arXiv subjects

Anna Marciniak-Czochra

Publications and source records attributed to Anna Marciniak-Czochra.

At least 37 records · Page 2Linked to original sources

arXiv2019

A structured population model of clonal selection in acute leukemias with multiple maturation stages

Recent progress in genetic techniques has shed light on the complex co-evolution of malignant cell clones in leukemias. However, several aspects of clonal selection still remain unclear. In this paper, we present a multi-compartmental continuously structured population model of selection dynamics in acute leukemias, which consists of a system of coupled integro-differential equations. Our model can be analysed in a more efficient way than classical models formulated in terms of ordinary differential equations. Exploiting the analytical tractability of this model, we investigate how clonal selection is shaped by the self-renewal fraction and the proliferation rate of leukemic cells at different maturation stages. We integrate analytical results with numerical solutions of a calibrated version of the model based on real patient data. In summary, our mathematical results formalise the biological notion that clonal selection is driven by the self-renewal fraction of leukemic stem cells and the clones that possess the highest value of this parameter are ultimately selected. Moreover, we demonstrate that the self-renewal fraction and the proliferation rate of non-stem cells do not have a substantial impact on clonal selection. Taken together, our results indicate that interclonal variability in the self-renewal fraction of leukemic stem cells provides the necessary substrate for clonal selection to act upon.

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arXiv2019

Oscillations in a white blood cell production model with multiple differentiation stages

In this work we prove occurrence of a super-critical Hopf bifurcation in a model of white blood cell formation structured by three maturation stages. We provide an explicit analytical expression for the bifurcation point depending on model parameters. The Hopf bifurcation is a unique feature of the multi-compartment structure as it does not exist in the corresponding two-compartment model. It appears for a parameter set different from the parameters identified for healthy hematopoiesis and requires changes in at least two cell properties. Model analysis allows identifying a range of biologically plausible parameter sets that can explain persistent oscillations of white blood cell counts observed in some hematopoietic diseases. Relating the identified parameter sets to recent experimental and clinical findings provides insights into the pathological mechanisms leading to oscillating blood cell counts.

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arXiv2018

The Escalator Boxcar Train Method for a System of Aged-structured Equations in the Space of Measures

The Escalator Boxcar Train (EBT) method is a well known and widely used numerical method for one-dimensional structured population models of McKendrick-von Foerster type. Recently the method, in its full generality, has been applied to aged-structured two-sex population model (Fredrickson-Hoppensteadt model), which consists of three coupled hyperbolic partial differential equations with nonlocal boundary conditions. We derive the simplified EBT method and prove its convergence to the solution of Fredrickson-Hoppensteadt model. The convergence can be proven, however only if we analyse the whole problem in the space of nonnegative Radon measures equipped with bounded Lipschitz distance (flat metric). Numerical simulations are presented to illustrate the results.

math.NA↗

arXiv2017

Dynamical spike solutions in a nonlocal model of pattern formation

Coupling a reaction-diffusion equation with ordinary differential equations (ODE) may lead to diffusion-driven instability (DDI) which, in contrast to the classical reaction-diffusion models, causes destabilization of both, constant solutions and Turing patterns. Using a shadow-type limit of a reaction-diffusion-ODE model, we show that in such cases the instability driven by nonlocal terms (a counterpart of DDI) may lead to formation of unbounded spike patterns.

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arXiv2016

Instability of Turing patterns in reaction-diffusion-ODE systems

The aim of this paper is to contribute to the understanding of the pattern formation phenomenon in reaction-diffusion equations coupled with ordinary differential equations. Such systems of equations arise, for example, from modeling of interactions between cellular processes such as cell growth, differentiation or transformation and diffusing signaling factors. We focus on stability analysis of solutions of a prototype model consisting of a single reaction-diffusion equation coupled to an ordinary differential equation. We show that such systems are very different from classical reaction-diffusion models. They exhibit diffusion-driven instability (Turing instability) under a condition of autocatalysis of non-diffusing component. However, the same mechanism which destabilizes constant solutions of such models, destabilizes also all continuous spatially heterogeneous stationary solutions, and consequently, there exist no stable Turing patterns in such reaction-diffusion-ODE systems. We provide a rigorous result on the nonlinear instability, which involves the analysis of a continuous spectrum of a linear operator induced by the lack of diffusion in the destabilizing equation. These results are extended to discontinuous patterns for a class of nonlinearities.

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arXiv2016

Stability of nonconstant stationary solutions in a reaction-diffusion equation coupled to the system of ordinary differential equations

In this paper we study pattern formation arising in a system of a single reaction-diffusion equation coupled with subsystem of ordinary differential equations, describing spatially-distributed growth of clonal populations of precancerous cells, whose proliferation is controled by growth factors diffusing in the extracellular medium and binding to the cell surface. We extend the results on the existence of nonhomogenous stationary solutions obtained in the previous work of one of the authors to a general Hill-type production function and full parameter set. Using spectral analysis and perturbation theory we derive conditions for the linearized stability of such spatial patterns.

q-bio.TO↗

arXiv2016

Stable patterns with jump discontinuity in systems with Turing instability and hysteresis

Classical models of pattern formation are based on diffusion-driven instability (DDI) of constant stationary solutions of reaction-diffusion equations, which leads to emergence of stable, regular Turing patterns formed around that equilibrium. In this paper we show that coupling reaction-diffusion equations with ordinary differential equations (ODE) may lead to a novel pattern formation phenomenon in which DDI causes destabilization of both constant solutions and Turing patterns. Bistability and hysteresis effects in the null sets of model nonlinearities yield formation of far from the equilibrium patterns with jump discontinuity. We derive conditions for stability of stationary solutions with jump discontinuity in a suitable topology which allows disclosing the discontinuity points and leads to the definition of (ε0 , A)-stability. Additionally, we provide conditions on stability of patterns in a quasi-stationary model reduction. The analysis is illustrated on the example of three-component model of receptor-ligand binding. The proposed model provides an example of a mechanism of de novo formation of far from the equilibrium patterns in reaction-diffusion-ODE models involving co-existence of DDI and hysteresis.

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arXiv2016

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.

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arXiv2015

Diffusion-driven blowup of nonnegative solutions to reaction-diffusion-ODE systems

In this paper we provide an example of a class of two reaction-diffusion-ODE equations with homogeneous Neumann boundary conditions, in which Turing-type instability not only destabilizes constant steady states but also induces blow-up of nonnegative spatially heterogeneous solutions. Solutions of this problem preserve nonnegativity and uniform boundedness of the total mass. Moreover, for the corresponding system with two non-zero diffusion coefficients, all nonnegative solutions are global in time. We prove that a removal of diffusion in one of the equations leads to a finite-time blow-up of some nonnegative spatially heterogeneous solutions.

math.AP↗

arXiv2015

The Escalator Boxcar Train method for a system of aged-structured equations

The Escalator Boxcar Train method (EBT) is a numerical method for structured population models of McKendrick-von Foerster type. Those models consist of a certain class of hyperbolic partial differential equations and describe time evolution of the distribution density of the structure variable describing a feature of individuals in the population. The method was introduced in late eighties and widely used in theoretical biology, but its convergence was proven only in recent years using the framework of measure-valued solutions. Till now the EBT method was developed only for scalar equation models. In this paper we derive a full numerical EBT scheme for age-structured, two-sex population model (Fredrickson-Hoppensteadt model), which consists of three coupled hyperbolic partial differential equations with nonlocal boundary conditions. It is the first step towards extending the EBT method to systems of structured population equations.

math.AP↗

arXiv2014

Clonal selection and therapy resistance in acute leukemias: Mathematical modelling explains different proliferation patterns at diagnosis and relapse

Recent experimental evidence suggests that acute myeloid leukemias may originate from multiple clones of malignant cells. Nevertheless it is not known how the observed clones may differ with respect to cell properties such as proliferation and self-renewal. There are scarcely any data on how these cell properties change due to chemotherapy and relapse. We propose a new mathematical model to investigate the impact of cell properties on multi-clonal composition of leukemias. Model results imply that enhanced self-renewal may be a key mechanism in the clonal selection process. Simulations suggest that fast proliferating and highly self-renewing cells dominate at primary diagnosis while relapse following therapy-induced remission is triggered mostly by highly self-renewing but slowly proliferating cells. Comparison of simulation results to patient data demonstrates that the proposed model is consistent with clinically observed dynamics based on a clonal selection process.

q-bio.TO↗

arXiv2014

Effective interface conditions for the forced infiltration of a viscous fluid into a porous medium using homogenization

It is generally accepted that the effective velocity of a viscous flow over a porous bed satisfies the Beavers-Joseph slip law. To the contrary, in the case of a forced infiltration of a viscous fluid into a porous medium the interface law has been a subject of controversy. In this paper, we prove rigorously that the effective interface conditions are: (i) the continuity of the normal effective velocities; (ii) zero Darcy's pressure and (iii) a given slip velocity. The effective tangential slip velocity is calculated from the boundary layer and depends only on the pore geometry. In the next order of approximation, we derive a pressure slip law. An independent confirmation of the analytical results using direct numerical simulation of the flow at the microscopic level is given, as well.

math.AP↗

arXiv2013

Pattern formation in a diffusion-ODE model with hysteresis

Coupling diffusion process of signaling molecules with nonlinear interactions of intracellular processes and cellular growth/transformation leads to a system of reaction-diffusion equations coupled with ordinary differential equations (diffusion-ODE models), which differ from the usual reaction-diffusion systems. One of the mechanisms of pattern formation in such systems is based on the existence of multiple steady states and hysteresis in the ODE subsystem. Diffusion tries to average different states and is the cause of spatio-temporal patterns. In this paper we provide a systematic description of stationary solutions of such systems, having the form of transition or boundary layers. The solutions are discontinuous in the case of non-diffusing variables whose quasi-stationary dynamics exhibit hysteresis. The considered model is motivated by biological applications and elucidates a possible mechanism of formation of patterns with sharp transitions.

math.AP↗

arXiv2013

Efficient algorithms computing distances between Radon measures on R

In this paper numerical methods of computing distances between two Radon measures on R are discussed. Efficient algorithms for Wasserstein-type metrics are provided. In particular, we propose a novel algorithm to compute the flat metric (bounded Lipschitz distance) with a computational cost O(nlogn). The flat distance has recently proven to be adequate for the Escalator Boxcar Train (EBT) method for solving transport equations with growth terms. Therefore, finding efficient numerical algorithms to compute the flat distance between two measures is important for finding the residual error and validating empirical convergence of different methods.

math.NA↗

arXiv2013

Spike patterns in a reaction-diffusion-ode model with Turing instability

We explore a mechanism of pattern formation arising in processes described by a system of a single reaction-diffusion equation coupled with ordinary differential equations. Such systems of equations arise from the modeling of interactions between cellular processes and diffusing growth factors. We focused on the model of early carcinogenesis proposed by Marciniak-Czochra and Kimmel, which is an example of a wider class of pattern formation models with an autocatalytic non-diffusing component. We present a numerical study showing emergence of periodic and irregular spike patterns due to diffusion-driven instability. To control the accuracy of simulations, we develop a numerical code based on the finite element method and adaptive mesh. Simulations, supplemented by numerical analysis, indicate a novel pattern formation phenomenon based on the emergence of nonstationary structures tending asymptotically to the sum of Dirac deltas.

math.AP↗

arXiv2013

A nonlinear effective slip interface law for transport phenomena between a fracture flow and a porous medium

We present modeling of an incompressible viscous flow through a fracture adjacent to a porous medium. We consider a fast stationary flow, predominantly tangential to the porous medium. Slow flow in such setting can be described by the Beavers-Joseph-Saffman slip. For fast flows, a nonlinear filtration law in the porous medium and a non- linear interface law are expected. In this paper we rigorously derive a quadratic effective slip interface law which holds for a range of Reynolds numbers and fracture widths. The porous medium flow is described by the Darcys law. The result shows that the interface slip law can be nonlinear, independently of the regime for the bulk flow. Since most of the interface and boundary slip laws are obtained via upscaling of complex systems, the result indicates that studying the inviscid limits for the Navier-Stokes equations with linear slip law at the boundary should be rethought.

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arXiv2013

Pressure jump interface law for the Stokes-Darcy coupling: Confirmation by direct numerical simulations

It is generally accepted that the effective velocity of a viscous flow over a porous bed satisfies the Beavers-Joseph slip law. To the contrary, interface law for the effective stress has been a subject of controversy. Recently, a pressure jump interface law has been rigorously derived by Marciniak-Czochra and Mikelić. In this paper, we provide a confirmation of the analytical result using direct numerical simulation of the flow at the microscopic level.

math.NA↗

arXiv2012

A Rigorous Derivation of the Equations for the Clamped Biot-Kirchhoff-Love Poroelastic plate

In this paper we investigate the limit behavior of the solution to quasi-static Biot's equations in thin poroelastic plates as the thickness tends to zero. We choose Terzaghi's time corresponding to the plate thickness and obtain the strong convergence of the three-dimensional solid displacement, fluid pressure and total poroelastic stress to the solution of the new class of plate equations. In the new equations the in-plane stretching is described by the 2D Navier's linear elasticity equations, with elastic moduli depending on Gassmann's and Biot's coefficients. The bending equation is coupled with the pressure equation and it contains the bending moment due to the variation in pore pressure across the plate thickness. The pressure equation is parabolic only in the vertical direction. As additional terms it contains the time derivative of the in-plane Laplacean of the vertical deflection of the plate and of the the elastic in-plane compression term.

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