Reaction Brownian Dynamics and the effect of spatial fluctuations on the gain of a push-pull network

Brownian Dynamics algorithms are widely used for simulating soft-matter and biochemical systems. In recent times, their application has been extended to the simulation of coarse-grained models of cellular networks in simple organisms. In these models, components move by diffusion, and can react with one another upon contact. However, when reactions are incorporated into a Brownian Dynamics algorithm, attention must be paid to avoid violations of the detailed-balance rule, and therefore introducing systematic errors in the simulation. We present a Brownian Dynamics algorithm for reaction-diffusion systems that rigorously obeys detailed balance for equilibrium reactions. By comparing the simulation results to exact analytical results for a bimolecular reaction, we show that the algorithm correctly reproduces both equilibrium and dynamical quantities. We apply our scheme to a ``push-pull'' network in which two antagonistic enzymes covalently modify a substrate. Our results highlight that the diffusive behaviour of the reacting species can reduce the gain of the response curve of this network.Comment: 25 pages, 7 figures, submitted to Journal of Chemical Physic

Eliminating fast reactions in stochastic simulations of biochemical networks: a bistable genetic switch

In many stochastic simulations of biochemical reaction networks, it is desirable to ``coarse-grain'' the reaction set, removing fast reactions while retaining the correct system dynamics. Various coarse-graining methods have been proposed, but it remains unclear which methods are reliable and which reactions can safely be eliminated. We address these issues for a model gene regulatory network that is particularly sensitive to dynamical fluctuations: a bistable genetic switch. We remove protein-DNA and/or protein-protein association-dissociation reactions from the reaction set, using various coarse-graining strategies. We determine the effects on the steady-state probability distribution function and on the rate of fluctuation-driven switch flipping transitions. We find that protein-protein interactions may be safely eliminated from the reaction set, but protein-DNA interactions may not. We also find that it is important to use the chemical master equation rather than macroscopic rate equations to compute effective propensity functions for the coarse-grained reactions.Comment: 46 pages, 5 figure

Radial Squeezed States and Rydberg Wave Packets

We outline an analytical framework for the treatment of radial Rydberg wave packets produced by short laser pulses in the absence of external electric and magnetic fields. Wave packets of this type are localized in the radial coordinates and have p-state angular distributions. We argue that they can be described by a particular analytical class of squeezed states, called radial squeezed states. For hydrogenic Rydberg atoms, we discuss the time evolution of the corresponding hydrogenic radial squeezed states. They are found to undergo decoherence and collapse, followed by fractional and full revivals. We also present their uncertainty product and uncertainty ratio as functions of time. Our results show that hydrogenic radial squeezed states provide a suitable analytical description of hydrogenic Rydberg atoms excited by short-pulsed laser fields.Comment: published in Physical Review

The instability of Alexander-McTague crystals and its implication for nucleation

We show that the argument of Alexander and McTague, that the bcc crystalline structure is favored in those crystallization processes where the first order character is not too pronounced, is not correct. We find that any solution that satisfies the Alexander-McTague condition is not stable. We investigate the implication of this result for nucleation near the pseudo- spinodal in near-meanfield systems.Comment: 20 pages, 0 figures, submitted to Physical Review

Spinodal-assisted crystallization in polymer melts

Recent experiments in some polymer melts quenched below the melting temperature have reported spinodal kinetics in small-angle x-ray scattering before the emergence of a crystalline structure. To explain these observations we propose that the coupling between density and chain conformation induces a liquid-liquid binodal within the equilibrium liquid-crystalline solid coexistence region. A simple phenomenological theory is developed to illustrate this idea, and several experimentally testable consequences are discussed. Shear is shown to enhance the kinetic role of the hidden binodal

The low temperature interface between the gas and solid phases of hard spheres with a short-ranged attraction

At low temperature, spheres with a very short-ranged attraction exist as a close-packed solid coexisting with an infinitely dilute gas. We find that the ratio of the interfacial tension between these two phases to the thermal energy diverges as the range of the attraction goes to zero. The large tensions when the interparticle attractions are short-ranged may be why globular proteins only crystallise over a narrow range of conditions.Comment: 6 pages, no figures (v2 has change of notation to agree with that of Stell

Nonergodicity transitions in colloidal suspensions with attractive interactions

The colloidal gel and glass transitions are investigated using the idealized mode coupling theory (MCT) for model systems characterized by short-range attractive interactions. Results are presented for the adhesive hard sphere and hard core attractive Yukawa systems. According to MCT, the former system shows a critical glass transition concentration that increases significantly with introduction of a weak attraction. For the latter attractive Yukawa system, MCT predicts low temperature nonergodic states that extend to the critical and subcritical region. Several features of the MCT nonergodicity transition in this system agree qualitatively with experimental observations on the colloidal gel transition, suggesting that the gel transition is caused by a low temperature extension of the glass transition. The range of the attraction is shown to govern the way the glass transition line traverses the phase diagram relative to the critical point, analogous to findings for the fluid-solid freezing transition.Comment: 11 pages, 7 figures; to be published in Phys. Rev. E (1 May 1999

Short-term prognosis of breakthrough venous thromboembolism in anticoagulated patients

Background: Evidence for guideline recommendations for the treatment of venous thromboembolism (VTE) during anticoagulant therapy is scarce. We aimed to observe and to describe the management of VTE occurring during anticoagulant therapy. Methods: This prospective multi-center, observational study included patients with objectively confirmed VTE during anticoagulant therapy (breakthrough event), with a follow-up of 3 months, after the breakthrough event. Results: We registered 121 patients with a breakthrough event, with a mean age of 56 years (range, 19 to 90); 61 were male (50%). Fifty-eight patients (48%) had an active malignancy. At the time of the breakthrough event, 57 patients (47%) were treated with a vitamin K antagonist (VKA), 53 patients (44%) with low-molecular-weight heparin (LMWH) and 11 patients (9%) with direct oral anticoagulants, unfractionated heparin, or VKA plu

A possible mechanism for cold denaturation of proteins at high pressure

We study cold denaturation of proteins at high pressures. Using multicanonical Monte Carlo simulations of a model protein in a water bath, we investigate the effect of water density fluctuations on protein stability. We find that above the pressure where water freezes to the dense ice phase ($\approx2$ kbar), the mechanism for cold denaturation with decreasing temperature is the loss of local low-density water structure. We find our results in agreement with data of bovine pancreatic ribonuclease A.Comment: 4 pages for double column and single space. 3 figures Added references Changed conten