| 1. |
|
|
| 2. |
- Menden, MP, et al.
(författare)
-
Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
-
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.
|
|
| 3. |
|
|
| 4. |
- Orsini, S., et al.
(författare)
-
Inner southern magnetosphere observation of Mercury via SERENA ion sensors in BepiColombo mission
- 2022
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Mercury’s southern inner magnetosphere is an unexplored region as it was not observed by earlier space missions. In October 2021, BepiColombo mission has passed through this region during its first Mercury flyby. Here, we describe the observations of SERENA ion sensors nearby and inside Mercury’s magnetosphere. An intermittent high-energy signal, possibly due to an interplanetary magnetic flux rope, has been observed downstream Mercury, together with low energy solar wind. Low energy ions, possibly due to satellite outgassing, were detected outside the magnetosphere. The dayside magnetopause and bow-shock crossing were much closer to the planet than expected, signature of a highly eroded magnetosphere. Different ion populations have been observed inside the magnetosphere, like low latitude boundary layer at magnetopause inbound and partial ring current at dawn close to the planet. These observations are important for understanding the weak magnetosphere behavior so close to the Sun, revealing details never reached before.
|
|
| 5. |
- Kangas, T., et al.
(författare)
-
Supernova 2013fc in a circumnuclear ring of a luminous infrared galaxy : the big brother of SN 1998S
- 2016
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 456:1, s. 323-346
-
Tidskriftsartikel (refereegranskat)abstract
- We present photometric and spectroscopic observations of SN 2013fc, a bright type II supernova (SN) in a circumnuclear star-forming ring in the luminous infrared galaxy ESO 154-G010, observed as part of the Public ESO Spectroscopic Survey of Transient Objects. SN 2013fc is both photometrically and spectroscopically similar to the well-studied type IIn SN 1998S and to the bright type II-L SN 1979C. It exhibits an initial linear decline, followed by a short plateau phase and a tail phase with a decline too fast for Co-56 decay with full. gamma-ray trapping. Initially, the spectrum was blue and featureless. Later on, a strong broad (similar to 8000 km s(-1)) H alpha emission profile became prominent. We apply a STARLIGHT stellar population model fit to the SN location (observed when the SN had faded) to estimate a high extinction of A(V) = 2.9 +/- 0.2 mag and an age of 10(+ 3) (- 2) Myr for the underlying cluster. We compare the SN to SNe 1998S and 1979C and discuss its possible progenitor star considering the similarities to these events. With a peak brightness of B = - 20.46 +/- 0.21 mag, SN 2013fc is 0.9 mag brighter than SN 1998S and of comparable brightness to SN 1979C. We suggest that SN 2013fc was consistent with a massive red supergiant (RSG) progenitor. Recent mass loss probably due to a strong RSG wind created the circumstellar matter illuminated through its interaction with the SN ejecta. We also observe a near- infrared excess, possibly due to newly condensed dust.
|
|
| 6. |
- Margutti, R., et al.
(författare)
-
A PANCHROMATIC VIEW OF THE RESTLESS SN 2009ip REVEALS THE EXPLOSIVE EJECTION OF A MASSIVE STAR ENVELOPE
- 2014
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 780:1
-
Tidskriftsartikel (refereegranskat)abstract
- The double explosion of SN 2009ip in 2012 raises questions about our understanding of the late stages of massive star evolution. Here we present a comprehensive study of SN 2009ip during its remarkable rebrightenings. High-cadence photometric and spectroscopic observations from the GeV to the radio band obtained from a variety of ground-based and space facilities (including the Very Large Array, Swift, Fermi, Hubble Space Telescope, and XMM) constrain SN 2009ip to be a low energy (E similar to 1050 erg for an ejecta mass similar to 0.5 M-circle dot) and asymmetric explosion in a complex medium shaped by multiple eruptions of the restless progenitor star. Most of the energy is radiated as a result of the shock breaking out through a dense shell of material located at similar to 5 x 10(14) cm with M similar to 0.1 M-circle dot, ejected by the precursor outburst similar to 40 days before the major explosion. We interpret the NIR excess of emission as signature of material located further out, the origin of which has to be connected with documented mass-loss episodes in the previous years. Our modeling predicts bright neutrino emission associated with the shock break-out if the cosmic-ray energy is comparable to the radiated energy. We connect this phenomenology with the explosive ejection of the outer layers of the massive progenitor star, which later interacted with material deposited in the surroundings by previous eruptions. Future observations will reveal if the massive luminous progenitor star survived. Irrespective of whether the explosion was terminal, SN 2009ip brought to light the existence of new channels for sustained episodic mass loss, the physical origin of which has yet to be identified.
|
|
| 7. |
- Appleton, O, et al.
(författare)
-
The next-generation ARC middleware
- 2010
-
Ingår i: ANNALS OF TELECOMMUNICATIONS-ANNALES DES TELECOMMUNICATIONS. - : Presses Polytechniques Romandes. - 0003-4347 .- 1958-9395. ; 65:11-12, s. 771-776
-
Tidskriftsartikel (refereegranskat)abstract
- The Advanced Resource Connector (ARC) is a light-weight, non-intrusive, simple yet powerful Grid middleware capable of connecting highly heterogeneous computing and storage resources. ARC aims at providing general purpose, flexible, collaborative computing environments suitable for a range of uses, both in science and business. The server side offers the fundamental job execution management, information and data capabilities required for a Grid. Users are provided with an easy to install and use client which provides a basic toolbox for job- and data management. The KnowARC project developed the next-generation ARC middleware, implemented as Web Services with the aim of standard-compliant interoperability.
|
|
| 8. |
|
|
| 9. |
- Farzan, N, et al.
(författare)
-
Rationale and design of the multiethnic Pharmacogenomics in Childhood Asthma consortium
- 2017
-
Ingår i: Pharmacogenomics. - : Future Medicine Ltd. - 1744-8042 .- 1462-2416. ; 18:10, s. 931-943
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: International collaboration is needed to enable large-scale pharmacogenomics studies in childhood asthma. Here, we describe the design of the Pharmacogenomics in Childhood Asthma (PiCA) consortium. Materials & methods: Investigators of each study participating in PiCA provided data on the study characteristics by answering an online questionnaire. Results: A total of 21 studies, including 14,227 children/young persons (58% male), from 12 different countries are currently enrolled in the PiCA consortium. Fifty six percent of the patients are Caucasians. In total, 7619 were inhaled corticosteroid users. Among patients from 13 studies with available data on asthma exacerbations, a third reported exacerbations despite inhaled corticosteroid use. In the future pharmacogenomics studies within the consortium, the pharmacogenomics analyses will be performed separately in each center and the results will be meta-analyzed. Conclusion: PiCA is a valuable platform to perform pharmacogenetics studies within a multiethnic pediatric asthma population.
|
|
| 10. |
- Fox, Ori D., et al.
(författare)
-
The slow demise of the long-lived SN 2005ip
- 2020
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 498:1, s. 517-531
-
Tidskriftsartikel (refereegranskat)abstract
- The Type IIn supernova (SN IIn) 2005ip is one of the most well-studied and long-lasting examples of an SN interacting with its circumstellar environment. The optical light curve plateaued at a nearly constant level for more than five years, suggesting ongoing shock interaction with an extended and clumpy circumstellar medium (CSM). Here, we present continued observations of the SN from ∼1000 to 5000 d post-explosion at all wavelengths, including X-ray, ultraviolet, near-infrared (NIR), and mid-infrared. The UV spectra probe the pre-explosion mass loss and show evidence for CNO processing. From the bolometric light curve, we find that the total radiated energy is in excess of 1050 erg, the progenitor star’s pre-explosion mass-loss rate was ≳1×10−2M⊙ yr−1, and the total mass lost shortly before explosion was ≳1M⊙, though the mass lost could have been considerably larger depending on the efficiency for the conversion of kinetic energy to radiation. The ultraviolet through NIR spectrum is characterized by two high-density components, one with narrow high-ionization lines, and one with broader low-ionization H i, He i, [O i], Mg ii, and Fe ii lines. The rich Fe ii spectrum is strongly affected by Lyα fluorescence, consistent with spectral modelling. Both the Balmer and He i lines indicate a decreasing CSM density during the late interaction period. We find similarities to SN 1988Z, which shows a comparable change in spectrum at around the same time during its very slow decline. These results suggest that, at long last, the shock interaction in SN 2005ip may finally be on the decline.
|
|
