| 1. |
- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 2. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 3. |
- Pelletier, F., et al.
(författare)
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Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C
- 2021
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:2
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Tidskriftsartikel (refereegranskat)abstract
- Context: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting: This was a multicenter retrospective study using information collected from 3 predominant centers. Patients: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.
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| 4. |
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| 6. |
- Aleksandrov, D., et al.
(författare)
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Halo excitations in fragmentation of He-6 at 240 MeV/u on carbon and lead targets
- 2000
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Ingår i: Nuclear Physics A. - 0375-9474. ; 669:1-2, s. 51-64
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Tidskriftsartikel (refereegranskat)abstract
- Dissociation of a 240 MeV/u beam of He-6, incident on carbon and lead targets, has been studied in kinematically complete experiments to investigate low-lying excitation modes in the halo nucleus He-6. It is shown that alignment effects characterize the inelastic scattering and allow an unambiguous assignment of the spin of a narrow resonance observed in the excitation energy spectrum. The differential cross sections for the He-6 inelastic scattering on carbon and lead targets were deduced from the measured moments of the two neutrons and the a-particle. An analysis of these distributions shows that quadrupole and, possibly, monopole excitations characterize the hadronic interaction, while the dipole mode is dominating in Coulomb dissociation. Neither theoretically predicted new resonance states in He-6 nor nuclear excitation of a dipole mode were found. Direct evidence has been obtained for strong suppression of Coulornb post-acceleration in direct Coulomb breakup in a lead target.
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| 7. |
- Aleksandrov, D., et al.
(författare)
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Invariant mass spectrum and alpha-n correlation function studied in the fragmentation of He-6 on a carbon target
- 1998
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Ingår i: Nuclear Physics A. - 0375-9474. ; 633:2, s. 234-246
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Tidskriftsartikel (refereegranskat)abstract
- Momentum distributions and invariant mass spectra from the breakup of He-6 ions with an energy of 240 MeV/u interacting with a carbon target have been studied. The data were used to extract information about the reaction mechanism which is influenced by the structure of He-6. It is found that the dominant reaction mechanism is a two-step process: knock out of one neutron followed by the decay of the He-5 resonance. The shape of the (alpha+n) two-body invariant mass spectrum is interpreted as mainly reflecting the 5He ground state which is a J(pi) = 3/2(-) resonance. However, no evidence for correlations between cu particles and neutrons is observed in the momentum widths of the distributions. It is demonstrated that a combined analysis of the two-body invariant mass spectrum and an appropriate correlation function may be used to determine the properties of the intermediate resonance. (C) 1998 Elsevier Science B.V.
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| 8. |
- Chulkov, L. V., et al.
(författare)
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Large spin alignment of the unbound He-5 fragment after fragmentation of 240 MeV/nucleon He-6
- 1997
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 79:2, s. 201-204
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral fragmentation of a 240 MeV/nucleon beam of the halo nucleus He-6 incident on carbon target has been studied in a kinematically complete experiment. It is found that one-neutron stripping to the unbound nucleus He-5 is the dominant fragmentation mechanism and that it leads to a spin alignment of He-5 in a plane perpendicular to the He-5 momentum vector. This is expected to be a common feature for all neutron halo nuclei.
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| 9. |
- Humbert, F., et al.
(författare)
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Longitudinal and Transverse-Momentum Distributions of Li-9 Fragments from Break-up of Li-11
- 1995
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 347:3-4, s. 198-204
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Tidskriftsartikel (refereegranskat)abstract
- Transverse and longitudinal momentum distributions of Li-9 fragments from Li-11 break-up reactions in C, Al and Pb targets have been measured at 280 MeV/u. The two-neutron removal cross-section was measured to be sigma(-2n), = 0.26 +/- 0.02 b for the carbon target, sigma(-2n) = 0.47 +/- 0.08 b for the aluminum target and sigma(-2n), = 1.9 +/- 0.4 b for the lead target. No significant difference is observed between the narrow widths (FWHM approximate to 47 MeV/c) of the transverse and longitudinal momentum distributions of the Li-9 fragments. The physical implications of this are discussed.
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| 10. |
- Johnson, D C, et al.
(författare)
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Genetic factors influencing the risk of multiple myeloma bone disease.
- 2016
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 30, s. 883-888
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Tidskriftsartikel (refereegranskat)abstract
- A major complication of multiple myeloma (MM) is the development of osteolytic lesions, fractures and bone pain. To identify genetic variants influencing the development of MM bone disease (MBD), we analyzed MM patients of European ancestry (totalling 3774) which had been radiologically surveyed for MBD. Each patient had been genotyped for ~600 000 SNPs with genotypes for six million common variants imputed using 1000Genomes Project and UK10K as reference. We identified a locus at 8q24.12 for MBD (rs4407910, OPG/TNFRSF11B, odds ratio [OR]=1.38, P=4.09 × 10(-9)) and a promising association at 19q13.43 (rs74676832, OR=1.97, P=9.33 × 10(-7)). Our findings demonstrate that germline variation influences MBD and highlights the importance of RANK/RANKL/OPG pathway in MBD development. These findings will contribute to the development of future strategies for prevention of MBD in the early precancerous phases of MM.Leukemia accepted article preview online, 16 December 2015. doi:10.1038/leu.2015.342.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Went, M, et al.
(författare)
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Author Correction: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 213-
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Tidskriftsartikel (refereegranskat)abstract
- The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Baumann, T., et al.
(författare)
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Longitudinal momentum distributions of C-16,C-18 fragments after one-neutron removal from C-17,C-19
- 1998
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 439:3-4, s. 256-261
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Tidskriftsartikel (refereegranskat)abstract
- The fragment separator FRS at GSI was used as an energy-loss spectrometer to measure the longitudinal momentum distributions of C-16,C-18 fragments after one-neutron removal reactions in C-17,C-19 impinging on a carbon target at about 910 MeV/u. The distributions in the projectile frames are characterized by a FWHM of 141 +/- 6 MeV/c for C-16 and 69 +/- 3 MeV/c for C-18. Th, results are compared with experimental data obtained at lower energies and discussed within existing theoretical models. (C) 1998 Elsevier Science B.V. AU rights reserved.
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| 21. |
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| 22. |
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| 23. |
- Dittrich, Th, et al.
(författare)
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Diffusion length of photo-generated charge carriers in layers and powders of CH3NH3PbI3 perovskite
- 2016
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 109:7
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Tidskriftsartikel (refereegranskat)abstract
- The diffusion or transport lengths of photo-generated charge carriers in CH3NH3PbI3 layers (thickness up to 1 μm) and powders have been directly measured with high accuracy by modulated surface photovoltage after Goodman. The values of the diffusion lengths of photo-generated charge carriers ranged from 200 nm to tenths of μm. In thin CH3NH3PbI3 layers, the transport lengths corresponded to the layer thickness whereas in thicker layers and in crystallites of CH3NH3PbI3 powders the grain size limited the diffusion length. For grains, the diffusion length of photo-generated charge carriers depended on the measurement conditions.
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| 24. |
- Johnson, David C, et al.
(författare)
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Genome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma.
- 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
- Survival following a diagnosis of multiple myeloma (MM) varies between patients and some of these differences may be a consequence of inherited genetic variation. In this study, to identify genetic markers associated with MM overall survival (MM-OS), we conduct a meta-analysis of four patient series of European ancestry, totalling 3,256 patients with 1,200 MM-associated deaths. Each series is genotyped for ∼600,000 single nucleotide polymorphisms across the genome; genotypes for six million common variants are imputed using 1000 Genomes Project and UK10K as the reference. The association between genotype and OS is assessed by Cox proportional hazards model adjusting for age, sex, International staging system and treatment. We identify a locus at 6q25.1 marked by rs12374648 associated with MM-OS (hazard ratio=1.34, 95% confidence interval=1.22-1.48, P=4.69 × 10(-9)). Our findings have potential clinical implications since they demonstrate that inherited genotypes can provide prognostic information in addition to conventional tumor acquired prognostic factors.
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| 25. |
- Liewald, C., et al.
(författare)
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Scanning photocurrent microscopy of electrons and holes in the pigment semiconductor epindolidione
- 2018
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Ingår i: Organic electronics. - : ELSEVIER SCIENCE BV. - 1566-1199 .- 1878-5530. ; 60, s. 51-56
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Tidskriftsartikel (refereegranskat)abstract
- Photocurrent microscopy is used to characterize the kinetics of electrons and holes in organic field-effect transistors (FETs) with the hydrogen-bonded pigment epindolidione as active layer. The method relies on electrons and holes, generated on local illumination, which are provided after exciton splitting, to probe charge trapping. In the dark, hole conduction is observed for negative gate voltage while no electron conduction is observed for positive gate voltage. However, under illumination, a fast displacement current with 60 mu s onset time and 1 ms exponential decay occurs for positive gate voltage, which can be explained by exciton splitting underneath the semitransparent top contact followed by subsequent electron trapping and hole extraction. Afterward, trapped electrons hop via further trap states within the film to the insulator into interface traps (13 ms exponential decay) which induce a positive threshold voltage shift in the FET transfer curves for hole transport. Photocurrent microscopy confirms that the displacement current occurs only for illumination under and near the semitransparent source/drain contacts, which act here as metal-insulator-semiconductor (MIS) diodes. For negative gate voltage instead, the photocurrent comprises an enhanced hole current in the FET channel between the contacts. In the channel region, the detrapping of holes at the interface with the insulator (3 ms time constant) enhances the transistor current at low frequencies amp;lt; 1 kHz, whereas the displacement current between the contacts and the gate is observed only at frequencies amp;gt; 10 kHz. Thus, we show here that photocurrent microscopy allows to identify the kinetics of electrons and holes in traps close to the contacts and in the FET channel of pigment transistors.
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| 26. |
- Liu, X, et al.
(författare)
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An IL13 coding region variant is associated with a high total serum IgE level and atopic dermatitis in the German Multicenter Atopy Study (MAS-90)
- 2000
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 106:1 I, s. 167-170
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergic diseases are one of the major causes of morbidity in the developed countries today, and the prevalence of these diseases is increasing steadily. Study of total serum IgE level is important in understanding the genetics of allergic diseases because IgE levels are considered to be a crucial pathogenic component. IL-13 plays an important role in the induction of IgE synthesis and in the pathogenesis of allergic diseases. Objective: We sought to examine potential variation at the IL13 gene and estimate its effect on elevated IgE level and atopic dermatitis (AD). Methods: We conducted mutational analyses of the IL13 gene by using single-stranded conformation polymorphism and DNA sequencing. Case control studies for high-IgE phenotype and AD were performed by using subjects from the German MAS-90 cohort. Results: A novel IL13 coding region variant at 4257 bp (G to A, fourth exon) was identified. Case control studies of a German sample from the MAS-90 cohort showed significant associations between the presence of the A allele and two atopic phenotypes: high IgE (odds ratio, 2.38, 95% confidence interval, 1.35-4.21, P = .0026) and AD (odds ratio, 1.77, 95% confidence interval, 1.06-2.96, P = .03). Conclusion: This IL13 coding region variant may be involved in the pathogenesis of AD and high total serum IgE level in a study population of white subjects.
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| 27. |
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| 28. |
- Markenroth, Karin, 1973, et al.
(författare)
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He-8-He-6: a comparative study of nuclear fragmentation reactions
- 2001
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Ingår i: Nuclear Physics A. - 0375-9474. ; 679:3-4, s. 462-480
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Tidskriftsartikel (refereegranskat)abstract
- Dissociation of 227 MeV/u He-8 in a carbon target has been studied in kinematically complete experiments. The data include the relative energy spectrum, angular distributions in the neutron knock-out channel (He-6 + n) as well as diffractive dissociation and inelastic scattering into the (He-6 + 2n) channel. The data are compared with corresponding results from the well-known halo nucleus He-6. In both cases it is found that neutron knock-out is the: dominating reaction channel. The relative energy spectrum (He-6 + n) shows a structure, which is interpreted as being due to the I-pi = 3/2(-) resonance in the He-7 ground state with about equal contribution from its I-pi = 1/2(-) spin-orbit partner. The He-7 resonance shows a spin alignment similar to that observed in He-5, but with a smaller anisotropy indicating that the structure of the He-8 ground state is more complicated than that of He-6. The data in the (He-6 + 2n) channel were used to identify resonances in the excitation energy spectrum of He-8. If the spectrum is interpreted as two overlapping resonances, the spin-parity assignment for these is found to be 2(+) and 1(-), respectively.
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| 29. |
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| 30. |
- Nilsson, Thomas, 1965, et al.
(författare)
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He-6 and neutron momentum distributions from He-8 in nuclear break-up reactions at 240 MeV/u
- 1996
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Ingår i: Nuclear Physics A. - 0375-9474. ; 598:3, s. 418-434
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Tidskriftsartikel (refereegranskat)abstract
- Neutron and He-6 momentum distributions from He-8 break-up reactions in a C target have been measured at 240 MeV/u. The two-neutron removal cross section was found to be sigma(-2n) = 0.27 +/- 0.03 b. The nature of the momentum distributions is interpreted in some simple reaction scenarios.
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| 31. |
- Nilsson, Thomas, 1965, et al.
(författare)
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Neutron Momentum Distributions from Core Break-up Reactions of Halo Nuclei
- 1995
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Ingår i: Europhysics Letters. - 0295-5075 .- 1286-4854. ; 30:1, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- Neutron angular distributions from violent break-up reactions of Li-11 and Be-11 have been measured at 28 MeV/u and 280 MeV/u and at 41 MeV/u and 460 MeV/u, respectively. The derived neutron momentum distributions show a narrow component in transverse momentum that is within uncertainties independent of beam energy and target charge. This component is suggested to be simply related to the momentum distribution of the loosely bound halo neutron(s) in the projectiles.
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| 32. |
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| 33. |
- Sieber, Maximilian, et al.
(författare)
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Corrosion Protection of Al/Mg Compounds by Simultaneous Plasma Electrolytic Oxidation
- 2015
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Ingår i: Materials Today: Proceedings, Volume 2, Supplement 1. - : Elsevier Ltd. ; , s. S149-S155
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Konferensbidrag (refereegranskat)abstract
- The application of Al/Mg compound materials for lightweight structures is limited by their corrosion susceptibility. The primary corrosion attack takes place at the Mg component. This may partly be caused by galvanic corrosion and partly by the insufficient formation of a natural passive layer on magnesium. Therefore, oxide coatings were produced on the co-extruded Al/Mg compounds by simultaneous plasma electrolytic oxidation (PEO). A silicate-alkaline and a silicate-phosphate-alkaline electrolyte were used for the coincident production of coatings with a thickness of several 10 microns on both the aluminum and the magnesium component. The inherent flaws of the coating (pores, cavities) allow for the infiltration with an epoxy-based sealant. The electrochemical behavior of the magnesium component covered with the oxide coatings with and without sealing was compared with reference to the unmodified surface. The surface modification (PEO w/wo sealing) significantly decreases the corrosion susceptibility of the Mg component, and thus of the compound.
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| 35. |
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