517 research outputs found

    Could You Read My Heart

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    https://digitalcommons.library.umaine.edu/mmb-vp/5388/thumbnail.jp

    Chemical master equation and Langevin regimes for a gene transcription model

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    Gene transcription models must take account of intrinsic stochasticity. The Chemical Master Equation framework is based on modelling assumptions that are highly appropriate for this context, and the Stochastic Simulation Algorithm (also known as Gillespie's algorithm) allows for practical simulations to be performed. However, for large networks and/or fast reactions, such computations can be prohibitatively expensive. The Chemical Langevin regime replaces the massive ordinary dierential equation system with a small stochastic dierential equation system that is more amenable to computation. Although the transition from Chemical Master Equation to Chemical Langevin Equation can be justied rigorously in the large system size limit, there is very little guidance available about how closely the two models match for a xed system. Here, we consider a transcription model from the recent literature and show that it is possible to compare rst and second moments in the two stochastic settings. To analyse the Chemical Master Equation we use some recent work of Gadgil, Lee and Othmer, and to analyse the Chemical Langevin Equation we use Ito's Lemma. We nd that there is a perfect match|both modelling regimes give the same means, variances and correlations for all components in the system. The model that we analyse involves 'unimolecular reactions', and we nish with some numerical simulations involving dimerization to show that the means and variances in the two regimes can also be close when more general 'bimolecular reactions' are involved

    It Makes A Lot Of Diff\u27rence When You\u27re With The Girl You Love

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    https://digitalcommons.library.umaine.edu/mmb-vp/1912/thumbnail.jp

    Diagonally Neighbour Transitive Codes and Frequency Permutation Arrays

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    Constant composition codes have been proposed as suitable coding schemes to solve the narrow band and impulse noise problems associated with powerline communication. In particular, a certain class of constant composition codes called frequency permutation arrays have been suggested as ideal, in some sense, for these purposes. In this paper we characterise a family of neighbour transitive codes in Hamming graphs in which frequency permutation arrays play a central rode. We also classify all the permutation codes generated by groups in this family

    Breathing dynamics in heteropolymer DNA

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    While the statistical mechanical description of DNA has a long tradition, renewed interest in DNA melting from a physics perspective is nourished by measurements of the fluctuation dynamics of local denaturation bubbles by single molecule spectroscopy. The dynamical opening of DNA bubbles (DNA breathing) is supposedly crucial for biological functioning during, for instance, transcription initiation and DNA's interaction with selectively single-stranded DNA binding proteins. Motivated by this, we consider the bubble breathing dynamics in a heteropolymer DNA based on a (2+1)-variable master equation and complementary stochastic Gillespie simulations, providing the bubble size and the position of the bubble along the sequence as a function of time. We utilize new experimental data that independently obtain stacking and hydrogen bonding contributions to DNA stability. We calculate the spectrum of relaxation times and the experimentally measurable autocorrelation function of a fluorophore-quencher tagged base-pair, and demonstrate good agreement with fluorescence correlation experiments. A significant dependence of opening probability and waiting time between bubble events on the local DNA sequence is revealed and quantified for a promoter sequence of the T7 phage. The strong dependence on sequence, temperature and salt concentration for the breathing dynamics of DNA found here points at a good potential for nanosensing applications by utilizing short fluorophore-quencher dressed DNA constructs.Comment: 11 pages, 8 figure

    Molecular Distributions in Gene Regulatory Dynamics

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    We show how one may analytically compute the stationary density of the distribution of molecular constituents in populations of cells in the presence of noise arising from either bursting transcription or translation, or noise in degradation rates arising from low numbers of molecules. We have compared our results with an analysis of the same model systems (either inducible or repressible operons) in the absence of any stochastic effects, and shown the correspondence between behaviour in the deterministic system and the stochastic analogs. We have identified key dimensionless parameters that control the appearance of one or two steady states in the deterministic case, or unimodal and bimodal densities in the stochastic systems, and detailed the analytic requirements for the occurrence of different behaviours. This approach provides, in some situations, an alternative to computationally intensive stochastic simulations. Our results indicate that, within the context of the simple models we have examined, bursting and degradation noise cannot be distinguished analytically when present alone.Comment: 14 pages, 12 figures. Conferences: "2010 Annual Meeting of The Society of Mathematical Biology", Rio de Janeiro (Brazil), 24-29/07/2010. "First International workshop on Differential and Integral Equations with Applications in Biology and Medicine", Aegean University, Karlovassi, Samos island (Greece), 6-10/09/201

    Markovian Dynamics on Complex Reaction Networks

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    Complex networks, comprised of individual elements that interact with each other through reaction channels, are ubiquitous across many scientific and engineering disciplines. Examples include biochemical, pharmacokinetic, epidemiological, ecological, social, neural, and multi-agent networks. A common approach to modeling such networks is by a master equation that governs the dynamic evolution of the joint probability mass function of the underling population process and naturally leads to Markovian dynamics for such process. Due however to the nonlinear nature of most reactions, the computation and analysis of the resulting stochastic population dynamics is a difficult task. This review article provides a coherent and comprehensive coverage of recently developed approaches and methods to tackle this problem. After reviewing a general framework for modeling Markovian reaction networks and giving specific examples, the authors present numerical and computational techniques capable of evaluating or approximating the solution of the master equation, discuss a recently developed approach for studying the stationary behavior of Markovian reaction networks using a potential energy landscape perspective, and provide an introduction to the emerging theory of thermodynamic analysis of such networks. Three representative problems of opinion formation, transcription regulation, and neural network dynamics are used as illustrative examples.Comment: 52 pages, 11 figures, for freely available MATLAB software, see http://www.cis.jhu.edu/~goutsias/CSS%20lab/software.htm

    Induction level determines signature of gene expression noise in cellular systems

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    Noise in gene expression, either due to inherent stochasticity or to varying inter- and intracellular environment, can generate significant cell-to-cell variability of protein levels in clonal populations. We present a theoretical framework, based on stochastic processes, to quantify the different sources of gene expression noise taking cell division explicitly into account. Analytical, time-dependent solutions for the noise contributions arising from the major steps involved in protein synthesis are derived. The analysis shows that the induction level of the activator or transcription factor is crucial for the characteristic signature of the dominant source of gene expression noise and thus bridges the gap between seemingly contradictory experimental results. Furthermore, on the basis of experimentally measured cell distributions, our simulations suggest that transcription factor binding and promoter activation can be modelled independently of each other with sufficient accuracy

    The Dynamics of Health and Return Migration

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    In the final article in a six-part PLoS Medicine; series on Migration & Health, Anita Davies and colleagues from the International Organization for Migration (IOM) discuss the specific health risks and policy needs associated with return migratio
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