Transmission of allosteric effects in DNA.

Binding of distamycin induces a cooperative transition of calf thymus DNA to a new form with higher affinity for the drug and altered structural properties.     

A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK

In metazoans, the Ras-Raf-MEK (mitogen-activated protein-kinase kinase)-ERK (extracellular signal-regulated kinase) signalling pathway relays extracellular stimuli to elicit changes in cellular function and gene expression. Aberrant activation of this pathway through oncogenic mutations is responsible for a large proportion of human cancer. Kinase suppressor of Ras (KSR) functions as an essential scaffolding protein to coordinate the assembly of Raf-MEK-ERK complexes. Here we integrate structural and biochemical studies to understand how KSR promotes stimulatory Raf phosphorylation of MEK (refs 6, 7). We show, from the crystal structure of the kinase domain of human KSR2 (KSR2(KD)) in complex with rabbit MEK1, that interactions between KSR2(KD) and MEK1 are mediated by their respective activation segments and C-lobe αG helices. Analogous to BRAF (refs 8, 9), KSR2 self-associates through a side-to-side interface involving Arg?718, a residue identified in a genetic screen as a suppressor of Ras signalling. ATP is bound to the KSR2(KD) catalytic site, and we demonstrate KSR2 kinase activity towards MEK1 by in vitro assays and chemical genetics. In the KSR2(KD)-MEK1 complex, the activation segments of both kinases are mutually constrained, and KSR2 adopts an inactive conformation. BRAF allosterically stimulates the kinase activity of KSR2, which is dependent on formation of a side-to-side KSR2-BRAF heterodimer. Furthermore, KSR2-BRAF heterodimerization results in an increase of BRAF-induced MEK phosphorylation via the KSR2-mediated relay of a signal from BRAF to release the activation segment of MEK for phosphorylation. We propose that KSR interacts with a regulatory Raf molecule in cis to induce a conformational switch of MEK, facilitating MEK's phosphorylation by a separate catalytic Raf molecule in trans.     

A structural basis for allosteric control of DNA recombination by lambda integrase

Site-specific DNA recombination is important for basic cellular functions including viral integration, control of gene expression, production of genetic diversity and segregation of newly replicated chromosomes, and is used by bacteriophage lambda to integrate or excise its genome into and out of the host chromosome. lambda recombination is carried out by the bacteriophage-encoded integrase protein (lambda-int) together with accessory DNA sites and associated bending proteins that allow regulation in response to cell physiology. Here we report the crystal structures of lambda-int in higher-order complexes with substrates and regulatory DNAs representing different intermediates along the reaction pathway. The structures show how the simultaneous binding of two separate domains of lambda-int to DNA facilitates synapsis and can specify the order of DNA strand cleavage and exchange. An intertwined layer of amino-terminal domains bound to accessory (arm) DNAs shapes the recombination complex in a way that suggests how arm binding shifts the reaction equilibrium in favour of recombinant products.     

海冰的粘性效应及模型理论

在实验的基础上对海冰的粘性效应及非线性特性进行了分析，并求出了对应常应变（ε＝０．１％）和常应力情况下的非线性因子．在理论分析方面，应用非线性粘弹性记忆衰退理论建立了积分型的本构方程；对线性Ｂｕｒｇｅｒｓ模型进行修正，建立了以应变表示的非线性微分型的本构方程，通过了实验验证，理论计算结果与实验曲线有较好吻合．     

The allosteric transition of glycogen phosphorylase

The crystal structure of R-state glycogen phosphorylase b has been determined at 2.9 A resolution. A comparison of T-state and R-state structures of the enzyme explains its cooperative behaviour on ligand binding and the allosteric regulation of its activity. Communication between catalytic sites of the dimer is provided by a change in packing geometry of two helices linking each site with the subunit interface. Activation by AMP or by phosphorylation results in a quaternary conformational change that switches these two helices into the R-state conformation.     

Observation of ligand effects during alkene hydrogenation catalysed by supported metal clusters

Homogeneous organometallic catalysts and many enzymes activate reactants through coordination to metal atoms; that is, the reactants are turned into ligands and their reactivity controlled through other ligands in the metal's coordination sphere. In the case of supported metal clusters, catalytic performance is influenced by the support and by adsorbed reactants, intermediates or products. The adsorbates are usually treated as ligands, whereas the influence of the supports is usually ascribed to electronic interactions, even though metal clusters supported on oxides and zeolites form chemical bonds to support oxygen atoms. Here we report direct observations of the structure of supported metal clusters consisting of four iridium atoms, and the identification of hydrocarbon ligands bound to them during propene hydrogenation. We find that propene and molecular hydrogen form propylidyne and hydride ligands, respectively, whereas simultaneous exposure of the reactants to the supported iridium cluster yields ligands that are reactive intermediates during the catalytic propane-formation reaction. These intermediates weaken the bonding within the tetrahedral iridium cluster and the interactions between the cluster and the support, while replacement of the MgO support with gamma-Al2O3 boosts the catalytic activity tenfold, by affecting the bonding between the reactant-derived ligands and the cluster and therefore also the abundance of individual ligands. This interplay between the support and the reactant-derived ligands, whereby each influences the interaction of the metal cluster with the other, shows that the catalytic properties of supported metal catalysts can be tuned by careful choice of their supports.     

二次引力理论中整体磁单极的引力效应

在二次引力理论F＝根号－g(R αR2），（aR＜＜1）中，研究整体磁单极的引力场，与爱因斯坦引力理论的结果相比较，其度规获得了一个相当于长程牛顿势的修正，表明在远处有一高阶的吸引力，在此基础上探讨了整体磁单极的引力效应，即运动粒子在经过整体磁单极附近时的偏折，其偏转角表现为整体磁单极空间的亏损角，负有效质量的二次引力项（耦合常数a)的效应。     

Structural basis of the allosteric behaviour of phosphofructokinase

Comparison between the crystal structures of low- and high-affinity forms of phosphofructokinase shows a close coupling between the change of quaternary structure and local changes triggered by binding of the allosteric effectors. These concerted changes link all the substrate and effector sites in the tetramer, and explain the change of affinity for the cooperative substrate.     

概率论基本部分与模糊集合理论的统一定义

提出一个概率论的基本部分与模糊集合理论的统一理论,称为W-理论．它可以解释为概率论,也可以解释为新模糊集合理论（称做P-模糊集合理论,它与C-模糊集合理论等价）,而Zadeh-模糊集合理论是新模糊集合理论的一个有三个缺点和两个错误的子系统．这里,模糊集合对应于（带概率的）事件,隶属度对应干概率,关系系数对应于条件概率,等等．模糊集合之间关系与概率论的事件之间关系一样,不仅有不相交,非一致包含,相交而不非一致包含,而且还有相互独立,等等．新模糊集合理论与概率论的基本部分是同构的．     

关于人体经络的一个试探性观点

在考察针刺穴位治疗作用的基础上，根据现有的实验事实，将人体经络的观念和经改进后的神经-内分泌-免疫系统的观念统一起来，提出人体经络是具有敏感节点和功能连接的神经-内分泌-免疫网络的假说。人体经络的复杂网络不仅是遍及全身的系统，而且可以通过敏感节点及其功能连接对身体起调控作用。