Reaction-diffusion models have been widely successful in explaining a large variety of patterning phenomena in biology ranging from embryonic development to cancer growth and angiogenesis. Firstly proposed by Alan Turing in 1952 and applied to a simple two-component system, reaction-diffusion models describe spontaneous spatial pattern formation, driven purely by interactions of the system components and their diffusion in space. Today, access to unprecedented amounts of quantitative biological data allows us to build and test biochemically accurate reaction-diffusion models of intracellular processes. However, any increase in model complexity increases the number of unknown parameters and thus the computational cost of model analysis. To efficiently characterize the behavior and robustness of models with many unknown parameters is, therefore, a key challenge in systems biology. Here, we propose a novel computational framework for efficient high-dimensional parameter space characterization of reaction-diffusion models. The method leverages the $L_p$-Adaptation algorithm, an adaptive-proposal statistical method for approximate high-dimensional design centering and robustness estimation. Our approach is based on an oracle function, which describes for each point in parameter space whether the corresponding model fulfills given specifications. We propose specific oracles to estimate four parameter-space characteristics: bistability, instability, capability of spontaneous pattern formation, and capability of pattern maintenance. We benchmark the method and demonstrate that it allows exploring the ability of a model to undergo pattern-forming instabilities and to quantify model robustness for model selection in polynomial time with dimensionality. We present an application of the framework to reconstituted membrane domains bearing the small GTPase Rab5 and propose molecular mechanisms that potentially drive pattern formation.

Ziel dieser Arbeit ist es zwei verschiedene Klassen von Systemen nichtlinearer parabolischer Gleichungen zu homogenisieren, und zwar Reaktions-Diffusions-Systeme mit verschiedenen Diffusionslängenskalen und Gleichungen vom Typ Cahn-Hilliard. Wir betrachten parabolische Gleichungen mit periodischen Koeffizienten, wobei die Periode dem Verhältnis der charakteristischen mikroskopischen zu der makroskopische Längenskala entspricht. Unser Ziel ist es, effektive Gleichungen rigoros herzuleiten, um die betrachteten Systeme besser zu verstehen und den Simulationsaufwand zu minimieren. Wir suchen also einen Konvergenzbegriff, mit dem die Lösung des Ausgangsmodells im Limes der Periode gegen Null gegen die Lösung des effektiven Modells konvergiert. Um die periodische Mikrostruktur und die verschiedenen Diffusivitäten zu erfassen, verwenden wir die Zwei-Skalen Konvergenz mittels periodischer Auffaltung. Der erste Teil der Arbeit handelt von Reaktions-Diffusions-Systemen, in denen einige Spezies mit der charakteristischen Diffusionslänge der makroskopischen Skala und andere mit der mikroskopischen diffundieren. Die verschiedenen Diffusivitäten führen zu einem Verlust der Kompaktheit, sodass wir nicht direkt den Grenzwert der nichtlinearen Terme bestimmen können. Wir beweisen mittels starker Zwei-Skalen Konvergenz, dass das effektive Modell ein zwei-skaliges Modell ist, welches von der makroskopischen und der mikroskopischen Skale abhängt. Unsere Methode erlaubt es uns, explizite Raten für die Konvergenz der Lösungen zu bestimmen. Im zweiten Teil betrachten wir Gleichungen vom Typ Cahn-Hilliard, welche ortsabhängige Mobilitätskoeffizienten und allgemeine Potentiale beinhalten. Wir beweisen evolutionäre Gamma-Konvergenz der zugehörigen Gradientensysteme basierend auf der Gamma-Konvergenz der Energien und der Dissipationspotentiale. / The aim of this thesis is to derive homogenization results for two different types of systems of nonlinear parabolic equations, namely reaction-diffusion systems involving different diffusion length scales and Cahn-Hilliard-type equations. The coefficient functions of the considered parabolic equations are periodically oscillating with a period which is proportional to the ratio between the charactersitic microscopic and macroscopic length scales. In view of greater structural insight and less computational effort, it is our aim to rigorously derive effective equations as the period tends to zero such that solutions of the original model converge to solutions of the effective model. To account for the periodic microstructure as well as for the different diffusion length scales, we employ the method of two-scale convergence via periodic unfolding. In the first part of the thesis, we consider reaction-diffusion systems, where for some species the diffusion length scale is of order of the macroscopic length scale and for other species it is of order of the microscopic one. Based on the notion of strong two-scale convergence, we prove that the effective model is a two-scale reaction-diffusion system depending on the macroscopic and the microscopic scale. Our approach supplies explicit rates for the convergence of the solution. In the second part, we consider Cahn-Hilliard-type equations with position-dependent mobilities and general potentials. It is well-known that the classical Cahn-Hilliard equation admits a gradient structure. Based on the Gamma-convergence of the energies and the dissipation potentials, we prove evolutionary Gamma-convergence, for the associated gradient system such that we obtain in the limit of vanishing periods a Cahn-Hilliard equation with homogenized coefficients.

Das Thema dieser Dissertation ist die Anwendung von Variationsmethoden auf Evolutionsgleichungen parabolischen und hyperbolischen Typs. Im ersten Teil der Arbeit beschäftigen wir uns mit Reaktions-Diffusions-Systemen, die sich als Gradientensysteme schreiben lassen. Hierbei verstehen wir unter einem Gradientensystem ein Tripel bestehend aus einem Zustandsraum, einem Entropiefunktional und einer Dissipationsmetrik. Wir geben Bedingungen an, die die geodätische Konvexität des Entropiefunktionals sichern. Geodätische Konvexität ist eine wertvolle aber auch starke strukturelle Eigenschaft und schwer zu zeigen. Wir zeigen anhand zahlreicher Beispiele, darunter ein Drift-Diffusions-System, dass dennoch interessante Systeme existieren, die diese Eigenschaft besitzen. Einen weiteren Punkt dieser Arbeit stellt die Anwendung von Gamma-Konvergenz auf Gradientensysteme dar. Wir betrachten hierbei zwei Modellsysteme aus dem Bereich der Mehrskalenprobleme: Erstens, die rigorose Herleitung einer Allen-Cahn-Gleichung mit dynamischen Randbedingungen und zweitens, einer Interface-Bedingung für eine eindimensionale Diffusionsgleichung jeweils aus einem reinen Bulk-System. Im zweiten Teil der Arbeit beschäftigen wir uns mit dem sog. Weighted-Inertia-Dissipation-Energy-Prinzip für Evolutionsgleichungen. Hierbei werden Trajektorien eines Systems als (Grenzwerte von) Minimierer(n) einer parametrisierten Familie von Funktionalen charakterisiert. Dies erlaubt es, Werkzeuge aus der Theorie der Variationsrechung auf Evolutionsprobleme anzuwenden. Wir zeigen, dass Minimierer der WIDE-Funktionale gegen Lösungen des Ausgangsproblems konvergieren. Hierbei betrachten wir getrennt voneinander den Fall des beschränkten und des unbeschränkten Zeitintervalls, die jeweils mit verschiedenen Methoden behandelt werden. / This thesis deals with the application of variational methods to evolution problems governed by partial differential equations. The first part of this work is devoted to systems of reaction-diffusion equations that can be formulated as gradient systems with respect to an entropy functional and a dissipation metric. We provide methods for establishing geodesic convexity of the entropy functional by purely differential methods. Geodesic convexity is beneficial, however, it is a strong structural property of a gradient system that is rather difficult to achieve. Several examples, including a drift-diffusion system, provide a survey on the applicability of the theory. Next, we demonstrate the application of Gamma-convergence, to derive effective limit models for multiscale problems. The crucial point in this investigation is that we rely only on the gradient structure of the systems. We consider two model problems: The rigorous derivation of an Allen-Cahn system with bulk/surface coupling and of an interface condition for a one-dimensional diffusion equation. The second part of this thesis is devoted to the so-called Weighted-Inertia-Dissipation-Energy principle. The WIDE principle is a global-in-time variational principle for evolution equations either of conservative or dissipative type. It relies on the minimization of a specific parameter-dependent family of functionals (WIDE functionals) with minimizers characterizing entire trajectories of the system. We prove that minimizers of the WIDE functional converge, up to subsequences, to weak solutions of the limiting PDE when the parameter tends to zero. The interest for this perspective is that of moving the successful machinery of the Calculus of Variations.

In this thesis we investigate the formation of patterns in a simple activator-inhibitor model supplemented with an inhibitory nonlocal coupling term. This model exhibits a wave instability for slow inhibitor diffusion, while, for fast inhibitor diffusion, a Turing instability is found. For moderate values of the inhibitor diffusion these two instabilities occur simultaneously at a codimension-2 wave-Turing instability. We perform a weakly nonlinear analysis of the model in the neighbourhood of this codimension-2 instability. The resulting amplitude equations consist in a set of coupled Ginzburg-Landau equations. These equations predict that the model exhibits bistability between travelling waves and Turing patterns. We present a study of interfaces separating wave and Turing patterns arising from the codimension-2 instability. We study theoretically and numerically the dynamics of such interfaces in the framework of the amplitude equations and compare these results with numerical simulations of the model near and far away from the codimension-2 instability. Near the instability, the dynamics of interfaces separating small amplitude Turing patterns and travelling waves is well described by the amplitude equations, while, far from the codimension-2 instability, we observe a locking of the interface velocities. This locking mechanism is imposed by the absence of defects near the interfaces and is responsible for the formation of drifting pattern domains, i.e. moving localised patches of travelling waves embedded in a Turing pattern background and vice versa.

L'objectif de cette thèse est l'étude qualitative de certains modèles de la dynamique et la distribution des bactéries dans une rivière. Il s'agit de la stabilité des états stationnaires et l'existence des solutions périodiques. Nous considérons, dans la première partie de la thèse, un système d'équations différentielles ordinaires qui modélise les interactions et la dynamique de quatre espèces de bactéries dans une rivière. Nous avons étudié le comportement asymptotique des états stationnaires. L'étude de la stabilité des états stationnaires est essentiellement faite par la construction d'une fonction de Lyapunov combinée avec le principe d'invariance de LaSalle. D'autre part, l'existence des solutions périodiques est démontrée en utilisant le théorème de continuation de Mawhin. La deuxième partie de la thèse est consacrée à l'étude d'un système de convection-diffusion non-autonome. Ce modèle tient compte du transport des bactéries. Nous étudions l'analyse qualitative des solutions, nous déterminons l'ensemble limite du système et nous démontrons l'existence des états stationnaires positifs. L'étude de l'existence des états stationnaires (les seuls qu'il soit possible d'obtenir) est basée sur le théorème de Leray-Schauder. / The objective of this thesis is the qualitative study of some models of the dynamic and the distribution of bacteria in a river. We are interested in the stability of equilibria and the existence of periodic solutions. The thesis can be divided into two parts; the first part is concerned with a mathematical analysis of a system of differential equations modelling the dynamics and the interactions of four species of bacteria in a river. The asymptotic behavior of equilibria is established. The stability study of equilibrium states is mainly done by construction of Lyapunov functions combined with LaSalle's invariance principle. On the other hand, the existence of periodic solutions is proved under certain conditions using the continuation theorem of Mawhin. In the second part of this thesis, we propose a non-autonomous convection-reaction diffusion system with nonlinear reaction source functions. This model refers to the quantification and the distribution of antibiotic resistant bacteria (ARB) in a river. Our main contributions are : (i) the determination of the limit set of the system; it is shown that it is reduced to the solutions of the associated elliptic system; (ii) sufficient conditions for the existence of a positive solution of the associated elliptic system based on the Leray Schauder's degree theory.

On considère des organismes qui mixent reproduction sexuée et asexuée, dans une situation où la reproduction sexuée fait intervenir à la fois de la dispersion spatiale et de la limitation d'appariement. Nous proposons un modèle qui implique deux équations couplées, la première étant une équation différentielle ordinaire de type logistique, la seconde étant une équation de réaction-diffusion. Grâce à des valeurs réalistes des différents coefficients, il s'avère que la deuxième équation fait intervenir une échelle de temps rapide, alors que la première fait intervenir une échelle de temps lente. Dans un premier temps, on montre l'existence et l'unicité de solutions au système original. Dans un second temps, dans la limite où l'échelle de temps rapide est considérée infiniment rapide, on montre la convergence vers une dynamique réduite d'état d'équilibre, dont les termes correctifs peuvent être calculés à tout ordre. Troisièmement, en utilisant des propriétés de monotonie de notre système coopératif, on montre l'existence d'ondes progressives dans une région particulière de l'espace des paramètres (cas monostable). / We consider organisms that mix sexual and asexual reproduction, in a situation where sexual reproduction involves both spatial dispersion and mate finding limitation. We propose a model that involves two coupled equations, the first one being an ordinary differential equation of logistic type, the second one being a reaction diffusion equation. According to realistic values of the various coefficients, the second equation turns out to involve a fast time scale, while the first one involves a separated slow time scale. First we show existence and uniqueness of solutions to the original system. Second, in the limit where the fast time scale is considered infinitely fast, we show the convergence towards a reduced quasi steady state dynamics, whose correctors can be computed at any order. Third, using monotonicity properties of our cooperative system, we show the existence of traveling wave solutions in a particular region of the parameter space (monostable case).

In this thesis we investigate the formation of patterns in a simple activator-inhibitor model supplemented with an inhibitory nonlocal coupling term. This model exhibits a wave instability for slow inhibitor diffusion, while, for fast inhibitor diffusion, a Turing instability is found. For moderate values of the inhibitor diffusion these two instabilities occur simultaneously at a codimension-2 wave-Turing instability. We perform a weakly nonlinear analysis of the model in the neighbourhood of this codimension-2 instability. The resulting amplitude equations consist in a set of coupled Ginzburg-Landau equations. These equations predict that the model exhibits bistability between travelling waves and Turing patterns. We present a study of interfaces separating wave and Turing patterns arising from the codimension-2 instability. We study theoretically and numerically the dynamics of such interfaces in the framework of the amplitude equations and compare these results with numerical simulations of the model near and far away from the codimension-2 instability. Near the instability, the dynamics of interfaces separating small amplitude Turing patterns and travelling waves is well described by the amplitude equations, while, far from the codimension-2 instability, we observe a locking of the interface velocities. This locking mechanism is imposed by the absence of defects near the interfaces and is responsible for the formation of drifting pattern domains, i.e. moving localised patches of travelling waves embedded in a Turing pattern background and vice versa.

<p dir="ltr">As aircraft engine manufacturers continue to embark on their pursuit of higher-efficiency, lower-emissions gas turbines, a prevailing theme in the industry has been the increase of the engine bypass ratio. As the optimization space for engine bypass ratios trends towards smaller and smaller engine core sizes, the feasibility of centrifugal compressors as the final stage in an axial-centrifugal compressor becomes apparent due to their performance advantages at smaller scales.</p><p dir="ltr">This study performed an investigation into the aerodynamics of a stationary diffusion system intended for use with a final stage aeroengine centrifugal compressor using experimental and numerical techniques. Experimental work was performed at the Purdue Compressor Research Lab at Purdue University’s Maurice J. Zucrow Laboratories. Data were collected from several iterations of rapidly prototyped, additively manufactured diffuser and deswirl parts with internal instrumentation features. Furthermore, computational work on the stage was conducted using the Ansys Turbosystem.</p><p dir="ltr">The goal of this research is to identify trends in stationary diffusion system designs and the geometric features that cause them. Furthermore, the ability of steady computational fluid dynamics methods to predict these changes was evaluated using two turbulence models to produce a simulation of the compressor flow field. When used in conjunction with one another, the efficient use of computational methods to identify an optimal design and rapid prototyping to validate it leads to the determination of the best diffusion system design at a lower cost and time requirement than what is otherwise currently possible.</p><p dir="ltr">The different geometries which were tested identified the negative effects of spanwise vane contouring on the diffuser performance and the ability of endwall divergence to augment the pressure recovery performance of a design at the expense of increased losses. A full understanding of the effect of each design parameter is enabled by iterative inclusion or exclusion of certain design parameters. Furthermore, the use of computational fluid dynamics showed that the BSLEARSM turbulence model performs reasonably well in predicting the build-to-build performance trends. However, neither the BSLEARSM nor the SST turbulence model were able to accurately identify performance trends for the deswirl. For this reason, additional work is warranted to identify an optimal set of parameters to characterize the high axial and meridional turning present in this component.</p>

Depuis l’article fondateur de Jordan, Kinderlehrer et Otto en 1998, il est bien connu qu’une large classe d’équations paraboliques peuvent être vues comme des flots de gradient dans l’espace de Wasserstein. Le but de cette thèse est d’étendre cette théorie à certaines équations et systèmes qui n’ont pas exactement une structure de flot de gradient. Les interactions étudiées sont de différentes natures. Le premier chapitre traite des systèmes avec des interactions non locales dans la dérive. Nous étudions ensuite des systèmes de diffusions croisées s’appliquant aux modèles de congestion pour plusieurs populations. Un autre modèle étudié est celui où le couplage se trouve dans le terme de réaction comme les systèmes proie-prédateur avec diffusion ou encore les modèles de croissance tumorale. Nous étudierons enfin des systèmes de type nouveau où l’interaction est donnée par un problème de transport multi-marges. Une grande partie de ces problèmes est illustrée de simulations numériques. / Since 1998 and the seminal work of Jordan, Kinderlehrer and Otto, it is well known that a large class of parabolic equations can be seen as gradient flows in the Wasserstein space. This thesis is devoted to extensions of this theory to equations and systems which do not have exactly a gradient flow structure. We study different kind of couplings. First, we treat the case of nonlocal interactions in the drift. Then, we study cross diffusion systems which model congestion for several species. We are also interested in reaction-diffusion systems as diffusive prey-predator systems or tumor growth models. Finally, we introduce a new class of systems where the interaction is given by a multi-marginal transport problem. In many cases, we give numerical simulations to illustrate our theorical results.