| 1. |
- Dupuis, Josee, et al.
(författare)
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New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
- 2010
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Ingår i: Nature Genetics. - 1061-4036. ; 42:2, s. 105-116
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Tidskriftsartikel (refereegranskat)abstract
- Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
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| 2. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - 0028-0836. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 3. |
- Morris, Andrew P., et al.
(författare)
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Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes
- 2012
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Ingår i: Nature Genetics. - Nature Publishing Group. - 1061-4036. ; 44:9, s. 981-
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Tidskriftsartikel (refereegranskat)abstract
- To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genomewide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
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| 4. |
- Scott, Robert A., et al.
(författare)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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Ingår i: Nature Genetics. - Nature Publishing Group. - 1061-4036. ; 44:9, s. 991-1005
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Tidskriftsartikel (refereegranskat)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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| 5. |
- Hedström, Peter, et al.
(författare)
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Load partitioning and strain-induced martensite formation during tensile loading of a metastable austenitic stainless steel
- 2009
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Ingår i: Metallurgical and Materials Transactions A - Physical Metallurgy and Materials Science. - Springer New York LLC. - 1073-5623. ; 40:5
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Tidskriftsartikel (övrigt vetenskapligt)abstract
- In-situ high-energy X-ray diffraction and material modeling are used to investigate the strain-rate dependence of the strain-induced martensitic transformation and the stress partitioning between austenite and α′ martensite in a metastable austenitic stainless steel during tensile loading. Moderate changes of the strain rate alter the strain-induced martensitic transformation, with a significantly lower α′ martensite fraction observed at fracture for a strain rate of 10-2 s-1, as compared to 10-3 s-1. This strain-rate sensitivity is attributed to the adiabatic heating of the samples and is found to be well predicted by the combination of an extended Olson-Cohen strain-induced martensite model and finite-element simulations for the evolving temperature distribution in the samples. In addition, the strain-rate sensitivity affects the deformation behavior of the steel. The α′ martensite transformation at high strains provides local strengthening and extends the time to neck formation. This reinforcement is witnessed by a load transfer from austenite to α′ martensite during loading.
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| 6. |
- Larsson, C., et al.
(författare)
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Measurement and modeling of residual stress in a welded Haynes® 25 cylinder
- 2005
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Ingår i: Materials Science and Engineering A: Structural Materials: Properties, Microstructures and Processing. - Elsevier S.A.. - 0921-5093. ; 399:1-2
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Tidskriftsartikel (övrigt vetenskapligt)abstract
- An experimental and simulation study of residual stresses was made in the vicinity of a gas tungsten arc weld, used to join a hemispherical end cap to a cylinder. The capped cylinder is used in a satellite application and was fabricated from a Co-based Haynes® 25 alloy. The cylinder was 34.7 mm in outer diameter and 3.3 mm in thickness. The experimental measurements were made by neutron diffraction and the simulation used the implicit Marc finite element code. The experimental resolution was limited to approximately 3 mm parallel to the axis of the cylinder (the weld was 6 mm in the same direction) and comparison over the same volume of the finite element prediction showed general agreement. Subject to the limited spatial resolution, the largest experimentally measured tensile residual stress was 180 MPa, located at the middle of the weld. However, the predictions suggest that there are regions in the weld where average tensile residual stresses as much as 400 MPa exist. One qualitative disparity between the model and the experiments was that the measurement included a larger degree of asymmetry on either side of the weld than predicted by the model.
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| 7. |
- Liu, J., et al.
(författare)
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Finite element modelling of superplastic-like forming using a dislocation density-based model for AA5083
- 2013
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Ingår i: Modelling and Simulation in Materials Science and Engineering. - Institute of Physics Publishing. - 0965-0393. ; 21:2
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Tidskriftsartikel (övrigt vetenskapligt)abstract
- Superplastic-like forming is a newly improved sheet forming process that combines the mechanical pre-forming (also called hot drawing) with gas-driven blow forming (gas forming). Non-superplastic grade aluminium alloy 5083 (AA5083) was successfully formed using this process. In this paper, a physical-based material model with dislocation density and vacancy concentration as intrinsic foundations was employed. The model describes the overall flow stress evolution of AA5083 from ambient temperature up to 550 °C and strain rates from 10−4 up to 10−1 s−1. Experimental data in the form of stress–strain curves were used for the calibration of the model. The calibrated material model was implemented into simulation to model the macroscopic forming process. Hereby, finite element modelling (FEM) was used to estimate the optimum strain-rate forming path, and experiments were used to validate the model. In addition, the strain-rate controlled forming was conducted for the purpose of maintaining the gas forming with an average strain rate of 2 × 10−3 s−1. The predicted necking areas closely approximate the localized thinning observed in the part. Strain rate gradients as a result of geometric effects were considered to be the main reason accounting for thinning and plastic straining, which were demonstrated during hot drawing and gas forming by simulations.
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| 8. |
- McDill, J. Moyra J., et al.
(författare)
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Continuous improvement in thermal-mechanical finite element analysis
- 2000
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Ingår i: International conference on processing and manufacturing of advanced materials : processing, fabrication, properties, applications, THERMEC 2000. - Elsevier. - 0-08-044026-6
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Annan publikation (populärvet., debatt m.m.)
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| 9. |
- J Lindgren, Lars, et al.
(författare)
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Synthesis, Characterization, and Devices of a Series of Alternating Copolymers for Solar Cells
- 2009
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Ingår i: CHEMISTRY OF MATERIALS. - 0897-4756. ; 21:15, s. 3491-3502
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Tidskriftsartikel (refereegranskat)abstract
- In this study we report the synthesis, characterization. and photovoltaic properties of a series of six Conjugated polymers based on donor-acceptor-donor (DAD) structure. The polymers are obtained via Suzuki polymerization of different alkoxy-substituted DAD monomers together with a substituted fluorene or phenylene monomer. Application of polymers as light-harvesting and electron-donating materials in solar cells, in conjunction with both [60]PCBM and [70]PCBM as acceptors, show power-conversion efficiencies (PCEs) up to 2.9%, values obtained without extensive optimization work. Furthermore, atomic force microscopy and field-effect transistor (FET) mobility measurements of acceptor-polymer mixtures show that differences in substitution on the polymers affect morphology, mobility, and device performance. Within the series of polymers, all showing similar optical absorption and redox behavior, substituents play an important role in phase separation on a micrometer scale, which in turn has a large impact on device performance. The phase-separation behavior is clearly seen in [70]PCBM devices where the best-performing devices are obtained using the polymers with short alkoxy groups or no substituents together with a high speed of spin coating during device preparation.
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| 10. |
- Näsström, Mats, et al.
(författare)
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Combined solid and shell element modelling of welding
- 1992
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Ingår i: Mechanical effects of welding : IUTAM symposium, Luleå/Sweden, June 10-14, 1991. - Berlin : Springer. - 0-387-55240-5 ; 197-206
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Annan publikation (populärvet., debatt m.m.)abstract
- Finite element calculations of residual stress distribution in a welded component from a hollow square section Inconel 600 tube are presented. Shell element can be successfully used in finite element calculations of thin walled structures. However, in the weld and the heat affected zone (HAZ) shell elements may not be sufficient, since the through thickness stress gradient is high in these regions. A combination of eight-nodes solid elements and four-nodes shell elements is used. The solid elements are used in and near the weld and shell elements are used elsewhere. This combination of solid elements and shell elements reduces the number of degrees of freedom in the problem in comparison with the use of solid elements only
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