A pseudoknot-like structure required for efficient self-cleavage of hepatitis delta virus RNA

Hepatitis delta virus genomic and antigenomic RNAs contain a self-cleavage site hypothesized to function in processing the viral RNA during replication. Self-cleavage requires only a divalent cation and is mediated at the genomic site by a sequence of less than 85 nucleotides. We propose that the genomic self-cleaving sequence element and a corresponding sequence from the anti-genomic RNA could generate related secondary structures. The region of the antigenomic sequence, predicted from the proposed structure, was synthesized and shown to be sufficient for self-cleavage. Evidence for two stems which form a tertiary interaction was obtained by site-specific mutagenesis of the antigenomic sequence. Efficient self-cleavage in 10 M formamide or 5 M urea, also a property of the genomic sequence, was dependent on base-pairing in both stems. But in the absence of denaturants, the stem distal to the site of cleavage was not required, suggesting that the tertiary interaction stabilizes the structure required for self-cleavage.     

The Tetrahymena ribozyme acts like an RNA restriction endonuclease

A shortened form of the Tetrahymena self-splicing ribosomal RNA intervening sequence acts as an endoribonuclease, catalysing the cleavage of large RNA molecules by a mechanism involving guanosine transfer. The sequence specificity approaches that of the DNA restriction endonucleases. Site-specific mutagenesis of the enzyme active site alters the substrate sequence specificity in a predictable manner, so that endoribonucleases can be synthesized to cut at a variety of tetranucleotide sequences.     

Microring-Assisted Coupling Between Dissimilar Waveguides

The use of microring resonators to assist in the evanescent field coupling between dissimilar waveguides is proposed and analyzed. Theoretical analysis based on the coupled mode theory and nu-merical example show that complete cross power transfers can be obtained near the microring resonances. Applications of the device include power dividers, low-power thermo-optic or electro-optic switches, and modulators.     

Ribozyme activity in the genomic and antigenomic RNA strands of hepatitis delta virus

In the hepatitis delta virus, ribozymes are encoded in both the genomic strand RNA and its complement, the antigenomic strand. The two ribozymes are similar in sequence and structure, are most active in the presence of divalent cation and catalyze RNA cleavage reactions which generate a 5′-hydroxyl group and a 2′,3′-cyclic phosphate group. Recent progress has been made in understanding the catalytic mechanism. One key was a crystal structure of the genomic ribozyme that revealed a specific cytosine positioned to act as a general acid-base catalyst. The folding of the ribozyme in the context of the longer viral RNA is another area of interest. The biology requires that each ribozyme act only once, and mechanisms proposed for regulation of ribozyme activity sometimes invoke alternative RNA structures. Likewise, interference of ribozyme function by polyadenylation of the antigenomic RNA strand could be controlled through alternative structures, and a model for such control is proposed. Received 21 June 2001; received after revision 18 July 2001; accepted 20 July 2001     

彩色多普勒超声在腹壁下动脉穿支选择中的应用

验证彩色多普勒超声对腹壁下动脉穿支血管术前探查的有效性,寻找腹壁下动脉穿支术前优势穿支的选择标准。利用彩色多普勒超声探查腹壁下动脉穿支皮瓣行乳房再造患者52例,重点记录穿支血管穿腹直肌前鞘点的体表投影、口径、血流信息,并通过分析比较以上信息,选择优势穿支。结果52例患者腹壁下动脉穿支穿腹直肌前鞘点于超声下均可显示,平均每侧下腹部3支,距脐平均(5.7±2.09)cm,其中条件适用于显微外科的穿支平均口径(0.95±0.32)cm,血流峰速平均约16.4 cm/s,阻力指数平均0.7。术中优势穿支采用率92.31%。说明高频彩色多普勒超声适用于腹壁下动脉穿支皮瓣术前血管探查,可精确指导穿支的术前选择,辅助手术方案制定以及皮瓣设计。     

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci

We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.     

Effective Approach to Elevate the Intelligence of Management Decision System

Based on the sticking point of the low intelligence of the existing management decision system, this paper puts forward the idea of enriching and refining the knowledge of the system and endowing it with the ability to learn by means of adopting three types of heterogeneous knowledge representation and knowledge management measures. At length, this paper outlines the basic framework of an intelligence system for the sake of management decision problem.     

Simulation and uniform design-based automatic generation of risk scenarios

This paper presents a methodology for automatically generating risk scenarios for dynamic reliability applications in which some dynamic characteristics(e.g.,the order,timing and magnitude of events,the value of relevant process parameters and initial conditions) have a significant influence on the evolution of the system.The main idea of the methodology is:(i) making the system model "express itself" through simulation by having the model driven by an elaborated simulation engine;(ii) exploiting uniform design to pick out a small subset of representative design points from the space of relevant dynamic characteristics;(iii) for each selected design point,employing a depth-first systematic exploration strategy to cover all possible scenario branches at each branch point.A highly dynamic example adapted from the literature(a chemical batch reactor) is studied to test the effectiveness of the proposed methodology.