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The spatial spread of an epidemic is investigated in the case of a bistable dynamics, where the effective transmission rate depends on the fraction of infected and the state of no epidemic is linearly stable. The front propagation phenomenon is investigated both numerically and theoretically, by an analysis in a four-dimensional phase plane. A good agreement between numerical and theoretical results has been found both for the front profiles and for the speed of invasion. We discovered a novel phenomenon of front stoppage: In some regime of parameters, the front solution ceases to exist, and the propagating pulse of infection decays despite the initial outbreak.

We consider the spread of epidemic in a spatial metapopulation system consisting of weakly interacting patches. Each local patch is represented by a network with a certain node degree distribution and individuals can migrate between neighboring patches. Stochastic particle simulations of the SIR model show that after a short transient, the spatial spread of epidemic has a form of a propagating front. A theoretical analysis shows that the speed of front propagation depends on the effective diffusion coefficient and on the local proliferation rate similarly to fronts described by the Fisher-Kolmogorov equation. To determine the speed of front propagation, first, the early-time dynamics in a local patch is computed analytically by employing degree based approximation for the case of a constant disease duration. The resulting delay differential equation is solved for early times to obtain the local growth exponent. Next, the reaction diffusion equation is derived from the effective master equation and the effective diffusion coefficient and the overall proliferation rate are determined. Finally, the fourth order derivative in the reaction diffusion equation is taken into account to obtain the discrete correction to the front propagation speed. The analytical results are in a good agreement with the results of stochastic particle simulations.

Continuum models of epidemics do not take into account the underlying microscopic network structure of social connections. This drawback becomes extreme during quarantine when most people dramatically decrease their number of social interactions, while others (like cashiers in grocery stores) continue maintaining hundreds of contacts per day. We formulate a two-level model of quarantine. On a microscopic level, we model a single neighborhood assuming a star-network structure. On a mesoscopic level, the neighborhoods are placed on a two-dimensional lattice with nearest-neighbors interactions. The modeling results are compared with the COVID-19 data for several counties in Michigan (USA) and the phase diagram of parameters is identified.

The empirical velocity of a reaction-diffusion front, propagating into an unstable state, fluctuates because of the shot noises of the reactions and diffusion. Under certain conditions these fluctuations can be described as a diffusion process in the reference frame moving with the average velocity of the front. Here we address pushed fronts, where the front velocity in the deterministic limit is affected by higher-order reactions and is therefore larger than the linear spread velocity. For a subclass of these fronts-strongly pushed fronts-the effective diffusion constant D_{f}∼1/N of the front can be calculated, in the leading order, via a perturbation theory in 1/N≪1, where N≫1 is the typical number of particles in the transition region. This perturbation theory, however, overestimates the contribution of a few fast particles in the leading edge of the front. We suggest a more consistent calculation by introducing a spatial integration cutoff at a distance beyond which the average number of particles is of order 1. This leads to a nonperturbative correction to D_{f} which even becomes dominant close to the transition point between the strongly and weakly pushed fronts. At the transition point we obtain a logarithmic correction to the 1/N scaling of D_{f}. We also uncover another, and quite surprising, effect of the fast particles in the leading edge of the front. Because of these particles, the position fluctuations of the front can be described as a diffusion process only on very long time intervals with a duration Δt≫τ_{N}, where τ_{N} scales as N. At intermediate times the position fluctuations of the front are anomalously large and nondiffusive. Our extensive Monte Carlo simulations of a particular reacting lattice gas model support these conclusions.

The granular Leidenfrost state consists of a dense granular cluster levitating above a hot granular gas. The density of particles inside the cluster can be very high and even close to the density of crystalline packing. To describe this state theoretically, one needs to know the density dependence of constitutive relations (pressure, heat losses, thermal conductivity) at these very high densities. However, the accurate expression for the coefficient of thermal conductivity is lacking. In this work, the constitutive relations were measured at high densities in molecular dynamics simulations in three different settings: a uniform freely cooling dense granulate (to measure heat losses), a uniform ensemble of elastically colliding particles (to measure pressure), and a dense granular medium between two thermal walls under gravity (to measure thermal conductivity). Next, the hydrodynamic equations with the resulting expressions were solved to describe the levitating cluster state in various parameter regimes. Separate molecular dynamics simulations were performed to test the theoretical predictions and measure the density and temperature profiles of the granular Leidenfrost state, and a good agreement with theoretical results was observed.

The phenotypic axis of invasion and proliferation in malignant glioma cells is a well-documented phenomenon. Invasive glioma cells exhibit a decreased proliferation rate and a resistance to apoptosis, and invasive tumor cells dispersed in brain subsequently revert to proliferation and contribute to secondary tumor formation. One miRNA can affect dozens of mRNAs, and some miRNAs are potent oncogenes. Multiple miRNAs are implicated in glioma malignancy, and several of which have been identified to regulate tumor cell motility and division. Using rat 9 L gliosarcoma and human U87 glioblastoma cell lines, we investigated miRNAs associated with the switch between glioma cell invasion and proliferation. Using micro-dissection of 9 L glioma tumor xenografts in rat brain, we identified disparate expression of miR-9 between cells within the periphery of the primary tumor, and those comprising tumor islets within the invasive zone. Modifying miR-9 expression in in vitro assays, we report that miR-9 controls the axis of glioma cell invasion/proliferation, and that its contribution to invasion or proliferation is biphasic and dependent upon local tumor cell density. In addition, immunohistochemistry revealed elevated hypoxia inducible factor 1 alpha (HIF-1α) in the invasive zone as compared to the primary tumor periphery. We also found that hypoxia promotes miR-9 expression in glioma cells. Based upon these findings, we propose a hypothesis for the contribution of miR-9 to the dynamics glioma invasion and satellite tumor formation in brain adjacent to tumor.

The granular Leidenfrost effect [B. Meerson, et al., Phys. Rev. Lett. 91, 024301 (2003)PRLTAO0031-900710.1103/PhysRevLett.91.024301; P. Eshuis et al., Phys. Rev. Lett. 95, 258001 (2005)PRLTAO0031-900710.1103/PhysRevLett.95.258001] is the levitation of a mass of granular matter when a wall below the grains is vibrated, giving rise to a hot granular gas below the cluster. We find by simulation that for a range of parameters the system is bistable: the levitated cluster can occasionally break and give rise to two clusters and a hot granular gas above and below. We use techniques from the theory of rare events to compute the mean transition time for breaking to occur. This requires the introduction of a two-component reaction coordinate.

We consider clustering of particles in the lattice gas model above the critical point. We find the probability for large density fluctuations over scales much larger than the correlation length. This fundamental problem is of interest in various biological contexts such as quorum sensing and clustering of motile, adhesive, cancer cells. In the latter case, it may give a clue to the problem of growth of recurrent tumors. We develop a formalism for the analysis of this rare event employing a phenomenological master equation and measuring the transition rates in numerical simulations. The spontaneous clustering is treated in the framework of the eikonal approximation to the master equation.

We consider population dynamics on a network of patches, having the same local dynamics, with different population scales (carrying capacities). It is reasonable to assume that if the patches are coupled by very fast migration the whole system will look like an individual patch with a large effective carrying capacity. This is called a "well-mixed" system. We show that, in general, it is not true that the total population has the same dynamics as each local patch when the migration is fast. Different global dynamics can emerge, and usually must be figured out for each individual case. We give a general condition which must be satisfied for the total population to have the same dynamics as the constituent patches.

Many populations in nature are fragmented: they consist of local populations occupying separate patches. A local population is prone to extinction due to the shot noise of birth and death processes. A migrating population from another patch can dramatically delay the extinction. What is the optimal migration rate that minimizes the extinction risk of the whole population? Here, we answer this question for a connected network of model habitat patches with different carrying capacities.

We investigate the migration of glioma cells as a front propagation phenomenon both theoretically (by using both discrete lattice modeling and a continuum approach) and experimentally. For small effective strength of cell-cell adhesion q, the front velocity does not depend on q. When q exceeds a critical threshold, a fingeringlike front propagation is observed due to cluster formation in the invasive zone. We show that the experiments correspond to the transient regime, before the regime of front propagation is established. We performed an additional experiment on cell migration. A detailed comparison with experimental observations showed that the theory correctly predicts the maximal migration distance but underestimates the migration of the main mass of cells.

We investigate the long-standing puzzle of phase separation in a granular monolayer vibrated from below. Although this system is three dimensional, an interesting dynamics occurs mostly in the horizontal plane, perpendicular to the direction of vibration. Experiments [Olafsen and Urbach, Phys. Rev. Lett. 81, 4369 (1998)] demonstrated that for a high amplitude of vibration the system is in the gaslike phase, but when the amplitude becomes smaller than a certain threshold, a phase separation occurs: A solidlike dense condensate of particles forms in the center of the system, surrounded by particles in the gaslike phase. We explain theoretically the experimentally observed coexistence of dilute and dense phases, employing Navier-Stokes granular hydrodynamics. We show that the phase separation is associated with a negative compressibility of granular gas.

We consider emergent collective behavior of a multicellular biological system. Specifically, we investigate the role of hypoxia (lack of oxygen) in migration of brain tumor cells. We performed two series of cell migration experiments. In the first set of experiments, cell migration away from a tumor spheroid was investigated. The second set of experiments was performed in a typical wound-healing geometry: Cells were placed on a substrate, a scratch was made, and cell migration into the gap was investigated. Experiments show a surprising result: Cells under normal and hypoxic conditions have migrated the same distance in the "spheroid" experiment, while in the "scratch" experiment cells under normal conditions migrated much faster than under hypoxic conditions. To explain this paradox, we formulate a discrete stochastic model for cell dynamics. The theoretical model explains our experimental observations and suggests that hypoxia decreases both the motility of cells and the strength of cell-cell adhesion. The theoretical predictions were further verified in independent experiments.

Thermal wall is a convenient idealization of a rapidly vibrating plate used for vibrofluidization of granular materials. The objective of this work is to incorporate the Knudsen temperature jump at thermal wall in the Navier-Stokes hydrodynamic modeling of dilute granular gases of monodisperse particles that collide nearly elastically. The Knudsen temperature jump manifests itself as an additional term, proportional to the temperature gradient, in the boundary condition for the temperature. Up to a numerical prefactor O(1) , this term is known from kinetic theory of elastic gases. We determine the previously unknown numerical prefactor by measuring, in a series of molecular dynamics (MD) simulations, steady-state temperature profiles of a gas of elastically colliding hard disks, confined between two thermal walls kept at different temperatures, and comparing the results with the predictions of a hydrodynamic calculation employing the modified boundary condition. The modified boundary condition is then applied, without any adjustable parameters, to a hydrodynamic calculation of the temperature profile of a gas of inelastic hard disks driven by a thermal wall. We find the hydrodynamic prediction to be in very good agreement with MD simulations of the same system. The results of this work pave the way to a more accurate hydrodynamic modeling of driven granular gases.

Recently we considered a stochastic discrete model which describes fronts of cells invading a wound [E. Khain, L. M. Sander, and C. M. Schneider-Mizell, J. Stat. Phys. 128, 209 (2007)]. In the model cells can move, proliferate, and experience cell-cell adhesion. In this work we focus on a continuum description of this phenomenon by means of a generalized Cahn-Hilliard equation (GCH) with a proliferation term. As in the discrete model, there are two interesting regimes. For subcritical adhesion, there are propagating "pulled" fronts, similar to those of the Fisher-Kolmogorov equation. The problem of front velocity selection is examined, and our theoretical predictions are in the good agreement with a numerical solution of the GCH equation. For supercritical adhesion, there is a nontrivial transient behavior, where density profile exhibits a secondary peak. To analyze this regime, we investigated relaxation dynamics for the Cahn-Hilliard equation without proliferation. We found that the relaxation process exhibits self-similar behavior. The results of continuum and discrete models are in good agreement with each other for the different regimes we analyzed.

We consider dense rapid shear flow of inelastically colliding hard disks. Navier-Stokes granular hydrodynamics is applied accounting for the recent finding that shear viscosity diverges at a lower density than the rest of the constitutive relations. New interpolation formulas for constitutive relations between dilute and dense cases are proposed and justified in molecular dynamics (MD) simulations. A linear stability analysis of the uniform shear flow is performed and the full phase diagram is presented. It is shown that when the inelasticity of particle collision becomes large enough, the uniform sheared flow gives way to a two-phase flow, where a dense "solidlike" striped cluster is surrounded by two fluid layers. The results of the analysis are verified in event-driven MD simulations, and a good agreement is observed.

We investigate shear-induced crystallization in a very dense flow of monodisperse inelastic hard spheres. We consider a steady plane Couette flow under constant pressure and neglect gravity. We assume that the granular density is greater than the melting point of the equilibrium phase diagram of elastic hard spheres. We employ a Navier-Stokes hydrodynamics with constitutive relations all of which (except the shear viscosity) diverge at the crystal-packing density, while the shear viscosity diverges at a smaller density. The phase diagram of the steady flow is described by three parameters: an effective Mach number, a scaled energy loss parameter, and an integer number m: the number of half-oscillations in a mechanical analogy that appears in this problem. In a steady shear flow the viscous heating is balanced by energy dissipation via inelastic collisions. This balance can have different forms, producing either a uniform shear flow or a variety of more complicated, nonlinear density, velocity, and temperature profiles. In particular, the model predicts a variety of multilayer two-phase steady shear flows with sharp interphase boundaries. Such a flow may include a few zero-shear (solidlike) layers, each of which moving as a whole, separated by fluidlike regions. As we are dealing with a hard sphere model, the granulate is fluidized within the "solid" layers: the granular temperature is nonzero there, and there is energy flow through the boundaries of the solid layers. A linear stability analysis of the uniform steady shear flow is performed, and a plausible bifurcation diagram of the system, for a fixed m, is suggested. The problem of selection of m remains open.

We study the in vitro dynamics of the malignant brain tumor glioblastoma multiforme. The growing tumor consists of a dense proliferating zone and an outer less dense invasive region. Experiments with different types of cells show qualitatively different behavior: one cell line invades in a spherically symmetric manner, but another gives rise to branches. We formulate a model for this sort of growth using two coupled reaction-diffusion equations for the cell and nutrient concentrations. When the ratio of the nutrient and cell diffusion coefficients exceeds some critical value, the plane propagating front becomes unstable with respect to transversal perturbations. The instability threshold and the full phase-plane diagram in the parameter space are determined. The results are in a qualitative agreement with experimental findings for the two types of cells.

Equations of granular hydrostatics are used to compute the phase diagram of the recently discovered van der Waals-like phase separation in a driven granular gas. The model two-dimensional system consists of smooth hard disks in a rectangular box, colliding inelastically with each other and driven by a "thermal" wall at zero gravity. The spinodal line and the critical point of the phase separation are determined. Close to the critical point, the spinodal and binodal (coexistence) lines are determined analytically. Effects of the finite size of the confining box in the direction parallel to the thermal wall are investigated. These include suppression of the phase separation by heat conduction in the lateral direction and a change from supercritical to subcritical bifurcation.

The Navier-Stokes granular hydrodynamics is employed for determining the threshold of thermal convection in an infinite horizontal layer of granular gas. The dependence of the convection threshold, in terms of the inelasticity of particle collisions, on the Froude and Knudsen numbers is found. A simple necessary condition for convection is formulated in terms of the Schwarzschild's criterion, well known in thermal convection of (compressible) classical fluids. The morphology of convection cells at the onset is determined. At large Froude numbers, the Froude number drops out of the problem. As the Froude number goes to zero, the convection instability turns into a recently discovered phase-separation instability.

Symmetry-breaking instability of a laterally uniform granular cluster (strip state) in a prototypical driven granular gas is investigated. The system consists of smooth hard disks in a two-dimensional box, colliding inelastically with each other and driven, at zero gravity, by a "thermal" wall. The limit of nearly elastic particle collisions is considered, and granular hydrodynamics with the Jenkins-Richman constitutive relations is employed. The hydrodynamic problem is completely described by two scaled parameters and the aspect ratio of the box. Marginal stability analysis predicts a spontaneous symmetry-breaking instability of the strip state, similar to that predicted recently for a different set of constitutive relations. If the system is big enough, the marginal stability curve becomes independent of the details of the boundary condition at the driving wall. In this regime, the density perturbation is exponentially localized at the elastic wall opposite the thermal wall. The short- and long-wavelength asymptotics of the marginal stability curves are obtained analytically in the dilute limit. The physics of the symmetry-breaking instability is discussed.

We investigate parametric autoresonance: a persisting phase locking that occurs when the driving frequency of a parametrically excited nonlinear oscillator slowly varies with time. In this regime, the resonant excitation is continuous and unarrested by the oscillator nonlinearity. The system has three characteristic time scales, the fastest one corresponding to the natural frequency of the oscillator. We perform averaging over the fastest time scale and analyze the reduced set of equations analytically and numerically. Analytical results are obtained by exploiting the scale separation between the two remaining time scales that enables one to use the adiabatic invariant of the perturbed nonlinear motion.