Capillaries in tumours are often severely buckled (in a plane perpendicular to the axis) and / or chaotic in their direction. We develop a model of these phenomena using nonlinear solid mechanics. Our model focusses on the immediate surrounding of a capillary. The vessel and surrounding tissue are modelled as concentric annulii. The growth is dependent on the concentration of a nutrient (oxygen) diffusing from the vessel into the tumour interstitium. The stress is modelled using a multiplicative decomposition of the deformation gradient F=F_e F_g. The stress is determined by substituting the elastic deformation gradient F_e (which gives the deformation gradient from the hypothetical configuration to the current configuration) into a hyperelastic constitutive model as per classical solid mechanics. We use a Blatz-Ko model, parameterised using uniaxial compression experiments. The entire system is in quasi-static equilibrium, with the divergence of the stress tensor equal to zero. We determine the onset of buckling using a linear stability analysis. We then investigate the postbuckling behaviour by introducing higher order perturbations in the deformation and growth before using the Fredholm Alternative to obtain the magnitude of the buckle. Our results demonstrate that the growth-induced stresses are sufficient for the capillary to buckle in the absence of external loading and / or constraints. Planar buckling usually occurs after 2-5 times the cellular proliferation timescale. Buckles with axial variation almost always go unstable after planar buckles. Buckles of fine wavelength are initially preferred by the system, but over time buckles of large wavelength become energetically more favourable. The tumoural hoop stress T_{ThetaTheta} is the most invariant (Eulerian) variable at the time of buckling: it is typically of the order of the tumoural Young's Modulus when this occurs.

Swarms of animals exhibit aggregations whose behavior is a challenge for mathematicians to understand. We analyze this behavior numerically and analytically by using the pairwise interaction model known as the Morse potential. Our goal is to prove the global stability of the candidate local minimizer in 1D found in A Primer of Swarm Equilibria. Using the calculus of variations and eigenvalues analysis, we conclude that the candidate local minimizer is a global minimum with respect to all solution smaller than its support. In addition, we manage to extend the global stability condition to any solutions whose support has a single component. We are still examining the local minimizers with multiple components to determine whether the candidate solution is the minimum-energy configuration.

Mathematical models apply to a multitude physiological processes and are used to make predictions and analyze outcomes of these processes. Specifically, in the medical field, a mathematical model uses a set of initial conditions that represents a physiological state as input and a set of parameter values are used to describe the interaction between variables being modeled. These models are used to analyze possible outcomes, and assist physicians in choosing the most appropriate treatment options for a particular situation. We aim to use mathematical modeling to analyze the dynamics of processes involved in the inflammatory process. First, we create a model of hematopoiesis, the processes of creating new blood cells. We analyze stem cell collection regimens and statistically sample parameter space in order to create a model accounts for the dynamics of multiple patients. Next, we modify an existing model of the wound healing response by introducing a variable for two inflammatory cell types. We analyze the timing of the inflammatory response and introduce the presence of systemic estrogen in the model, as there is evidence that the presence of estrogen leads to a more efficient wound healing response. Last, we mathematically model the gas exchange process in the lungs and body in order to lay the foundation for a model of the inflammatory response in the lung under conditions of mechanical ventilation. We introduce normal and ventilation breathing waveforms and a third state of hemoglobin in a closed loop partial differential equations model. We account for gas exchange in the lung and body compartments in addition to introducing a third discretized well-mixing compartment between the two. We use ordinary and partial differential equations to model these systems over one or more independent variables, as well as classical analysis techniques and computational methods to analyze systems. Statistical sampling is also used to investigate parameter values in order for the mathematical models developed to account for patient-to-patient variability. This alters the traditional mathematical model, which yields a single set of parameter values that represent one instance of the physiology, into a mathematical model that accounts for many different instances of physiology.}

The thesis concerns the mathematical study of the calculus of variations and its application to liquid crystals. In the first chapter we examine vectorial problems in the calculus of variations with an additional pointwise constraint so that any admissible function <strong>n</strong> ε W^1,1(ΩM), and M is a manifold of suitable regularity. We formulate necessary and sufficient conditions for any given state <strong>n</strong> to be a strong or weak local minimiser of I. This is achieved using a nearest point projection mapping in order to use the more classical results which apply in the absence of a constraint. In the subsequent chapters we study various static continuum theories of liquid crystals. More specifically we look to explain a particular cholesteric fingerprint pattern observed by HP Labs. We begin in Chapter 2 by focusing on a specific cholesteric liquid crystal problem using the theory originally derived by Oseen and Frank. We find the global minimisers for general elastic constants amongst admissible functions which only depend on a single variable. Using the one-constant approximation for the Oseen-Frank free energy, we then show that these states are global minimisers of the three-dimensional problem if the pitch of the cholesteric liquid crystal is sufficiently long. Chapter 3 concerns the application of the results from the first chapter to the situations investigated in the second. The local stability of the one-dimensional states are quantified, analytically and numerically, and in doing so we unearth potential shortcomings of the classical Oseen-Frank theory. In Chapter 4, we ascertain some equivalence results between the continuum theories of Oseen and Frank, Ericksen, and Landau and de Gennes. We do so by proving lifting results, building on the work of Ball and Zarnescu, which relate the regularity of line and vector fields. The results prove to be interesting as they show that for a director theory to respect the head to tail symmetry of the liquid crystal molecules, the appropriate function space for the director field is S BV² (Ω,S<sup>2,/sup>). We take this idea and in the final chapter we propose a mathematical model of liquid crystals based upon the Oseen-Frank free energy but using special functions of bounded variation. We establish the existence of a minimiser, forms of the Euler-Lagrange equation, and find solutions of the Euler-Lagrange equation in some simple cases. Finally we use our proposed model to re-examine the same problems from Chapter 2. By doing so we extend the analysis we were able to achieve using Sobolev spaces and predict the existence of multi-dimensional minimisers consistent with the known experimental properties of high-chirality cholesteric liquid crystals.

Os progressos computacionais nas últimas décadas e a teoria matemática cada vez mais sólida têm possibilitado a resolução de problemas de alta complexidade, permitindo uma modelagem cada vez mais detalhada da realidade. Tal verdade aplica-se inclusive para os sistemas rígidos de Equações Diferencias Ordinárias (EDOs): existem métodos numéricos altamente performáticos para este tipo de problema, que permitem uma grande variação no tamanho do passo de integração sem impactar na sua convergência. Este trabalho apresenta um estudo sobre o conceito de rigidez e técnicas numéricas para resolução de problemas rígidos de EDOs. O que nos motivou a estudar tais técnicas foram problemas oriundos da Física Nuclear que envolvem cadeias de decaimento radioativo. Estes problemas podem ser modelados por uma cadeia fechada de compartimentos que se traduz em um sistema de EDOs. Os elementos destas cadeias podem possuir constantes de decaimento com ordens de grandeza muito distintas, caracterizando a sua rigidez e exigindo cautela na resolução das equações que as modelam. Embora seja possível determinar a solução analítica para estes problemas, o uso de métodos numéricos facilita a obtenção da solução quando consideramos sistemas com um número elevado de equações. Além disso, soluções numéricas permitem adaptações na modelagem ou em ajustes de dados com mais facilidade. Métodos implícitos são indicados para a resolução deste tipo de problema, pois possuem uma região de estabilidade ilimitada. Neste trabalho, implementamos dois métodos numéricos que possuem esta característica: o método de Radau II e o método de Rosenbrock. Estes métodos foram utilizados para obtenção de soluções numéricas robustas para problemas rígidos de decaimento radioativo envolvendo cadeias naturais e artificiais, considerando retiradas de elementos das cadeias durante o processo de decaimento e quando queremos determinar qual era o estado inicial de uma cadeia que está em decaimento. Ambos os métodos foram implementados com estratégias de controle do tamanho do passo de integração e produziram resultados consistentes dentro de uma precisão pré-fixada. / The computational progress in the last decades and the increasingly solid mathematical theory have made possible the resolution of highly complex problems allowing an ever more detailed modelling of reality. This is true even for the systems of stiff Ordinary Differential Equations (ODEs): there are highly performative numerical methods for this kind of problem which allow a wide variation in the size of integration step without impacting on their convergence. This thesis presents a study about the concept of stiffness and numerical techniques to solve stiff problems of ODEs. What motivated us to study these techniques were problems from the Nuclear Physics involving radioactive decay chains. These problems could be modelled by a closed chain of compartments which is translated into a system of ODEs. The elements of these chains could have decay constants with very different orders of magnitude which characterizes the stiffness of the problem and requires caution in solving the model equations. Although it is possible to determine the analytical solution to these problems when we consider systems with a high number of equations, calculate the solution by numerical methods becomes easier. Furthermore, numerical solutions allow adaptations in modelling or data adjustments more easily. Implicit methods are indicated to solve this kind of problem because they have an unlimited region of stability. In this study, we implemented two numerical methods which have this feature: Radau II method and Rosenbrock method. These methods were used to obtain robust numerical solutions for stiff problems of radioactive decay involving natural and artificial chains, considering the removal of elements during the decay process and when we want to determine what was the initial state of a chain which is decaying. Both methods were implemented with control strategies for integration step size providing consistent results within a pre-established accuracy.

Réguler la prise alimentaire et la dépense énergétique permet en général de limiter d'importants changements de poids corporel. Hormones (leptine, ghréline, insuline) et nutriments sont impliqués dans ces régulations. La résistance à la leptine, souvent associée à l'obésité, limite la régulation de la prise alimentaire. La modélisation mathématique de la dynamique du poids contribue en particulier à une meilleure compréhension des mécanismes de régulation (notamment chez l’humain). Or les régulations hormonales sont largement ignorées dans les modèles existants.Dans cette thèse, nous considérons un modèle de régulation hormonale du poids appliqué aux rats, composé d'équations différentielles non-linéaires. Il décrit la dynamique de la prise alimentaire, du poids et de la dépense énergétique, régulés par la leptine, la ghréline et le glucose. Il reproduit et prédit l'évolution du poids et de la prise alimentaire chez des rats soumis à différents régimes hypocaloriques, et met en évidence l'adaptation de la dépense énergétique. Nous introduisons ensuite le premier modèle décrivant le développement de la résistance à la leptine, prenant en compte la régulation de la prise alimentaire par la leptine et ses récepteurs. Nous montrons que des perturbations de la prise alimentaire, ou de la concentration en leptine, peuvent rendre un individu sain résistant à la leptine et obèse. Enfin, nous présentons une simplification réaliste de la dynamique du poids dans ces modèles, permettant de construire un nouveau modèle combinant les deux modèles précédents / The regulation of food intake and energy expenditure usually limits important loss or gain of body weight. Hormones (leptin, ghrelin, insulin) and nutrients (glucose, triglycerides) are among the main regulators of food intake. Leptin is also involved in leptin resistance, often associated with obesity and characterized by a reduced efficacy to regulate food intake. Mathematical models describing the dynamics of body weight have been used to assist clinical weight loss interventions or to study an experimentally inaccessible phenomenon, such as starvation experiments in humans. Modeling of the effect of hormones on body weight has however been largely ignored.In this thesis, we first consider a model of body weight regulation by hormones in rats, made of nonlinear differential equations. It describes the dynamics of food intake, body weight and energy expenditure, regulated by leptin, ghrelin and glucose. It is able to reproduce and predict the evolution of body weight and food intake in rats submitted to different patterns of caloric restriction, showing the importance of the adaptation of energy expenditure. Second, we introduce the first model of leptin resistance development, based on the regulation of food intake by leptin and leptin receptors. We show that healthy individuals may become leptin resistant and obese due to perturbations in food intake or leptin concentration. Finally, modifications of these models are presented, characterized by simplified yet realistic body weight dynamics. The models prove able to fit the previous, as well as new sets of experimental data and allow to build a complete model combining both previous models regulatory mechanisms

Submitted by Maria Cristina (library@lncc.br) on 2015-10-08T14:40:37Z No. of bitstreams: 1 thesiskarine.pdf: 6490137 bytes, checksum: 5cfc4bafd419dffab8b58cc3783124ae (MD5) / Approved for entry into archive by Maria Cristina (library@lncc.br) on 2015-10-08T14:40:53Z (GMT) No. of bitstreams: 1 thesiskarine.pdf: 6490137 bytes, checksum: 5cfc4bafd419dffab8b58cc3783124ae (MD5) / Made available in DSpace on 2015-10-08T14:41:02Z (GMT). No. of bitstreams: 1 thesiskarine.pdf: 6490137 bytes, checksum: 5cfc4bafd419dffab8b58cc3783124ae (MD5) Previous issue date: 2015-03-30 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / In this work we develop a neurocomputational model based on ordinary differential equations which describes the interaction between the reward circuit and the thalamocortical circuit, taking into account the influence of astrocyte. The physiology for these circuits is studied by a coupled model, used to obtain numerical results that describe the action potential behavior associated to each neuron in the neural network. The initial value equations of the proposed models are discretized using classical numerical methods. Thus, it is possible to study the attentional focus behavior when an exogenous substance is added to the system, in particular, to study the influence of nicotine on the attentional focus. The proposed modeling is applied on problems arising in medicine, specifically, in neuropsychiatry. The study cases refer to patients with chemical dependence in nicotine and attention deficit hyperactivity disorder (ADHD) / Neste trabalho desenvolvemos um modelo neurocomputacional baseado em equações diferenciais ordinárias, que descreve a interação entre o circuito da recompensa e o circuito tálamo-cortical, considerando a influência do astrócito. O estudo da fisiologia destes circuitos inspira a construção de um modelo acoplado para ser usado na obtenção de resultados numéricos que descrevem o comportamento do potencial de ação associado a cada neurônio da rede neural. Os problemas de valor inicial que representam os modelos estudados são discretizados usando métodos numéricos clássicos. Desta forma, é possível estudar o comportamento do foco de atenção quando uma substância exógena é adicionada ao sistema, em particular, estudar a influência da nicotina no foco de atenção. A modelagem aqui proposta é aplicada em problemas advindos da medicina, especificamente, da área de neuropsiquiatria. Os casos de estudos estudo estão restritos a pacientes com problemas de dependência química em nicotina e pacientes com transtorno de déficit de atenção e hiperatividade (TDAH).

Being part of a research group on functional differential equations (FDEs, for short), due to my formation in non-absolute integration theory and because certain kinds of FDEs can be expressed as integral equations, I was motivated to investigate the latter. The purpose of this work, therefore, is to develop the theory of integral equations, when the integrals involved are in the sense of Kurzweil- Henstock or Kurzweil-Henstock-Stieltjes, through the correspondence between solutions of integral equations and solutions of generalized ordinary differential equations (we write generalized ODEs, for short). In order to be able to obtain results for integral equations, we propose extensions of both the Kurzweil integral and the generalized ODEs (found in [36]). We develop the fundamental properties of this new generalized ODE, such as existence and uniqueness of solutions results, and we propose stability concepts for the solutions of our new class of equations. We, then, apply these results to a class of nonlinear Volterra integral equations of the second kind. Finally, we consider a model of population growth (found in [4]) that can be expressed as an integral equation that belongs to this class of nonlinear Volterra integral equations. / Sendo parte de um grupo de pesquisa em equações diferenciais funcionais (escrevemos EDFs), por causa de minha formação em teoria de integração não absoluta e porque certos tipos de EDFs podem ser escritas como equações integrais, decidi estudar esse último tipo de equações. O objetivo desse trabalho, portanto, é desenvolver a teoria de equações integrais, quando as integrais envolvidas são no sentido de Kurzweil-Henstock ou Kurzweil-Henstock-Stieltjes, através da correspondência entre soluções de equações integrais e soluções de equações diferenciais ordinárias generalizadas (ou EDOs generalizadas). A fim de obter resultados para estas equações integrais, propomos extensões de ambas a integral de Kurzweil e as EDOs generalizadas (encontradas em [36]). Desenvolvemos propriedades fundamentais dessa nova EDO generalizada, como resultados de existência e unicidade de solução, e propomos conceitos de estabilidade para as soluções de nossa nova classe de equações. Nós, então, aplicamos esses resultados a uma classe de equações integrais de Volterra não lineares de segunda espécie. Finalmente, consideramos um modelo de crescimento de populações (encontrado em [4]) que pode ser escrito como uma equação integral pertencente a essa classe de equações integrais de Volterra não lineares.

Neste trabalho, nós consideramos o seguinte problema de valor inicial para uma equação diferencial funcional retardada com impulsos { \'x PONTO\' = \'varepsilon\' f (t, \'x IND.t\'), t \' DIFERENTE\' \'t IND. k\', \'DELTA\' x(\'t IND. k\') = \'varepsilon\' \' I IND. k\' (x ( \'t IND.k\')), k = 0, 1, 2, ... \'x IND. t IND.0\' = \' phi\', onde f está definida em um aberto \' OMEGA\' de R x \' G POT. -\' ([- r, 0], \' R POT. n\') e assume valores em \'R POT. n\', \' \'varepsilon\' \'G POT. - ([ - r, 0], \'R POT.n\'), r .0, onde \' G POT -\' ([ - r, 0], \' R POT. n\') denota o espaço das funções de [ - r, 0] em \' R POT. n\' que estão regradas e contínuas à esquerda. Além disso, \' t IND.0 < \' t IND. 1\'< ... \'t IND. k\' < ... são momentos pré determinados de impulsos tais que \'lim SOBRE k SETA + \' INFINITO\' \'t IND. k = + \' INFINITO\' e \'DELTA\'x (\' t IND.k\') = x ( \'t POT. + IND > k) - x (\'t IND. k). Os operadores de impulso \' I IND. k\', k = 0, 1, ... são funções contínuas de \'R POT. n\' em \' R POT. n\'. Consideramos, também, que para cada x \'varepsilon\' \' G POT. -\' ([- r, \' INFINITO\'), \'R POT. n\'), t \'SETA\' f (t, \'x IND. t\') é uma função localmente Lebesgue integrável e sua integral indefinida satisfaz uma condição do tipo Carathéodory. Além disso, f é Lipschitziana na segunda variável. Definimos \' f IND. 0\' ( \'phi\') = \' lim SOBRE T \' SETA\' \' INFINITO\' \'1 SUP. T \' INT. SUP. T INF. \' T IND.0\' f (t, \' PSI\') dt e \' I IND. 0(x) = \' lim SOBRE T \'SETA\' \' INFINITO\' \' 1 SUP. T\' \' SIGMA\' IND. 0 < ou = \' t IND. i\' < T onde \' psi\' \'varepsilon\' \' G POT. -\' ([ - r, 0], \' R POT. n\', e consideremos a seguinte equação diferencial funcioonal autônoma \" média\" y PONTO = \' varepsilon\' [ \' f IND. 0\' (\' y IND. t\' + \' I IND> 0\' (y (t))], \'y IND. t IND. 0 = \' phi\'. Então provamos que, sob certas condições, a solução x(t) de (1) se aproxima da solução y(t) de (2) em tempo assintoticamente grande / In this present work, we condider the following initial value problem for a retarded functional differential equation with impulses { \'x POINT\' = \'varepsilon\' f (t, \'x IND.t\'), t \' DIFFERENT\' \'t IND. k\', \'DELTA\' x(\'t IND. k\') = \'varepsilon\' \' I IND. k\' (x ( \'t IND.k\')), k = 0, 1, 2, ... \'x IND. t IND.0\' = \' phi\', where f está defined in a open set \' OMEGA\' de R x \' G POT. -\' ([- r, 0], \' R POT. n\'), r >0, and takes values in \'R POT. n\', \' \'varepsilon\' \'G POT. - ([ - r, 0], \'R POT.n\'), r .0, where \' G POT -\' ([ - r, 0], \' R POT. n\') denotes the space of regulated functions from [ - r, 0] to \' R POT. n\' which are left continuous. Furthermore, \' t IND.0 < \' t IND. 1\'< ... \'t IND. k\' < ... are pre-assigned moments of impulse effects such that \'lim ON k ARROW + \' THE INFINITE\' \'t IND. k = + \' THE INFINITE\' e \'DELTA\'x (\' t IND.k\') = x ( \'t POT. + IND>k) - x (\'t IND. k). The impulse operators \' I IND. k\', k = 0, 1, ... are continuous mappings from \'R POT. n\' to \' R POT. n\'. For each x \'varepsilon\' \' G POT. -\' ([- r, \' THE INFINITE\'), \'R POT. n\'), t \'ARROW\' f (t, \'x IND. t\') is locally Lebesgue integrable and its indefinite integral satisfies a Carathéodory. Moreover, f é Lipschitzian with respect to the second variable. We define \' f IND. 0\' ( \'phi\') = \' lim ON T \' ARROW\' \' THE INFINITE\' \'1 SUP. T \' INT. SUP. T INF. \' T IND.0\' f (t, \' PSI\') dt and \' I IND. 0(x) = \' lim ON T \'ARROW\' \' THE INFINITE\' \' 1 SUP. T\' \' SIGMA\' IND. 0 < or = \' t IND. i\' < T where \' psi\' \'varepsilon\' \' G POT. -\' ([ - r, 0], \' R POT. n\', and consider the \"averaged\" autonomous functional differential equation \'y PONTO = \' varepsilon\' [ \' f IND. 0\' (\' y IND. t\' + \' I IND> 0\' (y (t))], \'y IND. t IND. 0 = \' phi\'. Then we prove that, under certain conditions, the solution x(t) of (1) in aproximates the solution y(t) de (2) in an asymptotically large time interval

Este trabalho é dedicado à extensão do Método da Forma Normal para Equações Diferenciais Ordinárias às Equações Diferenciais Funcionais Retardadas. O método da forma normal para equações diferenciais funcionais retardadas nos dará o fluxo sobre uma variedade localmente invariante de dimensão finita através de uma equação diferencial ordinária. Como aplicação, calcularemos a forma normal para equação diferencial funcional retardada escalar com uma singularidade do tipo Bogdanov-Takens. Analisaremos também a forma normal para equações diferenciais funcionais retardadas com parâmetro. Finalizaremos este trabalho com o cálculo da forma normal de um sistema planar com singularidade do tipo Bogdanov-Takens. / In this work, we compute the normal forms associated with the flow on a finite dimensional invariant, manifold tangent to an invariant space for the infinitesimal generator of the linearized equation at the singularity. As an application, the Bogdanov-Takens singularity is considered.