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| 2. |
- 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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| 4. |
- Valiente-Dobon, J. J., et al.
(författare)
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Conceptual design of the AGATA 2 pi array at LNL
- 2023
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 1049
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Tidskriftsartikel (refereegranskat)abstract
- The Advanced GAmma Tracking Array (AGATA) has been installed at Laboratori Nazionali di Legnaro (LNL), Italy. In this installation, AGATA will consist, at the beginning, of 13 AGATA triple clusters (ATCs) with an angular coverage of 1n,and progressively the number of ATCs will increase up to a 2 pi angular coverage. This setup will exploit both stable and radioactive ion beams delivered by the Tandem-PIAVE-ALPI accelerator complex and the SPES facility. The new implementation of AGATA at LNL will be used in two different configurations, firstly one coupled to the PRISMA large-acceptance magnetic spectrometer and lately a second one at Zero Degrees, along the beam line. These two configurations will allow us to cover a broad physics program, using different reaction mechanisms, such as Coulomb excitation, fusion-evaporation, transfer and fission at energies close to the Coulomb barrier. These setups have been designed to be coupled with a large variety of complementary detectors such as charged particle detectors, neutron detectors, heavy-ion detectors, high-energy gamma-ray arrays, cryogenic and gasjet targets and the plunger device for lifetime measurements. We present in this paper the conceptual design, characteristics and performance figures of this implementation of AGATA at LNL.
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| 5. |
- Gehlen, J., et al.
(författare)
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First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B
- 2022
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Ingår i: Human Genetics and Genomics Advances. - : Elsevier BV. - 2666-2477. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes. © 2022 The Authors
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| 7. |
- van Cappellen, W., et al.
(författare)
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Apertif: Phased array feeds for the Westerbork Synthesis Radio Telescope: System overview and performance characteristics
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
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Tidskriftsartikel (refereegranskat)abstract
- We describe the APERture Tile In Focus (Apertif) system, a phased array feed (PAF) upgrade of the Westerbork Synthesis Radio Telescope that transforms this telescope into a high-sensitivity, wide-field-of-view L-band imaging and transient survey instrument. Using novel PAF technology, up to 40 partially overlapping beams are formed on the sky simultaneously, significantly increasing the survey speed of the telescope. With this upgraded instrument, an imaging survey covering an area of 2300 deg2 is being performed that will deliver both continuum and spectral line datasets, of which the first data have been publicly released. In addition, a time domain transient and pulsar survey covering 15 000 deg2 is in progress. An overview of the Apertif science drivers, hardware, and software of the upgraded telescope is presented, along with its key performance characteristics.
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| 8. |
- Aharonian, F., et al.
(författare)
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HESS observations of the 2021 periastron passage of PSR B1259-63/LS 2883
- 2024
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 687
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Tidskriftsartikel (refereegranskat)abstract
- PSR B1259-63/LS 2883 is a gamma-ray binary system that hosts a pulsar in an eccentric orbit, with a 3.4 yr period, around an O9.5Ve star (LS 2883). At orbital phases close to periastron passages, the system radiates bright and variable non-thermal emission, for which the temporal and spectral properties of this emission are, for now, poorly understood. In this regard, very high-energy (VHE) emission is especially useful to study and constrain radiation processes and particle acceleration in the system. We report on an extensive VHE observation campaign conducted with the High Energy Stereoscopic System, comprised of approximately 100 h of data taken over five months, from t(p) - 24 days to t(p) + 127 days around the system's 2021 periastron passage (where t(p) is the time of periastron). We also present the timing and spectral analyses of the source. The VHE light curve in 2021 is consistent overall with the stacked light curve of all previous observations. Within the light curve, we report a VHE maximum at times coincident with the third X-ray peak first detected in the 2021 X-ray light curve. In the light curve - although sparsely sampled in this time period - we see no VHE enhancement during the second disc crossing. In addition, we see no correspondence to the 2021 GeV flare in the VHE light curve. The VHE spectrum obtained from the analysis of the 2021 dataset is best described by a power law of spectral index Gamma = 2.65 +/- 0.04(stat) +/- 0.04(sys), a value consistent with the spectral index obtained from the analysis of data collected with H.E.S.S. during the previous observations of the source. We report spectral variability with a difference of Delta Gamma = 0.56 +/- 0.18(stat) +/- 0.10(sys) at 95% confidence intervals, between sub-periods of the 2021 dataset. We also detail our investigation into X-ray/TeV and GeV/TeV flux correlations in the 2021 periastron passage. We find a linear correlation between contemporaneous flux values of X-ray and TeV datasets, detected mainly after t(p) + 25 days, suggesting a change in the available energy for non-thermal radiation processes. We detect no significant correlation between GeV and TeV flux points, within the uncertainties of the measurements, from similar to t(p) - 23 days to similar to t(p) + 126 days. This suggests that the GeV and TeV emission originate from different electron populations.
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| 9. |
- Ciemala, M., et al.
(författare)
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Testing ab initio nuclear structure in neutron-rich nuclei : Lifetime measurements of second 2(+) state in C-16 and O-20
- 2020
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Ingår i: Physical Review C. - : AMER PHYSICAL SOC. - 2469-9985 .- 2469-9993. ; 101:2
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Tidskriftsartikel (refereegranskat)abstract
- To test the predictive power of ab initio nuclear structure theory, the lifetime of the second 2(+) state in neutron-rich O-20, tau(2(2)(+)) = 150(-30)(+80) fs, and an estimate for the lifetime of the second 2(+) state in C-16 have been obtained for the first time. The results were achieved via a novel Monte Carlo technique that allowed us to measure nuclear state lifetimes in the tens-to-hundreds of femtoseconds range by analyzing the Doppler-shifted gamma-transition line shapes of products of low-energy transfer and deep-inelastic processes in the reaction O-18 (7.0 MeV/u) + Ta-181. The requested sensitivity could only be reached owing to the excellent performances of the Advanced gamma-Tracking Array AGATA, coupled to the PARIS scintillator array and to the VAMOS++ magnetic spectrometer. The experimental lifetimes agree with predictions of ab initio calculations using two- and three-nucleon interactions, obtained with the valence-space in-medium similarity renormalization group for O-20 and with the no-core shell model for C-16. The present measurement shows the power of electromagnetic observables, determined with high-precision gamma spectroscopy, to assess the quality of first-principles nuclear structure calculations, complementing common benchmarks based on nuclear energies. The proposed experimental approach will be essential for short lifetime measurements in unexplored regions of the nuclear chart, including r-process nuclei, when intense beams, produced by Isotope Separation On-Line (ISOL) techniques, become available.
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| 10. |
- Korenblik, R., et al.
(författare)
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Dragon 1 Protocol Manuscript : Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy
- 2022
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Ingår i: Cardiovascular and Interventional Radiology. - : Springer. - 0174-1551 .- 1432-086X. ; 45, s. 1391-1398
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Tidskriftsartikel (refereegranskat)abstract
- Study Purpose The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. Methods The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. Results Not applicable. Conclusion DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR.
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