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- Tabassum, R, et al.
(författare)
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Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
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Tidskriftsartikel (refereegranskat)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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| 5. |
- Rivas, Manuel A., et al.
(författare)
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A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis
- 2016
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Ingår i: Nature Communications. - London, United Kingdom : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.
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| 8. |
- Baud, Patrick, et al.
(författare)
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The Brittle-Ductile Transition in Porous Limestone : Failure Mode, Constitutive Modeling of Inelastic Deformation and Strain Localization
- 2021
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Ingår i: Journal of Geophysical Research: Solid Earth. - 2169-9313. ; 126:5
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Tidskriftsartikel (refereegranskat)abstract
- Understanding of the mechanics of the brittle-ductile transition (BDT) in porous limestone is significantly more challenging than for sandstone because of the lack of consistent acoustic emission activity in limestone, meaning that one must rely on alternative techniques. In this paper, we investigate systematically the failure modes in Indiana limestone using X-ray microComputed Tomography imaging (μCT) and Digital Volume Correlation (DVC). Our new mechanical data show that the envelope for the onset of shear-enhanced compaction can be well approximated by an elliptical cap. The DVC analysis revealed the development of shear bands through the BDT, but no evidence of compaction bands. The shear band angles were between 29° and 46° with respect to the maximum principal stress. Compiling these new results with published data on Purbeck and Leitha limestones, we showed that inelastic compaction in each of these dual porosity allochemical limestones was in a good agreement with the normality condition, as defined in plasticity theory. Comparison of the observed failure modes with predictions based on bifurcation analysis showed that the shear band angles are consistently smaller than the theoretical predictions.
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| 9. |
- Baud, Patrick, et al.
(författare)
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The Brittle-Ductile Transition in Porous Limestone Imaged by X-Ray Computed Tomography and Digital Image Correlation
- 2017
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Ingår i: Poromechanics 2017 - Proceedings of the 6th Biot Conference on Poromechanics. - Reston, VA : American Society of Civil Engineers. - 9780784480779 ; , s. 1782-1788
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Konferensbidrag (refereegranskat)abstract
- We studied the brittle-ductile transition in three porous carbonates, Indiana, USA, Majella, Italy, and Leitha, Austria, with porosity ranging between 16 and 31%. A series of triaxial experiments were performed at room temperature, constant strain rate, and at effective pressures ranging from 5 to 150 MPa. Several sets of X-ray Tomography images were acquired before and after deformation. 3D digital image correlation (DIC) was performed on the images of the intact and deformed samples. The use of 3D-volumetric DIC allowed us to map out the subtle development of strain localization associated with the transition from brittle faulting to cataclastic flow in the three limestones. Our observations showed that strain localization may develop at relatively small axial strains of ~1%, in both the brittle faulting and transitional regimes. In Majella limestone (porosity = 31%), the localized deformation involved both shear and compaction. Compaction bands were only observed in less cemented samples of Leitha limestone.
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