We consider a generalized version of Hughes' macroscopic model for crowd motion in the one-dimensional case. It consists in a scalar conservation law accounting for the conservation of the number of pedestrians, coupled with an eikonal equation giving the direction of the flux depending on pedestrian density. As a result of this non-trivial coupling, we have to deal with a conservation law with space-time discontinuous flux, whose discontinuity depends non-locally on the density itself. We propose a definition of entropy weak solution, which allows us to recover a maximum principle. Moreover, we study the structure of the solutions to Riemann-type problems and we construct them explicitly for small times, depending on the choice of the running cost in the eikonal equation. In particular, aiming at the optimization of the evacuation time, we propose a strategy that is optimal in the case of high densities. All results are illustrated by numerical simulations.

Abstract. In this work we study the inflammatory process resulting in the development of atherosclerosis. We develop a one-and two-dimensional models based on reaction-diffusion systems to describe the set up of a chronic inflammatory response in the intima of an artery vessel wall. The concentration of the oxidized low density lipoproteins (ox-LDL) in the intima is the critical parameter of the model. Low ox-LDL concentrations do not lead to a chronic inflammatory reaction. Intermediate ox-LDL concentrations correspond to a bistable system and can lead to a travelling wave propagation corresponding to a chronic inflammatory reaction. In this case the disease development depends on the initial condition. If the concentration of monocytes in the intima is sufficiently high, which can be caused by an inflammation related to other factors, then the development of atherosclerosis can start. Otherwise, the system returns to the stable disease free equilibrium. High ox-LDL concentrations correspond to a monostable system and even a small perturbation of the non inflammatory case leads to a travelling wave propagation which corresponds to a chronic inflammatory response.

Atherosclerosis is an inflammatory disease. The atherosclerosis process starts when low-density lipoproteins (LDLs) enter the intima of the blood vessel, where they are oxidized (ox-LDLs). The anti-inflammatory response triggers the recruitment of monocytes. Once in the intima, the monocytes are transformed into macrophages and foam cells, leading to the production of inflammatory cytokines and further recruitment of monocytes. This auto-amplified process leads to the formation of an atherosclerotic plaque and, possibly, to its rupture. In this paper we develop two mathematical models based on reaction-diffusion equations in order to explain the inflammatory process. The first model is one-dimensional: it does not consider the intima's thickness and shows that low ox-LDL concentrations in the intima do not lead to a chronic inflammatory reaction. Intermediate ox-LDL concentrations correspond to a bistable system, which can lead to a travelling wave that can be initiated by certain conditions, such as infection or injury. High ox-LDL concentrations correspond to a monostable system, and even a small perturbation of the non-inflammatory case leads to travelling-wave propagation, which corresponds to a chronic inflammatory response. The second model we suggest is two-dimensional: it represents a reaction-diffusion system in a strip with nonlinear boundary conditions to describe the recruitment of monocytes as a function of the cytokines' concentration. We prove the existence of travelling waves and confirm our previous results, which show that atherosclerosis develops as a reaction-diffusion wave. The results of the two models are confirmed by numerical simulations. The latter show that the two-dimensional model converges to the one-dimensional one if the thickness of the intima tends to zero.

Atherosclerosis begins as an inflammation in blood vessel walls (intima).The inflammatory response of the organism leads to the recruitment of monocytes. Trapped in the intima, they differentiate into macrophages and foam cells leading to the production of inflammatory cytokines and further recruitment of white blood cells. This self-accelerating process, strongly influenced by low-density lipoproteins (cholesterol), results in a dramatic increase of the width of blood vessel walls, formation of an atherosclerotic plaque and, possibly, of its rupture. We suggest a 2D mathematical model of the initiation and development of atherosclerosis which takes into account the concentration of blood cells inside the intima and of pro-and antiinflammatory cytokines. The model represents a reaction-diffusion system in a strip with nonlinear boundary conditions which describe the recruitment of monocytes as a function of the concentration of inflammatory cytokines. We prove the existence of travelling waves described by this system and confirm our previous results which suggest that atherosclerosis develops as a reaction-diffusion wave. The theoretical results are confirmed by the results of numerical simulations.

The circadian clock and the cell cycle are two tightly coupled oscillators. Recent analytical studies have shown counter-intuitive effects of circadian gating of the cell cycle on growth rates of proliferating cells which cannot be explained by a molecular model or a population model alone. In this work, we present a combined molecular-population model that studies how coupling the circadian clock to the cell cycle, through the protein WEE1, affects a proliferating cell population. We show that the cell cycle can entrain to the circadian clock with different rational period ratios and characterize multiple domains of entrainment. We show that coupling increases the growth rate for autonomous periods of the cell cycle around 24 h and above 48 h. We study the effect of mutation of circadian genes on the growth rate of cells and show that disruption of the circadian clock can lead to abnormal proliferation. Particularly, we show that Cry 1, Cry 2 mutations decrease the growth rate of cells, Per 2 mutation enhances it and Bmal 1 knockout increases it for autonomous periods of the cell cycle less than 21 h and decreases it elsewhere. Combining a molecular model to a population model offers new insight on the influence of the circadian clock on the growth of a cell population. This can help chronotherapy which takes benefits of physiological rhythms to improve anti-cancer efficacy and tolerance to drugs by administering treatments at a specific time of the day.

A stenosis is the narrowing of the artery, this narrowing is usually the result of the formation of an atheromatous plaque infiltrating gradually the artery wall, forming a bump in the ductus arteriosus. This arterial lesion falls within the general context of atherosclerotic arterial disease that can affect the carotid arteries, but also the arteries of the heart (coronary), arteries of the legs (PAD), the renal arteries... It can cause a stroke (hemiplegia, transient paralysis of a limb, speech disorder, sailing before the eye). In this paper we study the bloodplaque and blood-wall interactions using a fluid-structure interaction model. We first propose a 2D analytical study of the generalized Navier-Stokes equations to prove the existence of a weak solution for incompressible non-Newtonian fluids with non standard boundary conditions. Then, coupled, based on the results of the theoretical study approach is given. And to form a realistic model, with high accuracy, additional conditions due to fluid-structure coupling are proposed on the border undergoing inetraction. This coupled model includes (a) a fluid model, where blood is modeled as an incompressible non-Newtonian viscous fluid, (b) a solid model, where the arterial wall and atherosclerotic plaque will be treated as non linear hyperelastic solids, and (c) a fluidstructure interaction (FSI) model where interactions between the fluid (blood) and structures (the arterial wall and atheromatous plaque) are conducted by an Arbitrary Lagrangian Eulerian (ALE) method that allows accurate fluid-structure coupling.

In this paper, we consider the blood flow in a stenosed artery. We give an analytical study of the equations for a non-Newtonian fluid modeling the blood for which the behavior is obeying to Carreau's law. The case we treat is different than classic cases where the total pressure is in the natural boundary conditions. For this, we use the Faedo-Galerkin method to prove the existence of a weak solution for the fluid problem. Then we use a coupled approach between the fluid equations and the solid model of the arterial wall and the atheromatous plaque. A special attention is paid to the effects of the wall motion on the local fluid displacement, on the stresses, and on strains in the diseased arterial wall. These relevant quantities are analyzed extensively through numerical results.

The review presents the state of the art in the atherosclerosis modelling. It begins with the biological introduction describing the mechanisms of chronic inflammation of artery walls characterizing the development of atherosclerosis. In particular, we present in more detail models describing this chronic inflammation as a reaction-diffusion wave with regimes of propagation depending on the level of cholesterol (LDL) and models of rolling monocytes initializing the inflammation. Further development of this disease results in the formation of atherosclerotic plaque, vessel remodelling and possible plaque rupture due its interaction with blood flow. We review plaque-flow interaction models as well as reduced models (0D and 1D) of blood flow in atherosclerotic vasculature.