| 1. |
- Munk, P., et al.
(författare)
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Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention.
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| 2. |
- Doornenbal, P., et al.
(författare)
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RISING: Gamma‐ray Spectroscopy with Radioactive Beams at GSI
- 2007
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Ingår i: AIP Conference Proceedings. - : AIP. - 0094-243X. - 9780735413283 ; 891, s. 99-107
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Konferensbidrag (refereegranskat)abstract
- The Rare Isotope Spectroscopic INvestigation at GSI (RISING) project is a major pan‐European collaboration. Its physics aims are the studies of exotic nuclear matter with abnormal proton‐to‐neutron ratios compared with naturally occurring isotopes. RISING combines the FRagment Separator (FRS) which allows relativistic energies and projectile fragmentation reactions with EUROBALL Ge Cluster detectors for γ spectroscopic research. The RISING setup can be used in two different configurations. Either the nuclei of interest are investigated after being stopped or the heavy ions hit a secondary target at relativistic energies and the thereby occurring excitations are studied. For the latter case, MINIBALL Ge detectors and the HECTOR array are used in addition. Example achievements of the Fast Beam setup are presented and compared to various shell model calculations, while for the Stopped Beam setup initial results are shown.
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| 3. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 4. |
- Chelban, V., et al.
(författare)
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PDXK mutations cause polyneuropathy responsive to pyridoxal 5′-phosphate supplementation
- 2019
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 86:2, s. 225-240
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification. Results: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5′-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization. Interpretation: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225–240. © 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
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| 5. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 6. |
- Lu, Yingchang, et al.
(författare)
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A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk.
- 2018
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:18, s. 5419-5430
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Tidskriftsartikel (refereegranskat)abstract
- .AbstractLarge-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.
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| 7. |
- Banu, A, et al.
(författare)
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108Sn Studied with Intermediate-energy Coulomb Excitation
- 2005
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 72:6
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Tidskriftsartikel (refereegranskat)abstract
- The unstable neutron-deficient Sn-108 isotope has been studied in inverse kinematics by intermediate-energy Coulomb excitation using the RISING/FRS experimental setup at GSI. This is the highest Z nucleus studied so far with this method. Its reduced transition probability B (E2;0(g.s.)(+)-> 2(1)(+)) has been measured for the first time. The extracted B(E2) value of 0.230(57)e(2) b(2) has been determined relative to the known value in the stable Sn-112 isotope. The result is discussed in the framework of recent large-scale shell model calculations performed with realistic effective interactions. The roles of particle-hole excitations of the Sn-100 core and of the Z=50 shell gap for the E2 polarization are investigated.
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| 8. |
- Cederkäll, Joakim, et al.
(författare)
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Sub-Barrier Coulomb Excitation of ^110Sn and Its Implications for the ^100Sn Shell Closure
- 2007
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Ingår i: Physical Review Letters. - 1079-7114. ; 98:17, s. 172501-
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Tidskriftsartikel (refereegranskat)abstract
- The first excited 2+ state of the unstable isotope 110Sn has been studied in safe Coulomb excitation at 2.82 MeV/u using the MINIBALL array at the REX-ISOLDE post accelerator at CERN. This is the first measurement of the reduced transition probability of this state using this method for a neutron deficient Sn isotope. The strength of the approach lies in the excellent peak-to-background ratio that is achieved. The extracted reduced transition probability, B(E2:0+-->2+)=0.220±0.022e2b2, strengthens the observation of the evolution of the B(E2) values of neutron deficient Sn isotopes that was observed recently in intermediate-energy Coulomb excitation of 108Sn. It implies that the trend of these reduced transition probabilities in the even-even Sn isotopes is not symmetric with respect to the midshell mass number A=116 as 100Sn is approached.
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| 9. |
- Grigorenko, L. V., et al.
(författare)
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Complete correlation studies of two-proton decays: Be-6 and Fe-45
- 2009
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 677:1-2, s. 30-35
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Tidskriftsartikel (refereegranskat)abstract
- The complete three-body correlation pictures are experimentally reconstructed for the two-proton decays of the Be-6 and (45)e ground states. We are able to see qualitative similarities and differences between these decays. They demonstrate very good agreement with the predictions of a theoretical three-body cluster model. Validity of the theoretical methods for treatment of the three-body Coulombic decays of this class is thus established by the broad range of lifetimes and nuclear masses spanned by these cases. Implementations for decay dynamics and nuclear structure of 2p emitters are discussed. (C) 2009 Elsevier B.V. All rights reserved.
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| 10. |
- Hamdi, Yosr, et al.
(författare)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 11. |
- Spolaore, P., et al.
(författare)
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Identification and study of the very neutron deficient nuclide I-111 : search for octupole correlations in the region of N approximate to Z approximate to 56
- 2001
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Ingår i: Nuclear Physics A. - 0375-9474 .- 1873-1554. ; 682, s. 387C-393C
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Tidskriftsartikel (refereegranskat)abstract
- High-spin states in the neutron-deficient nuclide I-111 have been populated with the fusion reaction Ni-58 + Ni-58 at a beam energy of 210 MeV, in an experiment performed at the Tandem Accelerator of the Laboratori Nazionali di Legnaro. The gamma spectrometer GASP was used in time coincidence with the ISIS Si-ball and the CAMEL recoil mass spectrometer for the positive identification of the nuclide. Gamma transitions and structure details previously attributed to I-111 by Other authors are only partially confirmed. The obtained level scheme includes new rotational bands and a new low lying structure which suggests the presence of octupole correlations at predicted rotational frequency values.
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| 12. |
- Becker, F, et al.
(författare)
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Status of the RISING Project at GSI
- 2005
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 25:Suppl 1, s. 719-722
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Tidskriftsartikel (refereegranskat)abstract
- The FRS-RISING set-up at GSI uses secondary radioactive beams at relativistic energies for nuclear structure studies. At GSI the fragmentation or fission of stable primary beams up to U-238 provide secondary beams with sufficient intensity to perform gamma-ray spectroscopy. The RISING set-up is described and results of the first RISING campaign are presented. New experimental methods at relativistic energies are being investigated. Future experiments focus on state-of-the art nuclear structure physics covering exotic nuclei all over the nuclear chart.
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| 13. |
- Bednarczyk, P, et al.
(författare)
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Status of the RISING Project at Relativistic Energies
- 2005
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 36:4, s. 1235-1244
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Tidskriftsartikel (refereegranskat)abstract
- The RISING project was designed to perform high-resolution gamma-ray spectroscopy with radioactive beams at GSI. Unstable beams were produced by fragmentation of relativistic heavy ion projectiles provided by the SIS synchrotron. The fragment separator FRS was used to select and to focus the exotic fragments at about 100A MeV energy on a secondary target. Various charged particle detectors enabled an event-by-event tracking of the incoming radioactive projectiles and the reaction products, thus allowing for a selection of the nuclei of interest and their velocity vector reconstruction. The gamma-ray detection system consisting of the EUROBALL Cluster Ge detectors and the large volume HECTOR BaF2 detectors measured prompt gamma-radiation from nuclei excited in the secondary target. Despite the huge Doppler shift due to the high recoil velocity (beta approximate to 40%), RISING achieved a gamma-energy resolution below 2%. The paper reviews the present status of the RISING project.
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| 14. |
- Gorska, M., et al.
(författare)
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Nuclear Structure far off Stability - RISING Campaigns
- 2007
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 38:4, s. 1219-1228
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Tidskriftsartikel (refereegranskat)abstract
- Nuclear structure studies at CST attracted recently increased interest for the results of present activities as well as for the future project FAIR. A broad range of physics phenomena can be addressed by high-resolution in-beam gamma-ray spectroscopy experiments with radioactive beams offered within the Rare Isotopes Spectroscopic INvestigation at GSI (RISING) project. It combined the EUROBALL Ge-Cluster detectors, the MINIBALL Ce detectors, the HECTOR-BaF detectors, and the fragment separator FRS. The secondary beams produced at relativistic energies were used for Coulomb excitation or secondary fragmentation experiments to study projectile like nuclei by measuring de-excitation photons. The first results of the "fast beam campaign" is discussed in comparison to various shell model calculations. The discussion focuses on the N = 32, 34 sub-shell closure based on neutron rich Cr isotopes. Alternatively, the relativistic radioactive beams, both in their ground and isomeric states, were implanted and their decay could be investigated. The "stopped beam campaign" has started in October 2005 with a series of g-factor measurements. It continued from February 2006 with the next, configuration and the main goal of identification of new isomers and angular momentum population in fragmentation reactions.
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| 15. |
- Grigorenko, L. V., et al.
(författare)
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Three-body decay of Be-6
- 2009
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Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 80:3
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Tidskriftsartikel (refereegranskat)abstract
- Three-body correlations for the ground-state decay of the lightest two-proton emitter Be-6 are studied both theoretically and experimentally. Theoretical studies are performed in a three-body hyperspherical-harmonics cluster model. In the experimental studies, the ground state of Be-6 was formed following the alpha decay of a C-10 beam inelastically excited through interactions with Be and C targets. Excellent agreement between theory and experiment is obtained demonstrating the existence of complicated correlation patterns that can elucidate the structure of Be-6 and, possibly, of the A = 6 isobars.
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| 16. |
- Hagander, Lars, et al.
(författare)
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Major Neonatal Surgery Under Local Anesthesia: A Cohort Study from Bangladesh.
- 2015
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 39:4, s. 953-960
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Tidskriftsartikel (refereegranskat)abstract
- Surgeons and anesthetists must respond to the perioperative mortality associated with general anesthesia in developing countries. The safety of performing major neonatal surgery under local anesthesia is one pragmatic response. This study describes and evaluates such practice in a tertiary pediatric surgery center in Bangladesh.
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| 17. |
- Hammond, G, et al.
(författare)
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Spectroscopy of T=3/2 Mirror Nuclei via Two-step Fragmentation using RISING
- 2005
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 36:4, s. 1253-1257
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Tidskriftsartikel (refereegranskat)abstract
- Two two-step fragmentation reactions were performed using RISING to populate excited states in A approximate to 50 mirror nuclei near to the proton-drip line, in order to test isospin symmetry. The experiments were designed to observe gamma decays of excited states in the mirror nuclei Ni-53(28)25/Mn-53(25)28, which have a large value of total isospin (T = 3/2). In the continuing off-line analysis, gamma transitions have been observed in Ni-54 indicating that two-step fragmentation is a successful technique for spectroscopic investigations of proton-rich nuclear systems in this mass region.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Taylor, MJ, et al.
(författare)
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Spectroscopy of Nuclei Approaching the Proton Drip-line Using a Secondary-fragmentation Technique with the RISING Detector Array
- 2005
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 31:10, s. 1527-1530
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Tidskriftsartikel (refereegranskat)abstract
- An experiment utilizing a double fragmentation reaction was performed to study isobaric analogue states in A similar to 50 nuclei approaching the proton drip-line. gamma-ray spectroscopy will be used to identify excited states in the neutron-deficient nuclei produced in the second fragmentation reaction. Excited state level schemes will be obtained, through comparison with states in their well-known mirror partners, along with information on Coulomb effects through measurements of the Coulomb energy differences between isobaric analogue excited states. The validity of isospin symmetry for nuclei approaching the proton drip-line can also be investigated and the information gained will aid in testing and improving fp shell model calculations. The analysis of the collected data is at a preliminary stage and current status of this work is reported.
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| 22. |
- Wollersheim, HJ, et al.
(författare)
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Rare ISotopes INvestigation at GSI (RISING) Using Gamma-ray Spectroscopy at Relativistic Energies
- 2005
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 537:3, s. 637-657
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Tidskriftsartikel (refereegranskat)abstract
- The Rare ISotopes INvestigation at GSI project combines the former EUROBALL Ge-Cluster detectors, the MINIBALL Ge detectors, BaF2--HECTOR detectors, and the fragment separator at GSI for high-resolution in-beam gamma-ray spectroscopy measurements with radioactive beams. These secondary beams produced at relativistic energies are used for Coulomb excitation or secondary fragmentation experiments in order to explore the nuclear structure of the projectiles or projectile like nuclei by measuring de-excitation photons. The newly designed detector array is described and the performance characteristics are given. Moreover, particularities of the experimental technique are discussed.
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