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Vuk Milisic

Publications and source records attributed to Vuk Milisic.

17 recordsLinked to original sources

A new comparison principle for discrete Volterra equations with an application to convex sweeping processes with infinite delays

Comparison principles for Volterra equations play a role analogous to maximum principles in PDEs: they provide positivity and stability information on the solution and allow one to control the output of bounded inputs. In the continuous setting, such results often rely on Laplace-transform or spectral methods (see Gripenberg, Londen, and Staffans, Volterra Integral and Functional Equations, 1990). However, these tools are not uniform in the discretization step $h$ hence fail in discrete or semi-discrete approximations. The present note introduces a resolvent-free argument yielding uniform $L^\infty(0,T)$-bounds for non-negative kernels. Compactness is a key ingredient in order to show existence of sweeping processes. While in the classical framework it is well established, adding an infinite distribution of delays complicates greatly the obtaining of such a result. In a first step we show a general energy decay estimate, which is then used to establish compactness. The argument is carried out in the discrete setting and that necessitates the introduction of the new comparison principle. In the classical sweeping process the previous position of the particle lies on the boundary of the constraint set, staying $O(h)$ close to the next projection point ($h$ is the discretization step). Our delay model projects the particle's averaged (by a unit measure kernel) past positions to the constraint set. Numerical simulations show that the projected point can lie at $O(1)$ distance from the convex set's boundary.

math.NA

Analysis of non-overlapping models with a weighted infinite delay

The framework of this article is cell motility modeling. Approximating cells as rigid spheres we take into account for both non-penetration and adhesions forces. Adhesions are modeled as a memory-like microscopic elastic forces. This leads to a delayed and constrained vector valued system of equations. We prove that the solution of these equations converges when {\epsilon}, the linkages turnover parameter, tends to zero to the a constrained model with friction. We discretize the problem and penalize the constraints to get an uncon?strained minimization problem. The well-posedness of the constrained problem is obtained by letting the penalty parameter to tend to zero. Energy estimates `a la De Giorgi are derived accounting for delay. Thanks to these estimates and the convexity of the constraints, we obtain compactness uniformly with respect to the discretisation step and {\epsilon}, this is the mathematically involved part of the article. Considering that the characteristic bonds lifetime goes to zero, we recover a friction model comparable to [Venel et al, ESAIM, 2011] but under more realistic assumptions on the external load, this part being also one of the challenging aspects of the work

math.AP

From transient elastic linkages to friction: a complete study of a penalized fourth order equation with delay

In this paper we consider a fourth order nonlinear parabolic delayed problem modelling a quasi-instantaneous turn-over of linkages in the context of cell-motility. The model depends on a small parameter $\epsilon$ which represents a typical time scale of the memory effect. We first prove global existence and uniqueness of solutions for $\epsilon$ fixed. This is achieved by combining suitable fixed-point and energy arguments and by uncovering a nonlocal in time, integral conserved quantity. After giving a complete classification of steady states in terms of elliptic functions, we next show that every solution converges to a steady state as $t \to \infty$. When $\epsilon \to 0$, we then establish convergence results on finite time intervals, showing that the solution tends in a suitable sense towards the solution of a parabolic problem without delay. Moreover, we establish the convergence of energies as $\epsilon \to 0$, which enables us to show that, for $\epsilon$ small enough, the $\epsilon$-dependent problem inherits part of the large time asymptotics of the limiting parabolic problem.

math.AP

Friction mediated by transient elastic linkages : asymptotic expansions and fat tails

Several results in previous works, strongly depend on the exponential tail of the linkages' distribution in our adhesive models. The purpose of this paper is to weaken this hypothesis and to allow more fat tails for large ages. From the biological point of view this means that we allow adhesions to be stronger, because linkages break less often. Moreover, in our previous articles, the asymptotic expansion of adhesion site's position and the corresponding error estimates also used some fast decay properties of the kernel, we show, when the kernel is a given function of age but constant in time, how to overcome this problem and construct asymptotic expansions in a systematic way at any order with respect to a small parameter $\epsilon$ representing the linkages' turnover.

math.AP

Asymptotic limits for a non-linear integro-differential equation modelling leukocytes' rolling on arterial walls

We consider a non-linear integro-differential model describing $z$, the position of the cell center on the real line presented in [Grec et al., J. Theo. Bio. 2018]. We introduce a new $\varepsilon$-scaling and we prove rigorously the asymptotics when $\varepsilon$ goes to zero. We show that this scaling characterizes the long-time behavior of the solutions of our problem in the cinematic regime (the velocity $\dot{z}$ tends to a limit). The convergence results are first given when $ψ$, the elastic energy associated to linkages, is convex and regular (the second order derivative of $ψ$ is bounded). In the absence of blood flow, when $ψ$, is quadratic, we compute the final position $z_\infty$ to which we prove that $z$ tends. We then build a rigorous mathematical framework for $ψ$ being convex but only Lipschitz. We extend convergence results with respect to $\varepsilon$ to this case when $ψ'$ admits a finite number of jumps. In the last part, we show that in the constant force case (see Model 3 in [Grec et al], $ψ$ is the absolute value), we solve explicitly the problem and recover the above asymptotic results.

math.AP

Reduction of a model for sodium exchanges in kidney nephron

This work deals with a mathematical analysis of sodium's transport in a tubular architecture of a kidney nephron. The nephron is modelled by two counter-current tubules. Ionic exchange occurs at the interface between the tubules and the epithelium and between the epithelium and the surrounding environment (interstitium). From a mathematical point of view, this model consists of a 5x5 semi-linear hyperbolic system. In the literature similar models neglect the epithelial layers. In this paper, we show rigorously that such models may be obtained by assuming that the permeabilities between lumen and epithelium are large. Indeed we show that when these grow, solutions of the 5x5 system converge in a certain way to solutions of a reduced 3x3 system where no epithelial layer is present. The problem is dened on a bounded spacial domain with initial and boundary data. Establishing BV compactness forces to introduce initial layers and to handle carefully the presence of lateral boundaries.

math.AP

From delayed minimization to the harmonic map heat equation

In the context of cell motility modelling and more particularly related to the Filament Based Lamelipodium Model [Manhart et al 2015 & 2017], this work deals with a rigorous mathematical proof of convergence between solutions of two problems : we start from a microscopic description of adhesions using a delayed and constrained vector valued equation with spacial diffusion and show the convergence towards the corresponding friction limit. The convergence is performed with respect to the bond characteristic lifetime $\varepsilon$ whose inverse is also proportional to the stifness of the bonds. The originality of this work is the extension of gradient flow techniques to our setting. Namely, the discrete finite difference term in the gradient flow energy is here replaced by a delay term which complicates greatly the mathematical analysis. Contrarily to the standard approach [Oelz SeMa 2011], compactness in time is not provided by the energy minimization process~: a series of past times are taken into account in our discrete energy. A supplementary equation on the time derivative is obtained requiring uniform estimate with respect to $\varepsilon$ of the Lagrange multiplier and provides compactness. Due to the non-linearity induced by the constraint, a specific stability estimate useful in our previous works, is not at hand here. Numerical simulations even showed that this estimate does not hold. Nevertheless, transposing our delay operator, we succeed in proving convergence under slightly weaker hypotheses. The result relies on a careful initial layer analysis, extending [Milisic Esaim Proc 2018] to the space dependent setting.

math.AP

Space dependent adhesion forces mediated by transient elastic linkages : new convergence and global existence results

In the first part of this work we show the convergence with respect to an asymptotic parameter ε of a delayed heat equation. It represents a mathematical extension of works considered previously by the authors [Milisic et al. 2011, Milisic et al. 2016]. Namely, this is the first result involving delay operators approximating protein linkages coupled with a spatial elliptic second order operator. For the sake of simplicity we choose the Laplace operator, although more general results could be derived. The main arguments are (i) new energy estimates and (ii) a stability result extended from the previous work to this more involved context. They allow to prove convergence of the delay operator to a friction term together with the Laplace operator in the same asymptotic regime considered without the space dependence in [Milisic et al, 2011]. In a second part we extend fixed-point results for the fully non-linear model introduced in [Milisic et al, 2016] and prove global existence in time. This shows that the blow-up scenario observed previously does not occur. Since the latter result was interpreted as a rupture of adhesion forces, we discuss the possibility of bond breaking both from the analytic and numerical point of view.

math.AP

Branching Random Walks on Binary Strings for Evolutionary Processes

In this article, we study branching random walks on graphs modeling division-mutation processes inspired by adaptive immunity. We apply the theory of expander graphs on mutation rules in evolutionary processes and obtain estimates for the cover times of the branching random walks. This analysis reveals an unexpected saturation phenomenon : increasing the mutation rate above a certain threshold does not enhance the speed of state-space exploration.

math.PR

Random walks on binary strings applied to the somatic hypermutation of B-cells

Within the germinal center in follicles, B-cells proliferate, mutate and differentiate, while being submitted to a powerful selection~: a micro-evolutionary mechanism at the heart of adaptive immunity. A new foreign pathogen is confronted to our immune system, the mutation mechanism that allows B-cells to adapt to it is called {\em somatic hypermutation}~: a programmed process of mutation affecting B-cell receptors at extremely high rate. By considering random walks on graphs, we introduce and analyze a simplified mathematical model in order to understand this extremely efficient learning process. The structure of the graph reflects the choice of the mutation rule. We focus on the impact of this choice on typical time-scales of the graphs' exploration. We derive explicit formulas to evaluate the expected hitting time to cover a given Hamming distance on the graphs under consideration. This characterizes the efficiency of these processes in driving antibody affinity maturation. In a further step we present a biologically more involved model and discuss its numerical outputs within our mathematical framework. We provide as well limitations and possible extensions of our approach.

math.PR

Tear-off versus global existence for a structured model of adhesion mediated by transient elastic linkages

We consider a microscopic model for friction mediated by transient elastic linkages introduced in [V. Milisic and D. Oelz. SIAM J. on Math. Anal. (2015). V. Milisic and D. Oelz. J. Math. Pures Appl. (2011)]. In the present study we prove existence and uniqueness of a solution to the coupled system under weaker hypotheses. The theory we present covers the case where the off-rate of linkages is unbounded but increasing at most linearly with respect to the mechanical load. The time of existence is typically bounded and corresponds to tear-off where the moving binding site does not have any bonds with the substrate. However, under additional assumptions on the external force we prove global in time existence of a solution that consequently stays attached to the substrate.

math.AP

Mathematical modeling of lymphocytes selection in the germinal center

Lymphocyte selection is a fundamental operation of adaptive immunity. In order to produce B-lymphocytes with a desired antigenic profile, a process of mutation-selection occurs in the germinal center, which is part of the lymph nodes. We introduce in this article a simplified mathematical model of this process, taking into account the main mechanisms of division, mutation and selection. This model is written as a non-linear, non-local, inhomogeneous second order partial differential equation, for which we develop a mathematical analysis in the case of piecewise-constant coefficients. We assess, mathematically and numerically, the performance of the biological function by evaluating the duration of this production process as a function of several parameters such as the mutation rate or the selection profile, in various asymptotic regimes.

math.AP

Weighted Sobolev spaces for the Laplace equation in periodic infinite strips

This paper establishes isomorphisms for the Laplace operator in weighted Sobolev spaces (WSS). These spaces are similar to standard Sobolev spaces, but they are endowed with weights prescribing functions growth or decay at infinity. Although well established in the whole space, these weighted results do not apply in the specific hypothesis of periodicity. This kind of problem appears when studying singularly perturbed domains (roughness, sieves, porous media, etc). When zooming on a single perturbation pattern, one often ends with a periodic problem set on an infinite strip. We present a unified framework that enables a systematic treatment of such problems. We provide existence and uniqueness of solutions in our WSS. This gives a refined description of solutions behavior at infinity which is of importance in the mutli-scale context. These isomorphism results hold for any weight exponent and any regularity index. We then identify these solutions with the convolution of a Green function (specific to periodical infinite strips) and the given data. This identification is valid again for any weight and any regularity index modulo some harmonic polynomials.

math.AP

Blood-Flow Modelling Along and Trough a Braided Multi-Layer Metallic Stent

In this work we study the hemodynamics in a stented artery connected either to a collateral artery or to an aneurysmal sac. The blood flow is driven by the pressure drop. Our aim is to characterize the flow-rate and the pressure in the contiguous zone to the main artery: using boundary layer theory we construct a homogenized first order approximation with respect to epsilon, the size of the stent's wires. This provides an explicit expression of the velocity profile through and along the stent. The profile depends only on the input/output pressure data of the problem and some homogenized constant quantities: it is explicit. In the collateral artery this gives the flow-rate. In the case of the aneurysm, it shows that : (i) the zeroth order term of the pressure in the sac equals the averaged pressure along the stent in the main artery, (ii) the presence of the stent inverses the rotation of the vortex. Extending the tools set up in [Bonnetier et al, Adv. Math. Fluids, 2009, Milisic, Meth. Apl. Ann., 2009] we prove rigorously that our asymptotic approximation is first order accurate with respect to . We derive then new implicit interface conditions that our approximation formally satisfies, generalizing our analysis to other possible geometrical configurations. In the last part we provide numerical results that illustrate and validate the theoretical approach.

math.AP

A priori convergence estimates for a rough Poisson-Dirichlet problem with natural vertical boundary conditions

Stents are medical devices designed to modify blood flow in aneurysm sacs, in order to prevent their rupture. Some of them can be considered as a locally periodic rough boundary. In order to approximate blood flow in arteries and vessels of the cardio-vascular system containing stents, we use multi-scale techniques to construct boundary layers and wall laws. Simplifying the flow we turn to consider a 2-dimensional Poisson problem that conserves essential features related to the rough boundary. Then, we investigate convergence of boundary layer approximations and the corresponding wall laws in the case of Neumann type boundary conditions at the inlet and outlet parts of the domain. The difficulty comes from the fact that correctors, for the boundary layers near the rough surface, may introduce error terms on the other portions of the boundary. In order to correct these spurious oscillations, we introduce a vertical boundary layer. Trough a careful study of its behavior, we prove rigorously decay estimates. We then construct complete boundary layers that respect the macroscopic boundary conditions. We also derive error estimates in terms of the roughness size epsilon either for the full boundary layer approximation and for the corresponding averaged wall law.

math.AP

Very weak estimates for a rough Poisson-Dirichlet problem with natural vertical boundary conditions

This work is a continuation of [E. Bonnetier, D.Bresch, V. Milisic, submitted]; it deals with rough boundaries in the simplified context of a Poisson equation. We impose Dirichlet boundary conditions on the periodic microscopic perturbation of a flat edge on one side and natural homogeneous Neumann boundary conditions are applied on the inlet/outlet of the domain. To prevent oscillations on the Neumann-like boundaries, we introduce a microscopic vertical corrector defined in a rough quarter-plane. In [E. Bonnetier, D.Bresch, V. Milisic, submitted] we studied a priori estimates in this setting; here we fully develop very weak estimates a la Necas [J. Necas. Les méthodes directes en théorie des équations elliptiques] in the weighted Sobolev spaces on an unbounded domain. We obtain optimal estimates which improve those derived in [E. Bonnetier, D.Bresch, V. Milisic, submitted]. We validate these results numerically, proving first order results for boundary layer approximation including the vertical correctors and a little less for the averaged wall-law introduced in the literature [W. Jäger and A. Mikelic. J. Diff. Equa., N. Neus, M. Neus, A. Mikelic, Appl. Anal. 2006].

math.AP

High Order Multi-Scale Wall-Laws, Part I : The Periodic Case

In this work we present new wall-laws boundary conditions including microscopic oscillations. We consider a newtonian flow in domains with periodic rough boundaries that we simplify considering a Laplace operator with periodic inflow and outflow boundary conditions. Following the previous approaches, see [A. Mikelic, W. Jäger, J. Diff. Eqs, 170, 96-122, (2001) ] and [Y. Achdou, O. Pironneau, F. Valentin, J. Comput. Phys, 147, 1, 187-218, (1998)], we construct high order boundary layer approximations and rigorously justify their rates of convergence with respect to epsilon (the roughness' thickness). We establish mathematically a poor convergence rate for averaged second-order wall-laws as it was illustrated numerically for instance in [Y. Achdou, O. Pironneau, F. Valentin, J. Comput. Phys, 147, 1, 187-218, (1998)]. In comparison, we establish exponential error estimates in the case of explicit multi-scale ansatz. This motivates our study to derive implicit first order multi-scale wall-laws and to show that its rate of convergence is at least of order epsilon to the three halves. We provide a numerical assessment of the claims as well as a counter-example that evidences the impossibility of an averaged second order wall-law. Our paper may be seen as the first stone to derive efficient high order wall-laws boundary conditions.

math.AP