Loss of autophagy in the central nervous system causes neurodegeneration in mice

Protein quality-control, especially the removal of proteins with aberrant structures, has an important role in maintaining the homeostasis of non-dividing neural cells. In addition to the ubiquitin-proteasome system, emerging evidence points to the importance of autophagy--the bulk protein degradation pathway involved in starvation-induced and constitutive protein turnover--in the protein quality-control process. However, little is known about the precise roles of autophagy in neurons. Here we report that loss of Atg7 (autophagy-related 7), a gene essential for autophagy, leads to neurodegeneration. We found that mice lacking Atg7 specifically in the central nervous system showed behavioural defects, including abnormal limb-clasping reflexes and a reduction in coordinated movement, and died within 28 weeks of birth. Atg7 deficiency caused massive neuronal loss in the cerebral and cerebellar cortices. Notably, polyubiquitinated proteins accumulated in autophagy-deficient neurons as inclusion bodies, which increased in size and number with ageing. There was, however, no obvious alteration in proteasome function. Our results indicate that autophagy is essential for the survival of neural cells, and that impairment of autophagy is implicated in the pathogenesis of neurodegenerative disorders involving ubiquitin-containing inclusion bodies.     

复合材料层合板的强度鲁棒性特征

针对复合材料强度行为的复杂性和准确预测的困难，首次提出复合材料强度鲁棒性的概念，即研究复合材料强度相对各种影响因素的变动所具有的稳定性特征，为复合材料的合理设计与利用提供新的分析思路和手段，通过对CFRP层合板进行试验和数值分析对比研究，讨论了加载方向对初始层失效应力（初始强度）的影响，在确认有限元计算的有效性之后，进一步讨论了加载方向以及单层板弹性常数的小范围变动对强度的影响。结果表明，为了获得较稳定的强度特征，当弹性模量E1较小时，应尽量控制E1本身的变动，而在E1较大的情况，控制加载方向的偏离更为重要。     

施加与铸型振动同步的电磁场消除连铸坯表面缺陷

用数值解析方法,计算了铸型在周期振动过程中,润滑剂流路内动压的分布和弯月面的形状;研究了当铸型外部施加高频交流磁场时,电磁压力对动压分布和弯月面形状的影响,分别用数值计算和连续铸模拟实验两种方法,探讨了施加与连铸铸振动同步的电磁场消除铸坯表面缺陷的可能性。     

Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome

Cardio-facio-cutaneous (CFC) syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. It phenotypically overlaps with Noonan and Costello syndrome, which are caused by mutations in PTPN11 and HRAS, respectively. In 43 individuals with CFC, we identified two heterozygous KRAS mutations in three individuals and eight BRAF mutations in 16 individuals, suggesting that dysregulation of the RAS-RAF-ERK pathway is a common molecular basis for the three related disorders.     

Numerical Simulation on Stratified Flow over an Isolated Mountain Ridge

The characteristics of stratified flow over an isolated mountain ridge have been investigated nu-merically. The two-dimensional model equations, based on the time-dependent Reynolds averaged Navier-Stokes equations, are solved numerically using an implicit time integration in a fitted body grid arrangement to simulate stratified flow over an isolated ideally bell-shaped mountain. The simulation results are in good agreement with the existing corresponding analytical and approximate solutions. It is shown that for atmos-pheric conditions where non-hydrostatic effects become dominant, the model is able to reproduce typical flow features. The dispersion characteristics of gaseous pollutants in the stratified flow have also been stud-ied. The dispersion patterns for two typical atmospheric conditions are compared. The results show that the presence of a gravity wave causes vertical stratification of the pollutant concentration and affects the diffu-sive characteristics of the pollutants.     

精确的时域三点法圆度误差分离技术

三点法圆度误差分离技术（ＥＳＴ）是成熟的圆度形状和回转误差的分离方法，然而在具体实施操作中，必须进行正反两次的快速傅里叶变换（ＦＦＴ和ＩＦＦＴ）。本文介绍一种新的方法；该方法同样基于误差分离技术的通则，但仅需在时域上直接对实测数据按简便代数式进行推即可进行分离虎，避免了ＦＦＴ和ＩＦＦＴ操作，因而更为方便，实时性也更强。     

A heterodimeric complex that promotes the assembly of mammalian 20S proteasomes

The 26S proteasome is a multisubunit protease responsible for regulated proteolysis in eukaryotic cells. It comprises one catalytic 20S proteasome and two axially positioned 19S regulatory complexes. The 20S proteasome is composed of 28 subunits arranged in a cylindrical particle as four heteroheptameric rings, alpha1-7beta1-7beta1-7alpha1-7 (refs 4, 5), but the mechanism responsible for the assembly of such a complex structure remains elusive. Here we report two chaperones, designated proteasome assembling chaperone-1 (PAC1) and PAC2, that are involved in the maturation of mammalian 20S proteasomes. PAC1 and PAC2 associate as heterodimers with proteasome precursors and are degraded after formation of the 20S proteasome is completed. Overexpression of PAC1 or PAC2 accelerates the formation of precursor proteasomes, whereas knockdown by short interfering RNA impairs it, resulting in poor maturation of 20S proteasomes. Furthermore, the PAC complex provides a scaffold for alpha-ring formation and keeps the alpha-rings competent for the subsequent formation of half-proteasomes. Thus, our results identify a mechanism for the correct assembly of 20S proteasomes.     

Transport of Yellow Sand in Stratified Flow over an Isolated Mountain Ridge

The transport of yellow sand over mountain regions in the presence of internal gravity waves has been investigated numerically. The motion of yellow sand particles has been simulated in a Lagrangian frame of reference by solving the time-dependent Reynolds averaged Navier-Stokes equations. An implicit time integration in a fitted body grid arrangement was used to simulate the stratified flow over an isolated ideally bell-shaped mountain. The transport and deposition of particles of various sizes, and of the altitudes where particles were released have been analyzed. Particular attention was given to transport patterns of different sized particles in various atmospheric conditions. The results show that the particle size and the re-lease altitude are both important factors in determining the trajectories of the particles. Small particles tend to be transported a long distance over the mountains, whereas heavier particles settle down around the re-lease source. Due to the existence of an internal gravity wave, the particle release altitude affects the trajec-tory of the particles. The analysis and results provide a very useful tool for the study of atmospheric flow and transport of pollutants over real topographies.