Biomedical subjects

Dmitri Volfson

Publications and source records attributed to Dmitri Volfson.

8 recordsLinked to original sources

PubMed2006

Thermal collapse of a granular gas under gravity.

Free cooling of a gas of inelastically colliding hard spheres represents a central paradigm of kinetic theory of granular gases. At zero gravity the temperature of a freely cooling homogeneous granular gas follows a power law in time. How does gravity, which brings inhomogeneity, affect the cooling? We combine molecular dynamics simulations, a numerical solution of hydrodynamic equations and an analytic theory to show that a granular gas cooling under gravity undergoes thermal collapse: it cools down to zero temperature and condenses on the bottom of the container in a finite time.

Journal Article↗

PubMed2005

Origins of extrinsic variability in eukaryotic gene expression.

Variable gene expression within a clonal population of cells has been implicated in a number of important processes including mutation and evolution, determination of cell fates and the development of genetic disease. Recent studies have demonstrated that a significant component of expression variability arises from extrinsic factors thought to influence multiple genes simultaneously, yet the biological origins of this extrinsic variability have received little attention. Here we combine computational modelling with fluorescence data generated from multiple promoter-gene inserts in Saccharomyces cerevisiae to identify two major sources of extrinsic variability. One unavoidable source arising from the coupling of gene expression with population dynamics leads to a ubiquitous lower limit for expression variability. A second source, which is modelled as originating from a common upstream transcription factor, exemplifies how regulatory networks can convert noise in upstream regulator expression into extrinsic noise at the output of a target gene. Our results highlight the importance of the interplay of gene regulatory networks with population heterogeneity for understanding the origins of cellular diversity.

Eukaryotic Cells↗

PubMed2005

Monitoring dynamics of single-cell gene expression over multiple cell cycles.

Recent progress in reconstructing gene regulatory networks has established a framework for a quantitative description of the dynamics of many important cellular processes. Such a description will require novel experimental techniques that enable the generation of time-series data for the governing regulatory proteins in a large number of individual living cells. Here, we utilize microfabrication to construct a Tesla microchemostat that permits single-cell fluorescence imaging of gene expression over many cellular generations. The device is used to capture and constrain asymmetrically dividing or motile cells within a trapping region and to deliver nutrients and regulate the cellular population within this region. We illustrate the operation of the microchemostat with Saccharomyces cerevisiae and explore the evolution of single-cell gene expression and cycle time as a function of generation. Our findings highlight the importance of novel assays for quantifying the dynamics of gene expression and cellular growth, and establish a methodology for exploring the effects of gene expression on long-term processes such as cellular aging.

Bacterial Proteins↗

PubMed2005

Delay-induced stochastic oscillations in gene regulation.

The small number of reactant molecules involved in gene regulation can lead to significant fluctuations in intracellular mRNA and protein concentrations, and there have been numerous recent studies devoted to the consequences of such noise at the regulatory level. Theoretical and computational work on stochastic gene expression has tended to focus on instantaneous transcriptional and translational events, whereas the role of realistic delay times in these stochastic processes has received little attention. Here, we explore the combined effects of time delay and intrinsic noise on gene regulation. Beginning with a set of biochemical reactions, some of which are delayed, we deduce a truncated master equation for the reactive system and derive an analytical expression for the correlation function and power spectrum. We develop a generalized Gillespie algorithm that accounts for the non-Markovian properties of random biochemical events with delay and compare our analytical findings with simulations. We show how time delay in gene expression can cause a system to be oscillatory even when its deterministic counterpart exhibits no oscillations. We demonstrate how such delay-induced instabilities can compromise the ability of a negative feedback loop to reduce the deleterious effects of noise. Given the prevalence of negative feedback in gene regulation, our findings may lead to new insights related to expression variability at the whole-genome scale.

Algorithms↗

PubMed2004

Anisotropy-driven dynamics in vibrated granular rods.

The dynamics of a set of rods bouncing on a vertically vibrated plate is investigated using experiments, simulations, and theoretical analysis. The experiments and simulations are performed within an annulus to impose periodic boundary conditions. Rods tilted with respect to the vertical are observed to spontaneously develop a horizontal velocity depending on the acceleration of the plate. For high plate acceleration, the rods are observed to always move in the direction of tilt. However, the rods are also observed to move opposite to direction of tilt for a small range of plate acceleration and rod tilt. A phase diagram of the observed motion is presented as a function of plate acceleration and the tilt of the rods which is varied by changing the number of rods inside the annulus. Next we introduce a molecular dynamics method to simulate the dynamics of the rods using the dimensions and dissipation parameters from the experiments. We reproduce the observed horizontal rod speeds as a function of rod tilt and plate acceleration in the simulations. By decreasing the friction between the rods and the base plate to zero in the simulation, we identify the friction during the collision as the crucial ingredient for occurrence of the horizontal motion. Guided by the data from the experiments and the simulations, we construct a mechanical model for the dynamics of the rods in the limit of thin rods. The starting point of the analysis is the collision of a single rod with an oscillating plate. Three friction regimes are identified: slide, slip-stick, and slip reversal. A formula is derived for the observed horizontal velocity as a function of tilt angle. Good agreement for the horizontal velocity as a function of rod tilt and plate acceleration is found between experiments, simulations and theory.

Journal Article↗

PubMed2004

Stick-slip dynamics of a granular layer under shear.

Stick-slip regime of shear granular flows is studied theoretically and numerically. Numerical experiments are carried out for a thin Couette cell using soft-particle molecular dynamics code in two dimensions. We apply order parameter theory of partially fluidized granular flows and find a good agreement with simulations and experiments by Nasuno et al.

Journal Article↗

PubMed2003

Partially fluidized shear granular flows: continuum theory and molecular dynamics simulations.

The continuum theory of partially fluidized shear granular flows is tested and calibrated using two-dimensional soft particle molecular dynamics simulations. The theory is based on the relaxational dynamics of the order parameter that describes the transition between static and flowing regimes of granular material. We define the order parameter as a fraction of static contacts among all contacts between particles. We also propose and verify by direct simulations the constitutive relation based on the splitting of the shear stress tensor into a"fluid part" proportional to the strain rate tensor, and a remaining "solid part." The ratio of these two parts is a function of the order parameter. The rheology of the fluid component agrees well with the kinetic theory of granular fluids even in the dense regime. Based on the hysteretic bifurcation diagram for a thin shear granular layer obtained in simulations, we construct the "free energy" for the order parameter. The theory calibrated using numerical experiments with the thin granular layer is applied to the surface-driven stationary two-dimensional granular flows in a thick granular layer under gravity.

Journal Article↗

PubMed2003

Order parameter description of stationary partially fluidized shear granular flows.

We carry out a detailed comparison of soft-particle molecular dynamics simulations with the theory of partially fluidized shear granular flows. We verify by direct simulations a constitutive relation based on the separation of the shear stress tensor into a fluid part proportional to the strain rate tensor, and a remaining solid part. The ratio of these two components is determined by the order parameter. Based on results of the simulations we construct the "free energy" function for the order parameter. We also present the simulations of the stationary deep 2D granular flows driven by an upper wall and compare it with the continuum theory.

Journal Article↗