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Mark Flegg

Publications and source records attributed to Mark Flegg.

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Reduction of a biochemical network mathematical model by means of approximating activators and inhibitors as perfect inverse relationships

Models of biochemical networks are usually presented as connected graphs where vertices indicate proteins and edges are drawn to indicate activation or inhibition relationships. These diagrams are useful for drawing qualitative conclusions from the identification of topological features, for example positive and negative feedback loops. These topological features are usually identified under the presumption that activation and inhibition are inverse relationships. The conclusions are often drawn without quantitative analysis, instead relying on rules of thumb. We investigate the extent to which a model needs to prescribe inhibition and activation as true inverses before models behave idiosyncratically; quantitatively dissimilar to networks with similar typologies formed by swapping inhibitors as the inverse of activators. The purpose of the study is to determine under what circumstances rudimentary qualitative assessment of network structure can provide reliable conclusions as to the quantitative behaviour of the network and how appropriate is it to treat activator and inhibitor relationships as opposite in nature.

math.DS

Multi-resolution dimer models in heat baths with short-range and long-range interactions

This work investigates multi-resolution methodologies for simulating dimer models. The solvent particles which make up the heat bath interact with the monomers of the dimer either through direct collisions (short-range) or through harmonic springs (long-range). Two types of multi-resolution methodologies are considered in detail: (a) describing parts of the solvent far away from the dimer by a coarser approach; (b) describing each monomer of the dimer by using a model with different level of resolution. These methodologies are then utilised to investigate the effect of a shared heat bath versus two uncoupled heat baths, one for each monomer. Furthermore the validity of the multi-resolution methods is discussed by comparison to dynamics of macroscopic Langevin equations.

physics.comp-ph

Adaptive two-regime method: application to front propagation

The Adaptive Two-Regime Method (ATRM) is developed for hybrid (multiscale) stochastic simulation of reaction-diffusion problems. It efficiently couples detailed Brownian dynamics simulations with coarser lattice-based models. The ATRM is a generalization of the previously developed Two-Regime Method [Flegg et al, Journal of the Royal Society Interface, 2012] to multiscale problems which require a dynamic selection of regions where detailed Brownian dynamics simulation is used. Typical applications include a front propagation or spatio-temporal oscillations. In this paper, the ATRM is used for an in-depth study of front propagation in a stochastic reaction-diffusion system which has its mean-field model given in terms of the Fisher equation [Fisher, Annals of Eugenics, 1937]. It exhibits a travelling reaction front which is sensitive to stochastic fluctuations at the leading edge of the wavefront. Previous studies into stochastic effects on the Fisher wave propagation speed have focused on lattice-based models, but there has been limited progress using off-lattice (Brownian dynamics) models, which suffer due to their high computational cost, particularly at the high molecular numbers that are necessary to approach the Fisher mean-field model. By modelling only the wavefront itself with the off-lattice model, it is shown that the ATRM leads to the same Fisher wave results as purely off-lattice models, but at a fraction of the computational cost. The error analysis of the ATRM is also presented for a morphogen gradient model.

physics.comp-ph