Krylov subspace approximations for the exponential Euler method: Error estimates and the harmonic Ritz approximant

We study Krylov subspace methods for approximating the matrix-function vector product φ(tA)b where φ(z) = [exp(z) - 1]/z. This product arises in the numerical integration of large stiff systems of differential equations by the Exponential Euler Method, where A is the Jacobian matrix of the system. Recently, this method has found application in the simulation of transport phenomena in porous media within mathematical models of wood drying and groundwater flow. We develop an a posteriori upper bound on the Krylov subspace approximation error and provide a new interpretation of a previously published error estimate. This leads to an alternative Krylov approximation to φ(tA)b, the so-called Harmonic Ritz approximant, which we find does not exhibit oscillatory behaviour of the residual error.

Generalized binomial Tau-leap method for biochemical kinetics incorporating both delay and intrinsic noise

The delay stochastic simulation algorithm (DSSA) by Barrio et al. [Plos Comput. Biol.2, 117–E (2006)] was developed to simulate delayed processes in cell biology in the presence of intrinsic noise, that is, when there are small-to-moderate numbers of certain key molecules present in a chemical reaction system. These delayed processes can faithfully represent complex interactions and mechanisms that imply a number of spatiotemporal processes often not explicitly modeled such as transcription and translation, basic in the modeling of cell signaling pathways. However, for systems with widely varying reaction rate constants or large numbers of molecules, the simulation time steps of both the stochastic simulation algorithm (SSA) and the DSSA can become very small causing considerable computational overheads. In order to overcome the limit of small step sizes, various τ-leap strategies have been suggested for improving computational performance of the SSA. In this paper, we present a binomial τ- DSSA method that extends the τ-leap idea to the delay setting and avoids drawing insufficient numbers of reactions, a common shortcoming of existing binomial τ-leap methods that becomes evident when dealing with complex chemical interactions. The resulting inaccuracies are most evident in the delayed case, even when considering reaction products as potential reactants within the same time step in which they are produced. Moreover, we extend the framework to account for multicellular systems with different degrees of intercellular communication. We apply these ideas to two important genetic regulatory models, namely, the hes1 gene, implicated as a molecular clock, and a Her1/Her 7 model for coupled oscillating cells.