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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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- Mani, K, et al.
(författare)
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Heparan/chondroitin/dermatan sulfate primer 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside preferentially inhibits growth of transformed cells
- 1998
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Ingår i: Cancer Research. - 0008-5472. ; 58:6, s. 104-1099
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Tidskriftsartikel (refereegranskat)abstract
- Xylose forms the direct carbohydrate-protein link in extra- or pericellular proteoglycans (PGs) that are substituted with either chondroitin sulfate (CS)/dermatan sulfate (DS) and/or heparan sulfate (HS). Cell surface PGs carrying HS are important regulators of cell growth. Xylose coupled to an aromatic compound can enter cells and initiate either CS/DS synthesis or both HS and CS/DS synthesis, depending on the nature of the aromatic adduct. Here, we show that 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside, which can prime both types of glycan chains, inhibits growth of a set of normal and transformed cells. Transformed cells are preferentially inhibited, and at a concentration of 0.15-0.20 mM xyloside, transformed cells are totally growth arrested, whereas normal cells are only < or = 50% inhibited. No inhibition of growth is observed with the stereoisomeric 2-(6-hydroxynaphthyl)-O-beta-L-xylopyranoside, which does not prime glycosaminoglycan synthesis at all; with the nonhydroxylated 2-naphthyl-O-beta-D-xylopyranoside, which only primes CS/DS synthesis under these conditions; or with p-nitrophenyl-O-beta-D-xylopyranoside, which is known to prime only CS/DS synthesis. We conclude that growth inhibition is due to priming of HS and/or CS/DS synthesis, which may either lead to the formation of specific antiproliferative glycans or glycan fragments or to interference with endogenous PG synthesis and turnover.
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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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- Bernstein, W. Z., et al.
(författare)
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An open web-based repository for capturing manufacturing process information
- 2016
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Ingår i: ASME 2016 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference, IDETC/CIE 2016, Charlotte, United States, 21-24 August. ; 4
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Konferensbidrag (refereegranskat)abstract
- With recent progress in developing more effective models for representing manufacturing processes, this paper presents an approach towards an open web-based repository for storing manufacturing process information. The repository is envisioned to include several new use cases in the context of information use in smart manufacturing. This paper examines several key benefits through usage scenarios engaging existing engineering activities. Based on the scenarios, the desired characteristics of an open web-based repository are presented, namely that it will be (1) complementary to existing practices, (2) open and netcentric, (3) able to enforce model consistency, (4) modular (5) extensible, and (5) able to govern contributions. A repository will support and motivate the ubiquitous and extended use of standardized representations of unit manufacturing processes in order to promote consistency of performance assessments across industries and provide a tangible, data-driven perspective for analysis-related activities. Furthermore, the paper presents additional benefits and possible applications that could result from a shared manufacturing repository.
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