Exome sequencing of liver fluke-associated cholangiocarcinoma

Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini-related CCA.     

Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer

Human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR frequently respond to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, but responses are not durable, as tumors acquire resistance. Secondary mutations in EGFR (such as T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR p.Thr790Met alteration or MET activation. Genetic or pharmacological inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to TKIs. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to EGFR TKIs in individuals with EGFR-mutant lung cancer.     

基于AFSA算法的掘进机外喷雾效率最高的参数优化设计

为了提高掘进工作面的降尘效率,通过对喷雾降尘机理的研究,分析了影响降尘效率的因素,建立了纵轴式掘进机外喷雾降尘效率的数学模型.以外喷雾降尘效率最高为优化目标,采用人工鱼群算法(AFSA)对喷雾压力、喷嘴和工作面的距离、喷嘴直径和喷嘴的雾化角进行了优化.优化的结果表明,在保证一定的雾流流量和一定的雾粒存活时间的条件下,喷雾的耗水量减少了3.48％,降尘效率增加了15.33％.该项研究对于合理设计掘进机外喷雾参数,提高喷雾降尘性能,改善掘进工作面环境等具有一定的指导作用和参考价值.     

CEP152 is a genome maintenance protein disrupted in Seckel syndrome

Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation.     

The genome of the extremophile crucifer Thellungiella parvula

Thellungiella parvula is related to Arabidopsis thaliana and is endemic to saline, resource-poor habitats, making it a model for the evolution of plant adaptation to extreme environments. Here we present the draft genome for this extremophile species. Exclusively by next generation sequencing, we obtained the de novo assembled genome in 1,496 gap-free contigs, closely approximating the estimated genome size of 140 Mb. We anchored these contigs to seven pseudo chromosomes without the use of maps. We show that short reads can be assembled to a near-complete chromosome level for a eukaryotic species lacking prior genetic information. The sequence identifies a number of tandem duplications that, by the nature of the duplicated genes, suggest a possible basis for T. parvula's extremophile lifestyle. Our results provide essential background for developing genomically influenced testable hypotheses for the evolution of environmental stress tolerance.     

压力传感器的硅玻静电键合

针对MEMS压力传感器封装关键技术,从结构仿真和工艺参数等方面研究了一款压力传感器的硅玻静电键合问题,旨在减小封接对压力传感器芯片输出性能的影响。设计并制作键合装置,进而完成实验,最终优化键合温度,电压等参数值,验证最佳温度350~C,理想电压范围500～900V。     

镐形截齿截割不同硬质岩石的随机载荷模拟

在假设截齿的截割阻力和牵引阻力服从Gamma分布、侧向力服从正态分布并考虑其相关性的条件下,运用随机过程理论通过MATLAB编程对其进行计算机模拟。结果表明,三向力随谱氏系数_厂呈剧增趋势;牵引阻力是栽荷最大峰值的最大分力。通过模拟,可单独研究某一参数对截齿截割性能的影响,从而部分地替代实验和工程实测,节省大量的实验费用。     

农田渍害遥感监测方法研究应用进展

首先介绍了农田渍害的表现特征;其次根据监测原理,将国内外农田溃害遥感监测的主要方法分为地表指示标志法、地下水位反演法和与非遥感方法相结合的综合分析法,并分别对各类方法的原理、技术、适用范围及优缺点进行分析,发现各种方法均能解决特定的农田渍害监测问题,同时也存在着缺陷和局限性;最后,进行了总结并指出了两种潜在的遥感监测方...     

东坪基岩气藏气水相对渗透率的确定方法

东坪基岩气藏储层岩性差异大,非均质性强.孔缝发育区岩石松散,无法钻取完整的岩芯,而致密带几乎不渗透,无法通过驱替实验获取相对渗透率曲线,这成为困扰气藏动态分析和开发指标计算的难题.基于水驱气藏物质平衡原理,建立了不依赖水侵量的储层含水饱和度计算方法,避免了水侵量计算方法中的不确定因素,提高了含水饱和度计算的准确性.建立...     

Al涂层/AZ91镁合金复合铸造界面的研究

对型芯预喷涂一层Al涂层,将AZ91镁合金液浇注到铸型中实现基体和涂层的结合,对凝固后的结合界面组织和相组成进行分析。结果表明,AZ91镁合金液和Al涂层表面的氧化物发生反应,实现了界面间的润湿,形成冶金结合界面。该界面包含3个扩散层:镁合金基体一侧为(Al₁₂Mg₁₇+δ_Mg)共晶组织;中间层为Al₁₂Mg₁₇金属间化合物;Al涂层一侧为Al₃Mg₂金属间化合物,并弥散分布着一些氧化物。试验结果证明,通过复合铸造的方法可以实现Al涂层和镁合金基体的冶金结合。