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1.
  • 2017
  • swepub:Mat__t
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4.
  • Röder, M., et al. (författare)
  • Coulomb dissociation of 20,21 N
  • 2016
  • Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993 .- 0556-2813. ; 93:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutron-rich light nuclei and their reactions play an important role in the creation of chemical elements. Here, data from a Coulomb dissociation experiment on N20,21 are reported. Relativistic N20,21 ions impinged on a lead target and the Coulomb dissociation cross section was determined in a kinematically complete experiment. Using the detailed balance theorem, the N19(n,γ)N20 and N20(n,γ)N21 excitation functions and thermonuclear reaction rates have been determined. The N19(n,γ)N20 rate is up to a factor of 5 higher at T
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5.
  • Heine, M., et al. (författare)
  • Determination of the neutron-capture rate of C-17 for r-process nucleosynthesis
  • 2017
  • Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 95:1, s. Article no 014613 -
  • Tidskriftsartikel (refereegranskat)abstract
    • With the (RB)-B-3-LAND setup at GSI we have measured exclusive relative-energy spectra of the Coulomb dissociation of C-18 at a projectile energy around 425A MeV on a lead target, which are needed to determine the radiative neutron-capture cross sections of C-17 into the ground state of C-18. Those data have been used to constrain theoretical calculations for transitions populating excited states in C-18. This allowed to derive the astrophysical cross section sigma(n gamma)*. accounting for the thermal population of C-17 target states in astrophysical scenarios. The experimentally verified capture rate is significantly lower than those of previously obtained Hauser-Feshbach estimations at temperatures T-9
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6.
  • Thies, Ronja, 1987, et al. (författare)
  • Systematic investigation of projectile fragmentation using beams of unstable B and C isotopes
  • 2016
  • Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993 .- 0556-2813. ; 93:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Models describing nuclear fragmentation and fragmentation fission deliver important input for planning nuclear physics experiments and future radioactive ion beam facilities. These models are usually benchmarked against data from stable beam experiments. In the future, two-step fragmentation reactions with exotic nuclei as stepping stones are a promising tool for reaching the most neutron-rich nuclei, creating a need for models to describe also these reactions. Purpose: We want to extend the presently available data on fragmentation reactions towards the light exotic region on the nuclear chart. Furthermore, we want to improve the understanding of projectile fragmentation especially for unstable isotopes. Method: We have measured projectile fragments from C10,12-18 and B10-15 isotopes colliding with a carbon target. These measurements were all performed within one experiment, which gives rise to a very consistent data set. We compare our data to model calculations. Results: One-proton removal cross sections with different final neutron numbers (1pxn) for relativistic C10,12-18 and B10-15 isotopes impinging on a carbon target. Comparing model calculations to the data, we find that the epax code is not able to describe the data satisfactorily. Using abrabla07 on the other hand, we find that the average excitation energy per abraded nucleon needs to be decreased from 27 MeV to 8.1 MeV. With that decrease abrabla07 describes the data surprisingly well. Conclusions: Extending the available data towards light unstable nuclei with a consistent set of new data has allowed a systematic investigation of the role of the excitation energy induced in projectile fragmentation. Most striking is the apparent mass dependence of the average excitation energy per abraded nucleon. Nevertheless, this parameter, which has been related to final-state interactions, requires further study.
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7.
  • Revel, A., et al. (författare)
  • Strong Neutron Pairing in core+4n Nuclei
  • 2018
  • Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 120:15
  • Tidskriftsartikel (refereegranskat)abstract
    • The emission of neutron pairs from the neutron-rich N=12 isotones C18 and O20 has been studied by high-energy nucleon knockout from N19 and O21 secondary beams, populating unbound states of the two isotones up to 15 MeV above their two-neutron emission thresholds. The analysis of triple fragment-n-n correlations shows that the decay N19(-1p)C18∗→C16+n+n is clearly dominated by direct pair emission. The two-neutron correlation strength, the largest ever observed, suggests the predominance of a C14 core surrounded by four valence neutrons arranged in strongly correlated pairs. On the other hand, a significant competition of a sequential branch is found in the decay O21(-1n)O20∗→O18+n+n, attributed to its formation through the knockout of a deeply bound neutron that breaks the O16 core and reduces the number of pairs.
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8.
  • Vandebrouck, M., et al. (författare)
  • Effective proton-neutron interaction near the drip line from unbound states in F-25,F-26
  • 2017
  • Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 96:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Odd-odd nuclei, around doubly closed shells, have been extensively used to study proton-neutron interactions. However, the evolution of these interactions as a function of the binding energy, ultimately when nuclei become unbound, is poorly known. The F-26 nucleus, composed of a deeply bound pi 0d(5/2) proton and an unbound v0d(3/2) neutron on top of an O-24 core, is particularly adapted for this purpose. The coupling of this proton and neutron results in a J(pi) = 1(1)(+) - 4(1)(+) multiplet, whose energies must be determined to study the influence of the proximity of the continuum on the corresponding proton-neutron interaction. The J(pi) = 1(1)(+), 2(1)(+), 4(1)(+) bound states have been determined, and only a clear identification of the J(pi) = 3(1)(+) is missing. Purpose: We wish to complete the study of the J(pi) = 1(1)(+) - 4(1)(+) multiplet in F-26, by studying the energy and width of the J(pi) = 3(1)(+) unbound state. The method was first validated by the study of unbound states in F-25, for which resonances were already observed in a previous experiment. Method: Radioactive beams of Ne-26 and Ne-27, produced at about 440AMeV by the fragment separator at the GSI facility were used to populate unbound states in F-25 and F-26 via one-proton knockout reactions on a CH2 target, located at the object focal point of the (RB)-B-3/LAND setup. The detection of emitted. rays and neutrons, added to the reconstruction of the momentum vector of the A - 1 nuclei, allowed the determination of the energy of three unbound states in F-25 and two in F-26. Results: Based on its width and decay properties, the first unbound state in F-25, at the relative energy of 49(9) keV, is proposed to be a J(pi) = 1/ 2(-) arising from a p1/2 proton- hole state. In F-26, the first resonance at 323(33) keV is proposed to be the J(pi) = 3(1)(+) member of the J(pi) = 1(1)(+) - 4(1)(+) multiplet. Energies of observed states in F-25,F-26 have been compared to calculations using the independent-particle shell model, a phenomenological shell model, and the ab initio valence-space in-medium similarity renormalization group method. Conclusions: The deduced effective proton- neutron interaction is weakened by about 30-40% in comparison to the models, pointing to the need for implementing the role of the continuum in theoretical descriptions or to a wrong determination of the atomic mass of F-26.
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9.
  • Diaz Fernandez, Paloma, 1983, et al. (författare)
  • Quasifree (p, pN) scattering of light neutron-rich nuclei near N=14
  • 2018
  • Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 97:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: For many years, quasifree scattering reactions in direct kinematics have been extensively used to study the structure of stable nuclei, demonstrating the potential of this approach. The (RB)-B-3 collaboration has performed a pilot experiment to study quasifree scattering reactions in inverse kinematics for a stable C-12 beam. The results from that experiment constitute the first quasifree scattering results in inverse and complete kinematics. This technique has lately been extended to exotic beams to investigate the evolution of shell structure, which has attracted much interest due to changes in shell structure if the number of protons or neutrons is varied. Purpose: In this work we investigate for the first time the quasifree scattering reactions (p, pn) and (p, 2p) simultaneously for the same projectile in inverse and complete kinematics for radioactive beams with the aim to study the evolution of single-particle properties from N = 14 to N = 15. Method: The structure of the projectiles O-23, O-22, and N-21 has been studied simultaneously via (p, pn) and (p, 2p) quasifree knockout reactions in complete inverse kinematics, allowing the investigation of proton and neutron structure at the same time. The experimental data were collected at the (RB)-B-3-LAND setup at GSI at beam energies of around 400 MeV/u. Two key observables have been studied to shed light on the structure of those nuclei: the inclusive cross sections and the corresponding momentum distributions. Conclusions: The knockout reactions (p, pn) and (p, 2p) with radioactive beams in inverse kinematics have provided important and complementary information for the study of shell evolution and structure. For the (p, pn) channels, indications of a change in the structure of these nuclei moving from N = 14 to N = 15 have been observed, i.e., from the 0d(5/2) shell to the 1s(1/2). This supports previous observations of a subshell closure at N = 14 for neutron-rich oxygen isotopes and its weakening for the nitrogen isotopes.
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10.
  • Atar, L., et al. (författare)
  • Quasifree (p, 2p) Reactions on Oxygen Isotopes: Observation of Isospin Independence of the Reduced Single-Particle Strength
  • 2018
  • Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 120:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Quasifree one-proton knockout reactions have been employed in inverse kinematics for a systematic study of the structure of stable and exotic oxygen isotopes at the R3B/LAND setup with incident beam energies in the range of 300-450 MeV/u. The oxygen isotopic chain offers a large variation of separation energies that allows for a quantitative understanding of single-particle strength with changing isospin asymmetry. Quasifree knockout reactions provide a complementary approach to intermediate-energy one-nucleon removal reactions. Inclusive cross sections for quasifree knockout reactions of the type OA(p,2p)NA-1 have been determined and compared to calculations based on the eikonal reaction theory. The reduction factors for the single-particle strength with respect to the independent-particle model were obtained and compared to state-of-the-art ab initio predictions. The results do not show any significant dependence on proton-neutron asymmetry.
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11.
  • Ribeiro, G., et al. (författare)
  • Structure of Be-13 studied in proton knockout from B-14
  • 2018
  • Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 98:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The neutron-unbound isotope Be-13 has been studied in several experiments using different reactions, different projectile energies, and different experimental setups. There is, however, no real consensus in the interpretation of the data, in particular concerning the structure of the low-lying excited states. Gathering new experimental information, which may reveal the Be-13 structure, is a challenge, particularly in light of its bridging role between Be-12, where the N = 8 neutron shell breaks down, and the Borromean halo nucleus Be-14. The purpose of the present study is to investigate the role of bound excited states in the reaction product Be-12 after proton knockout from B-14, by measuring coincidences between Be-12, neutrons, and gamma rays originating from de-excitation of states fed by neutron decay of Be-13. The Be-13 isotopes were produced in proton knockout from a 400 MeV/nucleon B-14 beam impinging on a CH2 target. The Be-12-n relative-energy spectrum d sigma/dE(fn) was obtained from coincidences between Be-12(g.s.) and a neutron, and also as threefold coincidences by adding gamma rays, from the de-excitation of excited states in Be-12. Neutron decay from the first 5/2(+) state in Be-13 to the 2(+) state in Be-12 at 2.11 MeV is confirmed. An energy independence of the proton-knockout mechanism is found from a comparison with data taken with a 35 MeV/nucleon B-14 beam. A low-lying p-wave resonance in Be-13(1/2(-)) is confirmed by comparing proton- and neutron-knockout data from B-14 and Be-14.
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  • Kuhle, J., et al. (författare)
  • Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study
  • 2015
  • Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 21:8, s. 1013-1024
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
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13.
  • Henstrom, M., et al. (författare)
  • Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome
  • 2018
  • Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 67:2, s. 263-270
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucraseisomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p. Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.
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  • Blanco, A., et al. (författare)
  • Performance of timing resistive plate chambers with relativistic neutrons from 300 to 1500 MeV
  • 2015
  • Ingår i: Journal of Instrumentation. - : IOP Publishing. - 1748-0221. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • A prototype composed of four resistive plate chamber layers has been exposed to quasi-monoenergetic neutrons produced from a deuteron beam of varying energy (300 to 1500 AMeV) in experiment S406 at GSI, Darmstad, Germany. Each layer, with an active area of about 2000 × 500 mm2, is made of modules containing the active gaps, all in multigap construction. Each gap is defined by 0.3 mm nylon mono-filaments positioned between 2.85 mm thick float glass electrodes. The modules are operated in avalanche mode with a non-flammable gas mixture composed of 90% C2H2F4 and 10% SF6. The signals are readout by a pick-up electrode formed by 15 copper strips (per layer), spaced at a pitch of 30 mm, connected at both sides to timing front end electronics. Measurements of the time of flight jitter of neutrons, in the mentioned energy range, point to a contribution of the resistive plate chamber in the order of 150 ps, independent of the neutron energy.
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15.
  • Holl, M., et al. (författare)
  • Quasi-free neutron and proton knockout reactions from light nuclei in a wide neutron-to-proton asymmetry range
  • 2019
  • Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 795, s. 682-688
  • Tidskriftsartikel (refereegranskat)abstract
    • The quasi-free scattering reactions 11C(p,2p) and 10,11,12C(p,pn) have been studied in inverse kinematics at beam energies of 300–400 MeV/u at the R3B-LAND setup. The outgoing proton-proton and proton-neutron pairs were detected in coincidence with the reaction fragments in kinematically complete measurements. The efficiency to detect these pairs has been obtained from GEANT4 simulations which were tested using the 12C(p,2p) and 12C(p,pn) reactions. Experimental cross sections and momentum distributions have been obtained and compared to DWIA calculations based on eikonal theory. The new results reported here are combined with previously published cross sections for quasi-free scattering from oxygen and nitrogen isotopes and together they enable a systematic study of the reduction of single-particle strength compared to predictions of the shell model over a wide neutron-to-proton asymmetry range. The combined reduction factors show a weak or no dependence on isospin asymmetry, in contrast to the strong dependency reported in nucleon-removal reactions induced by nuclear targets at lower energies. However, the reduction factors for (p,2p) are found to be 'significantly smaller than for (p,pn) reactions for all investigated nuclei.
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16.
  • Machado, J., et al. (författare)
  • Performance of timing Resistive Plate Chambers with protons from 200 to 800 MeV
  • 2015
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 10:1, s. C01043-
  • Tidskriftsartikel (refereegranskat)abstract
    • A prototype composed of four resistive plate chamber layers has been exposed to quasi-monoenergetic protons produced from a deuteron beam of varying energy (200 to 800 AMeV) in experiment S406 at GSI, Darmstadt, Germany. The aim of the experiment is to characterize the response of the prototype to protons in this energy range, which deposit from 1.75 to 6 times more energy than minimum ionizing particles. Each layer, with an active area of about 2000 × 500 mm 2 , is made of modules containing the active gaps, all in multigap construction. Each gap is defined by 0.3 mm nylon mono-filaments positioned between 2.85 mm thick float glass electrodes. The modules are operated in avalanche mode with a non-flammable gas mixture composed of 90% C 2 H 2 F 4 and 10% SF 6 . The signals are readout by a pick-up electrode formed by 15 copper strips (per layer), spaced at a pitch of 30 mm, connected at both sides to timing front end electronics. Results show an uniform efficiency close to 100% along with a timing resolution of around 60 ps on the entire 2000 × 500 mm 2 area.
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  • Bonfiglio, F., et al. (författare)
  • Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome
  • 2018
  • Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 155:1, s. 168-179
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 x 10(-8)) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0 x 10(-6)). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 x 10(-10) in UK Biobank) and also associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKB-KAP), which is mutated in patients with familial dysautonomia. CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.
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  • Donia, M., et al. (författare)
  • Acquired Immune Resistance Follows Complete Tumor Regression without Loss of Target Antigens or IFN gamma Signaling
  • 2017
  • Ingår i: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 77:17, s. 4562-4566
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer immunotherapy can result in durable tumor regressions in some patients. However, patients who initially respond often experience tumor progression. Here, we report mechanistic evidence of tumoral immune escape in an exemplary clinical case: a patient with metastatic melanoma who developed disease recurrence following an initial, unequivocal radiologic complete regression after T-cell-based immunotherapy. Functional cytotoxic T-cell responses, including responses to one mutant neoantigen, were amplified effectively with therapy and generated durable immunologic memory. However, these immune responses, including apparently effective surveillance of the tumor mutanome, did not prevent recurrence. Alterations of the MHC class I antigen-processing and presentation machinery (APM) in resistant cancer cells, but not antigen loss or impaired IFN gamma signaling, led to impaired recognition by tumor-specific CD8(+) T cells. Our results suggest that future immunotherapy combinations should take into account targeting cancer cells with intact and impaired MHC class I-related APM. Loss of target antigens or impaired IFN gamma signaling does not appear to be mandatory for tumor relapse after a complete radiologic regression. Personalized studies to uncover mechanisms leading to disease recurrence within each individual patient are warranted.
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  • IDS Collaboration, HASH(0x3dac240), et al. (författare)
  • Beta-delayed proton emission from 20Mg
  • 2016
  • Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-601X .- 1434-6001. ; 52:10, s. 304-
  • Tidskriftsartikel (refereegranskat)abstract
    • Beta-delayed proton emission from 20 Mg has been measured at ISOLDE, CERN, with the ISOLDE Decay Station (IDS) setup including both charged-particle and gamma-ray detection capabilities. A total of 27 delayed proton branches were measured including seven so far unobserved. An updated decay scheme, including three new resonances above the proton separation energy in 20 Na and more precise resonance energies, is presented. Beta-decay feeding to two resonances above the Isobaric Analogue State (IAS) in 20 Na is observed. This may allow studies of the 4032.9(2.4)keV resonance in 19 Ne through the beta decay of 20 Mg, which is important for the astrophysically relevant reaction 15O(?,?)19Ne. Beta-delayed protons were used to obtain a more precise value for the half-life of 20 Mg, 91.4(1.0)ms.
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  • Semb, G, et al. (författare)
  • Erratum
  • 2017
  • Ingår i: Journal of plastic surgery and hand surgery. - 2000-6764. ; 51:2, s. 158-158
  • Tidskriftsartikel (refereegranskat)
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23.
  • Wohlfarth, C., et al. (författare)
  • miR-16 and miR-103 impact 5-HT4 receptor signalling and correlate with symptom profile in irritable bowel syndrome
  • 2017
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Irritable bowel syndrome (IBS) is a gut-brain disorder involving alterations in intestinal sensitivity and motility. Serotonin 5-HT4 receptors are promising candidates in IBS pathophysiology since they regulate gut motor function and stool consistency, and targeted 5-HT4R selective drug intervention has been proven beneficial in subgroups of patients. We identified a single nucleotide polymorphism (SNP) (rs201253747) c.*61 T > C within the 5-HT4 receptor gene HTR4 to be predominantly present in diarrhoea-IBS patients (IBS-D). It affects a binding site for the miR-16 family and miR-103/miR-107 within the isoforms HTR4b/i and putatively impairs HTR4 expression. Subsequent miRNA-profiling revealed downregulation of miR-16 and miR-103 in the jejunum of IBS-D patients correlating with symptoms. In vitro assays confirmed expression regulation via three 3'UTR binding sites. The novel isoform HTR4b_2 lacking two of the three miRNA binding sites escapes miR-16/103/107 regulation in SNP carriers. We provide the first evidence that HTR4 expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or by diminished levels of miR-16 and miR-103 suggesting that HTR4 might be involved in the development of IBS-D.
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  • Deisenhammer, F, et al. (författare)
  • Prediction of natalizumab anti-drug antibodies persistency
  • 2019
  • Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 25:3, s. 392-398
  • Tidskriftsartikel (refereegranskat)abstract
    • Anti-drug antibodies (ADA) against natalizumab develop early during treatment. ADA persistency is defined by two consecutive positive results as performed by the current qualitative ELISA assay (positive/negative). Very little is known about the magnitude of the natalizumab ADA response and persistency. Design/methods: We developed a highly sensitive natalizumab ADA titration assay on the Meso Scale Discovery (MSD) platform and a pharmacokinetic (PK) assay. We included 43 patients with a positive ELISA-ADA result within 6 months of treatment initiation (baseline) of whom a follow-up serum sample was available 12–30 months after treatment start. MSD-ADA titres and drug levels were measured. Results: Median MSD-ADA titre at baseline was 4881 and 303 at follow-up. A titre of >400 at baseline had a 94% sensitivity and 89% specificity to predict ADA persistency. Reversion to ADA negativity occurred in 10 patients with mean drug levels of 10.8 μg/mL. The median trough drug level in ADA-positive samples was 0 µg/mL. PK levels and ADA titres correlated strongly negatively ( r = −0.67). Conclusion: High baseline natalizumab ADA titres accurately predict persistency. Despite continuous treatment, the majority of patients with persistent ADA had no detectable drug levels indicating loss of efficacy in line with phase 3 study results.
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  • Shahid, M., et al. (författare)
  • Serratia sp. CP-13 augments the growth of cadmium (Cd)-stressed Linum usitatissimum L. by limited Cd uptake, enhanced nutrient acquisition and antioxidative potential
  • 2019
  • Ingår i: Journal of Applied Microbiology. - : Oxford University Press (OUP). - 1364-5072 .- 1365-2672. ; 126:6, s. 1708-1721
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: The current study was aimed to evaluate the beneficial effects and bioremediation potential of a Cd-tolerant bacterial strain, Serratia sp. CP-13, on the physiological and biochemical functions of Linum usitatissimum L., under Cd stress.Methods and Results: The bacterial strain was isolated from the wastewater collection point of Chakera, Faisalabad, Pakistan, as this place contains industrial wastewater of the Faisalabad region. The Serratia sp. CP-13, identified through 16S rRNA gene sequence analysis, exhibited a significant phyto-beneficial potential in terms of in vitro inorganic phosphate solubilization, indole-3-acetic acid production and 1-aminocyclopropane-1-carboxylic acid deaminase activity. Effects of Serratia sp. CP-13 inoculation on L. usitatissimum were evaluated by growing the plants in CdCl2 (0, 5 or 10 mg kg(-1) dry soil)-spiked soil. Without inoculation of Serratia sp. CP-13, Cd stress significantly reduced the plant biomass as well as the quantity of proteins and photosynthetic pigments due to enhanced H2O2, malondialdehyde (MDA) contents and impaired nutrient homeostasis. Subsequently, Serratia sp. CP-13 increased the plant fresh and dry biomass, plant antioxidation capacity, whereas it decreased the lipid peroxidation under Cd stress. In parallel, Serratia sp. inoculation assisted the Cd-stressed plants to maintain an optimum level of nutrients (K, Ca, P, Mg, Fe and Mn).Conclusions: The isolated bacterial strain (Serratia sp. CP-13) when applied to Cd-stressed L. usitatissimum inhibited the Cd uptake, reduced Cd-induced lipid peroxidation, maintained the optimum level of nutrients and thereby, enhanced L. usitatissimum growth. The analysis of bio-concentration and translocation factor revealed that L. usitatissimum with Serratia sp. CP-13 inoculation sequestered Cd in plant rhizospheric zone.Significance and Impact of the Study: Serratia sp. CP-13 inoculation is a potential candidate for the development of low Cd-accumulating linseed and could be used for phytostabilization of Cd-contaminated rhizosphere/soil colloids.
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