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41.
A calcium sensor in the sodium channel modulates cardiac excitability. 总被引:11,自引:0,他引:11
Hanno L Tan Sabina Kupershmidt Rong Zhang Svetlana Stepanovic Dan M Roden Arthur A M Wilde Mark E Anderson Jeffrey R Balser 《Nature》2002,415(6870):442-447
Sodium channels are principal molecular determinants responsible for myocardial conduction and maintenance of the cardiac rhythm. Calcium ions (Ca2+) have a fundamental role in the coupling of cardiac myocyte excitation and contraction, yet mechanisms whereby intracellular Ca2+ may directly modulate Na channel function have yet to be identified. Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias. Mutations targeted to the IQ domain disrupted CaM binding and eliminated Ca2+/CaM-dependent slow inactivation, whereas the gating effects of Ca2+/CaM were restored by intracellular application of a peptide modelled after the IQ domain. A naturally occurring mutation (A1924T) in the IQ domain altered hH1 function in a manner characteristic of the Brugada arrhythmia syndrome, but at the same time inhibited slow inactivation induced by Ca2+/CaM, yielding a clinically benign (arrhythmia free) phenotype. 相似文献
42.
乙醇对小白鼠有致畸效应,尤其是对中枢神经系统(CNS)和骨骼系统.适量的维生素B_1和烟酰胺能解除由乙醇引起的小白鼠胎鼠毒害作用. 相似文献
43.
研究了新型无铅汽油添加剂甲基叔丁基醚(MTBE)、甲基叔戊基醚(TMAE)对正常人肝细胞系L-02的毒性作用,在较高浓度下,MTBE、TAME均对L-02正常人肝细胞的生长有影响,且TAME的毒性作用稍强,另外,用FT-IR法和^1H-NMR法研究了MTBE、TAME与人血红蛋白的体外作用,结果显示,MTBE、TAME与人血红蛋白无明显的直接作用。 相似文献
44.
根据中值点处展开的一次二阶矩法讨论了土中压缩波的升压时间及其不确定性,然后研究了按单自由度体系进行复合支护地下结构抗核爆设计时的动力系数(荷载系数)和等效静载的变异系数.数值结果表明,土中压缩波升压时间的不确定性,不仅与结构埋深和土参数的变异性有关,而且与土参数的均值有关,等效静载的不确定性,依赖于作用于结构上的动载变异性和结构自振频率变异性,而动载不确定性对等效静载变异性影响最大 相似文献
45.
对惯量张量、电四极矩用积分法计算和狄利克莱公式计算作对比,表明用狄利克莱公式[1]计算简洁、方便.并指出计算一类非均匀类椭球体惯量张量及电四极矩的计算方法. 相似文献
46.
47.
LIUYan HUYi-jun 《武汉大学学报:自然科学英文版》2004,9(4):399-403
We consider a risk model with a premium rate which varies with the level of free reserves. In this model, the occurrence of claims is described by a Cox process with Markov intensity process, and the influence of stochastic factors is considered by adding a diffusion process. The integro-differential equation for the ruin probability is derived by a infinitesimal method. 相似文献
48.
J. Bruce Brackenridge 《Archive for History of Exact Sciences》2003,57(4):313-336
In the 1687 Principia, Newton gave a solution to the direct problem (given the orbit and center of force, find the central force) for a conic-section
with a focal center of force (answer: a reciprocal square force) and for a spiral orbit with a polar center of force (answer:
a reciprocal cube force). He did not, however, give solutions for the two corresponding inverse problems (given the force
and center of force, find the orbit). He gave a cryptic solution to the inverse problem of a reciprocal cube force, but offered no solution for the reciprocal square force. Some take this omission as an indication that Newton could not solve the reciprocal square, for, they ask, why else
would he not select this important problem? Others claim that ``it is child's play' for him, as evidenced by his 1671 catalogue
of quadratures (tables of integrals). The answer to that question is obscured for all who attempt to work through Newton's
published solution of the reciprocal cube force because it is done in the synthetic geometric style of the 1687 Principia rather than in the analytic algebraic style that Newton employed until 1671. In response to a request from David Gregory
in 1694, however, Newton produced an analytic version of the body of the proof, but one which still had a geometric conclusion.
Newton's charge is to find both ``the orbit' and ``the time in orbit.' In the determination of the dependence of the time on orbital position, t(r), Newton
evaluated an integral of the form ∫dx/x
n
to calculate a finite algebraic equation for the area swept out as a function of the radius, but he did not write out the
analytic expression for time t = t(r), even though he knew that the time t is proportional to that area. In the determination
of the orbit, θ (r), Newton obtained an integral of the form ∫dx/√(1−x2) for the area that is proportional to the angle θ, an integral he had shown in his 1669 On Analysis by Infinite Equations to be equal to the arcsin(x). Since the solution must therefore contain a transcendental function, he knew that a finite
algebraic solution for θ=θ(r) did not exist for ``the orbit' as it had for ``the time in orbit.' In contrast to these two
solutions for the inverse cube force, however, it is not possible in the inverse square solution to generate a finite algebraic
expression for either ``the orbit' or ``the time in orbit.' In fact, in Lemma 28, Newton offers a demonstration that the
area of an ellipse cannot be given by a finite equation. I claim that the limitation of Lemma 28 forces Newton to reject the
inverse square force as an example and to choose instead the reciprocal cube force as his example in Proposition 41.
(Received August 14, 2002)
Published online March 26, 2003
Communicated by G. Smith 相似文献
49.
Zhongsheng WANG Zhigang ZENG Xiaoxin LIAODepartment of Control Science Engineering Huazhong University of Science Technology Wuhan Hubei P. R. China 《系统科学与系统工程学报(英文版)》2003,12(2):204-209
Some stability criteria are obtained for a class of uncertain systems with time-delay usingLyapunov functional and analytic techniques. It is easy to check the criteria by making use of theboundedness of the uncertainties. 相似文献
50.
Ju-liang ZHANG Jian CHENDepartment of Management Science EngineeringSchool of Economics Management Tsinghua University Beijing China. 《系统科学与系统工程学报(英文版)》2003,12(3):360-371
This paper investigates the impact of a secondary market, where retailers can buy and sell excessinventories, on the supply chain. We develop a two-period model with a single manufacturer and tworetailers. At the beginning of the first period the retailers order and receive products from themanufacturer, but at the beginning of the second period, they can trade surplus products betweenthemselves in the secondary market. We investigate the impact of the correlated dependence ofretailers' demand on both the quantity effect and the allocation effect under the secondary market.Lastly,we study potential strategies for the manufacturer to increase sales with the existence of thesecondary market. 相似文献