A new class of highly efficient exact stochastic simulation algorithms for chemical reaction networks

We introduce an alternative formulation of the exact stochastic simulation algorithm (SSA) for sampling trajectories of the chemical master equation for a well-stirred system of coupled chemical reactions. Our formulation is based on factored-out, partial reaction propensities. This novel exact SSA, called the partial propensity direct method (PDM), is highly efficient and has a computational cost that scales at most linearly with the number of chemical species, irrespective of the degree of coupling of the reaction network. In addition, we propose a sorting variant, SPDM, which is especially efficient for multiscale reaction networks.Comment: 23 pages, 3 figures, 4 tables; accepted by J. Chem. Phy

Finding unique PCR products on distributed databases

Thanks to the development of genetic engineering, various kinds of genomic information are being unveiled. Hence, now, it becomes feasible to study in molecular biology by analyzing the entire genomic information. On the other hand, the quantity of the genomic information stocked in database is increasing day after day. In order to process the whole information, we have to develop an effective method to deal with lots of data. It is indispensable not only to make an effective and rapid algorithm but also to use high-speed computer resource so as to analyze the biological information. For this purpose, as one of the most promised computing environments, the grid computing architecture has appeared recently. The European Data Grid (EDG) is one of the grid com-puting environments. In the first stage of designing hybridization probes and PCR primers, it is extremely important to find genuinely unique sequence on a target genome. We deployed a novel method to design PCR primers, which takes into account not only the specificity of the primer itself but also the uniqueness of the product length. In this paper, we improve our proposed method to find unique PCR products on distributed databases. We show also the sequences found by our method, which can not be uniquely observed by any probe sequence but by a pair of PCR primers on S. cerevisiae genome. 1

Feedback regulation of the heat shock response in E. coli

Survival of organisms in extreme conditions has necessitated the evolution of stress response networks that detect and respond to environmental changes. Among the extreme conditions that cells must face is the exposure to higher than normal temperatures. In this paper, we propose a detailed biochemical model that captures the dynamical nature of the heat-shock response in Escherichia coli. Using this model, we show that both feedback and feedforward control are utilized to achieve robustness, performance, and efficiency of the response to the heat stress. We discuss the evolutionary advantages that feedback confers to the system, as compared to other strategies that could have been implemented to get the same performance

Ten Years» Experience of Aortic Aneurysm Associated with Systemic Lupus Erythematosus

AbstractBackground: aortic aneurysm is a rare but life-threatening cardiovascular complication in patients with systemic lupus erythematosus (SLE). The purpose of this study was to clarify the characteristic clinical features and the pathological mechanism of aneurysmal formation in these patients. Methods: among 429 patients operated on for abdominal aortic aneurysm (AAA) during the past 10 years, five cases with SLE were treated surgically. Their clinical data were reviewed, and the resected aneurysmal wall of the five patients was also examined histologically. Results: the mean age of the patients with SLE was 55 years, which was statistically younger than that of the other patients (mean 77 years, s.d. 7.9, p <0.05). They had received long-term corticosteroid therapy for the treatment of SLE for a mean of 23 years. Histologically, destruction of the medial elastic lamina was characteristic. Four patients had no complications in the postoperative follow-up period (mean 4 years), while the remaining patient died of rupture of a dissecting aneurysm two years after operation.Conclusion : prolonged steroid therapy may play a major role in accelerating atherosclerosis, which can result in aortic aneurysmal enlargement, possibly together with primary aortic wall involvement and/or vasculitic damage in patients with SLE

Mathematical Identification of Critical Reactions in the Interlocked Feedback Model

Dynamic simulations are necessary for understanding the mechanism of how biochemical networks generate robust properties to environmental stresses or genetic changes. Sensitivity analysis allows the linking of robustness to network structure. However, it yields only local properties regarding a particular choice of plausible parameter values, because it is hard to know the exact parameter values in vivo. Global and firm results are needed that do not depend on particular parameter values. We propose mathematical analysis for robustness (MAR) that consists of the novel evolutionary search that explores all possible solution vectors of kinetic parameters satisfying the target dynamics and robustness analysis. New criteria, parameter spectrum width and the variability of solution vectors for parameters, are introduced to determine whether the search is exhaustive. In robustness analysis, in addition to single parameter sensitivity analysis, robustness to multiple parameter perturbation is defined. Combining the sensitivity analysis and the robustness analysis to multiple parameter perturbation enables identifying critical reactions. Use of MAR clearly identified the critical reactions responsible for determining the circadian cycle in the Drosophila interlocked circadian clock model. In highly robust models, while the parameter vectors are greatly varied, the critical reactions with a high sensitivity are uniquely determined. Interestingly, not only the per-tim loop but also the dclk-cyc loop strongly affect the period of PER, although the dclk-cyc loop hardly changes its amplitude and it is not potentially influential. In conclusion, MAR is a powerful method to explore wide parameter space without human-biases and to link a robust property to network architectures without knowing the exact parameter values. MAR identifies the reactions critically responsible for determining the period and amplitude in the interlocked feedback model and suggests that the circadian clock intensively evolves or designs the kinetic parameters so that it creates a highly robust cycle