cru, de forts changements se déroulent dans le désordre microscopique même à basses températures. Nous prétendons également que ces changements sont purement structuraux et viennent du fait de systèmes dont la distribution en énergie est très large. / The experimental work developed during this PhD is situated at the interface of two fields of condensed matter physics, namely spin glasses and mesoscopic physics. Spin glasses have been widely studied and are one of the problem that has been the most discussed over the years, both on a theoretical and experimental point of view. This state is characterized by very peculiar properties that come to light as it exhibits a magnetic phase transition at low temperatures that is already unusual. Indeed, this transition is due to a mix of frustration and disorder in the magnetic structure of the system, making it an exceptional model system for glasses and frustrated systems in general. After many efforts, theoreticians managed to described the fundamental state of the system by the mean of two different and apparently incompatible approaches. The first one, called RSB theory, is based on a mean-field approximation and predicts a complex phase space with an unconventional hierarchical organization. The second is based on more phenomenological approach and is named Droplet theory. It points towards a unique ground state and explain all the observation by slow relaxation processes. However, the question of the true nature of the spin glass phase is still heavily debated. Mesoscopic physics, for its part, addresses the question of electronic transport for samples in which the electrons keep their phase coherence. If the electrons remains coherent, it is possible to see interference effects that are quantum signs of what happens at the atomic level. In this work, it is used to probe the magnetic and static disorder in spin glasses. Indeed, it is possible to interpret the change in those interferences as changes in the microscopic disorder configuration and to know exactly how the spin glass state evolves. Some work have already tried to use coherent transport in spin glasses but this remains an open field. This work has then be dedicated to the implementation of transport measurement in spin glasses and mesocopic conductors. The first part will be focused on a the experimental setup that was used to perform very precise transport measurements and on the processing of the data taken out of them. In a second part, we will present some general physical characteristics of our samples such as their resistance dependence to the temperature or magnetic field, before extracting the quantum signature in magnetoresistance measurements. Finally, we will discuss the results obtained. We show that strong changes in the microscopic disorder happen even at low temperatures, in opposition to what is believed. We argue that those observed changes are purely structural and come from systems that are widely distributed in energy.

O efeito de instalação de estacas cravadas em areia, que promove um aumento da compacidade do solo e de seus parâmetros de resistência e deformabilidade, é analisado nesta dissertação em conjunto com o efeito de grupo. O procedimento estabelecido objetiva quantificar a melhoria após a instalação de um grupo de estacas e foi desenvolvido nesta pesquisa a partir da contribuição de Alves (1998). Para a utilização deste procedimento, foram propostas correlações do módulo de Young do solo em função da resistência à penetração NSPT (ou da resistência à penetração normalizada N60), a partir de um banco de dados obtido da literatura, visando não apenas as aplicações implementadas neste estudo, como também nortear futuras aplicações práticas. Na análise de casos documentados da literatura, foi utilizado o programa Plaxis 3D Foundation. Inicialmente foi procedida a calibração do programa através da reprodução de um caso de instrumentação de um grupo de estacas na argila rija de Londres, muito bem documentado por Cooke et al. (1980). Os resultados das simulações, com parâmetros do solo obtidos da literatura, se ajustaram muito bem aos resultados experimentais, seja nos valores de recalque, seja nos diagramas de transferência de carga. Posteriormente, a melhoria do solo por efeito da instalação foi estimada, através do procedimento estabelecido nesta dissertação, baseado em Alves (1998), a partir das características iniciais do solo antes da instalação de um grupo de estacas em modelo reduzido em solo arenoso. Obtidos os parâmetros melhorados previstos para o solo após a instalação, estes foram aplicados a um grupo de 9 estacas, para diferentes espaçamentos relativos, como dados de entrada no programa Plaxis. A comparação dos resultados experimentais com aqueles simulados numericamente sinaliza para o potencial tanto do programa Plaxis, na reprodução do comportamento do conjunto, como do modelo de Alves (1998), que norteou o procedimento proposto nesta pesquisa. O fator de escala, ressaltado na dissertação, bem como outros aspectos relevantes observados nas análises realizadas, são propostos como temas futuros a serem investigados na continuidade desta linha de pesquisa. / The installation effect of piles driven in sand, which increases soill density, strength and deformability parameters, is analyzed in this research, together with the pile-group effect. The procedure has been established aiming at the soil improvement achieved after installation of the piles. The proposed procedure is based on Alves (1998). In order to apply the procedure, correlations between the soil Young modulus and the NSPT blow count (or the normalized N60) have been established from a database obtained in the literature, aiming not only at the applications implemented in this study but also as a guideline for future practical applications. The program Plaxis 3D Foundation has been used in the analysis of documented cases from the literature, as an initial step to implement the procedure proposed in this thesis. Initially, the program has been calibrated by application to a well-documented piling group in the London stiff clay by Cooke et al. (1980). The results of the numerical simulations with soil parameters obtained from the literature have been very close to the experimental values, not only for the settlements, but also for the load transfer diagrams. The soil improvement due to pile installation has been implemented in this thesis based on Alves (1998). It has been applied to a case of small-scale model piling group in sands, taking into consideration the initial characteristics of the soil before installation and the soil improvement after driving. The updated parameters, together with different pile spacing in the 9-pile group, have been entered as input in the program Plaxis 3D Foundation. The comparison of the experimental results with those numerically simulated shows the potentiality of Plaxis program, due to its ability to properly reproduce the piling group behavior, and also of the model by Alves (1998), which guided the soil improvement procedure proposed in this research. The scale factor, highlighted in the thesis, as well as other relevant factors observed in the analyses, are topics for further investigation in continuity of this research.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Interleukin 11 (IL-11) is a multifunctional cytokine in the IL-6 type family of long-chain helical cytokines, which modulates the proliferation, differentiation and maturation of various types of hematopoietic cells. Recombinant human interleukin-11 (rhIL-11) produced by DNA technology in Escherichia coli is currently being used worldwide for the prevention of thrombocytopenia and to reduce the need for platelet transfusions after myelosuppressive chemotherapy in patients with nonmyeloid malignancies. A stability-indicating reversed-phase liquid chromatography (RP-LC) method was validated for the assessment of recombinant human interleukin-11 (rhIL-11) in biopharmaceutical formulations. The RP-LC method was carried out on a Jupiter C4 column (250 mm x 4.6 mm i.d.), maintained at 25ºC. The mobile phase A consisted of 0.1% TFA and the mobile phase B was acetonitrile with 0.1% TFA, run as follows: time 0 to 0.1 min 40% of B; from 0.1 to 30 min linear up to 65% of B; from 30.01 to 31 min linear down to 40% of B, maintained up to 40 min. The flow rate was 1 mL/min, and using photodiode array (PDA) detection at 214 nm. Chromatographic separation was obtained with a retention time of 27.6 min, and was linear over the concentration range of 1 200 μg/mL (r2 = 0.9995). The limits of detection and quantitation were 0.34 and 1.12 μg/mL, respectively. Specificity was established in degradation studies, which also showed that there was no interference of the excipients. The accuracy was 100.22% with bias lower than 1.25%. Moreover, the in vitro cytotoxicity test of the degraded products showed non-significant differences (p>0.05). The proposed method was applied to the assessment of rhIL-11 and related proteins in biopharmaceutical dosage forms, and the results were correlated to those of a bioassay, showing a higher mean difference of the estimated content/potencies of 2.60% for the RP-LC method, aiming to establish new alternatives to monitor stability, improve quality control and thereby assure therapeutic efficacy of the biological medicine. / A interleucina 11 (IL-11) é uma citocina multifuncional que pertence a família da interleucina- 6 e estimula a proliferação, diferenciação e maturação de células hematopoiéticas. A interleucina-11 humana recombinante (rhIL-11) é produzida pela tecnologia do DNA em Escherichia coli e é usada clinicamente para a prevenção de trombocitopenia grave e redução da necessidade de transfusão de plaquetas após quimioterapia mielossupressiva em pacientes com neoplasias malignas não mielóides. No presente trabalho foi desenvolvido e validado método por cromatografia líquida em fase reversa (CL-FR) para a avaliação de rhIL-11 em formulações de produtos farmacêuticos. Utilizou-se coluna Júpiter C4 (250 mm x 4,6 mm d.i.), mantida a 25ºC. A fase móvel A foi constituída de TFA 0,1% e a fase móvel B de acetonitrila com 0,1% TFA, eluídas no seguinte gradiente: 0 0,1 min, 40% de B; 0,1 30 min, 40 65% de B; 30,01 a 31 min, 65 40% de B, mantendo-se nesta proporção até 40 min. Utilizou-se vazão de 1 mL/min e detector de arranjo de diodos (DAD) a 214 nm. A eluição cromatográfica foi obtida no tempo de 27,6 min, sendo linear na faixa de concentração de 1 200 μg/mL (r2 = 0,9995). Os limites de detecção e quantificação foram 0,34 e 1,12 μg/mL, respectivamente. A especificidade foi avaliada em estudos de degradação, que também demonstraram que não houve interferência dos excipientes. A exatidão foi 100,20%, com bias inferior a 1,25%. Além disso, realizou-se o teste de citotoxicidade in vitro das formas degradadas, as quais não apresentaram diferença significativa em relação a forma intacta (p>0,05). O método proposto foi aplicado para a avaliação da potência de rhIL-11 e de proteínas relacionadas em formulações farmacêuticas, e os resultados foram comparados com o bioensaio, observando-se diferenças das médias de conteúdo/potência 2,60% superiores para o método por CL-FR. Contribuíu-se assim para estabelecer procedimentos que aprimoram o controle da qualidade, garantindo a segurança e eficácia terapêutica do produto biotecnológico.

Made available in DSpace on 2016-06-02T20:15:26Z (GMT). No. of bitstreams: 1 4780.pdf: 9997745 bytes, checksum: 24a1f1c6cc3ce4ef4b6ac0cc5009255c (MD5) Previous issue date: 2013-01-11 / Universidade Federal de Sao Carlos / In this thesis, we study the behavior of Quantum Discord in the contexts of open quantum systems and spin chains. Furthermore, we investigate the thermalization process of a spin chain due to interaction with the environment. First, we present a review on the concept of quantum correlation, beginning with the first ideas on non-locality, and leading to the measure of quantum correlations called Quantum Discord. Afterwards, we study the dynamics of the quantum correlations between two non-interacting qubits coupled to Markovian and non- Markovian thermal reservoirs. In the context of spin chains, we investigate the behavior of quantum correlations at finite temperatures, starting with a system composed of two interacting spins, described by XYZ model, in order to generalize this study to the case of infinite unidimensional spin chains, described by XY and XXZ models. In this context, we investigate the relationship between quantum correlations and quantum phase transitions present in these two models. We conclude this thesis with a study of the thermalization process of two interacting spins weakly coupled to independent bosonic thermal reservoirs, or to a single collective reservoir, besides presenting some results for larger systems, composed of an arbitrary number of spins. / Nesta tese estudamos o comportamento da Discórdia Quântica nos contextos de sistemas quânticos abertos e cadeias de spins. Além disso, investigamos também o processo de termalização de uma cadeia de spins sujeita a interação com o meio-ambiente. Primeiramente, apresentamos uma revisão do conceito de correlação quântica, partindo das ideias iniciais sobre não-localidade e tendo como ponto final a medida de correlações quânticas denominada Discórdia Quântica. Posteriormente, estudamos a dinâmica das correlações quânticas entre dois qubits não-interagentes acoplados a reservatórios térmicos markovianos e não-markovianos. No contexto de cadeias de spins, investigamos o comportamento das correlações quânticas a temperaturas finitas, começando com um sistema formado por dois spins interagentes, descrito pelo modelo XYZ para, em seguida, generalizar este estudo para o caso de cadeias de spins unidimensionais infinitas, descritas pelos modelos XY e XXZ. Neste contexto, investigamos a relação entre as correlações quânticas e as transições de fase quânticas presentes nestes dois modelos. Finalizamos esta tese com um estudo sobre o processo de termalização de dois spins interagentes fracamente acoplados a reservatórios térmicos bosônicos independentes ou um único reservatório coletivo, além de apresentar alguns resultados referentes a sistemas maiores, formados por um número arbitrário de spins.

Made available in DSpace on 2016-06-02T20:16:53Z (GMT). No. of bitstreams: 1 6362.pdf: 1897034 bytes, checksum: c83efb3252adeb24e85652c3a2f8240c (MD5) Previous issue date: 2014-08-26 / Universidade Federal de Sao Carlos / We are interested in understanding the process of Markovian thermalization in quantum systems when we have one or two qubits interacting with a quantum electromagnetic field mode, using the Rabi model, in situations where there is interaction with a reservoir modeling the environment surrounding the system. This analysis of the thermalization is based on the calculation of the eigenvalues of the Liouvillian of the Markovian master equation. We will focus mainly on situations where there is interaction with independent and collective reservoirs, for cases where the subsystems interact with reservoirs at T=0K and T >0K. We investigate situations where there is no thermalization of the system and how this may influence interesting physical properties, such as the statistical properties of the field in the ultra strong scheme using the theory of input-output and quantum correlations between qubits collectively interacting with Markovian reservoirs. / Estamos interessados em entender o processo de termalização em sistemas quânticos markovianos, quando temos um ou dois qubits interagindo com um modo quântico do campo eletromagnético, utilizando o modelo de Rabi, em situações onde há interação com estruturas de reservatório que modelam o ambiente que cerca o sistema. Essa análise da termalização é baseada no cálculo dos autovalores do liouvilliano da equação mestra markoviana. Iremos focar principalmente nas situações onde há interação com reservatórios independentes e coletivos, para casos onde o subsistema interage com reservatórios a T=0K e T >0K. Investigamos situações onde há termalização ou não do sistema e como esse fator pode influenciar nas propriedades físicas interessantes, como, por exemplo, a estatística de detecção de fótons no regime ultra forte utilizando a teoria de entrada e saída e correlações quânticas entre os qubits interagindo com reservatórios markovianos.

The rapid depletion of hydrocarbon fields around the world has led the industry to search for these resources in ever increasing water depths. In this context, the large diameter (D > 100mm) vertical riser has become a subject of great interest. In this research work, a major investigation was undertaken to determine the two phase flow hydrodynamics in a 254mm vertical riser. Two types of experiments were performed for range of air-water superficial velocities. The first experimental campaign addresses the issue of the two gas injector’s performances (conventional vs. novel design gas injector) in the large diameter vertical riser. The experimental results show that the novel design gas injector should be the preferential choice. The second set of the experimental work investigates the two phase flow hydrodynamics in the vertical riser in detail. The two phase flow patterns and their transitions were identified by combination of visual observations and statistical features. Based on the results, the experimental flow regime map was developed and compared with the existing vertical upflow regime maps/models. None of the flow regime transition models adequately predicted the flow regimes transitions in large diameter vertical risers as a whole. In this regard, the Taitel et al. (1980) bubble to slug flow transition model has been modified for large diameter vertical upflow conditions, based on the physical mechanism observed. The general trends of modified criteria agreed well with the current and other large diameter experimental results. The effect of upstream conditions on the vertical riser flow behaviour was also investigated in detail by two different inlet configurations (i) near riser base injection and (ii) upstream flowline injection. It was found that no significant differences exist in flow behaviour at low air-water superficial velocities for both the inlet configuration, at high air-water superficial velocities, the intermittent flow behavior in flowline influences the riser flow pattern characteristics and thereby controls the riser dynamics. It is found that liquid slugs from the flowline naturally dissipate to some extent in the riser as a consequence of compression of succeeding bubble that rapidly expands and break through the liquid slug preceding it when it enters the riser. The experimental work corroborates the general consensus that slug flow does not exist in large diameter vertical upflow condition. Experimental data has been further compared to increase the confidence on the existing two phase flow knowledge on large diameter vertical riser: (a) by comparing with other experimental studies on large diameter vertical upflow in which generally, a good agreement was found, (b) by assessing the predictive capability of void fraction correlations/pressure gradient methods. The important implication of this assessment is that the mechanistic approach based on specific flow regime in determining the void fraction and pressure gradient is more successful than conventional empirical based approaches. The assessment also proposes a proposed set a of flow regime specific correlations that recommends void fraction correlations based on their performances in the individual flow regimes. Finally, a numerical model to study the hydrodynamic behaviour in the large diameter horizontal flowline-vertical riser system is developed using multiphase flow simulator OLGA. The simulated results show satisfactory agreement for the stable flows while discrepancies were noted for highly intermittent flows. The real time boundary application was partially successful in qualitatively reproducing the trends. The discrepancies between the predicted results and experimental data are likely to be related to the incorrect closure relations used based on incorrect flow regimes predictions. The existence of the multiple roots in the OLGA code is also reported for the first time.

Le travail proposé dans cette thèse est basé sur des expérience de corrélation de photons faites sur un émetteur de photon unique semi conducteur: une boite quantique de CdSe dans un nanofil de ZnSe. La première démonstration d'émission de photons unique d'une boite quantique épitaxiée à température ambiante y est présentée. Pour expliquer ce résultat, nous avons étudie expérimentalement et théoriquement l'efficacité de couplage exciton-phonon et ses conséquences sur l'intensité de l'exciton avec la température. Nous présentons également des résultats optiques portant sur la robustesse de cette structure à haute température. La technique de corrélation de photons est également appliquée sur des boites quantiques chargées. la présence du exciton chargé nous a permis de sondé la structure fine du trio excité, de décrire ses processus de relaxations et d'obtenir une mesure direct du temps de spin flip du trou sur l'état p. Des indication sont également données sur la nature possible du dopage. Nous avons aussi étudié la diffusion spectrale de l'émetteur causée par les fluctuations électroniques de son environnement. Par un travail théorique nous montrons comment interpréter l'effet de l'élargissement phonon de la raie homogène, (processus poissonien) combiné avec l'effet de la diffusion spectral (processus markovien) sur la fonction de corrélation de la demi-raie. Grâce à l'expérience, nous concluons sur la statistique de l'énergie d'émission de l'émetteur à haute température. Nous appliquons cette théorie sur les nanofils et interprétons les dépendances en température et en puissance des fluctuations de l'environnement grâce au modèle de Kubo-Anderson. / The work proposed in this thesis is based on photon correlation experiments performed on a semi-conductor single photon emitter: CdSe/ZnSe nanowire quantum dot. Is presented the first demonstration of single photon emission at room temperature from an epitaxied quantum dot. To explain this result we investigated by a theoretical and experimental study, the exciton-phonon coupling efficiency and its consequence on the exciton luminescence intensity with temperature. We also present optical results on the robustness against temperature of this structure. Photon correlations techniques are also applied on charged quantum dots. Presence of the charged biexciton allowed to probe the fine structure of the excited trion, to describe its carrier relaxation processes, and to obtain a direct measurement of the p-shell hole spin flip time. Indications are also given on the possible doping nature. We also investigated spectral diffusion of the emitter caused by electronic fluctuations of the environnement. By a theoretical work, we show how to model the effect of the homogeneous phonon broadening, (poissonian emission energy process) combined with the spectral diffusion effect (markovian emission energy process) on the half line autocorrelation function. Thanks to experiments, We conclude on the statisic of the emission energy of the emitter at high temperature. We apply this theory on CdSe/ZnSe nanowire quantum dots and interpret temperature and power dependance of the environnement fluctuation thanks to the Kubo-Anderson Model.

Le présent travail se concentre sur l'étude des niveaux d'énergie et des processus de recombinaison de complexes excitoniques larges - jusqu'à quatre paires électron-trou - considérés au niveau d'une boîte quantique unique remplie optiquement. Les boîtes étudiées dans ces expériences, formées à partir d'une matrice de Ga(Al)As, représentent un système à zéro dimension avec un confinement relativement fort et peuvent en effet avoir plusieurs couches électroniques s, p, comme dans le cas d'atomes. Les boîtes peuvent être facilement sélectionnées à l'état individuel du fait de la très faible densité de surface des structures considérées. Les techniques expérimentales utilisée dans ce travail comprennent : les méthodes de spectroscopie sur boîtes uniques, la détection optique résolue en polarisation, l'utilisation de champs magnétiques intenses et des mesures de corrélation de photons. En ce qui concerne les expériences de photoluminescence, nous avons distingué les excitations en dessous de la barrière de celles se produisant en dessus. Finalement, des expériences de spectroscopie d'excitation de la photoluminescence ont aussi été réalisées en champ magnétique.En fonction des conditions d'excitation, les boîtes étudiées présentent une multitude de raies relativement étroites, chaque boîte révélant un schéma caractéristique de raies groupées en amas distincts, similaires à une série de couches électroniques pour un atome. La présente étude s'est concentrée sur l'intervalle spectral correspondant aux couches électroniques s et p. L'identification des raies spectrales s'est principalement basé sur les résultats obtenus lors d'observations résolues en polarisation ou bien lors de mesures de corrélation de photons. Ces expériences révèlent trois familles distinctes de raies d'émission, chacune étant respectivement reliée à un complexe électron-trou (excitonique) neutre, chargé positivement, ou bien négativement. Une attention particulière a été portée aux raies d'émission observées dans une cascade en quatre étapes partant d'un complexe à quatre excitons, jusqu'au niveau de la recombinaison d'un exciton neutre, ainsi que celles observées dans une cascade en deux étapes partant d'un bi-exciton chargé positivement, jusqu'à la recombinaison d'un état singulet ou triplet d'un exciton chargé positivement. La structure fine induite par les interactions d'échange - et préalablement observée lors des mesures résolues en polarisation à champ magnétique nul - a été étudiée pour différentes raies d'émission. L'évolution de ce dédoublement de raies a été examiné en fonction du champ magnétique. Les résultats sont interprétés en terme d'anisotropie de forme des boîtes et d'une interaction avec les effets spin-orbite, caractéristiques des différents processus de recombinaison. Une partie importante de ce travail a été dévolue à la comparaison entre le spectre d'émission mesuré pour des puissances d'excitations relativement importantes avec les spectres d'excitation de la photoluminescence. De telles expériences ont aussi été conduites sous champ magnétique. Comme attendu, les spectres d'émission des complexes excitoniques d'ordres élevés sont particulièrement affectés par les interactions coulombiennes entre porteurs, et sont par conséquent très différents des spectres d'excitation de la photoluminescence (quasi-absorption) des excitons neutre et chargés. Deux types d'évolution en champ magnétique de raies d'absorption observées (résonance) - reliées aux couches s et p - ont été mesurés. Les résonances de type s sont attribuées à la transition entre un niveau excité de trou de la bande de valence et l'état fondamental de la couche s dans la bande de conduction. Une raie d'émission, observée dans le groupement de la couche p, coïncide cependant avec la raie d'absorption. Nous concluons que cette résonance vient d'un état excitonique excité qui se recombine de manière radiative dû à un blocage efficace de sa relaxation vers l'état fondamental. / The studies of energy levels and of recombination processes of single quantum dots, optically filled with up to four electron-hole pairs are the subject of this work. The dots used in the present experiments, formed out of the Ga(Al)As matrix, represent relatively strongly confined zero-dimensional systems, and display several, atomic-like s-, p-,. . . shells. Single dots can be easily selected in our structures as they exhibit an extremely low surface density. Experimental techniques applied in this work include the methods of single dot spectroscopy, polarization resolved techniques, application of magnetic fields and photon correlation measurements. Distinct, below- and above-dot-barrier laser excitation has been used for photoluminescence experiments. Importantly, the photoluminescence excitations experiments (in magnetic fields) have been carried out, as well.Depending on excitation conditions (power and wavelength of laser), the investigated dots show a multitude of relatively sharp lines, each dot displaying the same, characteristic pattern of lines, grouped into distinct clusters corresponding to subsequent atomic-like shells. Spectral range covering the s- and p-shells region has been explored in the present studies. The assignment of spectral lines has been at large provided by the results of polarization resolved micro-photoluminescence and photon correlation experiments. Those experiments depict three distinct families of emission lines, each related to recombination of, correspondingly, neutral, positively charged and negatively charged electron-hole (excitonic) complexes. The emission lines observed within a four step cascade of a neutral quadexciton down to the recombination of a neutral exciton and two step cascades of positively charged biexcitons down to the recombination of a singlet and triplet state of positively charged excitons have been studied in details. The fine structure, induced by exchange interactions and preliminarily seen in (linear) polarization resolved emission experiment at zero magnetic field, has been studied for various emission lines (related to s- and p- shells). The evolution of this splitting has been then investigated as a function of the magnetic field. The results are interpreted in terms of the shape anisotropy of dots and an interplay between spin- and orbital-mediated effects, characteristic of different recombination processes. A significant portion of this work has aimed to compare the emission spectra measured at a relatively high excitation power (which include the recombination processes of up to quadexciton complexes) with photoluminescence excitation spectra (which probe the excited states of a single exciton). Such experiments have been also carried out as a function of the magnetic field. As expected the emission spectra of high order excitonic complexes are indeed greatly affected by Coulomb interactions between carriers and in consequence are in general very different from the photoluminescence excitation spectra (quasi absorption) of a neutral and charged exciton. Two types of the magnetic field evolution of detected absorption lines (resonant peaks), the s- and p-shell related, have been measured. The s-shell like resonant peaks were attributed to the transition between the excited hole levels in the valence band and the ground s-shell level in the conduction band. Nevertheless, there exists an emission line which is observed within the p-shell cluster, and which coincides with the absorption line. That "coinciding resonance" is concluded to be an excited excitonic state which recombines radiatively due to efficient blocking of its relaxation towards the ground state.