A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors

Heat shock protein 90 (Hsp90) is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signalling proteins, including HER-2/ErbB2, Akt, Raf-1, Bcr-Abl and mutated p53. Hsp90 inhibitors bind to Hsp90, and induce the proteasomal degradation of Hsp90 client proteins. Although Hsp90 is highly expressed in most cells, Hsp90 inhibitors selectively kill cancer cells compared to normal cells, and the Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG) is currently in phase I clinical trials. However, the molecular basis of the tumour selectivity of Hsp90 inhibitors is unknown. Here we report that Hsp90 derived from tumour cells has a 100-fold higher binding affinity for 17-AAG than does Hsp90 from normal cells. Tumour Hsp90 is present entirely in multi-chaperone complexes with high ATPase activity, whereas Hsp90 from normal tissues is in a latent, uncomplexed state. In vitro reconstitution of chaperone complexes with Hsp90 resulted in increased binding affinity to 17-AAG, and increased ATPase activity. These results suggest that tumour cells contain Hsp90 complexes in an activated, high-affinity conformation that facilitates malignant progression, and that may represent a unique target for cancer therapeutics.     

Lateral gene transfer and the nature of bacterial innovation

Unlike eukaryotes, which evolve principally through the modification of existing genetic information, bacteria have obtained a significant proportion of their genetic diversity through the acquisition of sequences from distantly related organisms. Horizontal gene transfer produces extremely dynamic genomes in which substantial amounts of DNA are introduced into and deleted from the chromosome. These lateral transfers have effectively changed the ecological and pathogenic character of bacterial species.     

影响铸造涂料工艺性能的因素分析

通过正交实验研究，测试了铸造涂料的碾压工艺、原材料以及原材料的处理工艺对涂料的悬浮性、表面强度、发气量等主要工艺性能的影响。结果表明：当选用轮碾机制作铸造涂料时，碾压时间达到１．５小时即可满足工艺性能的要求；涂料中无论是粘结剂还是悬浮剂的增加均会大幅度提高涂料的表面强度和悬浮性。     

一种基于CMAC网络的自学习控制器

通过分析了ＣＭＡＣ神经网络的学习机制和连续搅拌反应釜的结构，提出了一种自动选择学习率的ＣＭＡＣ自学习控制方法。给出了自学习控制器的结构和算法，并以连续搅拌反应釜模型为对象进行了仿真研究，这种网络每次学习少量参数，算法简单，仿真结果表明所提出的控制器优于传统的ＰＩＤ控制器。     

Sn—Pb／Cu润湿性测试分析研究

介绍了利用图象处理技术研究了Ｓｎ－Ｐｂ合金钱民铜润湿性的方法，提出了联机的图象特征提出算法和润湿参数求取算法，给出了Ｓｎ－Ｐｂ／Ｃｕ润湿特性在直流电影响下测试分析结果。     

Some relationships between water fertility and egg production in brown trout ( Salmo trutta ) from Montana streams

Relationships between water fertility (as measured by conductivity and alkalinity) of 17 Montana streams and the attainment of sexual maturity and fecundity of their resident female brown trout were studied. Fish from the streams having conductivity and alkalinity levels greater than 100 micromhos / cm and ppm CaCO 3 , respectively, were younger at sexual maturity than fish from waters with lower levels. The attainment of earlier sexual maturity in fish from the former streams could not be completely explained on the basis of greater growth rates. Fish from the stream having the highest levels of conductivity had the slowest growth rate but became sexually mature at the youngest age. A positive relationship was found between chemical fertility of streams and the fecundity of their fish. However, in the stream having the highest levels of conductivity, fish were the least fecund. It was concluded that the chemical fertility of these streams is generally related to the age at sexual maturity and fecundity of fish.       

Biotic and abiotic factors influencing the distribution of Coleogyne communities in southern Nevada

Woody plant community composition was analyzed throughout the range of Coleogyne ramosissima in the Spring and Sheep Mountain ranges of southern Nevada. The lower Coleogyne elevational boundary was analyzed in detail in Lucky Strike Canyon, on the eastern edge of the Spring Mountains. TWINSPAN (2-way indicator species analysis) identified 4 primary species and stand groups from the 2 mountain ranges (extensive survey). Analysis of DECORANA (detrended correspondence analysis) results indicated that elevation and soil depth were the environmental factors most significantly associated with distribution of species and stand groups in the extensive survey. Elevation was the only significant physical factor associated with distribution of species and stand groups in the intensive survey. Five vegetation zones form the 2 mountain ranges were identified based on their dominant species in 15 extensive transects. Coleogyne were subdivided into pure stands and upper and lower ecotones for further investigation of species distribution and environmental factors. Selected environmental factors appear to play an important role in structuring the Mojave Desert vegetation zones in southern Nevada.     

宇宙学与战略"大思维"

宇宙学在近当代获得了长足发展,而这一发展正是孕育于强大而极富创造性的思维母体。从一般系统理论的角度来说,公司或政府机构等大型商业或政治组织的领导人可以利用宇宙学及其思维方法,进行战略性“大思维”,从而做出正确的决策。在本文中,作者不仅对宇宙学的具体理论和原则进行了归纳总结,而且还提出具体实例,以为这些领导人运用宇宙学进行战略高度的“大思维”提供佐证,从而进一步证明,“大思维”对于在复杂的现代组织中取得成功具有重要意义。