| 1. |
- Khatri, B., et al.
(author)
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Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
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| 4. |
- Mayes, Maureen D, et al.
(author)
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Immunochip analysis identifies multiple susceptibility Loci for systemic sclerosis.
- 2014
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 94:1, s. 47-61
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Journal article (peer-reviewed)abstract
- In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.
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| 6. |
- Johannesson, M, et al.
(author)
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A resource for the simultaneous high-resolution mapping of multiple quantitative trait loci in rats: the NIH heterogeneous stock
- 2009
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In: Genome research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 19:1, s. 150-158
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Journal article (peer-reviewed)abstract
- The laboratory rat (Rattus norvegicus) is a key tool for the study of medicine and pharmacology for human health. A large database of phenotypes for integrated fields such as cardiovascular, neuroscience, and exercise physiology exists in the literature. However, the molecular characterization of the genetic loci that give rise to variation in these traits has proven to be difficult. Here we show how one obstacle to progress, the fine-mapping of quantitative trait loci (QTL), can be overcome by using an outbred population of rats. By use of a genetically heterogeneous stock of rats, we map a locus contributing to variation in a fear-related measure (two-way active avoidance in the shuttle box) to a region on chromosome 5 containing nine genes. By establishing a protocol measuring multiple phenotypes including immunology, neuroinflammation, and hematology, as well as cardiovascular, metabolic, and behavioral traits, we establish the rat HS as a new resource for the fine-mapping of QTLs contributing to variation in complex traits of biomedical relevance.
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| 11. |
- Khatri, B, et al.
(author)
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GENOME-WIDE ASSOCIATION STUDY OF SJOGREN'S SYNDROME IDENTIFIES TEN NEW RISK LOCI
- 2020
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 30-31
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Conference paper (other academic/artistic)abstract
- Sjögren’s syndrome (SS) is a complex autoimmune disease with exocrine gland dysfunction leading to substantial morbidity. There are 10 published genetic susceptibility loci.Objectives:Our genome-wide association study (GWAS) aimed to identify additional risk loci of genome-wide significance (GWS; p<5E-08) in European-derived primary SS.Methods:A total of 3232 cases and 17481 controls genotyped on GWAS arrays and 619 cases and 6171 controls genotyped on ImmunoChip (IC) arrays were imputed after quality control. Logistic regression was calculated adjusting for ancestry using the first 4 principal components to identify SS-associated SNPs. GWAS and IC results were meta-analyzed using weighted Z-scores. Bayesian statistics were used to assign posterior probabilities and define credible SNP sets for each locus. Bioinformatic analyses were used to predict functionality.Results:Seven novel loci exceeded GWS in the GWAS analysis:NAB1,MIR146A-PTTG1,XKR6,MAPT-CRHR1,RPTOR-CHMP6-BAIAP2,TYK2andSYNGR1. Meta-analysis with IC data identified three more novel loci exceeding GWS:CD247,PRDM1-ATG5andTNFAIP3. Several additional loci with suggestive association (p<1E-05) were also identified:ADAMTSL2,CGNL1andPHRF1.Several identified loci have reported functional implications in immune regulation and autoimmune disease. In lupus, rs2431697 correlated with rs2431098, which was shown to alterMIR146Aexpression, resulting in type I interferon pathway imbalance. Similarly,TYK2risk association reportedly drives interferon, IL10 and RET signaling pathways.PRDM1encodes Blimp-1, a master regulator of immune cell differentiation.CD247encodes the zeta subunit of the T cell receptor complex.XKR6is implicated in apoptotic cell ingestion.ATG5is also involved in apoptosis, as well as autophagy and antigen presentation.Additional bioinformatics analyses (Haploreg, Regulome DB, ENCODE, etc.) revealed immune-relevant functional implications for each risk locus. The SS-associated credible set included variants downstream ofTNFAIP3in a region reported to abolish looping between an enhancer and theTNFAIP3promoter in lupus and a coding variant that has been shown to alter NF-kB activity and neutrophil extra-cellular traps. The rs2293765 in the 5’ UTR ofNAB1showed evidence of enhancer/promoter activities. The rs2069235 in theSYNGR1locus showed enhancer and transcription start site activities in B and T cells. The rs7210219 in theMAPT-CRHR1locus showed enhancer/promotor activities in various tissues.Conclusion:We have identified ten novel genetic susceptibility loci associated with SS pathology. Our finding increases the current number of GWS regions in SS patients of European origin, from 10 to 20. Future work is needed to identify and characterize the functional variants in each region.Disclosure of Interests:Bhuwan Khatri: None declared, Tove Ragna Reksten: None declared, Kandice L Tessneer: None declared, Astrid Rasmussen Speakers bureau: Novartis, ThermoFischer, R Hal Scofield Grant/research support from: Pfizer, Simon J. Bowman Consultant of: Astrazeneca, Biogen, BMS, Celgene, Medimmune, MTPharma, Novartis, Ono, UCB, xtlbio, Glapagos, Speakers bureau: Novartis, Joel Guthridge Grant/research support from: Xencor, Bristol Myers Squibb, DXterity, Judith A. James Grant/research support from: Progentec Diagnostics, Inc, Consultant of: Abbvie, Novartis, Jannsen, Lars Ronnblom Grant/research support from: AZ, Speakers bureau: AZ, Blake M Warner: None declared, Xavier Mariette: None declared, Roald Omdal: None declared, Javier Martin Ibanez: None declared, Maria Teruel: None declared, Janicke Liaaen Jensen: None declared, Lara A Aqrawi: None declared, Øyvind Palm: None declared, Marie Wahren-Herlenius: None declared, Torsten Witte: None declared, Roland Jonsson: None declared, Maureen Rischmueller: None declared, A Darise Farris Speakers bureau: Biogen, Marta Alarcon-Riquelme: None declared, Wan-fai Ng: None declared, Kathy L Sivils: None declared, Gunnel Nordmark: None declared, Christopher Lessard: None declared
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| 12. |
- Teruel, M, et al.
(author)
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Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature
- 2021
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 23292-
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Journal article (peer-reviewed)abstract
- Primary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population.
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| 18. |
- Chen, Z. -L, et al.
(author)
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Artificial maxwell fisheye lens design and synthesis with using metasurface structure
- 2015
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In: 2015 International Workshop on Electromagnetics. - : Institute of Electrical and Electronics Engineers Inc.. - 9781467369527
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Conference paper (peer-reviewed)abstract
- In this paper, we use a periodic structure to produce a Maxwell's fisheye lens and investigate some important information such as power, efficiency, etc. At Chapter 1, we describe some introduction about the surface plasmon polariton (SPP), frequency selective surface (FSS), concentration power by using lens. At Chapter 2, we describe some theorem about we need to use like Transmission line modal, high impedance surface, periodic structure lens. At Chapter 3, we describe our design and we show some simulation results about the surface wave Maxwell's fisheye lens. At chapter 4, we discuss our results about the fisheye lens. At chapter 5, we will draw the conclusions.
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| 20. |
- Gorlova, Olga, et al.
(author)
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Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy
- 2011
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:7
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Journal article (peer-reviewed)abstract
- The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (IcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32x10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 x 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39x10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79x10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57x10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84x10(-21), OR = 0.55) and ATA (P = 1.14x10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and autoantibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.
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| 21. |
- Hsieh, K. -H, et al.
(author)
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The manipulation of surface plasmon polaritons and design of luneburg lens based on periodic patch arrays
- 2015
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In: 2015 International Workshop on Electromagnetics. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781467369527 ; , s. 1-2
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Conference paper (peer-reviewed)abstract
- We present a surface constitutes arrays of periodic patches, which may serve as the metasurface to synthesize the Luneburg lens. The main purpose is by using different sizes of patches to achieve different refractive index at each stage, and get the proper function of Luneburg lens.
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| 22. |
- McCall, Martin, et al.
(author)
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Roadmap on transformation optics
- 2018
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In: Journal of Optics. - : IOP Publishing. - 2040-8978 .- 2040-8986. ; 20:6
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Research review (peer-reviewed)abstract
- Transformation optics asks, using Maxwell's equations, what kind of electromagnetic medium recreates some smooth deformation of space? The guiding principle is Einstein's principle of covariance: that any physical theory must take the same form in any coordinate system. This requirement fixes very precisely the required electromagnetic medium. The impact of this insight cannot be overestimated. Many practitioners were used to thinking that only a few analytic solutions to Maxwell's equations existed, such as the monochromatic plane wave in a homogeneous, isotropic medium. At a stroke, transformation optics increases that landscape from 'few' to 'infinity', and to each of the infinitude of analytic solutions dreamt up by the researcher, there corresponds an electromagnetic medium capable of reproducing that solution precisely. The most striking example is the electromagnetic cloak, thought to be an unreachable dream of science fiction writers, but realised in the laboratory a few months after the papers proposing the possibility were published. But the practical challenges are considerable, requiring meta-media that are at once electrically and magnetically inhomogeneous and anisotropic. How far have we come since the first demonstrations over a decade ago? And what does the future hold? If the wizardry of perfect macroscopic optical invisibility still eludes us in practice, then what compromises still enable us to create interesting, useful, devices? While three-dimensional (3D) cloaking remains a significant technical challenge, much progress has been made in two dimensions. Carpet cloaking, wherein an object is hidden under a surface that appears optically flat, relaxes the constraints of extreme electromagnetic parameters. Surface wave cloaking guides sub-wavelength surface waves, making uneven surfaces appear flat. Two dimensions is also the setting in which conformal and complex coordinate transformations are realisable, and the possibilities in this restricted domain do not appear to have been exhausted yet. Beyond cloaking, the enhanced electromagnetic landscape provided by transformation optics has shown how fully analytic solutions can be found to a number of physical scenarios such as plasmonic systems used in electron energy loss spectroscopy and cathodoluminescence. Are there further fields to be enriched? A new twist to transformation optics was the extension to the spacetime domain. By applying transformations to spacetime, rather than just space, it was shown that events rather than objects could be hidden from view; transformation optics had provided a means of effectively redacting events from history. The hype quickly settled into serious nonlinear optical experiments that demonstrated the soundness of the idea, and it is now possible to consider the practical implications, particularly in optical signal processing, of having an 'interrupt-without-interrupt' facility that the so-called temporal cloak provides. Inevitable issues of dispersion in actual systems have only begun to be addressed. Now that time is included in the programme of transformation optics, it is natural to ask what role ideas from general relativity can play in shaping the future of transformation optics. Indeed, one of the earliest papers on transformation optics was provocatively titled 'General Relativity in Electrical Engineering'. The answer that curvature does not enter directly into transformation optics merely encourages us to speculate on the role of transformation optics in defining laboratory analogues. Quite why Maxwell's theory defines a 'perfect' transformation theory, while other areas of physics such as acoustics are not apparently quite so amenable, is a deep question whose precise, mathematical answer will help inform us of the extent to which similar ideas can be extended to other fields. The contributors to this Roadmap, who are all renowned practitioners or inventors of transformation optics, will give their perspectives into the field's status and future development.
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| 23. |
- Pan, C. -W, et al.
(author)
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Microwave focusing lenses by synthesized with positive or negative refractive index split-ring resonator metamaterials
- 2015
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In: 2015 International Workshop on Electromagnetics. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781467369527
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Conference paper (peer-reviewed)abstract
- Metamaterials had been widely investigated in literature and experiment in recent years, because of they are able to produce unusual permittivity and permeability which can be used to improve the performance of conventional devices [1]. Metamaterial structures designed to have simultaneously negative permittivity and permeability are known as left-handed materials (LHM) [2]. LHM produce negative refraction index and generate the backward-wave. LHM can be employed to design transformed lenses with better focusing efficiency than conventional ones. In this paper, we make use of squared split-ring resonators to synthesize a number of lenses. Particularly, we synthesize a negative refraction index lens and a parabolic refraction lens. CST has been employed to demonstrate the performance of the focusing system.
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| 24. |
- Quevedo-Teruel, Oscar, et al.
(author)
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Planar lenses by tailoring holey waveguides
- 2015
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In: 2015 USNC-URSI Radio Science Meeting (Joint with AP-S Symposium), USNC-URSI 2015 - Proceedings. - : IEEE. - 9781479978175 ; , s. 34-
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Conference paper (peer-reviewed)abstract
- In recent years there has been an increased demand for directive antennas at high frequencies. There are different solutions to increase the directivity of those antennas such as reflectors, lenses or arrays. Nevertheless, reflectors are bulky, devices at those frequencies. Thus, lenses have become a suitable solution for the new generation of antennas.
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