| 1. |
- Acosta-Herrera, M, et al.
(författare)
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Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:3, s. 311-319
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated inflammatory diseases (IMIDs) are heterogeneous and complex conditions with overlapping clinical symptoms and elevated familial aggregation, which suggests the existence of a shared genetic component. In order to identify this genetic background in a systematic fashion, we performed the first cross-disease genome-wide meta-analysis in systemic seropositive rheumatic diseases, namely, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and idiopathic inflammatory myopathies.MethodsWe meta-analysed ~6.5 million single nucleotide polymorphisms in 11 678 cases and 19 704 non-affected controls of European descent populations. The functional roles of the associated variants were interrogated using publicly available databases.ResultsOur analysis revealed five shared genome-wide significant independent loci that had not been previously associated with these diseases: NAB1, KPNA4-ARL14, DGQK, LIMK1 and PRR12. All of these loci are related with immune processes such as interferon and epidermal growth factor signalling, response to methotrexate, cytoskeleton dynamics and coagulation cascade. Remarkably, several of the associated loci are known key players in autoimmunity, which supports the validity of our results. All the associated variants showed significant functional enrichment in DNase hypersensitivity sites, chromatin states and histone marks in relevant immune cells, including shared expression quantitative trait loci. Additionally, our results were significantly enriched in drugs that are being tested for the treatment of the diseases under study.ConclusionsWe have identified shared new risk loci with functional value across diseases and pinpoint new potential candidate loci that could be further investigated. Our results highlight the potential of drug repositioning among related systemic seropositive rheumatic IMIDs.
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| 2. |
- Broen, J. C. A., et al.
(författare)
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A rare polymorphism in the gene for Toll-like receptor 2 is associated with systemic sclerosis phenotype and increases the production of inflammatory mediators
- 2012
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 64:1, s. 264-271
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate whether polymorphisms in Toll-like receptor (TLR) genes, previously reported to be associated with immune-mediated diseases, are involved in systemic sclerosis (SSc). Methods. We genotyped 14 polymorphisms in the genes for TLRs 2, 4, 7, 8, and 9 in a discovery cohort comprising 452 SSc patients and 537 controls and a replication cohort consisting of 1,170 SSc patients and 925 controls. In addition, we analyzed 15-year followup data on 964 patients to assess the potential association of TLR variants with the development of disease complications. We analyzed the functional impact of the associated polymorphism on monocyte-derived dendritic cells. Results. In the discovery cohort, we observed that a rare functional polymorphism in TLR2 (Pro631His) was associated with antitopoisomerase (antitopo) positivity (odds ratio 2.24 [95% confidence interval 1.24-4.04], P = 0.003). This observation was validated in the replication cohort (odds ratio 2.73 [95% confidence interval 1.85-4.04], P = 0.0001). In addition, in the replication cohort the TLR2 variant was associated with the diffuse subtype of the disease (P = 0.02) and with the development of pulmonary arterial hypertension (PAH) (Cox proportional hazards ratio 5.61 [95% confidence interval 1.53-20.58], P = 0.003 by log rank test). Functional analysis revealed that monocyte-derived dendritic cells carrying the Pro63His variant produced increased levels of inflammatory mediators (tumor necrosis factor alpha and interleukin-6) upon TLR-2-mediated stimulation (both P < 0.0001). Conclusion. Among patients with SSc, the rare TLR2 Pro631His variant is robustly associated with antitopoisomerase positivity, the diffuse form of the disease, and the development of PAH. In addition, this variant influences TLR-2-mediated cell responses. Further research is needed to elucidate the precise role of TLR-2 in the pathogenesis of SSc.
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| 3. |
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| 4. |
- Girard-Alcindor, V., et al.
(författare)
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New narrow resonances observed in the unbound nucleus F 15
- 2022
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Ingår i: Physical Review C. - : American Physical Society (APS). - 2469-9985 .- 2469-9993. ; 105:5
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Tidskriftsartikel (refereegranskat)abstract
- The structure of the unbound F15 nucleus is investigated using the inverse kinematics resonant scattering of a radioactive O14 beam impinging on a CH2 target. The analysis of H1(O14,p)O14 and H1(O14,2p)N13 reactions allowed the confirmation of the previously observed narrow 1/2- resonance, near the two-proton decay threshold, and the identification of two new narrow 5/2- and 3/2- resonances. The newly observed levels decay by 1p emission to the ground of O14, and by sequential 2p emission to the ground state of N13 via the 1- resonance of O14. Gamow shell model (GSM) analysis of the experimental data suggests that the wave functions of the 5/2- and 3/2- resonances may be collectivized by the continuum coupling to nearby 2p- and 1p-decay channels. The observed excitation function H1(O14,p)O14 and resonance spectrum in F15 are well reproduced in the unified framework of the GSM.
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| 5. |
- De Angelis, A., et al.
(författare)
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Science with e-ASTROGAM A space mission for MeV-GeV gamma-ray astrophysics
- 2018
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Ingår i: Journal of High Energy Astrophysics. - : Elsevier. - 2214-4048 .- 2214-4056. ; 19, s. 1-106
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Tidskriftsartikel (refereegranskat)abstract
- e-ASTROGAM ('enhanced ASTROGAM') is a breakthrough Observatory space mission, with a detector composed by a Silicon tracker, a calorimeter, and an anticoincidence system, dedicated to the study of the non-thermal Universe in the photon energy range from 0.3 MeV to 3 GeV - the lower energy limit can be pushed to energies as low as 150 keV for the tracker, and to 30 keV for calorimetric detection. The mission is based on an advanced space-proven detector technology, with unprecedented sensitivity, angular and energy resolution, combined with polarimetric capability. Thanks to its performance in the MeV-GeV domain, substantially improving its predecessors, e-ASTROGAM will open a new window on the non-thermal Universe, making pioneering observations of the most powerful Galactic and extragalactic sources, elucidating the nature of their relativistic outflows and their effects on the surroundings. With a line sensitivity in the MeV energy range one to two orders of magnitude better than previous generation instruments, e-ASTROGAM will determine the origin of key isotopes fundamental for the understanding of supernova explosion and the chemical evolution of our Galaxy. The mission will provide unique data of significant interest to a broad astronomical community, complementary to powerful observatories such as LIGO-Virgo-GEO600-KAGRA, SKA, ALMA, E-ELT, TMT, LSST, JWST, Athena, CTA, IceCube, KM3NeT, and LISA.
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| 6. |
- Glechner, T., et al.
(författare)
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Correlation between fracture characteristics and valence electron concentration of sputtered Hf-C-N based thin films
- 2020
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Ingår i: Surface & Coatings Technology. - : Elsevier BV. - 0257-8972 .- 1879-3347. ; 399
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Tidskriftsartikel (refereegranskat)abstract
- Hard protective coating materials based on transition metal nitrides and carbides typically suffer from limited fracture tolerance. To further tune these properties non-metal alloying - substituting C with N - has been proven favorable for magnetron sputtered Hf-C-N based thin films. A theoretically predicted increase in valence electron concentration (from 8.0 to 9.0 e/f.u. from Hf-C to Hf-N) through nitrogen alloying lead to an increase in fracture toughness (K-IC obtained during in-situ SEM cantilever bending) from 1.89 +/- 0.15 to 2.33 +/- 0.18 MPa.m(1/2) for Hf0.43C0.57 to Hf0.35C0.30N0.35, respectively. The hardness remains close to the super-hard regime with values of 37.8 +/- 2.1 to 39.9 +/- 2.7 GPa for these specific compositions. Already the addition of small amounts of nitrogen, while sputtering a ceramic Hf-C target, leads to a drastic increase of nitrogen on the non-metallic sublattice for fcc single phased structured HfC1-xNx films, where x = N/(C + N). The here obtained results also provide experimental proof for the correlation between fracture characteristics and valence electron concentration.
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| 7. |
- Jakob, Severin, 1991, et al.
(författare)
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Effect of boron doping on grain boundary cohesion in technically pure molybdenum investigated via meso-scale three-point-bending tests
- 2023
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Ingår i: International Journal of Refractory Metals and Hard Materials. - : Elsevier BV. - 0263-4368 .- 2213-3917. ; 113
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Tidskriftsartikel (refereegranskat)abstract
- Molybdenum has numerous advantageous functional and high-temperature properties. However, plastic deformation as well as structural applications are limited due to a propensity for brittle, intercrystalline failure, especially at low temperatures. It is well known that oxygen segregations have a detrimental effect, whereas it is assessed that carbon and/or boron have a beneficial effect on grain boundary cohesion. An advanced approach for the improvement of these interfaces is segregation engineering, e.g. the addition of cohesion enhancing elements segregating to the grain boundaries. To investigate early stages of crack formation, three-point bending tests on recrystallized commercially pure and boron micro-doped molybdenum were conducted between −28 °C and room temperature. The tensile-loaded top surface of the specimens was examined post-mortem close to the final fracture area via scanning electron microscopy. The occurring separations of grains are investigated for distinct features and the chemical composition of the interface is complementary measured by atom probe tomography.
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| 8. |
- Jakob, Severin, 1991, et al.
(författare)
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Evolution of nano-pores during annealing of technically pure molybdenum sheet produced from different sintered formats
- 2023
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Ingår i: International Journal of Refractory Metals and Hard Materials. - : Elsevier BV. - 0263-4368 .- 2213-3917. ; 110
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Tidskriftsartikel (refereegranskat)abstract
- Molybdenum is a refractory metal with no phase transformation in the solid state and a high melting point. It is therefore an excellent structural material for various high temperature applications. Especially in this field of operation, significant creep resistance is essential. To achieve this, a microstructure with grains in the range of millimeters is desired. However, as demonstrated in the present study, the onset temperature for secondary recrystallization, which would lead to a beneficial grain size, is among other things dependent on the initial dimensions of the sintered part. One possible reason for the different microstructural evolutions is the influence of residual pores in sub-micrometer size. Sheets were thus fabricated via three different production routes employing the same initial Mo powder to exclude chemical variation as an influencing factor. The samples were investigated by in-situ small-angle X-ray scattering at a synchrotron radiation source with two different heating rates. Additionally, selected annealed samples were studied ex-situ with high energy X-rays. The apparent volume fraction of pores is compared to a volatilization model for the vaporization of typical accompanying elements and the induced thermal expansion.
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