| 1. |
- Liu, Kui, et al.
(författare)
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Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans
- 2009
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.
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| 2. |
- Orozco, G., et al.
(författare)
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Study of the role of functional variants of SLC22A4, RUNX1 and SUMO4 in systemic lupus erythematosus
- 2006
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 65:6, s. 791-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Functional polymorphisms of the solute carrier family 22, member 4 (SLC22A4), runt related transcription factor 1 (RUNX1) and small ubiquitin-like modifier 4 (SUMO4) genes have been shown to be associated with several autoimmune diseases. OBJECTIVE: To test the possible role of these variants in susceptibility to or severity of systemic lupus erythematosus (SLE), on the basis that common genetic bases are shared by autoimmune disorders. METHODS: 597 SLE patients and 987 healthy controls of white Spanish origin were studied. Two additional cohorts of 228 SLE patients from Sweden and 122 SLE patients from Colombia were included. A case-control association study was carried out with six single nucleotide polymorphisms (SNP) spanning the SLC22A4 gene, one SNP in RUNX1 gene, and one additional SNP in SUM04 gene. RESULTS: No significant differences were observed between SLE patients and healthy controls when comparing the distribution of the genotypes or alleles of any of the SLC22A4, RUNX1, or SUMO4 polymorphisms tested. Significant differences were found in the distribution of the SUMO4 genotypes and alleles among SLE patients with and without nephritis, but after multiple testing correction, the significance of the association was lost. The association of SUMO4 with nephritis could not be verified in two independent SLE cohorts from Sweden and Colombia. CONCLUSIONS: These results suggest that the SLC22A4, RUNX1, and SUMO4 polymorphisms analysed do not play a role in the susceptibility to or severity of SLE.
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| 3. |
- Abdo, A. A., et al.
(författare)
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Multi-wavelength observations of the flaring gamma-ray blazar 3C 66A in 2008 October
- 2011
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 726:1, s. 43-
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Tidskriftsartikel (refereegranskat)abstract
- The BL Lacertae object 3C 66A was detected in a flaring state by the Fermi Large Area Telescope (LAT) and VERITAS in 2008 October. In addition to these gamma-ray observations, F-GAMMA, GASP-WEBT, PAIRITEL, MDM, ATOM, Swift, and Chandra provided radio to X-ray coverage. The available light curves show variability and, in particular, correlated flares are observed in the optical and Fermi-LAT gamma-ray band. The resulting spectral energy distribution can be well fitted using standard leptonic models with and without an external radiation field for inverse Compton scattering. It is found, however, that only the model with an external radiation field can accommodate the intra-night variability observed at optical wavelengths.
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| 4. |
- Ackermann, M., et al.
(författare)
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MULTI-WAVELENGTH OBSERVATIONS OF BLAZAR AO 0235+164 IN THE 2008-2009 FLARING STATE
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 751:2
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Tidskriftsartikel (refereegranskat)abstract
- The blazarAO 0235+164 (z=0.94) has been one of the most active objects observed by Fermi Large Area Telescope (LAT) since its launch in Summer 2008. In addition to the continuous coverage by Fermi, contemporaneous observations were carried out from the radio to gamma-ray bands between 2008 September and 2009 February. In this paper, we summarize the rich multi-wavelength data collected during the campaign (including F-GAMMA, GASP-WEBT, Kanata, OVRO, RXTE, SMARTS, Swift, and other instruments), examine the cross-correlation between the light curves measured in the different energy bands, and interpret the resulting spectral energy distributions in the context of well-known blazar emission models. We find that the gamma-ray activity is well correlated with a series of near-IR/optical flares, accompanied by an increase in the optical polarization degree. On the other hand, the X-ray light curve shows a distinct 20 day high state of unusually soft spectrum, which does not match the extrapolation of the optical/UV synchrotron spectrum. We tentatively interpret this feature as the bulk Compton emission by cold electrons contained in the jet, which requires an accretion disk corona with an effective covering factor of 19% at a distance of 100 R-g. We model the broadband spectra with a leptonic model with external radiation dominated by the infrared emission from the dusty torus.
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| 5. |
- Ginsburg, A., et al.
(författare)
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Dense gas in the Galactic central molecular zone is warm and heated by turbulence
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 586, s. Art nr A50-
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Galactic center is the closest region where we can study star formation under extreme physical conditions like those in high-redshift galaxies. Aims. We measure the temperature of the dense gas in the central molecular zone (CMZ) and examine what drives it. Methods. We mapped the inner 300 pc of the CMZ in the temperature-sensitive J = 3-2 para-formaldehyde (p-H2CO) transitions. We used the 3(2,1)-2(2,0)/3(0,3)-2(0,2) line ratio to determine the gas temperature in n similar to 10(4) - 10(5) cm(-3) gas. We have produced temperature maps and cubes with 30 0 0 and 1 km s(-1) resolution and published all data in FITS form. Results. Dense gas temperatures in the Galactic center range from similar to 60 K to > 100 K in selected regions. The highest gas temperatures T-G > 100 K are observed around the Sgr B2 cores, in the extended Sgr B2 cloud, the 20 km s(-1) and 50 km s(-1) clouds, and in "The Brick" (G0.253 + 0.016). We infer an upper limit on the cosmic ray ionization rate zeta(CR)
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| 6. |
- Gomez, E. S., et al.
(författare)
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Tunable entanglement distillation of spatially correlated down-converted photons
- 2018
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Ingår i: Optics Express. - : OPTICAL SOC AMER. - 1094-4087. ; 26:11, s. 13961-13972
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Tidskriftsartikel (refereegranskat)abstract
- We report on a new technique for entanglement distillation of the bipartite continuous variable state of spatially correlated photons generated in the spontaneous parametric down-conversion process ( SPDC), where tunable non-Gaussian operations are implemented and the post-processed entanglement is certified in real-time using a single-photon sensitive electron multiplying CCD (EMCCD) camera. The local operations are performed using non-Gaussian filters modulated into a programmable spatial light modulator and, by using the EMCCD camera for actively recording the probability distributions of the twin-photons, one has fine control of the Schmidt number of the distilled state. We show that even simple non-Gaussian filters can be finely tuned to a similar to 67% net gain of the initial entanglement generated in the SPDC process. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
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| 7. |
- Harada, N., et al.
(författare)
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Chemical features in the circumnuclear disk of the Galactic center
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 584
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The circumnuclear disk (CND) of the Galactic center is exposed to many energetic phenomena coming from the supermassive black hole Sgr A* and from stellar activities. These energetic activities can affect the chemical composition in the CND through interaction with UV photons, cosmic rays, X-rays, and shock waves. We aim to constrain the physical conditions present in the CND through chemical modeling of observed molecular species detected toward it. Methods. We analyzed a selected set of molecular line data taken toward a position in the southwest lobe of the CND with the IRAM 30m and APEX 12-m telescopes and derived the column density of each molecule via a large velocity gradient (LVG) analysis. The determined chemical composition is compared with a time-dependent, gas-grain chemical model based on the UCL_CHEM code, which includes the effects of shock waves with varying physical parameters. Results. We detect molecules, such as CO, HCN, HCO+, HNC, CS, SO, SiO, NO, CN, H2CO, HC3N, N2H+, and H3O+, and obtain their column densities. Total hydrogen densities obtained from LVG analysis range between 2x10(4) and 1x10(6) cm(-3) and most species indicate values around several x10(5) cm(-3). These values are lower than those corresponding to the Roche limit, which shows that the CND is tidally unstable. The chemical models show good agreement with the observations in cases where the density is similar to 10(4) cm(-3), the cosmic-ray ionization rate is high, > 10(-15) s(-1), or shocks with velocities > 40 km s(-)1 have occurred. Conclusions. Comparison of models and observations favors a scenario where the cosmic-ray ionization rate in the CND is high, but precise effects of other factors, such as shocks, density structures, UV photons, and X-rays from the Sgr A*, must be examined with higher spatial resolution data.
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| 8. |
- Langefeld, Carl D., et al.
(författare)
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Transancestral mapping and genetic load in systemic lupus erythematosus
- 2017
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
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| 9. |
- Lu, R, et al.
(författare)
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Genetic associations of LYN with systemic lupus erythematosus
- 2009
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 10:5, s. 397-403
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Tidskriftsartikel (refereegranskat)abstract
- We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case-control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P=1.1 x 10(-4), odds ratio (OR)=0.81 (95% confidence interval: 0.73-0.90)). This single nucleotide polymorphism (SNP) is located in the 5' untranslated region within the first intron near the transcription initiation site of LYN. In addition, SNPs upstream of the first exon also show weak and sporadic association in subsets of the total European-American population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for systemic lupus erythematosus (SLE) susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European-American female cases by American College of Rheumatology classification criteria shows a reduction in the risk of hematological disorder with rs6983130 compared with cases without hematological disorders (P=1.5 x 10(-3), OR=0.75 (95% CI: 0.62-0.89)). None of the 90 SNPs tested show significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.
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| 10. |
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