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- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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- Smartt, S. J., et al.
(författare)
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A kilonova as the electromagnetic counterpart to a gravitational-wave source
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 551:7678, s. 75-
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Tidskriftsartikel (refereegranskat)abstract
- Gravitational waves were discovered with the detection of binary black-hole mergers(1) and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova(2-5). The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate(6). Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short.-ray burst(7,8). The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 +/- 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 +/- 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 +/- 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.
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| 6. |
- Anderson, J. P., et al.
(författare)
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A nearby super-luminous supernova with a long pre-maximum plateau and strong C (II) features
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
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Tidskriftsartikel (refereegranskat)abstract
- Context. Super-luminous supernovae (SLSNe) are rare events defined as being significantly more luminous than normal terminal stellar explosions. The source of the additional power needed to achieve such luminosities is still unclear. Discoveries in the local Universe (i.e. z < 0.1) are scarce, but afford dense multi-wavelength observations. Additional low-redshift objects are therefore extremely valuable.Aims. We present early-time observations of the type I SLSN ASASSN-18km/SN 2018bsz. These data are used to characterise the event and compare to literature SLSNe and spectral models. Host galaxy properties are also analysed.Methods. Optical and near-IR photometry and spectroscopy were analysed. Early-time ATLAS photometry was used to constrain the rising light curve. We identified a number of spectral features in optical-wavelength spectra and track their time evolution. Finally, we used archival host galaxy photometry together with H( II )region spectra to constrain the host environment.Results. ASASSN-18km/SN 2018bsz is found to be a type I SLSN in a galaxy at a redshift of 0.0267 (111 Mpc), making it the lowest-redshift event discovered to date. Strong C- II lines are identified in the spectra. Spectral models produced by exploding a Wolf-Rayet progenitor and injecting a magnetar power source are shown to be qualitatively similar to ASASSN-18km/SN 2018bsz, contrary to most SLSNe-I that display weak or non-existent C (II) lines. ASASSN-18km/SN 2018bsz displays along, slowly rising, red plateau of >26 days, before a steeper, faster rise to maximum. The host has an absolute magnitude of -19.8 mag (r), a mass of M-* = 1.5(-0.33)(+0.08) x 10(9) M-circle dot, and a star formation rate of =0.50(-0.19)(+2.22) M-circle dot yr(-1). A nearby H (II) region has an oxygen abundance (O3N2) of 8.31 +/- 0.01 dex.
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- Magee, M. R., et al.
(författare)
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The type Iax supernova, SN 2015H A white dwarf deflagration candidate
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 589
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Tidskriftsartikel (refereegranskat)abstract
- We present results based on observations of SN 2015H which belongs to the small group of objects similar to SN 2002cx, otherwise known as type Iax supernovae. The availability of deep pre-explosion imaging allowed us to place tight constraints on the explosion epoch. Our observational campaign began approximately one day post-explosion, and extended over a period of about 150 days post maximum light, making it one of the best observed objects of this class to date. We find a peak magnitude of M-r = 17.27 +/- 0.07, and a (Delta m(15))(r) = 0.69 +/- 0.04. Comparing our observations to synthetic spectra generated from simulations of deflagrations of Chandrasekhar mass carbon-oxygen white dwarfs, we find reasonable agreement with models of weak deflagrations that result in the ejection of similar to 0.2 M-circle dot of material containing similar to 0.07 M-circle dot of Ni-56. The model light curve however, evolves more rapidly than observations, suggesting that a higher ejecta mass is to be favoured. Nevertheless, empirical modelling of the pseudo-bolometric light curve suggests that less than or similar to 0.6 M-circle dot of material was ejected, implying that the white dwarf is not completely disrupted, and that a bound remnant is a likely outcome.
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| 8. |
- Chen, T.-W., et al.
(författare)
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SN 2017ens : The Metamorphosis of a Luminous Broadlined Type Ic Supernova into an SN IIn
- 2018
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 867:2
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Tidskriftsartikel (refereegranskat)abstract
- We present observations of supernova (SN) 2017ens, discovered by the ATLAS survey and identified as a hot blue object through the GREAT program. The redshift z = 0.1086 implies a peak brightness of M-g = -21.1 mag, placing the object within the regime of superluminous supernovae. We observe a dramatic spectral evolution, from initially being blue and featureless, to later developing features similar to those of the broadlined Type Ic SN 1998bw, and finally showing 2000 km s(-1) wide H alpha and H beta emission. Relatively narrow Balmer emission (reminiscent of a SN IIn) is present at all times. We also detect coronal lines, indicative of a dense circumstellar medium. We constrain the progenitor wind velocity to similar to 50-60 km s(-1) based on P-Cygni profiles, which is far slower than those present in Wolf-Rayet stars. This may suggest that the progenitor passed through a luminous blue variable phase, or that the wind is instead from a binary companion red supergiant star. At late times we see the similar to 2000 km s(-1) wide H alpha emission persisting at high luminosity (similar to 3 x 10(40) erg s(-1)) for at least 100 day, perhaps indicative of additional mass loss at high velocities that could have been ejected by a pulsational pair instability.
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| 9. |
- Seitenzahl, I. R., et al.
(författare)
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5.9-keV Mn K-shell X-ray luminosity from the decay of Fe-55 in Type Ia supernova models
- 2015
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 447:2, s. 1484-1490
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Tidskriftsartikel (refereegranskat)abstract
- We show that the X-ray line flux of the Mn Ka line at 5.9 keV from the decay of Fe-55 is a promising diagnostic to distinguish between Type Ia supernova (SN Ia) explosion models. Using radiation transport calculations, we compute the line flux for two three-dimensional explosion models: a near-Chandrasekhar mass delayed detonation and a violent merger of two (1.1 and 0.9 M-circle dot) white dwarfs. Both models are based on solar metallicity zero-age main-sequence progenitors. Due to explosive nuclear burning at higher density, the delayed-detonation model synthesizes similar to 3.5 times more radioactive Fe-55 than the merger model. As a result, we find that the peak Mn K alpha line flux of the delayed-detonation model exceeds that of the merger model by a factor of similar to 4.5. Since in both models the 5.9-keV X-ray flux peaks five to six years after the explosion, a single measurement of the X-ray line emission at this time can place a constraint on the explosion physics that is complementary to those derived from earlier phase optical spectra or light curves. We perform detector simulations of current and future X-ray telescopes to investigate the possibilities of detecting the X-ray line at 5.9 keV. Of the currently existing telescopes, XMM-Newton/pn is the best instrument for close (less than or similar to 1-2 Mpc), non-background limited SNe Ia because of its large effective area. Due to its low instrumental background, Chandra/ACIS is currently the best choice for SNe Ia at distances above similar to 2 Mpc. For the delayed-detonation scenario, a line detection is feasible with Chandra up to similar to 3 Mpc for an exposure time of 10(6) s. We find that it should be possible with currently existing X-ray instruments (with exposure times less than or similar to 5 x 10(5) s) to detect both of our models at sufficiently high S/N to distinguish between them for hypothetical events within the Local Group. The prospects for detection will be better with future missions. For example, the proposed Athena/X-IFU instrument could detect our delayed-detonation model out to a distance of similar to 5 Mpc. This would make it possible to study future events occurring during its operational life at distances comparable to those of the recent supernovae SN 2011 fe (similar to 6.4 Mpc) and SN 2014J (similar to 3.5 Mpc).
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| 10. |
- Yuan, Fang, et al.
(författare)
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450 d of Type II SN 2013ej in optical and near-infrared
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 461:2, s. 2003-2018
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Tidskriftsartikel (refereegranskat)abstract
- We present optical and near-infrared photometric and spectroscopic observations of SN 2013ej, in galaxy M74, from 1 to 450 d after the explosion. SN 2013ej is a hydrogen-rich supernova, classified as a Type IIL due to its relatively fast decline following the initial peak. It has a relatively high peak luminosity (absolute magnitude M-V =-17.6) but a small 56Ni production of similar to 0.023 M-circle dot. Its photospheric evolution is similar to other Type II SNe, with shallow absorption in the H a profile typical for a Type IIL. During transition to the radioactive decay tail at similar to 100 d, we find the SN to grow bluer in B - V colour, in contrast to some other Type II supernovae. At late times, the bolometric light curve declined faster than expected from Co-56 decay and we observed unusually broad and asymmetric nebular emission lines. Based on comparison of nebular emission lines most sensitive to the progenitor core mass, we find our observations are best matched to synthesized spectral models with a M-ZAMS = 12-15 M-circle dot progenitor. The derived mass range is similar to but not higher than the mass estimated for Type IIP progenitors. This is against the idea that Type IIL are from more massive stars. Observations are consistent with the SN having a progenitor with a relatively low-mass envelope.
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