Genomic alterations in cultured human embryonic stem cells

Cultured human embryonic stem cell (hESC) lines are an invaluable resource because they provide a uniform and stable genetic system for functional analyses and therapeutic applications. Nevertheless, these dividing cells, like other cells, probably undergo spontaneous mutation at a rate of 10(-9) per nucleotide. Because each mutant has only a few progeny, the overall biological properties of the cell culture are not altered unless a mutation provides a survival or growth advantage. Clonal evolution that leads to emergence of a dominant mutant genotype may potentially affect cellular phenotype as well. We assessed the genomic fidelity of paired early- and late-passage hESC lines in the course of tissue culture. Relative to early-passage lines, eight of nine late-passage hESC lines had one or more genomic alterations commonly observed in human cancers, including aberrations in copy number (45%), mitochondrial DNA sequence (22%) and gene promoter methylation (90%), although the latter was essentially restricted to 2 of 14 promoters examined. The observation that hESC lines maintained in vitro develop genetic and epigenetic alterations implies that periodic monitoring of these lines will be required before they are used in in vivo applications and that some late-passage hESC lines may be unusable for therapeutic purposes.     

Chemical communication: chirality in elephant pheromones

Musth in male elephants is an annual period of heightened sexual activity and aggression that is linked to physical, sexual and social maturation. It is mediated by the release of chemical signals such as the pheromone frontalin, which exists in two chiral forms (molecular mirror images, or enantiomers). Here we show that enantiomers of frontalin are released by Asian elephants in a specific ratio that depends on the animal's age and stage of musth, and that different responses are elicited in male and female conspecifics when the ratio alters. This precise control of communication by molecular chirality offers insight into societal interactions in elephants, and may be useful in implementing new conservation protocols.     

重载列车装车地货流集中与装运方式问题探讨

针对铁路重载列车运输组织的装运作业环节，从产运总体角度出发，研究适应和配合干线的重载运输。为提高重载列车装运作业效率运用系统观点及技术经济分析等理论，并通过计算模拟分析，对有关重载列车装车地货物集运及其装车方式的选择等问题进行一些初步分析和探讨，提出有关结论和建议。     

可锻铸铁退火工艺的现状和发展

本文综述了我国可锻铸铁的生产状况和国内可锻铸铁生产中的各种退火新工艺,并重点介绍了盐浴加热快速退火新工艺以及它的配套措施。对可锻铸铁的退火工艺的发展方向及配套措施提出了自己的看法。     

The landscape of cancer genes and mutational processes in breast cancer

All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.     

有限算子值框架

本文研究了有限算子值框架的相似性和对偶性,并证明了在信息传输过程中,当丢失一个数据包时,等范数Parseval算子值框架是最优的．     

基于优化检测网络和MLP特征改进发音错误检测的方法

该文基于优化的检测网络和多层感知(multi-layerperception,MLP)特征,提出一种可以更加准确地检测出错误发音类型的方法。首先,从第二语言学习的语音库中提取出基本的发音规则以及组合的发音规则,并相应地计算它们发生的先验概率,再将这些具有先验概率的规则用于构建基于多发音的扩展检测网络。然后在检测过程中,引入基于发音特征的MLP特征来描述发音概率,替代了传统的语音声学特征。最后使用基于MLP特征的GMM-HMM框架从检测网络中识别出最可能的发音音素串。实验表明:该方法将音素识别正确率提高了3.11%,错误类型准确率提高了7.42%。     

基于吡咯环系的新型c-Met抑制剂的设计、合成与生物活性研究

基于Ⅱ型c-Met抑制剂的结合模式和骨架跃迁的策略,设计、合成了两类含吡咯环系的新型c-Met激酶抑制剂.目标化合物的结构经核磁共振氢谱、质谱和高效液相色谱予以确证.生化水平的活性筛选显示化合物9a～9c对c-Met激酶均表现出良好的抑制活性,IC50小于2.1μM;化合物9a还对VEGFR-2和c-kit等激酶均表现显示出良好的抑制活性,IC50小于8.0μM.细胞水平的活性测试进一步验证了化合物9a对c-Met靶点的抑制活性.已有结果表明,吡咯衍生物9a具有作为活性骨架开展后续改造的良好潜力.     

一类三层前向折线模糊神经网络的构造

为克服模糊数运算的复杂性引入了折线模糊数的概念,并应用其优良性质和折线模糊值函数的表示定理,通过插值神经网络的构造方法获得了一类三层前向折线模糊神经网络,证明了该折线模糊神经网络是连续折线模糊值函数的泛逼近器.