| 1. |
- Fresard, Laure, et al.
(författare)
-
Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
-
Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
-
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.
|
|
| 2. |
- France, Kevin, et al.
(författare)
-
HST-COS Observations of Hydrogen, Helium, Carbon, and Nitrogen Emission from the SN 1987A Reverse Shock
- 2011
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 743:2, s. 186-
-
Tidskriftsartikel (refereegranskat)abstract
- We present the most sensitive ultraviolet observations of Supernova 1987A to date. Imaging spectroscopy from the Hubble Space Telescope-Cosmic Origins Spectrograph shows many narrow (Δv ~ 300 km s-1) emission lines from the circumstellar ring, broad (Δv ~ 10-20 × 103 km s-1) emission lines from the reverse shock, and ultraviolet continuum emission. The high signal-to-noise ratio (>40 per resolution element) broad Lyα emission is excited by soft X-ray and EUV heating of mostly neutral gas in the circumstellar ring and outer supernova debris. The ultraviolet continuum at λ > 1350 Å can be explained by H I two-photon (2s 2 S 1/2-1s 2 S 1/2) emission from the same region. We confirm our earlier, tentative detection of N V λ1240 emission from the reverse shock and present the first detections of broad He II λ1640, C IV λ1550, and N IV] λ1486 emission lines from the reverse shock. The helium abundance in the high-velocity material is He/H = 0.14 ± 0.06. The N V/Hα line ratio requires partial ion-electron equilibration (Te /Tp ≈ 0.14-0.35). We find that the N/C abundance ratio in the gas crossing the reverse shock is significantly higher than that in the circumstellar ring, a result that may be attributed to chemical stratification in the outer envelope of the supernova progenitor. The N/C abundance may have been stratified prior to the ring expulsion, or this result may indicate continued CNO processing in the progenitor subsequent to the expulsion of the circumstellar ring. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained from the data archive at the Space Telescope Science Institute. STScI is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555.
|
|
| 3. |
- France, Kevin, et al.
(författare)
-
MAPPING HIGH-VELOCITY H alpha AND Ly alpha EMISSION FROM SUPERNOVA 1987A
- 2015
-
Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 801:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present new Hubble Space Telescope images of high-velocity H alpha and Ly alpha emission in the outer debris of SN 1987 A. The Ha images are dominated by emission from hydrogen atoms crossing the reverse shock (RS). For the first time we observe emission from the RS surface well above and below the equatorial. ring (ER), suggesting a bipolar or conical structure perpendicular to the ring plane. Using the H alpha imaging, we measure the mass flux of hydrogen atoms crossing the RS front, in the velocity intervals (-7500 < V-obs < -2800 km s(-1)) and (1000 < V-obs < 7500 km s(-1)), (M)(H) over dot = 1.2 x 10(-3) M-circle dot yr(-1). We also present the first Ly alpha imaging of the whole remnant and new Chandra X-ray observations. Comparing the spatial distribution of the Ly alpha and X-ray emission, we observe that the majority of the high-velocity Ly alpha emission originates interior to the ER. The observed Ly alpha/H alpha photon ratio, < R(L alpha/H alpha)> approximate to 17, is significantly higher than the theoretically predicted ratio of approximate to 5 for neutral atoms crossing the RS front. We attribute this excess to Ly alpha emission produced by X-ray heating of the outer debris. The spatial orientation of the Ly alpha and X-ray emission suggests that X-ray heating of the outer debris is the dominant Ly alpha production mechanism in SN 1987 A at this phase in its evolution.
|
|
| 4. |
- France, Kevin, et al.
(författare)
-
MAPPING high-velocity Hα and Lyα emission from supernova 1987A
- 2015
-
Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 801:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present new Hubble Space Telescope images of high-velocity H alpha and Ly alpha emission in the outer debris of SN 1987 A. The Ha images are dominated by emission from hydrogen atoms crossing the reverse shock (RS). For the first time we observe emission from the RS surface well above and below the equatorial. ring (ER), suggesting a bipolar or conical structure perpendicular to the ring plane. Using the H alpha imaging, we measure the mass flux of hydrogen atoms crossing the RS front, in the velocity intervals (-7500 < V-obs < -2800 km s(-1)) and (1000 < V-obs < 7500 km s(-1)), (M)(H) over dot = 1.2 x 10(-3) M-circle dot yr(-1). We also present the first Ly alpha imaging of the whole remnant and new Chandra X-ray observations. Comparing the spatial distribution of the Ly alpha and X-ray emission, we observe that the majority of the high-velocity Ly alpha emission originates interior to the ER. The observed Ly alpha/H alpha photon ratio, < R(L alpha/H alpha)> approximate to 17, is significantly higher than the theoretically predicted ratio of approximate to 5 for neutral atoms crossing the RS front. We attribute this excess to Ly alpha emission produced by X-ray heating of the outer debris. The spatial orientation of the Ly alpha and X-ray emission suggests that X-ray heating of the outer debris is the dominant Ly alpha production mechanism in SN 1987 A at this phase in its evolution.
|
|
| 5. |
- France, Kevin, et al.
(författare)
-
Observing Supernova 1987A with the Refurbished Hubble Space Telescope
- 2010
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 329:5999, s. 1624-1627
-
Tidskriftsartikel (refereegranskat)abstract
- Observations with the Hubble Space Telescope (HST), conducted since 1990, now offer an unprecedented glimpse into fast astrophysical shocks in the young remnant of supernova 1987A. Comparing observations taken in 2010 with the use of the refurbished instruments on HST with data taken in 2004, just before the Space Telescope Imaging Spectrograph failed, we find that the Ly alpha and H alpha lines from shock emission continue to brighten, whereas their maximum velocities continue to decrease. We observe broad, blueshifted Ly alpha, which we attribute to resonant scattering of photons emitted from hot spots on the equatorial ring. We also detect N v lambda lambda 1239, 1243 angstrom line emission, but only to the red of Ly alpha. The profiles of the N v lines differ markedly from that of H alpha, suggesting that the N4+ ions are scattered and accelerated by turbulent electromagnetic fields that isotropize the ions in the collisionless shock.
|
|
| 6. |
- Fransson, Claes, et al.
(författare)
-
DISCOVERY OF MOLECULAR HYDROGEN IN SN 1987A
- 2016
-
Ingår i: Astrophysical Journal Letters. - : Institute of Physics Publishing. - 2041-8205 .- 2041-8213. ; 821:1
-
Tidskriftsartikel (refereegranskat)abstract
- Both CO and SiO have been observed at early and late phases in SN 1987A. H-2 was predicted to form at roughly the same time as these molecules, but was not detected at early epochs. Here, we report the detection of NIR lines from H-2 at 2.12 and 2.40 mu m in VLT/SINFONI spectra obtained between days 6489 and 10,120. The emission is concentrated to the core of the SN in contrast to Ha and approximately coincides with the [Si I]/[Fe II] emission detected previously in the ejecta. Different excitation mechanisms and power sources of the emission are discussed. From the nearly constant H-2 luminosities, we favor excitation resulting from the Ti-44 decay.
|
|
| 7. |
- Fransson, Claes, et al.
(författare)
-
Late spectral evolution of the ejecta and reverse shock in SN 1987a
- 2013
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 768:1, s. 88-
-
Tidskriftsartikel (refereegranskat)abstract
- We present observations with the Very Large Telescope and Hubble Space Telescope (HST) of the broad emission lines from the inner ejecta and reverse shock of SN 1987A from 1999 February until 2012 January (days 4381-9100 after explosion). We detect broad lines from H alpha, H beta, Mg I], Na I, [O I], [Ca II], and a feature at similar to 9220 angstrom. We identify the latter line with Mg II lambda lambda 9218, 9244, which is most likely pumped by Ly alpha fluorescence. H alpha and H beta both have a centrally peaked component extending to similar to 4500 km s(-1) and a very broad component extending to greater than or similar to 11,000 km s(-1), while the other lines have only the central component. The low-velocity component comes from unshocked ejecta, heated mainly by X-rays from the circumstellar environment, whereas the very broad component comes from faster ejecta passing through the reverse shock, created by the collision with the circumstellar ring. The flux in H alpha from the reverse shock has increased by a factor of four to six from 2000 to 2007. After that there is a tendency of flattening of the light curve, similar to what may be seen in the optical lines from the shocked ring. The core component seen in H alpha, [Ca II], and Mg II has experienced a similar increase, which is consistent with that found from HST photometry. The energy deposition of the external X-rays is calculated using explosion models for SN 1987A and we predict that the outer parts of the unshocked ejecta will continue to brighten because of this. The external X-ray illumination also explains the edge-brightened morphology of the ejecta seen in the HST images. We finally discuss evidence for dust in the ejecta from line asymmetries.
|
|
| 8. |
- Fransson, Claes, et al.
(författare)
-
THE DESTRUCTION OF THE CIRCUMSTELLAR RING OF SN 1987A
- 2015
-
Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 806:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present imaging and spectroscopic observations with Hubble Space Telescope and Very Large Telescope of the ring of SN 1987A from 1994 to 2014. After an almost exponential increase of the shocked emission from the hotspots up to day similar to 8000 (similar to 2009), both this and the unshocked emission are now fading. From the radial positions of the hotspots we see an acceleration of these up to 500-1000 km s(-1), consistent with the highest spectroscopic shock velocities from the radiative shocks. In the most recent observations (2013 and 2014), we find several new hotspots outside the inner ring, excited by either X-rays from the shocks or by direct shock interaction. All of these observations indicate that the interaction with the supernova ejecta is now gradually dissolving the hotspots. We predict, based on the observed decay, that the inner ring will be destroyed by similar to 2025.
|
|
| 9. |
- Graves, Genevieve J. M., et al.
(författare)
-
Limits from the Hubble Space Telescope on a Point Source in SN 1987A
- 2005
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 629, s. 944-959
-
Tidskriftsartikel (refereegranskat)abstract
- We observed supernova 1987A (SN 1987A) with the Space Telescope Imaging Spectrograph (STIS) on the Hubble Space Telescope (HST) in 1999 September and again with the Advanced Camera for Surveys (ACS) on the HST in 2003 November. Our spectral observations cover ultraviolet (UV) and optical wavelengths from 1140 to 10266 Å, and our imaging observations cover UV and optical wavelengths from 2900 to 9650 Å. No point source is observed in the remnant. We obtain a limiting flux of Fopt<=1.6×10-14 ergs s-1 cm-2 in the wavelength range 2900-9650 Å for any continuum emitter at the center of the supernova remnant (SNR). This corresponds to an intrinsic luminosity of Lopt<=5×1033 ergs s-1. It is likely that the SNR contains opaque dust that absorbs UV and optical emission, resulting in an attenuation of ~35% due to dust absorption in the SNR. Correcting for this level of dust absorption would increase our upper limit on the luminosity of a continuum source by a factor of 1.54. Taking into account dust absorption in the remnant, we find a limit of Lopt<=8×1033 ergs s-1. We compare this upper bound with empirical evidence from point sources in other supernova remnants and with theoretical models for possible compact sources. We show that any survivor of a possible binary system must be no more luminous than an F6 main-sequence star. Bright young pulsars such as Kes 75 or the Crab pulsar are excluded by optical and X-ray limits on SN 1987A. Other nonplerionic X-ray point sources have luminosities similar to the limits on a point source in SN 1987A; RCW 103 and Cas A are slightly brighter than the limits on SN 1987A, while Pup A is slightly fainter. Of the young pulsars known to be associated with SNRs, those with ages <=5000 yr are all too bright in X-rays to be compatible with the limits on SN 1987A. Examining theoretical models for accretion onto a compact object, we find that spherical accretion onto a neutron star is firmly ruled out and that spherical accretion onto a black hole is possible only if there is a larger amount of dust absorption in the remnant than predicted. In the case of thin-disk accretion, our flux limit requires a small disk, no larger than 1010 cm, with an accretion rate no more than 0.3 times the Eddington accretion rate. Possible ways to hide a surviving compact object include the removal of all surrounding material at early times by a photon-driven wind, a small accretion disk, or very high levels of dust absorption in the remnant. It will not be easy to improve substantially on our optical-UV limit for a point source in SN 1987A, although we can hope that a better understanding of the thermal infrared emission will provide a more complete picture of the possible energy sources at the center of SN 1987A.
|
|
| 10. |
- Heng, Kevin, et al.
(författare)
-
Evolution of the Reverse Shock Emission from SNR 1987A
- 2006
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 644, s. 959-970
-
Tidskriftsartikel (refereegranskat)abstract
- We present new (2004 July) G750L and G140L Space Telescope Imaging Spectrograph (STIS) data of the Hα and Lyα emission from supernova remnant (SNR) 1987A. With the aid of earlier data, from 1997 October to 2002 October, we track the local evolution of Lyα emission and both the local and global evolution of Hα emission. The most recent observations allow us to directly compare the Hα and Lyα emission from the same slit position and at the same epoch. Consequently, we find clear evidence that, unlike Hα, Lyα is reflected from the debris by resonant scattering. In addition to emission that we can clearly attribute to the surface of the reverse shock, we also measure comparable emission, in both Hα and Lyα, that appears to emerge from supernova debris interior to the surface. New observations taken through slits positioned slightly eastward and westward of a central slit show a departure from cylindrical symmetry in the Hα surface emission. Using a combination of old and new observations, we construct a light curve of the total Hα flux, F, from the reverse shock, which has increased by a factor of ~4 over about 8 yr. However, due to large systematic uncertainties, we are unable to discern between the two limiting behaviors of the flux: F~t (self-similar expansion) and F~t5 (halting of the reverse shock). Such a determination is important for constraining the rate of hydrogen atoms crossing the shock, which is relevant to the question of whether the reverse shock emission will vanish in <~7 yr. Future deep, low- or moderate-resolution spectra are essential for accomplishing this task.
|
|
