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Yang J.,Peking University | Yang J.,Virginia Polytechnic Institute and State University | Yu H.,Virginia Polytechnic Institute and State University | Yu H.,Wake forest University | And 5 more authors.
Inverse Problems | Year: 2012

Recently, we developed an approach for solving the computed tomography (CT) interior problem based on the high-order TV (HOT) minimization, assuming that a region-of-interest (ROI) is piecewise polynomial. In this paper, we generalize this finding from the CT field to the single-photon emission computed tomography (SPECT) field, and prove that if an ROI is piecewise polynomial, then the ROI can be uniquely reconstructed from the SPECT projection data associated with the ROI through the HOT minimization. Also, we propose a new formulation of HOT, which has an explicit formula for any n-order piecewise polynomial function, while the original formulation has no explicit formula for n 2. Finally, we verify our theoretical results in numerical simulation, and discuss relevant issues. © 2012 IOP Publishing Ltd.

Lv C.,Peking University | Li X.,Peking University | Li F.,Peking University | Li T.,Peking University | Li T.,Beijing International Center for Mathematical Research
PLoS ONE | Year: 2014

Genetic switching driven by noise is a fundamental cellular process in genetic regulatory networks. Quantitatively characterizing this switching and its fluctuation properties is a key problem in computational biology. With an autoregulatory dimer model as a specific example, we design a general methodology to quantitatively understand the metastability of gene regulatory system perturbed by intrinsic noise. Based on the large deviation theory, we develop new analytical techniques to describe and calculate the optimal transition paths between the on and off states. We also construct the global quasi-potential energy landscape for the dimer model. From the obtained quasi-potential, we can extract quantitative results such as the stationary distributions of mRNA, protein and dimer, the noise strength of the expression state, and the mean switching time starting from either stable state. In the final stage, we apply this procedure to a transcriptional cascades model. Our results suggest that the quasi-potential energy landscape and the proposed methodology are general to understand the metastability in other biological systems with intrinsic noise. © 2014 Lv et al.

Jia C.,Peking University | Jia C.,Beijing International Center for Mathematical Research | Liu X.-F.,Peking University | Qian M.-P.,Peking University | And 2 more authors.
Journal of Theoretical Biology | Year: 2012

In this paper, we perform a complete analysis of the kinetic behavior of the general modifier mechanism of Botts and Morales in both equilibrium steady states and non-equilibrium steady states (NESS). Enlightened by the non-equilibrium theory of Markov chains, we introduce the net flux into discussion and acquire an expression of the rate of product formation in NESS, which has clear biophysical significance. Up till now, it is a general belief that being an activator or an inhibitor is an intrinsic property of the modifier. However, we reveal that this traditional point of view is based on the equilibrium assumption. A modifier may no longer be an overall activator or inhibitor when the reaction system is not in equilibrium. Based on the regulation of enzyme activity by the modifier concentration, we classify the kinetic behavior of the modifier into three categories, which are named hyperbolic behavior, bell-shaped behavior, and switching behavior, respectively. We show that the switching phenomenon, in which a modifier may convert between an activator and an inhibitor when the modifier concentration varies, occurs only in NESS. Effects of drugs on the Pgp ATPase activity, where drugs may convert from activators to inhibitors with the increase of the drug concentration, are taken as a typical example to demonstrate the occurrence of the switching phenomenon. © 2011 Elsevier Ltd.

Jia C.,Peking University | Jia C.,Beijing International Center for Mathematical Research | Qian M.,Peking University | Jiang D.,Peking University
IET Systems Biology | Year: 2014

A number of biological systems can be modelled by Markov chains. Recently, there has been an increasing concern about when biological systems modelled by Markov chains will perform a dynamic phenomenon called overshoot. In this study, the authors found that the steady-state behaviour of the system will have a great effect on the occurrence of overshoot. They showed that overshoot in general cannot occur in systems that will finally approach an equilibrium steady state. They further classified overshoot into two types, named as simple overshoot and oscillating overshoot. They showed that except for extreme cases, oscillating overshoot will occur if the system is far from equilibrium. All these results clearly show that overshoot is a non-equilibrium dynamic phenomenon with energy consumption. In addition, the main result in this study is validated with real experimental data. © The Institution of Engineering and Technology 2014.

Li T.,Peking University | Li T.,Beijing International Center for Mathematical Research | Min B.,Peking University | Wang Z.,Peking University
Journal of Chemical Physics | Year: 2013

The stochastic integral ensuring the Newton-Leibnitz chain rule is essential in stochastic energetics. Marcus canonical integral has this property and can be understood as the Wong-Zakai type smoothing limit when the driving process is non-Gaussian. However, this important concept seems not well-known for physicists. In this paper, we discuss Marcus integral for non-Gaussian processes and its computation in the context of stochastic energetics. We give a comprehensive introduction to Marcus integral and compare three equivalent definitions in the literature. We introduce the exact pathwise simulation algorithm and give the error analysis. We show how to compute the thermodynamic quantities based on the pathwise simulation algorithm. We highlight the information hidden in the Marcus mapping, which plays the key role in determining thermodynamic quantities. We further propose the tau-leaping algorithm, which advance the process with deterministic time steps when tau-leaping condition is satisfied. The numerical experiments and its efficiency analysis show that it is very promising. © 2013 American Institute of Physics.

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