| 1. |
- 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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| 2. |
- Jensen, Lisette Okkels, et al.
(författare)
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Intravascular ultrasound assessment of minimum lumen area and intimal hyperplasia in in-stent restenosis after drug-eluting or bare-metal stent implantation. The Nordic Intravascular Ultrasound Study (NIVUS)
- 2017
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Ingår i: Cardiovascular Revascularization Medicine. - : Elsevier BV. - 1553-8389. ; 18:8, s. 577-582
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Drug-eluting stents (DES) reduce the risk of restenosis after percutaneous coronary intervention. The aim of the study was to evaluate, by intravascular ultrasound (IVUS), the minimum lumen area site in the stented segment and the distribution of intimal hyperplasia in patients presenting with a DES or bare-metal stent (BMS) in-stent restenosis. Methods: The “Nordic Intravascular Ultrasound Study (NIVUS)” study was conducted in Nordic and Baltic countries as a prospective multicenter registry. Two hundred nine patients (DES n = 121 and BMS n = 88) with in-stent restenosis were enrolled. Results: At the minimum lumen area site in the stented segment, the stent area (5.8 ± 2.2 mm2 vs. 7.6 ± 2.4 mm2, p < 0.001) and intimal hyperplasia area (2.6 ± 2.0 mm2 vs. 5.0 ± 2.2 mm2, p < 0.001) were significantly lower in patients treated with DES compared to BMS. The percentage of stents that did not have a minimum stent area of at least 5.0 mm2 (under expansion) was higher in DES (58.7% vs. 37.7%, p = 0.008) compared to BMS. Intimal hyperplasia covered 55.4 ± 33.3% of the stent length in the DES compared to 90.7 ± 17.4% in the BMS group, p < 0.001. Focal in-stent restenosis was more often seen in DES treated patients compared to BMS treated patients (DES n = 84 (59.9%) vs. BMS n = 15 (17.0%), p < 0.001). Conclusion: Stent underexpansion was more often seen in DES than BMS in-stent restenosis. DES more often had focal in-stent restenosis with less intimal hyperplasia.
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| 3. |
- 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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| 4. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 5. |
- 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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| 6. |
- Afzal, Mohammad, et al.
(författare)
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An analytical calculation of the Jacobian matrix for 3D friction contact model applied to turbine blade shroud contact
- 2016
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Ingår i: Computers & structures. - : Elsevier. - 0045-7949 .- 1879-2243. ; 177, s. 204-217
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Tidskriftsartikel (refereegranskat)abstract
- An analytical expression is formulated to compute the Jacobian matrix for 3D friction contact modeling that efficiently evaluates the matrix while computing the friction contact forces in the time domain by means of the alternate frequency time domain approach. The developed expression is successfully used for the calculation of the friction damping on a turbine blade with shroud contact interface having an arbitrary 3D relative displacement. The analytical expression drastically reduces the computation time of the Jacobian matrix with respect to the classical finite difference method, with many points at the contact interface. Therefore, it also significantly reduces the overall computation time for the solution of the equations of motion, since the formulation of the Jacobian matrix is the most time consuming step in solving the large set of nonlinear algebraic equations when a finite difference approach is employed. The equations of motion are formulated in the frequency domain using the multiharmonic balance method to accurately capture the nonlinear contact forces and displacements. Moreover, the equations of motion of the full turbine blade model are reduced to a single sector model by exploiting the concept of cyclic symmetry boundary condition for a periodic structure. Implementation of the developed scheme in solving the equations of motion is proved to be effective and significant reduction in time is achieved without loss of accuracy.
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| 7. |
- Afzal, Md, et al.
(författare)
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INVESTIGATION OF DAMPING POTENTIAL OF STRIP DAMPER ON A REAL TURBINE BLADE
- 2016
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Ingår i: PROCEEDINGS OF THE ASME TURBO EXPO. - : AMER SOC MECHANICAL ENGINEERS.
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Konferensbidrag (refereegranskat)abstract
- This paper investigates the damping potential of strip dampers on a real turbine bladed disk. A 3D numerical friction contact model is used to compute the contact forces by means of the Alternate Frequency Time domain method. The Jacobian matrix required during the iterative solution is computed in parallel with the contact forces, by a quasi-analytical method. A finite element model of the strip dampers, that allows for an accurate description of their dynamic properties, is included in the steady-state forced response analysis of the bladed disk. Cyclic symmetry boundary conditions and the multiharmonic balance method are applied in the formulation of the equations of motion in the frequency domain. The nonlinear forced response analysis is performed with two different types of boundary conditions on the strip: (a) free-five and (b) elastic, and their influence is analyzed. The effect of the strip mass, thickness and the excitation levels on the forced response curve is investigated in detail.
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| 8. |
- Afzal, Mohammad, et al.
(författare)
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Numerical analysis of multiple friction contacts in bladed disks
- 2018
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Ingår i: International Journal of Mechanical Sciences. - : Elsevier. - 0020-7403 .- 1879-2162. ; 137, s. 224-237
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Tidskriftsartikel (refereegranskat)abstract
- The damping potential of multiple friction contacts in a bladed disk is investigated. Friction contacts at tip shrouds and strip dampers are considered. It is shown that friction damping effectiveness can be potentially increased by using multiple friction contact interfaces. Friction damping depends on many parameters such as rotational speed, engine excitation order and mode family and therefore it is not possible to damp all the critical resonances using a single kind of friction contact interface. For example, a strip damper is more effective for the low nodal diameters, where blade/disk coupling is strong. The equations of motion of the bladed disk with multiple friction contacts are derived in the frequency domain for a cyclic structure with rotating excitations. A highly accurate method is used to generate the frequency response function (FRF) matrix. Furthermore, a finite element contact analysis is performed to compute the normal contact load and the contact area of the shroud interface at operating rotational speed. The multiharmonic balance method is employed in combination with the alternate frequency time domain method to find the steady state periodic solution. A low-pressure turbine bladed disk is considered and the effect of the engine excitation level, strip mass, thickness and the accuracy of FRF matrix on the nonlinear response curve are investigated in detail.
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| 9. |
- Afzal, Mohammad, 1987-
(författare)
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Numerical modelling and analysis of friction contact for turbine blades
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- High cycle fatigue failure of turbine and compressor blades due to resonance in the operating frequency range is one of the main problems in the design of gas turbine engines. To suppress excessive vibrations in the blades and prevent high cycle fatigue, dry friction dampers are used by the engine manufacturers. However, due to the nonlinear nature of friction contact, analysis of such systems becomes complicated.This work focuses on the numerical modelling of friction contact and a 3D friction contact model is developed. To reduce the computation time in the Newton-iteration steps, a method to compute the Jacobian matrix in parallel to the contact forces is proposed. The developed numerical scheme is successfully applied on turbine blades with shroud contact having an arbitrary 3D relative displacement. The equations of motion are formulated in the frequency domain using the multiharmonic balance method to accurately capture the nonlinear contact forces and displacements. Moreover, the equations of motion of the full turbine blade model are reduced to a single sector model by exploiting the concept of the cyclic symmetry boundary condition for a periodic structure.The developed 3D coupled numerical contact model is compared with a 3D contact model having uncoupled tangential motion and drawback of the uncoupled contact model is discussed. Furthermore, presence of higher harmonics in the nonlinear contact forces is analyzed and their effect on the excitation of the different harmonic indices (nodal diameters) of the bladed disk are systematically presented. Moreover, due to the quasi-analytical computation of the Jacobian matrix, the developed scheme is proved to be effective in solving the equations of motion and significant reduction in time is achieved without loss of accuracy.
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| 10. |
- Afzal, Mohammad, 1987-
(författare)
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On efficient and adaptive modelling of friction damping in bladed disks
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This work focuses on efficient modelling and adaptive control of friction damping in bladed disks. To efficiently simulate the friction contact, a full-3D time-discrete contact model is reformulated and an analytical expression for the Jacobian matrix is derived that reduces the computation time drastically with respect to the classical finite difference method. The developed numerical solver is applied on bladed disks with shroud contact and the advantage of full-3D contact model compared to a quasi-3D contact model is presented. The developed numerical solver is also applied on bladed disks with strip damper and multiple friction contacts and obtained results are discussed. Furthermore, presence of higher harmonics in the nonlinear contact forces is analyzed and their effect on the excitation of the different nodal diameters of the bladed disk are systematically presented. The main parameters that influence the effectiveness of friction damping in bladed disks are engine excitation order, contact stiffnesses, friction coefficient, relative motion at the friction interface and the normal contact load. Due to variation in these parameters during operation, the obtained friction damping in practice may differ from the optimum value. Therefore, to control the normal load adaptively that will lead to an optimum damping in the system despite these variations, use of magnetostrictive actuator is proposed. The magnetostrictive material that develops an internal strain under the influence of an external magnetic field is employed to increase and decrease the normal contact load. A linearized model of the magnetostrictive actuator is used to characterize the magnetoelastic behavior of the actuator. A nonlinear static contact analysis of the bladed disk reveals that a change of normal load more than 700 N can be achieved using a reasonable size of the actuator. This will give a very good control on friction damping once applied in practice.
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