Most human tumors result from the accumulation of multiple genetic and epigenetic alterations in a single cell. Mutations that confer a fitness advantage to the cell are known as driver mutations and are causally related to tumorigenesis. Other mutat
ions, however, do not change the phenotype of the cell or even decrease cellular fitness. While much experimental effort is being devoted to the identification of the different functional effects of individual mutations, mathematical modeling of tumor progression generally considers constant fitness increments as mutations are accumulated. In this paper we study a mathematical model of tumor progression with random fitness increments. We analyze a multi-type branching process in which cells accumulate mutations whose fitness effects are chosen from a distribution. We determine the effect of the fitness distribution on the growth kinetics of the tumor. This work contributes to a quantitative understanding of the accumulation of mutations leading to cancer phenotypes.
In this work, we examine spectral properties of Markov transition operators corresponding to Gaussian perturbations of discrete time dynamical systems on the circle. We develop a method for calculating asymptotic expressions for eigenvalues (in the z
ero noise limit) and show that changes to the number or period of stable orbits for the deterministic system correspond to changes in the number of limiting modulus 1 eigenvalues of the transition operator for the perturbed process. We call this phenomenon a $lambda$-bifurcation. Asymptotic expressions for the corresponding eigenfunctions and eigenmeasures are also derived and are related to Hermite functions.
Integrate and fire oscillators are widely used to model the generation of action potentials in neurons. In this paper, we discuss small noise asymptotic results for a class of stochastic integrate and fire oscillators (SIFs) in which the buildup of m
embrane potential in the neuron is governed by a Gaussian diffusion process. To analyze this model, we study the asymptotic behavior of the spectrum of the firing phase transition operator. We begin by proving stro
We study the adaptive dynamics of predator-prey systems modeled by a dynamical system in which the traits of predators and prey are allowed to evolve by small mutations. When only the prey are allowed to evolve, and the size of the mutational change
tends to 0, the system does not exhibit long term prey coexistence and the trait of the resident prey type converges to the solution of an ODE. When only the predators are allowed to evolve, coexistence of predators occurs. In this case, depending on the parameters being varied, we see (i) the number of coexisting predators remains tight and the differences in traits from a reference species converge in distribution to a limit, or (ii) the number of coexisting predators tends to infinity, and we calculate the asymptotic rate at which the traits of the least and most fit predators in the population increase. This last result is obtained by comparison with a branching random walk killed to the left of a linear boundary and a finite branching-selection particle system.
