PTC124 targets genetic disorders caused by nonsense mutations

Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.     

数控机床补偿误差的激光干涉仪识别技术

提出了基于数控机床的空间误差模型,用激光干涉仪测量机床工作空间中的对角线位移误差来识别机床空间误差的方法,解决了机床垂直轴roll误差的测量难题。结果表明所提出的方法测量精度高,缩短了测量时间,减少了对光学器件的需求量。     

基于Web的虚拟数控系统的研究与开发

基于服务器／客户模式的的虚拟数控系统体系结构，讨论了虚拟数控系统的建模技术和基于VRML的实现方法，并指出虚拟数控机床的建模是虚拟数控加工过程仿真的实现关键．利用VRML语言、分布式对象技术和Java技术开发和建立了基于Web环境的虚拟数控系统原型。并对系统的开发平台进行了分析和介绍，同时给出了系统的运行实例．研究表明，所开发的系统是可行的和合理的．     

ANALYSIS AND COMPUTATIONAL ALGORITHM FOR QUEUES WITH STATE-DEPENDENT VACATIONS Ⅱ:M(n)/G/1/K

We study a single-server queueing system with state-dependent arrivals and general service-distribution.or simply M(n)/G/1/K.where the server follows an N policy and takes multiple vacationswhen the system is empty.We provide a recursive algorithm using the supplementary variable tech-nique to munerically compute the stationary queue length distribution of the system.The only inputrequirements are the Laplace-Stieltjes transforms of the service time distribution and the vacation timedistribution.and the state-dependent arrival rate.The computational complexity of the algorithm isO(K~3).     

基于主曲率匹配的五坐标刀位轨迹优化

为了克服传统五轴加工采用固定走刀方向和后跟角的加工方法的不足,提出了一种基于刀具扫描面与曲面主曲率匹配、以行距最大为目标的走刀方向和后跟角的优化算法,实践证明,这种方法能够优化刀位轨迹,提高加工效率。     

Giant histiocytes after cyclophosphamide

Riassunto Nel midollo osseo di topi intossicati con dosi elevate di ciclofosfamide compaiono elementi giganti, che, per la capacità fagocitaria di cui sono dotati, appaiono appartenere al sistema istiocitario (istiociti giganti).     

复杂曲面的无干涉刀位轨迹生成

提出了基于X－map思路的干涉处理方法，将干涉处理由空间三角片之间的距离判断简化为一维坐标轴上两点之间的位置比较，并构造了包括干涉检查、干涉消除及欠切区域处理等的完整干涉处理方法，此法可以提高干涉处理的效率及稳定性，简化欠切区域的单独处理，对三坐标加工的干涉处理具有很好的实用价值。     

基于现场总线的开放式数控系统体系结构研究

结合现场总线的特点和开放式系统的要求，提出了一种基于现场总线的开放式CNC系统的体系结构，并把该体系划分为应用层，功能层和设备层三个层次，对每一层的功能进行了系统的分析和描述。在实现方法上，采用COM／DCOM技术的OPC规范的软件方法，实现了数控系统的软件 模块的重用与扩充；采用Profibus现场总线实现了数控系统的硬件模块的互操作与互换，从而满足了数控系统开放性的要求。     

高速弧齿锥齿轮弹流润滑特性分析

以某航空发动机高速弧齿锥齿轮为研究对象,在弧齿锥齿轮加载接触分析基础上,建立起适合弹流润滑分析的动态坐标系。用点弹流润滑理论对高速弧齿锥齿轮在啮合过程中的最大油膜压力和最小油膜厚度变化情况进行描述,寻找出载荷、速度和润滑油粘度等因素对轮齿弹流润滑特性的影响规律。