A method for high-throughput gene expression signature analysis

Genome-wide transcriptional profiling has shown that different biologic states (for instance, disease and response to pharmacologic manipulation) can be recognized by the expression pattern of relatively small numbers of genes. However, the lack of a practical and cost-effective technology for detection of these gene expression 'signatures' in large numbers of samples has severely limited their exploitation in important medical and pharmaceutical discovery applications. Here, we describe a solution based on the combination of ligation-mediated amplification with an optically addressed microsphere and flow cytometric detection system

IL-1 receptor–associated kinase M is a central regulator of osteoclast differentiation and activation

Osteoporosis is a serious problem worldwide; it is characterized by bone fractures in response to relatively mild trauma. Osteoclasts originate from the fusion of macrophages and they play a central role in bone development and remodeling via the resorption of bone. Therefore, osteoclasts are important mediators of bone loss that leads, for example, to osteoporosis. Interleukin (IL)-1 receptor (IL-1R)–associated kinase M (IRAK-M) is only expressed in cells of the myeloid lineage and it inhibits signaling downstream of IL-1R and Toll-like receptors (TLRs). However, it lacks a functional catalytic site and, thus, cannot function as a kinase. IRAK-M associates with, and prevents the dissociation of, IRAK–IRAK-4–TNF receptor–associated factor 6 from the TLR signaling complex, with resultant disruption of downstream signaling. Thus, IRAK-M acts as a dominant negative IRAK. We show here that mice that lack IRAK-M develop severe osteoporosis, which is associated with the accelerated differentiation of osteoclasts, an increase in the half-life of osteoclasts, and their activation. Ligation of IL-1R or TLRs results in hyperactivation of NF-κB and mitogen-activated protein kinase signaling pathways, which are essential for osteoclast differentiation. Thus, IRAK-M is a key regulator of the bone loss that is due to osteoclastic resorption of bone

Impact of parasites on salmon recruitment in the Northeast Atlantic Ocean

Parasites may have large effects on host population dynamics, marine fisheries and conservation, but a clear elucidation of their impact is limited by a lack of ecosystem-scale experimental data. We conducted a meta-analysis of replicated manipulative field experiments concerning the influence of parasitism by crustaceans on the marine survival of Atlantic salmon (Salmo salar L.). The data include 24 trials in which tagged smolts (totalling 283 347 fish; 1996-2008) were released as paired control and parasiticide-treated groups into 10 areas of Ireland and Norway. All experimental fish were infectionfree when released into freshwater, and a proportion of each group was recovered as adult recruits returning to coastal waters 1 or more years later. Treatment had a significant positive effect on survival to recruitment, with an overall effect size (odds ratio) of 1.29 that corresponds to an estimated loss of 39 per cent (95% CI: 18-55%) of adult salmon recruitment. The parasitic crustaceans were probably acquired during early marine migration in areas that host large aquaculture populations of domesticated salmon, which elevate local abundances of ectoparasitic copepods-particularly Lepeophtheirus salmonis. These results provide experimental evidence from a large marine ecosystem that parasites can have large impacts on fish recruitment, fisheries and conservation

HopScotch - a low-power renewable energy base station network for rural broadband access

The provision of adequate broadband access to communities in sparsely populated rural areas has in the past been severely restricted. In this paper, we present a wireless broadband access test bed running in the Scottish Highlands and Islands which is based on a relay network of low-power base stations. Base stations are powered by a combination of renewable sources creating a low cost and scalable solution suitable for community ownership. The use of the 5~GHz bands allows the network to offer large data rates and the testing of ultra high frequency ``white space'' bands allow expansive coverage whilst reducing the number of base stations or required transmission power. We argue that the reliance on renewable power and the intelligent use of frequency bands makes this approach an economic green radio technology which can address the problem of rural broadband access

Information systems project manager soft competencies: A project-phase investigation

This article investigates the soft competencies by project phase that information systems (IS) project managers require for project success. The authors conducted 33 qualitative interviews to collect data from a sample of 22 IS project managers and business leaders located in Calgary, Alberta, Canada. The authors identified the key competencies for each of the IS project phases (initiation, planning, implementation, and close- out). The competencies were sorted into competency categories: personal attributes (e.g., eye for details), communication (e.g., effective questioning), leadership (e.g., create an effective project environment), negotiations (e.g., consensus building), professionalism (e.g., lifelong learning), social skills (e.g., charisma), and project management competencies (e.g., manage expectations). Each of the most important competencies is discussed and interconnections among competencies identified. How this research can be used by the practitioner and academic communities and the broader implications of this research are examined. © 2009 by the Project Management Institute

Collision Mortality Has No Discernible Effect on Population Trends of North American Birds

Avian biodiversity is threatened by numerous anthropogenic factors and migratory species are especially at risk. Migrating birds frequently collide with manmade structures and such losses are believed to represent the majority of anthropogenic mortality for North American birds. However, estimates of total collision mortality range across several orders of magnitude and effects on population dynamics remain unknown. Herein, we develop a novel method to assess relative vulnerability to anthropogenic threats, which we demonstrate using 243,103 collision records from 188 species of eastern North American landbirds. After correcting mortality estimates for variation attributable to population size and geographic overlap with potential collision structures, we found that per capita vulnerability to collision with buildings and towers varied over more than four orders of magnitude among species. Species that migrate long distances or at night were much more likely to be killed by collisions than year-round residents or diurnal migrants. However, there was no correlation between relative collision mortality and long-term population trends for these same species. Thus, although millions of North American birds are killed annually by collisions with manmade structures, this source of mortality has no discernible effect on populations

Antiviral CD8(+) T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion.

CD8(+) T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8(+) T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8(+) T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% of circulating CD8(+) T cells, and TCRα analysis revealed two distinct co-expressed TCRα chains, with only one contributing to binding of the class II HLA-peptide complex. These data indicate that class II-restricted CD8(+) T cell responses can exist in a chronic human viral infection, and may contribute to immune control

Inflation Inequality in Europe

We analyze cross-household inflation dispersion in Europe using fictitious monthly inflation rates for several household categories (grouped according to income levels, household size, socio-economic status, age) for the period from 1997 to 2008. Our analysis is carried out on a panel of 23 up to 27 household-specific inflation rates per country for 15 countries. In the first part of the paper, we employ time series and related non-stationary panel approaches to shed light on cross-country differences in inflation inequality with respect to the number of driving forces in the panel. In particular, we focus on the degree of persistence of the household-specific inflation rates and their the adjustment behaviour towards the inflation rate of a representative household. In the second part of the paper, we pool over the full sample of all countries and test if and by how much certain household categories across Europe are more prone to significant inflation differentials and significant differences in the volatility of inflation. Furthermore we search for the presence of clusters with respect to inflation susceptibility. On the national level, we find evidence for the existence of one main driving factor driving the non-stationarity of the panel and evidence for a single co-integration vector. Persistence of deviations, however, is high, and the adjustment speed towards the representative household is low. Even if there is no concern about a long-run stable distribution, at least in the short- to medium run deviations tend to last. On the European level, we find small but significant differences (mainly along income levels), we can separate 5 clusters and two main driving forces for the differences in the overall panel. All in all, even if differences are relatively small, they are not negligible and persistent enough to represent a serious matter of debate for economic and social policy