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| 2. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 5. |
- 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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| 6. |
- Acharyya, A., et al.
(författare)
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Monte Carlo studies for the optimisation of the Cherenkov Telescope Array layout
- 2019
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 111, s. 35-53
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Tidskriftsartikel (refereegranskat)abstract
- The Cherenkov Telescope Array (CTA) is the major next-generation observatory for ground-based veryhigh-energy gamma-ray astronomy. It will improve the sensitivity of current ground-based instruments by a factor of five to twenty, depending on the energy, greatly improving both their angular and energy resolutions over four decades in energy (from 20 GeV to 300 TeV). This achievement will be possible by using tens of imaging Cherenkov telescopes of three successive sizes. They will be arranged into two arrays, one per hemisphere, located on the La Palma island (Spain) and in Paranal (Chile). We present here the optimised and final telescope arrays for both CTA sites, as well as their foreseen performance, resulting from the analysis of three different large-scale Monte Carlo productions.
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| 8. |
- Acero, F., et al.
(författare)
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Prospects for Cherenkov Telescope Array Observations of the Young Supernova Remnant RX J1713.7-3946
- 2017
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 840:2
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Tidskriftsartikel (refereegranskat)abstract
- We perform simulations for future Cherenkov Telescope Array (CTA) observations of RX J1713.7-3946, a young supernova remnant (SNR) and one of the brightest sources ever discovered in very high energy (VHE) gamma rays. Special attention is paid to exploring possible spatial (anti) correlations of gamma rays with emission at other wavelengths, in particular X-rays and CO/H I emission. We present a series of simulated images of RX J1713.7-3946 for CTA based on a set of observationally motivated models for the gamma-ray emission. In these models, VHE gamma rays produced by high-energy electrons are assumed to trace the nonthermal X-ray emission observed by XMM-Newton, whereas those originating from relativistic protons delineate the local gas distributions. The local atomic and molecular gas distributions are deduced by the NANTEN team from CO and H I observations. Our primary goal is to show how one can distinguish the emission mechanism(s) of the gamma rays (i.e., hadronic versus leptonic, or a mixture of the two) through information provided by their spatial distribution, spectra, and time variation. This work is the first attempt to quantitatively evaluate the capabilities of CTA to achieve various proposed scientific goals by observing this important cosmic particle accelerator.
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- Ackermann, M., et al.
(författare)
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Unresolved Gamma-Ray Sky through its Angular Power Spectrum
- 2018
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 121:24
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Tidskriftsartikel (refereegranskat)abstract
- The gamma-ray sky has been observed with unprecedented accuracy in the last decade by the Fermi-large area telescope (LAT), allowing us to resolve and understand the high-energy Universe. The nature of the remaining unresolved emission [unresolved gamma-ray background (UGRB)] below the LAT source detection threshold can be uncovered by characterizing the amplitude and angular scale of the UGRB fluctuation field. This Letter presents a measurement of the UGRB autocorrelation angular power spectrum based on eight years of Fermi-LAT Pass 8 data products. The analysis is designed to be robust against contamination from resolved sources and noise systematics. The sensitivity to subthreshold sources is greatly enhanced with respect to previous measurements. We find evidence (with similar to 3.7 sigma significance) that the scenario in which two classes of sources contribute to the UGRB signal is favored over a single class. A double power law with exponential cutoff can explain the anisotropy energy spectrum well, with photon indices of the two populations being 2.55 +/- 0.23 and 1.86 +/- 0.15.
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| 10. |
- Ajello, M., et al.
(författare)
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A Decade of Gamma-Ray Bursts Observed by Fermi-LAT : The Second GRB Catalog
- 2019
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 878:1
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Tidskriftsartikel (refereegranskat)abstract
- The Large Area Telescope (LAT) aboard the Fermi spacecraft routinely observes high-energy emission from gamma-ray bursts (GRBs). Here we present the second catalog of LAT-detected GRBs, covering the first 10 yr of operations, from 2008 to 2018 August 4. A total of 186 GRBs are found; of these, 91 show emission in the range 30-100 MeV (17 of which are seen only in this band) and 169 are detected above 100 MeV. Most of these sources were discovered by other instruments (Fermi/GBM, Swift/BAT, AGILE, INTEGRAL) or reported by the Interplanetary Network (IPN); the LAT has independently triggered on four GRBs. This catalog presents the results for all 186 GRBs. We study onset, duration, and temporal properties of each GRB, as well as spectral characteristics in the 100 MeV-100 GeV energy range. Particular attention is given to the photons with the highest energy. Compared with the first LAT GRB catalog, our rate of detection is significantly improved. The results generally confirm the main findings of the first catalog: the LAT primarily detects the brightest GBM bursts, and the high-energy emission shows delayed onset as well as longer duration. However, in this work we find delays exceeding 1 ks and several GRBs with durations over 10 ks. Furthermore, the larger number of LAT detections shows that these GRBs not only cover the high-fluence range of GBM-detected GRBs but also sample lower fluences. In addition, the greater number of detected GRBs with redshift estimates allows us to study their properties in both the observer and rest frames. Comparison of the observational results with theoretical predictions reveals that no model is currently able to explain all results, highlighting the role of LAT observations in driving theoretical models.
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