| 1. |
- Aamodt, K., et al.
(författare)
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The ALICE experiment at the CERN LHC
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
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Forskningsöversikt (refereegranskat)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
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| 2. |
- Doornenbal, P., et al.
(författare)
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Spectroscopy of 32Ne and the "œIsland of Inversion"
- 2009
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Ingår i: Physical Review Letters. - American Physical Society. - 0031-9007 .- 1079-7114. ; 103:3, s. 032501-1-032501-4
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Tidskriftsartikel (refereegranskat)abstract
- We report on the first spectroscopic study of the N = 22 nucleus 32Ne at the newly completed RIKEN Radioactive Ion Beam Factory. A single γ-ray line with an energy of 722(9) keV was observed in both inelastic scattering of a 226 MeV=u 32Ne beam on a carbon target and proton removal from 33Na at 245 MeV=u. This transition is assigned to the deexcitation of the first Jπ = 2+ state in 32Ne to the 0+ ground state. Interpreted through comparison with state-of-the-art shell-model calculations, the low excitation energy demonstrates that the ‘‘island of inversion’’ extends to at least N = 22 for the Ne isotopes.
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| 3. |
- Boutachkov, P., et al.
(författare)
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High-spin isomers in 96Ag : excitations across the Z=38 and Z=50, N=50 closed shells
- 2011
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 84:4
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in (96)Ag were populated in fragmentation of an 850-MeV/u (124)Xe beam on a 4-g/cm(2) Be target. Three new high-spin isomers were identified and the structure of the populated states was investigated. The level scheme of (96)Ag was established, and a spin parity of (13(-)), (15(+)), and (19(+)) was assigned to the new isomeric states. Shell-model calculations were performed in various model spaces, including pi nu(p(1/2), g(9/2), f(5/2), p(3/2)) and the large-scale shell-model space pi nu(gds), to account for the observed parity changing M2 and E3 transitions from the (13(-)) isomer and the E2 and E4 transitions from the (19(+)) core-excited isomer, respectively. The calculated level schemes and reduced transition strengths are found to be in very good agreement with the experiment.
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| 4. |
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| 5. |
- Brock, T. S., et al.
(författare)
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Observation of a new high-spin isomer in Pd-94
- 2010
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 82:6, s. 061309-
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Tidskriftsartikel (refereegranskat)abstract
- A second gamma-decaying high-spin isomeric state, with a half-life of 197(22) ns, has been identified in the N = Z + 2 nuclide Pd-94 as part of a stopped-beam Rare Isotope Spectroscopic INvestigation at GSI (RISING) experiment. Weisskopf estimates were used to establish a tentative spin/parity of 19(-), corresponding to the maximum possible spin of a negative parity state in the restricted (p(1/2), g(9/2)) model space of empirical shell model calculations. The reproduction of the E3 decay properties of the isomer required an extension of the model space to include the f (5/2) and p(3/2) orbitals using the CD-Bonn potential. This is the first time that such an extension has been required for a high-spin isomer in the vicinity of Sn-100 and reveals the importance of such orbits for understanding the decay properties of high-spin isomers in this region. However, despite the need for the extended model space for the E3 decay, the dominant configuration for the 19(-) state remains (p p(1/2)(-1)g(9/2)(-3))(11)circle times(nu g(9/2)(-2))(8). The half-life of the known, 14(+), isomer was remeasured and yielded a value of 499(13) ns.
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| 6. |
- Grawe, H., et al.
(författare)
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The (6+) isomer in 102Sn revisited : Neutron and proton effective charges close to the double shell closure
- 2021
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Ingår i: Physics Letters B. - : Elsevier. - 0370-2693 .- 1873-2445. ; 820
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Tidskriftsartikel (refereegranskat)abstract
- In a high-energy fragmentation experiment at GSI an Iπ = (6+) isomer and its γ-decay are identified in 102Sn, the two-neutron neighbour of the doubly-magic 100Sn. Its half-life is measured to be T1/2 = 367(11) ns. The possible existence of further isomers is discussed in the framework of large-scale shell model (LSSM) calculations including up to five particle-hole excitations of the 100Sn core. From the precise B(E2; 6+ → 4+) strength and the recently remeasured value for B(E2; 8+ → 6+) in the two-proton hole neighbour 98Cd effective E2 polarization charges for protons and neutrons were inferred including LSSM corrections within the full N=4 0hω space. The results are discussed in comparison to predicted and empirically determined effective operators.
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| 7. |
- Hinke, C. B., et al.
(författare)
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Superallowed Gamow-Teller decay of the doubly magic nucleus 100Sn
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 486:7403, s. 341-345
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Tidskriftsartikel (refereegranskat)abstract
- The shell structure of atomic nuclei is associated with 'magic numbers' and originates in the nearly independent motion of neutrons and protons in a mean potential generated by all nucleons. During beta(+)-decay, a proton transforms into a neutron in a previously not fully occupied orbital, emitting a positron-neutrino pair with either parallel or antiparallel spins, in a Gamow-Teller or Fermi transition, respectively. The transition probability, or strength, of a Gamow-Teller transition depends sensitively on the underlying shell structure and is usually distributed among many states in the neighbouring nucleus. Here we report measurements of the half-life and decay energy for the decay of Sn-100, the heaviest doubly magic nucleus with equal numbers of protons and neutrons. In the beta-decay of Sn-100, a large fraction of the strength is observable because of the large decay energy. We determine the largest Gamow-Teller strength so far measured in allowed nuclear beta-decay, establishing the 'superallowed' nature of this Gamow-Teller transition. The large strength and the low-energy states in the daughter nucleus, In-100, are well reproduced by modern, large-scale shell model calculations.
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| 8. |
- Nara Singh, B. S., et al.
(författare)
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Exotic Nuclear Studies Around and Below A=100
- 2011
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Ingår i: 4th International Conference on Proton Emitting Nuclei and Related Topics, PROCON2011. - : AIP. - 9780735409835 ; 1409, s. 19-24
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Konferensbidrag (refereegranskat)abstract
- A RISING experiment with an aim to study exotic Cd nuclei was carried out at GSI-FRS facility. Some preliminary results from this experiment are presented here. In particular, the β decay of 96Cd to 96Ag revealed the existence of a high spin isomer predicted a few decades ago. In this context, the structures of both these nuclei are discussed. Shell model calculations using the Gross-Frenkel interaction are used to interpret the results.
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| 9. |
- Singh, B. S. Nara, et al.
(författare)
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16(+) Spin-Gap Isomer in (96)Cd
- 2011
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 107:17, s. 172502-
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Tidskriftsartikel (refereegranskat)abstract
- A beta-decaying high-spin isomer in (96)Cd, with a half-life T(1/2) = 0.29(-0.10)(+0.11) s, has been established in a stopped beam rare isotope spectroscopic investigations at GSI (RISING) experiment. The nuclei were produced using the fragmentation of a primary beam of (124)Xe on a (9)Be target. From the half-life and the observed gamma decays in the daughter nucleus, (96)Ag, we conclude that the beta-decaying state is the long predicted 16(+) "spin-gap'' isomer. Shell-model calculations, using the Gross-Frenkel interaction and the pi nu(p(1/2,)g(9/2)) model space, show that the isoscalar component of the neutron-proton interaction is essential to explain the origin of the isomer. Core excitations across the N = Z = 50 gaps and the Gamow-Teller strength, Bd(GT) distributions have been studied via large-scale shell-model calculations using the pi nu(g, d, s) model space to compare with the experimental B(GT) value obtained from the half-life of the isomer.
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| 10. |
- Singh, B. S. Nara, et al.
(författare)
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Influence of the np interaction on the beta decay of Pd-94
- 2012
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 86:4, s. 041301-
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Tidskriftsartikel (refereegranskat)abstract
- We present results from stopped beam rare isotope spectroscopic investigations at the GSI (RISING) experiment based on the detection of gamma-ray transitions following the beta decay of Pd-94. A comparison between the measured low-lying level scheme of Rh-94 and the prediction from shell-model calculations reveals the important roles of the g(7/2) and g(9/2) orbitals in explaining the structural features. The low values of the Gamow-Teller strengths B(GT) can be attributed to the influence of the neutron-proton interaction, which gives rise to an increased seniority mixing for the nuclear states, thereby leading to a fragmentation of the strength to several daughter levels. These results provide further strong indications that Pd-94 resides in the middle of a structural transition region in the Pd isotopes as the N = Z line is approached.
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| 11. |
- Wadsworth, R., et al.
(författare)
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Spin-gap Isomer in 96Cd
- 2012
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6596 .- 1742-6588. ; 381:1
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Tidskriftsartikel (refereegranskat)abstract
- Evidence has been obtained for the existence of the long predicted 16+ spin-gap isomer in 96Cd. The decay of the isomer was identified and studied following the use of an 850 MeV/u beam of 124Xe impinging on a Be target and the fragment recoil separator at the GSI Laboratory. Gamma decays from the fragments were detected using the RISING gamma ray array, in its stopped beam configuration, plus a silicon active stopper. The data obtained have been compared with shell model predictions, which indicate that the isoscalar neutron-proton interaction plays a key role in the formation of the isomer.
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| 12. |
- Blazhev, A, et al.
(författare)
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High-energy excited states in 98 Cd
- 2010
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Ingår i: Journal of Physics: Conference Series. ; 205:1
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Tidskriftsartikel (refereegranskat)abstract
- In 98 Cd a new high-energy isomeric γ -ray transition was identified, which confirms previous spin-parity assignments and enables for the first time the measurement of the E 2 and E 4 strength for the two decay branches of the isomer. Preliminary results on the 98 Cd high-excitation level scheme are presented. A comparison to shell-model calculations as well as implications for the nuclear structure around 100 Sn are discussed.
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| 13. |
- Boutachkov, P., et al.
(författare)
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Isomer and Beta-decay Spectroscopy of Tz=1 Isotopes Below the N=Z=50 Shell Gap
- 2011
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6596 .- 1742-6588. ; 312:9
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Tidskriftsartikel (refereegranskat)abstract
- The RISING setup at the GSI-FRS facility was used to investigate the isomer and beta decays in N~Z~50 Cd, Ag and Pd isotopes. A preliminary analysis of the data has revealed new results on the Tz=1, 94Pd, 96Ag and 98Cd isotopes. In 94Pd a new high-spin isomer was observed, whilst in 96Ag 3 new isomeric states were identified, including core-excited states. In 98Cd a new high-energy isomeric γ-ray transition is observed, thus enabling us to confirm the previous spin assignment for the core-excited 12+ isomer.
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| 14. |
- Lalkovski, S., et al.
(författare)
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Core-coupled states and split proton-neutron quasiparticle multiplets in Ag122-126
- 2013
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 87:3, s. 034308-
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Tidskriftsartikel (refereegranskat)abstract
- Neutron-rich silver isotopes were populated in the fragmentation of a Xe-136 beam and the relativistic fission of U-238. The fragments were mass analyzed with the GSI Fragment Separator and subsequently implanted into a passive stopper. Isomeric transitions were detected by 105 high-purity germanium detectors. Eight isomeric states were observed in Ag122-126 nuclei. The level schemes of Ag-122,Ag-123,Ag-125 were revised and extended with isomeric transitions being observed for the first time. The excited states in the odd-mass silver isotopes are interpreted as core-coupled states. The isomeric states in the even-mass silver isotopes are discussed in the framework of the proton-neutron split multiplets. The results of shell-model calculations, performed for the most neutron-rich silver nuclei are compared to the experimental data.
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| 15. |
- Blazhev, A, et al.
(författare)
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High-energy Excited States in 98Cd
- 2010
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6596. ; 205
-
Tidskriftsartikel (refereegranskat)abstract
- In 98Cd a new high-energy isomeric γ-ray transition was identified, which confirms previous spin-parity assignments and enables for the first time the measurement of the E2 and E4 strength for the two decay branches of the isomer. Preliminary results on the 98Cd high-excitation level scheme are presented. A comparison to shell-model calculations as well as implications for the nuclear structure around 100Sn are discussed.
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| 16. |
- Speakman, John R., et al.
(författare)
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Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure
- 2023
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Ingår i: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5:4, s. 579-588
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Obesity is caused by a prolonged positive energy balance(1,2). Whether reduced energy expenditure stemming from reduced activity levels contributes is debated(3,4). Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.
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| 17. |
- Gorska, M., et al.
(författare)
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Nuclear Structure Addressed At GSI/RISING
- 2009
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Ingår i: International Journal Of Modern Physics E - Nuclear Physics. - 0218-3013. ; 18:4, s. 759-766
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Konferensbidrag (refereegranskat)abstract
- Nuclear structure spectroscopy studies at GSI recently gained increased momentum within a broad international community with the installation of the Rare Isotopes Spectroscopic INvestigation at GSI (RISING) project. A wide range of physical phenomena has been addressed by high-resolution in-beam gamma-ray spectroscopy experiments with radioactive beams. Relativistic radioactive beams are implanted and their subsequent. and beta decay is investigated. Within this "stopped beam campaign" germanium detectors were arranged in a close geometry around the passive stopper or an array of DSSSD detectors. The exceptionally high gamma-ray efficiency of that configuration made it possible to identify decays of excited or ground states of nuclei which have not been observed before. The results discussed here include the astrophysically relevant shell structure of N=82 isotones, N=Z nuclei around Ni-54, and proton drip-line nuclei below Sn-100. The experimental data are compared to the results of large scale shell-model calculations using various sets of realistic residual two-body interaction.
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| 18. |
- Wadsworth, R., et al.
(författare)
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THE NORTHWEST FRONTIER : SPECTROSCOPY OF N similar to Z NUCLEI BELOW MASS 100
- 2009
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Ingår i: Acta Physica Polonica B. - 0587-4254 .- 1509-5770. ; 40:3, s. 611-620
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Tidskriftsartikel (refereegranskat)abstract
- The spectroscopy and structure of excited states of N similar to Z nuclei in the mass 70-100 region has been investigated using two techniques. In the A similar to 70-80 region fusion evaporation reactions coupled with the recoil-beta-tagging method have been employed at Jyvaskyla to study low-lying states in odd-odd N = Z nuclei. Results from these and other data for known odd-odd nuclei above mass 60 will be discussed. In the heavier mass 90 region a fragmentation experiment has been performed using the RIS-ING/FRS setup at GSI. This experiment was primarily aimed at searching for spin gap isomers in nuclei around A similar to 96. The objectives of the latter experiment will be discussed.
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| 19. |
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| 20. |
- Mach, Henryk, et al.
(författare)
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The single-particle and collective features in the nuclei just above Sn-132
- 2007
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Ingår i: Acta Physica Polonica B. - 0587-4254 .- 1509-5770. ; 38:4, s. 1213-1218
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Tidskriftsartikel (refereegranskat)abstract
- The Advanced Time Delayed method has been used to measure the lifetimes of excited states in the exotic nuclei Sb-134, Sb-135 and Te-136 populated in the beta decay of Sn-134, Sn-135 and Sn-136, respectively. High purity Sn beams were extracted at the ISOLDE separator using a novel production technique utilizing the molecular SnS+ beams to isolate Sn from contaminating other fission products. Among the new results we have identified the 1/2(+) state in Sb-135 and its E2 transition to the lower-lying 5/2(+) state was found to be surprisingly collective. This measurement represents also one of the first applications of the LaBr3 scintillator to ultra fast timing.
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| 21. |
- Heinz, Johanna L., et al.
(författare)
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Varicella zoster virus-induced autophagy in human neuronal and hematopoietic cells exerts antiviral activity
- 2024
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Ingår i: JOURNAL OF MEDICAL VIROLOGY. - 0146-6615 .- 1096-9071. ; 96:6
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Tidskriftsartikel (refereegranskat)abstract
- Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defense mechanism is recognized and some viruses hijack and modulate this process to their advantage in certain cell types. Here, we present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH-SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV-infected SH-SY5Y cells showed increased LC3-I-LC3-II conversion as well as co-localization of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with severe ocular and brain VZV infection were analyzed to identify potential autophagy-associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV-infected cells. In conclusion, these results demonstrate a neuro-protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease.
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| 22. |
- Siebinga, Hinke, et al.
(författare)
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A physiologically based pharmacokinetic model for [Ga-68]Ga-(HA-)DOTATATE to predict whole-body distribution and tumor sink effects in GEP-NET patients
- 2023
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known about parameters that have a relevant impact on (dis)similarities in biodistribution between various Ga-68-labeled somatostatin analogues. Additionally, the effect of tumor burden on organ uptake remains unclear. Therefore, the aim of this study was to describe and compare organ and tumor distribution of [Ga-68]Ga-DOTATATE and [Ga-68]Ga-HA-DOTATATE using a physiologically based pharmacokinetic (PBPK) model and to identify factors that might cause biodistribution and tumor uptake differences between both peptides. In addition, the effect of tumor burden on peptide biodistribution in gastroenteropancreatic (GEP) neuroendocrine tumor (NET) patients was assessed.Methods: A PBPK model was developed for [Ga-68]Ga-(HA-)DOTATATE in GEP-NET patients. Three tumor compartments were added, representing primary tumor, liver metastases and other metastases. Furthermore, reactions describing receptor binding, internalization and recycling, renal clearance and intracellular degradation were added to the model. Scan data from GEP-NET patients were used for evaluation of model predictions. Simulations with increasing tumor volumes were performed to assess the tumor sink effect.Results: Data of 39 and 59 patients receiving [Ga-68]Ga-DOTATATE and [Ga-68]Ga-HA-DOTATATE, respectively, were included. Evaluations showed that the model adequately described image-based patient data and that different receptor affinities caused organ uptake dissimilarities between both peptides. Sensitivity analysis indicated that tumor blood flow and blood volume impacted tumor distribution most. Tumor sink predictions showed a decrease in spleen uptake with increasing tumor volume, which seemed clinically relevant for patients with total tumor volumes higher than similar to 550 mL.Conclusion: The developed PBPK model adequately predicted tumor and organ uptake for this GEP-NET population. Relevant organ uptake differences between [Ga-68]Ga-DOTATATE and [Ga-68]Ga-HA-DOTATATE were caused by different affinity profiles, while tumor uptake was mainly affected by tumor blood flow and blood volume. Furthermore, tumor sink predictions showed that for the majority of patients a tumor sink effect is not expected to be clinically relevant.
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| 23. |
- Siebinga, Hinke, et al.
(författare)
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Predicting [177Lu]Lu-HA-DOTATATE kidney and tumor accumulation based on [68Ga]Ga-HA-DOTATATE diagnostic imaging using semi-physiological population pharmacokinetic modeling
- 2023
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Ingår i: EJNMMI Physics. - : Springer. - 2197-7364. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrediction of [177Lu]Lu-HA-DOTATATE kidney and tumor uptake based on diagnostic [68Ga]Ga-HA-DOTATATE imaging would be a crucial step for precision dosing of [177Lu]Lu-HA-DOTATATE. In this study, the population pharmacokinetic (PK) differences between [177Lu]Lu-HA-DOTATATE and [68Ga]Ga-HA-DOTATATE were assessed and subsequently [177Lu]Lu-HA-DOTATATE was predicted based on [68Ga]Ga-HA-DOTATATE imaging.MethodsA semi-physiological nonlinear mixed-effects model was developed for [68Ga]Ga-HA-DOTATATE and [177Lu]Lu-HA-DOTATATE, including six compartments (representing blood, spleen, kidney, tumor lesions, other somatostatin receptor expressing organs and a lumped rest compartment). Model parameters were fixed based on a previously developed physiologically based pharmacokinetic model for [68Ga]Ga-HA-DOTATATE. For [177Lu]Lu-HA-DOTATATE, PK parameters were based on literature values or estimated based on scan data (four time points post-injection) from nine patients. Finally, individual [177Lu]Lu-HA-DOTATATE uptake into tumors and kidneys was predicted based on individual [68Ga]Ga-HA-DOTATATE scan data using Bayesian estimates. Predictions were evaluated compared to observed data using a relative prediction error (RPE) for both area under the curve (AUC) and absorbed dose. Lastly, to assess the predictive value of diagnostic imaging to predict therapeutic exposure, individual prediction RPEs (using Bayesian estimation) were compared to those from population predictions (using the population model).ResultsPopulation uptake rate parameters for spleen, kidney and tumors differed by a 0.29-fold (15% relative standard error (RSE)), 0.49-fold (15% RSE) and 1.43-fold (14% RSE), respectively, for [177Lu]Lu-HA-DOTATATE compared to [68Ga]Ga-HA-DOTATATE. Model predictions adequately described observed data in kidney and tumors for both peptides (based on visual inspection of goodness-of-fit plots). Individual predictions of tumor uptake were better (RPE AUC –40 to 28%) compared to kidney predictions (RPE AUC –53 to 41%). Absorbed dose predictions were less predictive for both tumor and kidneys (RPE tumor and kidney –51 to 44% and –58 to 82%, respectively). For most patients, [177Lu]Lu-HA-DOTATATE tumor accumulation predictions based on individual PK parameters estimated from diagnostic imaging outperformed predictions based on population parameters.ConclusionOur semi-physiological PK model indicated clear differences in PK parameters for [68Ga]Ga-HA-DOTATATE and [177Lu]Lu-HA-DOTATATE. Diagnostic images provided additional information to individually predict [177Lu]Lu-HA-DOTATATE tumor uptake compared to using a population approach. In addition, individual predictions indicated that many aspects, apart from PK differences, play a part in predicting [177Lu]Lu-HA-DOTATATE distribution.
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| 24. |
- van den Berg, Emma, et al.
(författare)
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Profiling amyloid-β peptides as biomarkers for cerebral amyloid angiopathy
- 2024
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Ingår i: JOURNAL OF NEUROCHEMISTRY. - 0022-3042 .- 1471-4159.
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Tidskriftsartikel (refereegranskat)abstract
- Brain amyloid-beta (A beta) deposits are key pathological hallmarks of both cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Microvascular deposits in CAA mainly consist of the A beta(40) peptide, whereas A beta(42) is the predominant variant in parenchymal plaques in AD. The relevance in pathogenesis and diagnostic accuracy of various other A beta isoforms in CAA remain understudied. We aimed to investigate the biomarker potential of various A beta isoforms in cerebrospinal fluid (CSF) to differentiate CAA from AD pathology. We included 25 patients with probable CAA, 50 subjects with a CSF profile indicative of AD pathology (AD-like), and 23 age- and sex-matched controls. CSF levels of A beta(1-34), A beta(1-37), A beta(1-38), A beta(1-39), A beta(1-40), and A beta(1-42) were quantified by liquid chromatography mass spectrometry. Lower CSF levels of all six A beta peptides were observed in CAA patients compared with controls (p = 0.0005-0.03). Except for A beta(1-42) (p = 1.0), all peptides were decreased in CAA compared with AD-like subjects (p = 0.007-0.03). Besides A beta(1-42), none of the A beta peptides were decreased in AD-like subjects compared with controls. All A beta peptides combined differentiated CAA from AD-like subjects better (area under the curve [AUC] 0.84) than individual peptide levels (AUC 0.51-0.75). Without A beta(1-42) in the model (since decreased A beta(1-42) served as AD-like selection criterion), the AUC was 0.78 for distinguishing CAA from AD-like subjects. CAA patients and AD-like subjects showed distinct disease-specific CSF A beta profiles. Peptides shorter than A beta(1-42) were decreased in CAA patients, but not AD-like subjects, which could suggest different pathological mechanisms between vascular and parenchymal A beta accumulation. This study supports the potential use of this panel of CSF A beta peptides to indicate presence of CAA pathology with high accuracy.
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