Virulent Salmonella enterica infections can be exacerbated by concomitant infection of the host with a live attenuated S. enterica vaccine via Toll-like receptor 4-dependent interleukin-10 production with the involvement of both TRIF and MyD88.

During systemic disease in mice, Salmonella enterica grows intracellularly within discrete foci of infection in the spleen and liver. In concomitant infections, foci containing different S. enterica strains are spatially separated. We have investigated whether functional interactions between bacterial populations within the same host can occur despite the known spatial separation of the foci and independence of growth of salmonellae residing in different foci. In this study we have demonstrated that bacterial numbers of virulent S. enterica serovar Typhimurium C5 strain in mouse tissues can be increased by the presence of the attenuated aroA S. Typhimurium SL3261 vaccine strain in the same tissue. Disease exacerbation does not require simultaneous coinjection of the attenuated bacteria. SL3261 can be administered up to 48 hr after or 24 hr before the administration of C5 and still determine higher tissue numbers of the virulent bacteria. This indicates that intravenous administration of a S. enterica vaccine strain could potentially exacerbate an established infection with wild-type bacteria. These data also suggest that the severity of an infection with a virulent S. enterica strain can be increased by the prior administration of a live attenuated vaccine strain if infection occurs within 48 hr of vaccination. Exacerbation of the growth of C5 requires Toll-like receptor 4-dependent interleukin-10 production with the involvement of both Toll/interleukin-1 receptor-domain-containing adaptor inducing interferon-beta and myeloid differentiation factor 88.

LES and hybrid LES/RANS simulations for conjugate heat transfer over a matrix of cubes

Large Eddy Simulation (LES) and a novel k -l based hybrid LES/RANS approach have been applied to simulate a conjugate heat transfer problem involving flow over a matrix of surface mounted cubes. In order to assess the capability and reliability of the newly developed k -l based hybrid LES/RANS, numerical results are compared with new LES and existing RANS results. Comparisons include mean velocity profiles, Reynolds stresses and conjugate heat transfer. As well as for hybrid LES/RANS validation purposes, the LES results are used to gain insights into the complex flow physics and heat transfer mechanisms. Numerical simulations show that the hybrid LES/RANS approach is effective. Mean and instantaneous fluid temperatures adjacent to the cube surface are found to strongly correlate with flow structure. Although the LES captures more mean velocity field complexities, broadly time averaged wake temperature fields are found similar for the LES and hybrid LES/RANS. Copyright © 2005 by the American Institute of Aeronautics and Astronautics, Inc. All rights reserved.

Generation of conjugate meshes for complex geometries for coupled multi-physics simulations

Over recent years we have developed and published research aimed at producing a meshing, geometry editing and simulation system capable of handling large scale, real world applications and implemented in an end-to-end parallel, scalable manner. The particular focus of this paper is the extension of this meshing system to include conjugate meshes for multi-physics simulations. Two contrasting applications are presented: export of a body-conformal mesh to drive a commercial, third-party simulation system; and direct use of the cut-Cartesian octree mesh with a single, integrated, close-coupled multi-physics simulation system. Copyright © 2010 by W.N.Dawes.

Live Attenuated S. Typhimurium Vaccine with Improved Safety in Immuno-Compromised Mice

Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV). Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb-/-nos2-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb-/-nos2-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093), was >1000-fold attenuated in cybb-/-nos2-/- mice and ≈100 fold attenuated in tnfr1-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA) response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety. © 2012 Periaswamy et al.