<div>Public health policies increasingly rely on complex models that need to approximate epidemics realistically and be consistent with the available data. Choosing appropriate simplifying assumptions is one of the critical challenges in disease modeling. In this thesis, we focus on some of these assumptions to show how they impact model outcomes. </div><div>In this thesis, an ODE model with a gamma-distributed infectious period is studied and compared with an exponentially distributed infectious period. We show that, for childhood diseases, isolating infected children is a possible mechanism causing oscillatory behavior in incidence. This is shown analytically by identifying a Hopf bifurcation with the isolation period as the bifurcation parameter. The threshold value for isolation to generate sustained oscillations from the model with gamma-distributed isolation period is much more realistic than the exponentially distributed model.</div><div><br></div><div>The consequences of not modeling the spectrum of clinical symptoms of the 2014 Ebola outbreak in Liberia include overestimating the basic reproduction number and effectiveness of control measures. The outcome of this model is compared with those of models with typical symptoms, excluding moderate ones. Our model captures the dynamics of the recent outbreak of Ebola in Liberia better, and the basic reproduction number is more consistent with the WHO response team's estimate. Additionally, the model with only typical symptoms overestimates the basic reproduction number and effectiveness of control measures and exaggerates changes in peak size attributable to interventions' timing.</div><div><br></div>

Mathematical models, that depict the dynamics of a cancer cell population growing out of the human body (in vitro) in unconstrained microenvironment conditions, are considered in this thesis. Cancer cells in vitro grow and divide much faster than cancer cells in the human body, therefore, the effects of various cancer treatments applied to them can be identified much faster. These cell populations, when not exposed to any cancer treatment, exhibit exponential growth that we refer to as the balanced exponential growth (BEG) state. This observation has led to several effective methods of estimating parameters that thereafter are not required to be determined experimentally. We present derivation of the age-structured model and its theoretical analysis of the existence of the solution. Furthermore, we have obtained the condition for BEG existence using the Perron-Frobenius theorem. A mathematical description of the cell-cycle control is shown for one-compartment and two-compartment populations, where a compartment refers to a cell population consisting of cells that exhibit similar kinetic properties. We have incorporated into our mathematical model the required growing/aging times in each phase of the cell cycle for the biological viability. Moreover, we have derived analytical formulae for vital parameters in cancer research, such as population doubling time, the average cell-cycle age, and the average removal age from all phases, which we argue is the average cell-cycle time of the population. An estimate of the average cell-cycle time is of a particular interest for biologists and clinicians, and for patient survival prognoses as it is considered that short cell-cycle times correlate with poor survival prognoses for patients. Applications of our mathematical model to experimental data have been shown. First, we have derived algebraic expressions to determine the population doubling time from single experimental observation as an alternative to empirically constructed growth curve. This result is applicable to various types of cancer cell lines. One option to extend this model would be to derive the cell cycle time from a single experimental measurement. Second, we have applied our mathematical model to interpret and derive dynamic-depicting parameters of five melanoma cell lines exposed to radiotherapy. The mathematical result suggests there are shortcomings in the experimental methods and provides an insight into the cancer cell population dynamics during post radiotherapy. Finally, a mathematical model depicting a theoretical cancer cell population that comprises two sub-populations with different kinetic properties is presented to describe the transition of a primary culture to a cell line cell population.

In this study, we consider the mechanism design problem for the optimal allocation of fishing quotas at different total allowable catch (TAC) levels. An age-structured fish population model is employed. Fishing technologies are embedded in the economic model as a key determinant. As a result, we showed that the quota allocation mechanism is important to minimize the impact of fishing on total fish biomass or achieve maximum sustainable yield (MSY). Moreover, we indicated technology-based optimality conditions for allocation of quotas at different TAC levels, which minimize the impact of fishing on total fish biomass or enable us to achieve MSY. Under the consideration that the fishermen fulfill their remaining quotas through capturing untargeted (less revenue-generating) fish after the targeted fish population is fully caught, the fix ratio of the catch of targeted fish to untargeted fish is not valid anymore. Concordantly, we indicated technology-based optimal quota levels, including the interior solutions. In the EU, TACs are distributed among states according to the principle of &lsquo / relative stability&rsquo / which prescribes that the fishing quotas should be allocated based on historical catches of the EU states. In this context, rather than allocating the quotas based on historical catches, our main suggestion is that the structure of the fishing industry should be considered for allocation of quotas to provide the sustainability of EU fisheries and achieve responsible and effective management of the fishing industry in the EU.

Dans cette thèse on s'intéresse à un modèle mathématique décrivant l'adaptation du développement des populations de moustiques face à l'usage intensif des insecticides durant la nuit (moustiquaires imprégnées, répulsifs en spray, répulsifs avec diffuseur électrique, ...).Le modèle proposé dans cette thèse est structuré en âge et dépend du temps/moment où le moustique pique pour prendre son repas. Ceci nous conduità des modèles du type ultra parabolique. Le terme de renouvellement de lapopulation de moustiques est non-local, comme pour tous les problèmes démographiques, mais comporte ici un noyau qui permet à la nouvelle générationd'adapter son temps de piqure (repas). Ceci est dû à la sélection de certainsmoustiques qui piquent plus tôt ou plus tard que les autres moustiques, suite àla pression imposée par l'usage intensif des pesticides à l'intérieur des habitats et en particulier durant la nuit. Les conditions aux bords par rapport au moment de piqure (repas) seront périodiques car selon les espèces, les moustiques prennent toujours leurs repas au même moment de la journée.Les principaux résultats peuvent être classés dans 4 parties.Dans la première partie on présente un modèle structuré en âge décrivant laplasticité du moustique dans un environnement non contrôlé. On montre quele problème est bien posé via la théorie des semi-groupes. Le comportementasymptotique est décrit grâce à l'étude du spectre de l'opérateur A générateurdu C0 semi-groupe. On prouve également l'existence ou la non existence dessolutions stationnaires (sous certaines hypothèses).Dans la deuxième partie on s'intéresse à un problème de contrôle optimalde la population de moustiques. Le contrôle correspond à la proportion demoustiques éliminée et dépend du temps, de l'âge des moustiques et du tempsoù le moustique pique pour se nourrir. On démontre d’abord l’existence desolutions grâce à un argument de point fixe puis on établit des résultats decomparaisons pour notre problème. On établit ensuite l'existence d'un contrôleoptimal puis on dérive le système d'optimalité.Dans la troisième partie on s'intéresse à la question de contrôlabilité exacte locale pour le problème décrivant la capacité des moustiques à adapter leurdynamique face à l'usage intensif des insecticides. On établit une nouvelleinégalité de type Carleman pour le modèle structuré en âge avec diffusionet une condition au bord de renouvellement non-locale et des conditions auxbords périodiques par rapport au temps de piqure des moustiques.Dans la quatrième partie on s'intéresse au comportement en temps longd'un modèle non linéaire décrivant l'adaptation de la population des moustiques à l'usage intensif des insecticides. Quand le contrôle est petit (usage limité des insecticides) alors la population mature de moustiques devient grandeavec le temps et quand le contrôle est grand (usage intensif des insecticides)la population mature de moustiques devient petite avec le temps. Dans le casintermédiaire on obtient un modèle avec retard en temps pour la populationmature de moustiques qui peut être gouvernée par une sur-équation et unesous-équation. Finalement on montre que la sous-équation admet des ondesvoyageuses et la population mature de moustiques sera donc comprise entreces ondes voyageuses et les sur-solutions. / This dissertation is concerned with an age structured problem modelling mosquito plasticity. The main results can be divided into four parts.The first part presents an age structured problem modelling mosquito plasticity in a natural environment. We first investigate the analytical asymptotic solution through studying the spectrum of an operator A which is the infinitesimal generator of a C0-semigroup. Additionally, we get the existence and nonexistence of nonnegative steady solutions under some conditions.In the second part, we study the optimal control of an age structured problem. Firstly, we prove the existence of solutions and the comparison principle for a generalized system. Then, we prove the existence of the optimal control for the best harvesting. Finally, we establish necessary optimality conditions.In the third part, we investigate the local exact controllability of an age structured problem modelling the ability of malaria vectors to shift their biting time to avoid the stressful environmental conditions generated by the use of indoor residual spraying (IRs) and insecticide-treated nets (ITNs). We establish a new Carleman's inequality for our age diffusive model with non local birth processus and periodic biting-time boundary conditions.In the fourth part, we model a mosquito plasticity problem and investigate the large time behavior of matured population under different control strategies. Firstly, we prove that when the control is small, then the matured population will become large for large time and when the control is large, then the matured population will become small for large time. In the intermediate case, we derive a time-delayed model for the matured population which can be governed by a sub-equation and a super-equation. Finally, we prove the existence of traveling fronts for the sub-equation and use it to prove that the matured population will finally be between the positive states of the sub-equation and super-equation.

Dans cette thèse nous étudions l'influence de l'environnement sur le comportement d'une cellule dans deux situations différentes. Dans chacune de ces deux situations, apparaît un couplage non-linéaire sur le champ d'advection lié à un terme non-local provenant du bord du domaine. Dans une première partie, nous modélisons la polarisation cellulaire durant la conjugaison de la cellule de levure. Nous utilisons un modèle de type convection-diffusion avec un terme de convection non-linéaire et non-local. Ce modèle présente des similarités avec le modèle de Keller-Segel, la source du potentiel attractif étant sur le bord du domaine. Nous étudions le cas de la dimension un en utilisant des inégalités de Sobolev logarithmiques et HWI. En nous appuyant sur un raisonnement heuristique, nous ramenons l'étude de notre modèle en dimension deux au bord du domaine. Nous validons le modèle à l'aide des résultats expérimentaux obtenus par M. Piel en utilisant un bruit dynamique dans nos simulations numériques. Nous étudions ensuite le problème du dialogue cellulaire entre cellules de levure de sexe opposé. Dans une seconde partie, nous étudions la réaction immunitaire durant l'athérosclérose. Nous construisons puis développons un modèle structuré en âge pour décrire l'inflammation. Pour des paramètres particuliers, nous déterminons le comportement en temps long de notre système en utilisant une fonctionnelle de Lyapunov. / We investigate the influence of the environment on the behaviour of a cell in two different situations. In each of these situations, there is a non-linear coupling of the drift due to a non-local term coming from the boundary of the domain.The first part focuses on the modeling of cell polarisation during the mating of yeast. We use a convection-diffusion model with a non-linear and non-local drift. This model is similar to the Keller-Segel model, the source of the attractive potential comes from the boundary of the domain. We study the long time behaviour of the one-dimensional case by using logarithmic Sobolev and HWI inequalities.By relying on a heuristic, we reduce the study of our model in the two-dimensional case to the boundary of the domain. We validate the model with data provided by M. Piel. This validation requires adding a dynamical noise in our numerical simulations. We study then the cell discussion between yeast of opposite gender. In the second part we study the immune response in atherosclerosis. We build and then develop an age structured model in order to describe the inflammation. For specific parameters, we investigate the long time behaviour of our system by using a Lyapunov functional.

Ce mémoire concerne la modélisation mathématique de l’érythropoïèse, à savoir le processus de production des érythrocytes (ou globules rouges) et sa régulation par l’érythropoïétine, une hormone de contrôle. Nous proposons une extension d’un modèle d’érythropoïèse tenant compte du vieillissement des cellules matures. D’abord, nous considérons un modèle structuré en maturité avec condition limite mouvante, dont la dynamique est capturée par des équations d’advection. Biologiquement, la condition limite mouvante signifie que la durée de vie maximale varie afin qu’il y ait toujours un flux constant de cellules éliminées. Par la suite, des hypothèses sur la biologie sont introduites pour simplifier ce modèle et le ramener à un système de trois équations différentielles à retard pour la population totale, la concentration d’hormones ainsi que la durée de vie maximale. Un système alternatif composé de deux équations avec deux retards constants est obtenu en supposant que la durée de vie maximale soit fixe. Enfin, un nouveau modèle est introduit, lequel comporte un taux de mortalité augmentant exponentiellement en fonction du niveau de maturité des érythrocytes. Une analyse de stabilité linéaire permet de détecter des bifurcations de Hopf simple et double émergeant des variations du gain dans la boucle de feedback et de paramètres associés à la fonction de survie. Des simulations numériques suggèrent aussi une perte de stabilité causée par des interactions entre deux modes linéaires et l’existence d’un tore de dimension deux dans l’espace de phase autour de la solution stationnaire. / This thesis addresses erythropoiesis mathematical modeling, which is the process of erythrocytes production and its regulation by erythropeitin. We propose an erythropoiesis model extension which includes aging of mature cells. First, we consider an age-structured model with moving boundary condition, whose dynamics are represented by advection equations. Biologically, the moving boundary condition means that the maximal lifespan varies to account for a constant degraded cells flux. Then, hypotheses are introduced to simplify and transform the model into a system of three delay differential equations for the total population, the hormone concentration and the maximal lifespan. An alternative model composed of two equations with two constant delays is obtained by supposing that the maximal lifespan is constant. Finally, a new model is introduced, which includes an exponential death rate depending on erythrocytes maturity level. A linear stability analysis allows to detect simple and double Hopf bifurcations emerging from variations of the gain in the feedback loop and from parameters associated to the survival function. Numerical simulations also suggest a loss of stability caused by interactions between two linear modes and the existence of a two dimensional torus in the phase space close to the stationary solution.

We investigate the biological constraints determined by the complex relationships between ecological and immunological processes of host-pathogen interactions, with emphasis on influenza viruses in human, which are responsible for a number of pandemics in the last 150 years. We begin by discussing prolegomenous reviews of historical perspectives on the use of theoretical modelling as a complementary tool in public health and epidemiology, current biological background motivating the objective of the thesis, and derivations of mathematical models of multi-locus-allele systems for infectious diseases with co-circulating serotypes. We provide detailed analysis of the multi-locus-allele model and its age-specific extension. In particular, we establish the necessary conditions for the local asymptotic stability of the steady states and the existence of oscillatory behaviours. For the age-structured model, results on the existence of a mild solution and stability conditions are presented. Numerical studies of various strain spaces show that the dynamic features are preserved. Specifically, we demonstrate that discrete antigenic forms of pathogens can exhibit three distinct dynamic features, where antigenic variants (i) fully self-organize and co-exist with no strain structure (NSS), (ii) sort themselves into discrete strain structure (DSS) with non-overlapping or minimally overlapping clusters under the principle of competitive exclusion, or (iii) exhibit cyclical strain structure (CSS) where dominant antigenic types are cyclically replaced with sharp epidemics dominated by (1) a single strain dominance with irregular emergence and re-emergence of certain pathogenic forms, (2) ordered alternating appearance of a single antigenic type in periodic or quasi-periodic form similar to periodic travelling waves, (3) erratic appearance and disappearance of synchrony between discrete antigenic types, and (4) phase-synchronization with uncorrelated amplitudes. These analyses allow us to gain insight into the age-specific immunological profile in order to untangle the effects of strain structures as captured by the clustering behaviours, and to provide public health implications. The age-structured model can be used to investigate the effect of age-specific targeting for public health purposes.