Reversing the Stein Effect

The Reverse Stein Effect is identified and illustrated: A statistician who shrinks his/her data toward a point chosen without reliable knowledge about the underlying value of the parameter to be estimated but based instead upon the observed data will not be protected by the minimax property of shrinkage estimators such as that of James and Stein, but instead will likely incur a greater error than if shrinkage were not used.Comment: Published in at http://dx.doi.org/10.1214/09-STS278 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

MAVS expressed by hematopoietic cells is critical for control of West Nile virus infection and pathogenesis

West Nile virus (WNV) is the most important cause of epidemic encephalitis in North America. Innate immune responses, which are critical for control of WNV infection, are initiated by signaling through pathogen recognition receptors, RIG-I and MDA5, and their downstream adaptor molecule, MAVS. Here, we show that a deficiency of MAVS in hematopoietic cells resulted in increased mortality and delayed WNV clearance from the brain. In Mavs(−/−) mice, a dysregulated immune response was detected, characterized by a massive influx of macrophages and virus-specific T cells into the infected brain. These T cells were polyfunctional and lysed peptide-pulsed target cells in vitro. However, virus-specific T cells in the brains of infected Mavs(−/−) mice exhibited lower functional avidity than those in wild-type animals, and even virus-specific memory T cells generated by prior immunization could not protect Mavs(−/−) mice from WNV-induced lethal disease. Concomitant with ineffective virus clearance, macrophage numbers were increased in the Mavs(−/−) brain, and both macrophages and microglia exhibited an activated phenotype. Microarray analyses of leukocytes in the infected Mavs(−/−) brain showed a preferential expression of genes associated with activation and inflammation. Together, these results demonstrate a critical role for MAVS in hematopoietic cells in augmenting the kinetics of WNV clearance and thereby preventing a dysregulated and pathogenic immune response. IMPORTANCE West Nile virus (WNV) is the most important cause of mosquito-transmitted encephalitis in the United States. The innate immune response is known to be critical for protection in infected mice. Here, we show that expression of MAVS, a key adaptor molecule in the RIG-I-like receptor RNA-sensing pathway, in hematopoietic cells is critical for protection from lethal WNV infection. In the absence of MAVS, there is a massive infiltration of myeloid cells and virus-specific T cells into the brain and overexuberant production of proinflammatory cytokines. These results demonstrate the important role that MAVS expression in hematopoietic cells has in regulating the inflammatory response in the WNV-infected brain

The Utility of Trouble: Maximizing the Value of Our Human Services Dollars

Outlines recommendations to standardize service delivery areas and consolidate area offices of the state's seven largest human services agencies, as well as to close antiquated institutions. Projects benefits such as improved accessibility and savings

The HI Environment of Nearby Lyman-alpha Absorbers

We present the results of a VLA and WSRT search for HI emission from the vicinity of seven nearby clouds, which were observed in Lya absorption with HST toward Mrk335, Mrk501 and PKS2155-304. We searched a volume of 40' x 40' x 1000 km/s. The HI mass sensitivity (5 sigma) varies from 5x10^6 to 5x10^8 Msun. We detected HI emission in the vicinity of four out of seven absorbers. The closest galaxy is a small dwarf galaxy at a projected distance of 68/h kpc from the sight line toward Mrk335. It has the same velocity (V=1970 km/s) as one of the absorbers, and has an HI mass of only 4x10^7 Msun. We found a more luminous galaxy at the velocity (V=5100 km/s) of one of the absorbers toward PKS2155-304, 230/h kpc from the sight line. Two other, stronger absorbers toward PKS2155-304 at V=17,000 km/s are associated with a loose group of three bright spiral galaxies, at projected distances of 300 to 600/h kpc. These results support the conclusion that most nearby Lya forest clouds trace the large-scale structures outlined by optically luminous galaxies. We do not find any evidence for a physical association between an absorber and its closest galaxy.Comment: 4 Tables, 11 Figures, to be published in Astron J. (Oct 1996) Vol 11