分子马达定向运动的两态模型

采用非对称周期势来描述马达蛋白与具有周期性和极性的微丝轨道之间的相互作用,计算了马达蛋白两态模型的几率流和有效势之间的关系。计算结果表明：马达蛋白的定向运动不仅与有效势的整体倾斜密切相关,还与有效势的势垒高度有关。有效势倾斜等效于一个平均力的作用,而这一平均力的存在体现了两态跃迁细致平衡的破坏。同时将不同ATP浓度下力与速度的关系曲线与实验作了比较,这些曲线与实验定性吻合。     

一种生物分子马达的冲激力模型

基于动力冲程模型并结合布朗棘轮模型的扩散机制,提出了分子马达的冲激力模型。该模型基于一系列具有时间或空间周期性的啄函数来模拟分子马达的做功冲击,得到了关于几率流（速度）的解析结果。计算结果与实验数据相符合。为了产生非零的几率流,新模型并不要求分子马达与轨道间的势能必须是不对称的,因而相对于布朗棘轮模型来说更加稳健。     

神经细胞膜钠通道的门控电流和门控动力学

根据作者已提出的神经轴突钠离子通道蛋白质分子构象模型,组成通道闸门的极性氨基酸侧链可以有两种类型:偶极子和荷电离子基团.它们在两种构象间的跃迁导致通道呈现关闭或开放态,并产生了门控电流相应的两种组分.对两种侧链跃迁动力学参量的计算结果表明,门控电流曲线的时间常数、稳态开启几率及门控电荷随膜电位的变化是不同的.去极化脉冲引起通道状态的变化,可由关闭态经过活化态转变为失活态,也可由关闭态经部分关闭态转变为失活态,对不同膜电位条件下一个通道各种稳定状态几率的计算表明,活化和失活的耦联程度随膜电位而改变.     

肌球蛋白动力冲程分布研究

通过建立肌球蛋白工作循环的四态模型,利用化学动力学方法,讨论了动力冲程过程的几率和无机磷酸盐的释放率是影响动力冲程分布的两个重要因素,得到动力冲程的大小近似呈均值为（8-10）nm的高斯分布。     

内循环颗粒污泥床硝化反应器流动模型研究

采用脉冲刺激响应技术,对稳态内循环颗粒污泥床硝化反应器进行了示踪试验。根据试验结果,分别运用轴向扩散模型和多釜全混流反应器串联模型,对反应器沉淀区和循环区的流态进行了分析和判断。结果表明,反应器沉淀区的分散数D/uL为0.00148,该区域的流态接近于平推流反应器（PFR）;反应器循环区的串联级数为1.021,该区域的流态接近于全混流反应器（CSTR）。稳态时,反应器的理论水力停留时间为360min,实际水力停留时间为341.2min,反应器中死区所占的体积百分比为5.22％,其中生物体死区为0.75%,水力死区为4.47%,表明反应器结构性能良好。根据试验和分析结果,建立了内循环颗粒污泥床硝化反应器的流动模型,即全混流和平推流的串联组合模型。由流动模型所得的理论停留时间分布曲线与由试验所得的实际停留时间分布曲线吻合良好,两者的平均相对误差为8.56%,表明所建模型具有较高的准确性。     

田间非饱和流条件下土壤硝态氮运移的模拟

运用马尔可夫过程的理论 ,建立了土壤非饱和流条件下 ,模拟硝态氮通过土层运移的随机模型 .模型把时间可变系统假设为由紧密相连的时间均质情况相接而成 ,使得运用马尔可夫过程成为可能 ,在给定土壤水流量及汇源项转移强度的土壤层次中 ,给出了硝态氮溶质的统计分布 .模型将随机过程与确定性过程相结合 ,在计算各土层间的转移概率时考虑了硝态氮的作物吸收、淋洗、硝化和反硝化等主要过程 ,并用相关函数修正 N素转化关系 .在褐土农田土壤非饱和流条件下 ,用微区试验对该模型运行效果进行了验证 ,结果显示模拟计算值与实测值之间吻合性较好 ,说明模型可以用于相似类型区 ,预测和评价土壤 -作物系统中硝态氮溶质的运移行为 .     

椎动脉狭窄内血液两相流动数值模拟分析

目的:对应用三维重构得到的人体真实椎动脉进行血液两相流数值模拟,与经典单相流牛顿血液模型对比,分析动脉粥样硬化等病因与椎动脉狭窄处的血流动力学关系。方法:把考虑血细胞和血浆的两相流血液模型应用到逆向工程方法构建的基于人体生理解剖特征的椎动脉三维几何模型中去进行数值模拟,分析血细胞分布情况等血流动力学参数,并与单相流模型的模拟结果进行对比。结果:通过瞬态模拟计算,得到了椎动脉在心动周期内不同时刻的两相流和单相流模型的血流动力学参数。结论:通过对比单相流数值模拟结果,得出血管狭窄处血细胞出现聚集,血流更加复杂和低壁面切应力分布等与动脉粥样硬化及血栓的形成相关的结论。并且与两相流模型相比,单相流模型存在如无法获得如血细胞分布等不足,为进一步深入研究椎动脉等疾病的发病机理提供方法和理论支持。     

冬小麦生长条件下土壤硝态氮淋洗的传递函数模拟和预报

观测了地中渗透计的土壤在 3种不同施肥量下冬小麦自播种至返青期硝态氮的淋洗动态 ,由试验资料获得了硝态氮在土壤中迁移时间的概率密度函数 ,进而运用传递函数模型对土壤排水出流液中的硝态氮浓度和淋洗量动态进行了数学模拟和预报。     

蝮蛇抗栓酶对微循环作用的实验与临床研究

对实验性失血性休克的４０只大鼠和１５只家兔静注不同剂量的抗栓酶,用激光多普勒微循环血流计测定肾表面固定部位的微循环血流量,发现用药后血流量显著增加且与尿量相一致;阻断６０只沙鼠颈动脉造成脑缺血模型,在颅顶开窗用微循环显微镜观察用药后软脑膜微循环的变化,发现微循环血流速度加快并显示一定的冲击力,且能减少白细胞数及贴壁滚动;用２０只家兔做成ＤＩＣ模型,给抗栓酶后观察肠系膜微循环,发现毛细血管开放数增多,微循环流态改善。观察３３例脑血栓形成期病人用抗栓酶治疗前后甲襞微循环的变化,发现治疗后微循环总积分值改善,流态改善更明显     

藏东南色季拉山沟壑区土壤氮素空间分布特征

以西藏东南部色季拉山海拔3950—4350 m为研究区,采用30×50 m网格采样法,以地统计学半变异函数为工具,研究了色季拉山森林生态系统沟谷与坡面上土壤氮素空间变异特征及模型。结果表明:土壤全氮、硝态氮和铵态氮含量均表现为0—10 cm10—20 cm,两个层次上空间变异性表现为全氮和铵态氮0—10 cm10—20 cm,而硝态氮表现为10—20 cm0—10cm;不同海拔高度土壤氮含量表现为随着海拔高度的升高而增加,但这种海拔梯度效应并未达显著水平(P0.05);沟谷区土壤氮含量高于坡面,这可能与植被残体在沟谷区的堆积分解促进氮循环有关;土壤全氮、铵态氮和硝态氮均具有中等程度的空间依赖性,其中土壤全氮空间变异符合指数模型,块金值/基台值为50%;土壤铵态氮和硝态氮含量空间变异分布均符合高斯模型,块金值/基台值分别为70.91%和37.45%;该区域土壤全氮、铵态氮和硝态氮含量空间依赖性表现为:硝态氮全氮铵态氮,即土壤硝态氮更易受到空间结构因素的影响,而铵态氮含量空间变化则主要受随机因素的影响。     

钾离子通道两态跳跃的通透机制

采用两态跳跃模型研究离子通道的通透机制,从两态动力学方程得到了平衡态下的能斯特方程、稳态条件下的米氏动力学关系。得出：若电压小于100mV,电导-电压关系是线性的;在电流-浓度关系中,电流具有饱和特性。这些与实验结果是一致的。此外,还讨论了钾离子通道到达稳态前的暂态过程,并用特征时间来描述这一过程。发现采用两态跳跃模型用较少的参数就可以说明离子通透的机制。     

Permeation mechanism of a two-state potassium channel

A two-state hopping model was proposed to study the permeation of ion channel.The Nemst equation in equilibrium and the Michaelis-Menten relation in steady state were derived from the two-state kinetic model.The currentvoltage relationship obtained in the symmetrical solutions case was linear when the applied potential was less than 100 mV,which met Ohm's law.The conductance-concentration relationship exhibited the saturation property.Moreover,the characteristic time reaching the steady state of the KcsA channel was also discussed.     

Exploring the relationship between funneled energy landscapes and two-state protein folding

It should take an astronomical time span for unfolded protein chains to find their native state based on an unguided conformational random search. The experimental observation that folding is fast can be rationalized by assuming that protein energy landscapes are sloped towards the native state minimum, such that rapid folding can proceed from virtually any point in conformational space. Folding transitions often exhibit two-state behavior, involving extensively disordered and highly structured conformers as the only two observable kinetic species. This study employs a simple Brownian dynamics model of "protein particles" moving in a spherically symmetrical potential. As expected, the presence of an overall slope towards the native state minimum is an effective means to speed up folding. However, the two-state nature of the transition is eradicated if a significant energetic bias extends too far into the non-native conformational space. The breakdown of two-state cooperativity under these conditions is caused by a continuous conformational drift of the unfolded proteins. Ideal two-state behavior can only be maintained on surfaces exhibiting large regions that are energetically flat, a result that is supported by other recent data in the literature (Kaya and Chan, Proteins: Struct Funct Genet 2003;52:510-523). Rapid two-state folding requires energy landscapes exhibiting the following features: (i) A large region in conformational space that is energetically flat, thus allowing for a significant degree of random sampling, such that unfolded proteins can retain a random coil structure; (ii) a trapping area that is strongly sloped towards the native state minimum.     

The calorimetric criterion for a two-state process revisited.

The "calorimetric criterion" is one of the important experimental approaches for determining whether protein folding is an "all-or-none" two-state transition (i.e., whether intermediates are present at equilibrium). The calorimetric criterion states that the equivalence of the "measured" calorimetric enthalpy change and the effective two-state van't Hoff enthalpy change demonstrates that there is a two-state transition. This paper addresses the essential question of whether the calorimetric criterion is a necessary and sufficient condition for a two-state process and shows that it is necessary but not sufficient by means of specific examples. Analysis of simple models indicates that the heat capacity curve, regardless of whether it originates from a two-state process or not, can always be decomposed in such a way that the calorimetric criterion is satisfied. Exact results for a three-state model and a homopolymer tetramer demonstrate that the deviation from the calorimetric criterion is not simply related to the population of intermediate states. Analysis of a three-helix bundle protein model, which has a two-state folding from a random coil to ordered (molten) globule, shows that the calorimetric criterion may not be satisfied if the standard linear interpolation of baselines (weighted or unweighted) is employed. A specific example also suggests that the more recently introduced deconvolution method is not necessarily better than the simple calorimetric criterion for distinguishing a two-state transition from a three-state transition. Although the calorimetric criterion is not a sufficient condition for a two-state process, it is likely to continue to be of practical utility, particularly when its results are shown to be consistent with those from other experimental methods.     

Folding-unfolding of immunoglobulin domains in titin: a simple two-state model

The folding-unfolding reaction rate process in the giant protein titin is studied within a simple two-state model. The molecule is assumed to be stretched by an external force which modulates the potential barrier associated with the folded state. A two-state model for this process is assumed (i.e., the immunoglobulin domains are considered to be either folded or unfolded, with no intermediate states at all). Simple calculations yield a relation between the force and the pulling speed that agrees fairly well with data from experiments and Monte Carlo simulations performed recently. Moreover, in a regime involving ultrafast pulling, the results show that the detailed form of the potential barrier is irrelevant, a conclusion that agrees with the current theoretical work on molecular dynamics.     

The influence of transverse tubular delays on the kinetics of charge movement in mammalian skeletal muscle

A model was developed to describe the kinetics of slow, voltage-dependent charge movement in the rat omohyoid muscle. To represent the electrically distributed nature of the transverse tubular system (t-system), we followed an approach similar to that described by Adrian and Peachey (1973 J. Physiol. [Lond.]. 235:103), and approximated the fiber with 12 concentric cylindrical shells. Incorporated into each shell were capacitative and conductive elements that represented the passive electrical properties of the t-system, and an element representing the mobile charge. The charge was assumed to obey a two-state scheme, in which the redistribution of charge is governed by a first-order reaction, and the rate constants linking the two states were assumed to depend on potential according to the constant field expression. The predictions of this "distributed two-state model" were compared with charge movements experimentally measured in individual fibers. For this comparison, first, the passive electrical parameters of the model were adjusted to fit the experimental linear capacity transient. Next, the Boltzmann expression was fitted to the steady state Q vs. V data of the fiber, thereby constraining the voltage dependence of the rate constants, but not their absolute magnitude. The absolute magnitude was determined by fitting the theory to an experimental charge movement at a single test potential, which in turn constrained the fits at all other test potentials. The distributed two-state model well described the rising and falling phases of ON, OFF, and stepped OFF charge movements at temperatures ranging from 3 to 25 degrees C. We thus conclude that tubular delays are sufficient to account for the rounded rising phase of experimental charge movements, and that it is unnecessary to postulate higher-order reaction schemes for the underlying charge redistribution.     

Light scattering and excitation in lobster giant axon Effects of ion substitution

Changes in the light scattering signal from single giant axons of lobster were observed during the propagation of the action potential in order to correlate membrane excitability with possible structural changes reflected in the optical properties of the axolemma. Substitution of guanidine and aminoguanidine for sodium resulted in a decreased action potential amplitude to 69 and 50% of control values, respectively. The amplitude of the light signal was, however, not significantly changed by these substitutions and is, therefore, reported to be independent of the transmembrane potential and current. The venom of the scorpion Leiurus quinquestriatus caused a marked prolongation of the action potential and the light scattering signal without significantly altering their amplitudes. A two-state model of the early (sodium) activation channel is suggested, in which the light scattering signal is correlated with a possible difference in the scattering efficiency between the states of the channel.     

Structure of spontaneous UP and DOWN transitions self-organizing in a cortical network model

Synaptic plasticity is considered to play a crucial role in the experience-dependent self-organization of local cortical networks. In the absence of sensory stimuli, cerebral cortex exhibits spontaneous membrane potential transitions between an UP and a DOWN state. To reveal how cortical networks develop spontaneous activity, or conversely, how spontaneous activity structures cortical networks, we analyze the self-organization of a recurrent network model of excitatory and inhibitory neurons, which is realistic enough to replicate UP–DOWN states, with spike-timing-dependent plasticity (STDP). The individual neurons in the self-organized network exhibit a variety of temporal patterns in the two-state transitions. In addition, the model develops a feed-forward network-like structure that produces a diverse repertoire of precise sequences of the UP state. Our model shows that the self-organized activity well resembles the spontaneous activity of cortical networks if STDP is accompanied by the pruning of weak synapses. These results suggest that the two-state membrane potential transitions play an active role in structuring local cortical circuits.     

Folding rates and low-entropy-loss routes of two-state proteins

We develop a simple model for computing the rates and routes of folding of two-state proteins from the contact maps of their native structures. The model is based on the graph-theoretical concept of effective contact order (ECO). The model predicts that proteins fold by "zipping up" in a sequence of small-loop-closure events, depending on the native chain fold. Using a simple equation, with a few physical rate parameters, we obtain a good correlation with the folding rates of 24 two-state folding proteins. The model rationalizes data from Phi-value analysis that have been interpreted in terms of delocalized or polarized transition states. This model indicates how much of protein folding may take place in parallel, not along a single reaction coordinate or with a single transition state.