Φυσιολογικά επίπεδα της αγρίου τύπου απολιποπρωτεϊνης Ε (apoE) στο πλάσμα διαμεσολαβούν στην κάθαρση των αθηρογενετικών λιποπρωτεϊνών ενώ υψηλότερα επίπεδα από τα φυσιολογικά προκαλούν υπερτριγλυκεριδαιμία. Αυτή η ιδιότητα της αγρίου τύπου apoE μειώνει σημαντικά την θεραπευτική της αξία ως ένα πιθανό βιολογικό φάρμακο για την αντιμετώπιση της δυσλιπιδαιμίας. Πρόσφατα, έχει δημιουργηθεί και μελετηθεί μια μεταλλαγμένη μορφή της apoE, apoE4 [ L261A, W264A, F265A, L268A, V269A ] (apoE4mut1) με βελτιωμένες βιολογικές ιδιότητες. Συγκεκριμένα, αυτή η μεταλλαγμένη μορφή μπορεί να φέρει τα υψηλά επίπεδα χοληστερόλης σε φυσιολογικές τιμές χωρίς να προκαλέσει υπερτριγλυκεριδαιμία ακόμα και όταν υπερεκφράζεται. Στην παρούσα μελέτη, πραγματοποιήθηκε φαρμακοδυναμική και φαρμακοκινητική ανάλυση της apoE4mut1 σε πειραματόζωα. Με γονιδιακή μεταφορά μέσω ιού σε ποντίκια που είχαν έλλειψη στον LDL υποδοχέα (LDLr-/-) και σε ποντίκια που είχαν έλλειψη στην apoE (apoE-/-), δείχθηκε οτι η δράση της apoE4mut1 ( μείωση της χοληστερόλης ) εξαρτάται από την έκφραση ενός λειτουργικού κλασσικού LDL υποδοχέα. Εφάπαξ έγχυση της apoE4mut1 συνδεδεμένης με λιποσώματα σε apoE-/- ποντίκια που ήταν σε δίαιτα δυτικού τύπου για 6 εβδομάδες αποκάλυψε οτι η εξωγενώς συντιθέμενη apoE4mut1 διατηρεί άθικτη την ικανότητά της να κανονικοποιεί τα υψηλά επίπεδα χοληστερόλης αυτών των ποντικιών με μια μέγιστη φαρμακολογική απόκριση που παρατηρείται σε μόλις 10 ώρες μετά την έγχυση. Ενδιαφέρον παρουσίασε το γεγονός οτι τα επίπεδα χοληστερόλης του πλάσματος παρέμειναν σημαντικώς μειωμένα για τις επόμενες 24 ώρες μετά την έγχυση της apoE4mut1- λιποσώματα. Μετρήσεις συγκεντρώσεων της apoE έδειξαν οτι η apoE4mut1 στην μορφή των πρωτεολιποσωμάτων που χρησιμοποιήθηκαν σε αυτή τη μελέτη έχει χρόνο ημίσειας ζωής 15.8 h. Τα δεδομένα αυτά οδηγούν στο συμπέρασμα οτι η καθαρή apoE4mut1 μπορεί να αποτελέσει ένα νέο υποψήφιο φάρμακο για την άμεση αντιμετώπιση της υπερχοληστερολαιμίας σε άτομα που εκφράζουν έναν λειτουργικό LDL υποδοχέα. / Physiological levels of wild-type (wt) apolipoprotein E (apoE) in plasma mediate the clearance of cholesterol-rich atherogenic lipoprotein remnants while higher than normal plasma apoE concentrations fail to do so and trigger hypertriglyceridemia. This property of wt apoE reduces significantly its therapeutic value as a potential biological drug for dyslipidemia. Recently, we reported the generation of a recombinant apoE variant, apoE4 [L261A, W264A, F265A, L268A, V269A] (apoE4mut1) with improved biological functions. Specifically, this variant can normalize high plasma cholesterol levels without triggering hypertriglyceridemia, even at supraphysiological levels of expression. In the present study we performed pharmacodynamic and pharmacokinetic analysis of apoE4mut1 in experimental mice. Using adenovirus-mediated gene transfer in LDL receptor deficient (LDLr-/-) and apoE deficient (apoE-/-) mice, we show that the cholesterol lowering potential of apoE4mut1 is dependent on the expression of a functional classical LDLr. Bolus infusion of apoE4mut1-containing proteoliposomes in apoE-/- mice fed western-type diet for 6 weeks indicated that exogenously synthesized apoE4mut1 maintains intact its ability to normalize the high cholesterol levels of these mice with a maximum pharmacological effect obtained at only 10 hours post-treatment. Interestingly, plasma cholesterol levels remained significantly reduced even 24 hours following intravenous infusion of apoE4mut1 proteoliposomes. Measurements of plasma apoE levels indicated that apoE4mut1 in the form of proteoliposomes used in the study has a half-life of 15.8 h. Our data suggest that purified apoE4mut1 may be an attractive new candidate for the acute correction of hypercholesterolemia in subjects expressing functional LDL receptor.

At the Torpshammar dam two rectangular beams are situated upstream of the spillway gates to stabilize the sidewalls holding the embankment of the dam. A computational fluid dynamics (CFD) simulation of the dam with the bottom outlets open was made to investigate how the flow and discharge capacity is affected by the beams. The results can be used to avoid unexpected consequences due to turbulence caused by the beams, make the beams strong enough to hold the pressure from the flow and get an estimation of the discharge capacity with the beams. Turbulence is one of the hardest things to simulate so the results were compared with previous simulation work made without the beams and physical model tests to validate the results. Also, a sensitivity analysis was made to investigate the method used. The beams lowered the velocity (to 17 m/s) and the discharge capacity (to 255 m3/s) compared to the previous work. The force on the beams was directed upward and downstream. The beams increased the turbulence and the vortex shedding frequency was higher for the beam closest to the outlet. The velocity and discharge capacity differed with 6 % compared to model test results. The results can therefore only be used as an estimation, a more detailed computational model and more computational cells are needed to get a better result. The sensitivity analysis showed that the velocity and turbulence depend on the method and further studies need to be made to decide which method gives the closest similarity with reality.

Discharge of brine wastewater produced from industrial plants into adjacent coastal water bodies is considered as a preferable and common method currently used in many offshore industrial plants. Therefore, it is important to carefully study the behavior of jets and their environmental impacts on water bodies close to the discharge points, especially when the density is different between the jets and the receiving water. The main goal of this study is to improve the understanding of the mixing behaviour of jet trajectories for positively (offset) and negatively (inclined) buoyant jets when density is considered a significant factor, and also to examine the accuracy of some RANS turbulence models and one type of artificial neural network in predicting jet trajectory behaviours. In the first part of this study, experiments using a PIV system for offset buoyant jets were conducted in order to study the effect of the density differences (due to salinity [nonthermal] or temperature [thermal]) between the discharge and the receiving water body on the jet behavior, and the results showed that the nonthermal jets behaved differently as compared to the thermal jets, even though the densimetric Froude numbers (Frd) and density differences (∆ρ) were similar. In addition, a Reynolds-averaged Navier-Stokes (RANS) numerical model was performed using open-source CFD code (OpenFOAM) with a developed solver (modified form of the pisoFoam solver). The realizable k-ε model showed the best prediction among the models. Secondly, an extensive experimental study of an inclined dense jet for two angles (15°and 52°) was conducted to study the effect of these angles on the jets’ geometrical characteristics in the presence of a wide range of densimetric Froude numbers as well as with different discharge densities. More experimental data were obtained for these angles to be added to the previous data for the purpose of calibrating, validating, and comparing the various numerical models for future studies. The results of these experiments are used to evaluate the performance of a type of artificial neural network method called the group method of data handling (GMDH), and the GMDH results are then compared with existing analytical solutions in order to prove the accuracy of the GMDH method in simulating mixing behaviors in water bodies. Thirdly, a comprehensive study on predicting the geometrical characteristics of inclined negatively-buoyant jests using GMDH approach was conducted. The superiority of this model was demonstrated statistically by comparing to several previous analytical models. The results obtained from this study confirm that the GMDH model was highly accurate and was the best among others for predicting the geometrical characteristics of inclined negatively-buoyant jests.

L’objectif de ce travail a été de procéder au design de nouvelles structures hyperramifiées en procédant à la synthèse de polymères à base de glycidol utilisables dans l’élaboration de copolymères biodégradables, de macromonomères fonctionnels et de nanocomposites magnétiques biocompatibles. Une première partie de ces travaux s’est intéressée, à la synthèse de macromonomères hyperramifiés amorcés par l’hydroxyéthyle méthacrylate (HEMA), l’hydroxyéthyle acrylate (HEA) et le polyéthylène glycol méthacrylate (PEGMA), par polymérisation anionique, anionique coordinée ou cationique du glycidol. La synthèse de macromonomères poly(ε-caprolactone) en présence de différents systèmes catalytiques et amorceurs a également été investiguée. Cette partie se termine par la synthèse de dendrigrafts issus de la polymérisation de ces macromonomères, par voie radicalaire classique ou contrôlée (RAFT/ATRP). La seconde partie de ce travail a été consacrée à la synthèse de copolymères hyperramifiés biocompatibles obtenus par copolymérisation statistique du glycidol en présence d’ε-caprolactone, en vu de l’obtention de copolymères hydrolysables. L’impact de la structure sur les propriétés physico-chimiques des copolymères obtenus a été étudié. Enfin, le caractère biodégradable de ces polymères a été investigué à travers différents tests de dégradation enzymatique. Enfin, ce travail s’est focalisé sur l’élaboration de nanocomposites magnétiques biocompatibles par la synthèse de nanoparticules magnétiques, puis l’immobilisation de polymères linéaires ou hyperramifiés à leur surface selon différentes méthodes de greffage chimique. / The aim of this work was to proceed to the design of new hyperbranched structures through the synthesis of glycidol-based polymers which can be used in the development of biodegradable copolymers, functional macromonomers and biocompatible magnetic nanocomposites. The first part of this work was the synthesis of hyperbranched macromonomer initiated by hydroxyethyl methacrylate (HEMA), hydroxyethyl acrylate (HEA) and polyethylene glycol methacrylate (PEGMA), through the study of the synthesis of polyglycerol (PG) by anionic, anionic coordinated and cationic polymerization of glycidol. Synthesis of poly (ε-caprolactone) macromonomers in the presence of various catalyst systems and initiators was also investigated. This part ends by the synthesis of dendrigrafts derived from the copolymerization of the macromonomers, by free radical polymerization or by controlled radical polymerization. The 2nd part of this work has been devoted to the synthesis of hyperbranched biocompatible copolymers obtained by random copolymerization of glycidol with ε-caprolactone in order to obtain hydrolyzable copolymers. The impact of the structure of the copolymers on their physico-chemical properties was then investigated. The biodegradable behavior of these polymers was then investigated through different enzymatic degradation tests. Finally, this work was focused on the development of biocompatible magnetic nanocomposites by the synthesis of magnetic nanoparticles and the immobilization of linear or hyperbranched polymers on their surface by different chemical grafting methods.

Yes / The upper reach of the Yellow River from Daliushu to Shapotou consists of five bends and has complex topography. A two-dimensional Re-Normalisation Group (RNG) k-ε model was developed to simulate the flow in the reach. In order to take the circulation currents in the bends into account, the momentum equations were improved by adding an additional source term. Comparison of the numerical simulation with field measurements indicates that the improved two-dimensional depth-averaged RNG k-ε model can improve the accuracy of the numerical simulation. A rapid adaptive algorithm was constructed, which can automatically adjust Manning's roughness coefficient in different parts of the study river reach. As a result, not only can the trial computation time be significantly shortened, but the accuracy of the numerical simulation can also be greatly improved. Comparison of the simulated and measured water surface slopes for four typical cases shows that the longitudinal and transverse slopes of the water surface increase with the average velocity upstream. In addition, comparison was made between the positions of the talweg and the main streamline, which coincide for most of the study river reach. However, deviations between the positions of the talweg and the main streamline were found at the junction of two bends, at the position where the river width suddenly decreases or increases. / National Natural Science Foundation of China (Grants No. 11361002 and 91230111), the Natural Science Foundation of Ningxia, China (Grant No. NZ13086), the Project of Beifang University of Nationalities, China (Grant No. 2012XZK05), the Foreign Expert Project of Beifang University of Nationalities, China, and the Visiting Scholar Foundation of State Key Laboratory of Water Resources and Hydropower Engineering Science, Wuhan University, China (Grant No. 2013A011).

This thesis is an experimental investigation of the phase behavior, volumetric properties, and viscosity of poly (methyl methacrylate) (PMMA), poly (ε-caprolactone) (PCL) and their blends. Homopolymerization and copolymerizations of methyl methacrylate (MMA) and 2-methylene-1,3-dioxepane (MDO) in mixtures of acetone + CO2 have also been explored. The viscosities and densities of acetone + CO2 mixtures were measured in the temperature range 323-398 K at pressures up to 35 MPa. This is the first study in which viscosity of acetone + CO2 mixtures have been measured and the mixtures have been evaluated as solvents for PCL. It is shown that PCL can be readily dissolved in these fluid mixtures at modest pressures even at high carbon dioxide levels. Investigations have been conducted over a temperature range from 323 to 398 K at pressures up to 50 MPa for polymer concentrations up to 20 wt %, and CO2 concentrations up to 60 wt %. It is shown that in these mixtures PCL is dissolved at pressures that are much lower than the pressures reported for miscibility in the mixtures of carbon dioxide with other organic solvents. It is shown that PMMA also readily dissolves at modest pressures. Blends of PMMA and PCL require higher pressures than for the individual polymers for complete miscibility. Free-radical polymerizations of MMA in acetone at 343 K were followed using in-situ measurements of viscosity and density at different pressures from 7- 42 MPa. This is the first time viscosity has been used as a real-time probe of high pressure polymerizations. Two distinct kinetic regimes were identified. Homopolymerizations of MDO were conducted in carbon dioxide at 323 and 343 K at pressures up to 42 MPa. For the first time it is shown that high molecular weight PCL can be produced from MDO in high pressure CO2. Ring-opening free-radical copolymerizations of MDO with MMA, styrene and acrylonitrile were conducted for the first time in carbon dioxide and have been shown to lead to polymers with high molecular weights. / Ph. D.

Yes / This study uses an improved k –ε coupled shallow water equations (SWE) model that equipped with the numerical computation of the velocity fluctuation terms to investigate the turbulence structures of the open channel flows. We adapted the Kolmogorov K41 scaling model into the k –ε equations to calculate the turbulence intensities and Reynolds stresses of the SWE model. The presented model was also numerically improved by a recently proposed surface gradient upwind method (SGUM) to allow better accuracy in simulating the combined source terms from both the SWE and k –ε equations as proven in the recent studies. The proposed model was first tested using the flows induced by multiple obstructions to investigate the utilised k –ε and SGUM approaches in the model. The laboratory experiments were also conducted under the non-uniform flow conditions, where the simulated velocities, total kinetic energies (TKE) and turbulence intensities by the proposed model were used to compare with the measurements under different flow non-uniformity conditions. Lastly, the proposed numerical simulation was compared with a standard Boussinesq model to investigate its capability to simulate the measured Reynolds stress. The comparison outcomes showed that the proposed Kolmogorov k –ε SWE model can capture the flow turbulence characteristics reasonably well in all the investigated flows. / The Major State Basic Research Development Program (973 program) of China (No. 2013CB036402)

Yes / Based on the previous studies, the shallow water equations (SWEs) model was proven to be insufficient to consider the flow turbulence due to its simplified Reynolds-averaged form. In this study, the k-ε model was used to improve the ability of the SWEs model to capture the flow turbulence. In terms of the numerical source terms modelling, the combined k-ε SWEs model was improved by a recently proposed surface gradient upwind method (SGUM) to facilitate the extra turbulent kinetic energy (TKE) source terms in the simulation. The laboratory experiments on both the smooth and rough bed flows were also conducted under the uniform and non-uniform flow conditions for the validation of the proposed numerical model. The numerical simulations were compared to the measured data in the flow velocity, TKE and power spectrum. In the power spectrum comparisons, a well-studied Kolmogorov’s rule was also employed to complement both the numerical and experimental results and to demonstrate that the energy cascade trend was well-held by the investigated flows. / The Major State Basic Research Development Program (973 program) of China (Grant Number 2013CB036402). Open Fund from the State Key Laboratory of Hydraulics and Mountain River Engineering, Sichuan University, China (Grant Number SKLH-OF-1103).

Ce travail présente la synthèse de ligands mixtes germylène-sulfoxyde qui ont été utilisés en chimie de coordination avec plusieurs métaux de transitions et finalement appliqués en catalyse de transfert d'hydrogène. Une seconde partie de ce travail est axée sur la synthèse de nouveaux métallylènes stabilisés par un sulfonimidamide qui ont été appliqués en catalyse de polymérisation. Le premier chapitre présente l'état de l'art des germylènes avec leurs synthèses, modes de stabilisations et finalement leur chimie de coordination et leurs applications en catalyse. Les sulfoxydes seront aussi décrits pour leur application en tant que ligands hémilabiles. Le second chapitre décrit la synthèse de ligands germylène-α-sulfoxide avec une diversité structurale (cyclohexyle, tBu, tolyle..) et avec différents degrés d'oxydation du souffre (thioéther, sulfoxyde et sulfone). La chimie de coordination a permis la synthèse de complexes bis-germylène du groupe IV, bidentes du ruthénium ainsi que monodentes du ruthénium. Le troisième chapitre présente l'extension de la méthodologie à la formation de ligands germylène-β-sulfoxide. L'influence du groupement espaçant les deux entités sur la chimie de coordination a été étudiée et montre la formation de complexes bidentates du groupe IV. La coordination du ruthénium a mené à la surprenante synthèse d'un complexe bis-ruthénium caractérisé par diffraction des rayons X. Finalement, la nouvelle architecture a permis d'obtenir des complexes de nickel (0) dont une structure avec des ligands carbonyles permettant une comparaison TEP. Le chapitre quatre présente la synthèse de nouveaux ligands, analogues des amidinates, pour la stabilisation des métallylènes avec un atome central soufré. L'effet apporté sur les métallylènes par ces nouveaux ligands sulfonimidamides a été étudié par calcul DFT. Le dernier chapitre est centré sur l'application de plusieurs complexes de ruthénium en catalyse de transfert d'hydrogène avec plusieurs substrats carbonylés. L'utilisation de stannylènes stabilisés par des ligands sulfonimidamides a été étudiée en catalyse de polymérisation de la ε-caprolactone. / This work concerns the synthesis of mixed germylene-sulfoxide ligands that were involved in coordination chemistry with several transition metals and finally applied in hydrogen transfer catalysis. In a second part, the synthesis of new metallylenes stabilized by a sulfonimidamide group was develop, which were applied in polymerization catalysis. The first chapter is centered on the state of the art of germylenes with their synthesis, their stabilization and finally their coordination chemistry and applications in catalysis. Sulfoxides will also be described for their potential as hemilabile ligands. The second chapter describes the synthesis of germylene-α-sulfoxide ligands as structurally tunable structures (cyclohexyl, tBu, tolyl..) and with different oxidation states of the sulfur atom (thioether, sulfoxide and sulfone). The coordination chemistry led to the formation of bis-germylene group IV complexes, bidentate-ruthenium and monodentate ruthenium complexes. The third chapter shows the extension of the methodology to the formation of germylene-β-sulfoxide ligands. The influence of the spacer between the two entities on the coordination chemistry was studied and shows the formation of bidentate group IV complexes. Coordination to ruthenium led to obtain a surprising bis-ruthenium complex characterized by X-ray diffraction analysis. Finally, the novel architecture allowed to obtain two nickel (0) complexes, one of them including carbonyl ligands permitting a TEP comparison. The fourth chapter is centered on the synthesis of new ligands, analogue of amidinate substituents for metallylene stabilization with a central sulfur atom. The effect brought to the metallylene center by the sulfonimidamide was studied by DFT calculations. The last chapter concerns the application of several ruthenium complexes in hydrogen transfer reaction with various carbonyl compounds. The use of sulfonimidamide stannylenes was also investigated in polymerization catalysis of ε-caprolactone.

La représentation scalable de l'information s'impose aujourd'hui pour supporter l'hétérogénéité d'un réseau interconnecté tel que l'Internet. Le codage de source adopte, pour ce faire, une approche multi-résolution pouvant délivrer progressivement à un utilisateur le contenu de sa requête. Cependant, en supposant au cours de la transmission une gestion de bout en bout des priorités ainsi établies, ces schémas restent sommairement adaptés aux environnements de pertes de paquets et de qualité de service non garantie.<br />Les codages à description multiple offrent une alternative à la transmission hiérarchisée de l'information en brisant la scalabilité de la source aux abords du canal. Dans cette thèse, nous proposons une méthode originale de description multiple qui réalise une protection différenciée de chaque niveau hiérarchique de la source en fonction des propriétés dynamiques du canal de transmission.<br />La transformation Mojette (transformation de Radon discrète exacte) est une transformation unitaire qui permet de partager un volume de données en un ensemble plus ou moins redondant de projections équivalentes. L'évolution de ce type d'opérateur initialement utilisé dans un espace continu pour la reconstruction tomographique étend le concept de support d'image à celui de mémoire tampon géométrique pour données multimédias. Ce codage à description multiple, généralisé à N canaux, autorise la reconstruction de la mémoire initiale de manière déterministe par des sous-ensembles de projections dont le nombre caractérise le niveau de protection. Ce schéma est particulièrement adapté au mode de transport par paquets sans contrôle d'intégrité extensible du canal de transmission. La hiérarchie de la source est dans ce cas communiquée sous forme transparente pour le canal via des descriptions banalisées.<br />L'évaluation du codage est effectuée en comparant les débits engendrés avec ceux d'un code MDS (Maximum Distance Separable) qui fournissent une solution optimale dans le nombre de symboles nécessaires au décodage. La relaxation des propriétés MDS dans un code (1+ε)MDS avec la transformation Mojette demande une légère augmentation de débit au profit d'une complexité réduite.<br />L'application sur des schémas de compression d'images valide concrètement l'adaptation possible des sources actuelles à un canal de type best-effort. L'utilisation dans un environnement distribué (micro-paiement, stockage distribué de données multimédia) illustre en outre un partage sécurisé de l'information.<br />En perspectives de ce travail, nous avons abordé l'intégration de cette méthode dans un protocole de transmission scalable multimédia et étudié une version probabiliste du système.