Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

Power grid, mains filtering and power line communications ... a root cause for incompatibilities

The power grid is intentionally meant to distribute electrical energy at the mains frequency, as produced by the electricity generating plants, towards the end-users. The three-phase low-voltage distribution network can be utilized more efficiently when a power factor of 1 is achieved and no harmonic distortion is superimposed. Due to an increase of self-generated energy and the near to saturation increase of switching electronics, the loading of the mains distribution network is heavily affected. These same mains distribution networks are still considered for power line communication in two frequency bands: the lower one, 10 kHz – 150 kHz (EN50065), and the one above from 1,6 MHz to 30 MHz e.g. HomePlug, IEEE1901 - See more at: http://www.interferencetechnology.com/power-grid-mains-filtering-power-line-communications-root-cause-incompatibilities/#sthash.OdsKKG4w.dpu

A change in international EMC legislation : do industrial premises become outlawed?

During the last few years, many new EMC standards have been adopted; however, more and more standards are outside the scope of formal EMC legislation. The recent change in scope of IEC, ACEC, CISPR and the new European EMC Directive has created new challenges for industry, as their focus will be aimed at the protection of general broadcasting and communication services and at serving the main public interest

Automotive RF immunity test set-up analysis : why test results can't compare

Though the automotive RF emission and RF immunity requirements are highly justifiable, the application of those requirements in an non-intended manner leads to false conclusions and unnecessary redesigns for the electronics involved. When the test results become too dependent upon the test set-up itself, inter-laboratory comparison as well as the search for design solutions and possible correlation with other measurement methods looses ground. In this paper, the ISO bulk-current injection (BCI) and radiated immunity (RI) module-level tests are discussed together with possible relation to the DPI and TEM cell methods used at the IC level

Failure analysis in ITO-free all-solution processed organic solar cells

\u3cp\u3eIn this paper we discuss a problem-solving methodology and present guidance for troubleshooting defects in ITO-free all-solution processed organic solar cells with an inverted cell architecture. A systematic approach for identifying the main causes of failures in devices is presented. Comprehensive analysis of the identified failure mechanisms allowed us to propose practical solutions for further avoiding and eliminating failures in all-solution processed organic solar cells. Implementation of the proposed solutions has significantly improved the yield and quality of all-solution processed organic solar cells.\u3c/p\u3

Minimum Information about an Uncultivated Virus Genome (MIUViG)

International audienceWe present an extension of the Minimum Information about any (x) Sequence (MIxS) standard for reporting sequences of uncultivated virus genomes. Minimum Information about an Uncultivated Virus Genome (MIUViG) standards were developed within the Genomic Standards Consortium framework and include virus origin, genome quality, genome annotation, taxonomic classification, biogeographic distribution and in silico host prediction. Community-wide adoption of MIUViG standards, which complement the Minimum Information about a Single Amplified Genome (MISAG) and Metagenome-Assembled Genome (MIMAG) standards for uncultivated bacteria and archaea, will improve the reporting of uncultivated virus genomes in public databases. In turn, this should enable more robust comparative studies and a systematic exploration of the global virosphere