| 1. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
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.
|
|
| 2. |
|
|
| 3. |
- Aalbers, Jelle, et al.
(författare)
-
Solar neutrino detection sensitivity in DARWIN via electron scattering
- 2020
-
Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:12
-
Tidskriftsartikel (refereegranskat)abstract
- We detail the sensitivity of the proposed liquid xenon DARWIN observatory to solar neutrinos via elastic electron scattering. We find that DARWIN will have the potential to measure the fluxes of five solar neutrino components: pp, 7Be, 13N, 15O and pep. The precision of the 13N, 15O and pep components is hindered by the double-beta decay of 136Xe and, thus, would benefit from a depleted target. A high-statistics observation of pp neutrinos would allow us to infer the values of the electroweak mixing angle, sin2 theta w, and the electron-type neutrino survival probability, Pee, in the electron recoil energy region from a few keV up to 200 keV for the first time, with relative precision of 5% and 4%, respectively, with 10 live years of data and a 30 tonne fiducial volume. An observation of pp and 7Be neutrinos would constrain the neutrino-inferred solar luminosity down to 0.2%. A combination of all flux measurements would distinguish between the high- (GS98) and low-metallicity (AGS09) solar models with 2.1-2.5 sigma significance, independent of external measurements from other experiments or a measurement of 8B neutrinos through coherent elastic neutrino-nucleus scattering in DARWIN. Finally, we demonstrate that with a depleted target DARWIN may be sensitive to the neutrino capture process of 131Xe.
|
|
| 4. |
- Althueser, L., et al.
(författare)
-
GPU-based optical simulation of the DARWIN detector
- 2022
-
Ingår i: Journal of Instrumentation. - 1748-0221 .- 1748-0221. ; 17:7
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding propagation of scintillation light is critical for maximizing the discovery potential of next-generation liquid xenon detectors that use dual-phase time projection chamber technology. This work describes a detailed optical simulation of the DARWIN detector implemented using Chroma, a GPU-based photon tracking framework. To evaluate the framework and to explore ways of maximizing efficiency and minimizing the time of light collection, we simulate several variations of the conventional detector design. Results of these selected studies are presented. More generally, we conclude that the approach used in this work allows one to investigate alternative designs faster and in more detail than using conventional Geant4 optical simulations, making it an attractive tool to guide the development of the ultimate liquid xenon observatory.
|
|
| 5. |
- Suzuki, H., et al.
(författare)
-
Distinct spin and orbital dynamics in Sr2RuO4
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- The unconventional superconductor Sr2RuO4 has long served as a benchmark for theories of correlated-electron materials. The determination of the superconducting pairing mechanism requires detailed experimental information on collective bosonic excitations as potential mediators of Cooper pairing. We have used Ru L3-edge resonant inelastic x-ray scattering to obtain comprehensive maps of the electronic excitations of Sr2RuO4 over the entire Brillouin zone. We observe multiple branches of dispersive spin and orbital excitations associated with distinctly different energy scales. The spin and orbital dynamical response functions calculated within the dynamical mean-field theory are in excellent agreement with the experimental data. Our results highlight the Hund metal nature of Sr2RuO4 and provide key information for the understanding of its unconventional superconductivity.
|
|
| 6. |
- Wooldridge, G, et al.
(författare)
-
Challenges of implementing the Paediatric Surviving Sepsis Campaign International Guidelines 2020 in resource-limited settings: A real-world view beyond the academia
- 2021
-
Ingår i: Andes pediatrica : revista Chilena de pediatria. - : Sociedad Chilena de Pediatria. - 2452-6053. ; 92:6, s. 954-962
-
Tidskriftsartikel (refereegranskat)abstract
- Las Guías Internacionales de la Campaña Sobreviviendo a la Sepsis para el Manejo del Shock Séptico y la Disfunción de Órganos Asociada a la Sepsis en Niños, fueron publicadas en 2020 y están desti- nadas a ser utilizadas en todos los lugares que atienden a niños. Sin embargo, los profesionales que atienden a los niños con sepsis en entornos con recursos limitados se enfrentan a una serie de desafíos y perfiles de enfermedad distintos a los que se encuentran en entornos ricos en recursos. Basándonos en nuestra experiencia colectiva en entornos con recursos limitados, nos propusimos reflexionar so- bre las dificultades de aplicar las directrices internacionales. Creemos que hay una necesidad urgente de más evidencia de entornos con recursos limitados en enfoques factibles y eficaces para el trata- miento de la sepsis y el shock séptico que podrían incluirse en las futuras directrices para situaciones y contextos específicos.
|
|
