Lack of Effect of Murine Norovirus Infection on a Mouse Model of Bacteria-Induced Colon Cancer

Murine norovirus (MNV) is endemic in mouse research facilities in the United States and Europe, with a prevalence as high as 58% to 64%. Because of MNV's orofecal route of infection, clinically silent persistent infections in some mouse strains, and proclivity for macrophage and dendritic cells, its presence in mouse colonies has potential to alter phenotypes in experimental mouse models, particularly those involving inflammation and immunologic responses. Although MNV is subclinical, not causing overt disease in immunocompetent mice, we found that MNV infection can accelerate bacteria-induced inflammatory bowel disease (IBD) progression in Mdr1a^(-/-) mice. The studies presented here examined whether MNV infection also affects the phenotype of a bacterially driven mouse model of inflammation-associated colon cancer in genetically susceptible Smad3^(-/-) mice. In vitro culture of bone-marrow—derived macrophages (BMDM) was used to determine whether MNV4 influenced macrophage cytokine production. For in vivo studies, Smad3-/- mice were infected with MNV4 one week prior to infection with Helicobacter. Mice were monitored for 17 to 32 wk for development of IBD and colon cancer, and tissues were analyzed histopathologically. Although in vitro infection of BMDM with MNV4 led to increased inflammatory cytokine production, infection with MNV4 in vivo did not result in any statistically significant differences in survival, IBD scores, tumor incidence, or tumor phenotype in Smad3^(-/-) mice. In addition, MNV infection alone did not result in IBD or colon cancer. Therefore MNV infection alone or in conjunction with Helicobacter does not alter the development or progression of IBD or colon cancer in Smad3^(-/-) mice

Human Performance in Information Transmission: Part V: The Force of Habit

Control Systems Laboratory changed its name to Coordinated Science LaboratoryContract DA-36-039-SC-5669

RTDF2007-46016 ONBOARD LOCOMOTIVE EXHAUST EMISSIONS MEASUREMENT

ABSTRACT Limiting harmful locomotive exhaust emissions is important to the Nation's health and safety. The Environmental Protection Agency (EPA) has comprehensive gaseous exhaust emissions (or referred to as emissions hereto) testing requirements in place. All current tests are conducted on stationary locomotives. This paper discusses the development of an efficient stationary emissions measurement system that is compact, portable, easy to use, and applicable to onboard locomotives for in-use, over-the-road testing. More efficient locomotive emissions testing and better understanding of in-use emissions would be beneficial to all stakeholders. Sharma & Associates, Inc., (SA) adapted an off-the-shelf, portable, on-road, heavy-duty diesel truck emissions analyzer for locomotive use. This process included development of the necessary peripheral equipment and a computer program to take the raw emissions and report them as brake-specific emissions rates and duty cycle emissions. This paper describes the use of this system on a stationary locomotive. The system is currently being fitted and tested for over-the-road use. The measurement of particulate matter and smoke opacity were out of scope of the phase of the project that this paper is based on and not addressed hereto

Compilation of 59 sonic and density logs from 51 oil test wells

ABSTRACT Several relatively thick (>3 km deep) Cenozoic basins, including the Cupertino, Evergreen, Livermore, and San Pablo basins, may locally enhance strong ground motions in the San Francisco Bay area, California. As part of a crustal-scale, three-dimensional seismic velocity and density model for the Bay area, we have compiled data from sonic and density logs from oil test wells in the Bay area to better understand strong motion resonances generated by these basins. We have compiled the velocities and densities of sediments and rocks within these Cenozoic basins using 59 sonic and density logs from 51 oil test wells. The well data are primarily from the Livermore, Concord, and Los Medanos oil fields, and the Sacramento-San Joaquin delta, and provide measurements from the surface to as much as 5.3 km subsurface. Only a few logs from the South Bay are included in this compilation. The logs were hand digitized at non-uniform intervals between 3 and 30 m to capture the significant variations of the logs with depth for frequencies up to 2 Hz. Linear regression through 41 sonic logs yields Vp (km/s) = 2.24 + 0.599Z, where Z is depth in km. Shallow borehole data, generally from the South Bay, and from less than 30 m deep, indicate that the average surficial P-wave velocity at 10 holes in weathered Tertiary sedimentary units ranges from 2.21 and 2.32 km/s and is in close agreement with extrapolated P-wave velocities inferred from the oil test wells. A sonic log for Eocene sediments from Butano Ridge in San Mateo County shows that at a given depth, velocities are approximately 0.5 km/s higher than those near Livermore. The higher P-wave velocities for the Tertiary sedimentary rocks at Butano Ridge probably result from a combination of dense volcanic clasts in conglomerates plus very tight compaction of the sandstones. Density logs in Cenozoic sedimentary rocks show higher scatter. Linear regression of 18 density logs yield p (g/cm3) = 2.25 + 0.065Z. Average densities of weathered Tertiary sedimentary rocks measured on core samples from 5 shallow boreholes in the South Bay lie between 2.20 and 2.25 g/cm3 , in close agreement with the surficial density inferred from linear regression of oil well data. This report presents the locations, elevations, depths, stratigraphic and other information about the oil test wells, provides plots showing the density and sonic velocities as a function of depth for each well log, and compiles all data to better understand the velocities and densities of Cenozoic sedimentary rocks in the Bay area. CONTENT

Gammaherpesvirus Latency Accentuates EAE Pathogenesis: Relevance to Epstein-Barr Virus and Multiple Sclerosis

Epstein-Barr virus (EBV) has been identified as a putative environmental trigger of multiple sclerosis (MS), yet EBV's role in MS remains elusive. We utilized murine gamma herpesvirus 68 (γHV-68), the murine homolog to EBV, to examine how infection by a virus like EBV could enhance CNS autoimmunity. Mice latently infected with γHV-68 developed more severe EAE including heightened paralysis and mortality. Similar to MS, γHV-68EAE mice developed lesions composed of CD4 and CD8 T cells, macrophages and loss of myelin in the brain and spinal cord. Further, T cells from the CNS of γHV-68 EAE mice were primarily Th1, producing heightened levels of IFN-γ and T-bet accompanied by IL-17 suppression, whereas a Th17 response was observed in uninfected EAE mice. Clearly, γHV-68 latency polarizes the adaptive immune response, directs a heightened CNS pathology following EAE induction reminiscent of human MS and portrays a novel mechanism by which EBV likely influences MS and other autoimmune diseases

Gravity-driven instabilities: interplay between state-and-velocity dependent frictional sliding and stress corrosion damage cracking

We model the progressive maturation of a heterogeneous mass towards a gravity-driven instability, characterized by the competition between frictional sliding and tension cracking, using array of slider blocks on an inclined basal surface, which interact via elastic-brittle springs. A realistic state- and rate-dependent friction law describes the block-surface interaction. The inner material damage occurs via stress corrosion. Three regimes, controlling the mass instability and its precursory behavior, are classified as a function of the ratio $T_c/T_f$ of two characteristic time scales associated with internal damage/creep and with frictional sliding. For $T_c/T_f \gg 1$, the whole mass undergoes a series of internal stick and slip events, associated with an initial slow average downward motion of the whole mass, and progressively accelerates until a global coherent runaway is observed. For $T_c/T_f \ll 1$, creep/damage occurs sufficiently fast compared with nucleation of sliding, causing bonds to break, and the bottom part of the mass undergoes a fragmentation process with the creation of a heterogeneous population of sliding blocks. For the intermediate regime $T_c/T_f \sim 1$, a macroscopic crack nucleates and propagates along the location of the largest curvature associated with the change of slope from the stable frictional state in the upper part to the unstable frictional sliding state in the lower part. The other important parameter is the Young modulus $Y$ which controls the correlation length of displacements in the system.Comment: 40 pages, 13 figure

Efficiently stimulated adult microglia cross-prime naive CD8+T cells injected in the brain

Microglia are the major myeloid-immune cells of the brain parenchyma. In a steady state, microglia monitor their environment for pathogens or damaged cells. In response to neural injury or inflammation, microglia become competent APCs able to prime CD4+ and CD8+ T lymphocytes. We previously demonstrated that neonatal and adult microglia cross-present exogenous soluble Ags in vitro. However, whether microglia are able to cross-present Ag to naive CD8+ T cells in vivo, within the brain microenvironment, remains undetermined. Here, we have designed an original protocol in order to exclude the involvement in cross-presentation activity of peripheral migrating APCs and of CNS-associated APCs. In C57Bl/6 mice, in which the body but not the head has been properly irradiated, we analyzed the ability of resident microglia to stimulate intracerebrally injected CD8+ T cells in vivo. This study demonstrates for the first time that adult microglia cross-present Ag to naive CD8+ T cells in vivo and that full microglia activation is required to overcome the inhibitory constrains of the brain and to render microglia able to cross-prime naive CD8+ T cells injected in the brain. These observations offer new insights in brain-tumor immunotherapy based on the induction of cytotoxic antitumoral T cells