943 resultados para OVERLAPPING LINES


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Much has been made of the divide that opened up in 2015 between eastern and western member states as a result of acrimonious discussions on how to handle the refugee crisis and distribute asylum applicants across the EU. Against the prevailing political sentiment in certain member state capitals, Germany and France pushed through a plan devised by the European Commission to relocate 120,000 refugees, by a qualified majority vote in the Council. Rather than creating an east/west divide, however, the vote split the group of (relatively) new Central and Eastern European countries (CEECs) of the EU into two factions: Romania, Czechia, Slovakia and Hungary voted against the plan, whereas several other CEECs, namely Poland, Bulgaria and the Baltic states, joined the controversial motion on the side of the other (northern, southern and western) member states. Finland abstained. Few member states have shifted their positions in the meantime. If anything, in fact, they have coalesced among the Visegrad 4, following a change of government in Poland; and they have hardened, as a result of new proposals by the Commission to fine member states that refuse to accept refugees. With Hungary’s referendum on the Commission’s relocation scheme scheduled for October 2nd, tensions are set to intensify even further.

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BACKGROUND Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease triggered by allergic reactions involving IgE antibodies directed towards environmental allergens. We previously identified a ~1.5 Mb locus on canine chromosome 27 associated with CAD in German shepherd dogs (GSDs). Fine-mapping indicated association closest to the PKP2 gene encoding plakophilin 2. RESULTS Additional genotyping and association analyses in GSDs combined with control dogs from five breeds with low-risk for CAD revealed the top SNP 27:19,086,778 (p = 1.4 × 10(-7)) and a rare ~48 kb risk haplotype overlapping the PKP2 gene and shared only with other high-risk CAD breeds. We selected altogether nine SNPs (four top-associated in GSDs and five within the ~48 kb risk haplotype) that spanned ~280 kb forming one risk haplotype carried by 35 % of the GSD cases and 10 % of the GSD controls (OR = 5.1, p = 5.9 × 10(-5)), and another haplotype present in 85 % of the GSD cases and 98 % of the GSD controls and conferring a protective effect against CAD in GSDs (OR = 0.14, p = 0.0032). Eight of these SNPs were analyzed for transcriptional regulation using reporter assays where all tested regions exerted regulatory effects on transcription in epithelial and/or immune cell lines, and seven SNPs showed allelic differences. The DNA fragment with the top-associated SNP 27:19,086,778 displayed the highest activity in keratinocytes with 11-fold induction of transcription by the risk allele versus 8-fold by the control allele (pdifference = 0.003), and also mapped close (~3 kb) to an ENCODE skin-specific enhancer region. CONCLUSIONS Our experiments indicate that multiple CAD-associated genetic variants located in cell type-specific enhancers are involved in gene regulation in different cells and tissues. No single causative variant alone, but rather multiple variants combined in a risk haplotype likely contribute to an altered expression of the PKP2 gene, and possibly nearby genes, in immune and epithelial cells, and predispose GSDs to CAD.

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The approach of estimating the current state of the overhead transmission lines is considering. The performance functions of the overhead transmission lines has been generated on the basis of experimental data and reports. Results of simulation of the approximation functions for overhead transmission lines are analyzed.

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Mode of access: Internet.

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Title vignette.