无线网络的移动管理：数据的复制和应用

在无线通讯系统中，网络通过从数据库中查找用户信息来跟踪用户，这样就需要把用户信息事先存储在大量的数据库中。本书讨论了有关在数据库中复制用户信息并更新的若干问题。     

尾矿库溃坝灾害防控现状及发展

尾矿库溃坝灾害应急响应时间短、潜在威胁巨大,往往造成惨重人员伤亡与巨额财产损失.近些年尾矿库安全事故发生数量的总体下降趋势充分体现出现代化技术及安全管理方面的进步,然而重大事故发生频次却不减反增,2015年巴西Samarco铁矿与2014年加拿大Mount Polley重大溃坝事故及其惨重后果,再次为尾矿库安全敲响警钟.我国现存尾矿库8869座,含"头顶库"1425座,安全形势复杂.本文在收集大量相关领域文献的基础上,聚焦尾矿库溃坝灾害防控体系中的安全监测、灾害预警与应急准备、安全管理与标准规范这三大方面核心内容,分别综述对比国内外现状及前沿进展,探讨分析我国当前所面临的问题并尝试提出改进建议,为尾矿库防灾减灾理论研究与技术革新提供参考.结果表明:(1)我国尾矿库安全监测标准更高,但仪器耐久性、可靠度与实用性不足,专用监测器件与新技术的研发应用势在必行;(2)灾害预警方法单一且可信度不高,而信息技术融合应用成为发展趋势;(3)应急管理与预警决策需以充分的科学论证为基础,当前研究在试验手段与计算方法上存在局限;(4)我国拥有完善的安全管理标准规范体系,但在安全等别划分、全生命周期管理、主体变更、事故总结等方面相对欠缺.     

Chemical rescue of cleft palate and midline defects in conditional GSK-3beta mice

Glycogen synthase kinase-3beta (GSK-3beta) has integral roles in a variety of biological processes, including development, diabetes, and the progression of Alzheimer's disease. As such, a thorough understanding of GSK-3beta function will have a broad impact on human biology and therapeutics. Because GSK-3beta interacts with many different pathways, its specific developmental roles remain unclear. We have discovered a genetic requirement for GSK-3beta in midline development. Homozygous null mice display cleft palate, incomplete fusion of the ribs at the midline and bifid sternum as well as delayed sternal ossification. Using a chemically regulated allele of GSK-3beta (ref. 6), we have defined requirements for GSK-3beta activity during discrete temporal windows in palatogenesis and skeletogenesis. The rapamycin-dependent allele of GSK-3beta produces GSK-3beta fused to a tag, FRB* (FKBP/rapamycin binding), resulting in a rapidly destabilized chimaeric protein. In the absence of drug, GSK-3beta(FRB)*(/FRB)* mutants appear phenotypically identical to GSK-3beta-/- mutants. In the presence of drug, GSK-3betaFRB* is rapidly stabilized, restoring protein levels and activity. Using this system, mutant phenotypes were rescued by restoring endogenous GSK-3beta activity during two distinct periods in gestation. This technology provides a powerful tool for defining windows of protein function during development.     

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.     

A somitic Wnt16/Notch pathway specifies haematopoietic stem cells

Haematopoietic stem cells (HSCs) are a self-renewing population of cells that continuously replenish all blood and immune cells during the lifetime of an individual. HSCs are used clinically to treat a wide array of diseases, including acute leukaemias and congenital blood disorders, but obtaining suitable numbers of cells and finding immune-compatible donors remain serious problems. These difficulties have led to an interest in the conversion of embryonic stem cells or induced pluripotent stem cells into HSCs, which is not possible using current methodologies. To accomplish this goal, it is critical to understand the native mechanisms involved in the specification of HSCs during embryonic development. Here we demonstrate in zebrafish that Wnt16 controls a novel genetic regulatory network required for HSC specification. Non-canonical signalling by Wnt16 is required for somitic expression of the Notch ligands deltaC (dlc) and deltaD (dld), and these ligands are, in turn, required for the establishment of definitive haematopoiesis. Notch signalling downstream of Dlc and Dld is earlier than, and distinct from, known cell-autonomous requirements for Notch, strongly suggesting that novel Notch-dependent relay signal(s) induce the first HSCs in parallel to other established pathways. Our results demonstrate that somite-specific gene expression is required for the production of haemogenic endothelium.     

ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis

We recently identified angiogenin (ANG) as a candidate susceptibility gene for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by adult-onset loss of motor neurons. We now report the finding of seven missense mutations in 15 individuals, of whom four had familial ALS and 11 apparently 'sporadic' ALS. Our findings provide further evidence that variations in hypoxia-inducible genes have an important role in motor neuron degeneration.