Mannose binding lectin is required for alphavirus-induced arthritis/myositis

Mosquito-borne alphaviruses such as chikungunya virus and Ross River virus (RRV) are emerging pathogens capable of causing large-scale epidemics of virus-induced arthritis and myositis. The pathology of RRV-induced disease in both humans and mice is associated with induction of the host inflammatory response within the muscle and joints, and prior studies have demonstrated that the host complement system contributes to development of disease. In this study, we have used a mouse model of RRV-induced disease to identify and characterize which complement activation pathways mediate disease progression after infection, and we have identified the mannose binding lectin (MBL) pathway, but not the classical or alternative complement activation pathways, as essential for development of RRV-induced disease. MBL deposition was enhanced in RRV infected muscle tissue from wild type mice and RRV infected MBL deficient mice exhibited reduced disease, tissue damage, and complement deposition compared to wild-type mice. In contrast, mice deficient for key components of the classical or alternative complement activation pathways still developed severe RRV-induced disease. Further characterization of MBL deficient mice demonstrated that similar to C3(-/-) mice, viral replication and inflammatory cell recruitment were equivalent to wild type animals, suggesting that RRV-mediated induction of complement dependent immune pathology is largely MBL dependent. Consistent with these findings, human patients diagnosed with RRV disease had elevated serum MBL levels compared to healthy controls, and MBL levels in the serum and synovial fluid correlated with severity of disease. These findings demonstrate a role for MBL in promoting RRV-induced disease in both mice and humans and suggest that the MBL pathway of complement activation may be an effective target for therapeutic intervention for humans suffering from RRV-induced arthritis and myositis.This work was supported by NIH/NIAMS R01 AR 047190 awarded to MTH

Some Navigation Rules for D-Brane Monodromy

We explore some aspects of monodromies of D-branes in the Kahler moduli space of Calabi-Yau compactifications. Here a D-brane is viewed as an object of the derived category of coherent sheaves. We compute all the interesting monodromies in some nontrivial examples and link our work to recent results and conjectures concerning helices and mutations. We note some particular properties of the 0-brane.Comment: LaTeX2e, 28 pages, 4 figures, some typos corrected and refs adde

Halo Star Streams in the Solar Neighborhood

We have assembled a sample of halo stars in the solar neighborhood to look for halo substructure in velocity and angular momentum space. Our sample includes red giants, RR Lyrae, and red horizontal branch stars within 2.5 kpc of the Sun with [Fe/H] less than -1.0. It was chosen to include stars with accurate distances, space velocities, and metallicities as well as well-quantified errors. We confirm the existence of the streams found by Helmi and coworkers, which we refer to as the H99 streams. These streams have a double-peaked velocity distribution in the z direction. We use the results of modeling of the H99 streams by Helmi and collaborators to test how one might use v_z velocity information and radial velocity information to detect kinematic substructure in the halo. We find that detecting the H99 streams with radial velocities alone would require a large sample. We use the velocity distribution of the H99 streams to estimate their age. From our model of the progenitor of the H99 streams, we determine that it was accreted between 6 and 9 Gyr ago. The H99 streams have [alpha/Fe] abundances similar to other halo stars in the solar neighborhood, suggesting that the gas that formed these stars were enriched mostly by Type II SNe. We have also discovered in angular momentum space two other possible substructures, which we refer to as the retrograde and prograde outliers. The retrograde outliers are likely to be halo substructure, but the prograde outliers are most likely part of the smooth halo. The retrograde outliers have significant structure in the v_phi direction and show a range of [alpha/Fe]. The methods presented in this paper can be used to exploit the kinematic information present in future large databases like RAVE, SDSSII/SEGUE, and Gaia.Comment: 46 pages, 13 figures, and 9 tables. Minor changes to text to match proofed version of the paper. Low resolution figures. High resolution version at http://www.astro.wisc.edu/~kepley/solar_streams.p

Deep CCD Surface Photometry of Galaxy Clusters I: Methods and Initial Studies of Intracluster Starlight

We report the initial results of a deep imaging survey of galaxy clusters. The primary goals of this survey are to quantify the amount of intracluster light as a function of cluster properties, and to quantify the frequency of tidal debris. We outline the techniques needed to perform such a survey, and we report findings for the first two galaxy clusters in the survey: Abell 1413, and MKW 7 . These clusters vary greatly in richness and structure. We show that our surface photometry reliably reaches to a surface brightness of \mu_v = 26.5 mags per arcsec. We find that both clusters show clear excesses over a best-fitting r^{1/4} profile: this was expected for Abell 1413, but not for MKW 7. Both clusters also show evidence of tidal debris in the form of plumes and arc-like structures, but no long tidal arcs were detected. We also find that the central cD galaxy in Abell 1413 is flattened at large radii, with an ellipticity of $\approx 0.8$, the largest measured ellipticity of any cD galaxy to date.Comment: 58 pages, 24 figures, accepted for publication in the Astrophysical Journal. Version has extremely low resolution figures to comply with 650k limit. High resolution version is available at http://burro.astr.cwru.edu/johnf/icl1.ps.gz Obtaining high resolution version is strongly reccomende

Planetary Nebulae Kinematics in M31

We present kinematics of 135 planetary nebulae in M31 from a survey covering 3.9 square degrees and extending out to 15 kpc from the southwest major axis and more than 20 kpc along the minor axis. The majority of our sample, even well outside the disk, shows significant rotational support (mean line-of-sight velocity 116 km/s). We argue that these PN belong to the outer part of M31's large de Vaucouleurs bulge. Only five PN have velocities clearly inconsistent with this fast rotating bulge. All five may belong to tidal streams in M31's outer halo. One is projected on the Northern Spur, and is counter-rotating with respect to the disk there. Two are projected along the major axis at X=-10 kpc and have M32-like velocities; they could be debris from that galaxy. The remaining two halo PN are located near the center of the galaxy and their velocities follow the gradient found by Ibata et al. (2004), implying that these PN could belong to the Southern Stream. If M31 has a non-rotating, pressure-supported halo, we have yet to find it, and it must be a very minor component of the galaxy.Comment: accepted to ApJ; main body of paper is 36 pages, including 14 figure

The Breakdown of Topology at Small Scales

We discuss how a topology (the Zariski topology) on a space can appear to break down at small distances due to D-brane decay. The mechanism proposed coincides perfectly with the phase picture of Calabi-Yau moduli spaces. The topology breaks down as one approaches non-geometric phases. This picture is not without its limitations, which are also discussed.Comment: 12 pages, 2 figure

A longitudinal study of Sin Nombre virus prevalence in rodents, southeastern Arizona.

We determined the prevalence of Sin Nombre virus antibodies in small mammals in southeastern Arizona. Of 1,234 rodents (from 13 species) captured each month from May through December 1995, only mice in the genus Peromyscus were seropositive. Antibody prevalence was 14.3% in 21 white-footed mice (P. leucopus), 13.3% in 98 brush mice (P. boylii), 0.8% in 118 cactus mice (P. eremicus), and 0% in 2 deer mice (P. maniculatus). Most antibody-positive mice were adult male Peromyscus captured close to one another early in the study. Population dynamics of brush mice suggest a correlation between population size and hantavirus-antibody prevalence