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- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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- Radhakrishnan, M, et al.
(författare)
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Effect of chromium variation on evolution of magnetic properties in laser direct energy additively processed CoCrxFeNi alloys
- 2023
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Ingår i: Scripta Materialia. - : Elsevier BV. - 1359-6462. ; 226
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Tidskriftsartikel (refereegranskat)abstract
- The soft magnetic behavior of laser directed energy deposited CoCrxFeNi (x = 0 - 24 at.% Cr) alloys has been investigated as a function of chromium content. The saturation magnetization of these CoCrxFeNi alloys monotonically decreased with increasing concentration of Cr, and exhibited paramagnetic behavior at room temperature for equiatomic CoCrFeNi alloy composition. Similarly, the Curie temperature (Tc) of the ferromagnetic CoFeNi alloy linearly decreased with Cr content, while the paramagnetic equiatomic alloy indicated a ferromagnetic transition temperature of 94 K. Interestingly, all the as-deposited alloys exhibited coercivity values less than 2 Oe irrespective of the Cr content. The results indicate that the magnetic behavior of the ferromagnetic CoFeNi alloy can be systematically tuned with addition of antiferromagnetic Cr, and the additive manufacturing route was successful in rapid processing alloys of any desired composition, in a high throughput manner, with negligible chemical variation. These findings are promising for the fabrication of components for applications demanding gradient magnetic coatings and alloys.
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- Varahabhatla, S. M., et al.
(författare)
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Influence of energy density on the microstructure, growth orientation, and anisotropy of magnetic properties in additively manufactured Fe-3.8wt%Si transformer steels
- 2023
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Ingår i: Materialia. - 2589-1529. ; 30
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Tidskriftsartikel (refereegranskat)abstract
- Fe-3.8wt%Si transformer steels were processed using two different additive manufacturing (AM) techniques, laser powder bed fusion (LPBF) and directed energy deposition (DED). While the LPBF processed samples exhibited a strong <001> orientation of the BCC grains along the build axis, the DED processed samples exhibited a randomized texture along the build axis. DED processed samples showed substantially coarser columnar grains as compared to their LPBF counterparts. The columnar grains exhibited a substantial number of low-angle sub-grain boundaries. All samples exhibited very good soft magnetic properties, with saturation magnetization (Ms) values ranging from 205 - 232 emu/gm, and coercivity (Hc) values ranging from 1.2 – 4.2 Oe. The Coercivity (Hc) values were significantly lower when the magnetic field was applied parallel to the build axis, as compared to being perpendicular, which can be rationalized based on the columnar nature of the grains, resulting in a higher number density of grain boundaries in case of the field applied perpendicular to the build axis.
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- Aguggia, Julieta P., et al.
(författare)
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Growth hormone secretagogue receptor signaling in the supramammillary nucleus targets nitric oxide-producing neurons and controls recognition memory in mice
- 2022
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 139
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin is a stomach-derived hormone that acts via the growth hormone secretagogue receptor (GHSR). Recent evidence suggests that some of ghrelin's actions may be mediated via the supramammillary nucleus (SuM). Not only does ghrelin bind to cells within the mouse SuM, but ghrelin also activates SuM cells and intra-SuM ghrelin administration induces feeding in rats. In the current study, we aimed to further characterize ghrelin action in the SuM. We first investigated a mouse model expressing enhanced green fluorescent protein (eGFP) under the promoter of GHSR (GHSR-eGFP mice). We found that the SuM of GHSR-eGFP mice contains a significant amount of eGFP cells, some of which express neuronal nitric oxide synthase. Centrally-, but not systemically-, injected ghrelin reached the SuM, where it induced c-Fos expression. Furthermore, a 5-day 40% calorie restriction protocol, but not a 2-day fast, increased c-Fos expression in non-eGFP+ cells of the SuM of GHSR-eGFP mice, whereas c-Fos induction by calorie restriction was not observed in GHSR-deficient mice. Exposure of satiated mice to a binge-like eating protocol also increased c-Fos expression in non-eGFP+ cells of the SuM of GHSR-eGFP mice in a GHSR-dependent manner. Finally, intra-SuM-injected ghrelin did not acutely affect food intake, locomotor activity, behavioral arousal or spatial memory but increased recognition memory. Thus, we provide a compelling neuroanatomical characterization of GHSR SuM neurons and its behavioral implications in mice.
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