Senescence surveillance of pre-malignant hepatocytes limits liver cancer development

Upon the aberrant activation of oncogenes, normal cells can enter the cellular senescence program, a state of stable cell-cycle arrest, which represents an important barrier against tumour development in vivo. Senescent cells communicate with their environment by secreting various cytokines and growth factors, and it was reported that this 'secretory phenotype' can have pro- as well as anti-tumorigenic effects. Here we show that oncogene-induced senescence occurs in otherwise normal murine hepatocytes in vivo. Pre-malignant senescent hepatocytes secrete chemo- and cytokines and are subject to immune-mediated clearance (designated as 'senescence surveillance'), which depends on an intact CD4(+) T-cell-mediated adaptive immune response. Impaired immune surveillance of pre-malignant senescent hepatocytes results in the development of murine hepatocellular carcinomas (HCCs), thus showing that senescence surveillance is important for tumour suppression in vivo. In accordance with these observations, ras-specific Th1 lymphocytes could be detected in mice, in which oncogene-induced senescence had been triggered by hepatic expression of Nras(G12V). We also found that CD4(+) T cells require monocytes/macrophages to execute the clearance of senescent hepatocytes. Our study indicates that senescence surveillance represents an important extrinsic component of the senescence anti-tumour barrier, and illustrates how the cellular senescence program is involved in tumour immune surveillance by mounting specific immune responses against antigens expressed in pre-malignant senescent cells.     

S-nitrosylation of NADPH oxidase regulates cell death in plant immunity

Changes in redox status are a conspicuous feature of immune responses in a variety of eukaryotes, but the associated signalling mechanisms are not well understood. In plants, attempted microbial infection triggers the rapid synthesis of nitric oxide and a parallel accumulation of reactive oxygen intermediates, the latter generated by NADPH oxidases related to those responsible for the pathogen-activated respiratory burst in phagocytes. Both nitric oxide and reactive oxygen intermediates have been implicated in controlling the hypersensitive response, a programmed execution of plant cells at sites of attempted infection. However, the molecular mechanisms that underpin their function and coordinate their synthesis are unknown. Here we show genetic evidence that increases in cysteine thiols modified using nitric oxide, termed S-nitrosothiols, facilitate the hypersensitive response in the absence of the cell death agonist salicylic acid and the synthesis of reactive oxygen intermediates. Surprisingly, when concentrations of S-nitrosothiols were high, nitric oxide function also governed a negative feedback loop limiting the hypersensitive response, mediated by S-nitrosylation of the NADPH oxidase, AtRBOHD, at Cys 890, abolishing its ability to synthesize reactive oxygen intermediates. Accordingly, mutation of Cys 890 compromised S-nitrosothiol-mediated control of AtRBOHD activity, perturbing the magnitude of cell death development. This cysteine is evolutionarily conserved and specifically S-nitrosylated in both human and fly NADPH oxidase, suggesting that this mechanism may govern immune responses in both plants and animals.     

A terahertz metamaterial with unnaturally high refractive index

Controlling the electromagnetic properties of materials, going beyond the limit that is attainable with naturally existing substances, has become a reality with the advent of metamaterials. The range of various structured artificial 'atoms' has promised a vast variety of otherwise unexpected physical phenomena, among which the experimental realization of a negative refractive index has been one of the main foci thus far. Expanding the refractive index into a high positive regime will complete the spectrum of achievable refractive index and provide more design flexibility for transformation optics. Naturally existing transparent materials possess small positive indices of refraction, except for a few semiconductors and insulators, such as lead sulphide or strontium titanate, that exhibit a rather high peak refractive index at mid- and far-infrared frequencies. Previous approaches using metamaterials were not successful in realizing broadband high refractive indices. A broadband high-refractive-index metamaterial structure was theoretically investigated only recently, but the proposed structure does not lend itself to easy implementation. Here we demonstrate that a broadband, extremely high index of refraction can be realized from large-area, free-standing, flexible terahertz metamaterials composed of strongly coupled unit cells. By drastically increasing the effective permittivity through strong capacitive coupling and decreasing the diamagnetic response with a thin metallic structure in the unit cell, a peak refractive index of 38.6 along with a low-frequency quasi-static value of over 20 were experimentally realized for a single-layer terahertz metamaterial, while maintaining low losses. As a natural extension of these single-layer metamaterials, we fabricated quasi-three-dimensional high-refractive-index metamaterials, and obtained a maximum bulk refractive index of 33.2 along with a value of around 8 at the quasi-static limit.     

考虑员工移动成本的车缝生产线平衡问题

针对车缝生产线多品种小批量和自动化程度低等特点,提出了考虑员工多工序作业移动成本和为瓶颈工序增设适量设备的车缝生产线平衡问题。通过引入虚拟工作站和标准在制品（SWIP）库存概念,构建最大平衡率和最小生产节拍的双目标优化模型。最后,通过设计枚举算法和基于贪婪搜索策略的多目标遗传算法获取新增设备方案、标准在制品数量以及线平衡优化方案。车缝生产线实例计算结果表明,线平衡率及生产效率得到大幅提升,验证了模型和算法的合理性与有效性。     

无核白葡萄胚挽救机理的研究

选用无核白葡萄在开花后35￣60d,取其胚接种在含有GA3+IAA+6-BA的不同激素水平MS培养基上,进行胚挽救,以探讨研究无核葡萄的胚挽救机理.结果表明无核白在开花后50d胚挽救效果最好.在附加GA30.5mg.L-1+IAA1.5mg.L-1+6-BA 0.5mg.L-1的MS培养基上得到了84%的发育率和31.9%的成苗率(50d);开花后60d的发育率最高,得到了100%的发育率,却未得到成苗,说明在胚挽救中幼胚的不同部位其发育与败育过程不同步.对无核葡萄胚挽救适期的确定依据提出了新的见解.     

ESR测年法在黄土中的应用及存在的一些问题

ESR测年法近年来迅速发展,填补了铀系不平衡法及14C法所遗留下来的一些空白.介绍ESR法测年的基本原理及特点,重点阐述在黄土测年中的实际应用及存在的一些问题:石英类型的选择,年龄较轻黄土的ESR信号的选择,初始剂量的测定,宇宙射线对样品的贡献,石英重结晶作用对年剂量的影响,放射性元素的衰变规律的校正,含水量的校正,样品周围放射性元素的迁移等.     

基于幂函数控制指令的垂直飞行仿真性能分析

基于模态直接切换的飞行高度控制方法,在输入控制指令后,存在控制量输出震荡,甚至发散的问题。幂函数符合飞行高度指令变化规律,以此为原型函数,推导给定高度,当前高度和垂直速度之间的关系,将这一变换关系作为垂直速度控制回路的输入指令,设计了平稳控制系统,该系统不需要进行控制模态切换,就可以实现飞行高度保持,以及飞行高度的改变。通过A320飞行仿真平台对设计的平稳控制系统进行性能分析,结果表明该系统可以实现高度的平稳控制,且稳态误差得到了很好抑制。     

一种实用的VOWLAN认证计费系统

文章提出一种基于VOWLAN的简明认证计费系统。该系统是用GKGUI从网守获取通话详细记录并传输给后台的数据库,增强了服务器端的直观性和操作简单性;由于在网络服务器中Java Applet又将详细的计费信息以一种友好的界面形式随主页发布到网络中去,因此,不论服务器端还是客户端都能够享受到图形用户界面带来的操作简单、直观的好处。     

甲基丙烯酸氟烷基酯常规及核壳乳液聚合

以甲基丙烯酸氟烷基酯(Zonyl TM)、甲基丙烯酸甲酯、丙烯酸正丁酯为原料,分别采用常规乳液聚合和核壳乳液聚合两种方法制备了两组三元共聚物乳液。系统研究了聚合条件对乳液稳定性和聚合反应动力学的影响,计算出聚合反应的表观活化能为68.4 kJ/mol,恒速期反应速率与乳化剂浓度和引发剂浓度的关系为Rp∝[I]0.66[E]0.8。通过共聚物膜对水接触角的测定,比较了两种聚合方法制备的样品涂膜的表面性能,发现所制备的样品均具有良好的疏水性能。氟单体含量相同时,核壳乳液聚合样品的疏水性明显优于常规乳液聚合样品。