| 1. |
- Ahdida, C., et al.
(författare)
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The magnet of the scattering and neutrino detector for the SHiP experiment at CERN
- 2020
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 15:01
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Tidskriftsartikel (refereegranskat)abstract
- The Search for Hidden Particles (SHiP) experiment proposal at CERN demands a dedicated dipole magnet for its scattering and neutrino detector. This requires a very large volume to be uniformly magnetized at B > 1.2 T, with constraints regarding the inner instrumented volume as well as the external region, where no massive structures are allowed and only an extremely low stray field is admitted. In this paper we report the main technical challenges and the relevant design options providing a comprehensive design for the magnet of the SHiP Scattering and Neutrino Detector.
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| 2. |
- Ahdida, C., et al.
(författare)
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Measurement of the muon flux from 400 GeV/c protons interacting in a thick molybdenum/tungsten target
- 2020
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:3
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Tidskriftsartikel (refereegranskat)abstract
- The SHiP experiment is proposed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. About 1011muons per spill will be produced in the dump. To design the experiment such that the muon-induced background is minimized, a precise knowledge of the muon spectrum is required. To validate the muon flux generated by our Pythia and GEANT4 based Monte Carlo simulation (FairShip), we have measured the muon flux emanating from a SHiP-like target at the SPS. This target, consisting of 13 interaction lengths of slabs of molybdenum and tungsten, followed by a 2.4 m iron hadron absorber was placed in the H4 400 GeV/c proton beam line. To identify muons and to measure the momentum spectrum, a spectrometer instrumented with drift tubes and a muon tagger were used. During a 3-week period a dataset for analysis corresponding to (3.27 +/- 0.07)x1011protons on target was recorded. This amounts to approximatively 1% of a SHiP spill.
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| 3. |
- Willeit, P., et al.
(författare)
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Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients
- 2020
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Ingår i: Circulation. - 1524-4539. ; 142:7, s. 621-642
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. METHODS: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. RESULTS: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. CONCLUSIONS: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.
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| 4. |
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| 5. |
- Revel, A., et al.
(författare)
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Extending the Southern Shore of the Island of Inversion to F-28
- 2020
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 124:15
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Tidskriftsartikel (refereegranskat)abstract
- Detailed spectroscopy of the neutron-unbound nucleus F-28 has been performed for the first time following proton/neutron removal from Ne-29/F-29 beams at energies around 230 MeV=nucleon. The invariant-mass spectra were reconstructed for both the F-27((*)) + n and F-26((*)) + 2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the F-28 ground state, with S-n(F-28) = -199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S-n(F-27) = 1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of F-28. Importantly, in the case of the ground state, the reconstructed F-27 + n momentum distribution following neutron removal from F-29 indicates that it arises mainly from the 1p(3/2) neutron intruder configuration. This demonstrates that the island of inversion around N = 20 includes F-28, and most probably F-29, and suggests that O-28 is not doubly magic.
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| 6. |
- Bellouin, N., et al.
(författare)
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Bounding Global Aerosol Radiative Forcing of Climate Change
- 2020
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Ingår i: Reviews of geophysics. - 8755-1209 .- 1944-9208. ; 58:1
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Forskningsöversikt (refereegranskat)abstract
- Aerosols interact with radiation and clouds. Substantial progress made over the past 40 years in observing, understanding, and modeling these processes helped quantify the imbalance in the Earth's radiation budget caused by anthropogenic aerosols, called aerosol radiative forcing, but uncertainties remain large. This review provides a new range of aerosol radiative forcing over the industrial era based on multiple, traceable, and arguable lines of evidence, including modeling approaches, theoretical considerations, and observations. Improved understanding of aerosol absorption and the causes of trends in surface radiative fluxes constrain the forcing from aerosol-radiation interactions. A robust theoretical foundation and convincing evidence constrain the forcing caused by aerosol-driven increases in liquid cloud droplet number concentration. However, the influence of anthropogenic aerosols on cloud liquid water content and cloud fraction is less clear, and the influence on mixed-phase and ice clouds remains poorly constrained. Observed changes in surface temperature and radiative fluxes provide additional constraints. These multiple lines of evidence lead to a 68% confidence interval for the total aerosol effective radiative forcing of -1.6 to -0.6Wm(-2), or -2.0 to -0.4Wm(-2) with a 90% likelihood. Those intervals are of similar width to the last Intergovernmental Panel on Climate Change assessment but shifted toward more negative values. The uncertainty will narrow in the future by continuing to critically combine multiple lines of evidence, especially those addressing industrial-era changes in aerosol sources and aerosol effects on liquid cloud amount and on ice clouds. Plain Language Summary Human activities emit into the atmosphere small liquid and solid particles called aerosols. Those aerosols change the energy budget of the Earth and trigger climate changes, by scattering and absorbing solar and terrestrial radiation and playing important roles in the formation of cloud droplets and ice crystals. But because aerosols are much more varied in their chemical composition and much more heterogeneous in their spatial and temporal distributions than greenhouse gases, their perturbation to the energy budget, called radiative forcing, is much more uncertain. This review uses traceable and arguable lines of evidence, supported by aerosol studies published over the past 40 years, to quantify that uncertainty. It finds that there are two chances out of three that aerosols from human activities have increased scattering and absorption of solar radiation by 14% to 29% and cloud droplet number concentration by 5 to 17% in the period 2005-2015 compared to the year 1850. Those increases exert a radiative forcing that offsets between a fifth and a half of the radiative forcing by greenhouse gases. The degree to which human activities affect natural aerosol levels, and the response of clouds, and especially ice clouds, to aerosol perturbations remain particularly uncertain.
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| 7. |
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| 8. |
- Sekiguchi, M, et al.
(författare)
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Integrated multiomics analysis of hepatoblastoma unravels its heterogeneity and provides novel druggable targets
- 2020
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Ingår i: NPJ precision oncology. - : Springer Science and Business Media LLC. - 2397-768X. ; 4:1, s. 20-
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Tidskriftsartikel (refereegranskat)abstract
- Although hepatoblastoma is the most common pediatric liver cancer, its genetic heterogeneity and therapeutic targets are not well elucidated. Therefore, we conducted a multiomics analysis, including mutatome, DNA methylome, and transcriptome analyses, of 59 hepatoblastoma samples. Based on DNA methylation patterns, hepatoblastoma was classified into three clusters exhibiting remarkable correlation with clinical, histological, and genetic features. Cluster F was largely composed of cases with fetal histology and good outcomes, whereas clusters E1 and E2 corresponded primarily to embryonal/combined histology and poor outcomes. E1 and E2, albeit distinguishable by different patient age distributions, were genetically characterized by hypermethylation of the HNF4A/CEBPA-binding regions, fetal liver-like expression patterns, upregulation of the cell cycle pathway, and overexpression of NQO1 and ODC1. Inhibition of NQO1 and ODC1 in hepatoblastoma cells induced chemosensitization and growth suppression, respectively. Our results provide a comprehensive description of the molecular basis of hepatoblastoma and rational therapeutic strategies for high-risk cases.
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| 9. |
- Inagaki-Kawata, Y, et al.
(författare)
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Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants
- 2020
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 578-
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Tidskriftsartikel (refereegranskat)abstract
- The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1,995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants.
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