促红细胞生成素B螺旋表面肽的代谢稳定性结构修饰：设计、合成及其提高的肾保护作用

肾脏缺血缺氧以及再灌注过程都将导致肾小管上皮细胞凋亡,使肾功能严重受损.肾脏的缺血再灌注损伤是移植肾功能延迟恢复的主要原因并能诱导急慢性排斥,影响肾存活率.近年来发现,衍生于促红细胞生成素（EPO）的B螺旋亚基亲水表面序列的肽链（HBSP）,对肾脏缺血再灌注损伤具有显著的保护作用,但其在体内极短的半衰期（约2min）极大地限制了它的临床应用.因此,本研究采用构象约束、全D-构型氨基酸替换和N-端封闭策略,设计了3种类型的EPOB螺旋表面肽衍生物,旨在提高其代谢稳定性环肽的设计采用了对氧化还原稳定的硫醚键和相对刚性的亚砜键两种环合方式.在多肽的合成上,采用微波辅助多肽自动合成和手工合成两种模式有机结合;优化了硫醚环合工艺,应用微波加热进行硫醚环肽的合成,大大提高了产率和效率;利用圆二色（CD）谱确定了亚砜环肽的相对构型.活性实验表明,相对于线性母肽HBSP,本文设计合成的代谢稳定衍生肽对大/小鼠肾脏缺血再灌注损伤均有显著提高的保护作用,且硫醚和R-构型亚砜环肽的肾脏保护活性强于S-构型亚砜环肽.而且,环化确实提高了功能肽的血浆稳定性.因此,本文合成的硫醚环肽一周一次注射剂量等效于线性肽HBSP一日三次剂量对小鼠肾损伤的保护作用.     

临界点二级相变的有限时间热力学逼近

应用内可逆卡诺循环的方法,导出了各种物质在临界点附近可逆与不可逆二级相变普遍适用的比热跃变公式以及广义的爱伦菲斯特方程。对简单(P,V,T)系统、超导、电介质顺电一铁电二级相变进行了应用讨论。     

Pharmaceutical performance of solid dispersions containing poly(ethylene) glycol 6000 and diazepam or temazepamInfluence of grinding

The effect of grinding on the physical properties and pharmaceutical performance of solid dispersions made of poly(ethylene) glycol 6000 (PEG6000) and temazepam or diazepam was studied using differential scanning calorimetry (DSC), X-ray powder diffraction and dissolution experiments. DSC-analysis of flash-cooled dispersions revealed that amorphous PEG present immediately after grinding crystallised upon aging mainly into the twice folded modification and to a small extent into the extended form. DSC-analysis of dispersions kept in the slab form for 1 month and subsequently ground, revealed that in the abscence of the grinding impulse crystallisation of PEG6000 takes place in the same way as in dispersions ground immediately after preparation and then aged for 1 month. Grinding solid dispersions immediately after preparation resulted in superior dissolution properties compared with solid dispersions kept in the monolith-slab form and subsequently ground. This difference in dissolution properties was found to be attributed to the drug and not to the polymer, more precisely, it was suggested that the drug particle size in ground dispersions was smaller than in dispersions kept in the slab form and subsequently ground. These findings suggest that grinding of solid dispersions immediately after preparation is the preparation method of choice instead of liquid filling of hard gelatin capsules resulting in monoliths. This revised version was published online in July 2006 with corrections to the Cover Date.     

基于波动模态耦合的铝电解槽磁流体稳定性傅立叶级数法分析

铝电解槽内磁流体稳定性对铝电解生产有重要影响。本文结合铝电解槽实体仿真的电磁场计算结果,应用傅立叶级数法对槽内磁流体波动稳定性进行数值计算,并对波动的模态耦合问题进行了重点分析。在此基础上,本文以某320kA铝电解槽为研究载体分析了槽长宽比设计对磁流体稳定性的影响,结果表明:波动的不稳定分量集中分布在频谱图中重力波模态密集的低频区域;不考虑母线对体系的影响,增大槽的长宽比,有利于提高磁流体的稳定性。     

Machine Learning Approaches for Metalloproteins

Metalloproteins are a family of proteins characterized by metal ion binding, whereby the presence of these ions confers key catalytic and ligand-binding properties. Due to their ubiquity among biological systems, researchers have made immense efforts to predict the structural and functional roles of metalloproteins. Ultimately, having a comprehensive understanding of metalloproteins will lead to tangible applications, such as designing potent inhibitors in drug discovery. Recently, there has been an acceleration in the number of studies applying machine learning to predict metalloprotein properties, primarily driven by the advent of more sophisticated machine learning algorithms. This review covers how machine learning tools have consolidated and expanded our comprehension of various aspects of metalloproteins (structure, function, stability, ligand-binding interactions, and inhibitors). Future avenues of exploration are also discussed.     

Pole placement controllers for linear time-delay systems with commensurate point delays

This paper investigates the exact and approximate spectrum assignment properties associated with realizable output-feedback pole-placement type controllers for single-input single-output linear time-invariant time-delay systems with commensurate point delays. The controller synthesis problem is discussed through the solvability of a set of coupled diophantine equations of polynomials. An extra complexity is incorporated to the above design to cancel extra unsuitable dynamics being generated when solving the above diophantine equations. Thus, the complete controller tracks any arbitrary prefixed (either finite or delaydependent) closed-loop spectrum. However, if the controller is simplified by deleting the above mentioned extra complexity, then the robust stability and approximated spectrum assignment are still achievable for a certain sufficiently small amount of delayed dynamics. Finally, the approximate spectrum assignment and robust stability problems are revisited under plant disturbances if the nominal controller is maintained. In the current approach, the finite spectrum assignment is only considered as a particular case to the designer‘s choice of a (delay-dependent) arbitrary spectrum assignment objective.     

ATTRACTIVITY PROPERTIES OF SOLUTIONS FOR DEGENERATE QUASILINEAR PARABOLIC EQUATIONS OF HIGHER ORDER

1IntroductionIn[1]theexistence0fweaksoluti0ns0fdegeneratequasilinearparabolicinitialboundaryvaluepr0blemonthespaceXT=Lp(O,T;V)hasbeenpr0ved,whereQT=(O,T)xfl,V=W:"(v,fl),whichisaweightedS0b0levspace.Thedegenerati0nisdeterminedbyavectorfunctionv(x)=(v.(x)),IaI=m,withp0sitivec0mponentsv.(x)inflsatisfyingcertainintegrabilityassumptions.Theaim0fthispaperistosh0wsomeattractivitypr0perties0ftheso1ution(ast-oo).Similarresultsf0rparab0licequati0nscanbefounde-g.in[2],[3].Letflbeab0unded0pensubset…     

Nonnormality and stochastic differential equations

A highly nonnormal Jacobian may give rise to large transients. This behaviour has been shown to have implications for (a) the relevance of linearising a nonlinear system and (b) the timestep restrictions required to keep a numerical method stable. Here, we show that nonnormality also manifests itself for stochastic differential equations. We give an example of a family of systems that is stable without noise, but can be made exponentially unstable in mean-square by a noise perturbation that shrinks to zero as the nonnormality increases. We then show via finite-time convergence theory that an Euler approximation shares the same property, giving a discrete analogue of the result. In memory of Germund Dahlquist (1925–2005).AMS subject classification (2000) 65C30, 34F05     

Stability analysis of nonautonomous difference systems with delaying arguments

We present sufficient conditions for the stability of the nonautonomous difference system , k∈Z⁺, with m?1, when the (n×n)-matrices Aj(⋅) are slowly varying coefficients. The proposed approach is based on the generalization of the “freezing” method for ordinary differential equations. The stability conditions are formulated in terms of the corresponding Cauchy's function.     

关于一类四阶非线性系统李雅普诺夫函数构造的研究

本文导出了四维线性系统的李雅普诺夫函数公式,研究了一类四阶非线性系统平凡解的稳定性。