Stochastic models for regulatory networks of the genetic toggle switch

Bistability arises within a wide range of biological systems from the A phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. in this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks.

Genetic effects on alcohol dependence risk: re-evaluating the importance of psychiatric and other heritable risk factors

Background. Genetic influences have been shown to play a major role in determining the risk of alcohol dependence (AD) in both women and men; however, little attention has been directed to identifying the major sources of genetic variation in AD risk. Method. Diagnostic telephone interview data from young adult Australian twin pairs born between 1964 and 1971 were analyzed. Cox regression models were fitted to interview data from a total of 2708 complete twin pairs (690 MZ female, 485 MZ male, 500 DZ female, 384 DZ male, and 649 DZ female/male pairs). Structural equation models were fitted to determine the extent of residual genetic and environmental influences on AD risk while controlling for effects of sociodemographic and psychiatric predictors on risk. Results. Risk of AD was increased in males, in Roman Catholics, in those reporting a history of major depression, social anxiety problems, and conduct disorder, or (in females only) a history of suicide attempt and childhood sexual abuse; but was decreased in those reporting Baptist, Methodist, or Orthodox religion, in those who reported weekly church attendance, and in university-educated males. After allowing for the effects of sociodemographic and psychiatric predictors, 47 % (95 % CI 28-55) of the residual variance in alcoholism risk was attributable to additive genetic effects, 0 % (95 % CI 0-14) to shared environmental factors, and 53 % (95 % CI 45-63) to non-shared environmental influences. Conclusions. Controlling for other risk factors, substantial residual heritability of AD was observed, suggesting that psychiatric and other risk factors play a minor role in the inheritance of AD.

A study of organizational citizenship behaviors in a retail setting

This study investigates the potential antecedents of organizational citizenship behaviors (OCBs) in a retail setting. Much remains unknown about the factors affecting OCBs in retail settings. Several characteristics of retail jobs, as compared with other organizational behavior contexts, suggest the need to examine antecedents of OCBs. Job attitudes (job satisfaction and organizational commitment) are proposed as direct predictors of OCBs. Leadership support, professional development, and empowerment are posited as indirect predictors of OCBs and direct predictors of job attitudes. The possible moderating impacts of employee demographics and job types on the modeled relationships are also examined. The research hypotheses are tested using data collected from 211 frontline employees who work in a retail setting. The employees have customer-contact roles in the upscale food and grocery retailer that participated in the study. The pattern of results is more complex than hypothesized. Job attitudes are related to OCBs but the mediating role of job attitudes is not supported. The relationships between leadership support, professional development, and empowerment, and OCBs and job attitudes differ systematically. Evidence of how employee demographics can alter the modeled relationships is also presented. The findings have significant implications for the theory and practice of managing frontline employees. Limitations of the study are discussed and a program of further research is sketched. (C) 2003 Elsevier Inc. All rights reserved.

Gauge Poisson representations for birth/death master equations

Poisson representation techniques provide a powerful method for mapping master equations for birth/death processes -- found in many fields of physics, chemistry and biology -- into more tractable stochastic differential equations. However, the usual expansion is not exact in the presence of boundary terms, which commonly occur when the differential equations are nonlinear. In this paper, a gauge Poisson technique is introduced that eliminates boundary terms, to give an exact representation as a weighted rate equation with stochastic terms. These methods provide novel techniques for calculating and understanding the effects of number correlations in systems that have a master equation description. As examples, correlations induced by strong mutations in genetics, and the astrophysical problem of molecule formation on microscopic grain surfaces are analyzed. Exact analytic results are obtained that can be compared with numerical simulations, demonstrating that stochastic gauge techniques can give exact results where standard Poisson expansions are not able to.

The effect of service evaluations on behavioral intentions and quality of life

Understanding the contribution of marketing to economic and social outcomes is fundamental to broadening the focus of marketing. The authors develop a comprehensive model that integrates the impact of service quality and service satisfaction on both economic and societal outcomes. The model is validated using two random samples involving intensive health services. The results indicate that service quality and service satisfaction significantly enhance quality of life and behavioral intentions, highlighting that customer service has social as well as economic outcomes. This is an important finding given the movement toward recognizing social and environmental outcomes, such as emphasized through triple bottom-line reporting. The findings have important implications for managing service processes, for improving the quality of life of customers, and for enhancing customers' behavioral intentions toward the organization.

Stochastic delay differential equations for genetic regulatory networks

Time delay is an important aspect in the modelling of genetic regulation due to slow biochemical reactions such as gene transcription and translation, and protein diffusion between the cytosol and nucleus. In this paper we introduce a general mathematical formalism via stochastic delay differential equations for describing time delays in genetic regulatory networks. Based on recent developments with the delay stochastic simulation algorithm, the delay chemical masterequation and the delay reaction rate equation are developed for describing biological reactions with time delay, which leads to stochastic delay differential equations derived from the Langevin approach. Two simple genetic regulatory networks are used to study the impact of' intrinsic noise on the system dynamics where there are delays. (c) 2006 Elsevier B.V. All rights reserved.

On the estimation and comparison of short-rate models using the generalised method of moments

Subsequent to the influential paper of [Chan, K.C., Karolyi, G.A., Longstaff, F.A., Sanders, A.B., 1992. An empirical comparison of alternative models of the short-term interest rate. Journal of Finance 47, 1209-1227], the generalised method of moments (GMM) has been a popular technique for estimation and inference relating to continuous-time models of the short-term interest rate. GMM has been widely employed to estimate model parameters and to assess the goodness-of-fit of competing short-rate specifications. The current paper conducts a series of simulation experiments to document the bias and precision of GMM estimates of short-rate parameters, as well as the size and power of [Hansen, L.P., 1982. Large sample properties of generalised method of moments estimators. Econometrica 50, 1029-1054], J-test of over-identifying restrictions. While the J-test appears to have appropriate size and good power in sample sizes commonly encountered in the short-rate literature, GMM estimates of the speed of mean reversion are shown to be severely biased. Consequently, it is dangerous to draw strong conclusions about the strength of mean reversion using GMM. In contrast, the parameter capturing the levels effect, which is important in differentiating between competing short-rate specifications, is estimated with little bias. (c) 2006 Elsevier B.V. All rights reserved.

Generalized Perk-Schultz models: solutions of the Yang-Baxter equation associated with quantized orthosymplectic superalgebras

The Perk-Schultz model may be expressed in terms of the solution of the Yang-Baxter equation associated with the fundamental representation of the untwisted affine extension of the general linear quantum superalgebra U-q (gl(m/n)], with a multiparametric coproduct action as given by Reshetikhin. Here, we present analogous explicit expressions for solutions of the Yang-Baxter equation associated with the fundamental representations of the twisted and untwisted affine extensions of the orthosymplectic quantum superalgebras U-q[osp(m/n)]. In this manner, we obtain generalizations of the Perk-Schultz model.