RNAi-mediated gene silencing in non-human primates

The opportunity to harness the RNA interference (RNAi) pathway to silence disease-causing genes holds great promise for the development of therapeutics directed against targets that are otherwise not addressable with current medicines. Although there are numerous examples of in vivo silencing of target genes after local delivery of small interfering RNAs (siRNAs), there remain only a few reports of RNAi-mediated silencing in response to systemic delivery of siRNA, and there are no reports of systemic efficacy in non-rodent species. Here we show that siRNAs, when delivered systemically in a liposomal formulation, can silence the disease target apolipoprotein B (ApoB) in non-human primates. APOB-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP) and administered by intravenous injection to cynomolgus monkeys at doses of 1 or 2.5 mg kg(-1). A single siRNA injection resulted in dose-dependent silencing of APOB messenger RNA expression in the liver 48 h after administration, with maximal silencing of >90%. This silencing effect occurred as a result of APOB mRNA cleavage at precisely the site predicted for the RNAi mechanism. Significant reductions in ApoB protein, serum cholesterol and low-density lipoprotein levels were observed as early as 24 h after treatment and lasted for 11 days at the highest siRNA dose, thus demonstrating an immediate, potent and lasting biological effect of siRNA treatment. Our findings show clinically relevant RNAi-mediated gene silencing in non-human primates, supporting RNAi therapeutics as a potential new class of drugs.     

基于改进粒子群算法优化的自抗扰控制器（ADRC）及其应用

针对自抗扰控制器参数多,不利于整定的问题,提出了一种基于改进的粒子群算法（PSO）的自抗扰控制器参数整定方法。该方法引入了PSO中各个粒子的惯性权值的自适应调整机制,以此来维持粒子的多样性和加速粒子群算法的收敛性。利用改进粒子群算法优化的二阶自抗扰控制器控制主气温控制系统,仿真结果验证了算法的可行性和有效性。     

基于关系积的属性约简算法

粗糙集的属性约简是一个NP难问题,目前尚无高效的算法.基于集合理论,提出了关系积概念和基于关系积的属性约简算法,把决策表的属性约简过程转化为关系积的运算,减小了对决策表的扫描次数,提高了属性约简的效率;算法采用自底向上和宽度优先的搜索策略,可确保找到最小属性约简集.结合实例,给出了算法的具体实现.     

高压输电线路防鸟设施应用及效果研究

鸟害闪络是引起高压输电线路跳闸的主要原因之一.采用实地抽样调查的方法,对吉林省9个地区1 518基220kV高压杆塔上防鸟害设施的种类、损毁状况、防鸟效果和存在的问题进行了研究.结果表明:吉林省目前主要应用障碍性防鸟设施防止鸟类在输电杆塔上栖落和筑巢,以风力驱鸟器、鸟刺、滚动针式驱鸟器和防鸟罩为主;调查杆塔安装比例为53.6%,各地区存在差异;平均每基杆塔安装的防鸟设施数量为4.8个;不同类型防鸟设施损毁率不同,平均损毁率约为18.0%,其中带鸟刺风力驱鸟器和普通风力驱鸟器损坏率较高,分别为27.5%和27.3%.安装防鸟设施未能完全阻止鸟类在输电杆塔筑巢,但可在一定程度上改变鸟类在输电杆塔上的筑巢位置进而减少鸟害闪络的发生几率.     

Direct detection of more than 50% of the Duchenne muscular dystrophy mutations by field inversion gels

Duchenne muscular dystrophy (DMD) is an X-linked disorder affecting about 1 in 3,500 males. It is allelic with the milder Becker muscular dystrophy. The biochemical basis for both diseases is unknown and no effective treatment is available. Long-range physical mapping has shown that the DMD gene, localized in Xp21, is extremely large, exceeding 2 million base pairs. Until now, carrier detection and prenatal diagnosis has involved the use of linked restriction fragment length polymorphism markers which detect muscular dystrophy-associated deletions in about 10% of the cases. Field inversion gel electrophoresis (FIGE) allows the detection of structural rearrangements in 21 out of 39 of the DMD patients studied (54%), of which 14 (65%) were not detected by conventional methods. Large deletions seem to make up a much higher fraction of the DMD mutations than so far indicated by other methods. A region prone to deletion was located in the distal half of the gene. FIGE analysis could provide a valuable extension of information for carrier detection and prenatal diagnosis. The technique should be generally applicable to the study of diseases involving structural chromosomal rearrangements.     

两种前处理方法测定菜籽油中6种金属元素含量的比较

目的:比较不同前处理方法对菜籽油中6种金属元素含量测定的影响.方法:分别使用干灰化法和湿消化法进行前处理,并用火焰原子吸收分光光度法分别测定15个菜籽油样品中铅、镉、铜、铁等6种金属元素的含量.结果:干灰化法和湿消化法处理后所测菜籽油样品中Pb、Cu含量差异无统计学意义(P>0.05),Fe、Mn含量差异有统计学意义(P<0.05).各元素的R2均大于0.99,干灰化法的加标回收率81.90%~107.45%,湿消化法的加标回收率99.90%~108.05%.均满足痕量分析要求,相比之下,干灰化法与湿消化法的加标回收率比较差异有统计学意义(P<0.05),且湿消化法-火焰原子吸收分光光度法测定油样的回收率相对干灰化法的要高.结论:两种方法都能获得准确的测定结果;湿消化法要优于干灰化法.     

Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells

Embryonic stem (ES) cells, the totipotent outgrowths of blastocysts, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in M1 myeloid leukaemic cells and which we have recently purified, cloned and characterized. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice.     

盘式永磁无刷直流发电机

阐述了轴向磁场盘式永磁无刷直流发电机的结构及其特点，提出了气隙磁场的简化模型，并对三维磁场进行了分析，在此基础上探讨了这种电机的设计方法，以最大功率输出为优化目标，导出了几个简单实用的设计公式。６极９相样机的实测数据证实了分析和设计方法的正确性，这种无刷直流发电机结构紧凑，效率高，特别适用于由引擎驱动的发电系统。