Diffuse Light in the Virgo Cluster

We present deep optical imaging of the inner 1.5 x 1.5 degrees of the Virgo cluster to search for diffuse intracluster light (ICL). Our image reaches a 1 sigma depth of mu_v=28.5 mag/arcsec^2 -- 1.5 mag/arcsec^2 deeper than previous surveys -- and reveals an intricate web of diffuse intracluster light. We see several long (>100 kpc) tidal streamers, as well as a myriad of smaller-scale tidal tails and bridges between galaxies. The diffuse halo of M87 is traced out to nearly 200 kpc, appearing very irregular on these scales, while significant diffuse light is also detected around the M84/M86 pair. Several galaxies in the core are embedded in common envelopes, suggesting they are true physical subgroups. The complex substructure of Virgo's diffuse ICL reflects the hierarchical nature of cluster assembly, rather than being the product of smooth accretion around a central galaxy.Comment: 4 pages, 3 figures, accepted for publication in ApJ Letter

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

Greenland ice core “signal” characteristics: An expanded view of climate change

The last millenium of Earth history is of particular interest because it documents the environmental complexities of both natural variability and anthropogenic activity. We have analyzed the major ions contained in the Greenland Ice Sheet Project 2 (GISP 2) ice core from the present to ∼674 A.D. to yield an environmental reconstruction for this period that includes a description of nitrogen and sulfur cycling, volcanic emissions, sea salt and terrestrial influences. We have adapted and extended mathematical procedures for extracting sporadic (e.g., volcanic) events, secular trends, and periodicities found in the data sets. Finally, by not assuming that periodic components (signals) were “stationary” and by utilizing evolutionary spectral analysis, we were able to reveal periodic processes in the climate system which change in frequency, “turn on,” and “turn off” with other climate transitions such as\u27that between the little ice age and the medieval warm period

Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis. Methodology/Principal Findings: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p. Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B. Conclusions/Significance: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype

Deep CCD Surface Photometry of the Edge-On Spiral NGC 4244

We have obtained deep surface photometry of the edge-on spiral galaxy NGC 4244. Our data reliably reach 27.5 R magnitude arcsec^{-2}, a significant improvement on our earlier deep CCD surface photometry of other galaxies. NGC 4244 is a nearby Scd galaxy whose total luminosity is approximately one magnitude fainter than the peak of the Sc luminosity function. We find that it has a simple structure: a single exponential disk, with a scale height h_Z = 246 +/- 2 pc, a scale length h_R = 1.84 +/- 0.02 kpc and a disk cutoff at a radius R(max) = 10.0 kpc (5.4 scale lengths). We confirm a strong cutoff in the stellar disk at R(max), which happens over only 1 kpc. We do not see any statistically significant evidence for disk flaring with radius. Unlike the more luminous Sc galaxies NGC 5907 and M 33, NGC 4244 does not show any evidence for a second component, such as a thick disk or halo, at mu(R) < 27.5 magnitude arcsec^{-2}.Comment: 36 pages, including 12 figures; accepted for publication in Sept 99 A

HIV-1 Selection by Epidermal Dendritic Cells during Transmission across Human Skin

Macrophage tropic HIV-1 is predominant during the initial viremia after person to person transmission of HIV-1 (Zhu, T., H. Mo, N. Wang, D.S. Nam, Y. Cao, R.A. Koup, and D.D. Ho. 1993. Science. 261:1179–1181.), and this selection may occur during virus entry and carriage to the lymphoid tissue. Human skin explants were used to model HIV-1 selection that may occur at the skin or mucosal surface. Macrophage tropic, but not T cell line tropic strains of HIV-1 applied to the abraded epidermis were recovered from the cells emigrating from the skin explants. Dermis and epidermis were separated by dispase digestion after virus exposure to determine the site of viral selection within the skin. Uptake and transmission to T cells of all HIV-1 isolates was found with the dermal emigrant cells, but only macrophage tropic virus was transferred by emigrants from the epidermis exposed to HIV-1, indicating selection only within the epidermis. CD3+, CD4+ T cells were found in both the dermal and epidermal emigrant cells. After cell sorting to exclude contaminating T cells, macrophage tropic HIV-1 was found in both the dermal emigrant dendritic cells and in dendritic cells sorted from the epidermal emigrants. These observations suggest that selective infection of the immature epidermal dendritic cells represents the cellular mechanism that limits the initial viremia to HIV-1 that can use the CCR5 coreceptor

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

Mapping the Galactic Halo I. The `Spaghetti' Survey

We describe a major survey of the Milky Way halo designed to test for kinematic substructure caused by destruction of accreted satellites. We use the Washington photometric system to identify halo stars efficiently for spectroscopic followup. Tracers include halo giants (detectable out to more than 100 kpc), blue horizontal branch stars, halo stars near the main sequence turnoff, and the ``blue metal-poor stars'' of Preston et al (1994). We demonstrate the success of our survey by showing spectra of stars we have identified in all these categories, including giants as distant as 75 kpc. We discuss the problem of identifying the most distant halo giants. In particular, extremely metal-poor halo K dwarfs are present in approximately equal numbers to the distant giants for V fainter than 18, and we show that our method will distinguish reliably between these two groups of metal-poor stars. We plan to survey 100 square degrees at high galactic latitude, and expect to increase the numbers of known halo giants, BHB stars and turnoff stars by more than an order of magnitude. In addition to the strong test that this large sample will provide for the question `was the Milky Way halo accreted from satellite galaxies?', we will improve the accuracy of mass measurements of the Milky Way beyond 50 kpc via the kinematics of the many distant giants and BHB stars we will find. We show that one of our first datasets constrains the halo density law over galactocentric radii of 5-20 kpc and z heights of 2-15 kpc. The data support a flattened power-law halo with b/a of 0.6 and exponent -3.0. More complex models with a varying axial ratio may be needed with a larger dataset.Comment: 55 pages, 22 figures, to appear in the Astronomical Journa

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