Intragenic amplification and divergence in the mouse alpha-fetoprotein gene

The DNA sequences of the 14 exon junctions in the murine alpha-fetoprotein gene were determined using cloned genomic DNA. When these exons were examined with respect to the polypeptide segments they encoded, a direct correspondence between a threefold repeat of four exons and three protein domains was observed. Nucleotide sequence comparisons among the four exons of each domain were used to deduce the likely structure of the primordial domain, and the order and mechanism of its triplication to form the tripartite ancestral gene from which both alpha-fetoprotein and serum albumin arose. Sequence homologies among the four exons that constitute a single domain also suggest that they were derived, at least in part, from a common sequence which underwent successive amplification and divergence.     

Structural mechanism for sterol sensing and transport by OSBP-related proteins

The oxysterol-binding-protein (OSBP)-related proteins (ORPs) are conserved from yeast to humans, and are implicated in the regulation of sterol homeostasis and in signal transduction pathways. Here we report the structure of the full-length yeast ORP Osh4 (also known as Kes1) at 1.5-1.9 A resolution in complexes with ergosterol, cholesterol, and 7-, 20- and 25-hydroxycholesterol. We find that a single sterol molecule binds within a hydrophobic tunnel in a manner consistent with a transport function for ORPs. The entrance is blocked by a flexible amino-terminal lid and surrounded by basic residues that are critical for Osh4 function. The structure of the open state of a lid-truncated form of Osh4 was determined at 2.5 A resolution. Structural analysis and limited proteolysis show that sterol binding closes the lid and stabilizes a conformation favouring transport across aqueous barriers and signal transmission. The structure of Osh4 in the absence of ligand exposes potential phospholipid-binding sites that are positioned for membrane docking and sterol exchange. On the basis of these observations, we propose a model in which sterol and membrane binding promote reciprocal conformational changes that facilitate a sterol transfer and signalling cycle.     

Analysis of the DNA sequence and duplication history of human chromosome 15

Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplications in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.     

基于Workbench的防辐射挖掘机驾驶舱支座的有限元分析

增加了屏蔽层的防辐射驾驶舱较之原来驾驶舱增重了5.5 t,有必要对其支座的强度进行分析与校核.本文应用ANSYS Workbench对防辐射挖掘机驾驶舱支座进行有限元分析,得到其应变和应力分布情况;采取支撑板和回转平台底板加厚等措施对驾驶舱支座进行结构优化.最后对挖掘机回转平台进行模态分析,得出回转平台前十阶的固有频率和振型.模态分析为支撑座的强度设计,减少驾驶舱的振动提供了理论依据.     

智能工作流管理系统的设计

现存智能代理系统中存在许多问题．首先,现在绝大多数智能代理系统中所采用的推断方法效率都不高,其次,代理系统中各个子系统之间的通讯方法也不能满足需要．为得到一个更好的智能代理系统,提出了一种新的多元智能代理系统,它是传统的以知识为主体的系统与智能系统相结合的产物．另外,还提出了一种新的混合推断方法,它改进了现在普遍采用的混合推断方法．     

Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease.

Huntington's disease is an autosomal-dominant progressive neurodegenerative disorder resulting in specific neuronal loss and dysfunction in the striatum and cortex. The disease is universally fatal, with a mean survival following onset of 15-20 years and, at present, there is no effective treatment. The mutation in patients with Huntington's disease is an expanded CAG/polyglutamine repeat in huntingtin, a protein of unknown function with a relative molecular mass of 350,000 (M(r) 350K). The length of the CAG/polyglutamine repeat is inversely correlated with the age of disease onset. The molecular pathways mediating the neuropathology of Huntington's disease are poorly understood. Transgenic mice expressing exon 1 of the human huntingtin gene with an expanded CAG/polyglutamine repeat develop a progressive syndrome with many of the characteristics of human Huntington's disease. Here we demonstrate evidence of caspase-1 activation in the brains of mice and humans with the disease. In this transgenic mouse model of Huntington's disease, expression of a dominant-negative caspase-1 mutant extends survival and delays the appearance of neuronal inclusions, neurotransmitter receptor alterations and onset of symptoms, indicating that caspase-1 is important in the pathogenesis of the disease. In addition, we demonstrate that intracerebroventricular administration of a caspase inhibitor delays disease progression and mortality in the mouse model of Huntington's disease.     

郭守敬的《授时历》和朝鲜的《七政算内篇》

《授时历》被评价为中国历史上最优秀的历法,并且成为明朝《大统历》和朝鲜《七政算内篇》成书的基础。《七政算内篇》是朝鲜世宗时代(1418—1450年)取得的重要天文业绩之一,以《回回历》为基础,与《七政算外篇》一同于1444年编纂成书。《七政算内篇》的历元、天文常数和计算法等基本体系参照《授时历》,应数值则参照了《大统历》的辛巳应数。且把四余添加在推步的项目中,在计算日月食时使用的常数值则参考了元统1384年编纂的《大统历法通轨》,《七政算内篇》汲取了《授时历》和《大统历》的优点。