Self-induced switchings between multiple space-time patterns on complex networks of excitable units

We report on self-induced switchings between multiple distinct space--time patterns in the dynamics of a spatially extended excitable system. These switchings between low-amplitude oscillations, nonlinear waves, and extreme events strongly resemble a random process, although the system is deterministic. We show that a chaotic saddle -- which contains all the patterns as well as channel-like structures that mediate the transitions between them -- is the backbone of such a pattern switching dynamics. Our analyses indicate that essential ingredients for the observed phenomena are that the system behaves like an inhomogeneous oscillatory medium that is capable of self-generating spatially localized excitations and that is dominated by short-range connections but also features long-range connections. With our findings, we present an alternative to the well-known ways to obtain self-induced pattern switching, namely noise-induced attractor hopping, heteroclinic orbits, and adaptation to an external signal. This alternative way can be expected to improve our understanding of pattern switchings in spatially extended natural dynamical systems like the brain and the heart

Study of Virus Dynamics by Mathematical Models

This thesis studies virus dynamics within host by mathematical models, and topics discussed include viral release strategies, viral spreading mechanism, and interaction of virus with the immune system. Firstly, we propose a delay differential equation model with distributed delay to investigate the evolutionary competition between budding and lytic viral release strategies. We find that when antibody is not established, the dynamics of competition depends on the respective basic reproduction numbers of the two viruses. If the basic reproductive ratio of budding virus is greater than that of lytic virus and one, budding virus can survive. When antibody is established for both strains but the neutralization capacities are the same for both strains, consequence of the competition also depends only on the basic reproduction numbers of the budding and lytic viruses. Using two concrete forms of the viral production functions, we are also able to conclude that budding virus will outcompete if the rates of viral production, death rates of infected cells and neutralizing capacities of the antibodies are the same for budding and lytic viruses. In this case, budding strategy would have evolutionary advantage. However, if the antibody neutralization capacity for the budding virus is larger than that for the lytic virus, lytic virus can outcompete provided that its reproductive ratio is very high. An explicit threshold is derived. Secondly, we consider model containing two modes for viral infection and spread, one is the diffusion-limited free virus transmission and the other is the direct cell-to-cell transfer of viral particles. By incorporating infection age, a rigorous analysis of the model shows that the model demonstrates a global threshold dynamics, fully described by the basic reproduction number, which is identified explicitly. The formula for the basic reproduction number of our model reveals the effects of various model parameters including the transmission rates of the two modes, and the impact of the infection age. We show that basic reproduction number is underestimated in the existing models that only consider the cell-free virus transmission, or the cell-to-cell infection, ignoring the other. Assuming logistic growth for target cells, we find that if the basic reproduction number is greater than one, the infection can persist and Hopf bifurcation can occur from the positive equilibrium within certain parameter ranges. Thirdly, the repulsion effect of superinfecting virion by infected cells is studied by a reaction diffusion equation model for virus infection dynamics. In this model, the diffusion of virus depends not only on its concentration gradient but also on the concentration of infected cells. The basic reproduction number, linear stability of steady states, spreading speed, and existence of traveling wave solutions for the model are discussed. It is shown that viruses spread more rapidly with the repulsion effect of infected cells on superinfecting virions, than with random diffusion only. For our model, the spreading speed of free virus is not consistent with the minimal traveling wave speed. With our general model, numerical computations of the spreading speed shows that the repulsion of superinfecting vision promotes the spread of virus, which confirms, not only qualitatively but also quantitatively, some recent experimental results. Finally, the effect of chemotactic movement of CD8+ cytotoxic T lymphocytes (CTLs) on HIV-1 infection dynamics is studied by a reaction diffusion model with chemotaxis. Choosing a typical chemosensitive function, we find that chemoattractive movement of CTLs due to HIV infection does not change stability of the positive steady state of the model. However, chemorepulsion movement of CTLs destabilizes the positive steady state as the strength of the chemotactic sensitivity increases. In this case, Turing instability occurs, which can be Hopf bifurcation or steady state bifurcation, and spatial heterogeneous patterns may form

Propagating reaction fronts in moving fluids

La presente tesis tuvo como objetivo estudiar frentes de reacción modelados mediante la ecuación de Kuramoto-Sivashinsky sujetos a diferentes tipos de movimiento de fluido: flujo externo de Poiseuille, el cual es contrastado con el flujo de Couette, y flujo convectivo debido a la inestabilidad de Rayleigh-Taylor. En el primer caso, los frentes se propagan a favor o en contra de un flujo estacionario bidimensional entre dos placas paralelas que se conoce como flujo de Poiseuille. Para pequeñas distancias entre las placas, encontramos frentes estacionarios que pueden ser planos, simétricos o asimétricos, dependiendo de la separación de las placas y de la velocidad promedio del fluido externo. Adicionalmente, descubrimos que los frentes simétricos estables que se propagan en sentido opuesto al flujo simétrico externo se vuelven asimétricos al incrementar la rapidez del flujo externo. En el caso del flujo externo de Couette, el flujo es producido por el movimiento de dos placas paralelas en sentidos opuestos. Hallamos que la estabilidad y la forma de los frentes estacionarios dependen de la velocidad relativa entre las placas y de su separación. Estos parámetros desempeñan un papel importante, puesto que pueden convertir frentes inestables en estables. En el último caso, las inestabilidades en el frente producidas cuando un fluido más denso se encuentra encima de un fluido menos denso se conocen como inestabilidades de Rayleigh-Taylor y son causadas por la diferencia de densidades a través del frente bajo la acción de la gravedad. El frente describe la interfaz delgada que separa los fluidos de diferente densidad dentro de dos placas paralelas verticales; mientras que la convección causada por las fuerzas de flotación a través de la interfaz delgada determina el flujo debido a la inestabilidad de Rayleigh-Taylor. Para el estudio de los efectos del flujo externo sobre los frentes de reacción, primero obtuvimos los frentes y luego realizaremos un análisis de estabilidad lineal para determinar la estabilidad de los frentes bajo los tres tipos de movimiento del fluido. La forma de los frentes y sus respectivas regiones de estabilidad fueron contrastadas con los frentes en ausencia de flujo externo. Los resultados de la investigación fueron publicados en tres revistas internacionales arbitradas e indexadas: Physical Review E (2012), Chaos (2014), y European Physics Journal (2014). Adicionalmente, la tesis presenta resultados para frentes oscilantes y sus transiciones al caos debido a la interacción del frente de reacción con los flujos externos antes mencionados.Tesi

Lattice-gas cellular automata for the analysis of cancer invasion

Cancer cells display characteristic traits acquired in a step-wise manner during carcinogenesis. Some of these traits are autonomous growth, induction of angiogenesis, invasion and metastasis. In this thesis, the focus is on one of the latest stages of tumor progression, tumor invasion. Tumor invasion emerges from the combined effect of tumor cell-cell and cell-microenvironment interactions, which can be studied with the help of mathematical analysis. Cellular automata (CA) can be viewed as simple models of self-organizing complex systems in which collective behavior can emerge out of an ensemble of many interacting "simple" components. In particular, we focus on an important class of CA, the so-called lattice-gas cellular automata (LGCA). In contrast to traditional CA, LGCA provide a straightforward and intuitive implementation of particle transport and interactions. Additionally, the structure of LGCA facilitates the mathematical analysis of their behavior. Here, the principal tools of mathematical analysis of LGCA are the mean-field approximation and the corresponding Lattice Boltzmann equation. The main objective of this thesis is to investigate important aspects of tumor invasion, under the microscope of mathematical modeling and analysis: Impact of the tumor environment: We introduce a LGCA as a microscopic model of tumor cell migration together with a mathematical description of different tumor environments. We study the impact of the various tumor environments (such as extracellular matrix) on tumor cell migration by estimating the tumor cell dispersion speed for a given environment. Effect of tumor cell proliferation and migration: We study the effect of tumor cell proliferation and migration on the tumor’s invasive behavior by developing a simplified LGCA model of tumor growth. In particular, we derive the corresponding macroscopic dynamics and we calculate the tumor’s invasion speed in terms of tumor cell proliferation and migration rates. Moreover, we calculate the width of the invasive zone, where the majority of mitotic activity is concentrated, and it is found to be proportional to the invasion speed. Mechanisms of tumor invasion emergence: We investigate the mechanisms for the emergence of tumor invasion in the course of cancer progression. We conclude that the response of a microscopic intracellular mechanism (migration/proliferation dichotomy) to oxygen shortage, i.e. hypoxia, maybe responsible for the transition from a benign (proliferative) to a malignant (invasive) tumor. Computing in vivo tumor invasion: Finally, we propose an evolutionary algorithm that estimates the parameters of a tumor growth LGCA model based on time-series of patient medical data (in particular Magnetic Resonance and Diffusion Tensor Imaging data). These parameters may allow to reproduce clinically relevant tumor growth scenarios for a specific patient, providing a prediction of the tumor growth at a later time stage.Krebszellen zeigen charakteristische Merkmale, die sie in einem schrittweisen Vorgang während der Karzinogenese erworben haben. Einige dieser Merkmale sind autonomes Wachstum, die Induktion von Angiogenese, Invasion und Metastasis. Der Schwerpunkt dieser Arbeit liegt auf der Tumorinvasion, einer der letzten Phasen der Tumorprogression. Die Tumorinvasion ensteht aus der kombinierten Wirkung von den Wechselwirkungen Tumorzelle-Zelle und Zelle-Mikroumgebung, die mit die Hilfe von mathematischer Analyse untersucht werden können. Zelluläre Automaten (CA) können als einfache Modelle von selbst-organisierenden komplexen Systemen betrachtet werden, in denen kollektives Verhalten aus einer Kombination von vielen interagierenden "einfachen" Komponenten entstehen kann. Insbesondere konzentrieren wir uns auf eine wichtige CA-Klasse, die sogenannten Zelluläre Gitter-Gas Automaten (LGCA). Im Gegensatz zu traditionellen CA bieten LGCA eine einfache und intuitive Umsetzung der Teilchen und Wechselwirkungen. Zusätzlich erleichtert die Struktur der LGCA die mathematische Analyse ihres Verhaltens. Die wichtigsten Werkzeuge der mathematischen Analyse der LGCA sind hier die Mean-field Approximation und die entsprechende Lattice - Boltzmann - Gleichung. Das wichtigste Ziel dieser Arbeit ist es, wichtige Aspekte der Tumorinvasion unter dem Mikroskop der mathematischen Modellierung und Analyse zu erforschen: Auswirkungen der Tumorumgebung: Wir stellen einen LGCA als mikroskopisches Modell der Tumorzellen-Migration in Verbindung mit einer mathematischen Beschreibung der verschiedenen Tumorumgebungen vor. Wir untersuchen die Auswirkungen der verschiedenen Tumorumgebungen (z. B. extrazellulären Matrix) auf die Migration von Tumorzellen dürch Schätzung der Tumorzellen-Dispersionsgeschwindigkeit in einem gegebenen Umfeld. Wirkung von Tumor-Zellenproliferation und Migration: Wir untersuchen die Wirkung von Tumorzellenproliferation und Migration auf das invasive Verhalten der Tumorzellen durch die Entwicklung eines vereinfachten LGCA Tumorwachstumsmodells. Wir leiten die entsprechende makroskopische Dynamik und berechnen die Tumorinvasionsgeschwindigkeit im Hinblick auf die Tumorzellenproliferation- und Migrationswerte. Darüber hinaus berechnen wir die Breite der invasiven Zone, wo die Mehrheit der mitotischer Aktivität konzentriert ist, und es wird festgestellt, dass diese proportional zu den Invasionsgeschwindigkeit ist. Mechanismen der Tumorinvasion Entstehung: Wir untersuchen Mechanismen, die für die Entstehung von Tumorinvasion im Verlauf des Krebs zuständig sind. Wir kommen zu dem Schluss, dass die Reaktion eines mikroskopischen intrazellulären Mechanismus (Migration/Proliferation Dichotomie) zu Sauerstoffmangel, d.h. Hypoxie, möglicheweise für den Übergang von einem gutartigen (proliferative) zu einer bösartigen (invasive) Tumor verantwortlich ist. Berechnung der in-vivo Tumorinvasion: Schließlich schlagen wir einen evolutionären Algorithmus vor, der die Parameter eines LGCA Modells von Tumorwachstum auf der Grundlage von medizinischen Daten des Patienten für mehrere Zeitpunkte (insbesondere die Magnet-Resonanz-und Diffusion Tensor Imaging Daten) ermöglicht. Diese Parameter erlauben Szenarien für einen klinisch relevanten Tumorwachstum für einen bestimmten Patienten zu reproduzieren, die eine Vorhersage des Tumorwachstums zu einem späteren Zeitpunkt möglich machen

Some problems in nonlinear diffusion

In this thesis we investigate mathematical models for a number of topics in the field of nonlinear diffusion, using similarity, asymptotic and numerical methods and focussing on the time-asymptotic behaviour in most cases. Firstly, we consider `fast' diffusion in the vicinity of a mask-edge, with application to dopant diffusion into a semiconductor. A variety of approaches are used to determine concentration contours and aspect ratios. Next we consider flow by curvature. Using group analysis, we determine a number of new symmetries for the governing equations in two and three dimensions. By tracking a moving front numerically, we also construct single and double spiral patterns (reminiscent of those observed in the Belousov-Zhabotinskii chemical reaction), and classify the types of behaviour that can occur. Finally, we analyse travelling wave solutions and the behaviour near to extinction for closed loops. We next consider relaxation waves in a system that can be used to model target patterns, also observed in the Belousov-Zhabotinskii reaction. Numerical and asymptotic results are presented, and a number of new cases of front behaviour are obtained. Finally, we investigate a number of systems using an approach based on the WKB method, analysing the motion of invasive fronts and also the form of the pattern left behind. For Fisher's equation, we demonstrate how modulated travelling waves can be obtained by prescribing an oscillatory initial profile. The method is then extended, firstly to Turing systems and then to oscillatory systems, for which we use an additional periodic plane wave argument to determine the unequal front and pattern speeds, as well as the periodicity. Finally, we illustrate how these methods apply to a recently-used `chaotic' model from ecology