| 1. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 2. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 3. |
- Shimoura, S., et al.
(författare)
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Lifetime of the isomeric O-2(+) state in Be-12
- 2007
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 654:3-4, s. 87-91
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Tidskriftsartikel (refereegranskat)abstract
- Mean lifetime tau of the isomeric O-2(+) state in Be-12 has been determined by measuring decay spectra of delayed y-rays from stopped Be-12 2 nuclei produced by the projectile fragmentation of O-18 at 100 A MeV. A consistent value of tau = 331 +/- 12 ns was obtained from the time spectra of the E2 gamma decay to the 2(1)(+) state and the positron annihilation following the E0 decay to the ground state. Based on the observed branching ratio between the E2 and E0 decays, transition strengths of the two decay modes were deduced to be B(E2; O-2(+) -> 2(1)(+)) = 7.0 +/- 0.6 e(2) fm(4) and 2 1 1 (O-2(+) Sigma(i) e(i) r(i)(2) O-1(+)), = 0.87 +/- 0.03 e fM(2), respectively. (C) 2007 Elsevier B.V. All rights reserved.
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| 4. |
- Jensen, DR, et al.
(författare)
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Coexisting wobbling and quasiparticle excitations in the triaxial potential well of Lu-163
- 2004
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 19:2, s. 173-185
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Tidskriftsartikel (refereegranskat)abstract
- High-spin states of the nucleus Lu-163 have been populated through the fusion-evaporation reaction La-139(Si-29, 5n) with a beam energy of 157 MeV. In addition to the two lowest excited triaxial strongly deformed (TSD) bands, recently interpreted as one- and two-phonon wobbling excitations, a third excited TSD band has been firmly established decaying to the yrast TSD band. The assignment of this band as a three-quasiparticle band shows together with the normal deformed (ND) level scheme the presence not only of shape coexistence between ND and TSD structures, but also an interplay of wobbling and quasiparticle excitations in the triaxial strongly deformed potential well of Lu-163.
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| 5. |
- Jensen, DR, et al.
(författare)
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Evidence for second-phonon nuclear wobbling
- 2002
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Ingår i: Physical Review Letters. - 1079-7114. ; 89:14
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Tidskriftsartikel (refereegranskat)abstract
- The nucleus Lu-163 has been populated through the reaction La-139(Si-29,5n) with a beam energy of 157 MeV. Three triaxial, strongly deformed (TSD) bands have been observed with very similar rotational properties. The first excited TSD band has earlier been assigned as a one-phonon wobbling excitation built on the lowest-lying (yrast) TSD band. The large B(E2)(out)/B(E2)(in) value obtainable for one of four observed transitions between the second and first excited TSD bands is in good agreement with particle-rotor calculations for a two-phonon wobbling excitation.
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| 6. |
- Shein, A. M. S., et al.
(författare)
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Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection
- 2023
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Ingår i: Biomedicine & Pharmacotherapy. - 0753-3322. ; 168
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Tidskriftsartikel (refereegranskat)abstract
- Given the rise of multidrug-resistant (MDR) Pseudomonas aeruginosa infections, alternative treatments are needed. Anti-pseudomonal phage therapy shows promise, but its clinical application is limited due to the development of resistance and a lack of biofilm penetration. Recently, adjuvants like CaEDTA have shown the ability to enhance the effectiveness of combined antimicrobial agents. Here, we tested a phage-adjuvant com-bination and demonstrated the effectiveness of intranasally inhaled phage (KKP10) + CaEDTA in addition to ceftazidime/avibactam (CZA) for chronic P. aeruginosa lung infections. The results emphasize that intranasal inhalation of phage along with CaEDTA can successfully re-sensitize MDR P. aeruginosa to CZA in a triple combination treatment. This promising approach shows potential as a therapy for chronic respiratory tract infections.
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| 7. |
- Fujita, Y, et al.
(författare)
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Evidence for the existence of the [202]3/2 deformed band in mirror nuclei Mg-25 and Al-25
- 2004
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Ingår i: Physical Review Letters. - 1079-7114. ; 92:6
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Tidskriftsartikel (refereegranskat)abstract
- After 50 years of its prediction, the highest-lying [2 0 2]3/2 orbit among the six Nilsson single-particle orbits originating from the sd shells in prolately deformed nuclei and the rotational band on this orbit were identified. The band members were observed in Al-25 at excitation energies of 6-7.5 MeV in a high-resolution Mg-25(He-3,t) charge-exchange reaction at 0degrees having a strong selectivity for Gamow-Teller transitions. In the comparison with the analogous M1 transitions in Mg-25, the J(pi)=3/2(+) bandhead state and the excited 5/2(+) and 7/2(+) members were clearly assigned.
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| 8. |
- Fujita, Y., et al.
(författare)
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Identification of the [202]3/2 deformed band in mirror nuclei Mg-25 and Al-25 and implications for unstable nuclei
- 2006
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Ingår i: Physica Scripta. - 0031-8949. ; T125, s. 194-195
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Tidskriftsartikel (refereegranskat)abstract
- Fifty years after its prediction, the highest-lying [ 2 0 2] 3) 2 orbit among the six Nilsson single-particle orbits originating from the sd shell in prolately deformed nuclei and the rotational band on this orbit were identified. The band members were observed in Al-25 at excitation energies of 6-7.5MeV in a high-resolution Mg-25(He-3,t) charge-exchange reaction at 0 degrees having a strong selectivity for Gamow-Teller transitions. In comparison with the analogous M1 transitions in Mg-25, the J(pi) = 3/+ band-head state and the excited 5/+ and 7/2+ members were clearly assigned.
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| 9. |
- Hamamoto-Kuroda, Ikuko, et al.
(författare)
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Isoscalar dipole strength in Pb-208(82)126: The spurious mode and the strength in the continuum
- 2002
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 66:4
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Tidskriftsartikel (refereegranskat)abstract
- The isoscalar dipole (compression) mode is studied first using the schematic harmonic-oscillator model, and then the self-consistent Hartree-Fock (HF) and random-phase approximation (RPA) are solved in coordinate space. Taking Pb-208 and the SkyM* interaction as a numerical example, the spurious component and the strength in the continuum are carefully examined using the sum rules. It is pointed out that in the continuum calculation one has to use an extremely fine radial mesh in HF and RPA in order to separate, with good accuracy, the spurious component from intrinsic excitations.
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| 10. |
- Hamamoto-Kuroda, Ikuko, et al.
(författare)
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Weakly bound neutrons and quadrupole response function in the many-body pair correlation of neutron drip line nuclei
- 2006
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 32:8, s. 1105-1119
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Tidskriftsartikel (refereegranskat)abstract
- A simplified model of the Hartree-Fock Bogoliubov (HFB) equation with surface-type or volume-type pairing is solved in coordinate space with the correct asymptotic boundary conditions. By using the resulting HFB wavefunctions, the low-energy quadrupole (L = 2) response function is studied for the system with weakly bound s and d neutrons. As the binding energy of the neutrons becomes small or approaches zero, the discrete solutions of the HFB equation disappear. Then, without any further correlation ( for example, random phase approximation ( RPA) correlation), the threshold quadrupole response becomes broader and moves toward very low excitation energies, while the total strength increases very rapidly. The important role of the continuum character of the upper component u(lj) (r) of the HFB s(1/2) wavefunction in the increasing strength is pointed out. The large and broad quadrupole response with a very low peak energy is expected for neutron drip line nuclei with N approximate to 56 and Z approximate to 28, of which both the neutron 2d(5/2) and 3s(1/2) orbits may be weakly bound in the Hartree-Fock (HF) potential.
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| 11. |
- Jensen, DR, et al.
(författare)
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Wobbling phonon excitations, coexisting with normal deformed structures in Lu-163
- 2002
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Ingår i: Nuclear Physics, Section A. - 0375-9474. ; 703:1-2, s. 3-44
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Tidskriftsartikel (refereegranskat)abstract
- Wobbling is a rotational mode unique to a triaxial body. The Lu-Hf isotopes with N similar to 94 at high spin provide a possible region of nuclei with pronounced triaxiality. We have investigated Lu-163 through the fusion-evaporation reaction La-139(Si-29,5n)Lu-163 with a beam energy of 152 MeV. Three excited bands decaying into the known, presumably triaxial, superdeformed (TSD) band built on the i(13/2) proton orbital are observed. The electromagnetic properties of the connecting transitions from the two strongest populated excited TSD bands have been investigated. New particle-rotor calculations in which one i(13/2) quasiproton is coupled to the core of triaxial shape produce a variety of bands, whose properties can clearly be interpreted either as "wobbling" or "cranking" motion of the core. Evidence for the assignment of the excited TSD bands as one, and possibly even two wobbling phonon modes built on the yrast TSD band in Lu-163 is given. These triaxial bands coexist with bands built on quasiparticle excitations in the normal deformed (ND) minimum for which new data are also presented.
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| 12. |
- Shimbara, Y, et al.
(författare)
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Suppression of Gamow-Teller and M1 transitions in deformed mirror nuclei Mg-25 and Al-25 - Direct observation of K selection rules
- 2004
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 19:1, s. 25-31
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Tidskriftsartikel (refereegranskat)abstract
- The mirror nuclei Mg-25 and Al-25 are expected to have very similar structures. The Gamow-Teller (GT) transitions from the J(pi) = 5/2(+) ground state of Mg-25 to the excited states in Al-25 were studied by high-resolution measurements of the Mg-25(He-3,t) charge-exchange reaction at 0degrees and at 140 MeV/nucleon. Assuming the usual DeltaJ(pi) = 1(+) selection rule for the spin-isospin-type GT transitions, the states with J(pi) = 3/2(+), 5/2(+), and 7/2 (+) should be excited. However, of the more than ten states with these J(pi) values below 6 MeV excitation energy, only the 5/2 (+) ground state and the 7/2 (+) , 1.613 MeV state in Al-25 were strongly populated, while all other states were strongly suppressed. The analysis of M1 transitions in Mg-25 also suggested a very similar feature for the analogous M1 transitions. Both Mg-25 and Al-25 are known to be largely deformed, and most low-lying states can be interpreted in terms of one-particle quantum numbers in the deformed potential and the associated rotational spectra. The observed suppression can be explained in terms of the K quantum number selection rules that are inherent to axially deformed nuclei.
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| 13. |
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