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Biomedical subjects

J Hasty

Publications and source records attributed to J Hasty.

8 recordsLinked to original sources
PubMed2006

Stochastically driven genetic circuits.

Transcriptional regulation in small genetic circuits exhibits large stochastic fluctuations. Recent experiments have shown that a significant fraction of these fluctuations is caused by extrinsic factors. In this paper we review several theoretical and computational approaches to modeling of small genetic circuits driven by extrinsic stochastic processes. We propose a simplified approach to this problem, which can be used in the case when extrinsic fluctuations dominate the stochastic dynamics of the circuit (as appears to be the case in eukaryots). This approach is applied to a model of a single nonregulated gene that is driven by a certain gating process that affects the rate of transcription, and to a simplified version of the galactose utilization circuit in yeast.

Animals↗
PubMed2004

Cellular growth and division in the Gillespie algorithm.

Recent experimental studies elucidating the importance of noise in gene regulation have ignited widespread interest in Gillespie's stochastic simulation technique for biochemical networks. We formulate modifications to the Gillespie algorithm which are necessary to correctly simulate chemical reactions with time-dependent reaction rates. We concentrate on time dependence of kinetic rates arising from the periodic process of growth and division of the cellular volume, and demonstrate that a careful re-derivation of the Gillespie algorithm is important when all stochastically simulated reactions have rates slower or comparable to the cellular growth rate. For an unregulated single-gene system, we illustrate our findings using recently proposed hybrid simulation techniques, and systematically compare our algorithm with analytic results obtained from the chemical master equation.

Algorithms↗
PubMed2001

Complex ligand-protein systems: a globally convergent iterative method for the n x m case.

When n types of univalent ligands are competing for the binding to m types of protein sites, the determination of the system composition at equilibrium reduces to the solving of a non-linear system of n equations in C = [0; 1](n). We present an iterative method to solve such a system. We show that the sequence presented here is always convergent, regardless of the initial value in C. We also prove that the limit of this sequence is the unique solution in C of the non-linear system of equations.

Algorithms↗
PubMed2001

Computational studies of gene regulatory networks: in numero molecular biology.

Remarkable progress in genomic research is leading to a complete map of the building blocks of biology. Knowledge of this map is, in turn, setting the stage for a fundamental description of cellular function at the DNA level. Such a description will entail an understanding of gene regulation, in which proteins often regulate their own production or that of other proteins in a complex web of interactions. The implications of the underlying logic of genetic networks are difficult to deduce through experimental techniques alone, and successful approaches will probably involve the union of new experiments and computational modelling techniques.

Animals↗
PubMed2001

Wavelets of excitability in sensory neurons.

We have investigated variations in the excitability of mammalian cutaneous mechanoreceptor neurons. We focused on the phase dynamics of an action potential relative to a periodic stimulus, showing that the excitability of these sensory neurons has interesting nonstationary oscillations. Using a wavelet analysis, these oscillations were characterized through the depiction of their period as a function of time. It was determined that the induced oscillations are weakly dependent on the stimulus frequency, and that lower temperatures significantly reduce the frequency of the phase response. Our results reveal novel excitability properties in sensory neurons, and, more generally, could prove significant in the deduction of mechanistic attributes underlying the nonstationary excitability in neuronal systems. Since peripheral neurons feed information to the CNS, variable responses observed in higher regions may be generated in part at the site of sensory detection.

Animals↗
PubMed2000

Noise-based switches and amplifiers for gene expression.

The regulation of cellular function is often controlled at the level of gene transcription. Such genetic regulation usually consists of interacting networks, whereby gene products from a single network can act to control their own expression or the production of protein in another network. Engineered control of cellular function through the design and manipulation of such networks lies within the constraints of current technology. Here we develop a model describing the regulation of gene expression and elucidate the effects of noise on the formulation. We consider a single network derived from bacteriophage lambda and construct a two-parameter deterministic model describing the temporal evolution of the concentration of lambda repressor protein. Bistability in the steady-state protein concentration arises naturally, and we show how the bistable regime is enhanced with the addition of the first operator site in the promotor region. We then show how additive and multiplicative external noise can be used to regulate expression. In the additive case, we demonstrate the utility of such control through the construction of a protein switch, whereby protein production is turned "on" and "off" by using short noise pulses. In the multiplicative case, we show that small deviations in the transcription rate can lead to large fluctuations in the production of protein, and we describe how these fluctuations can be used to amplify protein production significantly. These results suggest that an external noise source could be used as a switch and/or amplifier for gene expression. Such a development could have important implications for gene therapy.

DNA-Binding Proteins↗
PubMed1990

Sequential gradient pneumatic compression enhances venous ulcer healing: a randomized trial.

The treatment of venous ulcers has remained largely unchanged for centuries. The application of properly applied graduated compression bandages, the use of graduated compression stockings, and surgery have been shown to achieve healing. However, some ulcers persist despite appropriate management. A randomized study was undertaken to compare two regimens of treatment for such patients. Both regimens included ulcer debridement, cleaning, nonadherent dressing, and graduated compression stockings. In one regimen, sequential gradient intermittent pneumatic compression was applied for 4 hours each day. Only one of 24 patients in the control group had complete healing of all ulcers compared with 10 of 21 patients healed in the intermittent pneumatic compression group. The median rate of ulcer healing in the control group was 2.1% area per week compared to 19.8% area per week in the intermittent pneumatic compression group. The results indicate that sequential gradient intermittent pneumatic compression is beneficial in the treatment of venous ulcers.

Adult↗