Enhanced virulence of Salmonella enterica serovar typhimurium after passage through mice.

The interaction between Salmonella enterica and the host immune system is complex. The outcome of an infection is the result of a balance between the in vivo environment where the bacteria survive and grow and the regulation of fitness genes at a level sufficient for the bacteria to retain their characteristic rate of growth in a given host. Using bacteriological counts from tissue homogenates and fluorescence microscopy to determine the spread, localization, and distribution of S. enterica in the tissues, we show that, during a systemic infection, S. enterica adapts to the in vivo environment. The adaptation becomes a measurable phenotype when bacteria that have resided in a donor animal are introduced into a recipient naïve animal. This adaptation does not confer increased resistance to early host killing mechanisms but can be detected as an enhancement in the bacterial net growth rate later in the infection. The enhanced growth rate is lost upon a single passage in vitro, and it is therefore transient and not due to selection of mutants. The adapted bacteria on average reach higher intracellular numbers in individual infected cells and therefore have patterns of organ spread different from those of nonadapted bacteria. These experiments help in developing an understanding of the influence of passage in a host on the fitness and virulence of S. enterica.

Design support for turbomachinery

From the steam turbines which provide most of our electricity to the jet engines which have shrunk our World, turbomachines undoubtedly play a major role in life today. Competition in the turbomachinery industry is fiercely strong [Wisler, 1998], hence good aerodynamic design is vital. However, with efficiency levels already close to their theoretical maxima, companies are increasingly looking to reduce costs and increase reliability through improved design practice. Computational Fluid Dynamics (CFD) can make a strong contribution to assisting this process as it has the potential to increase performance while reducing cost. The situation is, however, complicated by an ever decreasing number of engineers with sufficient design experience to reap the full benefits offered by CFD. With the large risks involved, novice designers of today are increasingly confined to refining old designs rather than gaining experience, like their forebears, through 'clean sheet' exercises. Hence it is desirable to capture the knowledge and experience of older designers, before it is lost, to assist the engineers of tomorrow. It is therefore the aim of this project to produce a design support tool which will not only store the appropriate CFD codes, but also provide a dynamic signpost (based on elicited knowledge and experience) to advise the engineer in their use. The signposting methodology developed for the aerospace industry [Clarkson and Hamilton, 1997] will provide the basic framework for the tool. This paper reviews current turbomachinery design practice (including an examination of the relevant CFD) in order to establish the important issues which a support tool must address. Current design support methodologies and their propriety are then reviewed, followed by a detailed description of the signposting concept. It then sets out a clear statement of the objectives for the research and the methods proposed to meet them. The paper concludes with a timetable of the work.