| 1. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
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| 3. |
- Rushton, A. P., et al.
(författare)
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Resolved, expanding jets in the Galactic black hole candidate XTE J1908+094
- 2017
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 468:3, s. 2788-2802
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Tidskriftsartikel (refereegranskat)abstract
- Black hole X-ray binaries undergo occasional outbursts caused by changing inner accretion flows. Here we report high angular resolution radio observations of the 2013 outburst of the black hole candidate X-ray binary system XTE J1908+094, using data from the Very Long Baseline Array and European VLBI Network. We show that following a hard-to-soft state transition, we detect moving jet knots that appear asymmetric in morphology and brightness, and expand to become laterally resolved as they move away from the core, along an axis aligned approximately -11. east of north. We initially see only the southern component, whose evolution gives rise to a 15-mJy radio flare and generates the observed radio polarization. This fades and becomes resolved out after 4 days, after which a second component appears to the north, moving in the opposite direction. From the timing of the appearance of the knots relative to the X-ray state transition, a 90. swing of the inferred magnetic field orientation, the asymmetric appearance of the knots, their complex and evolving morphology, and their low speeds, we interpret the knots as working surfaces where the jets impact the surrounding medium. This would imply a substantially denser environment surrounding XTE J1908+094 than has been inferred to exist around the microquasar sources GRS 1915+105 and GRO J1655-40.
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| 4. |
- Russell, T. D., et al.
(författare)
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Rapid compact jet quenching in the Galactic black hole candidate X-ray binary MAXI J1535-571
- 2020
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 498:4, s. 5772-5785
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Tidskriftsartikel (refereegranskat)abstract
- We present results from six epochs of quasi-simultaneous radio, (sub-)millimetre, infrared, optical, and X-ray observations of the black hole X-ray binary MAXI J1535-571. These observations show that as the source transitioned through the hard-intermediate X-ray state towards the soft-intermediate X-ray state, the jet underwent dramatic and rapid changes. We observed the frequency of the jet spectral break, which corresponds to the most compact region in the jet where particle acceleration begins (higher frequencies indicate closer to the black hole), evolves from the infrared band into the radio band (decreasing by approximate to 3 orders of magnitude) in less than a day. During one observational epoch, we found evidence of the jet spectral break evolving in frequency through the radio band. Estimating the magnetic field and size of the particle acceleration region shows that the rapid fading of the high-energy jet emission was not consistent with radiative cooling; instead, the particle acceleration region seems to be moving away from the black hole on approximately dynamical time-scales. This result suggests that the compact jet quenching is not caused by local changes to the particle acceleration, rather we are observing the acceleration region of the jet travelling away from the black hole with the jet flow. Spectral analysis of the X-ray emission shows a gradual softening in the few days before the dramatic jet changes, followed by a more rapid softening similar to 1-2 d after the onset of the jet quenching.
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| 5. |
- Echiburu-Trujillo, Constanza, et al.
(författare)
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Chasing the Break: Tracing the Full Evolution of a Black Hole X-Ray Binary Jet with Multiwavelength Spectral Modeling
- 2024
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 962:2
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Tidskriftsartikel (refereegranskat)abstract
- Black hole (BH) X-ray binaries (XRBs) are ideal targets to study the connection between accretion inflow and jet outflow. Here we present quasi-simultaneous, multiwavelength observations of the Galactic BH system MAXI J1820+070, throughout its 2018-2019 outburst. Our data set includes coverage from the radio through X-ray bands from 17 different instruments/telescopes, and encompasses 19 epochs over a 7 month period, resulting in one of the most well-sampled multiwavelength data sets of a BH XRB outburst to date. With our data, we compile and model the broadband spectra of this source using a phenomenological model that includes emission from the jet, a companion star, and an accretion flow. This modeling allows us to track the evolution of the spectral break in the jet spectrum, a key observable that samples the jet launching region. We find that the spectral break location changes over at least approximate to 3 orders of magnitude in electromagnetic frequency over this period. Using these spectral break measurements, we link the full cycle of jet behavior, including the rising, quenching, and reignition, to the changing accretion flow properties as the source evolves through its different accretion states. Our analysis shows consistent jet behavior with other sources in similar phases of their outbursts, reinforcing the idea that jet quenching and recovery may be a global feature of BH XRB systems in outburst. Our results also provide valuable evidence supporting a close connection between the geometry of the inner accretion flow and the base of the jet.
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| 6. |
- House, Robert A., et al.
(författare)
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Superstructure control of first-cycle voltage hysteresis in oxygen-redox cathodes
- 2020
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 577:7791, s. 502-508
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Tidskriftsartikel (refereegranskat)abstract
- In conventional intercalation cathodes, alkali metal ions can move in and out of a layered material with the charge being compensated for by reversible reduction and oxidation of the transition metal ions. If the cathode material used in a lithium-ion or sodium-ion battery is alkali-rich, this can increase the battery's energy density by storing charge on the oxide and the transition metal ions, rather than on the transition metal alone(1-10). There is a high voltage associated with oxidation of O2- during the first charge, but this is not recovered on discharge, resulting in reduced energy density(11). Displacement of transition metal ions into the alkali metal layers has been proposed to explain the first-cycle voltage loss (hysteresis)(9,12-16). By comparing two closely related intercalation cathodes, Na-0.75[Li0.25Mn0.75]O-2 and Na-0.6[Li0.2Mn0.8]O-2, here we show that the first-cycle voltage hysteresis is determined by the superstructure in the cathode, specifically the local ordering of lithium and transition metal ions in the transition metal layers. The honeycomb superstructure of Na-0.75[Li0.25Mn0.75]O-2, present in almost all oxygen-redox compounds, is lost on charging, driven in part by formation of molecular O-2 inside the solid. The O-2 molecules are cleaved on discharge, reforming O2-, but the manganese ions have migrated within the plane, changing the coordination around O2- and lowering the voltage on discharge. The ribbon superstructure in Na-0.6[Li0.2Mn0.8]O-2 inhibits manganese disorder and hence O-2 formation, suppressing hysteresis and promoting stable electron holes on O2- that are revealed by X-ray absorption spectroscopy. The results show that voltage hysteresis can be avoided in oxygen-redox cathodes by forming materials with a ribbon superstructure in the transition metal layers that suppresses migration of the transition metal. In oxygen-redox intercalation cathodes, voltage hysteresis can be avoided by forming cathode materials with a 'ribbon' superstructure in the transition metal layers that suppresses transition metal migration.
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| 7. |
- Shah, MY, et al.
(författare)
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Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations
- 2018
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 28:4, s. 432-447
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Tidskriftsartikel (refereegranskat)abstract
- The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA CCAT2 in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. We further identified that CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces global deregulation of gene expression by down-regulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel non-APOBEC, non-ADAR, RNA editing at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.
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| 8. |
- Tsygankov, Sergey S., et al.
(författare)
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The unusual behavior of the young X-ray pulsar SXP 1062 during the 2019 outburst
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 637
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of the first dedicated observation of the young X-ray pulsar SXP 1062 in the broad X-ray energy band obtained during its 2019 outburst with the NuSTAR and XMM-Newton observatories. The analysis of the pulse-phase averaged and phase-resolved spectra in the energy band from 0.5 to 70 keV did not reveal any evidence for the presence of a cyclotron line. The spin period of the pulsar was found to have decreased to 979.48 +/- 0.06 s implying a similar to 10% reduction compared to the last measured period during the monitoring campaign conducted about five years ago, and is puzzling considering that the system apparently has not shown major outbursts ever since. The switch of the pulsar to the spin-up regime supports the common assumption that torques acting on the accreting neutron star are nearly balanced and thus SXP 1062 likely also spins with a period close to the equilibrium value for this system. The current monitoring of the source also revealed a sharp drop in its soft X-ray flux right after the outburst, which is in drastic contrast to the behavior during the previous outburst when the pulsar remained observable for years with only a minor flux decrease after the end of the outburst. This unexpected off state of the source lasted for at most 20 days after which SXP 1062 returned to the level observed during previous campaigns. We discuss this and other findings in context of the modern models of accretion onto strongly magnetized neutron stars.
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| 9. |
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| 10. |
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