Nonlocal stochastic-partial-differential-equation limits of spatially correlated noise-driven spin systems derived to sample a canonical distribution.

For a noisy spin system, we derive a nonlocal stochastic version of the overdamped Landau-Lipshitz equation designed to respect the underlying Hamiltonian structure and sample the canonical or Gibbs distribution while being driven by spatially correlated (colored) noise that regularizes the dynamics, making this Stochastic partial differential equation mathematically well-posed. We begin from a microscopic discrete-time model motivated by the Metropolis-Hastings algorithm for a finite number of spins with periodic boundary conditions whose values are distributed on the unit sphere. We thus propose a future state of the system by adding to each spin colored noise projected onto the sphere, and then accept this proposed state with probability given by the ratio of the canonical distribution at the proposed and current states.

Trajectory stratification of stochastic dynamics.

We present a general mathematical framework for trajectory stratification for simulating rare events. Trajectory stratification involves decomposing trajectories of the underlying process into fragments limited to restricted regions of state space (strata), computing averages over the distributions of the trajectory fragments within the strata with minimal communication between them, and combining those averages with appropriate weights to yield averages with respect to the original underlying process. Our framework reveals the full generality and flexibility of trajectory stratification, and it illuminates a common mathematical structure shared by existing algorithms for sampling rare events.

SCALING LIMITS OF A MODEL FOR SELECTION AT TWO SCALES.

The dynamics of a population undergoing selection is a central topic in evolutionary biology. This question is particularly intriguing in the case where selective forces act in opposing directions at two population scales. For example, a fast-replicating virus strain outcompetes slower-replicating strains at the within-host scale.

The impact of host immune status on the within-host and population dynamics of antigenic immune escape.

Antigenically evolving pathogens such as influenza viruses are difficult to control owing to their ability to evade host immunity by producing immune escape variants. Experimental studies have repeatedly demonstrated that viral immune escape variants emerge more often from immunized hosts than from naive hosts. This empirical relationship between host immune status and within-host immune escape is not fully understood theoretically, nor has its impact on antigenic evolution at the population level been evaluated.

Long-range allosteric interactions between the folate and methionine cycles stabilize DNA methylation reaction rate.

Several metabolites in the folate and methionine cycles influence the activities of distant enzymes involved in one-carbon metabolism. Many hypotheses have been advanced about the functional impact of these long-range interactions. Using both steady-state and fluctuation analyses of a mathematical model of methionine metabolism, we investigate the biochemical basis for several of these hypotheses.

Propagation of fluctuations in biochemical systems, I: linear SSC networks.

We investigate the propagation of random fluctuations through biochemical networks in which the number of molecules of each species is large enough so that the concentrations are well modeled by differential equations. We study the effect of network topology on the emergent properties of the reaction system by characterizing the behavior of variance as fluctuations propagate down chains and studying the effect of side chains and feedback loops. We also investigate the asymptotic behavior of the system as one reaction becomes fast relative to the others.