Experimental demonstration of non-magnetic metamaterial cloak at microwave frequencies

Metamaterials have paved the way to unprecedented control of the electromagnetic field1,2. The conjunction with space coordinate transformation has led to a novel "relativity inspired" approach for the control of light propagation. "Invisibility cloak" is the most fascinating proposed devices3,4. However, the realized structures up to now used a graded "metamagnetic" so as to achieve the cloaking function11. Artificial magnetism is however still very challenging to obtain in optics despite the currently promising building blocks13-17, not suited for optical cloaking. We report here the first experimental demonstration of non-magnetic cloak at microwave frequencies by direct mapping of the magnetic field together with the first experimental characterization of a cloak in free space configuration. The diameter of the concealed region is as big as 4.4 in wavelength units, the biggest reported experimentally so far. The principle can be scaled down to optical domain while keeping the compatibility with current nanofabrication technologies.Comment: 6 pages, 3figure

Genome-wide investigation of DNA methylation marks associated with FV Leiden mutation.

In order to investigate whether DNA methylation marks could contribute to the incomplete penetrance of the FV Leiden mutation, a major genetic risk factor for venous thrombosis (VT), we measured genome-wide DNA methylation levels in peripheral blood samples of 98 VT patients carrying the mutation and 251 VT patients without the mutation using the dedicated Illumina HumanMethylation450 array. The genome-wide analysis of 388,120 CpG probes identified three sites mapping to the SLC19A2 locus whose DNA methylation levels differed significantly (p<3 10-8) between carriers and non-carriers. The three sites replicated (p<2 10-7) in an independent sample of 214 individuals from five large families ascertained on VT and FV Leiden mutation among which 53 were carriers and 161 were non-carriers of the mutation. In both studies, these three CpG sites were also associated (2.33 10-11<p<3.02 10-4) with biomarkers of the Protein C pathway known to be influenced by the FV Leiden mutation. A comprehensive linkage disequilibrium (LD) analysis of the whole locus revealed that the original associations were due to LD between the FV Leiden mutation and a block of single nucleotide polymorphisms (SNP) located in SLC19A2. After adjusting for this block of SNPs, the FV Leiden mutation was no longer associated with any CpG site (p>0.05). In conclusion, our work clearly illustrates some promises and pitfalls of DNA methylation investigations on peripheral blood DNA in large epidemiological cohorts. DNA methylation levels at SLC19A2 are influenced by SNPs in LD with FV Leiden, but these DNA methylation marks do not explain the incomplete penetrance of the FV Leiden mutation

Genetic variation 25.1 Mb upstream of tissue factor pathway inhibitor is associated with TFPI plasma levels and venous thromboembolism

International audienceBackgroundTissue factor pathway inhibitor (TFPI) regulates fibrin clot formation, and low TFPI plasma levels increase the risk of arterial and venous thromboembolism (VTE). TFPI plasma levels are also heritable, and a previous linkage scan implicated the chromosome 2q region, but no specific genes.ObjectivesWe sought to replicate the linkage region in an independent sample and to identify the causal locus. MethodsWe first ran a linkage analysis of microsatellite markers and TFPI plasma levels in 251 individuals from the F5L Family Study and replicated the linkage peak on chromosome 2q (LOD=3.06). We next defined a follow-up region that included 112603 SNPs under the linkage peak, and meta-analyzed associations between these SNPs and TFPI plasma levels across the F5L Family Study and MARTHA, a study of 1033 unrelated VTE patients. SNPs with FDR q<0.10 were tested for association with TFPI plasma levels in 892 patients with coronary artery disease in the AtheroGene study.Results and ConclusionsOne SNP, rs62187992, was associated with TFPI plasma levels in all three samples (β=+0.14 P=4.23x10-6 combined; β=+0.16, P=0.02 in F5L Family Study; β=+0.13, P=6.3x10-4 in MARTHA; β=+0.17, P=0.03 in AtheroGene) and contributed to the linkage peak in the F5L Family Study. rs62187992 was also associated with clinical VTE (odds ratio=0.90, P=0.03) in the INVENT consortium of over 7000 cases and their controls and was marginally associated with TFPI expression (β=+0.19, P=0.08) in human aortic endothelial cells, a primary site of TFPI synthesis. The biological mechanisms underlying these associations remain to be elucidated

Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci

International audienceThe interplay between genetic and epigenetic variation is only partially understood. One form of epigenetic variation is methylation at CpG sites, which can be measured as methylation quantitative trait loci (meQTL). Here we report that in a panel of lymphocytes from 1,748 individuals, methylation levels at 1,919 CpG sites are correlated with at least one distal (trans) single-nucleotide polymorphism (SNP) (Po3.2 Â 10 À 13 ; FDRo5%). These trans-meQTLs include 1,657 SNP–CpG pairs from different chromosomes and 262 pairs from the same chromosome that are 41 Mb apart. Over 90% of these pairs are replicated (FDRo5%) in at least one of two independent data sets. Genomic loci harbouring trans-meQTLs are significantly enriched (Po0.001) for long non-coding transcripts (2.2-fold), known epigenetic regulators (2.3-fold), piwi-interacting RNA clusters (3.6-fold) and curated transcription factors (4.1-fold), including zinc-finger proteins (8.75-fold). Long-range epigenetic networks uncovered by this approach may be relevant to normal and disease states

Characteristics of the studied populations.

(1)<p> In MARTHA, ACVn ratio was significantly (p = 1.63 10⁻³⁸) decreased in <i>F5</i> rs6025 carriers compared to non-carriers.</p>(2)<p> In families, APCR ratio was significantly (p = 9.98 10⁻⁴⁷) decreased in <i>F5</i> rs6205 carriers compared to non-carriers.</p><p>Characteristics of the studied populations.</p

Association⁽¹⁾ of <i>SLC19A2</i> CpG sites with ACVn (MARTHA) and APCR (F5L-families) phenotypes.

(1)<p> Association is expressed as % change in phenotype (95% Confidence Interval) for every 0.1 unit increase in methylation β-value.</p>(2)<p> Analysis were adjusted for age, sex, batch, chip and cell type composition.</p><p>Association^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108087#nt105" target="_blank">(1)</a>} of <i>SLC19A2</i> CpG sites with ACVn (MARTHA) and APCR (F5L-families) phenotypes.</p

Manhattan plot of the MWAS results at 388,120 CpG sites.

<p>Manhattan plot of the MWAS results at 388,120 CpG sites.</p