| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 3. |
- Williamson, Alice, et al.
(författare)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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| 4. |
- Fall, Andreas B., et al.
(författare)
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A physical cross-linking process of cellulose nanofibril gels with shear-controlled fibril orientation
- 2013
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 9:6, s. 1852-1863
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Tidskriftsartikel (refereegranskat)abstract
- Cellulose nanofibrils constitute the smallest fibrous components of wood, with a width of approximately 4 nm and a length in the micrometer range. They consist of aligned linear cellulose chains with crystallinity exceeding 60%, rendering stiff, high-aspect-ratio rods. These properties are advantageous in the reinforcement components of composites. Cross-linked networks of fibrils can be used as templates into which a polymer enters. In the semi-concentrated regime (i.e. slightly above the overlap concentration), carboxy methylated fibrils dispersed in water have been physically cross-linked to form a volume-spanning network (a gel) by reducing the pH or adding salt, which diminishes the electrostatic repulsion between fibrils. By applying shear during or after this gelation process, we can orient the fibrils in a preferred direction within the gel, for the purpose of fully utilizing the high stiffness and strength of the fibrils as reinforcement components. Using these gels as templates enables precise control of the spatial distribution and orientation of the dispersed phase of the composites, optimizing the potentially very large reinforcement capacity of the nanofibrils.
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| 5. |
- Lindström, Stefan B, 1974-
(författare)
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Lectures on engineering mechanics : statics and dynamics
- 2019
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Lectures on Engineering Mechanics: Statics and Dynamics is suitable for Bachelor's level education at schools of engineering with an academic profile. It gives a concise and formal account of the theoretical framework of elementary Engineering Mechanics.A distinguishing feature of this textbook is that its content is consistently structured into postulates, definitions and theorems, with rigorous derivations. The reader finds support in a wealth of illustrations and a cross-reference for each deduction. This textbook underscores the importance of properly drawn free-body diagrams to enhance the problem-solving skills of students.
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| 6. |
- Lindström, Stefan B, 1974-, et al.
(författare)
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Lectures on Engineering Mechanics : Statics and Dynamics with Exercises
- 2021
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Lectures on Engineering Mechanics: Statics and Dynamics with Exercises (SI version) is suitable for Bachelor's level education at schools of engineering with an academic profile. It gives a concise and formal account of the theoretical framework of elementary Engineering Mechanics.A distinguishing feature of this textbook is that its content is consistently structured into postulates, definitions and theorems, with rigorous derivations. The reader finds support in a wealth of illustrations and a cross-reference for each deduction. This textbook includes a comprehensive set of exercises to support the development of problem-solving skills of students.
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| 7. |
- Ried, Janina S., et al.
(författare)
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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| 8. |
- Surendran, Praveen, et al.
(författare)
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Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
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| 9. |
- Wemming, Hannes, 1984-
(författare)
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Experiments and Modelling of Composite–Aluminium Bolted Joints
- 2022
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aeronautical industry has always strived towards weight-efficient structures since they improve aircraft performance, enable more fuel or payload, reduce cost of manufacturing and operating the aircraft, and reduce the fuel consumption and emissions. Modern airframes are often built in materials with high strength-toweight and stiffness-to-weight ratio, such as aluminium or fibre composites. Fibre composite materials are becoming increasingly common, requiring bolted joints between composite and aluminium parts. Bolted joints are often weak points in the structure, and understanding their mechanical properties in terms of stiffness and strength is of great importance for designing aircraft that are safe to fly. The aim of the research presented in this licentiate thesis is to improve the understanding of shear-loaded, composite–aluminium, bolted joints in terms of structural compliance, deformation, load distribution, strength and failure, by performing experiments and developing simulation models that describe those experiments. Experiments are performed where the optical digital image correlation (DIC) technique is used to measure the deformation of the test specimen surface during quasistatic load application until specimen failure. The DIC method enables more detailed deformation measurements compared to traditional methods. Data processing algorithms for noise reduction of DIC measurement data are developed and the results are used in a novel way to detect beginning bearing damage within the material by observing the specimen surface. The experimental DIC data is used for adapting models, where the goal is to create a structural element that represents a fastener. A structural element is computationally efficient and suitable for implementation in large scale models of airframe structures in an industrial context. A model is proposed and the selection of parameters for this model are investigated. The parameters are identified by fitting to experimental data. This licentiate thesis is divided into two parts, where the first part gives an introduction and background to the research, while the second part consists of two appended papers.
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| 10. |
- Alimadadi, Majid, et al.
(författare)
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Role of microstructures in the compression response of three-dimensional foam-formed wood fiber networks
- 2018
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Ingår i: Soft Matter. - : ROYAL SOC CHEMISTRY. - 1744-683X .- 1744-6848. ; 14:44, s. 8945-8955
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Tidskriftsartikel (refereegranskat)abstract
- High-porosity, three-dimensional wood fiber networks made by foam forming present experimentally accessible instances of hierarchically structured, athermal fiber networks. We investigate the large deformation compression behavior of these networks using fiber-resolved finite element analyses to elucidate the role of microstructures in the mechanical response to compression. Three-dimensional network structures are acquired using micro-computed tomography and subsequent skeletonization into a Euclidean graph representation. By using a fitting procedure to the geometrical graph data, we are able to identify nine independent statistical parameters needed for the regeneration of artificial networks with the observed statistics. The compression response of these artificially generated networks and the physical network is then investigated using implicit finite element analysis. A direct comparison of the simulation results from the reconstructed and artificial network reveals remarkable differences already in the elastic region. These can neither be fully explained by density scaling, the size effect nor the boundary conditions. The only factor which provides the consistent explanation of the observed difference is the density and fiber orientation nonuniformities; these contribute to strain-localization so that the network becomes more compliant than expected for statistically uniform microstructures. We also demonstrate that the experimentally manifested strain-stiffening of such networks is due to development of new inter-fiber contacts during compression.
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