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.     

Extended megadroughts in the southwestern United States during Pleistocene interglacials

The potential for increased drought frequency and severity linked to anthropogenic climate change in the semi-arid regions of the southwestern United States (US) is a serious concern. Multi-year droughts during the instrumental period and decadal-length droughts of the past two millennia were shorter and climatically different from the future permanent, 'dust-bowl-like' megadrought conditions, lasting decades to a century, that are predicted as a consequence of warming. So far, it has been unclear whether or not such megadroughts occurred in the southwestern US, and, if so, with what regularity and intensity. Here we show that periods of aridity lasting centuries to millennia occurred in the southwestern US during mid-Pleistocene interglacials. Using molecular palaeotemperature proxies to reconstruct the mean annual temperature (MAT) in mid-Pleistocene lacustrine sediment from the Valles Caldera, New Mexico, we found that the driest conditions occurred during the warmest phases of interglacials, when the MAT was comparable to or higher than the modern MAT. A collapse of drought-tolerant C(4) plant communities during these warm, dry intervals indicates a significant reduction in summer precipitation, possibly in response to a poleward migration of the subtropical dry zone. Three MAT cycles ～2?°C in amplitude occurred within Marine Isotope Stage (MIS) 11 and seem to correspond to the muted precessional cycles within this interglacial. In comparison with MIS 11, MIS 13 experienced higher precessional-cycle amplitudes, larger variations in MAT (4-6?°C) and a longer period of extended warmth, suggesting that local insolation variations were important to interglacial climatic variability in the southwestern US. Comparison of the early MIS 11 climate record with the Holocene record shows many similarities and implies that, in the absence of anthropogenic forcing, the region should be entering a cooler and wetter phase.     

蔗渣浆纤维模塑装饰建筑材料的制备与性能

以天然蔗渣浆纤维为原料,利用模塑热压工艺复合成形,得到物理性能优良的纤维模塑装饰建筑材料.借助拉伸性能测试、热重分析、FT-IR等研究了影响该材料力学性能的因素.研究表明:该材料的拉伸性能主要受增强剂和阻燃剂添加量,干燥温度、时间和压力的影响;随着阻燃剂添加量的增加,材料的拉伸性能明显降低;最佳干燥温度为160℃,干燥...     

Skin collagen fiber-based radar absorbing materials

By using skin collagen fiber (CF) as raw material,Schiff base structure containing CF (Sa-CF) was synthesized through CF-salicylaldehyde reaction.Then a novel radar absorbing material (Fe-Sa-CF) was prepared by chelating reaction between Sa-CF and Fe 3+.The coaxial transmission and reflection method was used to analyze the complex permittivity and complex magnetic permeability of these CF-based materials,and the radar cross section (RCS) method was used to investigate their radar absorbing properties in the frequency range of 1.0-18.0 GHz.Experimental results indicated that the conductivity of CF increased from initial 1.08×10-11 to 2.86×10-6 S/cm after being transferred into Fe-Sa-CF,and its dielectric loss tangent (tanδ) in the frequency range of 1.0-17.0 GHz also increased.These facts suggest that the Fe-Sa-CF is electric-loss type radar absorbing material.In the frequency range of 3.0-18.0 GHz,Sa-CF (1.0 mm in thickness) exhibited somewhat radar absorbing property with maximum radar reflection loss (RL) of-4.73 dB.As for Fe-Sa-CF,the absorbing bandwidth was broadened,and the absorbing intensity significantly increased in the frequency range of 1.0-18.0 GHz where a maximum radar RL of-9.23 dB was observed.In addition,the radar absorbing intensity of Fe-Sa-CF can be further improved by increasing membrane thickness.When the thickness reached to 2.0 mm,the RL values of Fe-Sa-CF were-15.0-18.0 dB in the frequency range of 7.0-18.0 GHz.Consequently,a kind of novel radar absorbing material can be prepared by chemical modification of collagen fiber,which is characterized by thin thickness,low density,broad absorption bandwidth and high absorption intensity.     

9,10-环二氧-9,10-二(双苯基氧膦)蒽的合成及其晶体结构

化合物[(C14H8O2(PO(C6H5)2)2)]·H2O(Ⅱ)是9,10-二(双苯基膦)蒽(Ⅰ)在苯乙炔汞存在下,以乙腈为溶剂与空气中的氧气反应得到的一个化合物.用x-单晶衍射仪对该化合物的晶体结构进行了表征,结果表明,该化合物属于单斜晶系C2/c空间群,其结构参数为:a=28.908(4)(A),b=11.768...     

包络分析在超宽带信号采集中的应用

室内环境下超宽带信号具有丰富的多径分量,在时域中这些分量表现出簇（cluster）的形式,簇在时域上类似于幅度调制,可采用包络分析法对其进行分析。介绍了利用小波变换进行超宽带信号包络分析的方法,给出了接收信号包络的时域表达式,并对低信噪比下超宽带信号进行了包络提取,结果显示该方法实现了簇内多径分量的合并,并具有很强的去噪作用。包络分析方法对于那些难以建立模型的传输环境以及能够建立模型但难以提取参数的场合下超宽带信号的采集具有重要的意义,它指出了传统的包络分析技术可用于超宽带信号的采集。     

机器人足球训练中视觉感知与动作执行同步机制

主要研究RoboCup训练中球员视觉感知与动作执行同步的技术.在全面分析RoboCup现有同步方法存在问题的基础上,提出一种动态的视角调整方法,即通过对球员视角宽度的调整控制视觉信息到达的时刻,结合动作指令发送的特殊策略,实现球员向服务器发送指令时机的优化,以达到最佳同步效果.关于球员视角宽度动态切换的实现,具体包括:基于增强视觉检测的视角切换与分类视角动态切换2种方法.对比实验证实了该同步技术的优越性.     

支持地铁车体开发的工程数据库系统

在车体产品数据模块和数据库功能分析的基础上,建立以SQL Server 2000为后台数据库,以Java为W eb Service开发工具的工程数据库系统,完成前台功能化查询、可视化查询和参数化查询的功能设计.数据库内存储所有已建CAD模型和CAE模型的一般信息、分析结果信息及模型指针.该数据库系统管理设计过程、图纸文件、设计结果和分析结果,支持产品的设计变更、审批和发布,实现快速设计信息的检索与查询.实际应用表明,该系统能有效地管理车体开发中的产品数据.     

Estimation of Partially Linear Panel Data Models with Cross-Sectional Dependence

Journal of Systems Science and Complexity - This paper studies the estimation of the partially linear panel data models, allowing for cross-sectional dependence through a common factors structure....