Huntington’s disease: from huntingtin function and dysfunction to therapeutic strategies

Huntington’s disease (HD) is a neurodegenerative disorder that usually starts in middle age and is characterized by involuntary movements (chorea), personality changes and dementia, leading to death within 10–20 years. The defective gene in HD contains a trinucleotide CAG repeat expansion within its coding region that expresses a polyglutamine repeat in the protein huntingtin. Together with the characteristic formation of aggregates in HD, aberrant protein interactions and several post-translational modifications affect huntingtin during disease progression and lead to the dysfunction and death of selective neurons in the brains of patients. The exact molecular mechanisms by which mutant huntingtin induces cell death are not completely understood but may involve the gain of new toxic functions and the loss of the beneficial properties of huntingtin. This review focuses on the cellular functions in which huntingtin is involved and how a better understanding of pathogenic pathways can lead to new therapeutic approaches. Received 24 May 2006; received after revision 5 July 2006; accepted 23 August 2006     

The neurotrophic receptor TrkB: a drug target in anti-cancer therapy?

Increasing evidence implies altered signaling through the neurotrophic receptor tyrosine kinase TrkB in promoting tumor formation and metastasis. TrkB, sometimes in conjunction with its primary ligand BDNF, is often overexpressed in a variety of human cancers, ranging from neuroblastomas to pancreatic ductal adenocarcinomas, in which it may allow tumor expansion and contribute to resistance to anti-tumor agents. In vitro, TrkB acts as a potent suppressor of anoikis (detachment-induced apoptosis), which is associated with the acquisition of an aggressive tumorigenic and metastatic phenotype in vivo. In view of its predicted contribution to tumorigenicity and metastasis in humans, TrkB corresponds to a potential drug target, and preclinical models have already been established. The encouraging results of pharmacological Trk inhibitors in tumor xenograft models suggest that TrkB inhibition may represent a promising novel anti-tumor therapeutic strategy. This hypothesis is currently being evaluated in clinical trials. Here, we will discuss the latest developments on TrkB in these contexts as well as highlight some critical questions that remain to be addressed for evaluating TrkB as a therapeutic target in cancer. Received 12 October 2005; received after revision 19 December 2005; accepted 11 January 2006     

影响林木种子贮藏的因素

为了每年提供造林新需的具有生活力的种子及长期保存种质资源,贮藏种子是必要的手段。种子寿命具有遗传性,且因树种而异。种子的贮藏特性可以分成5类:正常型、亚正常型、温带顽拗型、热带顽拗型和中间型。种子含水量和贮藏温度是影响种子贮藏是否成功的两个最重要因素。但因树种及其贮藏特性不同,种子含水量和贮藏温度的最适值也不同。为了保持正常型和亚正常型种子的生活力,这类种子必须密封贮藏;但对顽拗型种子,因其需要保持种子的代谢活性及要进行有氧呼吸,则需要气体交换。     

BEM Analysis of Wave Propagation in a Water-Filled Borehole in an Anisotropic Solid

This paper describes a time-domain boundary element method developed to analyze the interactions of acoustic and elastic waves near the interfaces between water and an anisotropic elastic solid. Two models are analyzed with one being the interface between two half spaces of fluid and solid and the other being a fluid region sandwiched by half space domains of anisotropic elastic solids. Both monopole and dipole point sources are used to generate an initial pressure wave in the fluid. Some snapshots of the transient wave behavior near the fluid-solid interfaces are given. The effect of the anisotropy in the solid on the pressure waveforms in the fluid is discussed. The numerical results allow detailed arrival identification and interpretation of acoustic and elastic waves propagating along the fluid-solid interfaces.     

并六苯环石墨烯带的密度泛函研究

以并六苯环石墨烯带为研究对象,采用密度泛函理论的B3LYP方法,及6-31+G(d)基组,对该模型进行了分子轨道分析和频率计算。通过轨道分析得出了分子轨道能隙和轨道密度;经过频率计算得出模型的红外和拉曼光谱并说明了振动光谱中出现强峰的原因;最后与加氢并六苯环比较,对并六苯环石墨烯带的稳定性进行了讨论。     

对一种快速双重指数模算法的复杂度研究

最近提出了一种采用标准符号数二进制码(canonic signed-digit binary representation,CSDBR)来计算AXBY(modN)的快速双重指数模算法.该算法声明当指数的长度为k时,该算法平均仅需要1.306k次模乘.由于已知的此类算法至少需要1.503k次模乘,该算法具有明显的性能优势.然而,无论是该算法的提出者还是其他研究者均没有给出正确的复杂度分析.本文通过利用马尔科夫链模型对该算法进行正式的复杂度研究并进行一定规模的统计实验后证实,实际上该算法平均需要1.556k次模乘.这项研究的意义在于揭示到目前为止,基于标准符号数位码的双重指数模算法的最高性能仍然无法降低到1.5k次模乘以下.     

Expression of lysine-rich protein gene and analysis of lysine content in transgenic wheat

Expression vector pBPC102, which carries winged bean lysine-rich protein (wblrp) gene and dihydropicolinate synthase (DHDPS) gene, was transferred into hexaploid winter wheat cv. Jinghua No.l, Jing411, You899 and Yangnongl5 explants of immature inflorescence and immature embryos by particle bombardment. More than 100 transgenic plants were obtained under the selection of s-(2-aminoethyl)-L-cysteine (AEC). Confirmed transgenic plants of To and TI generation by PCR and PCR-Southern blotting analyses showed successful integration of wblrp gene into wheat genome. Analysis of transgenic plant lines of T2 by Northern dot-blotting showed good expression of wblrp gene in offspring seed. The content of free lysine in leaves, contents of bound lysine and total proteins in seeds of T2 transgenie wheat lines were determined and analyzed. Among 34 tested transgenic lines, levels of free lysine content in leaves of 9 transgenic lines are 2~3times higher than un-trans-formed wild-type cultivars. Among 17 analyzed transgenic lines, bound lysine content of 4 transgenic lines is more than 10% higher than that of wild-type cultivars. Our research suggests that introducing wblrp gene into wheat is an effective way to improve its nutrition quality.     

An Adaptive Design for Six Sigma（ ADFSS ） ： a Simulated Annealing and Regression Analysis Embedded Approach

Design for six sigma (DFSS) is a powerful approach of designing products,processes,and services with the objective of meeting the needs of customers in a cost-effective manner.DFSS activities are class...     

基于刚度及经济的CFRP与钢组合拉索设计理论

基于钢斜拉索、碳纤维增强塑料(CFRP)斜拉索适用跨径研究结果,针对1 400~2 800 m主跨斜拉桥整体刚度不足提出一种新型结构方案,即基于刚度及经济性能的CFRP与钢组合拉索方案.该方案将CFRP斜拉索与传统钢斜拉索同时应用于斜拉桥中,将２种材料高强轻质及弹性模量高的优点进行组合,以充分提高斜拉索的等效刚度,进而提高斜拉桥的整体刚度.详细介绍该组合方案设计思路与方法,通过比较等效刚度以及经济性能给出２种材料斜拉索推荐组合比例.最后,通过一座1 400 m主跨CFRP与钢组合拉索斜拉桥试设计说明该方案相对传统方案整体刚度上的优势,证明其工程应用的可行性,是主跨为1 400~2 800 m斜拉桥的优选方案之一.