Interfering with the inhibitory mechanism of serpins: crystal structure of a complex formed between cleaved plasminogen activator inhibitor type 1 and a reactive-centre loop peptide

BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is an important endogenous regulator of the fibrinolytic system. Reduction of PAI-1 activity has been shown to enhance dissolution of blood clots. Like other serpins, PAI-1 binds covalently to a target serine protease, thereby irreversibly inactivating the enzyme. During this process the exposed reactive-centre loop of PAI-1 is believed to undergo a conformational change becoming inserted into beta sheet A of the serpin. Incubation with peptides from the reactive-centre loop transform serpins into a substrate for their target protease. It has been hypothesised that these peptides bind to beta sheet A, thereby hindering the conformational rearrangement leading to loop insertion and formation of the stable serpin-protease complex. RESULTS: We report here the 1.95 A X-ray crystal structure of a complex of a glycosylated mutant of PAI-1, PAI-1-ala335Glu, with two molecules of the inhibitory reactive-centre loop peptide N-Ac-TVASS-NH2. Both bound peptide molecules are located between beta strands 3A and 5A of the serpin. The binding kinetics of the peptide inhibitor to immobilised PAI-1-Ala335Glu, as monitored by surface plasmon resonance, is consistent with there being two different binding sites. CONCLUSIONS: This is the first reported crystal structure of a complex formed between a serpin and a serpin inhibitor. The localisation of the inhibitory peptide in the complex strongly supports the theory that molecules binding in the space between beta strands 3A and 5A of a serpin are able to prevent insertion of the reactive-centre loop into beta sheet A, thereby abolishing the ability of the serpin to irreversibly inactivate its target enzyme. The characterisation of the two binding sites for the peptide inhibitor provides a solid foundation for computer-aided design of novel, low molecular weight PAI-1 inhibitors.     

连续式棒线材轧机孔型系统的选择

论述了连续式棒线材轧机孔型系统的种类和特点，介绍了粗轧机组和中轧机组孔型系统的选择原则和方法。     

高温合金材料在铝电解工业中的应用探讨

对高温合金在铝电解工业用作惰性金属阳极材料的选择进行阐述，并就实际应用过程中的抗氧化耐腐蚀性进行探讨；阐述适用于铝电解工业的惰性阳极合金所应具备的必要条件和必须解决的问题，并介绍目前有关的研究动态和研究方向。     

紧凑 Tokamak(球形环)聚变堆第一壁及中心导体柱上中子负荷及核热计算与分析

采用通用蒙特卡罗粒子输运程序ＭＣＮＰ／３８计算低环径比Ｔｏｋａｍａｋ（紧凑环或球形环）聚变堆第一壁及中心导体上的中子壁负荷分布和核热沉积分布，并与常规Ｔｏｋａｍａｋ堆第一壁上中子壁负荷分布和核热沉积分布进行比较、分析。结果表明，在中子壁负荷归一化为１ＭＷ／ｍ２时，与常规Ｔｏｋａｍａｋ相比，在低环径比Ｔｏｋａｍａｋ堆第一壁及中心柱表面上中子壁负荷分布峰值并不比常规Ｔｏｋａｍａｋ堆第一壁上的峰值高，而且低于低环径比Ｔｏｋａｍａｋ堆整个第一壁上的平均值，而中心柱上的核热沉积峰值稍高于常规Ｔｏｋａｍａｋ堆第一壁上的核热沉积峰值，但对较高中子壁负荷情况，中心导体柱上的核热沉积和辐照损伤仍可能是比较严重和值得特别研究的问题。     

基于智能模糊控制策略的有源消声

有源消声是一种有效的低频噪声控制方法，由于空间有源消声过程具有时变性和非线性，传统的自适应算法不能进行很有效的控制。本文采用智能模糊控制策略，建立了基于智能模糊控制策略的有源消声系统，通过实验与传统自适应控制算法的消声效果作对比分析，证明智能模糊控制器不但控制速度快，易于实现，而且消声效果明显优于后者，具有较大的应用推广价值。     

激光熔覆用钴基合金粉末的研究

对激光熔覆用WFLC－11钴基合金粉末的激光熔覆工艺和熔覆层性能进行了研究，获得了WFLC－11钴基合金粉末激光熔覆层厚度与最小比能量关系曲线和熔覆层的组织、高温硬度等性能数据，为选择和使用WFLC－11钴基合金粉末提供了依据。     

High concentration erbium doping of silicon-rich SiO2 thin films on silicon

In this work, high concentration erbium doping in silicon-rich SiO₂ thin films is demonstrated. Si plus Er dual-implanted thermal SiO₂ thin films on Si substrates have been fabricated by using a new method, the metal vapor vacuum arc ion source implantation with relatively low ion energy, strong flux and very high dose. X-Ray photoelectron spectroscopy measurement shows that very high Er concentrations on the surfaces of the samples, corresponding to 10 at.% or the doping level of 10²¹ atoms cm⁻³, are achieved. This value is much higher than that obtained by using other fabrication methods such as the high-energy ion implantation and molecular beam epitaxy. Reflective high-energy electron diffraction, atomic force microscopy and cross-section high-resolution transmission electron microscopy observations show that the excess Si atoms in SiO₂ matrix accumulate to form Si clusters and then crystallize gradually into Si nanoparticles embedded in SiO₂ films during dual-ion implantation followed by rapid thermal annealing. Er segregation and precipitates are not formed. Photoluminescence at the wavelength of 1.54 μm exhibits very weak temperature dependence due to the introduction of Si nanocrystals into the SiO₂ matrix. The 1.54-μm light emission signals from annealed samples decrease by less than a factor of 2 when the measuring temperature increases from 77 K to room temperature.     

月光之丽、变彩之奇的月光石

根据所藏月光石的光薄片鉴定研究，阐述了月光石的美学特征和产生原因。介绍了月光石的产出特征和相应的月光石文化，同时介绍了我国关于“和氏壁”属性与月光石关系的研究历史及现状。