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- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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- Pelló, R., et al.
(författare)
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The WIRCam Ultra Deep Survey (WUDS) I. Survey overview and UV luminosity functions at z similar to 5 and z similar to 6
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to introduce the WIRCam Ultra Deep Survey (WUDS), a near-IR photometric survey carried out at the CFH Telescope in the field of the CFHTLS-D3 field (Groth Strip). WUDS includes four near-IR bands (Y, J, H and K-s) over a field of view of similar to 400 arcmin(2). The typical depth of WUDS data reaches between similar to 26.8 in Y and J, and similar to 26 in H and K-s (AB, 3 sigma- in 1.3 '' aperture), whereas the corresponding depth of the CFHTLS-D3 images in this region ranges between 28.6 and 29 in ugr, 28.2 in i and 27.1 in z (same S/N and aperture). The area and depth of this survey were specifically tailored to set strong constraints on the cosmic star formation rate and the luminosity function brighter or around L* in the z similar to 6-10 redshift domain, although these data are also useful for a variety of extragalactic projects. This first paper is intended to present the properties of the public WUDS survey in details: catalog building, completeness and depth, number counts, photometric redshifts, and global properties of the galaxy population. We have also concentrated on the selection and characterization of galaxy samples at z similar to [4.5-7] in this field. For these purposes, we include an adjacent shallower area of similar to 1260 arcmin(2) in this region, extracted from the WIRCam Deep Survey (WIRDS), and observed in J, H and K-s bands. UV luminosity functions were derived at z - 5 and z - 6 taking advantage from the fact that WUDS covers a particularly interesting regime at intermediate luminosities, which allows a combined determination of M* and Phi* with increased accuracy. Our results on the luminosity function are consistent with a small evolution of both M* and Phi* between z = 5 and z = 6, irrespective of the method used to derive them, either photometric redshifts applied to blindly-selected dropout samples or the classical Lyman Break Galaxy color-preselected samples. Our results lend support to higher Phi* determinations at z = 6 than usually reported. The selection and combined analysis of different galaxy samples at z >= 7 will be presented in a forthcoming paper, as well as the evolution of the UV luminosity function between z similar to 4.5 and 9. WUDS is intended to provide a robust database in the near-IR for the selection of targets for detailed spectroscopic studies, in particular for the EMIR/GTC GOYA Survey.
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- Audibert, A., et al.
(författare)
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ALMA captures feeding and feedback from the active galactic nucleus in NGC 613
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 632
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Tidskriftsartikel (refereegranskat)abstract
- We report ALMA observations of CO(3-2) emission in the Seyfert/nuclear starburst galaxy NGC 613, at a spatial resolution of 17 pc, as part of our NUclei of GAlaxies (NUGA) sample. Our aim is to investigate the morphology and dynamics of the gas inside the central kiloparsec, and to probe nuclear fueling and feedback phenomena. The morphology of CO(3-2) line emission reveals a two-arm trailing nuclear spiral at r≤ 100 pc and a circumnuclear ring at a radius of ∼350 pc that is coincident with the star-forming ring seen in the optical images. Also, we find evidence for a filamentary structure connecting the ring and the nuclear spiral. The ring reveals two breaks into two winding spiral arms corresponding to the dust lanes in the optical images. The molecular gas in the galaxy disk is in a remarkably regular rotation, however the kinematics in the nuclear region are very skewed. The nuclear spectrum of CO and dense gas tracers HCN(4-3), HCO+(4-3), and CS(7-6) show broad wings up to ±300 km s-1, associated with a molecular outflow emanating from the nucleus (r ∼ 25 pc). We derive a molecular outflow mass Mout=2 × 106 M⊙ and a mass outflow rate of M out = 27 M⊙ yr-1. The molecular outflow energetics exceed the values predicted by AGN feedback models: the kinetic power of the outflow corresponds to PK, out=20%LAGN and the momentum rate is M outv ∼400LAGN/c. The outflow is mainly boosted by the AGN through entrainment by the radio jet, but given the weak nuclear activity of NGC 613, we might be witnessing a fossil outflow resulting from a previously strong AGN that has now faded. Furthermore, the nuclear trailing spiral observed in CO emission is inside the inner Lindblad resonance ring of the bar. We compute the gravitational torques exerted in the gas to estimate the efficiency of the angular momentum exchange. The gravity torques are negative from 25 to 100 pc and the gas loses its angular momentum in a rotation period, providing evidence for a highly efficient inflow towards the center. This phenomenon shows that the massive central black hole has significant dynamical influence on the gas, triggering the inflowing of molecular gas to feed the black hole.
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- Combes, F., et al.
(författare)
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ALMA observations of molecular tori around massive black holes
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 623
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Tidskriftsartikel (refereegranskat)abstract
- We report Atacama Large Millimeter/submillimeter Array (ALMA) observations of CO(3-2) emission in a sample of seven Seyfert/LINER galaxies at the unprecedented spatial resolution of 0 .″ 1 = 4-8 pc. Our aim is to explore the close environment of active galactic nuclei (AGN), and the dynamical structures leading to their fueling, through the morphology and kinematics of the gas inside the sphere of influence of the black hole. The selected galaxies host low-luminosity AGN and have a wide range of activity types (Seyferts 1 to 2, LINERs), and barred or ringed morphologies. The observed maps reveal the existence of circumnuclear disk structures, defined by their morphology and decoupled kinematics, in most of the sample. We call these structures molecular tori, even though they often appear as disks without holes in the center. They have varying orientations along the line of sight, unaligned with the host galaxy orientation. The radius of the tori ranges from 6 to 27 pc, and their mass from 0.7 × 10 7 to 3.9 × 10 7 M · . The most edge-on orientations of the torus correspond to obscured Seyferts. In only one case (NGC 1365), the AGN is centered on the central gas hole of the torus. On a larger scale, the gas is always piled up in a few resonant rings 100 pc in scale that play the role of a reservoir to fuel the nucleus. In some cases, a trailing spiral is observed inside the ring, providing evidence for feeding processes. More frequently, the torus and the AGN are slightly off-centered with respect to the bar-resonant ring position, implying that the black hole is wandering by a few 10 pc amplitude around the center of mass of the galaxy. Our spatial resolution allows us to measure gas velocities inside the sphere of influence of the central black holes. By fitting the observations with different simulated cubes, varying the torus inclination and the black hole mass, it is possible to estimate the mass of the central black hole, which is in general difficult for such late-type galaxies, with only a pseudo-bulge. In some cases, AGN feedback is revealed through a molecular outflow, which will be studied in detail in a subsequent article.
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| 8. |
- Stray-Pedersen, Asbjorg, et al.
(författare)
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Primary immunodeficiency diseases : Genomic approaches delineate heterogeneous Mendelian disorders
- 2017
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 232-245
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.
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| 9. |
- Huang, X., et al.
(författare)
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The Extinction Properties of and Distance to the Highly Reddened Type IA Supernova 2012cu
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 836:2
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Tidskriftsartikel (refereegranskat)abstract
- Correcting Type Ia Supernova brightnesses for extinction by dust has proven to be a vexing problem. Here we study the dust foreground to the highly reddened SN 2012cu, which is projected onto a dust lane in the galaxy NGC 4772. The analysis is based on multi-epoch, spectrophotometric observations spanning from 3300-9200 A degrees, obtained by the Nearby Supernova Factory. Phase-matched comparison of the spectroscopically twinned SN 2012cu and SN 2011fe across 10 epochs results in the best-fit color excess of (E(B-V), RMS) = (1.00, 0.03) and total-to-selective extinction ratio of (RV, RMS) = (2.95, 0.08) toward SN 2012cu within its host galaxy. We further identify several diffuse interstellar bands and compare the 5780 angstrom band with the dust- to-band ratio for the Milky Way (MW). Overall, we find the foreground dust-extinction properties for SN 2012cu to be consistent with those of the MW. Furthermore, we find no evidence for significant time variation in any of these extinction tracers. We also compare the dust extinction curve models of Cardelli et al., O'Donnell,. and Fitzpatrick, and find the predictions of Fitzpatrick fit SN 2012cu the best. Finally, the distance to NGC4772, the host of SN 2012cu, at a redshift of z = 0.0035, often assigned to the Virgo Southern Extension, is determined to be 16.6 +/- 1.1 Mpc. We compare this result with distance measurements in the literature.
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| 10. |
- Koo, J. H., et al.
(författare)
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Global climatology based on the ACE-FTS version 3.5 dataset: Addition of mesospheric levels and carbon-containing species in the UTLS
- 2017
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Ingår i: Journal of Quantitative Spectroscopy and Radiative Transfer. - : Elsevier BV. - 0022-4073. ; 186, s. 52-62
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we present a new climatology based on, the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) version 3.5 data set from February 2004 to February 2013. This extends the ACE-FTS climatology to include profile information in the mesosphere and carbon-containing species in the upper troposphere and lower stratosphere. Climatologies of 21 species, based on nine years of observations, are calculated, providing the most comprehensive and self-consistent climatology available from limb-viewing satellite measurements. Pressure levels from the upper troposphere to the mesosphere and lower thermosphere are included with similar to 3 to 4 km vertical resolution up to 10(-4) hPa (similar to 105 km). Volume mixing ratio values are filtered prior to the climatology estimation using the ACE-FTS data quality recommendations. The multi-year mean climatology contains zonal mean profiles for monthly and three-monthly (DJF, MAM, JJA, and SON) periods. These are provided with 5-degree spacing in either latitude or equivalent latitude. Also, the local daytime and nighttime distributions are provided separately for nitrogen-containing species, enabling diurnal differences to be investigated. Based on this climatology, examples of typical spatiotemporal patterns for trace gases in the mesosphere and for carbon-containing gases in the upper troposphere and lower stratosphere are discussed. (C) 2016 Elsevier Ltd. All rights reserved.
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