ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner

R-spondin proteins strongly potentiate Wnt signalling and function as stem-cell growth factors. Despite the biological and therapeutic significance, the molecular mechanism of R-spondin action remains unclear. Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. Inhibition of ZNRF3 enhances Wnt/β-catenin signalling and disrupts Wnt/planar cell polarity signalling in vivo. Notably, R-spondin mimics ZNRF3 inhibition by increasing the membrane level of Wnt receptors. Mechanistically, R-spondin interacts with the extracellular domain of ZNRF3 and induces the association between ZNRF3 and LGR4, which results in membrane clearance of ZNRF3. These data suggest that R-spondin enhances Wnt signalling by inhibiting ZNRF3. Our study provides new mechanistic insights into the regulation of Wnt receptor turnover, and reveals ZNRF3 as a tractable target for therapeutic exploration.     

Re-emerging superconductivity at 48 kelvin in iron chalcogenides

Pressure has an essential role in the production and control of superconductivity in iron-based superconductors. Substitution of a large cation by a smaller rare-earth ion to simulate the pressure effect has raised the superconducting transition temperature T(c) to a record high of 55?K in these materials. In the same way as T(c) exhibits a bell-shaped curve of dependence on chemical doping, pressure-tuned T(c) typically drops monotonically after passing the optimal pressure. Here we report that in the superconducting iron chalcogenides, a second superconducting phase suddenly re-emerges above 11.5?GPa, after the T(c) drops from the first maximum of 32?K at 1?GPa. The T(c) of the re-emerging superconducting phase is considerably higher than the first maximum, reaching 48.0-48.7?K for Tl(0.6)Rb(0.4)Fe(1.67)Se(2), K(0.8)Fe(1.7)Se(2) and K(0.8)Fe(1.78)Se(2).     

中国剩余定理及其应用——基于研究性学习的设计

中国剩余定理在数论及代数理论的研究中起着重要的作用,是一个极其重要的定理.通过中国剩余定理的历史起源来给出该定理及其证明方法,在此基础上对该定理的应用进行了讨论和分析,并给出了一些例子.     

基于分形布朗业务模型的差分队列服务建模

差分队列服务(DQS)是一种在有线与无线融合网络中能有效提供服务质量的服务质量模型,文中基于DQS的思想,将具有相同时延要求的到达业务作为一个分形布朗运动(FBM)业务,建立了一个针对多个FBM业务及对应时延要求的差分队列服务模型,并推导出该模型下的丢包率公式.仿真结果表明,文中模型分析的结果与基于数据包粒度的仿真结果是一致的.模型性能分析结果表明,实时业务的突发性对差分队列服务的服务质量保证影响较大.     

Preparation and cellular uptake of PLGA particles loaded with lamivudine

Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with lamivudine and coated with bovine serum albumin (BSA) were prepared via a double emulsion method. The influences of experiments parameters such as volume of inner aqueous phase, concentration of organic phase and ultrasonication time on the particle size and drug entrapment efficiency were investigated, obtaining PLGA particles with a diameter of ~260 nm and drug entrapment efficiency of ~35%. The particles were observed by scanning electron microscopy and transmittance electron microscopy, showing a core-shell structure. BCA assay found that 58 mg BSA was present on/in 1 g LPB particles. The loaded lamivudine showed a burst release at beginning and sustained release until 24 h in physiological conditions. Low pH could accelerate the release of lamivudine from PLGA particles, making the PLGA particles potential intelligent intracellular drug carriers. The PLGA particles were readily internalized into the human liver cells within a short time and increased gradually with the prolongation of incubation time regardless of the loading of lamivudine. The particles either resided within lysosomes or transferred to cytoplasm, but could not enter into the cell nucleus. The cell viability was not significantly influenced in the presence of the particles regardless of lamivudine encapsulation, suggesting that this kind of particles may be a good candidate for the intracellular anti-hepatitis B drug delivery.     

基于云平台的软件服务流引擎技术研究

传统的工作流自动化处理大多是针对固定的较为简单的执行单元,不能适应复杂的SaaS服务要求。为同时向大规模访问用户提供可靠实时的云计算服务,文章设计了软件服务流,高效、实时、稳定的调度算法是软件服务流成功实施的关键。通过服务抽象过程把复杂的用户自定制请求匹配成云平台的可执行单元后,软件服务流引擎利用文中提出的EOE实时调度算法处理用户请求,交付下层执行,监控执行进程、系统状态,实现软件服务流的自动化高效运行。最后,给出了在海洋环境信息云服务体系框架下的实现。     

外部扰动下一类参数未知的混沌系统的观测器H∞同步

在系统参数未知的情况下,讨论了一类受扰混沌系统的H∞同步问题,利用Lyapunov稳定性理论,给出了观测器的设计方法.此方法约束条件较少,容易实现.     

基于SWOT量化分析的丽江旅游业发展战略研究

在拟的投建的"丽江国际旅游集散中心"项目调研的基础上,结合调研内容对项目进行SWOT分析,通过量化分析因素,将SWOT定性分析问题转换成运筹学中"产销平衡"问题,然后运用LINGO对问题进行求解,最后根据求解结果,提出具体的发展策略和建议,以期进一步推动丽江旅游业的发展.     

煤矸石发电厂气力除灰控制系统分析研究

简要介绍了某煤矸石发电厂1号炉、2号炉气力正压密相气力输灰系统及其操作,论述了布袋除尘器飞灰输送逻辑描述、除灰步序,详细分析了DCS控制系统在电厂除灰控制系统中的应用特点。     

基于三维城市GIS的交互式三维隧道建模算法

为了建设城市地下空间三维GIS,解决城市地下隧道的三维建模问题,提出一种基于三维城市GIS的交互式三维隧道建模方法,详细讨论了交互式三维隧道建模的各个步骤以及交互控制、空间计算和三角剖分等算法,并以一个正在开展的三维城市GIS项目为基础,介绍了交互式三维隧道建模方法的应用。实践证明,交互式三维隧道建模方法相比传统方法操作更为方便,能够提高城市地下空间三维GIS的工作效率。交互式三维隧道建模方法将为基于三维城市GIS技术的城市空间信息化工作提供重要的技术支撑。