DNA损伤致p53-Mdm2相互作用的动力学模型

最新实验结果表明，在受到各种辐射而引起DNA损伤后，在单体细胞和群体细胞情况下，细胞中的p53蛋白浓度表现为非衰减振荡和衰减振荡两种不同的动力学行为.通过研究p53-Mdm2负反馈回路的非线性动力学行为，分析了各种(特别是DNA损伤、p53和 Mdm2蛋白浓度三者之间)动力学关系，提出了一个能同时描述这两种不同动力学行为的非线性模型. 关键词： p53-Mdm2负反馈回路 非衰减振荡和衰减振荡 非线性动力学模型     

A mathematical model of a P53 oscillation network triggered by DNA damage

Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damage signal in individual cells. The effects of the DNA damage signal and the delay time of P53-induced MDM2 expression on the behaviours of the P53 oscillation network are studied. In the oscillatory state of the P53--MDM2 oscillator, it is found that the pulse number of P53--P oscillation increases with the increase of the initial DNA damage signal, whereas the amplitude and the period of P53--P oscillation are fixed for different initial DNA damage signals, and the period numbers of P53--P oscillations decrease with the increase of time delay of MDM2 expression induced by P53. These theoretical predictions are consistent with previous experimental results. The combined negative feedback of P53--MDM2 with the time delay of P53-induced MDM2 expression causes oscillation behaviour in the P53 network.     

Mdm2生成速率调控的p53-Mdm2振子的全局动力学和稳定性

肿瘤抑制蛋白p53的动力学在一定程度上可以决定DNA损伤后的细胞命运.p53的动力学行为与p53信号通路中p53-Mdm2振子模块密切相关.然而,p53的负调控子Mdm2的生成速率的增加使其在一些癌细胞中过表达.因此探讨Mdm2生成速率对p53动力学的影响有重要意义.同时,PDCD5作为p53的激活子也调控p53的表达.因此,本文针对PDCD5调控的p53-Mdm2振子模型,通过分岔分析获得了Mdm2生成速率所调控的p53的单稳态、振荡以及单稳态与振荡共存的动力学行为,且稳定性通过能量面进行了分析.此外,噪声强度对p53动力学的稳定性有重要的影响.因此,针对p53的振荡行为,探讨了噪声强度对势垒高度和周期的影响.本文所获得的结果对理解DNA损伤后的p53信号通路调控起到一定的指导作用.     

基于衰减振荡信号特征参数和伪阻抗的电路参数计算方法

本文研究了基于暂态信号中衰减振荡信号的电路参数计算理论和方法.在电力系统线路发生故障时,通过计算暂态信号流通路径电路参数可确定故障位置、推断故障原因,而衰减振荡信号作为暂态信号主要成分,因此分析基于衰减振荡信号的电路参数计算在电力系统故障定位中有重要理论价值和实际工程意义.结合R-L电路和R-C电路,首先推导了时域衰减振荡电压、电流信号特征参数与各元件参数以及电路参数间定量关系;并分析了电路在衰减振荡信号下阻抗特性,结合稳态正弦分量阻抗概念,将电路流经衰减振荡信号时的阻抗特性定义为伪阻抗,并确定了伪阻抗与电路参数和信号特征参数间的关系;同时分析了串并联条件下伪阻抗与元件参数关系.以此为基础分别提出了基于信号特征参数和基于伪阻抗的电路参数计算理论,结合现有衰减振荡信号特征提取方法,提出具体计算方法,为基于衰减振荡信号的电路参数计算理论发展以及实际工程应用奠定了重要基础.通过MATLAB模拟产生故障信号对所提理论和方法进行验证,结果证明了所提理论和方法的正确性和准确性,并以实际电网故障信息为基础,基于PSCAD/EMTDC建立实际配网模型并对实际单相接地故障进行重现,对配网单相接地故障进行定位分析,结果证明了方法的可行性.     

Rijke管热声振荡的稳定性切换行为研究

采用数值方法模拟了强弱两种阻尼条件下传热迟滞时间对一维Rijke管热声系统稳定性的影响,发现Rijke管系统存在稳定性切换现象.在推导了无量纲形式的管内声波动量方程和能量方程之后,利用Galerkin方法对控制方程进行展开并在时间域内数值求解.分析了强阻尼和弱阻尼条件下,给定热源的Rijke管热声振荡的稳定性与传热迟滞时间的关系.结果显示:在两类阻尼条件下,持续增大传热与速度的迟滞时间,系统均呈现出稳定性切换现象,即系统在稳定和不稳定两个状态间持续转变;但弱阻尼系统的不稳定区域宽于强阻尼系统的不稳定区域,系统最大振幅相对增大,且系统热声振荡的主模态在不同模态之间发生转换.最后,通过求解系统各阶模态极限环幅值随传热迟滞时间的变化,发现Rijke管热声振荡稳定性切换现象与迟滞时间存在近似周期性关系.     

模型化研究两细胞间基因、蛋白耦合振荡中的噪声效应

本文基于Hill动力学与Michaelis-Menten方程，建立理论模型研究两细胞间基因、蛋白耦合振荡中的噪声效应.研究发现，在Notch信号通路中，两细胞间基因、蛋白耦合振荡呈现了周期振荡特性，表明了细胞间信号传导的同步振荡特性.“内在”噪声和“外在”噪声对两细胞间基因、蛋白耦合振荡有着不同的作用.内噪声有利于细胞间Notch信号通路中各基因、蛋白表达再次提升.外噪声诱导通路中基因、蛋白的表达水平降低，周期振荡变得阻尼.内、外噪声共同作用不仅可使得基因表达适当并呈现出持续振荡模式，而且还可使得细胞间基因转录合成相应的蛋白过程呈现出持续振荡模式.从而表明了基因表达的内、外噪声共同作用有利于控制细胞间基因激活、蛋白合成保持周期节律性.本文理论结果揭示了内外噪声对细胞间Notch信号通路动力学的一种调控机制，确定了内外噪声各自的调控效应，澄清了内外噪声共同作用调控体系持续周期振荡的物理机制，理论结果符合实验，可为设计阻止Notch体系基因、蛋白变异导致的多种疾病和癌症的通路治疗方案提供理论依据.     

Ultrafast magnetization reversal dynamics investigated by time domain imaging

Spatiotemporal magnetization reversal dynamics in a Ni(80)Fe(20) microstructure is studied using ps time scale scanning Kerr microscopy. Time domain images reveal a striking change in the reversal associated with the reduction in switching time when a transverse bias field is applied. Magnetization oscillations subsequent to reversal are observed at two resonance frequencies, which sensitively depend on the bias field strength. The oscillation at f = 2 GHz is caused by the damped precession of M, while the lower frequency approximately 0.8 GHz mode is interpreted in terms of domain wall oscillation.     

VPRBP 蛋白与Abl 激酶诱发、抑制前列腺癌的 一种物理机制

在本文基于Hill动力学与Michaelis-Menten方程,建立理论模型研究VPRBP蛋白与Abl激酶诱发、抑制前列腺癌的一种物理机制.研究发现,DNA损伤使得ATM(共济失调毛细血管扩张症突变)很快激活,并激活上调p53蛋白表达,DNA损伤的后续破坏会在很大程度上通过p53表达上调而被抑制. VPRBP通过上调MDM2蛋白的激活水平,使得p53表达水平异常,进而无法正常抑制前列腺癌的发生发展.通过考察Abl在前列腺癌进程中的作用发现,Abl使得AKT的表达水平下调,由于Abl对AKT的抑制作用,致使在AKT信号通路中MDM2表达水平受到抑制,进而稳定p53表达.由此表明了,过少的Abl对AKT的抑制程度减弱,不仅使得细胞代谢出现紊乱,而且还会促使p53正常的周期表达水平异常,对DNA损伤诱发的肿瘤抑制性减弱,进而促进前列腺癌的发生发展.基于本文模型,可以预测VPRBP与Abl作为诱发、抑制前列腺癌的调节剂对现有和潜在的抗癌治疗较为敏感. VPRBP与Abl在诱发、抑制前列腺癌过程中的时滞效应,导致信号通路中p53与PTEN蓄积量增多、AKT蓄积量减少,以及Plk1周期振荡相位转移...     

Self oscillations of a bistable element in two coupled hybrid ring resonators

A CdS crystal showing thermally induced optical bistability is incorporated into two coupled hybrid ring resonators with different delay times. Both delay times are much longer than the relaxation time of the nonlinearity. The resulting self-oscillations are investigated both experimentally and theoretically. We find two different types of oscillation modes. If the crystal is on the lower branch of the bistability during the longer delay time, step like oscillations similar to the case of a single resonator occur. If the crystal is in the lower state onlh for the shorter delay time (also the shorter of the two delay times is much longer than the relaxation time) we find more complicated modes with plateaus and stairs because the long resonator acts as a memory for the system state before the switching process. We find complex mode locking structures exhibiting Farey-tree like transitions between different oscillation modes as well as mode coexistence. Based on an adiabatic theory we compute the regions of extstence of the different oscillation modes and compare them with experimental results.     

时滞与噪声影响 Notch信号通路动力学的模型化研究

本文基于Hill动力学与Michaelis-Menten方程,建立理论模型研究时滞与噪声影响Notch信号通路动力学.研究发现,her1、her7基因转录的时滞性在很大程度上调控着Notch信号通路的动力学行为.由于时滞性的调控,Notch系统动力学经历Hopf分岔,由稳态转变为周期演化特性.通过考察Notch信号通路的噪声效应,我们发现,由于噪声的扰动,Notch系统周期振荡动力学改变.在较小噪声幅值条件下,Notch信号通路中改变的周期节律性可以通过时滞得以平衡恢复,由此表明了her1、her7转录的时滞性促进了Notch信号通路的周期振荡.对于较强噪声环境,时滞效应很难改变Notch信号的巨大突变,其信号通路动力学行为被噪声影响.理论结果符合实验,并揭示了时滞与噪声对Notch信号通路动力学的一种调控机制,可为设计阻止Notch功能异常导致的多种疾病和癌症的通路治疗方案提供理论依据.     

DNA损伤致p53-Mdm2相互作用的非线性动力学模型(英文)

p53-Mdm2相互作用在DNA损伤的细胞响应方面起着非常重要的作用。最新实验结果表明,在受到各种辐射损伤而引起DNA损伤后,细胞中的p53蛋白浓度在单体细胞和群体细胞情况下,表现为非衰减振荡和衰减振荡两种不同的动力学行为。通过研究p53 -Mdm2负反馈回路的非线性动力学,分析了各种（特别是DNA损伤,p53和Mdm2浓度三者之间的）动力学关系,提出了一个能同时描述这两种不同动力学行为的非线性模型。 Exploring the nonlinear dynamics of the negative feedback loop composed of p53 and Mdm2 proteins, we propose a signal-response model to study the dynamical mechanism of the different oscillatory behaviors for the activities of p53 and Mdm2 proteins both in individual and population of cells. It is shown that the sustained and damped oscillatory dynamics could be described in a unified way when the dynamics of damage-derived signal is properly introduced.     

Complex dynamics of a simple distributed self-oscillatory model system with delay

A simple model for a distributed self-oscillatory system with cubic nonlinearity and delay is presented. Conditions for oscillation self-excitation and stationary oscillation conditions, as well as the stability of the oscillations, are analyzed. Nonstationary self-modulation regimes (including conditions of complex dynamics and chaos) are simulated numerically over a wide range of control parameters. As the factor of nonequilibrium grows, regular and chaotic regimes alternate in a complex manner. The transitions to chaos may follow all scenarios known for finite-dimensional systems. The model suggested is somewhat akin to a number of earlier finite-dimensional models aimed at studying mode competition in resonance electron masers.     

Hopf bifurcation analysis of Chen circuit with direct time delay feedback

Direct time delay feedback can make non-chaotic Chen circuit chaotic. The chaotic Chen circuit with direct time delay feedback possesses rich and complex dynamical behaviours. To reach a deep and clear understanding of the dynamics of such circuits described by delay differential equations, Hopf bifurcation in the circuit is analysed using the Hopf bifurcation theory and the central manifold theorem in this paper. Bifurcation points and bifurcation directions are derived in detail, which prove to be consistent with the previous bifurcation diagram. Numerical simulations and experimental results are given to verify the theoretical analysis. Hopf bifurcation analysis can explain and predict the periodical orbit (oscillation) in Chen circuit with direct time delay feedback. Bifurcation boundaries are derived using the Hopf bifurcation analysis, which will be helpful for determining the parameters in the stabilisation of the originally chaotic circuit.     

Control coherence resonance by noise recycling

We study the effect of recycled noise, generated by the superposition of a primary Gaussian noise source with a second component of constant delay, in a parameter region below the threshold of supercritical Hopf bifurcation, by focussing on the performance of noise induced oscillations and coherence resonance. For fixed noise intensity, the amplitude and signal-to-noise ratio of the oscillation show periodic dependences on the delay time. The optimal noise intensity for the occurrence of coherence resonance also shows a periodic dependence on the delay. A theoretical analysis based on the stochastic normal form theory is presented, which qualitatively reproduces the simulation results with good agreement. This work presents a possible strategy for controlling noise induced oscillations and coherence resonance by deliberately adjusting the parameters of the recycled noise.     

The birhythmicity increases the diversity of p53 oscillation induced by DNA damage

The tumor suppressor p53 mediates the cellular response to various stresses. It was experimentally shown that the concentration of p53 can show oscillations with short or long periods upon DNA damage. The underlying mechanism for this phenomenon is still not fully understood. Here, we construct a network model comprising the ATM-p53-Wip1 and p53-Mdm2 negative feedback loops and ATM autoactivation. We recapitulate the typical features of p53 oscillations including p53 birhythmicity. We show the dependence of p53 birhythmicity on various factors such as the phosphorylation status of ATM. We also perform stochastic simulation and find the noise-induced transitions between two modes of p53 oscillation,which increases the p53 variability in both the amplitude and period. These results suggest that p53 birhythmicity enhances the responsiveness of p53 network, which may facilitate its tumor suppressive function.     

A unified model for studying DNA damage-induced p53–Mdm2 interaction

Exploring the nonlinear dynamics of the negative feedback loop composed of p53 and Mdm2 proteins, we propose a signal–response model to study the dynamical mechanism of the different oscillatory behaviors for the activities of p53 and Mdm2 proteins both in individual and populations of cells. It will be shown that the sustained and damped oscillatory dynamics could be described in a unified way when the dynamics of the damage-derived signal is properly introduced.     

Sustained high-frequency energy harvesting through a strongly nonlinear electromechanical system under single and repeated impulsive excitations

This work investigates a vibration-based energy harvesting system composed of two oscillators coupled with essential (nonlinearizable) stiffness nonlinearity and subject to impulsive loading of the mechanical component. The oscillators in the system consist of one grounded, weakly damped linear oscillator mass (primary system), which is coupled to a second light-weight, weakly damped oscillating mass attachment (the harvesting element) through a piezoelastic cable. Due to geometric/kinematic mechanical effects the piezoelastic cable generates a nonlinearizable cubic stiffness nonlinearity, whereas electromechanical coupling simply sees a resistive load. Under single and repeated impulsive inputs the transient damped dynamics of this system exhibit transient resonance captures (TRCs) causing high-frequency ‘bursts’ or instabilities in the response of the harvesting element. In turn, these high-frequency dynamic instabilities result in strong and sustained energy transfers from the directly excited primary system to the lightweight harvester, which, through the piezoelastic element, are harvested by the electrical component of the system or, in the present case, dissipated across a resistive element in the circuit. The primary goal of this work is to demonstrate the efficacy of employing this type of high-frequency dynamic instability to achieve enhanced nonlinear vibration energy harvesting under impulsive excitations.     

Femtosecond pump-probe photoionization-photofragmentation spectroscopy of azobenzene cation

We report the studies of ultrafast dynamics of azobenzene cations using femtosecond photoionization-photofragmentation spectroscopy. In our experiment,a femtosecond pump pulse first prepares an ensemble of azobenzene cations via photoionization of neutrals. A delayed probe pulse then brings the evolving ionic system to higher states that ultimately undergo ion fragmentation. The dynamics is followed by monitoring either the parent-ion depletion or fragment-ion formation as a function of the pump-probe delay time. The observed transients for azobenzene cations are characterized by a constant ion depletion modulated by a rapidly damped oscillatory signal with a period of about 1 ps. Theoretical calculations suggest that the oscillation arises from a vibration motion along the twisting inversion coordinate involving displacements in CNNC and phenyl-ring torsions. The oscillation is damped rapidly with a time constant of about 1.2 ps,suggesting that energy dissipation from the active mode to bath modes takes place on this time scale.     

Delayed feedback as a means of control of noise-induced motion

Time-delayed feedback is exploited for controlling noise-induced motion in coherence resonance oscillators. Namely, under the proper choice of time delay, one can either increase or decrease the regularity of motion. It is shown that in an excitable system, delayed feedback can stabilize the frequency of oscillations against variation of noise strength. Also, for fixed noise intensity, the phenomenon of entrainment of the basic oscillation period by the delayed feedback occurs. This allows one to steer the time scales of noise-induced motion by changing the time delay.