Mostafa Adimy

A mathematical study of the hematopoiesis process with applications to chronic myelogenous leukemia

This paper is devoted to the analysis of a mathematical model of blood cell production in the bone marrow (hematopoiesis). The model is a system of two age-structured partial differential equations. Integrating these equations over the age, we obtain a system of two nonlinear differential equations with distributed time delay corresponding to the cell cycle duration. This system describes the evolution of the total cell populations. By constructing a Lyapunov functional, it is shown that the trivial equilibrium is globally asymptotically stable if it is the only equilibrium. It is also shown that the nontrivial equilibrium, the most biologically meaningful one, can become unstable via a Hopf bifurcation. Numerical simulations are carried out to illustrate the analytical results. The study may be helpful in understanding the connection between the relatively short cell cycle durations and the relatively long periods of peripheral cell oscillations in some periodic hematological diseases.

Local existence and stability for some partial functional differential equations with infinite delay

Generally, this disclosure provides systems, methods and computer readable media for a protected memory view in a virtual machine (VM) environment enabling nested page table access by trusted guest software outside of VMX root mode. The system may include an editor module configured to provide access to a nested page table structure, by operating system (OS) kernel components and by user space applications within a guest of the VM, wherein the nested page table structure is associated with one of the protected memory views. The system may also include a page handling processor configured to secure that access by maintaining security information in the nested page table structure.

Modelling Hematopoiesis Mediated by Growth Factors With Applications to Periodic Hematological Diseases

Hematopoiesis is a complex biological process that leads to the production and regulation of blood cells. It is based upon differentiation of stem cells under the action of growth factors. A mathematical approach of this process is proposed to understand some blood diseases characterized by very long period oscillations in circulating blood cells. A system of three differential equations with delay, corresponding to the cell cycle duration, is proposed and analyzed. The existence of a Hopf bifurcation at a positive steady-state is obtained through the study of an exponential polynomial characteristic equation with delay-dependent coefficients. Numerical simulations show that long-period oscillations can be obtained in this model, corresponding to a destabilization of the feedback regulation between blood cells and growth factors, for reasonable cell cycle durations. These oscillations can be related to observations on some periodic hematological diseases (such as chronic myelogenous leukemia, for example).Hematopoiesis is a complex biological process that leads to the production and regulation of blood cells. It is based upon differentiation of stem cells under the action of growth factors. A mathematical approach of this process is proposed to understand some blood diseases characterized by very long period oscillations in circulating blood cells. A system of three differential equations with delay, corresponding to the cell cycle duration, is proposed and analyzed. The existence of a Hopf bifurcation at a positive steady-state is obtained through the study of an exponential polynomial characteristic equation with delay-dependent coefficients. Numerical simulations show that long-period oscillations can be obtained in this model, corresponding to a destabilization of the feedback regulation between blood cells and growth factors, for reasonable cell cycle durations. These oscillations can be related to observations on some periodic hematological diseases (such as chronic myelogenous leukemia, for example).

Global stability of a partial differential equation with distributed delay due to cellular replication

In this paper, we investigate a nonlinear partial differential equation, arising from a model of cellular proliferation. This model describes the production of blood cells in the bone marrow. It is represented by a partial differential equation with a retardation of the maturation variable and a distributed temporal delay. Our aim is to prove that the behaviour of primitive cells influences the global behaviour of the population.

Stability and Hopf bifurcation in a mathematical model of pluripotent stem cell dynamics

We study a mathematical model describing the dynamics of a pluripotent stem cell population involved in the blood production process in the bone marrow. This model is a differential equation with a time delay. The delay describes the cell cycle duration and is uniformly distributed on an interval. We obtain stability conditions independent of the delay. We also show that the distributed delay can destabilize the entire system. In particularly, it is shown that Hopf bifurcations can occur.

Discrete maturity-structured model of cell differentiation with applications to acute myelogenous leukemia

We propose and analyze a mathematical model of hematopoietic stem cell dynamics, that takes two cell populations into account, an immature and a mature one. All cells are able to self-renew, and immature cells can be either in a proliferating or in a resting compartment. The resulting model is a system of age-structured partial differential equations, that reduces to a system of delay differential equations, with several distributed delays. We investigate the existence of positive and axial steady states for this system, and we obtain conditions for their stability. Numerically, we concentrate on the influence of variations in differentiation coefficients on the behavior of the system. In particular, we focus on applications to acute myelogenous leukemia, a cancer of white cells characterized by a quick proliferation of immature cells that invade the circulating blood. We show that a blocking of differentiation at an early stage of immature cell development can result in the over-expression of very immature cells, with respect to the mature cell population.

Stability of Limit Cycles in a Pluripotent Stem Cell Dynamics Model

This paper is devoted to the study of the stability of limit cycles of a nonlinear delay differential equation with a distributed delay. The equation arises from a model of population dynamics describing the evolution of a pluripotent stem cells population. We study the local asymptotic stability of the unique nontrivial equilibrium of the delay equation and we show that its stability can be lost through a Hopf bifurcation. We then investigate the stability of the limit cycles yielded by the bifurcation using the normal form theory and the center manifold theorem. We illustrate our results with some numerics.

STABILITY AND HOPF BIFURCATION FOR A CELL POPULATION MODEL WITH STATE-DEPENDENT DELAY ∗

We propose a mathematical model describing the dynamics of a hematopoietic stem cell population. The method of characteristics reduces the age-structured model to a system of differential equations with a state-dependent delay. A detailed stability analysis is performed. A sufficient condition for the global asymptotic stability of the trivial steady state is obtained using a Lyapunov-Razumikhin function. A unique positive steady state is shown to appear through a transcritical bifurcation of the trivial steady state. The analysis of the positive steady state behavior, through the study of a first order exponential polynomial characteristic equation, concludes the existence of a Hopf bifurcation and gives criteria for stability switches. A numerical analysis confirms the results and stresses the role of each parameter involved in the system on the stability of the positive steady state.

Strict solutions of nonlinear hyperbolic neutral differential equations

Abstract In this work, we study a class of abstract semilinear functional differential equations of a neutral type. Our main results concern the existence, uniqueness, and regularity of solutions. We assume that the linear part is nondensely defined, closed, and satisfies the Hille-Yosida condition.

Mathematical model of hematopoiesis dynamics with growth factor-dependent apoptosis and proliferation regulations

We consider a nonlinear mathematical model of hematopoietic stem cell dynamics, in which proliferation and apoptosis are controlled by growth factor concentrations. Cell proliferation is positively regulated, while apoptosis is negatively regulated. The resulting age-structured model is reduced to a system of three differential equations, with three independent delays, and existence of steady states is investigated. The stability of the trivial steady state, describing cells dying out with a saturation of growth factor concentrations is proven to be asymptotically stable when it is the only equilibrium. The stability analysis of the unique positive steady state allows the determination of a stability area, and shows that instability may occur through a Hopf bifurcation, mainly as a destabilization of the proliferative capacity control, when cell cycle durations are very short. Numerical simulations are carried out and result in a stability diagram that stresses the lead role of the introduction rate compared to the apoptosis rate in the system stability.