The patterns and dynamics of genomic instability in metastatic pancreatic cancer

Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97-98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations, but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours, including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites, and how the tumour disseminates. Here we harness advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2-M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection.     

Plasma devices to guide and collimate a high density of MeV electrons

The development of ultra-intense lasers has facilitated new studies in laboratory astrophysics and high-density nuclear science, including laser fusion. Such research relies on the efficient generation of enormous numbers of high-energy charged particles. For example, laser-matter interactions at petawatt (10(15) W) power levels can create pulses of MeV electrons with current densities as large as 10(12) A cm(-2). However, the divergence of these particle beams usually reduces the current density to a few times 10(6) A cm(-2) at distances of the order of centimetres from the source. The invention of devices that can direct such intense, pulsed energetic beams will revolutionize their applications. Here we report high-conductivity devices consisting of transient plasmas that increase the energy density of MeV electrons generated in laser-matter interactions by more than one order of magnitude. A plasma fibre created on a hollow-cone target guides and collimates electrons in a manner akin to the control of light by an optical fibre and collimator. Such plasma devices hold promise for applications using high energy-density particles and should trigger growth in charged particle optics.     

壮药“国虾薄”（绞股蓝）碱水解产物对A549细胞的抑制活性

本文比较了绞股蓝（Gynostemma pentaphyllum）碱水解前后的正丁醇提取物对肺癌A549细胞的抑制活性.方法：绞股蓝叶用12倍量的80％乙醇超声提取3h,正丁醇萃取,90 ℃碱水解反应6h,利用HPLC分析方法,分析了绞股蓝碱水解前后的正丁醇提取物中色谱峰的变化,并对它们进行肺癌A549细胞的抑制活性检测.结果发现碱水解使绞股蓝中的成分有转化,而且绞股蓝的碱水解产物对肺癌A549细胞的抑制活性显著增强.从而证实,碱水解可使绞股蓝成分发生转化,并且增强了对肺癌A549细胞的抑制活性,为绞股蓝有效成分的转化提供实验依据.     

溪洛渡水电站出线竖井整体式滑模混凝土施工技术

本出线竖井类属于大直径开挖断面,其衬砌结构体型复杂,大井内被中隔墙分隔为7个小井,通过整体式滑模施工技术的设计与运用,实现了多个联体仓位同步滑升,确保了结构的整体性,具有施工速度快、机械化运用程度高、省掉支模和搭设脚手架施工工序等优势,大幅度降低了施工难度,显著提高了施工工效。     

Patterns of somatic mutation in human cancer genomes

Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.     

企业能力对企业技术市场进入时机选择的影响

企业技术市场进入时机选择是企业发展过程中的重要决策之一。在分析企业能力的基础上,从创新能力和运营能力两方面构建了企业技术市场进入时机选择的矩阵模型,基于该模型对企业的技术市场进入时机选择的问题进行了研究。分别讨论了企业在不同创新能力和运营能力组合情况下,企业可采取的技术市场进入战略。     

Conservation of hotspots for recombination in low-copy repeats associated with the NF1 microdeletion

Several large-scale studies of human genetic variation have provided insights into processes such as recombination that have shaped human diversity. However, regions such as low-copy repeats (LCRs) have proven difficult to characterize, hindering efforts to understand the processes operating in these regions. We present a detailed study of genetic variation and underlying recombination processes in two copies of an LCR (NF1REPa and NF1REPc) on chromosome 17 involved in the generation of NF1 microdeletions and in a third copy (REP19) on chromosome 19 from which the others originated over 6.7 million years ago. We find evidence for shared hotspots of recombination among the LCRs. REP19 seems to contain hotspots in the same place as the nonallelic recombination hotspots in NF1REPa and NF1REPc. This apparent conservation of patterns of recombination hotspots in moderately diverged paralogous regions contrasts with recent evidence that these patterns are not conserved in less-diverged orthologous regions of chimpanzees.     

基于ReHo方法的原发性痛经静息态功能磁共振成像研究

目的利用静息态功能磁共振成像（rsfMRI,Resting．statefunctionalMagneticResonanceImaging）技术观察原发性痛经患者艾灸关元穴前后脑局部r致性（ReHo,RegionalHomogeneity）变化的特点,从脑区局部神经元协调性的角度探讨艾灸关元穴治疗原发性痛经的中枢镇痛机制。方法20例符合纳入标准的原发性痛经患者分别在艾灸关元穴前及艾灸关元穴5分钟后接受静息状态fMRI扫描,采用局部一致性方法作为测量指标进行数据分析。结果史灸后,患者多个与疼痛相关的脑区存在局部神经元活动的一致性的改变。艾灸后右侧颞上回一、左颞中回、额中回、中央前回、左侧额上回、右侧前扣带回皮质ReHo值较艾灸前显著升高（P〈0．05,校正后）;左额下回、枕叶、双侧丘脑ReHo值较艾灸前显著降低（P〈0．05,校正后）。结论艾灸关元穴可以引起多个疼痛脑区的局部一致性增高或降低,这些脑区可能是艾灸关元穴发挥镇痛作用的靶点,可能阐明了艾灸关元穴治疗原发性痛经的中枢镇痛机制。     

Interpreting principal component analyses of spatial population genetic variation

Nearly 30 years ago, Cavalli-Sforza et al. pioneered the use of principal component analysis (PCA) in population genetics and used PCA to produce maps summarizing human genetic variation across continental regions. They interpreted gradient and wave patterns in these maps as signatures of specific migration events. These interpretations have been controversial, but influential, and the use of PCA has become widespread in analysis of population genetics data. However, the behavior of PCA for genetic data showing continuous spatial variation, such as might exist within human continental groups, has been less well characterized. Here, we find that gradients and waves observed in Cavalli-Sforza et al.'s maps resemble sinusoidal mathematical artifacts that arise generally when PCA is applied to spatial data, implying that the patterns do not necessarily reflect specific migration events. Our findings aid interpretation of PCA results and suggest how PCA can help correct for continuous population structure in association studies.