This dissertation consists of a development of the notion of equilibrium in non-cooperative games (introduced by John Nash in his doctoral dissertation submitted in May 1950) from the point of view of games played by complex adaptive systems (such as States) who adapt to an asymmetric distribution of bargaining power. The main ingredient of this dissertation is the notion of the contextually normalized solution, that implies that players routinely repeat strategies that work, and that an asymmetric complex game will be in a stable state so long as the set of normal strategies consists of the stronger players’ most preferred and the weaker players’ least disliked strategies. There is no other generality in rational behaviour; all else is relative to the frame of reference.

This thesis is a part of the French national project called MACAO (Modélisation Avancée de Composants Aéronautiques et Outils associés). In collaboration with Messier-Dowty company (a landing gears manufacturer), the thesis has contributed to better understand the actual literature studies in the field of aircraft tyre-road interaction modelling and therefore, to help making an optimal choice of model for a specifie application. The objectives have been to propose models for representing the tyre behaviour on the ground with respect to the aircraft run types. Physical oriented models are preferred. To complete this study, a literature survey of the previous researches in tyre modelling for steady­state responses is first carried out. Then, based on the main factors playing an important role in tyre modelling, it is proposed a classification for the physical and the semi-empirical models, which are also investigated. Based on this classification, the study requirements and the measurement data constraints, an a priori choice of suitable models are studied. A further investigation of the tyre deformation at pure lateral slip is carried out. It has allowed to physically describe the mechanism of generation of the longitudinal component of the tyre force at pure lateral slip. This force is refened as induced longitudinal force. By taking this force into consideration, it has been possible to explain why the self-aligning moment can drop to zero before the tyre gets to full sliding at pure lateral slip. Besides, the sensitivity analysis is proposed as a means for determining the parameters that have most influence on the model output and thus, are responsible for the output uncertainty.

La présente thèse est une partie du projet national français dénommé MACAO (Modélisation Avancée de Composants Aéronautiques et Outils associés). En collaboration avec Messier-Dowty (constructeur d'atterrisseurs d'avion), cette thèse contribue à une meilleure compréhension du comportement du pneu sur piste dans le domaine de l'aéronautique. L'objectif est de mettre en place des modèles capables de représenter le torseur des efforts au niveau de l'interface pneu-piste lors des différentes manœuvres de l'avion au sol en régime établi. Une priorité est accordée aux modèles dont les paramètres sont physiquement interprétables. De ce fait, un état de l'art des modèles de pneu en régime établi est d'abord réalisé. Un classement de ces modèles selon leurs motivations et limitations est aussi proposé. A l'aide de cette classification et en prenant en compte les exigences de l'étude, un choix a priori de modèles a été analysé. Les limites de ces modèles sont soulignées et une amélioration est proposée. Par ailleurs, une étude exhaustive de la déformation du pneu en situation de virage a été menée. Elle a permis de décrire la génération de la composante longitudinale de la force totale au niveau de l'interface pneu-piste. Elle est dite force longitudinale induite. Puis, en prenant en compte cette force, il a été possible d'expliquer pourquoi le moment d'auto-alignement peut repasser par zéro sans que le pneu ne soit en glissement total. Enfin, l'analyse de sensibilité est proposée comme une méthode permettant de déterminer les paramètres les plus influents de chaque modèle. Ces paramètres doivent alors être déterminés avec précision afin de réduire l'incertitude sur le modèle. / This thesis is a part of the French national project called MACAO (Modélisation Avancée de Composants Aéronautiques et Outils associés). In collaboration with Messier-Dowty company (a landing gears manufacturer), the thesis has contributed to better understand the actual literature studies in the field of aircraft tyre-road interaction modelling and therefore, to help making an optimal choice of model for a specifie application. The objectives have been to propose models for representing the tyre behaviour on the ground with respect to the aircraft run types. Physical oriented models are preferred. To complete this study, a literature survey of the previous researches in tyre modelling for steady­state responses is first carried out. Then, based on the main factors playing an important role in tyre modelling, it is proposed a classification for the physical and the semi-empirical models, which are also investigated. Based on this classification, the study requirements and the measurement data constraints, an a priori choice of suitable models are studied. A further investigation of the tyre deformation at pure lateral slip is carried out. It has allowed to physically describe the mechanism of generation of the longitudinal component of the tyre force at pure lateral slip. This force is refened as induced longitudinal force. By taking this force into consideration, it has been possible to explain why the self-aligning moment can drop to zero before the tyre gets to full sliding at pure lateral slip. Besides, the sensitivity analysis is proposed as a means for determining the parameters that have most influence on the model output and thus, are responsible for the output uncertainty.

<p>The main aim of the thesis was to explore the potential of supercritical fluid (SF) techniques in the field of drug delivery. In particular, the relatively recently developed solution-enhanced dispersion by supercritical fluids (SEDS) technology has been employed in the preparation of particles/powders. </p><p>The manufacturing, stability and bioavailability of a dosage form strongly depend on the physicochemical properties of the formulation particles. For example, dry powder inhalation (DPI) for administering drugs to the respiratory tract require particles in a narrow size range (1-5 μm) to be effective. The identification of polymorphs and control of purity are also important issues since the physicochemical properties and therapeutic effects of the alternative forms of a drug may differ substantially. Solvent-based traditional crystallisation processes provide the product that may require further down-stream processing to obtain particles for advanced drug delivery applications. This can result in unwanted changes in the physicochemical properties of the particles and thus affect the performance of the dosage form. SF processing has addressed many of the challenges in particle formation research. Among several SF technologies developed for particle processing over the last decade, the SEDS process with its specially designed co-axial nozzle with mixing chamber has resulted in improved control over the particle formation process. Carbon dioxide (CO₂) was used as the SF, because it has low critical points and is non-toxic, non-flammable and relatively inexpensive. </p><p>The initial part of the thesis concerns the formation of particles of model drugs such as hydrocortisone, budesonide and flunisolide using SEDS technology and the determination of the influence of processing conditions and solvents on particle characteristics such as size, shape and crystal structure. Particles of model drugs of differing shapes in a size range suitable for inhalation delivery were prepared. In the process, two new polymorphic forms of flunisolide were identified. This was the first report of SEDS technology being shown as a polymorph-screening tool. The remainder of the thesis deals with the development of SEDS technology for precipitating therapeutic proteins such as recombinant human growth hormone (hGH) from aqueous solutions. Powders of hGH were precipitated using SEDS without significant changes in the chemical or physical stability of the protein. The addition of sucrose to hGH in the feed solution promoted precipitation and minimised the detrimental effects of the solvent and/or the process on the physical aggregation of the protein. </p><p>In conclusion, this thesis highlights the applicability of the SEDS process in drug delivery research and advances general understanding of the particle formation phenomenon. The SEDS process may also prove to be a potential alternative technology for the precipitation of stable powders of therapeutic proteins.</p>

The main aim of the thesis was to explore the potential of supercritical fluid (SF) techniques in the field of drug delivery. In particular, the relatively recently developed solution-enhanced dispersion by supercritical fluids (SEDS) technology has been employed in the preparation of particles/powders. The manufacturing, stability and bioavailability of a dosage form strongly depend on the physicochemical properties of the formulation particles. For example, dry powder inhalation (DPI) for administering drugs to the respiratory tract require particles in a narrow size range (1-5 μm) to be effective. The identification of polymorphs and control of purity are also important issues since the physicochemical properties and therapeutic effects of the alternative forms of a drug may differ substantially. Solvent-based traditional crystallisation processes provide the product that may require further down-stream processing to obtain particles for advanced drug delivery applications. This can result in unwanted changes in the physicochemical properties of the particles and thus affect the performance of the dosage form. SF processing has addressed many of the challenges in particle formation research. Among several SF technologies developed for particle processing over the last decade, the SEDS process with its specially designed co-axial nozzle with mixing chamber has resulted in improved control over the particle formation process. Carbon dioxide (CO2) was used as the SF, because it has low critical points and is non-toxic, non-flammable and relatively inexpensive. The initial part of the thesis concerns the formation of particles of model drugs such as hydrocortisone, budesonide and flunisolide using SEDS technology and the determination of the influence of processing conditions and solvents on particle characteristics such as size, shape and crystal structure. Particles of model drugs of differing shapes in a size range suitable for inhalation delivery were prepared. In the process, two new polymorphic forms of flunisolide were identified. This was the first report of SEDS technology being shown as a polymorph-screening tool. The remainder of the thesis deals with the development of SEDS technology for precipitating therapeutic proteins such as recombinant human growth hormone (hGH) from aqueous solutions. Powders of hGH were precipitated using SEDS without significant changes in the chemical or physical stability of the protein. The addition of sucrose to hGH in the feed solution promoted precipitation and minimised the detrimental effects of the solvent and/or the process on the physical aggregation of the protein. In conclusion, this thesis highlights the applicability of the SEDS process in drug delivery research and advances general understanding of the particle formation phenomenon. The SEDS process may also prove to be a potential alternative technology for the precipitation of stable powders of therapeutic proteins.