| 1. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
- 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.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Aalbers, J., et al.
(författare)
-
DARWIN : towards the ultimate dark matter detector
- 2016
-
Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :11
-
Tidskriftsartikel (refereegranskat)abstract
- DARk matter WImp search with liquid xenoN (DARWIN(2)) will be an experiment for the direct detection of dark matter using a multi-ton liquid xenon time projection chamber at its core. Its primary goal will be to explore the experimentally accessible parameter space for Weakly Interacting Massive Particles (WIMPs) in a wide mass-range, until neutrino interactions with the target become an irreducible background. The prompt scintillation light and the charge signals induced by particle interactions in the xenon will be observed by VUV sensitive, ultra-low background photosensors. Besides its excellent sensitivity to WIMPs above a mass of 5 GeV/c(2), such a detector with its large mass, low-energy threshold and ultra-low background level will also be sensitive to other rare interactions. It will search for solar axions,galactic axion-like particles and the neutrinoless double-beta decay of Xe-136, as well as measure the low-energy solar neutrino flux with <1% precision, observe coherent neutrino-nucleus interactions, and detect galactic supernovae. We present the concept of the DARWIN detector and discuss its physics reach, the main sources of backgrounds and the ongoing detector design and R&D efforts.
|
|
| 6. |
- 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.
|
|
| 7. |
- Elhai, M, et al.
(författare)
-
Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
- 2019
-
Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
-
Tidskriftsartikel (refereegranskat)abstract
- To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
|
|
| 8. |
|
|
| 9. |
- Althueser, L., et al.
(författare)
-
GPU-based optical simulation of the DARWIN detector
- 2022
-
Ingår i: Journal of Instrumentation. - 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.
|
|
| 10. |
|
|
| 11. |
- Amendola, L., et al.
(författare)
-
Cosmology and fundamental physics with the Euclid satellite
- 2018
-
Ingår i: Living Reviews in Relativity. - : Springer. - 1433-8351 .- 2367-3613. ; 21:1
-
Tidskriftsartikel (refereegranskat)abstract
- Euclid is a European Space Agency medium-class mission selected for launch in 2020 within the cosmic vision 2015–2025 program. The main goal of Euclid is to understand the origin of the accelerated expansion of the universe. Euclid will explore the expansion history of the universe and the evolution of cosmic structures by measuring shapes and red-shifts of galaxies as well as the distribution of clusters of galaxies over a large fraction of the sky. Although the main driver for Euclid is the nature of dark energy, Euclid science covers a vast range of topics, from cosmology to galaxy evolution to planetary research. In this review we focus on cosmology and fundamental physics, with a strong emphasis on science beyond the current standard models. We discuss five broad topics: dark energy and modified gravity, dark matter, initial conditions, basic assumptions and questions of methodology in the data analysis. This review has been planned and carried out within Euclid’s Theory Working Group and is meant to provide a guide to the scientific themes that will underlie the activity of the group during the preparation of the Euclid mission.
|
|
| 12. |
- Kajdic, P., et al.
(författare)
-
ULF Wave Transmission Across Collisionless Shocks : 2.5D Local Hybrid Simulations
- 2021
-
Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 126:11
-
Tidskriftsartikel (refereegranskat)abstract
- We study the interaction of upstream ultralow frequency (ULF) waves with collisionless shocks by analyzing the outputs of 11 2D local hybrid simulation runs. Our simulated shocks have Alfvenic Mach numbers between 4.29 and 7.42 and their theta BN angles are 15 degrees, 30 degrees, 45 degrees, and 50 degrees. The ULF wave foreshocks develop upstream of all of them. The wavelength and the amplitude of the upstream waves exhibit a complex dependence on the shock's MA and theta BN. The wavelength positively correlates with both parameters, with the dependence on theta BN being much stronger. The amplitude of the ULF waves is proportional to the product of the reflected beam velocity and density, which also depend on MA and theta BN. The interaction of the ULF waves with the shock causes large-scale (several tens of upstream ion inertial lengths) shock rippling. The properties of the shock ripples are related to the ULF wave properties, namely their wavelength and amplitude. In turn, the ripples have a large impact on the ULF wave transmission across the shock because they change local shock properties (theta BN, strength), so that different sections of the same ULF wavefront encounter shock with different characteristics. Downstream fluctuations do not resemble the upstream waves in terms the wavefront extension, orientation or their wavelength. However, some features are conserved in the Fourier spectra of downstream compressive waves that present a bump or flattening at wavelengths approximately corresponding to those of the upstream ULF waves. In the transverse downstream spectra, these features are weaker.
|
|
| 13. |
|
|
| 14. |
- Chang, Kuang Yu, et al.
(författare)
-
Substantial hysteresis in emergent temperature sensitivity of global wetland CH4 emissions
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 2266-2266
-
Tidskriftsartikel (refereegranskat)abstract
- Wetland methane (CH4) emissions ([Formula: see text]) are important in global carbon budgets and climate change assessments. Currently, [Formula: see text] projections rely on prescribed static temperature sensitivity that varies among biogeochemical models. Meta-analyses have proposed a consistent [Formula: see text] temperature dependence across spatial scales for use in models; however, site-level studies demonstrate that [Formula: see text] are often controlled by factors beyond temperature. Here, we evaluate the relationship between [Formula: see text] and temperature using observations from the FLUXNET-CH4 database. Measurements collected across the globe show substantial seasonal hysteresis between [Formula: see text] and temperature, suggesting larger [Formula: see text] sensitivity to temperature later in the frost-free season (about 77% of site-years). Results derived from a machine-learning model and several regression models highlight the importance of representing the large spatial and temporal variability within site-years and ecosystem types. Mechanistic advancements in biogeochemical model parameterization and detailed measurements in factors modulating CH4 production are thus needed to improve global CH4 budget assessments.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Gadea, A., et al.
(författare)
-
Observation of Ni-54 : Cross-conjugate symmetry in f(7/2) mirror energy differences
- 2006
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 97:15, s. 152501-
-
Tidskriftsartikel (refereegranskat)abstract
- Gamma decays from excited states up to J(pi)=6(+) in the N=Z-2 nucleus Ni-54 have been identified for the first time. Level energies are compared with those of the isobars Co-54 and Fe-54 and of the cross-conjugate nuclei of mass A=42. The good but puzzling f(7/2) cross-conjugate symmetry in mirror and triplet energy differences is analyzed. Shell model calculations reproduce the new data but the necessary nuclear charge-dependent phenomenology is not fully explained by modern nucleon-nucleon potentials.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Knox, Sara H., et al.
(författare)
-
FLUXNET-CH4 Synthesis Activity : Objectives, Observations, and Future Directions
- 2019
-
Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 100:12, s. 2607-2632
-
Tidskriftsartikel (refereegranskat)abstract
- This paper describes the formation of, and initial results for, a new FLUXNET coordination network for ecosystem-scale methane (CH4) measurements at 60 sites globally, organized by the Global Carbon Project in partnership with other initiatives and regional flux tower networks. The objectives of the effort are presented along with an overview of the coverage of eddy covariance (EC) CH4 flux measurements globally, initial results comparing CH4 fluxes across the sites, and future research directions and needs. Annual estimates of net CH4 fluxes across sites ranged from -0.2 +/- 0.02 g C m(-2) yr(-1) for an upland forest site to 114.9 +/- 13.4 g C m(-2) yr(-1) for an estuarine freshwater marsh, with fluxes exceeding 40 g C m(-2) yr(-1) at multiple sites. Average annual soil and air temperatures were found to be the strongest predictor of annual CH4 flux across wetland sites globally. Water table position was positively correlated with annual CH4 emissions, although only for wetland sites that were not consistently inundated throughout the year. The ratio of annual CH4 fluxes to ecosystem respiration increased significantly with mean site temperature. Uncertainties in annual CH4 estimates due to gap-filling and random errors were on average +/- 1.6 g C m(-2) yr(-1) at 95% confidence, with the relative error decreasing exponentially with increasing flux magnitude across sites. Through the analysis and synthesis of a growing EC CH4 flux database, the controls on ecosystem CH4 fluxes can be better understood, used to inform and validate Earth system models, and reconcile differences between land surface model- and atmospheric-based estimates of CH4 emissions.
|
|
| 21. |
|
|
| 22. |
- Sardu, C, et al.
(författare)
-
Endothelial Dysfunction Drives CRTd Outcome at 1-Year Follow-Up: A Novel Role as Biomarker for miR-130a-5p
- 2023
-
Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:2
-
Tidskriftsartikel (refereegranskat)abstract
- Endothelial dysfunction (ED) causes worse prognoses in heart failure (HF) patients treated with cardiac resynchronization therapy (CRTd). ED triggers the downregulation of microRNA-130 (miR-130a-5p), which targets endothelin-1 (ET-1). Thus, we evaluated ED and the response to CRTd by assessing miR-130a-5p and ET-1 serum levels. We designed a prospective multi-center study with a 1-year follow-up to evaluate ED, ET-1, and miR-130a-5p in CRTd patients with ED (ED-CRTd) vs. patients without ED (NED-CRTd). Clinical outcomes were CRTd response, HF hospitalization, cardiac death, and all-cause death. At 1-year follow-up, NED-CRTd (n = 541) vs. ED-CRTd (n = 326) patients showed better clinical statuses, lower serum values of B type natriuretic peptide (BNP: 266.25 ± 10.8 vs. 297.43 ± 16.22 pg/mL; p < 0.05) and ET-1 (4.57 ± 0.17 vs. 5.41 ± 0.24 pmol/L; p < 0.05), and higher values of miR-130a-5p (0.51 ± 0.029 vs. 0.41 ± 0.034 A.U; p < 0.05). Compared with NED-CRTd patients, ED-CRTd patients were less likely to be CRTd responders (189 (58%) vs. 380 (70.2%); p < 0.05) and had higher rates of HF hospitalization (115 (35.3%) vs. 154 (28.5%); p < 0.05) and cardiac deaths (30 (9.2%) vs. 21 (3.9%); p < 0.05). Higher miR-130a-5p levels (HR 1.490, CI 95% [1.014–2.188]) significantly predicted CRTd response; the presence of hypertension (HR 0.818, CI 95% [0.669–0.999]), and displaying higher levels of ET-1 (HR 0.859, CI 98% [0.839–0.979]), lymphocytes (HR 0.820, CI 95% [0.758–0.987]), LVEF (HR 0.876, CI 95% [0.760–0.992]), and ED (HR 0.751, CI 95% [0.624–0.905]) predicted CRTd non-response. Higher serum miR-130a-5p levels (HR 0.332, CI 95% [0.347–0.804]) and use of ARNI (HR 0.319, CI 95% [0.310–0.572]) predicted lower risk of HF hospitalization, whereas hypertension (HR 1.818, CI 95% [1.720–2.907]), higher BNP levels (HR 1.210, CI 95% [1.000–1.401]), and presence of ED (HR 1.905, CI 95% [1.238–2.241]) predicted a higher risk of HF hospitalization. Hence, serum miR-130a-5p could identify different stages of ED and independently predict CRTd response, therefore representing a novel prognostic HF biomarker.
|
|
| 23. |
|
|
| 24. |
- Torsello, D., et al.
(författare)
-
Expected radiation environment and damage for YBCO tapes in compact fusion reactors
- 2023
-
Ingår i: Superconductors Science and Technology. - : IOP Publishing Ltd. - 0953-2048 .- 1361-6668. ; 36:1
-
Tidskriftsartikel (refereegranskat)abstract
- We investigate the neutron damage expected in high-temperature superconducting tapes that will be employed in compact fusion reactors. Monte Carlo simulations yield the expected neutron spectrum and fluence at the magnet position, from which the primary knock-on atom energy distributions can be computed for each atomic species comprising the superconductor. This information is then employed to characterize the displacement cascades, in terms of size and morphology, through molecular dynamics simulations. The expected radiation environment is then compared with the neutron spectrum and fluences achievable at the facilities currently available for experimental investigation in order to highlight similarities and differences that could be relevant to the understanding of the radiation hardness of these materials in real fusion conditions. We find that the different neutron spectra result in different damage regimes, the irradiation temperature influences the number of generated defects, and the interaction of the neutrons with the superconductor results in a local increase in temperature. These observations suggest that further experimental investigations are needed in different regimes and that some neutron shielding will be necessary in compact fusion reactors.
|
|
| 25. |
- Trotta, D., et al.
(författare)
-
Three-dimensional modelling of the shock-turbulence interaction
- 2023
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 525:2, s. 1856-1866
-
Tidskriftsartikel (refereegranskat)abstract
- The complex interaction between shocks and plasma turbulence is extremely important to address crucial features of energy conversion in a broad range of astrophysical systems. We study the interaction between a supercritical, perpendicular shock and pre-existing, fully developed plasma turbulence, employing a novel combination of magnetohydrodynamic and small-scale, hybrid-kinetic simulations where a shock is propagating through a turbulent medium. The variability of the shock front in the unperturbed case and for two levels of upstream fluctuations is addressed. We find that the behaviour of shock ripples, i.e. shock surface fluctuations with short (a few ion skin depths, di) wavelengths, is modified by the presence of pre-existing turbulence, which also induces strong corrugations of the shock front at larger scales. We link this complex behaviour of the shock front and the shock downstream structuring with the proton temperature anisotropies produced in the shock-turbulence system. Finally, we put our modelling effort in the context of spacecraft observations, elucidating the role of novel cross-scale, multispacecraft measurements in resolving shock front irregularities at different scales. These results are relevant for a broad range of astrophysical systems characterized by the presence of shock waves interacting with plasma turbulence.
|
|
