Cette thèse est une étude, au niveau moléculaire, par des méthodes de simulation numérique, des propriétés des aérosols organiques, notamment des aérosols marins, et de leur interaction avec des espèces présentes dans l’atmosphère. L’organisation de la matière organique au sein de ces aérosols joue un rôle fondamental pour leurs propriétés optiques, chimiques et leur rôle comme noyau de condensation pour les nuages.Dans une première partie, on présente contexte atmosphérique et les méthodes de dynamique moléculaire classique et les méthodes mixtes quantique/classique utilisées pour simuler ces aérosols. Ensuite, on décrit l’application de ces méthodes à trois cas.Tout d’abord, on a étudié, par dynamique moléculaire classique (logiciel Gromacs), l’organisation, notamment l’orientation, de molécules d’acide palmitique absorbées sur une surface de sel (NaCl) en fonction du taux de couverture en acide gras et de la température. On présente aussi une étude détaillée de l’influence de l’humidité sur l’organisation de ce film organique à la surface du sel, mettant en évidence l’existence d’îlots d’acide gras monocouches structurés. Dans une seconde étude, la réactivité de NO2 avec cet aérosol marin est traitée par une approche mixte quantique/classique (logiciel CP2K), avec prise en compte de l’impact de l’humidité sur cette réactivité.Enfin, la dernière étude concerne une étude par dynamique moléculaire de phases condensées organiques (n-butanol) et de leur interaction avec des molécules d’eau. Cette étude théorique, complémentaire d’expériences de jets moléculaires, a pour but de mieux comprendre le rôle fondamental que jouent ces interactions pour les propriétés des aérosols et des nuages. / In this thesis numerical methods are used to study the properties, described at the molecular level, of organic aerosols, especially marine aerosols, and their interaction with species in the atmosphere. The organisation of the organic matter in these aerosols plays a key role for their optical, chemical properties, and their ability to act as a cloud condensation nuclei.The first part reviews atmospheric context and the methods (classical molecular dynamics and hybrid quantum/classical approaches) used in this thesis. Then applications to three cases are detailed.Firstly, the organization, more particularly the orientation, of palmitic acid molecules adsorbed on a salt (NaCl) surface as a function of the fatty acid coverage and temperature has been studied using classical molecular dynamics (Gromacs package). The impact of the humidity on the structuration of this organic coating has been described in details, showing the existence of structured fatty acid island-like monolayers on NaCl surface.In a second study, the reactivity of NO2 with these heterogeneous marine aerosols has been investigated by a hybrid quantum/classical method (CP2K package), with taking into account the effect of the humidity.The last study is a classical molecular dynamics of n-butanol crystal, water accommodation at these surfaces and simulation of water jet collision with n-butanol surface. These simulations, complementary to experiments, were performed to better understand the fundamental role of the water-organic matter interaction on the properties of the aerosols and clouds.

Magíster en Ciencias, Mención Computación / El principal objetivo de esta tesis es encontrar casos tratables y buenas técnicas para computar Certain Answers sobre bases de datos de grafos incompletas, en tiempo polinomial. Las bases de datos de grafos surgen naturalmente de la necesidad de almacenar información de redes, tales como Facebook, mapas de rutas o la web. La idea de "incompletitud" viene de la falta de información completa, complejidad con la cual tenemos que trabajar a diario. Sobre estas bases de datos de grafos carentes de información completa, queremos realizar preguntas en la forma de consultas particulares y determinar si la pregunta puede ser contestada de la misma forma en cada posible completación de la base de datos. La respuesta a estas preguntas en cada posible completación de una base de datos de grafos incompleta es llamada Certain Answers. El problema de Certain Answers sobre bases de datos de grafos incompletas ya ha sido estudiado, y es conocido que este problema es en general co-NP completo. En esta tesis convertimos el problema de computar Certain Answers en un problema 3-SAT con su fórmula lógica booleana asociada. Podemos probar que bajo ciertas condiciones esta fórmula lógica tiene un número de variables que nos permite determinar si es satisfacible en tiempo polinomial. Luego, probamos que estas condiciones son exhaustivas: sin cualquiera de ellas el problema se vuelve co-NP completo otra vez. Para analizar más clases tratables del problema de Certain Answers, convertimos el problema Certain Answers en un problema de programación lineal entera. Con esta formulación de programación lineal, encontramos algunos casos tratables, algoritmos y heurísticas para resolverlo. Sin embargo, el principal logro es la nueva formulación en sí, porque nos permite usar las bien conocidas técnicas de programación lineal para encontrar más casos tratables y mejores heurísticas.

Dans ce travail de thèse tant théorique que numérique, on étudie les différentes instabilités pouvant se développer dans un milieu poreux saturé par un fluide viscoélastique et chauffé par le bas. La formulation mathématique des équations de ce problème repose sur la loi phénoménologique de Darcy généralisée à un fluide viscoélastique vérifiant l’approximation de Boussinesq. Ce problème admet une solution de conduction, et on trouve que deux types de structures sont susceptibles d’apparaître lorsque l’état de conduction perd sa stabilité : des structures stationnaires et des structures oscillatoires. Les seuils d’apparition de ces structures sont étudiés en fonction des paramètres adimensionnés du problème, à savoir le nombre de Rayleigh, les temps de relaxation et de retardation associés à l’élasticité du fluide. Une étude linéaire et non linéaire est donc menée. Il est intéressant de noter qu’une compétition entre les structures stationnaires et oscillatoires peut exister au voisinage d’un point appelé point de codimension 2. Une analyse non linéaire est donc menée au voisinage de ce point et est confrontée aux résultats issus des simulations numériques. Enfin, s’appuyant sur les propriétés de mélanges binaires des fluides viscoélastiques, une étude théorique est réalisée et nous montrons qu’il y a une compétition entre deux régimes : un régime où la viscoélasticité est dominante et un autre où l’aspect mélange binaire l’emporte. Ce résultat permet d’expliquer certaines observations expérimentales. / In this theoretical and numerical work, we study differents instabilities which can develop in a porous media saturated by viscoelastic fluid and heated from below. The mathematical formulation of the equations of this problem is based on phenomenological Darcy law generalized to a viscoelastic fluid verifying Boussinesq estimate. This problem admits a solution of conduction, and we find that two types of structures may appear when the conduction state loses his stability : stationary and oscillatory structures.The apparition thresholds of these thermo-convectives structures are studied and depend on the non-dimensionnalized parameters of the problem, Rayleigh number, relaxation and retardation time associated to the fluid elasticity. A linear and non linear stability is also realized. It is interesting to note that it can have a competition between stationary and oscillatory structures near a point named codimension 2 point. A linear analysis is also realized near this point and is compared to the numerical simulation results.Finally, by taking into account binary mixtures properties of the viscoelastic fluids, a theoretical study is realized and we show that there is a competition between two states : a state in which viscoelasticity is dominant and another state in which binaries properties are also dominants. This result can explain experimental observations.

This thesis examines the exegesis of I Corinthians 5:3-5 between the years of 200, when the text is first cited, and 451, by which time the text had been subjected to a variety of exegetical approaches and applied to a number of different situations. A chronological (rather than topical) approach has been adopted; each writer's overall use of the passage is studied, in hope that this will give better insight into his exegesis of the Corinthian text. Although penitential theology was beginning to develop, with one major penance allowed for grievous post-baptismal sin (an idea found in the Shepherd of Hermas), the earliest extant exegesis of I Corinthians 5 :3-5 occurs in the works of Tertullian during his Montanist phase; he cites it to support his argument that certain grave sins are beyond remission by the Church. For Tertullian, the interitum earn is refers to irrevocable excommunication and possible death for a serious offender. The spiritus which is to be saved is that of the Church, since the offender's spirit cannot possibly be saved after a descent into serious sin. Later in the same century, Origen takes a different position; since Paul counseled the church at Corinth to forgive a penitent sinner (II Corinthians 2: 5-11), this was presumably the same man who had so grievously sinned (I Corinthians 5). Therefore, all sins are remissible by the Church. Origen construes the 7tv£uμa to be saved as the offender's spirit. The oA.£0pov -cilc; crapx:oc; refers to the destruction of the cpp6v11μa -cilc; crapx:oc; and may be identified with the sufferings and humiliations which penitents undergo. These approaches to the Corinthian passage are joined by a third in the following century: Basil, although he at times cites I Corinthians 5 :3-5 in a congregational context, also transplants the passage into a monastic setting, deriving support from it for his method of chastising recalcitrant monks. Here xxx is construed as the individualistic, self-asserting human nature. This thesis will show that these three methods of interpreting the Corinthian text remain normative for the period under discussion, although by the end of the period under discussion, writers such as John Chrysostom, Pacian, and Jerome suggest that the punishment may involve more than mere excommunication, although it does include that. By the mid-fifth century, the exegesis of I Corinthians 5 is closely bound to the penitential procedure of the Church, and there is general agreement that the passage's overall character is remedial and restorative; crap~ refers to the carnal nature which must be destroyed in order for a person to become spiritual again, and this is done through penance. The punishment imposed by Paul is seen to be temporary and restorative, not final and destructive. Although the patristic consensus differs from most modem commentators in identifying the offenders of I Corinthians 5 and II Corinthians 2, nevertheless the exegesis of this passage by the Fathers retains its interest and value. Some of the more exceptional interpretations are now echoed in recent commentaries.

Le carbure de zirconium (ZrC) est une céramique non oxyde utilisée dans l'industrie nucléaire et aéronautique. Cependant, ses excellentes propriétés mécaniques et physiques sont entravées par la formation d'oxydes à des températures de 500 à 600 ° C. Il est ainsi nécessaire de protéger la surface de ZrC avec d'autres matériaux tels que du carbure de silicium (SiC). La théorie de la fonctionnelle de la densité (DFT) combinée à une approche thermodynamique a été utilisée pour étudier la structure, les propriétés et la réactivité des surfaces de ZrC en vue de leurs fonctionnalisation. La stabilité des différentes surfaces à faible indice de ZrC a été étudiée afin de déterminer les surfaces exposées lors de la fonctionnalisation et le revêtement avec le SiC. Une étude préliminaire de la réactivité de petites molécules inorganiques telles que H2O, O2 et H2 a été effectuée. Ensuite, les propriétés des surfaces dans une atmosphère oxydante ont été modélisées pour développer des modèles pour les surfaces oxydées et les différents types de couches d'oxyde exposées. Plusieurs techniques expérimentales ont été combinées avec les études théoriques pour valider ces modèles. La Fonctionnalisation de ZrC a ensuite été étudiée en partant des différents modèles de surfaces oxydées. Les molécules utilisées classiquement pour la fonctionnalisation telles que le 3-bromopropyne et le chloro-allylediméthylsilane interagissant très peu avec la surface, nous avons proposé l’acide 3-buténoïque comme molécule qui se lie très fortement à la surface tout en montrant une très réactivité très intéressante vis à vis du diphénylsilane qui est le précurseur de SiC (après une étape de pyrolyse). / ZrC is a non-oxide ceramic applied in the nuclear and aerospace industries but the excellent mechanical and physical properties are hampered by formation of low refractory oxides at temperatures of 500-600 oC. A need exists for coating the surface with other materials like SiC. Density functional theory (DFT) combined with thermodynamic modelling was used for this study. Stabilities of the various low index surfaces of ZrC are studied to determine the appropriate surfaces for coating with SiC. A preliminary study of reactivity of small inorganic molecules such as H2O, O2, and H2 is carried out. The properties of ZrC surfaces towards oxidation is then studied to develop proper models and understanding of the different types of oxide layers exhibited at real oxidizing conditions. Several experimental techniques were combined with the theoretical studies to analyse the oxide layers formed on ZrC surfaces. Mechanical and thermodynamic models were developed to characterize the interface formed between ZrC surfaces and the oxide layer. Functionalization of ZrC was finally carried out on the exposed facets of the oxidized ZrC. The functionalized surfaces were first grafted with 3-bromo propyne and allyl(chloro)dimethylsilane followed by hydrosilylation from diphenylsilane and 1,4-diethylnylbenzene (these two monomers form a polymer macromolecule). The resulting particles are finally subjected to laser pyrolysis to yield the resulting ZrC/SiC core/shell nanocomposites. The use of H2O as functionalizing group however did not yield grafted polymer units and hence a dual functional group organic molecule (3-butenoic acid) was used to yield the desired ZrC/SiC nanocomposites.

À l'heure actuelle, il y a un intérêt croissant pour l’adaptation des propriétés physique des solides contenant des métaux de transition en modifiant leurs réseaux ioniques. Ces changements topologiques modifient non seulement le degré d’oxydation du métal de transition, mais peuvent également modifier sa sphère de coordinence, ainsi que les connectivités cation-anion-cation à longue distance, pouvant conduire à des changements radicaux de leurs propriétés physiques.Dans ce contexte, mon travail de thèse, réalisé au laboratoire UCCS à Lille (France), a consisté en une étude approfondie de deux différents exemples de transformations topotactiques. Premièrement, je présente l´échange anionique ainsi que l'exfoliation en nano-feuillets chargés positivement, de l'oxo-bromure de cobalt 14H-Ba7Co6BrO17. Le processus d'exfoliation a été caractérisé structuralement à l’aide de techniques telles que les microscopies, la diffraction ou l’absorption des rayons X.Dans la deuxième partie de mon travail, une étude complète du processus d’exsolution reversible du fer dans BaFe2(PO4)2 a été effectuée, en établissant une relation entre les évolutions structurales et la quantité de fer exsoluté. Une étude sur l'insertion éventuelle du lithium dans la structure de la phase la plus lacunaire en fer, BaFe1.33(PO4)2, ainsi que ses capacités en tant que cathode pour batteries au lithium, a également été réalisée. En outre, des études structurales et magnétiques des solutions solides BaFe2-YMY (PO4)2 par substitution du métal par Co2+ ou Ni2+a aussi été réalisée.Enfin, dans la dernière partie de ce manuscrit, je présente trois phases différentes à base de fer qui ont été découvertes lors de prospection pour trouver de nouvelles phases ayant des capacités de transformations topotactique. / At present, there is growing interest in tuning the physical behavior of solids containing transition metals by modifying their ionic lattices. These topological changes modify not only the electron count (through reduction or oxidation) but can also modify the local transition metal coordination sphere and the long-range cation-anion-cation connectivity, potentially leading to dramatic changes in their physical behavior. In this context, my PhD work developed in the UCCS laboratory at Lille (France), has consisted in a deep study of two different examples of topotactic transformations. Firstly I have performed anionic exchange as well as exfoliation into positively-charged nanoflakes, on the oxybromide cobaltites 15H-Ba7Co6BrO17. This exfoliation process has been structurally characterized by different techniques as microscopies, X-Rays diffractions and absorptions. For the last two, synchrotron radiation was used, the experiments being performed at SOLEIL.Secondely, a full study of the reversible iron exsolution process in BaFe2(PO4)2 has been carried out, establishing a relation between the structural features and the amount of iron exsoluted. A study about a possible lithium insertion in the lattice of the most exsoluted phase, BaFe1.33(PO4)2, as well as its capabilities determination as cathode in Li batteries was also performed. In addition, structural and magnetic studies has been realized in the substituted solid solutions of BaFe2-yMy(PO4)2 with M2+ = Co2+, Ni2+.Finally, the last part of the manuscript presents three different iron phases discovered during my prospecting work for new phases having abilities for topotactic transformation.

In adult cardiomyocytes, the established mechanism of excitation-contraction coupling is calcium-induced calcium release (CICR) mediated by L-type Ca2+ channels (Cav1.2). Briefly, membrane depolarization opens voltage-gated Cav1.2 to allow for the influx of extracellular Ca2+ into the cytosol. This small sarcolemmal (SL) Ca2+ influx is necessary for triggering a larger release of Ca2+ from the intracellular Ca2+ storage site, the sarcoplasmic reticulum (SR), through the SR Ca2+ release channel also known as the ryanodine receptor (RyR). RyR-mediated release of SR Ca2+ effectively raises the cytosolic free Ca2+ concentration, allowing for Ca2+ binding to troponin C on the troponin-tropomysin complex, leading to cross-bridge formation and cell contraction. However, previous functional data suggests an additional CICR modality involving reverse mode Na+-Ca2+ exchanger (NCX) activity also exists in neonate cardiomyocytes. To further our understanding of how CICR changes occur during development, we investigated the spatial arrangement of caveolin-3 (cav-3), the principle structural protein of small membrane invaginations named caveolae, and NCX in developing rabbit ventricular myocytes. Using traditional as well as novel image processing and analysis techniques, both qualitative and quantitative findings firmly establish the highly robust and organized nature of NCX and cav-3 distributions during development. Specifically, our results show that NCX and cav-3 are distributed on the peripheral membrane as discrete clusters and are not highly colocalized throughout development. 3D distance analysis revealed that NCX and cav-3 clusters are organized with a distinct longitudinal and transverse periodicity of 1-1.5 μm and that NCX and cav-3 cluster have a pronounced tendency to be mutually exclusive on the cell periphery. Although these findings do not support the original hypothesis that caveolae is the structuring element for a restricted microdomain facilitating NCX-CICR, our results cannot rule out the existence of such microdomain organized by other anchoring proteins. The developmentally stable distributions of NCX and cav-3 imply that the observed developmental CICR changes are achieved by the spatial re-organization of other protein partners of NCX or non-spatial modifications. In addition, the newly developed image processing and analysis techniques can have wide applicability to the investigations on the spatial distribution of other proteins and cellular structures. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

Background and Aim: Microalgae are a potential economical source of omega-3 fatty acids, which are known for their health benefits. Omega-3 fatty acids derived from microalgae are however still expensive due to high costs involved in production. These costs can partly be attributed to cultivation of microalgae in unialgal cultures, which are prone to contamination, difficult to scale up and require stringent control of growth conditions. This study therefore is aimed to investigate the feasibility of using a mixed microalgae culture for the production of omega-3 fatty acids. Methods and materials: The microalgae were grown under uncontrolled conditions in a hanging-bag photo-bioreactor, with only the phosphorus-nitrogen ratio (P:N-ratio) varied. Variations in the different population proportions in the culture were studied and related to the biomass, total fatty acid and omega-3 fatty acid productivity of the culture. Finally, a comparison was made between the results obtained in this study and similar studies found in literature. Results and discussion: The mixed culture used was composed of several green microalgae, whose proportions varied with P:N-ratio, season, and age of the culture. Different interactions between the populations were observable, and these were thought to influence the culture’s biomass, total fatty acids (TFAs) and omega-3 fatty acid productivity. The TFA content of the culture was ~10-20% by the end of the exponential phase, depending on the nutrients supplied. The fatty acids were composed of mostly unsaturated fatty acids, the majority of which were omega-3 fatty acids; C18:3ω3 (up to 50% of TFA), C16:4ω3 (up to 15%) and C18:4ω3 (up to 5%). Other fatty acids observed included C16:0 (up to 25%), C18:1ω9/C18:1ω8 (up to 20%), C18:2ω6 (up to 5%), traces of C18:0, C18:3ω6, C17:0, C16:3ω3 and C16:1ω7 were also detected. The presence of these fatty acids was found to vary depending on season, P:N-ratio, and age of the culture. When compared to studies in the literature, the mixed culture was found to perform better than, or as well as reported studies, where unialgal cultures were cultivated under controlled laboratory conditions. Conclusion: In view of the reported advantages of cultivating mixed cultures, the production of omega-3 fatty acids via such cultures appears attractive. More research however is needed to optimise the culture; study interactions between the organisms and their effect on biomass, total fatty acid and omega-3 fatty acid productivity. Finally, the economic implications of using mixed cultures need to be evaluated as well.

It has been demonstrated that EGCG and caffeine, naturally present in green tea, have thermogenic properties in thermoneutral conditions. The purpose of this study was to quantify the effect of the combined ingestion of EGCG/caffeine on thermogenic responses during a 3h mild cold exposure. Eight healthy males (22± 1 y) were exposed in a randomized, cross over, single blinded fashion to the cold (liquid conditioned suit perfused with 15°C water), after ingesting either a placebo (CON) or an extract of 1600mg of EGCG and 600mg of caffeine (EXP). Thermic, metabolic and electromyographic measurements were monitored at baseline and during cold exposure. After 180min of cold exposure, shivering intensity was significantly reduced by ~32% in EXP condition compared to CON. Area under the curve calculations for total shivering intensity was also reduced by ~21% in EXP (457±99 %MVC.min) compared to CON (361±81 %MVC.min; p=0.007). In contrast, the total area under curve of VO2 was ~25% higher in EXP (33.3±5.5 L O2) compared to CON (25.3±5.1 L O2; p=0.03). Total Heat production (Hprod) also increased by about 11% in the EXP condition (1535±112 kJ) compared to control (1372 ±106 kJ; p=0.002). The decrease in shivering activity combined with an increase in VO2 and Hprod, following the ingestion of EGCG and caffeine in the cold, indicates that nonshivering thermogenesis pathways can be significantly stimulated in adult humans.

Mitochondria are a major site of reactive oxygen species (ROS) production in cells. While ROS can cause oxidative damage, they are vital in many signaling processes. Recently, mitochondrial superoxide flashes (mSOF) were defined through sensitive measurements of temporal and spatial differences in superoxide production. mSOF are stochastic events of quantal bursts in superoxide production, which are temporally linked to transient mitochondrial inner membrane depolarizations. The aims of the present study were to characterize a hydrogen peroxide sensitive biosensor to monitor these events and elucidate a role for uncoupling protein 3 (UCP3) and the mechanistic details of mSOF. While pHyPer- dmito was sensitive enough to monitor these dynamic changes its kinetics were insufficient to detect these ~20s long flashes. Additionally, analyses showed a prolonged duration of flashes in the absence of UCP3. Furthermore, we unearthed a novel relationship between flash amplitude and mitochondrial depolarization. Finally, investigations of mSOF in muscles of various fiber type compositions showed no differences, though additional investigations are warranted.