Tissue-specific and reversible RNA interference in transgenic mice

Genetically engineered mice provide powerful tools for understanding mammalian gene function. These models traditionally rely on gene overexpression from transgenes or targeted, irreversible gene mutation. By adapting the tetracycline (tet)-responsive system previously used for gene overexpression, we have developed a simple transgenic system to reversibly control endogenous gene expression using RNA interference (RNAi) in mice. Transgenic mice harboring a tet-responsive RNA polymerase II promoter driving a microRNA-based short hairpin RNA targeting the tumor suppressor Trp53 reversibly express short hairpin RNA when crossed with existing mouse strains expressing general or tissue-specific 'tet-on' or 'tet-off' transactivators. Reversible Trp53 knockdown can be achieved in several tissues, and restoring Trp53 expression in lymphomas whose development is promoted by Trp53 knockdown leads to tumor regression. By leaving the target gene unaltered, this approach permits tissue-specific, reversible regulation of endogenous gene expression in vivo, with potential broad application in basic biology and drug target validation.     

Observation of conformation-specific pathways in the photodissociation of 1-iodopropane ions.

Many molecules can rotate freely around single bonds and thereby interconvert between different conformations, such as gauche and anti 1,2-disubstituted ethane, a classic example of conformational isomerism. Even though rotation occurs rapidly at room temperature, the product selectivity seen in some reactions has been explained by conformation-dependent reaction mechanisms: if reactant molecules differing only in their conformation are located at different positions on the reaction path, they may undergo different reactions. But a direct verification of this effect is difficult, because the energy barrier separating conformational isomers is so low that under ambient conditions reactants with more than one conformation will be present. But by using temperatures low enough to suppress the interconversion between different conformations, gauche-1-iodopropane ions and anti-1-iodopropane ions have been selectively generated. Here we show that the kinetic energy released during the photodissociation of 1-iodopropane ions depends strongly on the conformation of the ions. Thermodynamic arguments and ab initio calculations indicate that this difference in kinetic energy release results from differences in the reaction mechanism, with gauche-1-iodopropane ions forming 2-propyl ions and anti-1-iodopropane ions forming protonated cyclopropane ions. These findings suggest that the well-known concept of conformation selection forms the basis of a simple scheme for reaction control, thus providing in some cases an attractive alternative for more involved schemes that utilize the phase and pulse shape of laser beams to control chemical reactions.     

基于RBF网络的增量学习

提出了一种基于径向网络的增量学习算法 ,在对新样本进行学习时 ,通过恢复受干扰样本的方式来尽可能保持已有的知识不变 .模拟实验证明了本算法的正确性和有效性 .     

无机盐和十二烷基磺酸钠对丙烯酰胺──烯丙基磺酸钠共聚物粘度的影响

测定了丙烯酰胺──烯丙基磺酸钠共聚物（ＰＡＳＡ）与无机盐和阴离子表面活性剂（ＡＳ）复配体系的粘度，结果表明，无机盐降低ＰＡＳＡ溶液的粘度，而在ＡＳ存在下却随ＡＳ浓度的升高溶液粘度升高．ＮａＣｌ和ＡＳ共存时，二者的共同作用，使溶液粘度呈下降趋势．     

基于广义RoI的遥感图像压缩

针对已有的基于RoI的图像压缩方法的不足，提出在初步分割出目标后，进一步在目标的语义方面进行改善，不仅保留对视觉有重要作用的边缘信息，而且基于图像的内容以及目标的语义，保留与目标相关的区域信息．并把这部分区域与已分割出的目标构成广义ROI，最后，对广义的ROI和背景分别用不同的压缩方法进行压缩．对广义ROI采用无损压缩以保留区域信息，对其余部分采用有损压缩以保留边缘信息．实验证明本文方法允许目标近无损分割，并能在不降低压缩比的前提下增强对重建目标的理解．     

光周期条件对罗氏沼虾幼体存活率及体长生长率的影响

用４Ｌ：２０Ｄ、８Ｌ；１６Ｄ；１２Ｌ；１２Ｄ和２４Ｌ：０Ｄ四种光周期条件培养罗氏沼虾骚状幼体，观察其存活率和生长、发育情况。研究结果表明，随着光照时间的延长，特别是在连续照明的条件下，与最短的光照条件相比，幼体的存活率及体长生长率分别提高１５７．７％和２．２％ｄ，而育成Ｐ１的时间却相应缩短了１０ｄ。     

螺旋输送机螺旋体挠度有限元分析

首次使用ＳＡＰ５软件对螺旋体整体结构进行了有限元分析，并分别使用ＦＯＲＴＲＡＮ和ＢＡＳＩＣ语言编制了可供实用的前后处理程序．笔者认为：采用有限元法对螺旋体挽度分析计算结果较过去的使用值为小，从而在同样工况下，可减小螺旋轴直径，使结构紧凑轻便，成本降低．实验证实了其结果的正确性．     

楼兰的兴衰与环境变迁、灾变

通过对楼兰兴衰史及同一时期的环境变化的综合研究表明 :楼兰的兴衰与环境的变迁、灾变密切相关 ,自然环境变迁、灾变是楼兰消亡的重要原因 .     

Development of liquid-nitrogen-cooling friction stir spot welding for AZ31 magnesium alloy joints

A liquid-nitrogen-cooling friction stir spot welding (C-FSSW) technology was developed for welding AZ31 magnesium alloy sheets. The liquid-nitrogen cooling degraded the deformability of the welded materials such that the width of interfacial cracks increased with increasing cooling time. The grain size of the stirred zone (SZ) and the heat-affected zone (HAZ) of the C-FSSW-welded joints decreased, whereas that of the thermomechanically affected zone (TMAZ) increased with increasing cooling time. The maximum tensile shear load of the C-FSSW-welded joints welded with a cooling time of 5 or 7 s was larger than that of the friction stir spot welding (FSSW)-welded joint, and the tensile shear load decreased with increasing cooling time. The microhardness of the C-FSSW-welded joints was greater than that of the FSSW-welded joint. Moreover, the microhardness of the SZ and the HAZ of the C-FSSW-welded joints increased, whereas that of the TMAZ decreased, with increasing cooling time.     

BRD7 regulates the insulin-signaling pathway by increasing phosphorylation of GSK3β

Reduced hepatic expression levels of bromodomain-containing protein 7 (BRD7) have been suggested to play a role in the development of glucose intolerance in obesity. However, the molecular mechanism by which BRD7 regulates glucose metabolism has remained unclear. Here, we show that BRD7 increases phosphorylation of glycogen synthase kinase 3β (GSK3β) in response to activation of the insulin receptor-signaling pathway shortly after insulin stimulation and the nutrient-sensing pathway after feeding. BRD7 mediates phosphorylation of GSK3β at the Serine 9 residue and this effect on GSK3β occurs even in the absence of AKT activity. Using both in vitro and in vivo models, we further demonstrate that BRD7 mediates phosphorylation of ribosomal protein S6 kinase (S6K) and leads to increased phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and, therefore, relieves its inhibition of the eukaryotic translation initiation factor 4E (eIF4E). However, the increase in phosphorylation of 4E-BP1 with BRD7 overexpression is blunted in the absence of AKT activity. In addition, using liver-specific BRD7 knockout (LBKO) mice, we show that BRD7 is required for mTORC1 activity on its downstream molecules. These findings show a novel basis for understanding the molecular dynamics of glucose metabolism and suggest the unique function of BRD7 in the regulation of glucose homeostasis.