| 1. |
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| 2. |
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| 3. |
- Abgrall, N., et al.
(författare)
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The large enriched germanium experiment for neutrinoless double beta decay (LEGEND)
- 2017
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Ingår i: AIP Conference Proceedings. - : Author(s). - 1551-7616 .- 0094-243X. ; 1894
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Konferensbidrag (refereegranskat)abstract
- The observation of neutrinoless double-beta decay (0νββ) would show that lepton number is violated, reveal that neu-trinos are Majorana particles, and provide information on neutrino mass. A discovery-capable experiment covering the inverted ordering region, with effective Majorana neutrino masses of 15 - 50 meV, will require a tonne-scale experiment with excellent energy resolution and extremely low backgrounds, at the level of ∼0.1 count /(FWHM·t·yr) in the region of the signal. The current generation 76Ge experiments GERDA and the Majorana Demonstrator, utilizing high purity Germanium detectors with an intrinsic energy resolution of 0.12%, have achieved the lowest backgrounds by over an order of magnitude in the 0νββ signal region of all 0νββ experiments. Building on this success, the LEGEND collaboration has been formed to pursue a tonne-scale 76Ge experiment. The collaboration aims to develop a phased 0νββ experimental program with discovery potential at a half-life approaching or at 1028 years, using existing resources as appropriate to expedite physics results.
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| 4. |
- Teslovich, Tanya M., et al.
(författare)
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Biological, clinical and population relevance of 95 loci for blood lipids
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7307, s. 707-713
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Tidskriftsartikel (refereegranskat)abstract
- Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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| 5. |
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| 6. |
- Chatzikonstantinou, T, et al.
(författare)
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COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:12, s. 3444-3454
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.
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| 7. |
- Luyssaert, S., et al.
(författare)
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CO2 balance of boreal, temperate, and tropical forests derived from a global database
- 2007
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 13:12, s. 2509-2537
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Forskningsöversikt (refereegranskat)abstract
- Terrestrial ecosystems sequester 2.1 Pg of atmospheric carbon annually. A large amount of the terrestrial sink is realized by forests. However, considerable uncertainties remain regarding the fate of this carbon over both short and long timescales. Relevant data to address these uncertainties are being collected at many sites around the world, but syntheses of these data are still sparse. To facilitate future synthesis activities, we have assembled a comprehensive global database for forest ecosystems, which includes carbon budget variables (fluxes and stocks), ecosystem traits (e.g. leaf area index, age), as well as ancillary site information such as management regime, climate, and soil characteristics. This publicly available database can be used to quantify global, regional or biome-specific carbon budgets; to re-examine established relationships; to test emerging hypotheses about ecosystem functioning [e.g. a constant net ecosystem production (NEP) to gross primary production (GPP) ratio]; and as benchmarks for model evaluations. In this paper, we present the first analysis of this database. We discuss the climatic influences on GPP, net primary production (NPP) and NEP and present the CO2 balances for boreal, temperate, and tropical forest biomes based on micrometeorological, ecophysiological, and biometric flux and inventory estimates. Globally, GPP of forests benefited from higher temperatures and precipitation whereas NPP saturated above either a threshold of 1500 mm precipitation or a mean annual temperature of 10 degrees C. The global pattern in NEP was insensitive to climate and is hypothesized to be mainly determined by nonclimatic conditions such as successional stage, management, site history, and site disturbance. In all biomes, closing the CO2 balance required the introduction of substantial biome-specific closure terms. Nonclosure was taken as an indication that respiratory processes, advection, and non-CO2 carbon fluxes are not presently being adequately accounted for.
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| 8. |
- Saunois, M., et al.
(författare)
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The global methane budget 2000–2012
- 2016
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 8:2, s. 697-751
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Tidskriftsartikel (refereegranskat)abstract
- The global methane (CH4) budget is becoming an increasingly important component for managing realistic pathways to mitigate climate change. This relevance, due to a shorter atmospheric lifetime and a stronger warming potential than carbon dioxide, is challenged by the still unexplained changes of atmospheric CH4 over the past decade. Emissions and concentrations of CH4 are continuing to increase, making CH4 the second most important human-induced greenhouse gas after carbon dioxide. Two major difficulties in reducing uncertainties come from the large variety of diffusive CH4 sources that overlap geographically, and from the destruction of CH4 by the very short-lived hydroxyl radical (OH). To address these difficulties, we have established a consortium of multi-disciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate research on the methane cycle, and producing regular (∼ biennial) updates of the global methane budget. This consortium includes atmospheric physicists and chemists, biogeochemists of surface and marine emissions, and socio-economists who study anthropogenic emissions. Following Kirschke et al. (2013), we propose here the first version of a living review paper that integrates results of top-down studies (exploiting atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up models, inventories and data-driven approaches (including process-based models for estimating land surface emissions and atmospheric chemistry, and inventories for anthropogenic emissions, data-driven extrapolations). For the 2003–2012 decade, global methane emissions are estimated by top-down inversions at 558 Tg CH4 yr−1, range 540–568. About 60 % of global emissions are anthropogenic (range 50–65 %). Since 2010, the bottom-up global emission inventories have been closer to methane emissions in the most carbon-intensive Representative Concentrations Pathway (RCP8.5) and higher than all other RCP scenarios. Bottom-up approaches suggest larger global emissions (736 Tg CH4 yr−1, range 596–884) mostly because of larger natural emissions from individual sources such as inland waters, natural wetlands and geological sources. Considering the atmospheric constraints on the top-down budget, it is likely that some of the individual emissions reported by the bottom-up approaches are overestimated, leading to too large global emissions. Latitudinal data from top-down emissions indicate a predominance of tropical emissions (∼ 64 % of the global budget, < 30° N) as compared to mid (∼ 32 %, 30–60° N) and high northern latitudes (∼ 4 %, 60–90° N). Top-down inversions consistently infer lower emissions in China (∼ 58 Tg CH4 yr−1, range 51–72, −14 %) and higher emissions in Africa (86 Tg CH4 yr−1, range 73–108, +19 %) than bottom-up values used as prior estimates. Overall, uncertainties for anthropogenic emissions appear smaller than those from natural sources, and the uncertainties on source categories appear larger for top-down inversions than for bottom-up inventories and models. The most important source of uncertainty on the methane budget is attributable to emissions from wetland and other inland waters. We show that the wetland extent could contribute 30–40 % on the estimated range for wetland emissions. Other priorities for improving the methane budget include the following: (i) the development of process-based models for inland-water emissions, (ii) the intensification of methane observations at local scale (flux measurements) to constrain bottom-up land surface models, and at regional scale (surface networks and satellites) to constrain top-down inversions, (iii) improvements in the estimation of atmospheric loss by OH, and (iv) improvements of the transport models integrated in top-down inversions. The data presented here can be downloaded from the Carbon Dioxide Information Analysis Center (http://doi.org/10.3334/CDIAC/GLOBAL_METHANE_BUDGET_2016_V1.1) and the Global Carbon Project.
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| 9. |
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| 10. |
- Riley, M A, et al.
(författare)
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Beyond band termination in Er-157 and the search for wobbling excitations in strongly deformed Hf-174
- 2005
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 31:10, s. 1735-1740
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Tidskriftsartikel (refereegranskat)abstract
- High-spin terminating bands in heavy nuclei were first identified in nuclei around Er-158(90). While examples of special terminating states have been identified in a number of erbium isotopes, almost nothing is known about the states lying beyond band termination. In the present work the high-spin structure of Er-157 has been studied using the Gammasphere spectrometer. The subject of triaxial superdeformation and 'wobbling' modes in Lu nuclei has rightly attracted a great deal of attention. Very recently, four strongly or superdeformed (SD) sequences have been observed in Hf-174 and ultimate cranker calculations predict, such structures may have significant triaxial deformation. We have performed two experiments in an attempt to verify the possible triaxial nature of these bands. A lifetime measurement was performed to confirm the large (and similar) deformation of the bands. In addition, a high-statistics, thin-target experiment was run to search for linking transitions between the SD bands and possible wobbling modes.
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| 11. |
- Riley, M. A., et al.
(författare)
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Observation of states beyond band termination in Er-156,Er-157,Er-158 and strongly deformed structures in Hf-173,Hf-174,Hf-175
- 2006
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Ingår i: Physica Scripta. - 0031-8949. ; T125, s. 123-126
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Tidskriftsartikel (refereegranskat)abstract
- High-spin terminating bands in heavy nuclei were first identified in nuclei around Er-158(90). While examples of terminating states have been identified in a number of erbium isotopes, almost nothing is known about the states lying beyond band termination. In the present work, the high-spin structure of Er-156,Er-157,Er-158 has been studied using the Gammasphere spectrometer. The subject of triaxial superdeformation and 'wobbling' modes in Lu nuclei has rightly attracted a great deal of attention. Very recently four strongly or superdeformed (SD) sequences have been observed in Hf-174, and cranking calculations using the Ultimate Cranker code predict that such structures may have significant triaxial deformation. We have performed two experiments in an attempt to verify the possible triaxial nature of these bands. A lifetime measurement was performed to confirm the large (and similar) deformation of the bands. In addition, a high-statistics, thin-target experiment took place to search for linking transitions between the SD bands, possible wobbling modes, and new SD band structures.
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| 12. |
- Saunois, M., et al.
(författare)
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Variability and quasi-decadal changes in the methane budget over the period 2000–2012
- 2017
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 17:18, s. 11135-11161
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Tidskriftsartikel (refereegranskat)abstract
- Following the recent Global Carbon Project (GCP) synthesis of the decadal methane (CH4) budget over 2000–2012 (Saunois et al., 2016), we analyse here the same dataset with a focus on quasi-decadal and inter-annual variability in CH4 emissions. The GCP dataset integrates results from top-down studies (exploiting atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up models (including process-based models for estimating land surface emissions and atmospheric chemistry), inventories of anthropogenic emissions, and data-driven approaches. The annual global methane emissions from top-down studies, which by construction match the observed methane growth rate within their uncertainties, all show an increase in total methane emissions over the period 2000–2012, but this increase is not linear over the 13 years. Despite differences between individual studies, the mean emission anomaly of the top-down ensemble shows no significant trend in total methane emissions over the period 2000–2006, during the plateau of atmospheric methane mole fractions, and also over the period 2008–2012, during the renewed atmospheric methane increase. However, the top-down ensemble mean produces an emission shift between 2006 and 2008, leading to 22 [16–32] Tg CH4 yr−1 higher methane emissions over the period 2008–2012 compared to 2002–2006. This emission increase mostly originated from the tropics, with a smaller contribution from mid-latitudes and no significant change from boreal regions. The regional contributions remain uncertain in top-down studies. Tropical South America and South and East Asia seem to contribute the most to the emission increase in the tropics. However, these two regions have only limited atmospheric measurements and remain therefore poorly constrained. The sectorial partitioning of this emission increase between the periods 2002–2006 and 2008–2012 differs from one atmospheric inversion study to another. However, all top-down studies suggest smaller changes in fossil fuel emissions (from oil, gas, and coal industries) compared to the mean of the bottom-up inventories included in this study. This difference is partly driven by a smaller emission change in China from the top-down studies compared to the estimate in the Emission Database for Global Atmospheric Research (EDGARv4.2) inventory, which should be revised to smaller values in a near future. We apply isotopic signatures to the emission changes estimated for individual studies based on five emission sectors and find that for six individual top-down studies (out of eight) the average isotopic signature of the emission changes is not consistent with the observed change in atmospheric 13CH4. However, the partitioning in emission change derived from the ensemble mean is consistent with this isotopic constraint. At the global scale, the top-down ensemble mean suggests that the dominant contribution to the resumed atmospheric CH4 growth after 2006 comes from microbial sources (more from agriculture and waste sectors than from natural wetlands), with an uncertain but smaller contribution from fossil CH4 emissions. In addition, a decrease in biomass burning emissions (in agreement with the biomass burning emission databases) makes the balance of sources consistent with atmospheric 13CH4 observations. In most of the top-down studies included here, OH concentrations are considered constant over the years (seasonal variations but without any inter-annual variability). As a result, the methane loss (in particular through OH oxidation) varies mainly through the change in methane concentrations and not its oxidants. For these reasons, changes in the methane loss could not be properly investigated in this study, although it may play a significant role in the recent atmospheric methane changes as briefly discussed at the end of the paper.
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| 13. |
- Abila, R., et al.
(författare)
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Oil extraction imperils Africa’s Great Lakes
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6312, s. 561-562
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- As the world's demands for hydrocarbons increase (1), remote areas previously made inaccessible by technological limitations are now being prospected for oil and gas deposits. Virtually unnoticed by the public, such activities are ongoing in the East African Great Lakes region, threatening these ecosystems famed for their hyper-diverse biota, including the unique adaptive radiations of cichlid fishes (2). Countries in the region see exploitation of hydrocarbon reserves as a vital economic opportunity. In the Lake Albert region of Uganda, for example, the government foresees a $3.6 billion oil profit per year starting in 2018—a sum almost as high as the country's current annual budget (3). However, oil extraction in the East African Great Lakes region poses grave risks to the environment and local communities.
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| 14. |
- Basu, Anwesha, et al.
(författare)
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Highly deformed band structures due to core excitations in Xe 123
- 2021
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Ingår i: Physical Review C. - 2469-9985. ; 103:1
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Tidskriftsartikel (refereegranskat)abstract
- High-spin states in Xe123 were populated in the Se80(Ca48, 5n)Xe123 reaction at a beam energy of 207 MeV. γ-ray coincidence events were recorded with the Gammasphere spectrometer. Four new high-spin bands have been discovered in this nucleus. The bands are compared with those calculated within the framework of cranked Nilsson-Strutinsky and cranked Nilsson-Strutinsky-Bogoliubov models. It is concluded that the configurations of the bands involve two-proton excitations across the Z=50 as well as excitation of neutrons across the N=82 shell gaps resulting in a large deformation, 2≈0.30 and γ≈5°C.
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| 15. |
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| 16. |
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| 17. |
- Stolk, Lisette, et al.
(författare)
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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
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Tidskriftsartikel (refereegranskat)abstract
- To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
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| 18. |
- Yadav, R. B., et al.
(författare)
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Identification of triaxial strongly deformed bands in Hf-168
- 2008
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 78:4
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Tidskriftsartikel (refereegranskat)abstract
- Possible decay pathways associated with three candidates for triaxial strongly deformed (TSD) bands in Hf-168 have been investigated. The spin and excitation energy of the strongest band, TSD1, were determined approximately based on gamma-ray coincidence relationships. Discrete links were established for the second band. The overall agreement between the observed properties of the bands and cranking calculations using the ULTIMATE CRANKER code provides strong support for an interpretation where band TSD1 is associated with a TSD minimum, (epsilon(2),gamma)similar to(0.43,20(degrees)), involving the pi(i(13/2))(2) and the nu(j(15/2)) high-j orbitals. This constitutes the first identification of a TSD band in Hf isotopes, which has been long-predicted by theoretical studies. The second band is understood as being associated with a near-prolate shape and a deformation enhanced with respect to the normal deformed bands. It is proposed to be built on the pi(i(13/2)h(9/2))circle times nu(i(13/2))(2) configuration.
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| 19. |
- Al-Khatib, A, et al.
(författare)
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Transition to non-collective states at high spin in Xe-124
- 2008
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 36:1, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in Xe-124 were populated in the reaction Se-82(Ca-48, 6n) Xe-124 and gamma-ray coincidence relationships were measured with the Gammasphere spectrometer. Two new bands are observed and several of the previously known bands are extended in the high-as well as in the low-spin region. Two irregular high-spin structures are also added. The irregularities are a fingerprint of a transition from collective to non-collective behaviour. Configuration assignments to the new structures are proposed on the basis of systematics and by comparing experimental properties with calculations within the framework of the cranking model.
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| 20. |
- Aulchenko, Yurii S, et al.
(författare)
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Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:1, s. 47-55
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
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| 21. |
- Basu, Anwesha, et al.
(författare)
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Evolution of collective and noncollective structures in Xe 123
- 2020
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Ingår i: Physical Review C. - 2469-9985. ; 101:2
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Tidskriftsartikel (refereegranskat)abstract
- An experiment involving a heavy-ion-induced fusion-evaporation reaction was carried out where high-spin states of Xe123 were populated in the Se80(Ca48,5n)Xe123 reaction at 207 MeV beam energy. Gamma-ray coincidence events were recorded with the Gammasphere Ge detector array. The previously known level scheme was confirmed and enhanced with the addition of five new band structures and several interband transitions. Cranked Nilsson-Strutinsky (CNS) calculations were performed and compared with the experimental results in order to assign configurations to the bands.
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| 22. |
- Granier, A., et al.
(författare)
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Evidence for soil water control on carbon and water dynamics in European forests during the extremely dry year: 2003
- 2007
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Ingår i: Agricultural and Forest Meteorology. - : Elsevier BV. - 1873-2240 .- 0168-1923. ; 143:1-2, s. 123-145
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Tidskriftsartikel (refereegranskat)abstract
- The drought of 2003 was exceptionally severe in many regions of Europe, both in duration and in intensity. In some areas, especially in Germany and France, it was the strongest drought for the last 50 years, lasting for more than 6 months. We used continuous carbon and water flux measurements at 12 European monitoring sites covering various forest ecosystem types and a large climatic range in order to characterise the consequences of this drought on ecosystems functioning. As soil water content in the root zone was only monitored in a few sites, a daily water balance model was implemented at each stand to estimate the water balance terms: trees and understorey transpiration, rainfall interception, throughfall, drainage in the different soil layers and soil water content. This model calculated the onset date, duration and intensity of the soil water shortage (called water stress) using measured climate and site properties: leaf area index and phenology that both determine tree transpiration and rainfall interception, soil characteristics and root distribution, both influencing water absorption and drainage. At sites where soil water content was measured, we observed a good agreement between measured and modelled soil water content. Our analysis showed a wide spatial distribution of drought stress over Europe, with a maximum intensity within a large band extending from Portugal to NE Germany. Vapour fluxes in all the investigated sites were reduced by drought, due to stomatal closure, when the relative extractable water in soil (REW) dropped below ca. 0.4. Rainfall events during the drought, however, typically induced rapid restoration of vapour fluxes. Similar to the water vapour fluxes, the net ecosystem production decreased with increasing water stress at all the sites. Both gross primary production (GPP) and total ecosystem respiration (TER) also decreased when REW dropped below 0.4 and 0.2, for GPP and TER, respectively. A higher sensitivity to drought was found in the beech, and surprisingly, in the broadleaved Mediterranean forests; the coniferous stands (spruce and pine) appeared to be less drought-sensitive. The effect of drought on tree growth was also large at the three sites where the annual tree growth was measured. Especially in beech, this growth reduction was more pronounced in the year following the drought (2004). Such lag effects on tree growth should be considered an important feature in forest ecosystems, which may enhance vulnerability to more frequent climate extremes.
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| 23. |
- Henning, G., et al.
(författare)
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Exploring the stability of super heavy elements: First measurement of the fission barrier of 254No
- 2014
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Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 2101-6275 .- 2100-014X. ; 66
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Konferensbidrag (refereegranskat)abstract
- The gamma-ray multiplicity and total energy emitted by the heavy nucleus 254No have been measured at 2 different beam energies. From these measurements, the initial distributions of spin I and excitation energy E * of 254No were constructed. The distributions display a saturation in excitation energy, which allows a direct determination of the fission barrier. 254No is the heaviest shell-stabilized nucleus with a measured fission barrier. © Owned by the authors, published by EDP Sciences, 2014.
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| 24. |
- Henning, G., et al.
(författare)
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Fission Barrier of Superheavy Nuclei and Persistence of Shell Effects at High Spin: Cases of No-254 and Th-220
- 2014
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 113:26
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Tidskriftsartikel (refereegranskat)abstract
- We report on the first measurement of the fission barrier height in a heavy shell-stabilized nucleus. The fission barrier height of No-254 is measured to be B-f = 6.0 +/- 0.5 MeV at spin 15 (h) over bar and, by extrapolation, B-f = 6.6 +/- 0.9 MeV at spin 0 (h) over bar. This information is deduced from the measured distribution of entry points in the excitation energy versus spin plane. The same measurement is performed for Th-220 and only a lower limit of the fission barrier height can be determined: B-f (I) > 8 MeV. Comparisons with theoretical fission barriers test theories that predict properties of superheavy elements.
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| 25. |
- Hyvonen, R., et al.
(författare)
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The likely impact of elevated [CO2], nitrogen deposition, increased temperature and management on carbon sequestration in temperate and boreal forest ecosystems: a literature review
- 2007
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Ingår i: New Phytologist. - Cambridge : Wiley. - 0028-646X .- 1469-8137. ; 173:3, s. 463-480
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Forskningsöversikt (refereegranskat)abstract
- Temperate and boreal forest ecosystems contain a large part of the carbon stored on land, in the form of both biomass and soil organic matter. Increasing atmospheric [CO2], increasing temperature, elevated nitrogen deposition and intensified management will change this C store. Well documented single-factor responses of net primary production are: higher photosynthetic rate (the main [CO2] response); increasing length of growing season (the main temperature response); and higher leaf-area index (the main N deposition and partly [CO2] response). Soil organic matter will increase with increasing litter input, although priming may decrease the soil C stock initially, but litter quality effects should be minimal (response to [CO2], N deposition, and temperature); will decrease because of increasing temperature; and will increase because of retardation of decomposition with N deposition, although the rate of decomposition of high-quality litter can be increased and that of low-quality litter decreased. Single-factor responses can be misleading because of interactions between factors, in particular those between N and other factors, and indirect effects such as increased N availability from temperature-induced decomposition. In the long term the strength of feedbacks, for example the increasing demand for N from increased growth, will dominate over short-term responses to single factors. However, management has considerable potential for controlling the C store.
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| 26. |
- Kelsall, N. S., et al.
(författare)
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Testing mean-field models near the N=Z line : gamma-ray spectroscopy of the T-z=1/2 nucleus Kr-73
- 2002
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 65:4
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in the N=Z+1 nucleus Kr-73 have been investigated using the Ca-40(Ar-36,2pn) and Ca-40(Ca-40,alpha2pn) reactions at 145 and 160 MeV, respectively. gamma rays were detected using the Gammasphere array and events were recorded in coincidence with charged-particle and neutron detectors. The three previously observed bands were extended to high spin, and a new unfavored positive-parity band has been observed. The alignment characteristics and decay properties of the bands are all consistent with large-deformation prolate rotation, with no clear evidence for oblate bands or shape coexistence. This is quite different from neighboring Kr-72,Kr-74, indicating a strong shape-stabilizing role for the valence neutron. The experimental results are compared to extended total Routhian surface, cranked Nilsson Strutinsky, and cranked relativistic mean-field calculations. The results suggest that the paired calculations lack some important physics. Neutron-proton correlations may be the missing ingredient. There is also evidence for an unusual band crossing in the negative-parity bands, which may indicate the presence of T=0 pairing correlations. At high spin all the models can reproduce the experimental data.
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| 27. |
- Lopez-Martens, A., et al.
(författare)
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Stability and synthesis of superheavy elements: Fighting the battle against fission - example of No-254
- 2016
-
Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 2101-6275 .- 2100-014X. - 9782759890118 ; 131
-
Konferensbidrag (refereegranskat)abstract
- Superheavy nuclei exist solely due to quantum shell effects, which create a pocket in the potential-energy surface of the nucleus, thus providing a barrier against spontaneous fission. Determining the height of the fission barrier and its angular-momentum dependence is important to quantify the role that microscopic shell corrections play in enhancing and extending the limits of nuclear stability. In this talk, the first measurement of a fission barrier in the very heavy nucleus No-254 will be presented.
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| 28. |
- Marsh, J. C., et al.
(författare)
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Identification of triaxial strongly deformed bands in Hf-164
- 2013
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 88:4
-
Tidskriftsartikel (refereegranskat)abstract
- Two new rotational bands of distinct character have been identified in Hf-164. They are suggested to correspond to the long-anticipated triaxial strongly deformed (TSD) bands predicted by theoretical studies. The bands have been linked to known states, and the level spins and energies could be determined. The bands are also substantially stronger in intensity and are located at lower spins than the previously observed TSD bands in Hf-168, hereby making Hf-164 the best even-even system so far for the study of TSD structures in the A similar to 160 mass region. Cranking calculations based on the modified-oscillator model suggest that the bands are associated with four-quasiparticle configurations that involve high-j intruder (i(13/2))(2) proton orbitals.
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| 29. |
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| 30. |
- Nag, Somnath, et al.
(författare)
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Collective and noncollective excitations in Te-122
- 2013
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 88:4
-
Tidskriftsartikel (refereegranskat)abstract
- High-spin states in Te-122 were populated in the reaction Se-82(Ca-48, alpha 4n) Te-122 at a beam energy of 200 MeV and gamma-ray coincidences weremeasured with the Gammasphere spectrometer. The previously known level scheme was extended to considerably higher spin. Maximally aligned states and several high-energy transitions feeding into some of these levels were observed. In addition, seven collective high-spin bands were discovered for the first time in this nucleus. The experimental results are compared with cranked Nilsson-Strutinsky model calculations and possible configuration assignments to the new high-spin structures are discussed.
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| 31. |
- Nag, Somnath, et al.
(författare)
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Observation of high-spin bands with large moments of inertia in Xe 124
- 2016
-
Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 94:3
-
Tidskriftsartikel (refereegranskat)abstract
- High-spin states in Xe124 have been populated using the Se80(Ca48,4n) reaction at a beam energy of 207 MeV and high-multiplicity, γ-ray coincidence events were measured using the Gammasphere spectrometer. Six high-spin bands with large moments of inertia, similar to those observed in neighboring nuclei, have been observed. The experimental results are compared with calculations within the framework of the cranked Nilsson-Strutinsky model. It is suggested that the configurations of the bands involve excitations of protons across the Z=50 shell gap coupled to neutrons within the N=50-82 shell or excited across the N=82 shell closure.
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| 32. |
- Nag, Somnath, et al.
(författare)
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Revised level structure of Te-120
- 2014
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 90:3
-
Tidskriftsartikel (refereegranskat)abstract
- The level scheme of the nucleus Te-120, populated in the reaction Se-80(Ca-48, alpha 4n), was reinvestigated using gamma-ray coincidence data measured with the Gammasphere spectrometer. Previously, five high-spin rotational bands were discovered in this nucleus. The present reinvestigation revealed that the decay of band b1 is more complex than suggested in the earlier work and that it cannot be uniquely determined. Furthermore, a number of new transitions are added to the level scheme. The implications for the spin assignments and excitation energies of the five bands and for comparisons with cranked Nilsson-Strutinsky calculations are discussed.
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| 33. |
- Singh, Purnima, et al.
(författare)
-
High-spin rotational bands in I-123
- 2012
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 86:6
-
Tidskriftsartikel (refereegranskat)abstract
- High-spin states in I-123 were populated in the reaction Se-80(Ca-48,p4n)I-123 at a beam energy of 207 MeV and gamma-ray coincidence events were measured using the Gammasphere spectrometer. Three weakly populated, high-spin rotational bands have been discovered with characteristics similar to those of the long collective bands recently observed in other nuclei of this mass region. Configuration assignments are proposed based on calculations within the framework of the cranked Nilsson-Strutinsky approach. DOI: 10.1103/PhysRevC.86.067305
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| 34. |
- Singh, Purnima, et al.
(författare)
-
Highly deformed high-spin band in I-125
- 2011
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 84:2
-
Tidskriftsartikel (refereegranskat)abstract
- High-spin states in I-125 have been investigated using the reaction Se-82(Ca-48, p4n) at a beam energy of 200 MeV and gamma-ray coincidence events were detected using the Gammasphere spectrometer. A deformed rotational band, extending up to I-pi = 95/2(-), was observed for the first time in a heavier odd-A iodine nucleus. The characteristics of the band are very similar to those of the highly deformed bands observed recently in neighboring nuclei and it is essentially identical to one of the previously known bands in Xe-126. The experimental results are compared to cranked Nilsson-Strutinsky calculations and possible configurations for the band are discussed.
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| 35. |
- Singh, Purnima, et al.
(författare)
-
Noncollective aligned and antialigned states in I-125
- 2010
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 82:3
-
Tidskriftsartikel (refereegranskat)abstract
- High-spin states in I-125 were populated using the reaction Se-82(Ca-48, p4n) at a beam energy of 200 MeV and gamma-ray coincidence events were acquired with the Gammasphere spectrometer. The level scheme of I-125 was extended considerably. In particular, maximally aligned states involving all eleven particles outside the Sn-114 core were observed. Comparison with cranked Nilsson-Strutinsky calculations suggests that three of these states are the final I-max states in terminating bands with all spin vectors aligned along a common axis. In two of these, one spin vector is antialigned and points in the opposite direction. In one of the states two spin vectors are antialigned. This is the first observation of a state with such a structure.
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| 36. |
- Sohler, D., et al.
(författare)
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Yrast states of the proton drip line nucleus 106 Sb
- 1999
-
Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993 .- 0556-2813 .- 1089-490X. ; 59:3, s. 1324-1327
-
Tidskriftsartikel (refereegranskat)abstract
- Yrast states of [Formula Presented] have been investigated in the [Formula Presented] reaction using in-beam [Formula Presented]-spectroscopic methods and in the [Formula Presented] reaction performing delayed [Formula Presented] and conversion electron studies. A new isomeric state was found at 103 keV with [Formula Presented] The number of states and transitions in the proposed level scheme have been doubled. The experimental results are discussed within the framework of the shell model. © 1999 The American Physical Society.
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| 37. |
- Svensson, C. E., et al.
(författare)
-
Collective rotational motion in the N=Z nucleus 36Ar
- 2001
-
Ingår i: Nuclear Physics A. - 0375-9474. ; 682:1-4, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- A superdeformed rotational band has been identified in the N = Z nucleus 36Ar, firmly linked to known low-spin states, and observed to its high-spin termination at Iπ = 16+. Lifetime measurements by the Doppler shift attenuation method establish a large low-spin deformation (β2 ≈ 0.46) and a decrease in the collectivity as the band approaches termination. Comparisons with cranked Nilsson-Strutinsky and large-scale spherical shell model calculations lead to a consistent description of the band based on a configuration in which four particles are promoted to the pf shell. With two major shells active for both protons and neutrons, yet a valence space dimension small enough to be approached from the shell model perspective, this band offers an excellent opportunity to investigate the microscopic structure of collective rotational motion in nuclei.
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| 38. |
- Svensson, C. E., et al.
(författare)
-
Decay Out of the Doubly Magic Superdeformed Band in the N=Z Nucleus 60Zn
- 1999
-
Ingår i: Physical Review Letters. - 1079-7114. ; 82:17, s. 3400-3403
-
Tidskriftsartikel (refereegranskat)abstract
- The doubly magic superdeformed band in the N = Z nucleus Zn-60 has been identified. Linking transitions connecting this band to the yrast line provide the first spin, parity, and excitation energy measurements for superdeformed states in the A similar to 60 region. The stretched-E2 character and relatively large B(E2) values of these transitions suggest a nonstatistical decay-out process.
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| 39. |
- Svensson, C. E., et al.
(författare)
-
Lifetimes of superdeformed rotational states in 36Ar
- 2001
-
Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 63:6, s. 613011-613015
-
Tidskriftsartikel (refereegranskat)abstract
- Lifetimes have been measured in a superdeformed rotational band recently identified in the N = Z nucleus 36Ar. A large low-spin quadrupole deformation (β2=0.46±0.03) is confirmed and a decrease in the collectivity is observed as the high-spin band termination at Iπ=16+ is approached. Detailed comparisons of the experimental B(E2) values with the results of cranked Nilsson-Strutinsky and large-scale (s1/2d3/2)-pf spherical shell model calculations indicate the need for a more refined treatment of transition matrix elements close to termination in the former, and the inclusion of the complete sd-pf model space in the latter description of this highly-collective rotational band.
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| 40. |
- Svensson, C. E., et al.
(författare)
-
Lifetimes of superdeformed rotational states in [Formula Presented]
- 2001
-
Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 63:6, s. 5-5
-
Tidskriftsartikel (refereegranskat)abstract
- Lifetimes have been measured in a superdeformed rotational band recently identified in the [Formula Presented] nucleus [Formula Presented] A large low-spin quadrupole deformation [Formula Presented] is confirmed and a decrease in the collectivity is observed as the high-spin band termination at [Formula Presented] is approached. Detailed comparisons of the experimental [Formula Presented] values with the results of cranked Nilsson-Strutinsky and large-scale [Formula Presented] spherical shell model calculations indicate the need for a more refined treatment of transition matrix elements close to termination in the former, and the inclusion of the complete [Formula Presented] model space in the latter description of this highly-collective rotational band.
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| 41. |
- Svensson, C. E., et al.
(författare)
-
Superdeformation in the N = z Nucleus 36Ar : Experimental, deformed mean field, and spherical shell model descriptions
- 2000
-
Ingår i: Physical Review Letters. - 0031-9007. ; 85:13, s. 2693-2696
-
Tidskriftsartikel (refereegranskat)abstract
- A superdeformed rotational band has been identified in 36Ar, linked to known low-spin states, and observed to its high-spin termination at Iπ = 16+. Cranked Nilsson-Strutinsky and spherical shell model calculations assign the band to a configuration in which four pf-shell orbitals are occupied, leading to a low-spin deformation β2 ≈ 0.45. Two major shells are active for both protons and neutrons, yet the valence space remains small enough to be confronted with the shell model. This band thus provides an ideal case to study the microscopic structure of collective rotational motion.
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| 42. |
- Wadsworth, R., et al.
(författare)
-
Terminating states in the positive-parity structures of As 67
- 2018
-
Ingår i: Physical Review C. - 2469-9985. ; 98:2
-
Tidskriftsartikel (refereegranskat)abstract
- The energy levels and γ-ray decay scheme of the positive-parity states in the Tz=12 nucleus As67 have been studied by using the Ca40(Ar36,2αp)As67 reaction at a beam energy of 145 MeV. Two new band structures have been identified which can be connected to the previously known levels. The results for these bands are compared with configuration-dependent cranked Nilsson-Strutinsky calculations. The good level of agreement between theory and experiment suggests that these structures can be interpreted in terms of configurations that involve three g92 particles and that both possess noncollective terminating states.
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| 43. |
- Wijns, W, et al.
(författare)
-
Myocardial revascularization
- 2011
-
Ingår i: REVISTA PORTUGUESA DE CARDIOLOGIA. - : Elsevier BV. - 0870-2551 .- 2174-2049. ; 30:12, s. 951-1005
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 44. |
- Yuan, W., et al.
(författare)
-
Thermal adaptation of net ecosystem exchange
- 2011
-
Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 8:6, s. 1453-1463
-
Tidskriftsartikel (refereegranskat)abstract
- Thermal adaptation of gross primary production and ecosystem respiration has been well documented over broad thermal gradients. However, no study has examined their interaction as a function of temperature, i.e. the thermal responses of net ecosystem exchange of carbon (NEE). In this study, we constructed temperature response curves of NEE against temperature using 380 site-years of eddy covariance data at 72 forest, grassland and shrubland ecosystems located at latitudes ranging from similar to 29 degrees N to 64 degrees N. The response curves were used to define two critical temperatures: transition temperature (T-b) at which ecosystem transfer from carbon source to sink and optimal temperature (T-o) at which carbon uptake is maximized. T-b was strongly correlated with annual mean air temperature. T-o was strongly correlated with mean temperature during the net carbon uptake period across the study ecosystems. Our results imply that the net ecosystem exchange of carbon adapts to the temperature across the geographical range due to intrinsic connections between vegetation primary production and ecosystem respiration.
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| 45. |
- Baeten, P., et al.
(författare)
-
Determination of the subcriticality level using the Cf-252 source-detector method
- 2010
-
Ingår i: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 37:5, s. 740-752
-
Tidskriftsartikel (refereegranskat)abstract
- Measurement and monitoring of reactivity in a subcritical state, e.g. during the loading of a power reactor, has a clear safety relevance. The methods currently available for the measurement of k(eff) in stationary subcritical conditions should be improved as they refer to the critical state. This is also very important in the framework of ADS (accelerator driven systems) where the measurement of a subcritical level without knowledge of the critical state is looked for. An alternative way to achieve this is by mean of the Cf-252 source-detector method. The method makes use of three detectors inserted in the reactor: two "ordinary" neutron detectors and one Cf-252 source-detector which contains a small amount of Cf-252 that introduces neutrons in the system through spontaneous fission. By observing fissions through the detection system and correlating the signals of the three detectors, the reactivity rho (and hence the multiplication factor k) can be determined. Before the actual measurements took place, a suitable data acquisition system was realized in order to process the signals and compute the auto and cross power spectral densities. The measurements were then performed in the VENUS reactor, using the Cf-252 source-detector and two BF3 neutron detectors. The multiplication factor was determined using the Cf source method and compared with measurements using other methods and with computational results (Monte Carlo simulations). The Cf method was benchmarked at a UOX core to other experimental methods that used the critical state as reference and to calculations. Afterwards, the Cf source technique was analyzed in a MOX core to study the possible impact of a significant intrinsic source on the results. This benchmarking gives the possibility to validate the Cf method as a reliable technique for the measurement of subcritical levels in steady state and for cores with an intrinsic source like MOX or burnt fuel cores. (C) 2010 Elsevier Ltd. All rights reserved.
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| 46. |
- Bergström, Anders, et al.
(författare)
-
Grey wolf genomic history reveals a dual ancestry of dogs
- 2022
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 607:7918, s. 313-320
-
Tidskriftsartikel (refereegranskat)abstract
- The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000–30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.
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| 47. |
- Chiara, C. J., et al.
(författare)
-
Probing sd-fp Cross-shell Interactions via Terminating Configurations in 42Sc,43Sc
- 2007
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 75:5
-
Tidskriftsartikel (refereegranskat)abstract
- An experimental study of the lower fp-shell nuclei Sc-42,Sc-43 was performed via alpha pn and alpha p evaporation, respectively, from Ne-20 + Si-28 and Mg-24 + Mg-24 fusion-evaporation reactions. The experiments were conducted with the Gammasphere and Microball detector arrays. The level schemes of both nuclei have been extended considerably. Terminating states associated with the f(7/2)(n) and d(3/2)(-1)f(7/2)(n+1) configurations were identified in each nuclide and incorporated into detailed comparisons with neighboring nuclei and with shell model calculations. The energy differences between the terminating states provide a test of the sd-fp cross-shell interactions in these calculations.
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| 48. |
- Dahal, Prabin, et al.
(författare)
-
Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria : a WorldWide Antimalarial Resistance Network individual participant data meta-analysis
- 2019
-
Ingår i: Malaria Journal. - : BMC. - 1475-2875. ; 18
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections.Methods: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model.Results: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (rho): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [rho: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold.Conclusions: The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.
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| 49. |
- Dahal, Prabin, et al.
(författare)
-
Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy : an individual participant data meta-analysis
- 2022
-
Ingår i: Malaria Journal. - : Springer Nature. - 1475-2875. ; 21
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria.Methods: Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up.Results: Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged < 5 years) and 23 studies conducted in Asia and South America (5272 patients of all ages). Using molecular genotyping, 519 (14.0%) recurrences were ascribed as recrudescent infections. A 28 day artemether-lumefantrine (AL) efficacy trial would not have detected 58% [95% confidence interval (CI) 47-74%] of recrudescences in African children and 32% [95% CI 15-45%] in patients of all ages in Asia/South America. The corresponding estimate following a 42 day dihydroartemisinin-piperaquine (DP) efficacy trial in Africa was 47% [95% CI 19-90%] in children under 5 years old treated with > 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0-22%] in those treated with <= 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up following AL underestimated the risk of recrudescence by a median of 2.8 percentage points compared to day 63 estimates and those limited to 42 days following DP underestimated the risk of recrudescence by a median of 2.0 percentage points compared to day 42 estimates. The analysis was limited by few clinical trials following patients for longer than 42 days (9 out of 83 trials) and the imprecision of PCR genotyping which overcalls recrudescence in areas of higher transmission biasing the later distribution.Conclusions: Restricting follow-up of clinical efficacy trials to day 28 for AL and day 42 for DP will miss a proportion of late recrudescent treatment failures but will have a modest impact in derived efficacy. The results highlight that as genotyping methods improve consideration should be given for trials with longer duration of follow-up to detect early indications of emerging drug resistance.
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| 50. |
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