EVR-CB-001: An evolving, progenitor, white dwarf compact binary discovered with the Evryscope

We present EVR-CB-001, the discovery of a compact binary with an extremely low mass ($.21 \pm 0.05 M_{\odot}$) helium core white dwarf progenitor (pre-He WD) and an unseen low mass ($.32 \pm 0.06 M_{\odot}$) helium white dwarf (He WD) companion. He WDs are thought to evolve from the remnant helium-rich core of a main-sequence star stripped during the giant phase by a close companion. Low mass He WDs are exotic objects (only about .2$\%$ of WDs are thought to be less than .3 $M_{\odot}$), and are expected to be found in compact binaries. Pre-He WDs are even rarer, and occupy the intermediate phase after the core is stripped, but before the star becomes a fully degenerate WD and with a larger radius ($\approx .2 R_{\odot}$) than a typical WD. The primary component of EVR-CB-001 (the pre-He WD) was originally thought to be a hot subdwarf (sdB) star from its blue color and under-luminous magnitude, characteristic of sdBs. The mass, temperature ($T_{\rm eff}=18,500 \pm 500 K$), and surface gravity ($\log(g)=4.96 \pm 0.04$) solutions from this work are lower than values for typical hot subdwarfs. The primary is likely to be a post-RGB, pre-He WD contracting into a He WD, and at a stage that places it nearest to sdBs on color-magnitude and $T_{\rm eff}$-$\log(g)$ diagrams. EVR-CB-001 is expected to evolve into a fully double degenerate, compact system that should spin down and potentially evolve into a single hot subdwarf star. Single hot subdwarfs are observed, but progenitor systems have been elusive.Comment: 14 pages, 11 figures. Published in The Astrophysical Journa

Genetic Heterogeneity in Colorectal Cancer Associations in Americans of African vs. European Descent

Genome-wide association studies of colorectal cancer (CRC) have identified risk variants in 10 genomic regions. None of these studies included African Americans, who have the highest incidence and mortality from CRC in the US. For the 10 genomic regions, we performed an association study of Americans of African and European descent

Biomarkers in advanced larynx cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102058/1/lary24245.pd

Genetic Associations in the Vitamin D Receptor and Colorectal Cancer in African Americans and Caucasians

Low vitamin D levels are associated with an increased incidence of colorectal cancer (CRC) and higher mortality from the disease. In the US, African Americans (AAs) have the highest CRC incidence and mortality and the lowest levels of vitamin D. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been previously associated with CRC, but few studies have included AAs. We studied 795 AA CRC cases and 985 AA controls from Chicago and North Carolina as well as 1324 Caucasian cases and 990 Caucasian controls from Chicago and Spain. We genotyped 54 tagSNPs in VDR (46586959 to 46521297 Mb) and tested for association adjusting for West African ancestry, age, gender, and multiple testing. Untyped markers were imputed using MACH1.0. We analyzed associations by gender and anatomic location in the whole study group as well as by vitamin D intake in the North Carolina AA group. In the joint analysis, none of the SNPs tested was significantly associated with CRC. For four previously tested restriction fragment length polymorphisms, only one (referred to as ApaI), tagged by the SNP rs79628898, had a nominally significant p-value in AAs; none of these polymorphisms were associated with CRC in Caucasians. In the North Carolina AAs, for whom we had vitamin D intake data, we found a significant association between an intronic SNP rs11574041 and vitamin D intake, which is evidence for a VDR gene-environment interaction in AAs. In summary, using a systematic tagSNP approach, we have not found evidence for significant associations between VDR and CRC in AAs or Caucasians

Genetic Associations in the Vitamin D Receptor and Colorectal Cancer in African Americans and Caucasians

Low vitamin D levels are associated with an increased incidence of colorectal cancer (CRC) and higher mortality from the disease. In the US, African Americans (AAs) have the highest CRC incidence and mortality and the lowest levels of vitamin D. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been previously associated with CRC, but few studies have included AAs. We studied 795 AA CRC cases and 985 AA controls from Chicago and North Carolina as well as 1324 Caucasian cases and 990 Caucasian controls from Chicago and Spain. We genotyped 54 tagSNPs in VDR (46586959 to 46521297 Mb) and tested for association adjusting for West African ancestry, age, gender, and multiple testing. Untyped markers were imputed using MACH1.0. We analyzed associations by gender and anatomic location in the whole study group as well as by vitamin D intake in the North Carolina AA group. In the joint analysis, none of the SNPs tested was significantly associated with CRC. For four previously tested restriction fragment length polymorphisms, only one (referred to as ApaI), tagged by the SNP rs79628898, had a nominally significant p-value in AAs; none of these polymorphisms were associated with CRC in Caucasians. In the North Carolina AAs, for whom we had vitamin D intake data, we found a significant association between an intronic SNP rs11574041 and vitamin D intake, which is evidence for a VDR gene-environment interaction in AAs. In summary, using a systematic tagSNP approach, we have not found evidence for significant associations between VDR and CRC in AAs or Caucasians

Representative Landscapes in the Forested Area of Canada

Canada is a large nation with forested ecosystems that occupy over 60% of the national land base, and knowledge of the patterns of Canada’s land cover is important to proper environmental management of this vast resource. To this end, a circa 2000 Landsat-derived land cover map of the forested ecosystems of Canada has created a new window into understanding the composition and configuration of land cover patterns in forested Canada. Strategies for summarizing such large expanses of land cover are increasingly important, as land managers work to study and preserve distinctive areas, as well as to identify representative examples of current land-cover and land-use assemblages. Meanwhile, the development of extremely efficient clustering algorithms has become increasingly important in the world of computer science, in which billions of pieces of information on the internet are continually sifted for meaning for a vast variety of applications. One recently developed clustering algorithm quickly groups large numbers of items of any type in a given data set while simultaneously selecting a representative—or “exemplar”—from each cluster. In this context, the availability of both advanced data processing methods and a nationally available set of landscape metrics presents an opportunity to identify sets of representative landscapes to better understand landscape pattern, variation, and distribution across the forested area of Canada. In this research, we first identify and provide context for a small, interpretable set of exemplar landscapes that objectively represent land cover in each of Canada’s ten forested ecozones. Then, we demonstrate how this approach can be used to identify flagship and satellite long-term study areas inside and outside protected areas in the province of Ontario. These applications aid our understanding of Canada’s forest while augmenting its management toolbox, and may signal a broad range of applications for this versatile approach

Plasma Dynamics

Contains reports on five research projects.U.S. Air Force - Office of Scientifc Research (Contract AFOSR 84-0026)National Science Foundation (Grant ECS 85-14517)Lawrence Livermore National Laboratory (Subcontract 6264005)National Science Foundation (Grant ECS 85-15032)U.S. Department of Energy (Contract DE-ACO2-78-ET-51013)U.S. Department of Energy (Contract DE-ACO2-ET-51013

Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP Transgenic Mice

A new variant of Creutzfeldt Jacob Disease (vCJD) was identified in humans and linked to the consumption of Bovine Spongiform Encephalopathy (BSE)-infected meat products. Recycling of ruminant tissue in meat and bone meal (MBM) has been proposed as origin of the BSE epidemic. During this epidemic, sheep and goats have been exposed to BSE-contaminated MBM. It is well known that sheep can be experimentally infected with BSE and two field BSE-like cases have been reported in goats. In this work we evaluated the human susceptibility to small ruminants-passaged BSE prions by inoculating two different transgenic mouse lines expressing the methionine (Met) allele of human PrP at codon 129 (tg650 and tg340) with several sheep and goat BSE isolates and compared their transmission characteristics with those of cattle BSE. While the molecular and neuropathological transmission features were undistinguishable and similar to those obtained after transmission of vCJD in both transgenic mouse lines, sheep and goat BSE isolates showed higher transmission efficiency on serial passaging compared to cattle BSE. We found that this higher transmission efficiency was strongly influenced by the ovine PrP sequence, rather than by other host species-specific factors. Although extrapolation of results from prion transmission studies by using transgenic mice has to be done very carefully, especially when human susceptibility to prions is analyzed, our results clearly indicate that Met129 homozygous individuals might be susceptible to a sheep or goat BSE agent at a higher degree than to cattle BSE, and that these agents might transmit with molecular and neuropathological properties indistinguishable from those of vCJD. Our results suggest that the possibility of a small ruminant BSE prion as vCJD causal agent could not be ruled out, and that the risk for humans of a potential goat and/or sheep BSE agent should not be underestimated

Adaptor SKAP-55 Binds p21ras Activating Exchange Factor RasGRP1 and Negatively Regulates the p21ras-ERK Pathway in T-Cells

While the adaptor SKAP-55 mediates LFA-1 adhesion on T-cells, it is not known whether the adaptor regulates other aspects of signaling. SKAP-55 could potentially act as a node to coordinate the modulation of adhesion with downstream signaling. In this regard, the GTPase p21ras and the extracellular signal-regulated kinase (ERK) pathway play central roles in T-cell function. In this study, we report that SKAP-55 has opposing effects on adhesion and the activation of the p21ras -ERK pathway in T-cells. SKAP-55 deficient primary T-cells showed a defect in LFA-1 adhesion concurrent with the hyper-activation of the ERK pathway relative to wild-type cells. RNAi knock down (KD) of SKAP-55 in T-cell lines also showed an increase in p21ras activation, while over-expression of SKAP-55 inhibited activation of ERK and its transcriptional target ELK. Three observations implicated the p21ras activating exchange factor RasGRP1 in the process. Firstly, SKAP-55 bound to RasGRP1 via its C-terminus, while secondly, the loss of binding abrogated SKAP-55 inhibition of ERK and ELK activation. Thirdly, SKAP-55−/− primary T-cells showed an increased presence of RasGRP1 in the trans-Golgi network (TGN) following TCR activation, the site where p21ras becomes activated. Our findings indicate that SKAP-55 has a dual role in regulating p21ras-ERK pathway via RasGRP1, as a possible mechanism to restrict activation during T-cell adhesion