Si de nombreuses études ont été consacrées à l’analyse des grands tours préparatoires aux sorties, aux sorties elles-mêmes et aux lâchers de barre en barre fixe ou barre supérieure de barres asymétriques, les éléments avec envol pour passer d’une barre à l’autre aux barres asymétriques (lâcher la barre inférieure pour saisir la barre supérieure ou l’inverse) n’ont, à notre connaissance, pas fait l’objet de telles études. Cette thèse de doctorat présente dans sa première partie une analyse cinématique du « pieds barre temps de ventre » ainsi qu’une analyse des moments cinétique et d’inertie mis en jeu par deux groupes de gymnastes, des expertes et des novices, lors de la réalisation de ce mouvement. La deuxième partie met en évidence des lois de contrôle moteur utilisées par les deux groupes pour réaliser l’élément. Afin de déterminer si les mouvements des deux groupes sont susceptibles d’améliorations et si la trajectoire créée au lâcher de la barre inférieure ou la gestuelle mise en jeu influence davantage la performance, une optimisation du pieds barre temps de ventre est proposée dans la troisième partie. Enfin, l’effet de l’introduction d’une loi de contrôle moteur dans le processus d’optimisation sur le réalisme des mouvements optimisés est envisagé. / Many studies were dedicated to the analysis of backward giant circles prior to release, releases itself or release-regrasp skills on high bar or uneven bars. To our knowledge, skills with flight phase to release low bar and regrasp high bar or the contrary were not studied yet. The first chapter of this doctoral thesis is dedicated to a kinematic analysis of the “counter movement forward in flight” on uneven bars and to the moment of inertia and angular momentum recorded for two groups of gymnasts performing this task: an expert group and a novice group. The second chapter highlights motor control laws used by the gymnasts of both groups. An optimization of the counter movement forward in flight was carried out in the third chapter in order to know if the movements of both groups may be improved and whether body mass center trajectory or body movements in flight most influence final performance. Effects of introducing a motor control law in the optimization process on the realism of optimized movements were studied.

Advancements in material science and manufacturing techniques are enabling the use of lightweight metal alloys and polymer composites in several combinations and shapes for producing more efficient and lightweight structures for automotive applications without compromising strength, stiffness and/or durability. When evaluating the strength of the structure, the joints are of importance. For multi-material structures adhesives are often the best type of joints. However, traditional finite element methods using stress criteria cannot accurately predict the failure of these adhesive joints under static loading. In this thesis work a strength and fatigue model, formulated using energy release rate theory, is implemented in a post processing tool. Given a finite element model of an adhesive joint and a list of boundary elements and nodes this tool calculates the energy release rates in mode I and mode II, and if the fracture toughness of the adhesive is known, a prescribed mixed-mode failure index is calculated. To evaluate its predictions joint strength results are correlated to experiments. Specimens with combined shear and normal load forms the underlying experimental setup with change in strain rate and adhesive thickness as varying parameters. Methods for implementing the model for a car body structure with multiple adhesive joints is investigated, the tool proves to be scalable, however, the required finite element setup at the adhesive boundaries may not be present in a car body model and thus further work needs to carried out to accommodate irregularities like non-matching mesh in the car body finite element model. This model may be used for assessing the strength and durability of a car body structure comprising different materials joined together using adhesives.

La toxicité potentielle des nanomatériaux présente un intérêt sociétal et scientifique élevé en raison de la promesse d'innovations pour de nombreuses applications techniques. Cependant, elle n’est pas forcément liée à la taille réelle, à la masse, à la surface des nanoparticules (NP) ou à leurs agglomérats. La toxicité des NPs pourrait être fortement influencée par d'autres propriétés inhérentes et encore incomprises telles que le relargage d’ions, de la particule elle-même, sa surface, ou des molécules adhérentes à la surface, qui interfèreraient avec l'absorption cellulaires des NPs. Le projet « NANOGAM» étroitement lié au projet « FNR CORE2012 NANION », vise à définir certains processus et facteurs impliqués dans l'absorption des NPs et leur toxicité. Une telle compréhension est une condition préalable au développement des nanomatériaux, fondement de la philosophie « safer-by-design ». Les objectifs de ce projet de thèse sont multiples. En tenant compte des caractéristiques des principaux paramètres physico-chimiques tels que la taille et l’aspect de la surface, l’étude a porté sur l'absorption de NPs d'argent et d'or, et leurs effets biologiques via une approche multi-biomarqueurs (mortalité, effets comportementaux, effets physiologiques, effets transcriptomiques, etc.) sur une espèce sensible, Gammarus fossarum (Crustacea Amphipoda). Le but de cette investigation est de comprendre si la toxicité des nanomatériaux est inhérente aux propriétés intrinsèques des NPs ou plutôt aux ions relargués, ce qui contribuera à la prédiction de la toxicité des NPs en rapport avec leurs propriétés physico-chimiques et ce afin de limiter le nombre d’essais répétitifs sur de nouveaux nanomatériaux. G. fossarum ont été exposés à de faibles concentrations d'AgNPs et AuNPs pendant 72h à jeun et 15 jours nourris. Les résultats obtenus ont montré que (i) la nature de l’enrobage de surface est le principal facteur responsable de l'absorption d'AgNPs et d'AuNPs par G. fossarum ; (ii) les ions libérés et les NPs elles-mêmes jouent un rôle dans la toxicité des AgNPs et AuNPs étudiées ; (iii) la composition chimique des NPs a conduit à des effets différents aux niveaux sub-individuels (transcriptomique), ainsi qu’à une distribution différente dans les tissues selon la nature métallique de la NP. Les AgNPs ont été localisées dans les branchies de G. fossarum tandis que les AuNPs ont été observées dans les caeca intestinaux. Cette étude a également révélé que Gammarus sp. est un excellent modèle pour l'étude de la toxicité et des effets des AgNPs et des AuNPs / The potential toxicity of nanomaterials is of high societal and scientific interest due to the promise of ground-breaking innovations for many technical applications. However, toxicity can often not be related to the actual size, mass or surface area of the single nanoparticles (NPs) or the NP agglomerates. Therefore, it can be proposed that the toxicity is greatly influenced by other inherent and non-understood properties of the particles to which ions dissolving from the particle, surface or molecules adhering to the surface interfering with the uptake of NPs into cells, may have important contributions. The PhD project “NANOGAM”, closely linked up to CORE2012 NANION project that aims to obtain knowledge to understand some of the processes and factors involved in NP uptake and toxicity as such understanding is a prerequisite for the development of nanomaterials following the safer-by-design philosophy. This PhD project aims to investigate, based on known characteristics of the key physico-chemical parameters; as size and surface functionalities, of a well-chosen list of silver and gold NPs, the uptake, and dependent biological effects of different complexity (mortality, behavioural effects, physiological effects, transcriptomic effects, etc.), on a sensitive species; Gammarus fossarum (Crustacea Amphipoda), in order to understand to which extent toxicity of nanomaterials is due to intrinsic material properties or ion leaching. Such understanding will contribute to the prediction of toxicity based on material properties rather than repetitive testing of an indefinite number of new nanomaterials. G. fossarum were exposed at low concentrations of AgNPs and AuNPs for 72h or 15 days in presence or absence of food. The obtained results showed that (i) surface coating is the main factor governing AgNPs and AuNPs uptake by G. fossarum, (ii) both released ions and NPs themselves play a role in the potency of the studied AgNPs and AuNPs and (iii) chemical composition led to different effects at the sub-individual levels (target genes expression) and different tissue distribution as AgNPs were found in G. fossarum gills while AuNPs were found in the intestinal caeca. Additionally, this work shows that Gammarus sp. are valuable models for the study of the effects of AgNPs and AuNPs

Countless electron transport/transfer (ET) processes occur in living organisms every day. Therefore, their study is a crucial field of modern structural and functional proteomics. In many cases model proteins like azurin from P. aeruginosa are utilised in experiments. This blue copper protein is favoured due to a characteristic absorbance maximum at 630 nm in Cu(II) redox state of the central Cu atom. During its oxidation to Cu(I) state the A630 value decreases allowing UV-Vis detection of ET reaction progress. We have introduced a structural photoinducible analogue of canonical amino acid Met - L-2-amino-5,5-azihexanoic acid (photo-Met) - into azurin structure to study oligomerization in solution via photo-induced cross-linking (PIXL). Using previously optimised protocols for recombinant expression in E. coli B834 we have inserted photo-Met into azurin moieties: wild type azurin and Az2W mutant where two adjacent W residues with confirmed role in electron hopping across protein-protein interface are present. The incorporation percentage of photo-Met in analysed samples was determined after SDS-PAGE and in-gel protease digestion via MALDI-TOF MS. PIXL was employed to study azurin-azurin interaction and oligomerization under different total concentrations of protein (in range of 15-300 µM). The...

Magister Chirurgiae Dentium (MChD) / Background: This study aimed to determine the association between dimensional change and surface roughness (Ra) of Vitremer, Activa and Cention N after immersing them into two different media: acidic and artificial saliva media for the period of a year. Measurements were made at 10 time intervals during the observation period. Methodology: This was a quantitative and qualitative study. For the quantitative part, a total of 60 specimens were tested, 20 specimens for each material. The 20 specimens were further divided into 10 specimens. Ten were immersed in acidic media and the rest in saliva media. A measurement of the weight, height, and Ra was carried out as follows: day 0, day 1, day 2, day 7, day 21, day 28, day 60, day 90, day 180 and day 365. Scanning electron microscopy (SEM) was used to examine the surface of each material qualitatively pre and post immersion in the two media. For fluoride measurements, an additional five samples from each material were left suspended in the de-ionized water by the use of dental floss. The materials were moved to new specimen jars after the completion of day 1, 2, 3, 4, 5, 6, 7, 14, 21 and 28. All the specimen jars had been kept for the fluoride measurements. Results: Non-parametric tests were used to analyze the data. Linear regression analysis was used to measure the association between weight, height or surface roughness (Ra) and immersion time for a year. The result of this test showed that Vitremer had a significant association between the weight (p = 0.000), height (p = 0.007) and Ra (p = 0.001) when it was immersed in acidic media. On the other hand, when Vitremer was immersed in saliva media, only the weight variable showed a significant association (p = 0.002). For Cention N, significant association was found for only Ra when immersed in acidic media (p = 0.000). Finally, for Activa, all the studied associations; the weight, height and Ra in both media were found to be insignificant. For saliva media, there was a significant weight change between the three materials during all 10 periods of time (p = 0.000). In the first six months, Cention N demonstrated a significant increase in weight changes followed by Vitremer, then Activa. Yet, after a year, the difference between Cention N and Vitremer became insignificant and Activa showed the least weight changes. There was not a significant difference between the materials in terms of height and Ra measurements. The fluoride experiment was not successful due to technical issues during pH measurements of the collected solutions. For comparison of the studied parameters between the three materials, the Kruskal-Wallis test was used. In acidic media, there was a significant difference between the materials in term of weight change in 10 periods of time (p = 0.000). In particular, after a two month period, Cention N had the highest weight, followed by Vitremer and then by Activa. The difference between Vitremer and Activa became insignificant throughout the rest of the experimental time frame. All the height measurements between the three materials were found to be insignificant except for day 365 (p = 0.048), where both Activa and Cention N were found to be significantly higher than Vitremer. For the Ra comparison, in the first two weeks, particularly day 1, 7 and 14, Cention N had significantly the lowest Ra among the other materials. As the three materials aged in the acidic media (day 180), Vitremer had significantly the highest Ra values. Cention N showed higher Ra values than Activa; nonetheless this difference was not significant. The SEM images showed loss of some particles in all post-experimental images of the materials in acidic media. Vitremer showed the widest cracks with the loss of fillers. In saliva media, there was also loss of particles but to a lesser extent than in acidic media. Yet, the post-experimental image of Activa in saliva resembled the pre-experimental one. Conclusion: Within the limitations of the study, the best material to resist Ra from prolonged acidic attack was Activa followed by Cention N and then Vitremer. Except for Vitremer, no significant changes in the Ra of the other materials were detected when the three materials were immersed in saliva media in the long term. In acidic media Vitremer tended to lose weight and height faster than Cention N and Activa over a year. Cention N is the best material to resist dimensional change. However, in artificial saliva Vitremer gained water rapidly. Activa did not absorb a lot of water and did not reject a lot of water; Activa demonstrated good dimensional stability and this property may be beneficial when compared to the other two materials tested. The clinical significance of the study: All the materials studied were subjected to dimensional and Ra changes following long-term exposure to acidic substances, but the newer materials (Cention N and Activa) seemed to be more dimensionally stable and resistant to Ra changes than the older, well-known material (Vitremer). This may influence a clinician’s choice of restorative material for use in pediatric dentistry.

Forest-cover in the tropics is changing rapidly due to indiscriminate removal of timber from many localities. The main focus of the study is to develop an operational tool for monitoring biomass and carbon pool of tropical forest ecosystems. The method was applied to a test site of Bangladesh. The research used Landsat ETM+, Landsat TM and IRS pan images of 2001, 1992 and 1999 respectively. Geometrically corrected Landsat ETM+ imagery was obtained from USGS and adjusted to the field using GPS. Historical images were corrected using image-to-image registration. Atmospheric correction was done by modified dark object subtraction method. Stratified sampling design based on the remote sensing image was applied for assessing the above-ground biomass and carbon content of the study area. Field sampling was done during 2002-2003. Dbh and height of all the trees inside the sample plots were measured. Field measurement was finally converted to carbon content using allometric relations. Three different methods: stratification, regression and k-nearest neighbors were tested for combining remote sensing image information and field-based terrestrial carbon pool. Additional field sampling was conducted during 2003-2004 for testing the accuracy. Finally regression method was selected. The amount of carbon released and sequestrated from the ecosystem was estimated. The application of the developed method would be quite useful for understating the terrestrial carbon dynamics and global climate change.

Externe Einträge von Nährstoffen, vor allem von Phosphor, fördern die Phytoplanktonentwicklung und sind damit die primäre Ursache für die Verschlechterung der Gewässergüte in Seen. Die pelagische Nahrungsnetzstruktur kann dabei sowohl positiv als auch negativ auf die Gewässergüte einwirken. Deshalb lässt sich der Gewässerzustand durch eine gezielte Steuerung der Räuber-Beute-Verhältnisse verändern. In der vorliegenden Arbeit wurden Ergebnisse der Groß-Enclosure-Experimente zu den Auswirkungen von Nährstoffen (mit/ohne Zugabe von Nährstoffen) sowie von einer manipulierten Nahrungsnetzstruktur (mit/ohne Zugabe von planktivoren Fischen) auf die pelagische Phyto- und Zooplanktongemeinschaft eines thermisch geschichteten Sees (Dagowsee, Brandenburg) präsentiert. Im Schwerpunkt der Untersuchungen lagen dabei die qualitativen und quantitativen Effekte dieser beiden Faktoren auf die Sedimentationsprozesse sowie den mikrobiellen Umsatz von Kohlenstoff und Phosphor im Hypolimnion und an der Sediment-Wasser-Kontaktzone des Sees. Es wurde gezeigt, dass die Manipulation der Nahrungsnetzstruktur sich auf die Menge und Zusammensetzung des Phyto- und Zooplanktons im Epilimnion des Sees sowie auf den quantitativen vertikalen Transport von Kohlenstoff und Phosphor auswirkte, während die unterschiedliche Nährstoffbelastung im Epilimnion die spezifischen Stoffgehalte des Kohlenstoffs und Phosphors im sedimentierten Material beeinflussten. Anhand der Sauerstoff- und Methanmessungen wurde festgestellt, dass die Intensität des mikrobiellen Abbaus der sedimentierten organischen Substanz vor allem von ihrer Menge abhängig war. Weiterhin konnten die Auswirkungen der manipulierten Nahrungsnetzstruktur auf die Effizienz während des Abbaus vom organischen Kohlenstoff in den Laborversuchen nachgewiesen werden. Diese Effekte waren allerdings in den Freilandexperimenten schwer nachweisbar aufgrund der Beteiligung der Abbauprodukte in anderen oxidativ-reduktiven Prozessen, die gleichzeitig im See verliefen. Anhand des Phosphor-Fraktionierungsverfahrens konnte festgestellt werden, dass dieser Stoff nicht organisch sondern zum größten Teil an Eisen und Mangen gebunden sowie labil adsorbiert die Sedimentoberfläche erreichte. An dieser Stelle zeigten diese beiden Fraktionen einen systematischen Unterschied, der nur auf eine Wirkung der epilimnischen Nährstoffkonzentration und nicht auf die des manipulierten Nahrungsnetzes hinwies. Weitere Analysen der Sedimente zeigten starke Transformationen des sedimentierten Phosphors, aufgrund deren vor allem die dominierenden labilen und redoxsensitiven Phosphorfraktionen betroffen waren. Sie wurden zum einen ins Wasser zurückgelöst und zum anderen in die organische Biomasse gespeichert. Die Veränderungen des Phosphorgehaltes in den Sedimenten waren wieder auf die vorherigen Effekte der Nährstoffe als der manipulierten Nahrungsnetzstruktur zurückzuführen. Die Effekte der Nahrungsnetzmanipulation waren also vor allem an der pelagischen Planktongemeinschaft im Epilimnion und an den Sedimentations- und Kohlenumsatzprozessen in tieferen Schichten des Sees zu sehen. Der vertikale Phosphortransport wurde weniger von der Nahrungsnetzstruktur beeinflusst. Dafür spielte dabei die epilimnische Nährstoffkonzentration sowie die Phosphorbindungspotenzial des Wassers für den internen Kreislauf des Stoffes eine wichtige Rolle. / External load of nutrients, above all from phosphorus, promote the phytoplankton development and are with it the primary cause for the deterioration of the waters quality in lakes. Further, the pelagic food web structure can affect the water quality in a positive as well as in a negative way. Therefore, the water trophic state can be changed by a specific control of the predator-prey relations. In the present study the results of the large enclosure experiments to the impact by nutrients (with/without addition of nutrients) as well as by a manipulated food web structure (with/without addition of planktivorous fish) on the pelagic phyto- and zooplankton community of a thermally stratified lake (Dagowsee, Brandenburg) were presented. Furthermore, the qualitative and quantitative effects of these both factors on the sedimentation processes as well as the microbial turnover of settled carbon and phosphorus in the hypolimnion and at the sediment-water layer of the lake were in the main focus of the investigations. It has been shown that the manipulation of the food web structure affected the amount and composition of the phyto- and zooplankton in the epilimnion as well as the quantitative vertical transport of carbon and phosphorus, while the different nutrient load in the epilimnion influenced the specific material content of the carbon and phosphorus in the sedimented material. With the help of the oxygen and methane measurements it was found out that the intensity of the microbial decomposition of the settled organic matter was dependent above all on her quantity. Furthermore, the effects of the manipulated food web structure on the decomposition efficiency of the organic carbon could be proved in the laboratory tests. However, these effects were in the free land experiments hardly provably due to the participation of the endproducts in other redox processes which ran at the same time in the lake. With the help of the phosphorus fractionation procedure could be found out that settled phosphorus for the most part not organically but in iron and manganese bound as well as loosely adsorbed the sediment surface reached. At this point these both forms showed a systematic difference which pointed only to an effect of the epilimnetic nutrient concentration and not on those of the manipulated food web. Other analyses of the sediments showed strong transformations of the settled phosphorus, which influenced above all the dominating labile and redox sensitive phosphorus fractions. They were released, on the one hand, in the water and stored, on the other hand, in the organic biomass. The changes of the phosphorus content in the sediments were to be led on the previous effects of the nutrients than of the manipulated food web structure. To conclude, the effects of the food net manipulation were to be seen above all in the pelagic plankton community in the epilimnion, and further in sedimentation and carbon turnover processes in deeper layers of the lake. The vertical phosphorus transport was influenced of less by the food web structure. Moreover, for it the epilimnic nutrient concentration as well as the phosphorus binding potential of the water played an important role for the internal circulation of the material.

Die Spumaretrovirinae, mit ihrer einzigen Gattung der Foamyviren (FV), nehmen aufgrund einer recht ungewöhnlichen Replikationsstrategie und Ähnlichkeiten mit den Hepadnaviren eine Sonderstellung innerhalb der Familie der Retroviren ein. Eine Besonderheit der FV ist, daß sie für die Partikelfreisetzung, im Gegensatz zu den Orthoretroviren, die beiden strukturellen Proteine Gag und Env benötigen. Das Gag- Protein trägt alle für den Kapsidzusammenbau nötigen strukturellen Komponenten, kann jedoch durch eine fehlende Membranbindungsdomäne nicht mit Zellmembranen assoziieren. Der Membrantransport der bereits im Zytoplasma zusammen gebauten FV Kapside wird vermutlich durch das FV Env-Protein vermittelt. Das FV Hüllprotein ist jedoch auch alleine zur Freisetzung von Kapsidlosen, Hüllprotein-haltigen subviralen Partikeln (SVP) fähig. Da eine Envunabhängige Freisetzung virus-ähnlicher Partikel durch ein FV Gag-Protein mit künstlichem Membrananker möglich ist, scheint das FV Gag-Protein auch essentielle strukturelle Elemente für die Partikelfreisetzung zu enthalten. In den letzten Jahren wurden große Fortschritte in der Erforschung der Freisetzung von membranumhüllten Viren und den daran beteiligten viralen Determinanten und zellulären Mechanismen gemacht. Wobei den meist in den viralen Kapsidproteinen vorkommenden Late (L)-Domänen und deren Interaktion mit dem zellulären Proteinsortierungsweg in Multivesikuläre Körperchen (MVB) eine besondere Bedeutung zu kommt. Über die FV virale und subvirale Partikelfreisetzung und die dabei involvierten strukturellen viralen Domänen und zellulären Proteinen war jedoch bisher wenig bekannt. Im Rahmen dieser Arbeit konnte durch Mutationsanalysen von drei potentiellen L-Domän Sequenzmotiven im Prototyp FV (PFV) Gag-Protein ein, innerhalb der Primaten FV konserviertes, PSAP Konsensusmotiv als funktionelle L-Domäne charakterisiert werden. Dessen Mutation führte zu klassischen L-Domän Defekten mit verringerter Partikelfreisetzung, sowie einer elektronenmikroskopisch sichtbaren Arretierung der Virusknospung und seine Funktion war durch homo- und heterologe L-Domän Motive anderer Retroviren teilweise oder vollständig ersetzbar. Ein PPPI Motiv in PFV Gag, mit Ähnlichkeit zur L-Domän PPXY Konsensussequenz, schien jedoch keinen Einfluß auf die FV Freisetzung zu besitzen. Die Charakterisierung eines in allen FV Gag-Proteinen konservierten YXXL Motivs ließ eher auf eine wichtige Rolle beim korrekten Kapsidzusammenbau, als auf eine klassische LDomän Funktion schließen. Eine korrekte Kapsidmorphogenese schien entscheidend für die reverse Transkription des Virusgenoms zu sein. Durch Koexpression verschiedener dominant-negativer Mutanten des zellulären ESCRT-Proteinssortierungsweges konnte gezeigt werden, daß die virale Partikelfreisetzung von PFV augenscheinlich dem generellen Model der Freisetzung vieler membranumhüllter Viren über das VPS-System folgt. Eine spezifische Interaktion des PFV Gag PSAP L-Domän Motivs mit TSG101, einer frühen Komponente der ESCRT-Komplexe, verbindet PFV mit dem VPS-Sortierungsweg der Zelle. Die besondere Fähigkeit des FV Env-Proteins zur Freisetzung von SVPs wurde bereits vor einiger Zeit entdeckt, dennoch war bisher nichts über die viralen und zellulären Determinanten bekannt, die zu einer Knospung des Env-Proteins in Vesikel führten. Durch eine Reihe von Deletions- und Mutationsanalysen des PFV Env-Proteins konnten in dieser Arbeit zwei für die SVP-Freisetzung inhibitorische Abschnitte am N- und C-Terminus der zytoplasmatischen Domänen des Env- Proteins ermittelt werden. Weiterhin wurden essentielle Sequenzen im Leaderpeptid, sowie die Notwendigkeit der Membranspannenden Domäne der Transmembran- Untereinheit für die SVP-Freisetzung festgestellt. Obwohl das PFV Env-Protein kein bekanntes L-Domän Sequenzmotiv enthält, konnte ein Einfluß später Komponenten der ESCRT-Maschinerie auf die SVP-Bildung beobachtet werden. Wobei die genaue Eintrittsstelle in den VPS-Weg im Rahmen dieser Arbeit nicht definiert werden konnte. Die vorgenommen Analysen lassen vermuten, daß die Bildung von SVPs durch die Konzentration der Env-Proteine in der Zellmembranen reguliert wird. Welche genauen Mechanismen dabei zu Grunde liegen und wieweit die zelluläre Ubiquitinylierungsmaschinerie involviert ist, bedarf jedoch weiterer Erforschung. Die Ergebnisse dieser Arbeit verdeutlichen erneut die Sonderstellung der FV innerhalb der Familie der Retroviren. Auf der einen Seite folgt die foamyvirale Viruspartikelfreisetzung den typischen Mechanismen der retroviralen Virusknospung. Andererseits zeigt die Freisetzung von subviralen Partikeln, die bei keinem anderen Retrovirus bisher beobachtet wurde, eine weitere Parallele zur Replikationsstrategie der Hepadnaviren auf.

Ce travail de thèse s’articule autour de la génération et de la caractérisation de capsules d’organo-hydrogel ou simplement bi-gels, obtenues par la technologie du prilling et destinées à la délivrance contrôlée d’un principe actif (P.A), après administration par voie orale. L’Efavirenz (EFV), un antirétroviral utilisé dans le traitement du VIH/Sida, a été le P.A utilisé comme modèle de molécule de faible solubilité dans l’eau. Il a été dissous dans l’organogel composé d’huile de tournesol et d’acide 12-hydroxystéarique (12-HSA). L’organogel a été caractérisé par sa température de transition de phase sol-gel-sol. Et la thermoréversibilité caractéristique de cet organogel n’a pas changé avec l’introduction de l’EFV. Pour la caractérisation des organogels comme véhicule de P.A, ils ont été produits à deux températures (5°C et 25 °C) et avec deux concentrations de 12-HSA (5% et 20%). Pour les essais de libération de l’EFV deux milieux de dissolution ont été utilisés (pH 1,2 et 6,8) avec et sans enzymes. Le profil de libération de l’EFV à partir de capsules bi-gels (2500 à3000 μm de diamètre) est essentiellement lié à la quantité d’organogélifiant dans le coeur, à la présence de la membrane d’alginate et à l’état physique de cette membrane (hydratée ou sèche). Une réduction de 50% a pu être observée à pH acide en présence de la membrane externe. A pH acide la libération est plus lente qu’à pH 6,8, quand la membrane perd sa fonction protectrice et le coeur organogel passe à régler la libération. Deux mécanismes de relargage sont observés : l’érosion et la diffusion, expliqués par le modèle de Korsmeyer-Peppas. / This thesis focuses on the generation and characterization of organo-hydrogel capsules (bigels), manufactured by prilling technology for controlled drug delivery after oral administration. Efavirenz (EFV), an antiretroviral medications used to treat HIV/AIDS, is the active pharmaceutical ingredient (API) used as a model molecule of low solubility in water. It was dissolved in the organogel, which is compound of sunflower oil and 12-hydroxystearic acid (12-HSA). The organogel was characterized by its phase transition temperature sol-gel-sol. The typical thermoreversibility of this organogel has not changed with introduction of EFV. The organogels were produced at two temperatures (5 °C and 25 °C) and with two concentrations of 12-HSA (5% and 20%) for being characterized as an API vehicle. Two dissolution media were used with and without enzymes (pH 1.2 and 6.8), for EFV release quantification. The EFV release profile from bi-gels capsules (diameter from 2500 to 3000 μm) is essentially related to the amount of organogelator in their core, to the presence of the alginate membrane and to the state physics of this membrane (hydrated or dry). The release of EFV has reduced 50% at acid pH in the presence of the external membrane. In simulated gastric fluid, the release is slower than at pH 6.8 (simulated intestinal fluid). In the intestine, the membrane loses its protective function and the organogel’s core begins to control the release of EFV. Two release mechanisms are observed: erosion and diffusion, which can be explained by the Korsmeyer-Peppas model.

Rocket combustors and other high-performance chemical propulsion systems are prone to combustion instability. Recent simulations of rocket combustors using detailed chemical kinetics show that the constant pressure assumption used in classical treatments may be suspect due to high rates of heat release. This study is a exploration on the effects of these extraordinary rates of heat addition on the local pressure field, and interactions between the heat release and an acoustic field. <br> <br>The full problem is decomposed into simpler unit problems focused on the particular interactions of physical phenomena involved in combustion instability. The overall strategy consists of analyzing fundamental problems with simplified scenarios and then build up the complexity by adding more phenomena to the analysis. Seven unit problems are proposed in this study. <br> <br>The first unit problem consists of the pressure response to an unsteady heat release source in an unconfined one-dimensional domain. An analytical model based on the acoustic wave equation with planar symmetry and an unsteady heat source is derived and then compared against results from highly-resolved numerical simulations. Two different heat release profiles, one a Gaussian spatial distribution with a step temporal profile, and the other a Gaussian spatial distribution with a Gaussian temporal distribution, are used to model the heat source. The analytical solutions predict two different regimes in the pressure response depending on the Helmholtz number, which is defined as the ratio of the acoustic time over the duration of the heat release pulse. A critical Helmholtz number is found to dictate the pressure response regime. For compact cases, in the subcritical regime, the amplitude of the pressure pulse remains constant in space. For noncompact cases, above the critical Helmholtz number, the pressure pulse reaches a maximum at the center of the heat source, and then decays in space converging to a lower far field amplitude. At the limits of very small and very large Helmholtz numbers, the heat release response tends to be a constant pressure process and a constant volume process, respectively. The parameters of the study are chosen to be representative of the extreme conditions in a rocket combustor. The analytical models for both heat source profiles closely match the simulations with a slight overprediction. The differences observed in the analytical solutions are due to neglecting mean flow property variations and the absence of loss mechanisms. The numerical simulations also reveal the presence of nonlinear effects such as weak shocks that cannot be captured by the linear acoustic wave equation. <br> <br>The second unit problem extends the analysis of the pressure response of an unsteady heat release source to an unconfined three-dimensional domain. An analytical model based on the spherical acoustic wave equation with an unsteady heat source is derived and then compared against results from highly-resolved three-dimensional numerical simulations. Two different heat release profiles, a three-dimensional Gaussian spherical distribution with either a step or a Gaussian temporal distribution, are used to model the heat source. Two different regimes in the pressure response depending on the Helmholtz number are found. This analysis also reveals that whereas for the one-dimensional case the pressure amplitude is constant over the distance, for the three-dimensional case it decays with the radial distance from the heat source. In addition, although for moderate heat release values the analytical solution is able to capture the dynamics of the fluid response, for large heat release values the nonlinear effects deviate the highly-resolved numerical solution from the analytical model. <br> <br>The third unit problem studies the pressure response of a fluctuating unsteady heat release source to an unconfined one-dimensional domain. An analytical model based on the acoustic wave equation with planar symmetry and an unsteady heat source is derived and then compared against results from highly-resolved numerical simulations. Two different heat release profiles, a flat spatial distribution with sinusoidal temporal profile and a Gaussian spatial distribution and sinusoidal temporal profile, are used to model the heat source. For both cases, the acoustically compact and noncompact regimes depending on the Helmholtz number are analyzed. While in the compact regime the amplitude of the pressure is constant over the distance, in the noncompact regime the amplitude of the pressure fluctuation is larger within the heat source area of application, and once outside the heat source decays to a far field pressure value. In addition, the analytical model does not capture the nonlinear effects present in the highly-resolved numerical simulations for large rates of heat release such as the ones present in rocket combustors.<br> <br>Finally, the last four unit problems focus on the interaction between unsteady heat release and the longitudinal acoustic modes of a combustor. The goal is to assess and quantify how pressure fluctuations due to unsteady heat release amplify a longitudinal acoustic mode. To investigate the nonlinear effects and the limitations based on the acoustic wave equation, the analytical models are compared against highly-resolved numerical simulations. The fourth unit problem consists of the pressure response to a moving rigid surface that generates a forced sinusoidal velocity fluctuation in a one-dimensional open-ended cavity. The fifth unit problem combines an analytical solution from the velocity harmonic fluctuation with an unsteady heat pulse with Gaussian spatial and temporal distribution developed in the first unit problem. The choice of an open-ended cavity simplifies the analysis and serves as a stepping stone to the sixth unit problem, which also includes the pressure reflections provoked by the acoustic boundaries of the duct. This sixth unit problem describes the establishment of a 1L acoustic longitudinal mode inside a closed duct using the harmonic velocity fluctuations from the fourth unit problem. A wall on the left end of the duct is only moved for one cycle at the 1L mode frequency to establish a 1L mode in the initially quiescent fluid. The last unit problem combines the analytical solution of the 1L mode acoustic field developed in the sixth unit problem with an unsteady heat pulse with Gaussian spatial and temporal distribution, and also accounts for pressure reflections. The derivation of the present analytical models includes the identification of relevant length and time scales that are condensed into the Helmholtz number, the phase shift between the longitudinal fluctuating pressure field and the heat source, and ratio of the fluctuating periods. The analytical solution is able to capture with an acceptable degree of accuracy the pressure trace of the numerical solution during the fist few cycles of the 1L mode, but it quickly deviates very significantly from the numerical solution due to wave steepening and the formation of weak shocks. Therefore, models based on the acoustic wave equation can provide a good understanding of the combustion instability behavior, but not accurately predict the evolution of the pressure fluctuations as the nonlinear effects play a major role in the combustion dynamics of liquid rocket engines.