Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived "null" variant of the Duffy Antigen Receptor for Chemokines (DARC) ...gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P<2.5×10-8). The lead SNP (rs9131) on chromosome 4q13 is located in the CXCL2 gene, which encodes a chemotactic cytokine for polymorphonuclear leukocytes. Independent evidence of the novel CXCL2 association with WBC was present in 3,551 Hispanic Americans, 14,767 Japanese, and 19,509 European Americans. The index SNP (rs12149261) on chromosome 16q22 associated with WBC count is located in a large inter-chromosomal segmental duplication encompassing part of the hydrocephalus inducing homolog (HYDIN) gene. We demonstrate that the chromosome 16q22 association finding is most likely due to a genotyping artifact as a consequence of sequence similarity between duplicated regions on chromosomes 16q22 and 1q21. Among the WBC loci recently identified in European or Japanese populations, replication was observed in our African-American meta-analysis for rs445 of CDK6 on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21. In summary, the CXCL2, CDK6, and PSMD3-CSF3 regions are associated with WBC count in African American and other populations. We also demonstrate that large inter-chromosomal duplications can result in false positive associations in GWAS.
Background Opioids are associated with wide inter-individual variability in the analgesic response and a narrow therapeutic index. This may be partly explained by the presence of single nucleotide ...polymorphisms (SNPs) in genes encoding molecular entities involved in opioid metabolism and receptor activation. This paper describes the investigation of SNPs in three genes that have a functional impact on the opioid response: OPRM1, which codes for the mu-opioid receptor; ABCB1 for the ATP-binding cassette B1 transporter enzyme; and the calcium channel complex subunit CACNA2D2. The genotyping was combined with an analysis of plasma levels of the opioid peptide beta-endorphin in 80 well-defined patients with chronic low back pain scheduled for spinal fusion surgery, and with differential sensitivity to the opioid analgesic remifentanil. This patient group was compared with 56 healthy controls. Results The plasma beta-endorphin levels were significantly higher in controls than in pain patients. A higher incidence of opioid-related side effects and sex differences was found in patients with the minor allele of the ABCB1 gene. Further, a correlation between increased opioid sensitivity and the major CACNA2D2 allele was confirmed. A tendency of a relationship between opioid sensitivity and the minor allele of OPRM1 was also found. Conclusions Although the sample cohort in this study was limited to 80 patients it appears that it was possible to observe significant correlations between polymorphism in relevant genes and various items related to pain sensitivity and opioid response. Of particular interest is the new finding of a correlation between increased opioid sensitivity and the major CACNA2D2 allele. These observations may open for improved strategies in the clinical treatment of chronic pain with opioids. Keywords: Chronic pain, Opioid sensitivity, Gene polymorphism, beta-endorphin, mu-1-opioid peptide receptor (OPRM1), Calcium channel subunit 2 (CACNA2D2), ATP-binding cassette B1 (ABCB1)
In the last decades, Ingvar Johansson has made a formidable contribution to the development of philosophy and particularly that of metaphysics. This volume consists of original papers written by 50 ...philosophers from all over the world to celebrate his 70th birthday. The papers cover traditional issues in metaphysics and the philosophy of mind, applied ethics, applied metaphysics, the nature of human rights, the philosophy of economics and sports.
Virtual machine technology allows for the reuse of applications and code over various heterogeneous platforms. A virtual machine simply adds another layer of abstraction between the application and ...the native hardware. A major drawback of an application running on a virtual machine, however, is that the performance is below that of an application targeted for a native platform. Previous work has dealt with improving the performance of a virtual machine through hardware support using field programmable gate arrays (FPGAs). With the growing capacities of FPGAs it is becoming possible to provide higher levels of hardware support. This work examines the Java virtual machine (JVM), by implementing it in hardware, using a network-on-chip (NoC) design methodology. A subset of the JVM instructions are implemented in a hardware engine, with the more complex operations performed in software, and this hardware engine is replicated numerous times within the FPGA. By having several JVM instances execute in hardware concurrently, multiple applications and/or threads can simultaneously benefit from hardware implementation
Revisionist trends in anthropology over the past two decades have criticized ethnographic models of societies -- particularly hunting & gathering ones -- for considering them as isolated & unaffected ...by time, & have emphasized the need to study societies within wider regional & global economies, histories, & polities. It is argued that such revisionism may cause anthropologists to assume dependency links between societies that come into contact with each other, especially in trade situations, implying the surrender of one society's autonomy in the process. Here, a comparison of the different historical experiences of two San foraging groups in the African Kalahari desert -- one dependent on neighboring Bantu farmers & one substantially autonomous -- reveals that cross-cultural contact does not automatically lead to dependency & the degradation of foragers. Ways that twentieth-century foragers remain autonomous though no longer isolated, & resist incorporation into "more powerful" social formations, are discussed. Comments are offered by: Alan Barnard (U of Edinburgh, Scotland); M. G. Bicchieri (Central Washington U, Ellensburg); Alec C. Campbell (Crocodile Pools, PO Box 71, Gaborone, Botswana); James Denbow (U of Texas, Austin); Robert Gordon (U of Vermont, Burlington); Mathias Guenther (Wilfrid Laurier U, Waterloo, Ontario); Henry Harpending & Patricia Draper (Pennsylvania State U, University Park); Robert K. Hitchcock (U of Nebraska, Lincoln); Tim Ingold (U of Manchester, England); L. Jacobson (McGregor Museum, PO Box 316, 8300 Kimberley, South Africa); Susan Kent (Old Dominion U, Norfolk, Va); Pnina Motzafi-Haller (Harvard U, Cambridge, Mass); Thomas C. Patterson (Temple U, Philadelphia, Pa); Carmel Schrire (Rutgers U, New Brunswick, NJ); Bruce G. Trigger (McGill U, Montreal, Quebec); Polly Wiessner (Max-Planck-Instit fur Humanethologie, D-8138 Andechs, Federal Republic of Germany); Edwin N. Wilmsen (African Studies Center, Boston U, Mass); John E. Yellen (National Science Foundation, Washington, DC 20550); & Aram A. Yengoyan (U of California, Davis). In Reply, Solway & Lee respond to each contributor in turn & reiterate their view that foraging societies, while not immune to change, deserve recognition of their identity & historical agency. 1 Figure, 194 References. K. Hyatt
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