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- Okada, Yukinori, et al.
(författare)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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| 2. |
- Poulopoulos, P., et al.
(författare)
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Induced spin-polarization of EuS at room temperature in Ni/EuS multilayers
- 2014
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 104:11, s. 112411-
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Tidskriftsartikel (refereegranskat)abstract
- Ni/EuS multilayers with excellent multilayer sequencing are deposited via e-beam evaporation on the native oxide of Si(100) wafers at 4 x 10(-9) millibars. The samples have very small surface and interface roughness and show sharp interfaces. Ni layers are nanocrystalline 4-8 nm thick and EuS layers are 2-4 nm thick and are either amorphous or nanocrystalline. Unlike for Co/EuS multilayers, all Eu ions are in divalent (ferromagnetic) state. We show a direct antiferromagnetic coupling between EuS and Ni layers. At room temperature, the EuS layers are spin-polarized due to the proximity of Ni. Therefore, Ni/EuS is a candidate for room-temperature spintronics applications. (C) 2014 AIP Publishing LLC.
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| 3. |
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| 4. |
- Pappas, S. D., et al.
(författare)
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Natural Nanomorphous Ni/NiO Magnetic Multilayers : Structure and Magnetism of the High-Ar Pressure Series
- 2014
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Ingår i: Journal of Nanoscience and Nanotechnology. - : American Scientific Publishers. - 1533-4880 .- 1533-4899. ; 14:8, s. 6103-6107
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Tidskriftsartikel (refereegranskat)abstract
- Natural nanomorphous Ni/NiO multilayers have exhibited interesting magnetic properties, such as an unusual positive surface anisotropy and perpendicular magnetic anisotropy. Most attention has been paid to multilayers prepared by radio frequency magnetron sputtering under relatively low (3x10(-3) mbar) Ar pressure. Here we report on the correlation between structural and magnetic properties for a new series of multilayers, prepared under relatively high (3x10(-2) mbar) Ar pressure. The crystalline Ni individual layer thickness ranges between 5-8 nm. The amorphous NiO layer thickness is constant, about 1.1 nm thick. X-ray reflectivity showed that in some of the multilayers the high-order Bragg peaks become broader and diminish quickly. Cross-section transmission electron microscopy reveals that this occurs because the first bilayers are formed in accordance to the growth conditions, while the ones near the top are vanished. Despite the deterioration of the interface quality, all samples show tendency for perpendicular magnetic anisotropy even for large bilayer thickness of about 9 nm. Similar tendency is observed even by a 330 nm thick non-multilayered Ni film grown under the same conditions. This observation reveals the important role of strain and magnetoelastic anisotropy as a source of perpendicular magnetic anisotropy in the Ni/NiO multilayers.
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