Mass concentration in a nonlocal model of clonal selection

Self-renewal is a constitutive property of stem cells. Testing the cancer stem cell hypothesis requires investigation of the impact of self-renewal on cancer expansion. To understand better this impact, we propose a mathematical model describing dynamics of a continuum of cell clones structured by the self-renewal potential. The model is an extension of the finite multi-compartment models of interactions between normal and cancer cells in acute leukemias. It takes a form of a system of integro-differential equations with a nonlinear and nonlocal coupling, which describes regulatory feedback loops in cell proliferation and differentiation process. We show that such coupling leads to mass concentration in points corresponding to maximum of the self-renewal potential and the model solutions tend asymptotically to a linear combination of Dirac measures. Furthermore, using a Lyapunov function constructed for a finite dimensional counterpart of the model, we prove that the total mass of the solution converges to a globally stable equilibrium. Additionally, we show stability of the model in space of positive Radon measures equipped with flat metric. The analytical results are illustrated by numerical simulations

Continuous time random walk, Mittag-Leffler waiting time and fractional diffusion: mathematical aspects

We show the asymptotic long-time equivalence of a generic power law waiting time distribution to the Mittag-Leffler waiting time distribution, characteristic for a time fractional CTRW. This asymptotic equivalence is effected by a combination of "rescaling" time and "respeeding" the relevant renewal process followed by a passage to a limit for which we need a suitable relation between the parameters of rescaling and respeeding. Turning our attention to spatially 1-D CTRWs with a generic power law jump distribution, "rescaling" space can be interpreted as a second kind of "respeeding" which then, again under a proper relation between the relevant parameters leads in the limit to the space-time fractional diffusion equation. Finally, we treat the `time fractional drift" process as a properly scaled limit of the counting number of a Mittag-Leffler renewal process.Comment: 36 pages, 3 figures (5 files eps). Invited lecture by R. Gorenflo at the 373. WE-Heraeus-Seminar on Anomalous Transport: Experimental Results and Theoretical Challenges, Physikzentrum Bad-Honnef (Germany), 12-16 July 2006; Chairmen: R. Klages, G. Radons and I.M. Sokolo

Theoretical connections between mathematical neuronal models corresponding to different expressions of noise

Identifying the right tools to express the stochastic aspects of neural activity has proven to be one of the biggest challenges in computational neuroscience. Even if there is no definitive answer to this issue, the most common procedure to express this randomness is the use of stochastic models. In accordance with the origin of variability, the sources of randomness are classified as intrinsic or extrinsic and give rise to distinct mathematical frameworks to track down the dynamics of the cell. While the external variability is generally treated by the use of a Wiener process in models such as the Integrate-and-Fire model, the internal variability is mostly expressed via a random firing process. In this paper, we investigate how those distinct expressions of variability can be related. To do so, we examine the probability density functions to the corresponding stochastic models and investigate in what way they can be mapped one to another via integral transforms. Our theoretical findings offer a new insight view into the particular categories of variability and it confirms that, despite their contrasting nature, the mathematical formalization of internal and external variability are strikingly similar

Continuous time random walk and parametric subordination in fractional diffusion

The well-scaled transition to the diffusion limit in the framework of the theory of continuous-time random walk (CTRW)is presented starting from its representation as an infinite series that points out the subordinated character of the CTRW itself. We treat the CTRW as a combination of a random walk on the axis of physical time with a random walk in space, both walks happening in discrete operational time. In the continuum limit we obtain a generally non-Markovian diffusion process governed by a space-time fractional diffusion equation. The essential assumption is that the probabilities for waiting times and jump-widths behave asymptotically like powers with negative exponents related to the orders of the fractional derivatives. By what we call parametric subordination, applied to a combination of a Markov process with a positively oriented L\'evy process, we generate and display sample paths for some special cases.Comment: 28 pages, 18 figures. Workshop 'In Search of a Theory of Complexity'. Denton, Texas, August 200

A Recipe for State Dependent Distributed Delay Differential Equations

We use the McKendrick equation with variable ageing rate and randomly distributed maturation time to derive a state dependent distributed delay differential equation. We show that the resulting delay differential equation preserves non-negativity of initial conditions and we characterise local stability of equilibria. By specifying the distribution of maturation age, we recover state dependent discrete, uniform and gamma distributed delay differential equations. We show how to reduce the uniform case to a system of state dependent discrete delay equations and the gamma distributed case to a system of ordinary differential equations. To illustrate the benefits of these reductions, we convert previously published transit compartment models into equivalent distributed delay differential equations.Comment: 28 page

Numerical equilibrium analysis for structured consumer resource models

In this paper, we present methods for a numerical equilibrium and stability analysis for models of a size structured population competing for an unstructured resource. We concentrate on cases where two model parameters are free, and thus existence boundaries for equilibria and stability boundaries can be defined in the (two-parameter) plane. We numerically trace these implicitly defined curves using alternatingly tangent prediction and Newton correction. Evaluation of the maps defining the curves involves integration over individual size and individual survival probability (and their derivatives) as functions of individual age. Such ingredients are often defined as solutions of ODE, i.e., in general only implicitly. In our case, the right-hand sides of these ODE feature discontinuities that are caused by an abrupt change of behavior at the size where juveniles are assumed to turn adult. So, we combine the numerical solution of these ODE with curve tracing methods. We have implemented the algorithms for “Daphnia consuming algae” models in C-code. The results obtained by way of this implementation are shown in the form of graphs