arXiv subjects

Benoît Perthame

Publications and source records attributed to Benoît Perthame.

69 records · Page 4Linked to original sources

arXiv2014

Direct competition results from strong competiton for limited resource

We study a model of competition for resource through a chemostat-type model where species consume the common resource that is constantly supplied. We assume that the species and resources are characterized by a continuous trait. As already proved, this model, although more complicated than the usual Lotka-Volterra direct competition model, describes competitive interactions leading to concentrated distributions of species in continuous trait space. Here we assume a very fast dynamics for the supply of the resource and a fast dynamics for death and uptake rates. In this regime we show that factors that are independent of the resource competition become as important as the competition efficiency and that the direct competition model is a good approximation of the chemostat. Assuming these two timescales allows us to establish a mathematically rigorous proof showing that our resource-competition model with continuous traits converges to a direct competition model. We also show that the two timescales assumption is required to mathematically justify the corresponding classic result on a model consisting of only finite number of species and resources (MacArthur, R. Theor. Popul. Biol. 1970:1, 1-11). This is performed through asymptotic analysis, introducing different scales for the resource renewal rate and the uptake rate. The mathematical difficulty relies in a possible initial layer for the resource dynamics. The chemostat model comes with a global convex Lyapunov functional. We show that the particular form of the competition kernel derived from the uptake kernel, satisfies a positivity property which is known to be necessary for the direct competition model to enjoy the related Lyapunov functional.

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arXiv2014

Traveling wave solution of the Hele-Shaw model of tumor growth with nutrient

Several mathematical models of tumor growth are now commonly used to explain medical observations and predict cancer evolution based on images. These models incorporate mechanical laws for tissue compression combined with rules for nutrients availability which can differ depending on the situation under consideration, in vivo or in vitro. Numerical solutions exhibit, as expected from medical observations, a proliferative rim and a necrotic core. However, their precise profiles are rather complex, both in one and two dimensions.

math.AP↗

arXiv2014

Derivation of a Hele-Shaw type system from a cell model with active motion

We formulate a Hele-Shaw type free boundary problem for a tumor growing under the combined effects of pressure forces, cell multiplication and active motion, the latter being the novelty of the present paper. This new ingredient is considered here as a standard diffusion process. The free boundary model is derived from a description at the cell level using the asymptotic of a stiff pressure limit. Compared to the case when active motion is neglected, the pressure satisfies the same complementarity Hele-Shaw type formula. However, the cell density is smoother (Lipschitz continuous), while there is a deep change in the free boundary velocity, which is no longer given by the gradient of the pressure, because some kind of 'mushy region' prepares the tumor invasion.

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arXiv2013

Effects of space structure and combination therapies on phenotypic heterogeneity and drug resistance in solid tumors

Histopathological evidence supports the idea that the emergence of phenotypic heterogeneity and resistance to cytotoxic drugs can be considered as a process of adaptation, or evolution, in tumor cell populations. In this framework, can we explain intra-tumor heterogeneity in terms of cell adaptation to local conditions? How do anti-cancer therapies affect the outcome of cell competition for nutrients within solid tumors? Can we overcome the emergence of resistance and favor the eradication of cancer cells by using combination therapies? Bearing these questions in mind, we develop a model describing cell dynamics inside a tumor spheroid under the effects of cytotoxic and cytostatic drugs. Cancer cells are assumed to be structured as a population by two real variables standing for space position and the expression level of a cytotoxic resistant phenotype. The model takes explicitly into account the dynamics of resources and anti-cancer drugs as well as their interactions with the cell population under treatment. We analyze the effects of space structure and combination therapies on phenotypic heterogeneity and chemotherapeutic resistance. Furthermore, we study the efficacy of combined therapy protocols based on constant infusion and/or bang-bang delivery of cytotoxic and cytostatic drugs.

q-bio.TO↗

arXiv2013

The Hele-Shaw asymptotics for mechanical models of tumor growth

Models of tumor growth, now commonly used, present several levels of complexity, both in terms of the biomedical ingredients and the mathematical description. The simplest ones contain competition for space using purely fluid mechanical concepts. Another possible ingredient is the supply of nutrients through vasculature. The models can describe the tissue either at the level of cell densities, or at the scale of the solid tumor, in this latter case by means of a free boundary problem. Our first goal here is to formulate a free boundary model of Hele-Shaw type, a variant including growth terms, starting from the description at the cell level and passing to a certain limit. A detailed mathematical analysis of this purely mechanical model is performed. Indeed, we are able to prove strong convergence in passing to the limit, with various uniform gradient estimates; we also prove uniqueness for the asymptotic Hele-Shaw type problem. The main tools are nonlinear regularizing effects for certain porous medium type equations, regularization techniques à la Steklov, and a Hilbert duality method for uniqueness. At variance with the classical Hele-Shaw problem, here the geometric motion governed by the pressure is not sufficient to completely describe the dynamics. A complete description requires the equation on the cell number density. Using this theory as a basis, we go on to consider the more complex model including nutrients. We obtain the equation for the limit of the coupled system; the method relies on some BV bounds and space/time a priori estimates. Here, new technical difficulties appear, and they reduce the generality of the results in terms of the initial data. Finally, we prove uniqueness for the system, a main mathematical difficulty.

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arXiv2012

Optimal Regularizing Effect for Scalar Conservation Laws

We investigate the regularity of bounded weak solutions of scalar conservation laws with uniformly convex flux in space dimension one, satisfying an entropy condition with entropy production term that is a signed Radon measure. The proof is based on the kinetic formulation of scalar conservation laws and on an interaction estimate in physical space.

math.AP↗

arXiv2012

Nonlinear stability of a Vlasov equation for magnetic plasmas

The mathematical description of laboratory fusion plasmas produced in Tokamaks is still challenging. Complete models for electrons and ions, as Vlasov-Maxwell systems, are computationally too expensive because they take into account all details and scales of magneto-hydrodynamics. In particular, for most of the relevant studies, the mass electron is negligible and the velocity of material waves is much smaller than the speed of light. Therefore it is useful to understand simplified models. Here we propose and study one of those which keeps both the complexity of the Vlasov equation for ions and the Hall effect in Maxwell's equation. Based on energy dissipation, a fundamental physical property, we show that the model is nonlinear stable and consequently prove existence.

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arXiv2011

Relaxation and self-sustained oscillations in the time elapsed neuron network model

The time elapsed model describes the firing activity of an homogeneous assembly of neurons thanks to the distribution of times elapsed since the last discharge. It gives a mathematical description of the probability density of neurons structured by this time. In an earlier work, based on generalized relative entropy methods, it is proved that for highly or weakly connected networks the model exhibits relaxation to the steady state and for moderately connected networks it is obtained numerical evidence of appearance of self-sustained periodic solutions. Here, we go further and, using the particular form of the model, we quantify the regime where relaxation to a stationary state occurs in terms of the network connectivity. To introduce our methodology, we first consider the case where the neurons are not connected and we give a new statement showing that total asynchronous firing of neurons appears asymptotically. In a second step, we consider the case with connections and give a low connectivity condition that still leads to asynchronous firing. Our low connectivity condition is somehow sharp because we can give an example, when this condition is not fulfilled, where synchronous rhythmic activity occurs. Indeed, we are able to build several explicit families of periodic solutions. Our construction is fully nonlinear and the resynchronization of the neural activity in the network does not follow from bifurcation analysis. It relies on an algebraically nonlinear boundary condition that occurs in the model.These analytic results are compared with numerical simulations under broader hypotheses and shown to be robust.

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arXiv2010

Analysis of Nonlinear Noisy Integrate\&Fire Neuron Models: blow-up and steady states

Nonlinear Noisy Leaky Integrate and Fire (NNLIF) models for neurons networks can be written as Fokker-Planck-Kolmogorov equations on the probability density of neurons, the main parameters in the model being the connectivity of the network and the noise. We analyse several aspects of the NNLIF model: the number of steady states, a priori estimates, blow-up issues and convergence toward equilibrium in the linear case. In particular, for excitatory networks, blow-up always occurs for initial data concentrated close to the firing potential. These results show how critical is the balance between noise and excitatory/inhibitory interactions to the connectivity parameter.

q-bio.NC↗

arXiv2009

Mathematical description of bacterial traveling pulses

The Keller-Segel system has been widely proposed as a model for bacterial waves driven by chemotactic processes. Current experiments on {\em E. coli} have shown precise structure of traveling pulses. We present here an alternative mathematical description of traveling pulses at a macroscopic scale. This modeling task is complemented with numerical simulations in accordance with the experimental observations. Our model is derived from an accurate kinetic description of the mesoscopic run-and-tumble process performed by bacteria. This model can account for recent experimental observations with {\em E. coli}. Qualitative agreements include the asymmetry of the pulse and transition in the collective behaviour (clustered motion versus dispersion). In addition we can capture quantitatively the main characteristics of the pulse such as the speed and the relative size of tails. This work opens several experimental and theoretical perspectives. Coefficients at the macroscopic level are derived from considerations at the cellular scale. For instance the stiffness of the signal integration process turns out to have a strong effect on collective motion. Furthermore the bottom-up scaling allows to perform preliminary mathematical analysis and write efficient numerical schemes. This model is intended as a predictive tool for the investigation of bacterial collective motion.

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arXiv2009

Stability Analysis of a Simplified Yet Complete Model for Chronic Myelegenous Leukemia

We analyze the asymptotic behavior of a partial differential equation (PDE) model for hematopoiesis. This PDE model is derived from the original agent-based model formulated by (Roeder et al., Nat. Med., 2006), and it describes the progression of blood cell development from the stem cell to the terminally differentiated state. To conduct our analysis, we start with the PDE model of (Kim et al, JTB, 2007), which coincides very well with the simulation results obtained by Roeder et al. We simplify the PDE model to make it amenable to analysis and justify our approximations using numerical simulations. An analysis of the simplified PDE model proves to exhibit very similar properties to those of the original agent-based model, even if for slightly different parameters. Hence, the simplified model is of value in understanding the dynamics of hematopoiesis and of chronic myelogenous leukemia, and it presents the advantage of having fewer parameters, which makes comparison with both experimental data and alternative models much easier.

math.AP↗

arXiv2009

Exponential decay for the growth-fragmentation/cell-division equation

We consider the linear growth-fragmentation equation arising in the modelling of cell division or polymerisation processes. For constant coefficients, we prove that the dynamics converges to the steady state with an exponential rate. The control on the initial data uses an elaborate $L^1$-norm that seems to be necessary. It also reflects the main idea of the proof which is to use an anti-derivative of the solution. The main technical difficulty is related to the entropy dissipation rate which is too weak to produce a Poincaré inequality.

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arXiv2008

Numerical Solution of an Inverse Problem in Size-Structured Population Dynamics

We consider a size-structured model for cell division and address the question of determining the division (birth) rate from the measured stable size distribution of the population. We propose a new regularization technique based on a filtering approach. We prove convergence of the algorithm and validate the theoretical results by implementing numerical simulations, based on classical techniques. We compare the results for direct and inverse problems, for the filtering method and for the quasi-reversibility method proposed in [Perthame-Zubelli].

math.NA↗

arXiv2008

Bimodality, prion aggregates infectivity and prediction of strain phenomenon

We consider a model for the polymerization (fragmentation) process involved in infectious prion self-replication and study both its dynamics and non-zero steady state. We address several issues. Firstly, we give conditions leading to size repartitions of PrPsc aggregates that exhibit bimodal distributions, as indicated by recent experimental studies of prion aggregates distribution. Secondly, we show stability results for this steady state for general coefficients where reduction to a system of differential equations is not possible. We use a duality method based on recent ideas developed for population models. These results underline the potential influence of the amyloid precursor production rate in promoting amyloidogenic diseases. Finally, we numerically investigate the influence of different parameters of the model on PrPsc accumulation kinetics, in the aim to study specific features of prion strains.

math.AP↗

arXiv2007

Global existence for a kinetic model of chemotaxis via dispersion and Strichartz estimates

We investigate further the existence of solutions to kinetic models of chemotaxis. These are nonlinear transport-scattering equations with a quadratic nonlinearity which have been used to describe the motion of bacteria since the 80's when experimental observations have shown they move by a series of 'run and tumble'. The existence of solutions has been obtained in several papers [Chalub et al. Monatsh. Math. 142, 123--141 (2004), Hwang et al. SIAM J. Math. Anal. 36, 1177--1199 (2005)] using direct and strong dispersive effects. Here, we use the weak dispersion estimates of [Castella et al. C. R. Acad. Sci. Paris 322, 535--540 (1996)] to prove global existence in various situations depending on the turning kernel. In the most difficult cases, where both the velocities before and after tumbling appear, with the known methods, only Strichartz estimates can give a result, with a smallness assumption.

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