| 1. |
- Figlioli, G, et al.
(författare)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 2. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 3. |
- Goldkuhle, A., et al.
(författare)
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Lifetime measurements in Ti-52,Ti-54 to study shell evolution toward N=32
- 2019
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 100:5
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Tidskriftsartikel (refereegranskat)abstract
- Lifetimes of the excited states in the neutron-rich Ti-52,Ti-54 nuclei, produced in a multinucleon-transfer reaction, were measured by employing the Cologne plunger device and the recoil-distance Doppler-shift method. The experiment was performed at the Grand Accelerateur National d'Ions Lourds facility by using the Advanced Gamma Tracking Array for the gamma-ray detection, coupled to the large-acceptance variable mode spectrometer for an event-by-event particle identification. A comparison between the transition probabilities obtained from the measured lifetimes of the 2(1)(+) to 8(1)(+) yrast states in Ti-52,Ti-54 and that from the shell-model calculations based on the well-established GXPF1A, GXPF1B, and KB3G fp shell interactions support the N = 32 subshell closure. The B(E2) values for Ti-52 determined in this work are in disagreement with the known data, but are consistent with the predictions of the shell-model calculations and reduce the previously observed pronounced staggering across the even-even titanium isotopes.
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| 4. |
- Biswas, S., et al.
(författare)
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Effects of one valence proton on seniority and angular momentum of neutrons in neutron-rich(51)( 122-)(131)Sb isotopes
- 2019
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 99:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Levels fulfilling the seniority scheme and relevant isomers are commonly observed features in semimagic nuclei; for example, in Sn isotopes (Z = 50). Seniority isomers in Sn, with dominantly pure neutron configurations, directly probe the underlying neutron-neutron (vv) interaction. Furthermore, an addition of a valence proton particle or hole, through neutron-proton (v pi) interaction, affects the neutron seniority as well as the angular momentum. Purpose: Benchmark the reproducibility of the experimental observables, like the excitation energies (E-x) and the reduced electric-quadrupole transition probabilities [B(E2)], with the results obtained from shell-model interactions for neutron-rich Sn and Sb isotopes with N < 82. Study the sensitivity of the aforementioned experimental observables to the model interaction components. Furthermore, explore from a microscopic point of view the structural similarity between the isomers in Sn and Sb, and thus the importance of the valence proton. Methods: The neutron-rich Sb122-131 isotopes were produced as fission fragments in the reaction Be-9(U-238, f) with 6.2 MeV/u beam energy. A unique setup, consisting of AGATA, VAMOS++, and EXOGAM detectors, was used which enabled the prompt-delayed gamma-ray spectroscopy of fission fragments in the time range of 100 ns to 200 mu s. Results: New isomers and prompt and delayed transitions were established in the even-A Sb122-131 isotopes. In the odd-A Sb122-131 isotopes, new prompt and delayed gamma-ray transitions were identified, in addition to the confirmation of the previously known isomers. The half-lives of the isomeric states and the B(E2) transition probabilities of the observed transitions depopulating these isomers were extracted. Conclusions: The experimental data was compared with the theoretical results obtained in the framework of large-scale shell-model (LSSM) calculations in a restricted model space. Modifications of several components of the shell-model interaction were introduced to obtain a consistent agreement with the excitation energies and the B(E2) transition probabilities in neutron-rich Sn and Sb isotopes. The isomeric configurations in Sn and Sb were found to be relatively pure. Furthermore, the calculations revealed that the presence of a single valence proton, mainly in the g(7/2) orbital in Sb isotopes, leads to significant mixing (due to the v pi interaction) of (i) the neutron seniorities (upsilon(v)) and (ii) the neutron angular momentum (I-v). The above features have a weak impact on the excitation energies, but have an important impact on the B(E2) transition probabilities. In addition, a constancy of the relative excitation energies irrespective of neutron seniority and neutron number in Sn and Sb was observed.
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| 5. |
- Delafosse, C., et al.
(författare)
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Pseudospin Symmetry and Microscopic Origin of Shape Coexistence in the Ni-78 Region : A Hint from Lifetime Measurements
- 2018
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Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 121:19
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Tidskriftsartikel (refereegranskat)abstract
- Lifetime measurements of excited states of the light N = 52 isotones Kr-88, Se-86, and Ge-84 have been performed, using the recoil distance Doppler shift method and VAMOS and AGATA spectrometers for particle identification and gamma spectroscopy, respectively. The reduced electric quadrupole transition probabilities B(E2; 2(+)-> 0(+)) and B(E2; 4(+)-> 2(+)) were obtained for the first time for the hard-to-reach 84Ge. While the B(E2; 2(+)-> 0(+) ) values of Kr-88, Se-86 saturate the maximum quadrupole collectivity offered by the natural valence (3s, 2d, 1g(7/2), 1h(11/2)) space of an inert Ni-78 core, the value obtained for Ge-84 largely exceeds it, suggesting that shape coexistence phenomena, previously reported at N less than or similar to 49, extend beyond N = 50. The onset of collectivity at Z = 32 is understood as due to a pseudo-SU(3) organization of the proton single-particle sequence reflecting a clear manifestation of pseudospin symmetry. It is realized that the latter provides actually reliable guidance for understanding the observed proton and neutron single particle structure in the whole medium-mass region, from Ni to Sn, pointing towards the important role of the isovector-vector rho field in shell-structure evolution.
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| 6. |
- Ledoux, X., et al.
(författare)
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The Neutrons for Science Facility at SPIRAL-2
- 2018
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Ingår i: Radiation Protection Dosimetry. - : OXFORD UNIV PRESS. - 0144-8420 .- 1742-3406. ; 180:1-4, s. 115-119
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Tidskriftsartikel (refereegranskat)abstract
- The neutrons for science (NFS) facility is a component of SPIRAL-2, the new superconducting linear accelerator built at GANIL in Caen (France). The proton and deuteron beams delivered by the accelerator will allow producing intense neutron fields in the 100 keV-40 MeV energy range. Continuous and quasi-mono-kinetic energy spectra, respectively, will be available at NFS, produced by the interaction of a deuteron beam on a thick Be converter and by the Li-7(p, n) reaction on thin converter. The pulsed neutron beam, with a flux up to two orders of magnitude higher than those of other existing time-of-flight facilities, will open new opportunities of experiments in fundamental research as well as in nuclear data measurements. In addition to the neutron beam, irradiation stations for neutron-, proton- and deuteron-induced reactions will be available for cross-sections measurements and for the irradiation of electronic devices or biological cells. NFS, whose first experiment is foreseen in 2018, will be a very powerful tool for physics, fundamental research as well as applications like the transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors.
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| 7. |
- Ledoux, X., et al.
(författare)
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The neutrons for science facility at SPIRAL-2
- 2017
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Ingår i: ND 2016. - Les Ulis : EDP Sciences.
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Konferensbidrag (refereegranskat)abstract
- Numerous domains, in fundamental research as well as in applications, require the study of reactions induced by neutrons with energies from few MeV up to few tens of MeV. Reliable measurements also are necessary to improve the evaluated databases used by nuclear transport codes. This energy range covers a large number of topics like transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors. A new facility called Neutrons For Science (NFS) is being built for this purpose on the GANIL site at Caen (France). NFS is composed of a pulsed neutron beam for time-of-flight facility as well as irradiation stations for cross-section measurements. Neutrons will be produced by the interaction of deuteron and proton beams, delivered by the SPIRAL-2 linear accelerator, with thick or thin converters made of beryllium or lithium. Continuous and quasi-mono-energetic spectra will be available at NFS up to 40 MeV. In this fast energy region, the neutron flux is expected to be up to 2 orders of magnitude higher than at other existing time-of-flight facilities. In addition, irradiation stations for neutron-, proton- and deuteron-induced reactions will allow performing cross-section measurements by the activation technique. After a description of the facility and its characteristics, the experiments to be performed in the short and medium term will be presented.
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| 8. |
- Klintefjord, M., et al.
(författare)
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Measurement of lifetimes in Fe-62,Fe-64, Co-61,Co-63, and Mn-59
- 2017
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Ingår i: PHYSICAL REVIEW C. - 2469-9985. ; 95:2
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Tidskriftsartikel (refereegranskat)abstract
- Lifetimes of the 4(1)(+) states in Fe-62,Fe-64 and the 11/2(1)(-) states in Co-61,Co-63 and Mn-59 were measured at the Grand Accelerateur National d'Ions Lourds (GANIL) facility by using the Advanced Gamma Tracking Array (AGATA) and the large-acceptance variable mode spectrometer (VAMOS++). The states were populated through multinucleon transfer reactions with a U-238 beam impinging on a Ni-64 target, and lifetimes in the picosecond range were measured by using the recoil distance Doppler shift method. The data show an increase of collectivity in the iron isotopes approaching N = 40. The reduction of the subshell gap between the nu 2p(1/2) and nu 1g(9/2) orbitals leads to an increased population of the quasi-SU(3) pair (nu 1g(9/2), nu 2d(5/2)), which causes an increase in quadrupole collectivity. This is not observed for the cobalt isotopes withN < 40 for which the neutron subshell gap is larger due to the repulsive monopole component of the tensor nucleon-nucleon interaction. The extracted experimental B(E2) values are compared with large-scale shell-model calculations and with beyond-mean-field calculations with the Gogny D1S interaction. A good agreement between calculations and experimental values is found, and the results demonstrate in particular the spectroscopic quality of the Lenzi, Nowacki, Poves, and Sieja (LNPS) shell-model interaction.
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