A Dynamic P53-MDM2 Model with Time Delay

Specific activator and repressor transcription factors which bind to specific regulator DNA sequences, play an important role in gene activity control. Interactions between genes coding such transcription factors should explain the different stable or sometimes oscillatory gene activities characteristic for different tissues. Starting with the model P53-MDM2 described into [6] and the process described into [5] we developed a new model of this interaction. Choosing the delay as a bifurcation parameter we study the direction and stability of the bifurcating periodic solutions. Some numerical examples are finally given for justifying the theoretical results.Comment: 16 pages, 12 figure

Eigenelements of a General Aggregation-Fragmentation Model

We consider a linear integro-differential equation which arises to describe both aggregation-fragmentation processes and cell division. We prove the existence of a solution (\lb,\U,\phi) to the related eigenproblem. Such eigenelements are useful to study the long time asymptotic behaviour of solutions as well as the steady states when the equation is coupled with an ODE. Our study concerns a non-constant transport term that can vanish at $x=0,$ since it seems to be relevant to describe some biological processes like proteins aggregation. Non lower-bounded transport terms bring difficulties to find $a\ priori$ estimates. All the work of this paper is to solve this problem using weighted-norms

Quantitative Analysis of Mechanisms That Govern Red Blood Cell Age Structure and Dynamics during Anaemia

Mathematical modelling has proven an important tool in elucidating and quantifying mechanisms that govern the age structure and population dynamics of red blood cells (RBCs). Here we synthesise ideas from previous experimental data and the mathematical modelling literature with new data in order to test hypotheses and generate new predictions about these mechanisms. The result is a set of competing hypotheses about three intrinsic mechanisms: the feedback from circulating RBC concentration to production rate of immature RBCs (reticulocytes) in bone marrow, the release of reticulocytes from bone marrow into the circulation, and their subsequent ageing and clearance. In addition we examine two mechanisms specific to our experimental system: the effect of phenylhydrazine (PHZ) and blood sampling on RBC dynamics. We performed a set of experiments to quantify the dynamics of reticulocyte proportion, RBC concentration, and erythropoietin concentration in PHZ-induced anaemic mice. By quantifying experimental error we are able to fit and assess each hypothesis against our data and recover parameter estimates using Markov chain Monte Carlo based Bayesian inference. We find that, under normal conditions, about 3% of reticulocytes are released early from bone marrow and upon maturation all cells are released immediately. In the circulation, RBCs undergo random clearance but have a maximum lifespan of about 50 days. Under anaemic conditions reticulocyte production rate is linearly correlated with the difference between normal and anaemic RBC concentrations, and their release rate is exponentially correlated with the same. PHZ appears to age rather than kill RBCs, and younger RBCs are affected more than older RBCs. Blood sampling caused short aperiodic spikes in the proportion of reticulocytes which appear to have a different developmental pathway than normal reticulocytes. We also provide evidence of large diurnal oscillations in serum erythropoietin levels during anaemia

Local Asymptotic Stability Conditions for the Positive Equilibrium of a System Modeling Cell Dynamics in Leukemia

International audienceA distributed delay system with static nonlinearity has been considered in the literature to study the cell dynamics in leukemia. In this chapter local asymptotic stability conditions are derived for the positive equilibrium point of this nonlinear system. The stability conditions are expressed in terms of inequalities involving parameters of the system. These inequality conditions give guidelines for development of therapeutic actions