FAS and NF-κB signalling modulate dependence of lung cancers on mutant EGFR

Human lung adenocarcinomas with activating mutations in EGFR (epidermal growth factor receptor) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient. This heterogeneity in treatment response could result from genetic modifiers that regulate the degree to which tumour cells are dependent on mutant EGFR. Through a pooled RNA interference screen, we show that knockdown of FAS and several components of the NF-κB pathway specifically enhanced cell death induced by the EGFR TKI erlotinib in EGFR-mutant lung cancer cells. Activation of NF-κB through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively), or silencing of IκB (also known as NFKBIA), rescued EGFR-mutant lung cancer cells from EGFR TKI treatment. Genetic or pharmacologic inhibition of NF-κB enhanced erlotinib-induced apoptosis in erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models. Increased expression of the NF-κB inhibitor IκB predicted for improved response and survival in EGFR-mutant lung cancer patients treated with EGFR TKI. These data identify NF-κB as a potential companion drug target, together with EGFR, in EGFR-mutant lung cancers and provide insight into the mechanisms by which tumour cells escape from oncogene dependence.     

A Pluto-like radius and a high albedo for the dwarf planet Eris from an occultation

The dwarf planet Eris is a trans-Neptunian object with an orbital eccentricity of 0.44, an inclination of 44 degrees and a surface composition very similar to that of Pluto. It resides at present at 95.7 astronomical units (1?AU is the Earth-Sun distance) from Earth, near its aphelion and more than three times farther than Pluto. Owing to this great distance, measuring its size or detecting a putative atmosphere is difficult. Here we report the observation of a multi-chord stellar occultation by Eris on 6 November 2010 UT. The event is consistent with a spherical shape for Eris, with radius 1,163?±?6?kilometres, density 2.52?±?0.05 grams per cm(3) and a high visible geometric albedo, Pv = 0.96(+0.09)(-0.04). No nitrogen, argon or methane atmospheres are detected with surface pressure larger than ～1?nanobar, about 10,000 times more tenuous than Pluto's present atmosphere. As Pluto's radius is estimated to be between 1,150 and 1,200 kilometres, Eris appears as a Pluto twin, with a bright surface possibly caused by a collapsed atmosphere, owing to its cold environment. We anticipate that this atmosphere may periodically sublimate as Eris approaches its perihelion, at 37.8 astronomical units from the Sun.     

Role of sulphuric acid, ammonia and galactic cosmic rays in atmospheric aerosol nucleation

Atmospheric aerosols exert an important influence on climate through their effects on stratiform cloud albedo and lifetime and the invigoration of convective storms. Model calculations suggest that almost half of the global cloud condensation nuclei in the atmospheric boundary layer may originate from the nucleation of aerosols from trace condensable vapours, although the sensitivity of the number of cloud condensation nuclei to changes of nucleation rate may be small. Despite extensive research, fundamental questions remain about the nucleation rate of sulphuric acid particles and the mechanisms responsible, including the roles of galactic cosmic rays and other chemical species such as ammonia. Here we present the first results from the CLOUD experiment at CERN. We find that atmospherically relevant ammonia mixing ratios of 100 parts per trillion by volume, or less, increase the nucleation rate of sulphuric acid particles more than 100-1,000-fold. Time-resolved molecular measurements reveal that nucleation proceeds by a base-stabilization mechanism involving the stepwise accretion of ammonia molecules. Ions increase the nucleation rate by an additional factor of between two and more than ten at ground-level galactic-cosmic-ray intensities, provided that the nucleation rate lies below the limiting ion-pair production rate. We find that ion-induced binary nucleation of H(2)SO(4)-H(2)O can occur in the mid-troposphere but is negligible in the boundary layer. However, even with the large enhancements in rate due to ammonia and ions, atmospheric concentrations of ammonia and sulphuric acid are insufficient to account for observed boundary-layer nucleation.     

一种新颖的含有隧道结构的二维钠钼磷多酸盐的合成和晶体结构

利用中温水热技术合成了一种未见报道的含有隧道结构的二维钠钼磷多酸盐[NH3(CH2)2NH3]6[Na2Mo12O30(HPO4)6(H2PO4)2].5H2O(Ⅰ),并测定了其晶体结构.化合物Ⅰ属于三斜晶系:P1-空间群;晶胞参数a=1.204 5(8)nm,b=1.459 1(0)nm,c=2.134 8(3)nm,α=80.587 2°,β=82.688 3°,γ=76.241 0°,V=3.580 1(2)nm3,Z=2,R1=0.054 4,wR2=0.110 6.     

面向建筑健康监测的无人机自主巡检与裂缝识别

面向建筑健康的高时效监测需求,为提升表面病害视觉检测的自动化水平,提出了场景信息引导的无人机自主巡检任务规划方法。利用场景先验信息,针对建筑结构特征,设计了平行观测和包络观测两种观测模式,实现了狭窄空间中独栋建筑的全覆盖避障巡检,获取了毫米级分辨率的整体建筑观测影像,并对巡检质量的整体评估提出了有效的量化指标。将建筑立面划分为3 720个子区域,利用深度残差网络开展了裂缝识别分类。错分13个子区域,漏分14个子区域,裂缝识别精度高。将裂缝骨架线映射到建筑三维模型,为裂缝形态与建筑整体的一体化表达提供了数据支撑。该研究将高精度三维重建与表面病害识别相结合,为建筑健康一体化监测提供了有效的观测分析手段。     

星系的生命和呼吸

<正>科学家追踪气体随时间和空间的变化,探寻恒星群出生及死亡的方式。天文学家对宇宙的大部分了解来自他们能够看到的东西,因此,他们的理论总是偏爱明亮的恒星和星系。然而,宇宙中的大部分常规物质都是以昏暗的气体形式存在的。称作星系际介质的气体充满星系间的空间;而环星系介质的气体则环绕在星系附近。这两个区域的气体管控星系诞生、成长和死亡,也详细记录了整个宇宙的     

西北地区人口-经济-水环境质量耦合协调发展研究

基于2005～2014年西北五省人口-经济-水环境质量相关数据,构建耦合协调评价指标体系。运用统计学和GIS方法对近10年来西北地区人口-经济-水耦合协调发展的时空演变进行分析,发现2005～2014年,耦合类别变化情况为勉强耦合-初级耦合-中级耦合,耦合协调度持续上升表明三个子系统之间的协调促进作用增强,系统逐步由无序走向有序;近10年来,西北五省耦合协调度均有不同程度提升,其中青海省提升幅度最大,达到了0.44,陕西省提升幅度为0.044,是五省中提升幅度最小的省区;不论是区域整体还是区域内部各个省份,经济和人口对系统的推动作用均逐步增强,而水环境质量则逐步失去对各区域发展的推动力,表明区域发展的动力逐步由资源转向经济和人口,发展的可持续性增强。     

Direct inhibition of phospholipid scrambling activity in erythrocytes by potassium ions

The exposure of phosphatidylserine (PS) at the cell surface plays a critical role in blood coagulation and serves as a macrophage recognition moiety for the engulfment of apoptotic cells. Previous observations have shown that a high extracellular [K⁺] and selective K⁺ channel blockers inhibit PS exposure in platelets and erythrocytes. Here we show that the rate of PS exposure in erythrocytes decreases by ~50% when the intracellular [K⁺] increases from 0 to physiological concentrations. Using resealed erythrocyte membranes, we further show that lipid scrambling is inducible by raising the intracellular [Ca²⁺] and that K⁺ ions have a direct inhibitory effect on this process. Lipid scrambling in resealed ghosts occurs in the absence of cell shrinkage and microvesicle formation, processes that are generally attributed to Ca²⁺-induced lipid scrambling in intact erythrocytes. Thus, opening of Ca²⁺-sensitive K⁺ channels causes loss of intracellular K⁺ that results in reduced intrinsic inhibitory effect of these ions on scramblase activity. Received 11 September 2008; received after revision 17 October 2008; accepted 27 October 2008     

Structural characterization of two papaya chitinases, a family GH19 of glycosyl hydrolases

Two chitinases, able to use tetra-N-acetylglucosamine, chitin and chitosan as substrates, were characterized after purification from Carica papaya latex. The complete amino acid sequence of the major form and about 40% of the minor one were determined through proteolytic digestions and mass spectroscopy analysis. Sequencing demonstrated that both papaya chitinases are members of the family 19 of glycosyl hydrolases (GH19). Based on the known 3-D structures of other members of family GH19, it was expected that papaya chitinases would adopt all-alpha structures. However, circular dichroism and infrared spectroscopy indicated, for the papaya chitinases, a content of 15–20% of extended structures besides the expected 40% of alpha helices. Since the fully sequenced papaya chitinase contains a large number of proline residues the possibility that papaya chitinase contains polyproline II stretches was examined in the context of their resistance against proteolytic degradation. Received 11 July 2006; received after revision 13 October 2006; accepted 25 October 2006