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Romain Yvinec

Publications and source records attributed to Romain Yvinec.

25 records · Page 2Linked to original sources

First passage times in homogeneous nucleation: dependence on the total number of particles

Motivated by nucleation and molecular aggregation in physical, chemical and biological settings, we present an extension to a thorough analysis of the stochastic self-assembly of a fixed number of identical particles in a finite volume. We study the statistic of times it requires for maximal clusters to be completed, starting from a pure-monomeric particle configuration. For finite volume, we extend previous analytical approaches to the case of arbitrary size-dependent aggregation and fragmentation kinetic rates. For larger volume, we develop a scaling framework to study the behavior of the first assembly time as a function of the total quantity of particles. We find that the mean time to first completion of a maximum-sized cluster may have surprisingly a very weak dependency on the total number of particles. We highlight how the higher statistic (variance, distribution) of the first passage time may still help to infer key parameters (such as the size of the maximum cluster) from data. And last but not least, we present a framework to quantify the formation of cluster of macroscopic size, whose formation is (asymptotically) very unlikely and occurs as a large deviation phenomenon from the mean-field limit. We argue that this framework is suitable to describe phase transition phenomena, as inherent infrequent stochastic processes, in contrast to classical nucleation theory.

q-bio.BM↗

Boundary value for a nonlinear transport equation emerging from a stochastic coagulation-fragmentation type model

We investigate the connection between two classical models of phase transition phenomena, the (discrete size) stochastic Becker-Döring, a continous time Markov chain model, and the (continuous size) deterministic Lifshitz-Slyozov model, a nonlinear transport partial differential equation. For general coefficients and initial data, we introduce a scaling parameter and prove that the empirical measure associated to the stochastic Becker-Döring system converges in law to the weak solution of the Lifshitz-Slyozov equation when the parameter goes to 0. Contrary to previous studies, we use a weak topology that includes the boundary of the state space (\ie\ the size $x=0$) allowing us to rigorously derive a boundary value for the Lifshitz-Slyozov model in the case of incoming characteristics. The condition reads $\lim_{x\to 0} (a(x)u(t)-b(x))f(t,x) = αu(t)^2$ where $f$ is the volume distribution function, solution of the Lifshitz-Slyozov equation, $a$ and $b$ the aggregation and fragmentation rates, $u$ the concentration of free particles and $α$ a nucleation constant emerging from the microscopic model. It is the main novelty of this work and it answers to a question that has been conjectured or suggested by both mathematicians and physicists. We emphasize that this boundary value depends on a particular scaling (as opposed to a modeling choice) and is the result of a separation of time scale and an averaging of fast (fluctuating) variables.

math.PR↗

Adiabatic reduction of a model of stochastic gene expression with jump Markov process

This paper considers adiabatic reduction in a model of stochastic gene expression with bursting transcription considered as a jump Markov process. In this model, the process of gene expression with auto-regulation is described by fast/slow dynamics. The production of mRNA is assumed to follow a compound Poisson process occurring at a rate depending on protein levels (the phenomena called bursting in molecular biology) and the production of protein is a linear function of mRNA numbers. When the dynamics of mRNA is assumed to be a fast process (due to faster mRNA degradation than that of protein) we prove that, with appropriate scalings in the burst rate, jump size or translational rate, the bursting phenomena can be transmitted to the slow variable. We show that, depending on the scaling, the reduced equation is either a stochastic differential equation with a jump Poisson process or a deterministic ordinary differential equation. These results are significant because adiabatic reduction techniques seem to have not been rigorously justified for a stochastic differential system containing a jump Markov process. We expect that the results can be generalized to adiabatic methods in more general stochastic hybrid systems.

math.PR↗

Adiabatic reduction of models of stochastic gene expression with bursting

This paper considers adiabatic reduction in both discrete and continuous models of stochastic gene expression. In gene expression models, the concept of bursting is a production of several molecules simultaneously and is generally represented as a compound Poisson process of random size. In a general two-dimensional birth and death discrete model, we prove that under specific assumptions and scaling (that are characteristics of the mRNA-protein system) an adiabatic reduction leads to a one-dimensional discrete-state space model with bursting production. The burst term appears through the reduction of the first variable. In a two-dimensional continuous model, we also prove that an adiabatic reduction can be performed in a stochastic slow/fast system. In this gene expression model, the production of mRNA (the fast variable) is assumed to be bursty and the production of protein (the slow variable) is linear as a function of mRNA. When the dynamics of mRNA is assumed to be faster than the protein dynamics (due to a mRNA degradation rate larger than for the protein) we prove that, with the appropriate scaling, the bursting phenomena can be transmitted to the slow variable. We show that the reduced equation is either a stochastic differential equation with a jump Markov process or a deterministic ordinary differential equation depending on the scaling that is appropriate. These results are significant because adiabatic reduction techniques seem to have not been applied to a stochastic differential system containing a jump Markov process. Last but not least, for our particular system, the adiabatic reduction allows us to understand what are the necessary conditions for the bursting production-like of protein to occur.

math.PR↗

First passage times in homogeneous nucleation and self-assembly

Motivated by nucleation and molecular aggregation in physical, chemical and biological settings, we present a thorough analysis of the general problem of stochastic self-assembly of a fixed number of identical particles in a finite volume. We derive the Backward Kolmogorov equation (BKE) for the cluster probability distribution. From the BKE we study the distribution of times it takes for a single maximal cluster to be completed, starting from any initial particle configuration. In the limits of slow and fast self-assembly, we develop analytical approaches to calculate the mean cluster formation time and to estimate the first assembly time distribution. We find, both analytically and numerically, that faster detachment can lead to a shorter mean time to first completion of a maximum-sized cluster. This unexpected effect arises from a redistribution of trajectory weights such that upon increasing the detachment rate, paths that take a shorter time to complete a cluster become more likely.

cond-mat.stat-mech↗

On the bursting of gene products

In this article we demonstrate that the so-called bursting production of molecular species during gene expression may be an artifact caused by low time resolution in experimental data collection and not an actual burst in production. We reach this conclusion through an analysis of a two-stage and binary model for gene expression, and demonstrate that in the limit when mRNA degradation is much faster than protein degradation they are equivalent. The negative binomial distribution is shown to be a limiting case of the binary model for fast "on to off" state transitions and high values of the ratio between protein synthesis and degradation rates. The gene products population increases by unity but multiple times in a time interval orders of magnitude smaller than protein half-life or the precision of the experimental apparatus employed in its detection. This rare-and-fast one-by-one protein synthesis has been interpreted as bursting.

math.PR↗

Molecular Distributions in Gene Regulatory Dynamics

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.

q-bio.MN↗