The copper-transporting capacity of ATP7A mutants associated with Menkes disease is ameliorated by COMMD1 as a result of improved protein expression

Menkes disease (MD) is an X-linked recessive disorder characterized by copper deficiency resulting in a diminished function of copper-dependent enzymes. Most MD patients die in early childhood, although mild forms of MD have also been described. A diversity of mutations in the gene encoding of the Golgi-resident copper-transporting P_1B-type ATPase ATP7A underlies MD. To elucidate the molecular consequences of the ATP7A mutations, various mutations in ATP7A associated with distinct phenotypes of MD (L873R, C1000R, N1304S, and A1362D) were analyzed in detail. All mutants studied displayed changes in protein expression and intracellular localization parallel to a dramatic decline in their copper-transporting capacity compared to ATP7A the wild-type. We restored these observed defects in ATP7A mutant proteins by culturing the cells at 30°C, which improves the quality of protein folding, similar to that which as has recently has been demonstrated for misfolded ATP7B, a copper transporter homologous to ATP7A. Further, the effect of the canine copper toxicosis protein COMMD1 on ATP7A function was examined as COMMD1 has been shown to regulate the proteolysis of ATP7B proteins. Interestingly, in addition to adjusted growth temperature, binding of COMMD1 partially restored the expression, subcellular localization, and copper-exporting activities of the ATP7A mutants. However, no effect of pharmacological chaperones was observed. Together, the presented data might provide a new direction for developing therapies to improve the residual exporting activity of unstable ATP7A mutant proteins, and suggests a potential role for COMMD1 in this process.     

Nonlinear vibrations of nano-beams accounting for nonlocal effect using a multiple scale method

The nonlinear free transverse vibrations of a nano-beam on simple supports are investigated based on nonlocal elasticity theory.The governing equation is proposed by considering geometric nonlinearity due to finite stretching of the beam.The method of multiple scales is applied to the governing equation to evaluate the nonlinear natural frequencies.Numerical examples are presented to demonstrate the analytical results and highlight the contributions of the nonlinear term and nonlocal effect.     

装配式板桥的横向预应力设计

基于摩擦抗剪的概念,提出一种确定横向预应力张拉设计值的方法.计算表明:在考虑板间铰缝及混凝土桥面板纵向开裂的情形下,装配式板桥的横向联结性能随着横向预应力的增大而增加;但是当横向预应力水平达到一定的程度(如NPO)之后,其横向联结性能基本不变,横向预应力的设计张拉值应大干NPO.通过美国马里兰州的一座装配式实心板桥的车载试验,研究了横向预应力对桥梁横向联结性能的影响.理论及试验表明,当桥面板及铰缝没有纵向开裂时,板间具备了足够的荷载横向传递能力,横向预应力对桥梁的横向联结性能影响不大.但横向预应力的存在,保证了铰缝和铺装层开裂后桥梁具有良好的横向联结性能,可以有效地抑制纵向裂缝病害的发展,确保桥梁的使用性能和安全性.     

C颗粒对Cp/AZ91D复合材料铸态显微组织的影响

通过复合铸造工艺制备了C_p/AZ91D复合材料，研究了C颗粒含量和保温时间等参数对该复合材料显微组织和力学性能的影响。结果表明，与保温时间相比，C_p的晶粒细化作用更为显著。当添加C_p质量分数为1.5%，保温时间15 min时，C_p/AZ91D复合材料铸锭平均晶粒尺寸由176 μm降低至32 μm，组织整体细化均匀，增强相C颗粒在复合材料基体中均匀分布，并且硬度值最高，达到89.07 HV。     

低能~(12)C+~(12)C反应的测量

在鲁尔大学DTL实验室4MV串列加速器上利用12C束流轰击高纯度的C靶.通过γ谱学方法测量了Ec.m.=2.10-4.75MeV12C+12C熔合蒸发反应,并导出了12C(12C,α)20Ne和12C(12C,p)23Na反应的天体物理S(E)*因子.在Ec.m.≤3.0MeV时发现新的共振.特别是在Gamow峰的高能尾部Ec.m.=2.14MeV处出现强共振峰.当T=8×108K时,这些共振使得α链的反应率比无共振情况下提高了近5倍.     

Investigations of ZnO thin films deposited by a reactive pulsed laser ablation

Highly transparent ZnO thin films were deposited at different substrate temperatures by pulsed laser deposition in an oxygen atmosphere.The thin films were characterized by various techniques including X-ray diffraction,scanning electron microscopy,optical absorption,and photoluminescence.We demonstrated that oriented wurtzite ZnO thin films could be deposited at room temperature using a high purity zinc target.Variable temperature photoluminescence revealed new characteristics in the band edge emission.The...     

A family study of endophenotypes for psychosis within an early intervention programme in Hong Kong: Rationale and preliminary findings

The study of endophenotypes may be a viable strategy to tackle the genetic complexity and phenotypic heterogeneity of psychosis, but this research direction is relatively under-developed in China as compared to Western countries. We have recently initiated one of the first family studies of endophenotypes for psychosis in China. Patients entering an established early psychosis intervention service are recruited into this research project for phenotyping, endophenotyping and genotyping. At the endophenotypic...     

狂犬疫苗——宠物之家须知

狂犬病又名恐水病,是由狂犬病毒所致的人畜共患的急性传染病.人多因被病兽咬伤而感染,亦可由染毒唾液污染各种伤口粘膜甚至结膜而引起感染.狗、猫、猪、牛、马及其他野生食肉类动物以及松鼠、家鼠都可以携带狂犬病病毒,而人对狂犬病毒普遍易感.狂犬病的潜伏期长短不一,短的几日,长的数十年,多数是1～3个月.     

Maintenance of multi-state production systems deteriorated by random shocks and production

We consider the preventive maintenance of a production system that is deteriorated by random shocks and the production process itself. The degree of deterioration is modeled by discrete and finite states. Shocks arrive according to a Poisson process and deteriorate the system by random amounts. The system may deteriorate whenever it produces an item. The system is continuously monitored and repaired if the system state is at or above a predetermined level for maintenance. We analyze the lifetime, product quantity, average cost, and average profit considering revenue from the product and cost due to setup, operation, and repair. Assuming a structure of system parameters and costs, using numerical examples, we investigate the impact of production and shock arrivals on the average profit and the optimal maintenance level that maximizes the average profit. The proposed model is applicable to manufacturing tasks in which machines wear due to production, for example, press processes, milling, turning, punching, and drilling.     

二十一世纪的科技预测与展望

没有人能准确地预见将来 ,尽管我能对几年后大多数意想不到地发明或事件作出大胆的预言。这里我所做的一切只是对将来作一个轮廓的描述。当然我没有资格对事物的发展作结论。在 1 971年 ,我曾预言人类将于 1 994年可登上火星。此事现在看来要到 2 0 1 0年我们才会实现这一愿望。还有 ,在 1 951年 ,我极其乐观地提出人类将于 1 978年登上月球 ,而尼尔·阿姆斯特朗和拜兹·奥尔德林对我的预见整整提前了 1 0年实现。另外 ,在 1 94 5年 ,我曾提出“克拉克轨道”的设想 ,后来通讯卫星便是以此轨道运行 ,为此我感到骄傲。这里所举的众多例子 ,尤…