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2. |
- de Jong, R. S., et al.
(författare)
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4MOST : Project overview and information for the First Call for Proposals
- 2019
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Ingår i: The Messenger. - : European Southern Observatory. - 0722-6691. ; 175, s. 3-11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We introduce the 4-metre Multi-Object Spectroscopic Telescope (4MOST), a new high-multiplex, wide-field spectroscopic survey facility under development for the four-metre-class Visible and Infrared Survey Telescope for Astronomy (VISTA) at Paranal. Its key specifications are: a large field of view (FoV) of 4.2 square degrees and a high multiplex capability, with 1624 fibres feeding two low-resolution spectrographs (R = λ/Δλ ~ 6500), and 812 fibres transferring light to the high-resolution spectrograph (R ~ 20 000). After a description of the instrument and its expected performance, a short overview is given of its operational scheme and planned 4MOST Consortium science; these aspects are covered in more detail in other articles in this edition of The Messenger. Finally, the processes, schedules, and policies concerning the selection of ESO Community Surveys are presented, commencing with a singular opportunity to submit Letters of Intent for Public Surveys during the first five years of 4MOST operations.
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3. |
- Bonham, LW, et al.
(författare)
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Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10854-
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Tidskriftsartikel (refereegranskat)abstract
- The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
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4. |
- Schulze, S., et al.
(författare)
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GRB 120422A/SN 2012bz : Bridging the gap between low- and high-luminosity gamma-ray bursts
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 566
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Tidskriftsartikel (refereegranskat)abstract
- Context. At low redshift, a handful of gamma-ray bursts (GRBs) have been discovered with luminosities that are substantially lower (L-iso less than or similar to 10(48.5) erg s(-1)) than the average of more distant ones (L-iso greater than or similar to 10(49.5) erg s(-1)). It has been suggested that the properties of several low-luminosity (low-L) GRBs are due to shock break-out, as opposed to the emission from ultrarelativistic jets. This has led to much debate about how the populations are connected. Aims. The burst at redshift z = 0.283 from 2012 April 22 is one of the very few examples of intermediate-L GRBs with a gamma-ray luminosity of L-iso similar to 10(49.6-49.9) erg s(-1) that have been detected up to now. With the robust detection of its accompanying supernova SN 2012bz, it has the potential to answer important questions on the origin of low-and high-L GRBs and the GRB-SN connection. Methods. We carried out a spectroscopy campaign using medium-and low-resolution spectrographs with 6-10-m class telescopes, which covered a time span of 37.3 days, and a multi-wavelength imaging campaign, which ranged from radio to X-ray energies over a duration of similar to 270 days. Furthermore, we used a tuneable filter that is centred at H alpha to map star-formation in the host and the surrounding galaxies. We used these data to extract and model the properties of different radiation components and fitted the spectral energy distribution to extract the properties of the host galaxy. Results. Modelling the light curve and spectral energy distribution from the radio to the X-rays revealed that the blast wave expanded with an initial Lorentz factor of Gamma(0) similar to 50, which is a low value in comparison to high-L GRBs, and that the afterglow had an exceptionally low peak luminosity density of less than or similar to 2 x 10(30) erg s(-1) Hz(-1) in the sub-mm. Because of the weak afterglow component, we were able to recover the signature of a shock break-out in an event that was not a genuine low-L GRB for the first time. At 1.4 hr after the burst, the stellar envelope had a blackbody temperature of k(B)T similar to 16 eV and a radius of similar to 7 x 10(13) cm (both in the observer frame). The accompanying SN 2012bz reached a peak luminosity of M-V = -19.7 mag, which is 0.3 mag more luminous than SN 1998bw. The synthesised nickel mass of 0.58 M-circle dot, ejecta mass of 5.87 M-circle dot, and kinetic energy of 4.10x10(52) erg were among the highest for GRB-SNe, which makes it the most luminous spectroscopically confirmed SN to date. Nebular emission lines at the GRB location were visible, which extend from the galaxy nucleus to the explosion site. The host and the explosion site had close-to-solar metallicity. The burst occurred in an isolated star-forming region with an SFR that is 1/10 of that in the galaxy's nucleus. Conclusions. While the prompt gamma-ray emission points to a high-L GRB, the weak afterglow and the low Gamma(0) were very atypical for such a burst. Moreover, the detection of the shock break-out signature is a new quality for high-L GRBs. So far, shock break-outs were exclusively detected for low-L GRBs, while GRB 120422A had an intermediate L-iso of similar to 10(49.6-49.9) erg s(-1). Therefore, we conclude that GRB 120422A was a transition object between low-and high-L GRBs, which supports the failed-jet model that connects low-L GRBs that are driven by shock break-outs and high-L GRBs that are powered by ultra-relativistic jets.
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5. |
- Cano, Z., et al.
(författare)
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GRB 161219B/SN 2016jca : A low-redshift gamma-ray burst supernova powered by radioactive heating
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 605
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Tidskriftsartikel (refereegranskat)abstract
- Since the first discovery of a broad-lined type Ic supernova (SN) with a long-duration gamma-ray burst (GRB) in 1998, fewer than fifty GRB-supernovae (SNe) have been discovered. The intermediate-luminosity Swift GRB 161219B and its associated supernova SN 2016jca, which occurred at a redshift of z = 0.1475, represents only the seventh GRB-SN to have been discovered within 1 Gpc, and hence provides an excellent opportunity to investigate the observational and physical properties of these very elusive and rare type of SN. As such, we present optical to near-infrared photometry and optical spectroscopy of GRB 161219B and SN 2016jca, spanning the first three months since its discovery. GRB 161219B exploded in the disk of an edge-on spiral galaxy at a projected distance of 3.4 kpc from the galactic centre. GRB 161219B itself is an outlier in the E-p,E-i - E-gamma,E-iso plane, while SN 2016jca had a rest-frame, peak absolute V-band magnitude of M-V = -19.0 +/- 0.1, which it reached after 12.3 +/- 0.7 rest-frame days. We find that the bolometric properties of SN 2016jca are inconsistent with being powered solely by a magnetar central engine, and demonstrate that it was likely powered exclusively by energy deposited by the radioactive decay of nickel and cobalt into their daughter products, which were nucleosynthesised when its progenitor underwent core collapse. We find that 0.22 +/- 0.08 M-circle dot of nickel is required to reproduce the peak luminosity of SN 2016jca, and we constrain an ejecta mass of 5.8 +/- 0.3 M-circle dot and a kinetic energy of 5.1 +/- 0.8 x 10(52) erg. Finally, we report on a chromatic, pre-maximum bump in the g-band light curve, and discuss its possible origin.
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6. |
- Fynbo, J. P. U., et al.
(författare)
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On the two high-metallicity DLAs at z=2.412 and 2.583 towards Q 0918+1636
- 2013
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 436:1, s. 361-370
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Tidskriftsartikel (refereegranskat)abstract
- The quasar Q0918+1636 (z = 3.07) has two intervening high-metallicity Damped Lyman a Absorbers (DLAs) along the line of sight, at redshifts of z = 2.412 and 2.583. The z = 2.583 DLA is located at a large impact parameter of 16.2 kpc, and despite this large impact parameter it has a very high metallicity (consistent with solar), a substantial fraction of H-2 molecules and it is dusty as inferred from the reddened spectrum of the background QSO. The z = 2.412 DLA has a metallicity of [M/H] = -0.6 (based on Zn II and Si II). In this paper we present new observations of this interesting sightline consisting of deep multiband imaging and further VLT spectroscopy. By fitting stellar population synthesis models to the photometric Spectral Energy Distribution we constrain the physical properties of the z = 2.583 DLA galaxy, and we infer its morphology by fitting a Sersic model to its surface brightness profile. We find it to be a relatively massive (M-* approximate to 10(10) M-circle dot), strongly star-forming (SFR approximate to 30 M-circle dot yr(-1)), dusty (E(B - V) = 0.4) galaxy with a disc-like morphology. We detect strong emission lines from the z = 2.583 DLA ([O II] lambda 3727, [O III] lambda lambda 4960, 5007, H beta and H alpha, albeit at low signal-to-noise ratio except for the [O III] lambda 5007 line). The metallicity derived from the emission lines is consistent with the absorption metallicity (12 + log (O/H) = 8.8 +/- 0.2). We also detect [O III] lambda 5007 emission from the galaxy counterpart of the z = 2.412 DLA at a small impact parameter (<2 kpc). Overall our findings are consistent with the emerging picture that high-metallicity DLAs are associated with relatively luminous and massive galaxy counterparts, compared to typical DLAs.
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7. |
- Pastorello, A., et al.
(författare)
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A luminous stellar outburst during a long-lasting eruptive phase first, and then SN IIn 2018cnf
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 628
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of the monitoring campaign of the Type IIn supernova (SN) 2018cnf (a.k.a. ASASSN-18mr). It was discovered about ten days before the maximum light (on MJD = 58 293.4 +/- 5.7 in the V band, with M-V = -18.13 +/- 0.15 mag). The multiband light curves show an immediate post-peak decline with some minor luminosity fluctuations, followed by a flattening starting about 40 days after maximum. The early spectra are relatively blue and show narrow Balmer lines with P Cygni profiles. Additionally, Fe II, O I, He I, and Ca II are detected. The spectra show little evolution with time and with intermediate-width features becoming progressively more prominent, indicating stronger interaction of the SN ejecta with the circumstellar medium. The inspection of archival images from the Panoramic Survey Telescope and Rapid Response System (Pan-STARRS) survey has revealed a variable source at the SN position with a brightest detection in December 2015 at M-r = -14.66 +/- 0.17 mag. This was likely an eruptive phase from the massive progenitor star that started from at least mid-2011, and that produced the circumstellar environment within which the star exploded as a Type IIn SN. The overall properties of SN 2018cnf closely resemble those of transients such as SN 2009ip. This similarity favours a massive hypergiant, perhaps a luminous blue variable, as progenitor for SN 2018cnf.
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8. |
- Xu, D., et al.
(författare)
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DISCOVERY OF THE BROAD-LINED TYPE Ic SN 2013cq ASSOCIATED WITH THE VERY ENERGETIC GRB 130427A
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 776:2, s. 98-
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Tidskriftsartikel (refereegranskat)abstract
- Long-duration gamma-ray bursts (GRBs) at z < 1 are found in most cases to be accompanied by bright, broadlined Type Ic supernovae (SNe Ic-BL). The highest-energy GRBs are mostly located at higher redshifts, where the associated SNe are hard to detect observationally. Here, we present early and late observations of the optical counterpart of the very energetic GRB 130427A. Despite its moderate redshift, z = 0.3399+/-0.0002, GRB 130427A is at the high end of the GRB energy distribution, with an isotropic-equivalent energy release of E-iso similar to 9.6 x 10(53) erg, more than an order of magnitude more energetic than other GRBs with spectroscopically confirmed SNe. In our dense photometric monitoring, we detect excess flux in the host-subtracted r-band light curve, consistent with that expected from an emerging SN, similar to 0.2 mag fainter than the prototypical SN 1998bw. A spectrum obtained around the time of the SN peak (16.7 days after the GRB) reveals broad undulations typical of SNe Ic-BL, confirming the presence of an SN, designated SN 2013cq. The spectral shape and early peak time are similar to those of the high expansion velocity SN 2010bh associated with GRB 100316D. Our findings demonstrate that high-energy, long-duration GRBs, commonly detected at high redshift, can also be associated with SNe Ic-BL, pointing to a common progenitor mechanism.
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10. |
- Fynbo, J. P. U., et al.
(författare)
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The galaxy counterpart and environment of the dusty damped Lyman-α absorber at z = 2.226 towards Q 1218+0832
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 679
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Tidskriftsartikel (refereegranskat)abstract
- We report on further observations of the field of the quasar Q 1218+0832. Geier et al. (2019, A&A, 625, L9) presented the discovery of the quasar resulting from a search for quasars reddened and dimmed by dust in foreground damped Lyman-α absorbers (DLAs). The DLA is remarkable by having a very large H I column density close to 1022 cm−2. Its dust extinction curve shows the 2175 Å bump known from the Local Group. It also shows absorption from cold gas exemplified by C I and CO molecules. For this paper, we present narrow-band observations of the field of Q 1218+0832 and also use an archival Hubble Space Telescope (HST) image to search for the galaxy counterpart of the DLA. No emission from the DLA galaxy is found in either the narrow-band imaging or in the HST image. In the HST image, we could probe down to an impact parameter of 0.3 arcsec and a 3-σ detection limit of 26.8 mag per arcsec2. In the narrow-band image, we probed down to a 0 arcsec impact parameter and detected nothing down to a 3-σ detection limit of about 3 × 10−17 erg s−1 cm−2. We did detect a bright Lyman-α emitter 59 arcsec south of Q 1218+0832 with a flux of 3 × 10−16 erg s−1 cm−2. We conclude that the DLA galaxy must be located at a very small impact parameter (< 0.3 arcsec, 2.5 kpc) or it is optically dark. Also, the DLA galaxy most likely is part of a galaxy group.
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11. |
- Gandolfi, D., et al.
(författare)
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Kepler-423b: a half-Jupiter mass planet transiting a very old solar-like star
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 576
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Tidskriftsartikel (refereegranskat)abstract
- We report the spectroscopic confirmation of the Kepler object of interest KOI-183.01 (Kepler-423b), a half-Jupiter mass planet transiting an old solar-like star every 2.7 days. Our analysis is the first to combine the full Kepler photometry (quarters 1 17) with high-precision radial velocity measurements taken with the FIES spectrograph at the Nordic Optical Telescope. We simultaneously modelled the photometric and spectroscopic data-sets using Bayesian approach coupled with Markov chain Monte Carlo sampling. We found that the Kepler pre-search data conditioned light curve of Kepler-423 exhibits quarter-to-quarter systematic variations of the transit depth, with a peak-to-peak amplitude of similar to 4.3% and seasonal trends reoccurring every four quarters. We attributed these systematics to an incorrect assessment of the quarterly variation of the crowding metric. The host star Kepler-423 is a G4 dwarf with M-* = 0.85 +/- 0.04 M-circle dot, R-* = 0.95 +/- 0.04 R-circle dot, T-eff = 5560 +/- 80 K, [M/H] = -0.10 +/- 0.05 dex, and with an age of 11 +/- 2 Gyr. The planet Kepler-423b has a mass of M-p = 0.595 +/- 0.081 M-Jup and a radius of R-p = 1.192 +/- 0.052 R-Jup, yielding a planetary bulk density of rho(p) = 0.459 +/- 0.083 g cm(-3). The radius of Kepler-423b is consistent with both theoretical models for irradiated coreless giant planets and expectations based on empirical laws. The inclination of the stellar spin axis suggests that the system is aligned along the line of sight. We detected a tentative secondary eclipse of the planet at a 2 sigma confidence level (Delta F-ec = 14.2 +/- 6.6 ppm) and found that the orbit might have a small non-zero eccentricity of 0.019(-0.014)(+0.028) . With a Bond albedo of A(B) = 0.037 +/- 0.019, Kepler-423b is one of the gas-giant planets with the lowest albedo known so far.
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12. |
- Hardy, Timothy, et al.
(författare)
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The European NAFLD Registry : A real-world longitudinal cohort study of nonalcoholic fatty liver disease
- 2020
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Ingår i: Contemporary Clinical Trials. - : Elsevier. - 1551-7144 .- 1559-2030. ; 98
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Tidskriftsartikel (refereegranskat)abstract
- Non-Alcoholic Fatty Liver Disease (NAFLD), a progressive liver disease that is closely associated with obesity, type 2 diabetes, hypertension and dyslipidaemia, represents an increasing global public health challenge. There is significant variability in the disease course: the majority exhibit only fat accumulation in the liver but a significant minority develop a necroinflammatory form of the disease (non-alcoholic steatohepatitis, NASH) that may progress to cirrhosis and hepatocellular carcinoma. At present our understanding of pathogenesis, disease natural history and long-term outcomes remain incomplete. There is a need for large, well characterised patient cohorts that may be used to address these knowledge gaps and to support the development of better biomarkers and novel therapies. The European NAFLD Registry is an international, prospectively recruited observational cohort study that aims to establish a large, highly-phenotyped patient cohort and linked bioresource. Here we describe the infrastructure, data management and monitoring plans, and the standard operating procedures implemented to ensure the timely and systematic collection of high-quality data and samples. Already recruiting subjects at secondary/tertiary care centres across Europe, the Registry is supporting the European Union IMI2-funded LITMUS Liver Investigation: Testing Marker Utility in Steatohepatitis consortium, which is a major international effort to robustly validate biomarkers that diagnose, risk stratify and/or monitor NAFLD progression and liver fibrosis stage. The European NAFLD Registry has the demonstrable capacity to support research and biomarker development at scale and pace.
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14. |
- Kupfer, T., et al.
(författare)
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The OmegaWhite Survey for Short-period Variable Stars. V. Discovery of an Ultracompact Hot Subdwarf Binary with a Compact Companion in a 44-minute Orbit
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 851:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of the ultracompact hot subdwarf (sdOB) binary OW J074106.0-294811.0 with an orbital period of P-orb = 44.66279 +/- 1.16 x 10(-4) minutes, making it the most compact hot subdwarf binary known. Spectroscopic observations using the VLT, Gemini and Keck telescopes revealed a He-sdOB primary with an intermediate helium abundance, T-eff = 39 400 +/- 500 K and log g = 5.74 +/- 0.09. High signal-to-noise ratio light curves show strong ellipsoidal modulation resulting in a derived sdOB mass M-sdOB= 0.23 +/- 0.12 M-circle dot with a WD companion (M-WD = 0.72 +/- 0.17 M-circle dot). The mass ratio was found to be q = M-sdOB/M-WD = 0.32 +/- 0.10. The derived mass for the He-sdOB is inconsistent with the canonical mass for hot subdwarfs of approximate to 0.47 M-circle dot. To put constraints on the structure and evolutionary history of the sdOB star we compared the derived T-eff, log g, and sdOB mass to evolutionary tracks of helium stars and helium white dwarfs calculated with Modules for Experiments in Stellar Astrophysics (MESA). We find that the best-fitting model is a helium white dwarf with a mass of 0.320 M-circle dot, which left the common envelope approximate to 1.1 Myr ago, which is consistent with the observations. As a helium white dwarf with a massive white dwarf companion, the object will reach contact in 17.6 Myr at an orbital period of 5 minutes. Depending on the spin-orbit synchronization timescale the object will either merge to form an R CrB star or end up as a stably accreting AM CVn-type system with a helium white dwarf donor.
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17. |
- Fiore, Achille, et al.
(författare)
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Detailed spectrophotometric analysis of the superluminous and fast evolving SN 2019neq
- 2024
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Ingår i: Monthly notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 527:3, s. 6473-6494
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Tidskriftsartikel (refereegranskat)abstract
- SN 2019neq was a very fast evolving superluminous supernova. At a redshift z = 0.1059, its peak absolute magnitude was −21.5 ± 0.2 mag in g band. In this work, we present data and analysis from an extensive spectrophotometric follow-up campaign using multiple observational facilities. Thanks to a nebular spectrum of SN 2019neq, we investigated some of the properties of the host galaxy at the location of SN 2019neq and found that its metallicity and specific star formation rate are in a good agreement with those usually measured for SLSNe-I hosts. We then discuss the plausibility of the magnetar and the circumstellar interaction scenarios to explain the observed light curves, and interpret a nebular spectrum of SN 2019neq using published SUMO radiative-transfer models. The results of our analysis suggest that the spin-down radiation of a millisecond magnetar with a magnetic field B ≃ 6×1014 G could boost the luminosity of SN 2019neq.
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19. |
- Lee, Jenny, et al.
(författare)
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Machine learning algorithm improves the detection of NASH (NAS-based) and at-risk NASH: A development and validation study
- 2023
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Ingår i: Hepatology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0270-9139 .- 1527-3350. ; 78:1, s. 258-271
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Detecting NASH remains challenging, while at-risk NASH (steatohepatitis and F >= 2) tends to progress and is of interest for drug development and clinical application. We developed prediction models by supervised machine learning techniques, with clinical data and biomarkers to stage and grade patients with NAFLD. Approach and Results: Learning data were collected in the Liver Investigation: Testing Marker Utility in Steatohepatitis metacohort (966 biopsy-proven NAFLD adults), staged and graded according to NASH CRN. Conditions of interest were the clinical trial definition of NASH (NAS >= 4;53%), at-risk NASH (NASH with F >= 2;35%), significant (F >= 2;47%), and advanced fibrosis (F >= 3;28%). Thirty-five predictors were included. Missing data were handled by multiple imputations. Data were randomly split into training/validation (75/25) sets. A gradient boosting machine was applied to develop 2 models for each condition: clinical versus extended (clinical and biomarkers). Two variants of the NASH and at-risk NASH models were constructed: direct and composite models.Clinical gradient boosting machine models for steatosis/inflammation/ballooning had AUCs of 0.94/0.79/0.72. There were no improvements when biomarkers were included. The direct NASH model produced AUCs (clinical/extended) of 0.61/0.65. The composite NASH model performed significantly better (0.71) for both variants. The composite at-risk NASH model had an AUC of 0.83 (clinical and extended), an improvement over the direct model. Significant fibrosis models had AUCs (clinical/extended) of 0.76/0.78. The extended advanced fibrosis model (0.86) performed significantly better than the clinical version (0.82). Conclusions: Detection of NASH and at-risk NASH can be improved by constructing independent machine learning models for each component, using only clinical predictors. Adding biomarkers only improved the accuracy of fibrosis.
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20. |
- Lévy, Romain, et al.
(författare)
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Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.
- 2023
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 220:2
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Tidskriftsartikel (refereegranskat)abstract
- Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-κB but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and low blood counts of CD4+ and CD8+ memory T cells and CD4+ TREGs. Unlike CD28-deficient patients, they have low counts of NK cells and memory B cells, and their antibody responses are weak. CARMIL2 deficiency is fully penetrant by the age of 10 yr and is characterized by numerous infections, EBV+ smooth muscle tumors, and mucocutaneous inflammation, including inflammatory bowel disease. Patients with somatic reversions of a mutant allele in CD4+ T cells have milder phenotypes. Our study suggests that CARMIL2 governs immunological pathways beyond CD28.
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21. |
- Maccari, Maria Elena, et al.
(författare)
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Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity.
- 2023
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Ingår i: The Journal of allergy and clinical immunology. - 1097-6825. ; 152:4
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Tidskriftsartikel (refereegranskat)abstract
- Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking.This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS.Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs.The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS.APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.
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22. |
- Mozes, Ferenc E., et al.
(författare)
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Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis
- 2023
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Ingår i: The Lancet Gastroenterology & Hepatology. - : ELSEVIER INC. - 2468-1253. ; 8:8, s. 704-713
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Tidskriftsartikel (refereegranskat)abstract
- Background Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. Methods This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score >= 15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs >= 20 kPa; FIB-4: <1<middle dot>3 vs 1<middle dot>3 to <= 2<middle dot>67 vs >2<middle dot>67; NFS: <-1<middle dot>455 vs -1<middle dot>455 to <= 0<middle dot>676 vs >0<middle dot>676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.Findings Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44<middle dot>7%] were female, median age was 54 years [IQR 44-63), and 1161 [46<middle dot>1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5<middle dot>8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0<middle dot>0001 for all comparisons). The tAUC at 5 years were 0<middle dot>72 (95% CI 0<middle dot>62-0<middle dot>81) for histology, 0<middle dot>76 (0<middle dot>70-0<middle dot>83) for LSM-VCTE, 0<middle dot>74 (0<middle dot>64-0<middle dot>82) for FIB-4, and 0<middle dot>70 (0<middle dot>63-0<middle dot>80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.Interpretation Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases.
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23. |
- Pastorello, A., et al.
(författare)
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Supernovae 2016bdu and 2005gl, and their link with SN 2009ip-like transients : another piece of the puzzle
- 2018
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 474:1, s. 197-218
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Tidskriftsartikel (refereegranskat)abstract
- Supernova (SN) 2016bdu is an unusual transient resembling SN 2009ip. SN 2009ip-like events are characterized by a long-lasting phase of erratic variability that ends with two luminous outbursts a few weeks apart. The second outburst is significantly more luminous (about 3 mag) than the first. In the case of SN 2016bdu, the first outburst (Event A) reached an absolute magnitude M-r approximate to -15.3 mag, while the second one (Event B) occurred over one month later and reached M-r approximate to -18 mag. By inspecting archival data, a faint source at the position of SN 2016bdu is several times in the past few years. We interpret these detections as signatures of a phase of erratic variability, similar to that experienced by SN 2009ip between 2008 and mid-2012, and resembling the currently observed variability of the luminous blue variable SN 2000ch in NGC 3432. Spectroscopic monitoring of SN 2016bdu during the second peak initially shows features typical of an SN IIn. One month after the Event B maximum, the spectra develop broad Balmer lines with P Cygni profiles and broad metal features. At these late phases, the spectra resemble those of a typical Type II SN. All members of this SN 2009ip-like group are remarkably similar to the Type IIn SN 2005gl. For this object, the claim of a terminal SN explosion is supported by the disappearance of the progenitor star. While the similarity with SN 2005gl supports a genuine SN explosion scenario for SN 2009ip-like events, the unequivocal detection of nucleosynthesized elements in their nebular spectra is still missing.
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24. |
- Pastorello, A., et al.
(författare)
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The evolution of luminous red nova AT 2017jfs in NGC 4470
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 625
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of our photometric and spectroscopic follow-up of the intermediate-luminosity optical transient AT 2017jfs. At peak, the object reaches an absolute magnitude of M-g = 15.46 +/- 0.15 mag and a bolometric luminosity of 5.5 x 10(41) erg s(-1). Its light curve has the double-peak shape typical of luminous red novae (LRNe), with a narrow first peak bright in the blue bands, while the second peak is longer-lasting and more luminous in the red and near-infrared (NIR) bands. During the first peak, the spectrum shows a blue continuum with narrow emission lines of H and Fe II. During the second peak, the spectrum becomes cooler, resembling that of a K-type star, and the emission lines are replaced by a forest of narrow lines in absorption. About 5 months later, while the optical light curves are characterized by a fast linear decline, the NIR ones show a moderate rebrightening, observed until the transient disappears in solar conjunction. At these late epochs, the spectrum becomes reminiscent of that of M-type stars, with prominent molecular absorption bands. The late-time properties suggest the formation of some dust in the expanding common envelope or an IR echo from foreground pre-existing dust. We propose that the object is a common-envelope transient, possibly the outcome of a merging event in a massive binary, similar to NGC4490-2011OT1.
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25. |
- Pavlides, Michael, et al.
(författare)
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Liver investigation: Testing marker utility in steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol
- 2023
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Ingår i: Contemporary Clinical Trials. - : ELSEVIER SCIENCE INC. - 1551-7144 .- 1559-2030. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721
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26. |
- Romanczuk, P., et al.
(författare)
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Motion of Euglena gracilis : Active fluctuations and velocity distribution
- 2015
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Ingår i: The European Physical Journal Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 224:7, s. 1215-1229
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Tidskriftsartikel (refereegranskat)abstract
- We study the velocity distribution of unicellular swimming algae Euglena gracilis using optical microscopy and active Brownian particle theory. To characterize a peculiar feature of the experimentally observed distribution at small velocities we use the concept of active fluctuations, which was recently proposed for the description of stochastically self-propelled particles [Romanczuk, P. and Schimansky-Geier, L., Phys. Rev. Lett. 106, 230601 (2011)]. In this concept, the fluctuating forces arise due to internal random performance of the propulsive motor. The fluctuating forces are directed in parallel to the heading direction, in which the propulsion acts. In the theory, we introduce the active motion via the depot model [Schweitzer, et al., Phys. Rev. Lett. 80(23), 5044 (1998)]. We demonstrate that the theoretical predictions based on the depot model with active fluctuations are consistent with the experimentally observed velocity distributions. In addition to the model with additive active noise, we obtain theoretical results for a constant propulsion with multiplicative noise.
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27. |
- Vali, Yasaman, et al.
(författare)
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Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project) : a comparative diagnostic accuracy study
- 2023
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Ingår i: The Lancet Gastroenterology & Hepatology. - : Elsevier Ltd. - 2468-1253. ; 8:8, s. 714-725
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Tidskriftsartikel (refereegranskat)abstract
- Background: The reference standard for detecting non-alcoholic steatohepatitis (NASH) and staging fibrosis—liver biopsy—is invasive and resource intensive. Non-invasive biomarkers are urgently needed, but few studies have compared these biomarkers in a single cohort. As part of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) project, we aimed to evaluate the diagnostic accuracy of 17 biomarkers and multimarker scores in detecting NASH and clinically significant fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) and identify their optimal cutoffs as screening tests in clinical trial recruitment. Methods: This was a comparative diagnostic accuracy study in people with biopsy-confirmed NAFLD from 13 countries across Europe, recruited between Jan 6, 2010, and Dec 29, 2017, from the LITMUS metacohort of the prospective European NAFLD Registry. Adults (aged ≥18 years) with paired liver biopsy and serum samples were eligible; those with excessive alcohol consumption or evidence of other chronic liver diseases were excluded. The diagnostic accuracy of the biomarkers was expressed as the area under the receiver operating characteristic curve (AUC) with liver histology as the reference standard and compared with the Fibrosis-4 index for liver fibrosis (FIB-4) in the same subgroup. Target conditions were the presence of NASH with clinically significant fibrosis (ie, at-risk NASH; NAFLD Activity Score ≥4 and F≥2) or the presence of advanced fibrosis (F≥3), analysed in all participants with complete data. We identified thres holds for each biomarker for reducing the number of biopsy-based screen failures when recruiting people with both NASH and clinically significant fibrosis for future trials. Findings: Of 1430 participants with NAFLD in the LITMUS metacohort with serum samples, 966 (403 women and 563 men) were included after all exclusion criteria had been applied. 335 (35%) of 966 participants had biopsy-confirmed NASH and clinically significant fibrosis and 271 (28%) had advanced fibrosis. For people with NASH and clinically significant fibrosis, no single biomarker or multimarker score significantly reached the predefined AUC 0·80 acceptability threshold (AUCs ranging from 0·61 [95% CI 0·54–0·67] for FibroScan controlled attenuation parameter to 0·81 [0·75–0·86] for SomaSignal), with accuracy mostly similar to FIB-4. Regarding detection of advanced fibrosis, SomaSignal (AUC 0·90 [95% CI 0·86–0·94]), ADAPT (0·85 [0·81–0·89]), and FibroScan liver stiffness measurement (0·83 [0·80–0·86]) reached acceptable accuracy. With 11 of 17 markers, histological screen failure rates could be reduced to 33% in trials if only people who were marker positive had a biopsy for evaluating eligibility. The best screening performance for NASH and clinically significant fibrosis was observed for SomaSignal (number needed to test [NNT] to find one true positive was four [95% CI 4–5]), then ADAPT (six [5–7]), MACK-3 (seven [6–8]), and PRO-C3 (nine [7–11]). Interpretation: None of the single markers or multimarker scores achieved the predefined acceptable AUC for replacing biopsy in detecting people with both NASH and clinically significant fibrosis. However, several biomarkers could be applied in a prescreening strategy in clinical trial recruitment. The performance of promising markers will be further evaluated in the ongoing prospective LITMUS study cohort. Funding: The Innovative Medicines Initiative 2 Joint Undertaking. © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
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