Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7

Microtubules have pivotal roles in fundamental cellular processes and are targets of antitubulin chemotherapeutics. Microtubule-targeted agents such as Taxol and vincristine are prescribed widely for various malignancies, including ovarian and breast adenocarcinomas, non-small-cell lung cancer, leukaemias and lymphomas. These agents arrest cells in mitosis and subsequently induce cell death through poorly defined mechanisms. The strategies that resistant tumour cells use to evade death induced by antitubulin agents are also unclear. Here we show that the pro-survival protein MCL1 (ref. 3) is a crucial regulator of apoptosis triggered by antitubulin chemotherapeutics. During mitotic arrest, MCL1 protein levels decline markedly, through a post-translational mechanism, potentiating cell death. Phosphorylation of MCL1 directs its interaction with the tumour-suppressor protein FBW7, which is the substrate-binding component of a ubiquitin ligase complex. The polyubiquitylation of MCL1 then targets it for proteasomal degradation. The degradation of MCL1 was blocked in patient-derived tumour cells that lacked FBW7 or had loss-of-function mutations in FBW7, conferring resistance to antitubulin agents and promoting chemotherapeutic-induced polyploidy. Additionally, primary tumour samples were enriched for FBW7 inactivation and elevated MCL1 levels, underscoring the prominent roles of these proteins in oncogenesis. Our findings suggest that profiling the FBW7 and MCL1 status of tumours, in terms of protein levels, messenger RNA levels and genetic status, could be useful to predict the response of patients to antitubulin chemotherapeutics.     

老采区及地表残余变形对建筑物的影响

浅部开采条件下地表残余变形分析是岩层移动领域的一个棘手问题．通过老采空区影响下地表残余变形和地基承载能力变化对地面新建建筑物的影响分析,提出了老采区上方新建建筑物地基稳定性计算公式、岩层移动参数、评价方法．应用鹤岗市和谐花园小区建筑物实例进行了验证．     

循环码周期分布的反问题

研究循环码周期分布的反问题,即对于给定的正整数ｎ和非负整数序列,是否存在Ｆｑ上的某个〔ｎ,ｋ〕－循环码,使得其周期分布恰好为（Ａ１,Ａ２,．．．Ａｎ）。     

Effects of Ru on microstructure stability and mechanical properties of Ni3Al single crystal alloy

The effect of Ru on microstructure stability and stress rupture properties of a Ni3Al single-crystal alloy was investigated. The experimental results showed that the addition of 2% Ru (mass fraction) improved the microstructure stability due to the res traint of harmful Y-NiMo phase formation during the thermal exposure at the high temperature above 1 000 °C. And the reason may be that the addition of Ru increased the degree of Mo supersaturation in both γ and γ′ phases, and hence suppressed the precipitation of Y-NiMo phase. The results of stress rupture tests under the testing condition of 1 100 °C, 120 MPa showed that the addition of 2% Ru in the alloy improved the stress rupture lives significantly for ther mal exposed samples. The improvement of the stress rupture properties may be attributed to the restraint of Y-NiMo phase precipitation and growth by the addition of the proper amount Ru.     

天文大气折射与映射函数的数值模拟

为了研究天文大气折射与中性大气折射延迟之间的内在联系,利用天文大气折射表的表列数据对大气折射延迟的映射函数进行了数值模拟.计算结果表明,用天文大气折射测定值模拟映射函数是可行的;同时也表明,映射函数的形式是次要的,随着连分式项数的增加可以提高模拟的精度.该结论对于改善大气折射数据处理的归算精度,降低仪器的观测截止角,和提高仪器的使用效应具有一定的参考价值和指导意义.     

重轨表面缺陷机器视觉检测的关键技术

针对重轨生产线中重轨表面缺陷在线检测的困难,提出了基于机器视觉检测的系列关键技术,包括缺陷成像机理、多CCD组合采集器、图像处理技术、基于多空间的缺陷参数提取等.通过图像校正、基于支持向量机(SVM)的直线(面)边缘搜索算法和缺陷特征参数提取等核心技术,可获得完整的重轨全表面的图像,其提纯的缺陷特征参数可以进行模式识别.实验验证表明,采用上述关键技术对重轨表面常见的缺陷识别,正确率在80%以上,达到了工程检测的需要.