Genome sequence of enterohaemorrhagic Escherichia coli O157:H7

The bacterium Escherichia coli O157:H7 is a worldwide threat to public health and has been implicated in many outbreaks of haemorrhagic colitis, some of which included fatalities caused by haemolytic uraemic syndrome. Close to 75,000 cases of O157:H7 infection are now estimated to occur annually in the United States. The severity of disease, the lack of effective treatment and the potential for large-scale outbreaks from contaminated food supplies have propelled intensive research on the pathogenesis and detection of E. coli O157:H7 (ref. 4). Here we have sequenced the genome of E. coli O157:H7 to identify candidate genes responsible for pathogenesis, to develop better methods of strain detection and to advance our understanding of the evolution of E. coli, through comparison with the genome of the non-pathogenic laboratory strain E. coli K-12 (ref. 5). We find that lateral gene transfer is far more extensive than previously anticipated. In fact, 1,387 new genes encoded in strain-specific clusters of diverse sizes were found in O157:H7. These include candidate virulence factors, alternative metabolic capacities, several prophages and other new functions--all of which could be targets for surveillance.     

Microfluidic systems: high radial acceleration in microvortices

Microfluidic systems can conveniently be used for rapid analysis of biological samples. Here we describe a single re-circulating flow, or microvortex, that can generate a maximum fluid rotational velocity of up to 12 m s(-1) and a corresponding radial acceleration in excess of 10(6)g. Such microvortices may be exploited in centrifugal microdevices to investigate the effects of high radial acceleration on biological and chemical processes.     

ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway

The rare diseases ataxia-telangiectasia (AT), caused by mutations in the ATM gene, and Nijmegen breakage syndrome (NBS), with mutations in the p95/nbs1 gene, share a variety of phenotypic abnormalities such as chromosomal instability, radiation sensitivity and defects in cell-cycle checkpoints in response to ionizing radiation. The ATM gene encodes a protein kinase that is activated by ionizing radiation or radiomimetic drugs, whereas p95/nbs1 is part of a protein complex that is involved in responses to DNA double-strand breaks. Here, because of the similarities between AT and NBS, we evaluated the functional interactions between ATM and p95/nbs1. Activation of the ATM kinase by ionizing radiation and induction of ATM-dependent responses in NBS cells indicated that p95/nbs1 may not be required for signalling to ATM after ionizing radiation. However, p95/nbs1 was phosphorylated on serine 343 in an ATM-dependent manner in vitro and in vivo after ionizing radiation. A p95/nbs1 construct mutated at the ATM phosphorylation site abrogated an S-phase checkpoint induced by ionizing radiation in normal cells and failed to compensate for this functional deficiency in NBS cells. These observations link ATM and p95/nbs1 in a common signalling pathway and provide an explanation for phenotypic similarities in these two diseases.     

Direct measurement of exocytosis and calcium currents in single vertebrate nerve terminals

The release of neurohormone is widely thought to be exocytotic, involving Ca2(+)-dependent fusion of secretory vesicles with the plasma membrane. The inaccessibility of most nerve ending has so far hampered direct time-resolved measurements of neuronal exocytosis in response to brief depolarization. By using 'whole-terminal' patch-clamp and circuit-analysis techniques to measure membrane capacitance, we have now monitored changes in the surface membrane area of individual nerve terminals isolated from the mammalian neurohypophysis. A single depolarizing pulse leading to Ca2+ entry through voltage-gated calcium channels, rapidly and reproducibly increases the membrane area by an amount corresponding to the fusion of 1-100 secretory vesicles. The magnitude of the capacitance increase depends not only on Ca2+ entry and buffering, but also on the pattern of stimulation revealing facilitation, fatigue and recovery of the release process.     

Short-range linkage relationships, genomic organisation and sequence comparisons of a cluster of five HSP70 genes in Fugu rubripes

Twelve cosmids containing sequences resembling genes encoding members of the 70-kDa heat-shock protein family, HSP70, have been isolated from Fugu rubripes. They can be broadly divided into three groups of overlapping cosmids. Restriction analysis and sequencing of one set of five cosmids have revealed five intronless Fugu HSP70 genes spanning 42 kb, arranged in a combined head-to-head, tail-to-tail and head-to-tail orientation. The levels of DNA and amino acid identity are very high with respect to one another, and are most similar to HSP70 sequences linked to the major histocompatibility complex (MHC) region in other species. Putative heat-shock consensus elements are identified. Non-HSP70 sequences with homology to known genes have been found physically linked to this Fugu HSP70 cluster: the Drosophila melanogaster SOL gene, the Drosophila melanogaster nemo gene, the Caenorhabditis elegans T17E9.1 gene and the sequence encoding the serine protease domain. The linkage relationships described here so far bear no resemblance to those of HSP70 in other organisms. Convergence of mammalian HSP70 and MHC class I and II loci probably occurred after fish had diverged. Received 17 November 1998; received after revision 25 February 1999; accepted 26 February 1999     

Total quality management in manufacturing: A study in the Singapore context

The paper presents a total quality management (TQM) framework combining the concepts underlying the notions of total quality control (TQC), Just in Time (JIT), manufacturing resource planning (MRP), and quality control circles (QCCs). An integrative model, in which these notions and the related issues are complementarily connected on the same logical plane is presented and it is argued that this is akin to the total systems intervention (TSI) approach in its endeavor to seek manufacturing excellence. It also has similarities to creative problem solving, especially with regard to corporate strategy, but here with an emphasis on the role of manufacturing. However, TQM is an idea of its own, and not a conceptual derivative of systems theory.     

域上矩阵方程∑A~iXB_i＝C的显式解

本文讨论了域上矩阵方程有解或有唯一解的条件，并给出了几个显式解公式。参５。