| 1. |
- Ip, H. F., et al.
(författare)
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Genetic association study of childhood aggression across raters, instruments, and age
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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| 2. |
- Jami, E. S., et al.
(författare)
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Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
- 2022
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 61:7, s. 934-945
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n(effective) = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (vertical bar r(g)vertical bar > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range vertical bar r(g)vertical bar = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
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| 3. |
- Muus, Christoph, et al.
(författare)
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Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 546-559
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention. An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.
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| 4. |
- Schweinsberg, Martin, et al.
(författare)
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Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
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Ingår i: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
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Tidskriftsartikel (refereegranskat)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
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| 5. |
- Das, P., et al.
(författare)
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Study of exotic decay of Cs isotope close to the proton drip line
- 2020
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Ingår i: 27th International Nuclear Physics Conference (INPC2019) 29 July - 2 August 2019, Glasgow, UK. - : IOP Publishing. - 1742-6588. ; 1643
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Konferensbidrag (refereegranskat)abstract
- The neutron-deficient 115Cs was produced at ISOLDE, CERN by spallation reaction using 1.4 GeV proton on LaC2 target. The exotic decay modes were studied by using a charged particle array (DSSD and pad detectors) and a γ-detector array (four Clovers) at the ISOLDE decay station (IDS). In this report, results on observed β-delayed particle emission from 115Cs, a nucleus close to proton drip line, is presented. By measuring the time distribution in the delayed proton spectrum, the half-life of the ground state of 115Cs was extracted. The obtained half-life is in agreement with previous reported value. For the first time, the p-unbound states of 115Xe, obtained by measuring beta-delayed protons from 115Cs is reported.
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| 6. |
- Pereira-López, X., et al.
(författare)
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In-beam γ -ray spectroscopy of 94 Ag
- 2023
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 59:3
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Tidskriftsartikel (refereegranskat)abstract
- A recoil-beta-tagging experiment has been performed to study the excited T= 0 and T= 1 states in the odd–odd N= Z nucleus 94Ag, populated via the 40Ca(58Ni,1p3n)94Ag reaction. The experiment was conducted using the MARA recoil separator and JUROGAM3 array at the Accelerator Laboratory of the University of Jyväskylä. Through correlating fast, high-energy beta decays at the MARA focal plane with prompt γ rays emitted at the reaction target, a number of transitions between excited states in 94Ag have been identified. The timing characteristics of these transitions confirm that they fall within decay sequences that feed the short-lived T= 1 ground state of 94Ag. The transitions are proposed to proceed within and between the sets of states with T= 0 and T= 1. Possible correspondence between some of these transitions from analog states in 94Pd has been discussed, and shell-model calculations including multipole and monopole electromagnetic effects have been presented, in order to enable predictions of the decay patterns between the T= 0 and T= 1 states and to allow a theoretical set of Coulomb energy differences to be calculated for the A= 94 T= 1 analog states.
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| 7. |
- Stryjczyk, M., et al.
(författare)
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Decay studies of the long-lived states in Tl 186
- 2020
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Ingår i: Physical Review C. - 2469-9985. ; 102:2
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Tidskriftsartikel (refereegranskat)abstract
- Decay spectroscopy of the long-lived states in Tl186 has been performed at the ISOLDE Decay Station at ISOLDE, CERN. The α decay from the low-spin (2-) state in Tl186 was observed for the first time and a half-life of 3.4-0.4+0.5 s was determined. Based on the α-decay energy, the relative positions of the long-lived states were fixed, with the (2-) state as the ground state, the 7(+) state at 77(56) keV, and the 10(-) state at 451(56) keV. The level scheme of the internal decay of the Tl186(10(-)) state [T1/2=3.40(9) s], which was known to decay solely through emission of 374-keV γ-ray transition, was extended and a lower limit for the β-decay branching bβ>5.9(3)% was determined. The extracted retardation factors for the γ decay of the 10(-) state were compared to the available data in neighboring odd-odd thallium isotopes indicating the importance of the πd3/2 shell in the isomeric decay and significant structure differences between Tl184 and Tl186.
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| 8. |
- Das, P., et al.
(författare)
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Exotic decay of 115Cs
- 2023
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Ingår i: Physical Review C. - 2469-9985. ; 108:6
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Tidskriftsartikel (refereegranskat)abstract
- The detailed study of the β+/EC decay of the very neutron-deficient and alpha-unbound nucleus 115Cs is presented. The measurement was performed at the ISOLDE, CERN where delayed charged particles and γ rays were detected. The observed delayed γ rays are in agreement with the previously reported characteristics γ rays of 115Xe. Based on the experimental observations, the tentative ground-state spin of 115Cs is suggested to be 7/2+ or 9/2+. Furthermore, the measured decay branching ratio of delayed protons exceeds the previously reported value. Additionally, new delayed α-branching ratio and several reconstructed proton and α-unbound excited states of 115Xe are being reported for the first time. The properties of proton-unbound states at excitation energies from 3.9–7.9 MeV have been obtained by fitting the delayed proton spectrum via the Bayesian method. The measured lifetimes of these proton-unbound states are in the order of zeptoseconds.
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| 9. |
- Ertoprak, A., et al.
(författare)
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Lifetimes of core-excited states in semi-magic Rh-95
- 2020
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Ingår i: European Physical Journal A. - : SPRINGER. - 1434-6001 .- 1434-601X. ; 56:11
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Tidskriftsartikel (refereegranskat)abstract
- Lifetimes of negative-parity states have been determined in the neutron deficient semi-magic (N = 50) nucleus Rh-95. The fusion-evaporation reaction Ni-58(Ca-40, 3p) was used to populate high-spin states in Rh-95 at the Grand Accelerateur National d'Ions Lourds (GANIL) accelerator facility. The results were obtained using the Doppler Shift Attenuation Method (DSAM) based on the Doppler broadened line shapes produced during the slowing down process of the residual nuclei in a thick 6 mg/cm(2) metallic target. B(M1) and B(E2) reduced transition strengths are compared with predictions from large-scale shell-model calculations. state-of-the-art theory. Remarkably, the structural features up to moderate angular momentum of nuclei immediately below the N = Z = 50 shell closures can be described with high accuracy in a very simple way by shell-model calculations including only the g(9/2) and p(1/2) subshells. Of special interest is the neutron-proton pair coupling scheme which is expected to appear in the heaviest N=Z nuclei [1,2] and the seniority structure of the N = 50 isotones [3-7]. However, multiple core-excited states have been observed in the semi-magic nuclei of the Sn-100 region [8-10]. The theoretical study of those states is a challenging task, which requires a significantly larger model space for their interpretation. Transition probabilities between nuclear states provide important constraints for theoretical modelling of the structure of the nuclei of interest. Our previous lifetime study of the semimagic (N = 50) nucleus Ru-94 [ 11,12] provided information on the electromagnetic decay properties of neutron-core excited states. We now address lifetime measurements in its closest, more neutron deficient, isotone Rh-95 using the same DSAM technique. The experimental results have been interpreted within the framework of large-scale shell-model (LSSM) calculations.
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| 10. |
- Fernández, A., et al.
(författare)
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Mirror energy differences above the 0f7/2 shell: First γ-ray spectroscopy of the Tz=−2 nucleus 56Zn
- 2021
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693. ; 823
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in 56Zn were populated following one-neutron removal from a 57Zn beam impinging on a Be target at intermediate energies in an experiment conducted at the Radioactive Isotope Beam Factory at RIKEN. Three γ rays were observed and tentatively assigned to the 6+ → 4+ → 2+ → 0+ yrast sequence. This turns 56Zn into the heaviest Tz=−2 nucleus in which excited states are known. The excitation-energy differences between these levels and the isobaric analogue states in the Tz=+2 mirror partner, 56Fe, are compared with large-scale shell-model calculations considering the full pf valence space and various isospin-breaking contributions. This comparison, together with an analysis of the mirror energy differences in the A=58, Tz=±1 pair 58Zn and 58Ni, provides valuable information with respect to the size of the monopole radial and the isovector multipole isospin-breaking terms in the region above doubly-magic 56Ni.
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| 11. |
- Cederwall, B., et al.
(författare)
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Isospin Properties of Nuclear Pair Correlations from the Level Structure of the Self-Conjugate Nucleus Ru-88
- 2020
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Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 124:6
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Tidskriftsartikel (refereegranskat)abstract
- The low-lying energy spectrum of the extremely neutron-deficient self-conjugate (N = Z) nuclide Ru-88(44)44 has been measured using the combination of the Advanced Gamma Tracking Array (AGATA) spectrometer, the NEDA and Neutron Wall neutron detector arrays, and the DIAMANT charged particle detector array. Excited states in Ru-88 were populated via the Fe-54(Ar-36, 2n gamma)Ru-88* fusion-evaporation reaction at the Grand Accelerateur National d'Ions Lourds (GANIL) accelerator complex. The observed gamma-ray cascade is assigned to Ru-88 using clean prompt gamma-gamma-2-neutron coincidences in anticoincidence with the detection of charged particles, confirming and extending the previously assigned sequence of low-lying excited states. It is consistent with a moderately deformed rotating system exhibiting a band crossing at a rotational frequency that is significantly higher than standard theoretical predictions with isovector pairing, as well as observations in neighboring N > Z nuclides. The direct observation of such a "delayed" rotational alignment in a deformed N = Z nucleus is in agreement with theoretical predictions related to the presence of strong isoscalar neutron-proton pair correlations.
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| 12. |
- Cederwall, Bo, 1964-, et al.
(författare)
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Isospin Properties of Nuclear Pair Correlations from the Level Structure of the Self-Conjugate Nucleus Ru 88
- 2020
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Ingår i: Physical Review Letters. - : American Physical Society (APS). - 0031-9007 .- 1079-7114. ; 124:6
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Tidskriftsartikel (refereegranskat)abstract
- The low-lying energy spectrum of the extremely neutron-deficient self-conjugate (N = Z) nuclide 88Ru has been measured using the combination of the Advanced Gamma Tracking Array (AGATA)spectrometer, the NEDA, and Neutron Wall neutron detector arrays, and the DIAMANT charged particle detector array. Excited states in 88 Ru were populated via the 54 Feð 36 Ar; 2nγÞ 88 Ru fusion-evaporationreaction at the Grand Accélérateur National d’Ions Lourds (GANIL) accelerator complex. The observed γ-ray cascade is assigned to 88 Ru using clean prompt γ-γ-2-neutron coincidences in anticoincidence with the detection of charged particles, confirming and extending the previously assigned sequence of low-lying excited states. It is consistent with a moderately deformed rotating system exhibiting a band crossing at a rotational frequency that is significantly higher than standard theoretical predictions with isovector pairing, as well as observations in neighboring N > Z nuclides. The direct observation of such a “delayed” rotational alignment in a deformed N 1⁄4 Z nucleus is in agreement with theoretical predictions related to the presence of strong isoscalar neutron-proton pair correlations.
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| 13. |
- Fabian, X., et al.
(författare)
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Artificial neural networks for neutron/gamma discrimination in the neutron detectors of NEDA
- 2021
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 986
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Tidskriftsartikel (refereegranskat)abstract
- Three different Artificial Neural Network architectures have been applied to perform neutron/gamma discrimination in NEDA based on waveform and time-of-flight information. Using the coincident gamma-rays from AGATA, we have been able to measure and compare on real data the performances of the Artificial Neural Networks as classifiers. While the general performances are quite similar for the data set we used, differences, in particular related to the computing times, have been highlighted. One of the Artificial Neural Network architecture has also been found more robust to time misalignment of the waveforms. Such a feature is of great interest for online processing of waveforms.
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| 14. |
- Liu, X., et al.
(författare)
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Evidence for enhanced neutron-proton correlations from the levelstructure of the N= Z+ 1 nucleus 8743Tc44
- 2021
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 104:2
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Tidskriftsartikel (refereegranskat)abstract
- The low-lying excited states in the neutron-deficient N = Z + 1 nucleus (87)(43)Tcc(44) have been studied via the fusion-evaporation reaction Fe-54(Ar-36, 2n1p)Tc-87 at the Grand Accelerateur National d'Ions Lourds (GANIL), France. The AGATA spectrometer was used in conjunction with the auxiliary NEDA, Neutron Wall, and DIAMANT detector arrays to measure coincident prompt gamma rays, neutrons, and charged particles emitted in the reaction. A level scheme of Tc-87 from the (9/2(g.s.)(+)) state to the (33/2(1)(+)) state was established based on six mutually coincident gamma-ray transitions. The constructed level structure exhibits a rotational behavior with a sharp backbending at (h) over bar omega approximate to 0.50 MeV. A decrease in alignment frequency and increase in alignment sharpness in the odd-mass isotonic chains around N = 44 is proposed as an effect of the enhanced isoscalar neutron-proton interactions in odd-mass nuclei when approaching the N = Z line.
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| 15. |
- Liu, Xiaoyu, et al.
(författare)
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Evidence for spherical-oblate shape coexistence in Tc-87
- 2022
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 106:3
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in the neutron-deficient nucleus Tc-87 have been studied via the fusion-evaporation reaction 54Fe(36Ar, 2n1p) Tc-87 at 115 MeV beam energy. The AGATA gamma-ray spectrometer coupled to the DIAMANT, NEDA, and Neutron Wall detector arrays for light-particle detection was used to measure the prompt coincidence of gamma rays and light particles. Six transitions from the deexcitation of excited states belonging to a new band in Tc-87 were identified by comparing gamma-ray intensities in the spectra gated under different reaction channel selection conditions. The constructed level structure was compared with the shell model and total Routhian surface calculations. The results indicate that the new band structure in 87Tc is built on a spherical configuration, which is different from that assigned to the previously identified oblate yrast rotational band.
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| 16. |
- Argyriou, A, et al.
(författare)
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SINGLE CELL SEQUENCING REVEALS CLONALLY EXPANDED CYTOTOXIC CD4+T CELLS IN THE JOINTS OF ACPA plus RA PATIENTS
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 38-39
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- CD4+ T cells with cytotoxic functions (CD4+ CTL) have gained attention in recent years. Accumulating evidence supports their importance in defense against human viral infections such as CMV1, EBV2, dengue3, HIV4, 5 and SARS-CoV-26. Moreover, expansion of so called CD28null cytotoxic CD4+ T cells have been reported in the blood of patients with rheumatic diseases such as rheumatoid arthritis (RA)7, myositis8 and vasculitis9 as well as in cardiovascular diseases10.Objectives:Here, we aimed to investigate the presence and clonal expansion of CD4+ CTL in the peripheral blood (PB) and synovial fluid (SF) of RA patients using single cell technologies.Methods:We assessed the expression of cytotoxic effector molecules and transcription factors in CD4+ T cells in synovial fluid (n=21) and paired peripheral blood (n=16) from ACPA- and APCA+ RA patients by multi-parameter flow cytometry. We performed single cell sequencing, in combination with 5´ TCRab sequencing, on purified CD4+ T cells from the peripheral blood (PB) and synovial fluid (SF) of ACPA+ RA patients (n=7).Results:Flow cytometry experiments show that Granzyme-B+ Perforin-1+ CD4+ CTL are significantly increased in the SF of ACPA+ RA patients as compared to ACPA- RA patients (p=0.0072). The presence of CD4+ CTL could be confirmed by single cell sequencing in SF of each ACPA+ RA patient tested (n=7). Moreover, we found that the adhesion G-protein coupled receptor GPR56 is selectively expressed on the recently described peripheral helper (TPH) T-cell subset11 and associates with the expression of tissue resident memory markers LAG-3, CXCR6 and CD69. In blood, we confirmed a previous report12 showing that GPR56 delineates cytotoxic CD4+ T cells. Finally, expanded TCR clones expressing cytotoxic effector molecules were identified in synovial fluid of ACPA+ RA patients and, for some patients, in their corresponding peripheral blood.Conclusion:We identified GPR56 as a marker of TPH cells in SF of ACPA+ RA patients that associates with tissue residency receptors. The combination of single cell sequencing and multi-parameter flow cytometry highlights the importance of CD4+ CTL in ACPA+ RA and suggests a potential therapeutic target (Figure 1).References:[1]Casazza J. P. et al., J Exp Med2006,203 (13), 2865-77.[2]Landais E. et al., Blood2004,103 (4), 1408-16.[3]Kurane I. et al. J Exp Med1989,170 (3), 763-75.[4]Appay V. et al. J Immunol2002,168 (11), 5954-8.[5]Juno J. A. et al. Front Immunol2017,8, 19.[6]Meckiff B. J. et al. Cell2020,183 (5), 1340-1353 e16.[7]Schmidt D. et al. J Clin Invest1996,97 (9), 2027-37.[8]Fasth A. E. et al. J Immunol2009,183 (7), 4792-9.[9]Moosig F. et al. Clin Exp Immunol1998,114 (1), 113-8.[10]Sato K. et al. J Exp Med2006,203 (1), 239-50.[11]Rao D. A., et al. Nature2017,542 (7639), 110-114.[12]Peng Y. M. et al. J Leukoc Biol2011,90 (4), 735-40.Acknowledgements:We thank the patients who donated samples and the medical staff at the Rheumatology Clinic of Karolinska University Hospital. Julia Boström, Gloria Rostvall, and Susana Hernandez Machado are acknowledged for organizing the sampling, storage, and administration of biomaterial. This study is supported by grants from Dr. Margaretha Nilssons, the Nanna Svartz, the Ulla and Gustaf af Ugglas foundations and the Swedish association against rheumatism.Disclosure of Interests:Alexandra Argyriou: None declared, Marc H Wadsworth II Employee of: Pfizer, Inc, Cambridge, MA 02139, United States, Adrian Lendvai: None declared, Stephen Christensen Employee of: Pfizer, Inc, Cambridge, MA 02139, United States, Aase Hensvold: None declared, Christina Gerstner: None declared, Kellie Kravarik Employee of: Pfizer, Inc, Cambridge, MA 02139, United States, Aaron Winkler Employee of: Pfizer, Inc, Cambridge, MA 02139, United States, Vivianne Malmström: None declared, Karine Chemin: None declared
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| 17. |
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| 18. |
- Hurley, Carolyn K., et al.
(författare)
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Common, intermediate and well-documented HLA alleles in world populations : CIWD version 3.0.0
- 2020
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Ingår i: HLA. - : WILEY. - 2059-2302 .- 2059-2310. ; 95:6, s. 516-531
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Tidskriftsartikel (refereegranskat)abstract
- A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (>= 1 in 10 000), intermediate (>= 1 in 100 000), well-documented (>= 5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole.
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| 19. |
- Llewellyn, R. D. O., et al.
(författare)
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Establishing the Maximum Collectivity in Highly Deformed N = Z Nuclei
- 2020
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 124:15
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Tidskriftsartikel (refereegranskat)abstract
- The lifetimes of the first excited 2(+) states in the N = Z nuclei Zr-80, Y-78, and Sr-76 have been measured using the gamma-ray line shape method following population via nucleon-knockout reactions from intermediate-energy rare-isotope beams. The extracted reduced electromagnetic transition strengths yield new information on where the collectivity is maximized and provide evidence for a significant, and as yet unexplained, odd-odd vs even-even staggering in the observed values. The experimental results are analyzed in the context of state-of-the-art nuclear density-functional model calculations.
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| 20. |
- Llewellyn, R. D. O., et al.
(författare)
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Spectroscopy of proton-rich Zr-79 : Mirror energy differences in the highly-deformed fpg shell
- 2020
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 811
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Tidskriftsartikel (refereegranskat)abstract
- Energy differences between isobaric analogue states have been extracted for the A = 79, Zr-79/Y-79 mirror pair following their population via nucleon-knockout reactions from intermediate-energy rare-isotope beams. These are the heaviest nuclei where such measurements have been made to date. The deduced mirror energy differences (MED) are compared with predictions from a new density-functional based approach, incorporating isospin-breaking effects of both Coulomb and nuclear charge-symmetry breaking and configuration mixing.
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| 21. |
- Thompson, Andrew G B, et al.
(författare)
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Evaluation of plasma tau and neurofilament light chain biomarkers in a 12-year clinical cohort of human prion diseases.
- 2021
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26, s. 5955-5966
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Tidskriftsartikel (refereegranskat)abstract
- Prion diseases are fatal neurodegenerative conditions with highly accurate CSF and imaging diagnostic tests, but major unmet needs for blood biomarkers. Using ultrasensitive immuno-assays, we measured tau and neurofilament light chain (NfL) protein concentrations in 709 plasma samples taken from 377 individuals with prion disease during a 12year prospective clinical study, alongside healthy and neurological control groups. This provides an unprecedented opportunity to evaluate their potential as biomarkers. Plasma tau and NfL were increased across all prion disease types. For distinguishing sCJD from control groups including clinically-relevant "CJD mimics", both show considerable diagnostic value. In sCJD, NfL was substantially elevated in every sample tested, including during early disease with minimal functional impairment and in all follow-up samples. Plasma tau was independently associated with rate of clinical progression in sCJD, while plasma NfL showed independent association with severity of functional impairment. In asymptomatic PRNP mutation carriers, plasma NfL was higher on average in samples taken within 2years of symptom onset than in samples taken earlier. We present biomarker trajectories for nine mutation carriers healthy at enrolment who developed symptoms during follow-up. NfL started to rise as early as 2years before onset in those with mutations typically associated with more slowly progressive clinical disease. This shows potential for plasma NfL as a "proximity marker", but further work is needed to establish predictive value on an individual basis, and how this varies across different PRNP mutations. We conclude that plasma tau and NfL have potential to fill key unmet needs for biomarkers in prion disease: as a secondary outcome for clinical trials (NfL and tau); for predicting onset in at-risk individuals (NfL); and as an accessible test for earlier identification of patients that may have CJD and require more definitive tests (NfL). Further studies should evaluate their performance directly in these specific roles.
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| 22. |
- Zhang, Wei, et al.
(författare)
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Observation of the proton emitter 11657La59
- 2022
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Ingår i: Communications Physics. - : Springer Science and Business Media LLC. - 2399-3650. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The quantum tunneling and emission of a single constituent nucleon provide a beautifully simple and unique window into the complex properties of atomic nuclei at the extreme edge of nuclear existence. In particular, for odd-odd proton emitting nuclides, the associated decay energy and partial half-life can be used to probe the correlations between the valence neutrons and protons which have been theoretically predicted to favour a new type of nuclear superfluidity, isoscalar neutron-proton pairing, for which the experimental “smoking gun" remains elusive. In the present work, proton emission from the lanthanum isotope 1165757116La59, 23 neutrons away from the only stable isotope 1395757139La82, is reported. 116La nuclei were synthesised in the fusion-evaporation reaction 58Ni(64Zn, p5n)116La and identified via their proton radioactivity using the mass spectrometer MARA (Mass Analysing Recoil Apparatus) and the silicon detectors placed at its focal plane. Comparisons of the measured proton energy (Ep = 718 ± 9 keV) and half-life (T1/2 = 50 ± 22 ms) with values calculated using the Universal Decay Law approach indicate that the proton is emitted with an orbital angular momentum l = 2 and that its emission probability is enhanced relative to its closest, less exotic, odd-even lanthanum isotope (1175757117La60) while the proton-emission Q-value is lower. We propose this to be a possible signature for the presence of strong neutron-proton pair correlations in this exotic, neutron deficient system. The observations of γ decays from isomeric states in 116La and 117La are also reported.
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