A calcium sensor in the sodium channel modulates cardiac excitability.

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.     

基于Agent的农田生态细胞自动机模型

提出一种基于Agent的细胞自动机(CA)演化模型，并采用整体建模仿真的方法，对农田虫害的演化进行了模拟．它采用自底向上的建模思想，利用Agent的局部连接规则，建立复杂系统的整体模型．针对不同环境条件设定相应的仿真参数，可以得到恰当的害虫种群演化结果，有助于农田生态管理的科学决策．同时，农田虫害的管理是预测专家系统的重要应用领域，该模型与专家系统的最终集成，可以提高专家系统的预测能力．     

五台山滹沱群SHRIMP锆石U-Pb年龄: 华北克拉通早元古代拼合新证据

采自五台山台怀镇南8 km处滹沱群变质火山-沉积岩层中的长英质凝灰岩样品含有两组锆石, 所记录的SHRIMP锆石方法²⁰⁷Pb/²⁰⁶Pb年龄分别为2180±5 Ma和2087±9 Ma. 在误差范围内, 较老的一组年龄与五台山大洼梁花岗岩年龄相当, 表明它们来自相似的地壳岩浆源; 而较年轻的一组锆石年龄与相邻地区阜平杂岩湾子表壳岩中变沉积岩和变火山岩及南营花岗片麻岩年龄相当, 因而被解释为滹沱群火山作用年龄. 这两组年龄的存在表明: (1) 滹沱群形成于早元古代而非太古宙; (2) 早元古代火山-沉积作用在五台和阜平地区同时间发生. 这样, 早元古代沉积作用在该区是广泛的, 它们代表了华北克拉通东部陆块西侧大陆边缘相沉积. 滹沱群火山作用年龄的确定也表明该群所经历的变质-变形事件发生在2087±9 Ma 之后, 这进一步佐证我们最近根据其他方面研究结果所得出的吕梁造山事件(约1.8 Ga)是该区主要构造事件的结论: 该事件导致华北克拉通东部陆块和西部陆块的最终拼合, 并成为全球早-中元古代超级大陆组成部分之一.     

PTC124 targets genetic disorders caused by nonsense mutations

Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.     

两种消除Klebsiella pneumoniae重组型质粒的方法

对于工业发酵菌种肺炎克雷伯氏菌(Klebsiella pneumoniae),研究发现有两种消除其重组型质粒的有效方法,一种是连续传代培养,另一种是使用消除剂十二烷基硫酸钠(SDS)。对K.pneumoniae重组菌连续20代传代培养后,发现其质粒具有较高的消除率;而以0.2%SDS复合Ca2+处理K.pneumoniae重组菌,也能有效消除其重组型质粒,且该方法省却了反复的传代培养,能快速得到质粒消除菌,更具简便易操作性。消除了质粒的K.pneumoniae能再次接纳新的质粒,有效避免了因质粒不相容性带来的转化不成功,进而可用作宿主菌积累更多的生理性状。     

高位钻孔瓦斯抽采参数优化设计

基于采空区覆岩裂隙分布规律、覆岩裂隙瓦斯流动规律和高位钻孔抽采技术研究现状,从覆岩"竖三带"、"O"形圈和U型通风条件下采动裂隙瓦斯流动规律出发,找出高位钻孔的理论合理布置区域,指出工作面后方50m范围内覆岩裂隙发育状况是高位钻孔层位设计的关键,针对祁南煤矿32煤层的特点,结合现场采用数值模拟方法模拟不同开采速度条件下覆岩裂隙发育规律,优化设计高位钻孔的抽采参数,在34下2工作面和3410工作面的现场试验中,高位钻孔抽采浓度和抽采率得到大大提高,取得了较好的抽采效果,验证了研究的正确性。     

早-中元古代Columbia超级大陆研究进展

地球在过去25亿年里曾发生过几次全球性大规模碰撞造山事件（如 Grenville事件,Pan-African事件等）;地质学家由此推测大陆块自早元古代以来曾发生过周期性拼合和分离,从而导致古超级大陆的形成和裂解[1].在过去10年里（1991～2001年）,被认为由约1.0 Ga Grenville造山事件所形成的超级大陆Rodinia已成为古大陆重建的一个热点[2,3].然而,地质学家们在重建Rodinia 过程中发现,并非全部Rodinia组成陆块都是由Grenville造山带所焊接,而     

非线性映象的Mann迭代的收敛性与不动点

在可度量化拓扑线性空间中，讨论一些非线性映象的不动点与Mann迭代序列的收敛性问题，在一定条件下，得到了一些新的结果，推广和发展了Khan,Ghosh及Rhoades等人的工作。     

导出矩阵与基底的正交化

给出导出矩阵的概念并利用它将Ｒｎ中任意一组基底正交化     

导出矩阵与基底的正交化

给出导出矩阵的概念并利用它将Rn中任意一组基底正交化.