| 1. |
- Campbell, PJ, et al.
(author)
-
Pan-cancer analysis of whole genomes
- 2020
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Journal article (peer-reviewed)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. |
- Sugai, H., et al.
(author)
-
Updated Design of the CMB Polarization Experiment Satellite LiteBIRD
- 2020
-
In: Journal of Low Temperature Physics. - : Springer Science and Business Media LLC. - 0022-2291 .- 1573-7357. ; 199:3-4, s. 1107-1117
-
Journal article (peer-reviewed)abstract
- Recent developments of transition-edge sensors (TESs), based on extensive experience in ground-based experiments, have been making the sensor techniques mature enough for their application on future satellite cosmic microwave background (CMB) polarization experiments. LiteBIRD is in the most advanced phase among such future satellites, targeting its launch in Japanese Fiscal Year 2027 (2027FY) with JAXA's H3 rocket. It will accommodate more than 4000 TESs in focal planes of reflective low-frequency and refractive medium-and-high-frequency telescopes in order to detect a signature imprinted on the CMB by the primordial gravitational waves predicted in cosmic inflation. The total wide frequency coverage between 34 and 448 GHz enables us to extract such weak spiral polarization patterns through the precise subtraction of our Galaxy's foreground emission by using spectral differences among CMB and foreground signals. Telescopes are cooled down to 5 K for suppressing thermal noise and contain polarization modulators with transmissive half-wave plates at individual apertures for separating sky polarization signals from artificial polarization and for mitigating from instrumental 1/f noise. Passive cooling by using V-grooves supports active cooling with mechanical coolers as well as adiabatic demagnetization refrigerators. Sky observations from the second Sun-Earth Lagrangian point, L2, are planned for 3 years. An international collaboration between Japan, the USA, Canada, and Europe is sharing various roles. In May 2019, the Institute of Space and Astronautical Science, JAXA, selected LiteBIRD as the strategic large mission No. 2.
|
|
| 3. |
- Poley, L., et al.
(author)
-
The ABC130 barrel module prototyping programme for the ATLAS strip tracker
- 2020
-
In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 15:9
-
Journal article (peer-reviewed)abstract
- For the Phase-II Upgrade of the ATLAS Detector [1], its Inner Detector, consisting of silicon pixel, silicon strip and transition radiation sub-detectors, will be replaced with an all new 100% silicon tracker, composed of a pixel tracker at inner radii and a strip tracker at outer radii. The future ATLAS strip tracker will include 11,000 silicon sensor modules in the central region (barrel) and 7,000 modules in the forward region (end-caps), which are foreseen to be constructed over a period of 3.5 years. The construction of each module consists of a series of assembly and quality control steps, which were engineered to be identical for all production sites. In order to develop the tooling and procedures for assembly and testing of these modules, two series of major prototyping programs were conducted: an early program using readout chips designed using a 250 nm fabrication process (ABCN-250) [2, 3] and a subsequent program using a follow-up chip set made using 130 nm processing (ABC130 and HCC130 chips). This second generation of readout chips was used for an extensive prototyping program that produced around 100 barrel-type modules and contributed significantly to the development of the final module layout. This paper gives an overview of the components used in ABC130 barrel modules, their assembly procedure and findings resulting from their tests.
|
|
| 4. |
- Tarrío, Diego, et al.
(author)
-
Neutron-induced fission cross sections of Th-232 and U-233 up to 1 GeV using parallel plate avalanche counters at the CERN n_TOF facility
- 2023
-
In: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 107:4
-
Journal article (peer-reviewed)abstract
- The neutron-induced fission cross sections of Th-232 and U-233 were measured relative to U-235 in a wide neutron energy range up to 1 GeV (and from fission threshold in the case of Th-232, and from 0.7 eV in case of U-233), using the white-spectrum neutron source at the CERN Neutron Time-of-Flight (n_TOF) facility. Parallel plate avalanche counters (PPACs) were used, installed at the Experimental Area 1 (EAR1), which is located at 185 m from the neutron spallation target. The anisotropic emission of fission fragments were taken into account in the detection efficiency by using, in the case of U-233, previous results available in EXFOR, whereas in the case of Th-232 these data were obtained from our measurement, using PPACs and targets tilted 45 degrees with respect to the neutron beam direction. Finally, the obtained results are compared with past measurements and major evaluated nuclear data libraries. Calculations using the high-energy reaction models INCL++ and ABLA07 were performed and some of their parameters were modified to reproduce the experimental results. At high energies, where no other neutron data exist, our results are compared with experimental data on proton-induced fission. Moreover, the dependence of the fission cross section at 1 GeV with the fissility parameter of the target nucleus is studied by combining those ( p, f) data with our (n, f) data on Th-232 and U-233 and on other isotopes studied earlier at n_TOF using the same experimental setup.
|
|
| 5. |
|
|
| 6. |
- Ramonet, M., et al.
(author)
-
The fingerprint of the summer 2018 drought in Europe on ground-based atmospheric CO 2 measurements : Atmospheric CO 2 anomaly
- 2020
-
In: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1810
-
Journal article (peer-reviewed)abstract
- During the summer of 2018, a widespread drought developed over Northern and Central Europe. The increase in temperature and the reduction of soil moisture have influenced carbon dioxide (CO 2) exchange between the atmosphere and terrestrial ecosystems in various ways, such as a reduction of photosynthesis, changes in ecosystem respiration, or allowing more frequent fires. In this study, we characterize the resulting perturbation of the atmospheric CO 2 seasonal cycles. 2018 has a good coverage of European regions affected by drought, allowing the investigation of how ecosystem flux anomalies impacted spatial CO 2 gradients between stations. This density of stations is unprecedented compared to previous drought events in 2003 and 2015, particularly thanks to the deployment of the Integrated Carbon Observation System (ICOS) network of atmospheric greenhouse gas monitoring stations in recent years. Seasonal CO 2 cycles from 48 European stations were available for 2017 and 2018. Earlier data were retrieved for comparison from international databases or national networks. Here, we show that the usual summer minimum in CO 2 due to the surface carbon uptake was reduced by 1.4 ppm in 2018 for the 10 stations located in the area most affected by the temperature anomaly, mostly in Northern Europe. Notwithstanding, the CO 2 transition phases before and after July were slower in 2018 compared to 2017, suggesting an extension of the growing season, with either continued CO 2 uptake by photosynthesis and/or a reduction in respiration driven by the depletion of substrate for respiration inherited from the previous months due to the drought. For stations with sufficiently long time series, the CO 2 anomaly observed in 2018 was compared to previous European droughts in 2003 and 2015. Considering the areas most affected by the temperature anomalies, we found a higher CO 2 anomaly in 2003 (+3 ppm averaged over 4 sites), and a smaller anomaly in 2015 (+1 ppm averaged over 11 sites) compared to 2018. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
|
|
| 7. |
- Berndt, Sonja, I, et al.
(author)
-
Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
-
In: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
-
Journal article (peer-reviewed)abstract
- Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
|
|
| 8. |
- Moore, Amy, et al.
(author)
-
Genetically Determined Height and Risk of Non-hodgkin Lymphoma
- 2020
-
In: Frontiers in Oncology. - : FRONTIERS MEDIA SA. - 2234-943X. ; 9
-
Journal article (peer-reviewed)abstract
- Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
|
|
| 9. |
- Fallows, Richard A., et al.
(author)
-
A LOFAR observation of ionospheric scintillation from two simultaneous travelling ionospheric disturbances
- 2020
-
In: Journal of Space Weather and Space Climate. - : EDP Sciences. - 2115-7251. ; 10
-
Journal article (peer-reviewed)abstract
- This paper presents the results from one of the first observations of ionospheric scintillation taken using the Low-Frequency Array (LOFAR). The observation was of the strong natural radio source Cassiopeia A, taken overnight on 18-19 August 2013, and exhibited moderately strong scattering effects in dynamic spectra of intensity received across an observing bandwidth of 10-80 MHz. Delay-Doppler spectra (the 2-D FFT of the dynamic spectrum) from the first hour of observation showed two discrete parabolic arcs, one with a steep curvature and the other shallow, which can be used to provide estimates of the distance to, and velocity of, the scattering plasma. A cross-correlation analysis of data received by the dense array of stations in the LOFAR "core" reveals two different velocities in the scintillation pattern: a primary velocity of similar to 20-40 ms(-1) with a north-west to south-east direction, associated with the steep parabolic arc and a scattering altitude in the F-region or higher, and a secondary velocity of similar to 110 ms(-1) with a north-east to south-west direction, associated with the shallow arc and a scattering altitude in the D-region. Geomagnetic activity was low in the mid-latitudes at the time, but a weak sub-storm at high latitudes reached its peak at the start of the observation. An analysis of Global Navigation Satellite Systems (GNSS) and ionosonde data from the time reveals a larger-scale travelling ionospheric disturbance (TID), possibly the result of the high-latitude activity, travelling in the north-west to south-east direction, and, simultaneously, a smaller-scale TID travelling in a north-east to south-west direction, which could be associated with atmospheric gravity wave activity. The LOFAR observation shows scattering from both TIDs, at different altitudes and propagating in different directions. To the best of our knowledge this is the first time that such a phenomenon has been reported.
|
|
| 10. |
|
|
