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Gene products required for in vivo growth and survival of microbial pathogens comprise a unique functional class and may represent new targets for antimicrobial chemotherapy, vaccine construction, or diagnostics. Although some factors governing Staphylococcus aureus pathogenicity have been identified and studied, a comprehensive genomic analysis of virulence functions will be a prerequisite for developing a global understanding of interactions between this pathogen and its human host. In this study, we describe a genetic screening strategy and demonstrate its use in screening a collection of 6,300 S. aureus insertion mutants for virulence attenuation in a murine model of systemic infection. Ninety-five attenuated mutants were identified, reassembled into new pools, and rescreened using the same murine model. This effort identified 24 highly attenuated mutants, each of which was further characterized for virulence attenuation in vivo and for growth phenotypes in vitro. Mutants were recovered in numbers up to 1,200-fold less than wild type in the spleens of systemically infected animals and up to 4,000-fold less than wild type in localized abscess infections. Genetic analysis of the mutants identified insertions in 23 unique genes. The largest gene classes represented by these mutants encoded enzymes involved in small-molecule biosynthesis and cell surface transmembrane proteins involved in small-molecule binding and transport. Additionally, three insertions defined two histidine kinase sensor-response regulator gene pairs important for S. aureus in vivo survival. Our findings extend the understanding of pathogenic mechanisms employed by S. aureus to ensure its successful growth and survival in vivo. Many of the gene products we have identified represent attractive new targets for antibacterial chemotherapy.

Four-dimensional (4D) models link three-dimensional geometrical models with construction schedule data. The visual link between the schedule and construction site conditions is capable of facilitating decision making during both the planning and construction stages. The emphases of these 4D developments have often been placed at the level of construction components. Practical features assisting site management are at times lacking in the following areas: (1) generation of site usage layouts; (2) estimation of quantities of construction materials; and (3) cost evaluation. In order to pinpoint these deficiencies, the objective of this work is to enable visual study of the effects of job progress on the logistics and resource schedules. This paper presents a 4D visualization model that is intended both to help construction managers plan day-to-day activities more efficiently in a broader and more practical site management context and to thereby add to our knowledge and understanding of the relevance of modern computer graphics to the responsibilities of the construction site manager. A brief site trial of the software is described at the conclusion of the paper. CE Database subject headings: Computer aided scheduling; Graphic methods; Construction management; Construction planning; Three-dimensional models; Construction sites.

Carbon nanotubes may behave as metallic, insulating or semiconducting wires, indicating their use in nanometre-scale engineering and electronics. Carbon-arc discharge techniques, catalytic pyrolysis of hydrocarbons and condensed-phase electrolysis are commonly used to generate nanotubes, but polyhedral particles are also formed. A method of producing aligned carbon nanotubes through pyrolysis of 2-amino-4, 6-dichloro-s-triazine over a thin patterned catalyst on a silica substrate by laser etching, is described.