Cardioviral internal ribosomal entry site is functional in a genetically engineered dicistronic poliovirus.

High mutation rates have driven RNA viruses to shorten their genomes to the minimum possible size. Mammalian (+)-strand RNA viruses and retroviruses have responded by reducing the number of cis-acting regulatory elements, a constraint that has led to the emergence of the polyprotein. Poliovirus is a (+)-stranded picornavirus whose polyprotein, encoded by an open reading frame spanning most of the viral RNA, is processed by virus-encoded proteinases. Despite their genetic austerity, picornaviruses have retained long 5' untranslated regions, which harbour cis-acting elements that promote initiation of translation independently of the uncapped 5' end of the viral messenger RNA. These elements are termed 'internal ribosomal entry sites' and are formed from highly structured RNA segments of at least 400 nucleotides. How these elements function is not known, but special RNA-binding proteins may be involved. The ribosome or its 40S subunit probably binds at or near a YnXmAUG motif (where Y is a pyrimidine and X is a purine) at the 3' border of the internal ribosomal entry site, which either provides the initiating codon or enables the ribosome to translocate to one downstream (E.W. et al., submitted). Initiation from most eukaryotic messenger RNAs usually occurs by ribosomal recognition of the 5' and subsequent scanning to the AUG codon. Here we describe a genetic strategy for the dissection of polyproteins which proves that an internal ribosomal entry site element can initiate translation independently of the 5' end.     

Critical role of an eight-amino acid sequence of VP1 in neutralization of poliovirus type 3

The three serotypes of poliovirus are members of the picornaviradae, a group of viruses which cause a variety of diseases of considerable importance in man and animals. We have previously used antigenic mutants resistant to neutralizing monoclonal antibodies to identify a single antigenic site for the neutralization of poliovirus type 3 (ref. 1). Evidence based on oligonucleotide mapping suggested that this site corresponded largely to one physicochemical region of the capsid protein viral polypeptide 1 (VP1). We now present conclusive evidence that most of the mutations conferring resistance to neutralization are confined to an eight-amino acid region of VP1, specified by a sequence of viral RNA 277-300 bases from the start of the region coding for VP1. These data strongly suggest that this small region constitutes a major antigenic site involved in virus neutralization and they provide the most detailed information currently available on the antigenic site of a human virus.     

Iscom, a novel structure for antigenic presentation of membrane proteins from enveloped viruses

We describe here a novel type of immunostimulating complex, called 'iscom', in which virus membrane proteins are presented in a multimeric form. The matrix of the iscom is the glycoside Quil A (Spikoside; Iscotec AB), extracted from the bark of Quillaja saponaria Molina, which forms micelles at the critical micellar concentration of 0.03%. In micelle form, Quil A probably has regions accessible for hydrophobic interaction with the membrane proteins so that it can form complexes with them. Iscoms have been prepared with membrane proteins of para-influenza-3 (PI-3), measles and rabies viruses, and their immunizing potency tested in animals. In these experiments, iscoms prove to be at least 10 times more potent than micelles formed by aggregation of the membrane proteins alone. Iscoms of PI-3 and measles viruses also stimulate the formation of antibody to the fusion (F) protein, which is considered to be poorly immunogenic. No side effects of iscoms or of protein micelles have been observed.     

Primary structure, gene organization and polypeptide expression of poliovirus RNA

The primary structure of the poliovirus genome has been determined. The RNA molecule is 7,433 nucleotides long, polyadenylated at the 3' terminus, and covalently linked to a small protein (VPg) at the 5' terminus. An open reading frame of 2,207 consecutive triplets spans over 89% of the nucleotide sequence and codes for the viral polyprotein NCVPOO. Twelve viral polypeptides have been mapped by amino acid sequence analysis and were found to be proteolytic cleavage products of the polyprotein, cleavages occurring predominantly at Gln-Gly pairs.     

大震下高层型钢混凝土结构弹塑性分析

为研究钢-混凝土高层混合结构在大震下的抗震性能,对某实际型钢-混凝土高层建筑进行了动力弹塑性分析。运用三维有限元分析程序CANNY06,得出了结构在大震下的内力和变形规律,并与静力弹塑性分析结果进行对比。研究推覆分析是否适用于评价混合结构抗震性能。研究钢-混凝土组合楼盖在大震下的工作性。结果表明:静力推覆分析不一定能满足"大震不倒"的抗震设防要求;当结构高宽比大于3时,组合楼盖在弹塑性阶段仍可按刚性楼盖考虑;而且高宽比越大,简化带来的误差越小。     

大震下高层型钢混凝土结构弹塑性分析

为研究钢-混凝土高层混合结构在大震下的抗震性能,对某实际型钢-混凝土高层建筑进行了动力弹塑性分析。运用三维有限元分析程序CANNY06,得出了结构在大震下的内力和变形规律,并与静力弹塑性分析结果进行对比。研究推覆分析是否适用于评价混合结构的抗震性能。研究钢-混凝土组合楼盖在大震下的工作性。结果表明:静力推覆分析不一定能满足“大震不倒”的抗震设防要求;当结构高宽比大于3时,组合楼盖在弹塑性阶段仍可按刚性楼盖考虑,而且高宽比越大,简化带来的误差越小。     

Three-dimensional structure of an antigenic mutant of the influenza virus haemagglutinin

Antigenic variation in the haemagglutinin (HA) glycoprotein of influenza virus is associated with recurrent epidemics of respiratory disease in man (for review see ref. 1). We have examined the size of structural changes necessary to alter the antigenicity of HA by determining the three-dimensional structure of the HA from an antigenic mutant containing a single amino acid substitution which was selected by growth of virus in the presence of monoclonal antibodies. Here we present evidence that the simple addition of an amino acid side chain which results in only minor local distortions of the structure of the HA is sufficient structural alteration for a virus to escape neutralization by a monoclonal antibody. Our results also demonstrate that single amino acid substitutions can cause only local changes in the HA structure, verifying the assumption made in several studies to locate antigenic sites on the HA and other molecules, and indicate that proposals of large conformational changes to account for variations in HA antigenicity are unnecessary in this case. The structure of the variant antigen has independently been successfully predicted (M. Karplus, personal communication).     

Location of the ATPase site of myosin determined by three-dimensional electron microscopy

Both ATP hydrolysis by myosin and the accompanying cyclic association-dissociation of actin and myosin are essential for muscle contraction. It is important for understanding the molecular mechanism of contraction to know the three-dimensional locations of the two major functional sites of myosin: the ATPase site and the actin-binding site. We have determined the position of the ATPase site of myosin using three-dimensional image reconstruction from electron micrographs and site-specific labelling with the avidin-biotin system. The ATPase site is about 5 nm from the tip of the myosin head and is about 4 nm away from the actin-binding site of myosin. This is the first report of the three-dimensional location of an enzyme active site by electron microscopy.     

网络选址的两级决策模型

本文提出了以用户优化为下级决策,以设施选址优化为上级决策的网络选址两级决策模型,给出了树状网络下模型求解的基本定理及相应的算法,并从一个重要的反例出发,讨论了Braess佯谬与模型的联系。     

Evaluation method of Web site structure based on Web structure mining

0　IntroductionSincethemostservicesinInternetareofferedviaWeb ,WorldWideWebbecomesmoreimportantthanbefore.TheWebsitestructureisbecomingmorecomplex .InWebsite’splanninganddesigning ,theWebsitestructureisdependantonthedesigner’sexperienceforlackingofmodelandmethod,whichleadstounreasonableWebstructureforusersaccessingandlossesmanyvisitors.Itisagreatpityforcommercesiteorenterprisebusinesssite.Fromtheviewofthepointofsoftwareengineering ,theperformanceofWebsiteshouldbeevaluatedineveryperiodof…     

Human genes for U2 small nuclear RNA map to a major adenovirus 12 modification site on chromosome 17

U2 RNA is one of the abundant, highly conserved species of small nuclear RNA (snRNA) molecules implicated in RNA processing. As is typical of mammalian snRNAs, human U1 and U2 are each encoded by a multigene family. In the human genome, defective copies of the genes (pseudogenes) far outnumber the authentic genes. The majority or all of the 35 to 100 bona fide U1 genes have at least 20 kilobases (kb) of nearly perfect 5' and 3' flanking homology in common with each other; these U1 genes are clustered loosely in chromosome band 1p36 (refs 5, 7) with intergenic distances exceeding 44 kb. In contrast, the 10 to 20 U2 genes are clustered tightly in a virtually perfect tandem array which has a strict 6-kb repeating unit. We report here the assignment, by in situ hybridization, of the U2 gene cluster to chromosome 17, bands q21-q22. Surprisingly, this region is one of three major adenovirus 12 modification sites which undergo chromosome decondensation ('uncoiling') in permissive human cells infected by highly oncogenic strains of adenovirus. The two other major modification sites, 1p36 and 1q21, coincide with the locations of U1 genes and class I U1 pseudogenes, respectively. We suggest that snRNA genes are the major targets of viral chromosome modification.     

Solution structure of the major binding protein for the immunosuppressant FK506

The major FK506 binding protein (FKBP, relative molecular mass approximately 11,800; Mr 11.8K) and cyclophilin (Mr approximately 17K) belong to a class of proteins termed immunophilins. Although unrelated at the amino-acid sequence level, they both possess peptidyl-prolyl cis-trans isomerase activities which are inhibited by immunosuppressants that block signal transduction pathways leading to T-lymphocyte activation. FK506 and rapamycin strongly inhibit the peptidyl-prolyl cis-trans isomerase activity of FKBP, whereas cyclosporin A inhibits that of cyclophilin. The significance of this enzyme activity and the role of the immunophilins in immunoregulation is unknown. To understand better the function of the immunophilins and their interaction with inhibitors, we are investigating the solution structures of FKBP and FKBP-inhibitor complexes by multidimensional NMR methods. Here we report the solution conformation of FKBP, as generated by NMR, distance geometry and molecular dynamics methods. The regular secondary structure of FKBP is composed mainly of beta sheet (approximately 35%) with little helical structure (less than 10%). The hydrophobic core of the molecule, containing the buried side chains of six of the protein's nine aromatic amino acids, is enclosed by a five-stranded antiparallel beta sheet on one side, a loop and a short helix at residues 51-56 and 57-65, and an aperiodic loop at residues 81-95. Examination of the structure suggests a possible site of interaction with FK506.     

车辆定位导航系统的新定位算法

依据大数定律及其相关的假设,用计算几何的若干知识,设计车辆定位导航系统的一种新定位算法.该算法通过计算凸壳、凸多边形三角剖分、凸多边形面积及直径等诸量获得车辆运行的近似路线.计算结果表明,用该算法可以提高车辆定位导航系统的定位精度,并优于基于卡尔曼滤波的GPS/INU/MM组合导航算法的结果.     

用部分中和法制备超细二氧化钛粉体

采用部分中和法制备超细TiO2粉体,通过TEM、XRD和TG-DTA对产品进行了表征,指出水合TiO2在煅烧过程中逐步失去游离水和化合水,再形成TiO2结晶,且随着煅烧温度的上升,颗粒的粒度迅速增大.在600℃以下煅烧时所形成的TiO2颗粒为锐钛型,在800*!℃时完全转化为金红石型.     

Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences

Two related, but distinct, cDNA clones have been isolated and sequenced from a functional murine cytotoxic T-lymphocyte clone. The genes corresponding to these cDNA are expressed and rearranged specifically in T cells and both have similarities to immunoglobulin variable and constant region genes. It is concluded that these genes code for the two subunits of the heterodimeric antigen receptor on the surface of the T cell; its complete deduced primary structure is presented.