| 1. |
- Berndt, Sonja I., et al.
(author)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Journal article (peer-reviewed)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 2. |
- Kosonen, Petteri, et al.
(author)
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Intravascular ultrasound assessed incomplete stent apposition and stent fracture in stent thrombosis after bare metal versus drug-eluting stent treatment the Nordic Intravascular Ultrasound Study (NIVUS)
- 2013
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 168:2, s. 1010-1016
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Journal article (peer-reviewed)abstract
- Background: This prospective multicenter registry used intravascular ultrasound (IVUS) in patients with definite stent thrombosis (ST) to compare rates of incomplete stent apposition (ISA), stent fracture and stent expansion in patients treated with drug-eluting (DES) versus bare metal (BMS) stents. ST is a rare, but potential life threatening event after coronary stent implantation. The etiology seems to be multifactorial. Methods: 124 patients with definite ST were assessed by IVUS during the acute ST event. The study was conducted in 15 high-volume percutaneous coronary intervention -centers in the Nordic-Baltic countries. Results: In early or late ST there were no differences in ISA between DES and BMS. In very late ST, ISA was a more frequent finding in DES than in BMS (52% vs. 16%; p=0.005) and the maximum ISA area was larger in DES compared to BMS(1.1 +/- 2.3 mm(2) vs. 0.1 +/- 0.5 mm(2); p=0.004). Further, ISA was more prevalent in sirolimus-eluting than in paclitaxel-eluting stents (58% vs. 37%; p-0.02). Stent fractures were found both in DES (16%) and BMS (24%); p=0.28, and not related to time of stent thrombosis occurrence. For stents with nominal diameters >= 2.75 mm, 38% of the DES and 22% of the BMS had a minimum stent area of less than 5 mm(2); p=0.14. Conclusions: Very late stent thrombosis was more prevalent and associated with more extensive ISA in DES than in BMS treated patients. Stent fracture was a common finding in ST after DES and BMS implantation. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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| 3. |
- Shungin, Dmitry, et al.
(author)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Journal article (peer-reviewed)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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| 4. |
- Fall, Tove, et al.
(author)
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The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis
- 2013
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In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 10:6, s. e1001474-
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Journal article (peer-reviewed)abstract
- Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
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| 5. |
- Heid, Iris M, et al.
(author)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Journal article (peer-reviewed)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 6. |
- Jensen, Jan S., et al.
(author)
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Safety in simple versus complex stenting of coronary artery bifurcation lesions : The nordic bifurcation study 14-month follow-up results
- 2008
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In: EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. - 1774-024X. ; 4:2, s. 229-233
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Journal article (peer-reviewed)abstract
- AIMS: The risk of stent thrombosis has been reported to increase with percutaneous coronary intervention (PCI) complexity. The present study reports the pre-specified secondary endpoint of a 14-month stent thrombosis and major adverse cardiac events in patients stented with a simple versus a complex bifurcation technique using sirolimus eluting stents (SES). METHODS AND RESULTS: A total of 413 patients with a coronary bifurcation lesion were randomised to a simple treatment strategy; stenting of main vessel and optional stenting of side branch (MV group), or to a complex stenting strategy; stenting of both main vessel and side branch (MV+SB group). Mortality data were available in all patients and 14-month clinical follow-up data in 395 (96%) of the patients. After 14 months, the rates of definite, probable and possible stent thrombosis (ARC criteria) were 1.0% vs. 0.5%, 1.0% vs. 0% and 0.5% vs. 0% (ns) in the MV and in the MV+SB groups, respectively. Rates of MACE were 9.5% in the MV group and 8.2% in the MV+SB group (ns). Total death was seen in 2.4% vs. 1.0% and non-PCI related myocardial infarction in 2.0% vs. 1.0% in the MV and the MV+SB groups, respectively. CONCLUSIONS: After 14 months, two months after recommended cessation of dual antiplatelet therapy, the rates of stent thrombosis and major adverse cardiac events were low and independent of treatment complexity in patients treated with SES for coronary artery bifurcation lesions.
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| 7. |
- Jensen, Lisette Okkels, et al.
(author)
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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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In: Cardiovascular Revascularization Medicine. - : Elsevier BV. - 1553-8389. ; 18:8, s. 577-582
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Journal article (peer-reviewed)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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| 8. |
- Lango Allen, Hana, et al.
(author)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Journal article (peer-reviewed)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 9. |
- Locke, Adam E, et al.
(author)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Journal article (peer-reviewed)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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| 10. |
- Maeng, Michael, et al.
(author)
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Long-Term Results After Simple Versus Complex Stenting of Coronary Artery Bifurcation Lesions : Nordic Bifurcation Study 5-Year Follow-Up Results
- 2013
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 62:1, s. 30-34
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Journal article (peer-reviewed)abstract
- Objectives This study sought to report the 5-year follow-up results of the Nordic Bifurcation Study. Background Randomized clinical trials with short-term follow-up have indicated that coronary bifurcation lesions may be optimally treated using the optional side branch stenting strategy. Methods A total of 413 patients with a coronary bifurcation lesion were randomly assigned to a simple stenting strategy of main vessel (MV) and optional stenting of side branch (SB) or to a complex stenting strategy, namely, stenting of both MV and SB. Results Five-year clinical follow-up data were available for 404 (98%) patients. The combined safety and efficacy endpoint of cardiac death, non-procedure-related myocardial infarction, and target vessel revascularization were seen in 15.8% in the optional SB stenting group as compared to 21.8% in the MV and SB stenting group (p = 0.15). All-cause death was seen in 5.9% versus 10.4% (p = 0.16) and non-procedure-related myocardial infarction in 4% versus 7.9% (p = 0.09) in the optional SB stenting group versus the MV and SB stenting group, respectively. The rates of target vessel revascularization were 13.4% versus 18.3% (p = 0.14) and the rates of definite stent thrombosis were 3% versus 1.5% (p = 0.31) in the optional SB stenting group versus the MV and SB stenting group, respectively. Conclusions At 5-year follow-up in the Nordic Bifurcation Study, the clinical outcomes after simple optional side branch stenting remained at least equal to the more complex strategy of planned stenting of both the main vessel and the side branch.
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| 11. |
- Mahajan, Anubha, et al.
(author)
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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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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Journal article (peer-reviewed)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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| 12. |
- Mahajan, Anubha, et al.
(author)
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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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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Journal article (peer-reviewed)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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| 13. |
- Ried, Janina S., et al.
(author)
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)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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| 14. |
- Speliotes, Elizabeth K., et al.
(author)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Journal article (peer-reviewed)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 15. |
- Steigen, Terje K., et al.
(author)
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Randomized study on simple versus complex stenting of coronary artery bifurcation lesions : the Nordic bifurcation study
- 2006
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In: Circulation. - 0009-7322 .- 1524-4539. ; 114:18, s. 1955-1961
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Journal article (peer-reviewed)abstract
- Background - The optimal stenting strategy in coronary artery bifurcation lesions is unknown. In the present study, a strategy of stenting both the main vessel and the side branch ( MV + SB) was compared with a strategy of stenting the main vessel only, with optional stenting of the side branch ( MV), with sirolimus-eluting stents. Methods and Results - A total of 413 patients with a bifurcation lesion were randomized. The primary end point was a major adverse cardiac event: cardiac death, myocardial infarction, target-vessel revascularization, or stent thrombosis after 6 months. At 6 months, there were no significant differences in rates of major adverse cardiac events between the groups ( MV + SB 3.4%, MV 2.9%; P = NS). In the MV + SB group, there were significantly longer procedure and fluoroscopy times, higher contrast volumes, and higher rates of procedure-related increases in biomarkers of myocardial injury. A total of 307 patients had a quantitative coronary assessment at the index procedure and after 8 months. The combined angiographic end point of diameter stenosis > 50% of main vessel and occlusion of the side branch after 8 months was found in 5.3% in the MV group and 5.1% in the MV + SB group ( P = NS). Conclusions - Independent of stenting strategy, excellent clinical and angiographic results were obtained with percutaneous treatment of de novo coronary artery bifurcation lesions with sirolimus-eluting stents. The simple stenting strategy used in the MV group was associated with reduced procedure and fluoroscopy times and lower rates of procedure-related biomarker elevation. Therefore, this strategy can be recommended as the routine bifurcation stenting technique.
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| 16. |
- Surendran, Praveen, et al.
(author)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Journal article (peer-reviewed)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 17. |
- Yang, Jian, et al.
(author)
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FTO genotype is associated with phenotypic variability of body mass index
- 2012
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 490:7419, s. 267-272
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Journal article (peer-reviewed)abstract
- There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using similar to 170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)(5-7), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of similar to 0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation(9,10). Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.
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| 18. |
- Zeggini, Eleftheria, et al.
(author)
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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
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Journal article (peer-reviewed)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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| 19. |
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| 20. |
- Afzal, Mohammad, 1987-, et al.
(author)
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A formulation of the Jacobian matrixfor 3D numerical friction contact model applied to turbine blade shroud contact
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In: Journal of Sound and Vibration. - 0022-460X .- 1095-8568.
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Journal article (other academic/artistic)abstract
- An analytical expression is formulated to compute the Jacobian matrix for 3D friction contact modelling that eciently 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 thecalculation of the friction damping on a turbine blade with shroud contact interface having an arbitrary 3Drelative displacement. The analytical expression drastically reduces the computation time of the Jacobian matrix with respect to the classical finite dierence 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 dierence 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 aperiodic 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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| 21. |
- Afzal, Mohammad, 1987-, et al.
(author)
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Adaptive control of normal load at the friction interface of bladed disks using giant magnetostrictive material
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In: Journal of Vibration and Control. - 1077-5463 .- 1741-2986.
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Journal article (other academic/artistic)abstract
- A novel application of magnetostrictive actuators in underplatform dampers of bladed disks is proposed for adaptive control of the normal load at the friction interface in order to achieve the desired friction damping in the structure. Friction damping in a bladed disk depends on many parameters such as rotational speed, engine excitation order, nodal diameter, contact stiffness, friction coefficient and normal contact load. However, all these parameters have a fixed value at an operating point. On the other hand, the ability to vary some of these parameters such as the normal contact load is desirable in order to obtain an optimum damping in the bladed disk at different operating conditions. Under the influence of an external magnetic field, magnetostrictive materials develop an internal strain that can be exploited to vary the normal contact load at the friction interface, which makes them a potentially good candidate for this application. A commercially available magnetostrictive alloy, Terfenol-D is considered in this analysis that is capable of providing magnetostrain up to 0.002 under prestress and a blocked force over 1500 N. A linearized model of the magnetostrictive material, which is accurate enough for a DC application, is employed to compute the output displacement and the blocked force of the actuator. A nonlinear finite element contact analysis is performed to compute the normal contact load between the blade platform and the underplatform damper as a result of magnetostrictive actuation. The contact analysis is performed for different mounting configurations of the actuator and the obtained results are discussed. The proposed solution is potentially applicable to adaptively control vibratory stresses in bladed disks and consequently to reduce failure due to high-cycle fatigue. Finally, the practical challenges in employing magnetostrictive actuators in underplatform dampers are discussed.
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| 22. |
- Afzal, Mohammad, 1987-, et al.
(author)
-
Adaptive control of normal load at the friction interface of bladed disks using giant magnetostrictive material
- 2020
-
In: Journal of Intelligent Materials Systems and Structures. - : SAGE Publications. - 1045-389X .- 1530-8138. ; 31:8, s. 1111-1125
-
Journal article (peer-reviewed)abstract
- A novel application of magnetostrictive actuators in underplatform dampers of bladed disks is proposed for adaptive control of the normal load at the friction interface to achieve the desired friction damping in the structure. Friction damping in a bladed disk depends on operating parameters, such as rotational speed, engine excitation order, nodal diameter normal contact load, and contact interface parameters, such as contact stiffness and friction coefficient. The operating parameters have a fixed value, whereas the contact interface parameters vary in an unpredictable way at an operating point. However, the ability to vary some of these parameters such as the normal contact load in a controlled manner is desirable to attain an optimum damping in the bladed disk at different operating conditions. Under the influence of an external magnetic field, magnetostrictive materials develop an internal strain that can be exploited to vary the normal contact load at the friction interface, which makes them a potentially good candidate for this application. A commercially available magnetostrictive alloy, Terfenol-D is considered in this analysis that is capable of providing magnetostrain up to 2 × 10-3 under prestress and a blocked force over 1500 N. A linearized model of the magnetostrictive material, which is accurate enough for a direct current application, is employed to compute the output force of the actuator. A nonlinear finite element contact analysis is performed to compute the normal contact load between the blade platform and the underplatform damper as a result of magnetostrictive actuation. The nonlinear contact analysis is performed for different actuator mounting configurations and the obtained results are discussed. The proposed solution is potentially applicable to adaptively control vibratory stresses in bladed disks and consequently to reduce failure due to high-cycle fatigue. Finally, the practical challenges in employing magnetostrictive actuators in underplatform dampers are discussed.
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| 23. |
- Afzal, Mohammad, et al.
(author)
-
An analytical calculation of the Jacobian matrix for 3D friction contact model applied to turbine blade shroud contact
- 2016
-
In: Computers & structures. - : Elsevier. - 0045-7949 .- 1879-2243. ; 177, s. 204-217
-
Journal article (peer-reviewed)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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| 24. |
- Afzal, Md, et al.
(author)
-
INVESTIGATION OF DAMPING POTENTIAL OF STRIP DAMPER ON A REAL TURBINE BLADE
- 2016
-
In: PROCEEDINGS OF THE ASME TURBO EXPO. - : AMER SOC MECHANICAL ENGINEERS.
-
Conference paper (peer-reviewed)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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| 25. |
- Afzal, Mohammad, 1987-, et al.
(author)
-
Numerical analysis of multiple friction contacts in bladed disks
-
In: International Journal of Mechanical Sciences. - 0020-7403 .- 1879-2162.
-
Journal article (other academic/artistic)abstract
- The damping potential of multiple friction contacts in a bladed disk, tip shroud and strip damper is investigated, showing 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 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 and 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 approximate 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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| 26. |
- Afzal, Mohammad, et al.
(author)
-
Numerical analysis of multiple friction contacts in bladed disks
- 2018
-
In: International Journal of Mechanical Sciences. - : Elsevier. - 0020-7403 .- 1879-2162. ; 137, s. 224-237
-
Journal article (peer-reviewed)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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| 27. |
- Afzal, Mohammad, 1987-
(author)
-
Numerical modelling and analysis of friction contact for turbine blades
- 2015
-
Licentiate thesis (other academic/artistic)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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| 28. |
- Afzal, Mohammad, 1987-
(author)
-
On efficient and adaptive modelling of friction damping in bladed disks
- 2017
-
Doctoral thesis (other academic/artistic)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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| 29. |
- Alberdi, A., et al.
(author)
-
Dynamic characterisation of different magneto-sensitive natural rubbers for application in vibration isolation
- 2010
-
In: Proceedings of ISMA 2010 - International Conference on Noise and Vibration Engineering, including USD 2010. - : Katholieke Universiteit Leuven. - 9789073802872 ; , s. 227-231
-
Conference paper (peer-reviewed)abstract
- Dynamic properties of magneto-sensitive natural rubber components were experimentally studied. Different magneto-sensitive rubbers were manufactured, consisting of irregularly shaped micron-sized iron particles embedded in a natural rubber matrix, and the influence of the hardness of the matrix material and the particle volume concentration were analyzed. Vibration isolators consisting of magneto-sensitive elastomers promise to have more functionality than conventional isolators as they can change their dynamic stiffness rapidly, continuously and reversibly under the application of an external magnetic field. Experimental measurements on MS components show that a better performance may be obtained at applications where small amplitudes are required, using soft matrix materials and with concentration close to a critical particle volume fraction.
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| 30. |
- Alberdi-Muniain, Ane, et al.
(author)
-
An experimental study of magneto-sensitive natural rubber components applied in a vibration isolation system
- 2009
-
In: CONSTITUTIVE MODELS FOR RUBBER VI. - London : Taylor & Francis. - 9780415563277 ; , s. 99-104
-
Conference paper (peer-reviewed)abstract
- The effectiveness of magneto-sensitive natural rubber components applied in a vibration isolation system is experimentally investigated, where influences of excitation position, amplitude, frequency and magnetic field are examined. The magneto-sensitive elastomer consists of micron-sized, irregularly shaped iron particles blended in soft natural rubber at a concentration close to the critical particle volume fraction, shown to be the most favorable composition for optimum behaviour. A rigid aluminium mass supported on four vibration isolators is excited by an electro-dynamic shaker. Each component of this vibration isolation system is composed of two thin, square shaped, symmetrically positioned magneto-sensitive elements excited in simple shear with a magnetic field applied perpendicularly to the motion by an electromagnet. The magnetic field is varied by applying different intensities through the coil. The excitation position is either on the centre or on the edge of the surface of the mass, using step-sine excitation of various amplitudes in the frequency range of 0 to 300 Hz. The results show that it is possible to use magneto-sensitive rubber for vibration control purposes.
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| 31. |
- Alberdi-Muniain, Ane, et al.
(author)
-
Direct energy flow measurement in magneto-sensitive vibration isolator systems
- 2012
-
In: Journal of Sound and Vibration. - : Elsevier. - 0022-460X .- 1095-8568. ; 331:9, s. 1994-2006
-
Journal article (peer-reviewed)abstract
- The effectiveness of highly nonlinear, frequency, amplitude and magnetic field dependent magneto-sensitive natural rubber components applied in a vibration isolation system is experimentally investigated by measuring the energy flow into the foundation. The energy flow, including both force and velocity of the foundation, is a suitable measure of the effectiveness of a real vibration isolation system where the foundation is not perfectly rigid. The vibration isolation system in this study consists of a solid aluminium mass supported on four magneto-sensitive rubber components and is excited by an electro-dynamic shaker while applying various excitation signals, amplitudes and positions in the frequency range of 20-200 Hz and using magneto-sensitive components at zero-field and at magnetic saturation. The energy flow through the magneto-sensitive rubber isolators is directly measured by inserting a force transducer below each isolator and an accelerometer on the foundation close to each isolator. This investigation provides novel practical insights into the potential of using magneto-sensitive material isolators in noise and vibration control, including their advantages compared to traditional vibration isolators. Finally, nonlinear features of magneto-sensitive components are experimentally verified.
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| 32. |
- Alberdi-Muniain, Ane, et al.
(author)
-
Indirect energy flow measurement in magneto-sensitive vibration isolator systems
- 2013
-
In: Applied Acoustics. - : Elsevier BV. - 0003-682X .- 1872-910X. ; 74:4, s. 575-584
-
Journal article (other academic/artistic)abstract
- The indirect energy flow measurement method is extended to cover highly nonlinear, frequency, amplitude and magnetic field dependent magneto-sensitive natural rubber isolators applied in a real vibration isolation system. Energy flow is an effective measure of vibration isolation while being a single quantity that considers both force and velocity. The use of the indirect technique is of interest while requiring only accelerometers since it is usually difficult to directly measure the force in a real application. The vibration isolation system is composed of four magneto-sensitive rubber isolators that are inserted under a vibrating source consisting of a solid aluminium mass excited by an electro-dynamic shaker. Magneto-sensitive rubber isolators are more useful than conventional rubber isolators since the dynamic stiffness varies with the application of an external magnetic field, thus resulting in more effective vibration isolation. Various approximations regarding the indirect technique are investigated, concluding that average stiffness of magneto-sensitive isolators can be used and auto-spectrum of the foundation velocity ignored. In addition, various error analyses are performed. Finally, the indirect measurement of the energy flow is validated by direct measurements, showing very good agreement.
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| 33. |
- Alberdi-Muniain, Ane, et al.
(author)
-
Influence of carbon black and plasticisers on dynamic properties of isotropic magnetosensitive natural rubber
- 2012
-
In: Plastics, rubber and composites. - 1465-8011 .- 1743-2898. ; 41:7, s. 310-317
-
Journal article (peer-reviewed)abstract
- The dynamic shear modulus of magnetosensitive (MS) natural rubber composites is experimentallystudied, where influences of carbon black, plasticiser and iron particle concentrations areinvestigated at various dynamic shear strain amplitudes and external magnetic fields within thelower structure borne frequency range. The iron particles embedded in natural rubber areirregularly shaped and randomly distributed; the plasticisers simplify the iron particle blendingprocess, while carbon black reduces the production costs and improves the mechanicalproperties. The results show that the relative MS effect on the shear modulus magnitude increaseswith increased plasticiser and iron particle concentration and decreases with increased carbonblack concentration. Furthermore, their relative contributions are quantified. Consequently, thestudy provides a basis for optimising the composition of MS natural rubber to meet a variety ofrequirements, including those of vibration isolation, a promising application area for MS materials.
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| 34. |
- Alberdi-Muniain, Ane, 1983-
(author)
-
Magneto-sensitive elastomers in vibration isolation
- 2012
-
Doctoral thesis (other academic/artistic)abstract
- Vibration isolators made of rubber are used in numerous engineeringapplications to isolate structures from undesirable effects of vibrations.However, once a vibration isolator is installed in an application, it is not possible to modify its characteristics to adjust to changing conditions. An alternative to obtain more adaptive characteristics is touse magneto-sensitive (MS) elastomers. MS elastomers are a type of smart material consisting of an elastomer matrix, such as natural or synthetic rubber, to which iron particles are added displaying properties that vary rapidly, continuously and reversibly by applying an external magnetic field.The aim of this thesis is to investigate the possibility to use MS natural rubber in vibration isolation.Firstly, dynamic shear properties of MS natural rubber are experimentally studied at various frequencies, dynamic amplitudes and magnetic fields. In addition, the influence on the dynamic properties of adding carbon black and plasticisers to MS rubber is investigated. Carbon black is the most popular reinforcing filler that rubber usually contains in engineering applications to improve mechanical properties where as plasticisers simplify the filler blending process.Furthermore, the effectiveness of MS rubber applied in a vibration isolation system is experimentally investigated by measuring the energy flow into the foundation. The energy flow, including both force and velocity of the foundation, is a suitable measure of the effectiveness of a real vibration isolation system where the foundation is not perfectly rigid. The vibration isolation system in this study consists of a solid aluminium mass excitedby an electro-dynamic shaker and mounted upon four nonlinear frequency,amplitude and magnetic field dependent MS isolators being connected to a relatively stiff foundation. The energy flow through the MS isolators is directly measured by inserting a force transducer below each isolator andan accelerometer on the foundation close to each isolator. MS isolators are shown to be more useful than conventional rubber isolators since the dynamic stiffness varies with the application of an external magnetic field,thus resulting in more effective vibration isolation. In addition, the indirect technique is employed to measure the energy flow while requiring only accelerometers since it is usually difficult to directly measure the force in a real application. The indirect technique is validated by direct measurements.Finally, a model of the energy flow through the nonlinear frequency,amplitude and magnetic field dependent MS isolators is developed for the tested vibration isolation system. Vibration isolators are usually only a small connecting component within a more complex system. Hence, simple discrete models are frequently used to characterise the frequency and dynamic amplitude dependence of rubber. Recently, a model of this type has been modified to include magneto-sensitivity and thus model MS rubber. In this study, this novel MS rubber model is incorporated into the full system to model the MS isolators while the foundation is characterised by its driving-point and transfer inertances at and between the connection points.The energy flow model results are compared to those of measurements,showing good agreement. The developed energy flow model provides a basis to design vibration isolator systems made of MS isolators.
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| 35. |
- Alberdi-Muniain, Ane, et al.
(author)
-
Modelling energy flow through magneto-sensitive vibration isolators
- 2013
-
In: International Journal of Engineering Science. - : Elsevier BV. - 0020-7225 .- 1879-2197. ; 65, s. 22-39
-
Journal article (peer-reviewed)abstract
- A highly nonlinear model of the energy flow in a magneto-sensitive (MS) vibration isolation system is developed where it is possible to investigate the influences of MS rubber material parameters; magnetic field strength; MS isolator dimension and position; excitation force magnitude, position and frequency; engine mass, inertia and dimension and, finally, foundation inertance. The MS vibration isolation system consists of an engine modelled by a solid mass, excited by a vertical force and mounted upon four MS isolators being connected to a relatively stiff foundation characterised by its driving-point and transfer inertances at and between the connection points. The energy flow into the foundation is the most appropriate indicator of the effectiveness of a real vibration isolation system while considering both foundation velocity and force. The MS isolator model applied is a nonlinear MS rubber model including frequency, dynamic amplitude and magnetic field dependence. The energy flow model results are compared to those of measurements, showing good agreement. Finally, parameter studies are carried out. The developed energy flow model provides a basis for designing MS vibration isolation systems to meet specific requirements.
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| 36. |
- Austrell, Per Erik, et al.
(author)
-
Survey of Design Methods and Material Characteristics in Rubber Engineering
- 1999
-
Reports (other academic/artistic)abstract
- The unique properties of elastomeric materials are taken advantage of in many engineering applications. Elastomeric units are used as couplings or mountings between stiff structures. Examples of these are shock absorbers, vibration insulators, flexible joints, seals and suspensions.The development of computers and of analysis programs in this area has given engineers a new tool for the design of elastomeric components. Computer simulation by finite element analysis has become increasingly important, allowing the mechanical behavior of products with for complex geometries, as well as loading cases of different kinds to be evaluated. Computer simulations enable both static and dynamic aspects to be analyzed. These matters have been recognized by the manufacturers of rubber products and by their customers. The benefits are shorter time for product development and also quality improvements.However, the possibilities available for finding less complicated technical solutions at lower cost with the use of elastomers, has not been fully utilized. Rubber components could be employed more frequently in design if engineers were more familiar with materials of this sort.Part of the problem lies in education and in the dissemination of information. Engineers working in the design area tend to not be very familiar with elastomeric materials and their properties. The offerings of courses on the mechanics of polymers at schools and universities are very limited. Skillful engineers in this field have usually acquired their knowledge through many years of experience and not formal education.Moreover, the complicated nature of the material behavior involved makes it difficult to devise general design rules and design tools. Only recently have computers and analysis programs become powerful enough for the analysis of nonlinear elastic problems involving large strains.It is essential, if one is to become competitive in high-tech applications, to possess a thorough knowledge of computer methods, material models and test methods available.There has likewise been a lack of relevant data for the computer analysis of elastomeric materials. The design tools employed rely on the material models available and on the test data required for the calibration of these models. In many cases, the only information available for analysis is a value for the hardness of the rubber in question. The wide variety of rubber compounds is also a problem. The characterization of different materials is costly and time-consuming. There is thus a need for simple and reliable methods to characterize the different vulcanizates.
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| 37. |
- Azhdar, Bruska, et al.
(author)
-
Determination of dynamic and sliding friction, and observation of stick-slip phenomenon on compacted polymer powders during high-velocity compaction
- 2006
-
In: Polymer testing. - : Elsevier BV. - 0142-9418 .- 1873-2348. ; 25:8, s. 1069-1080
-
Journal article (peer-reviewed)abstract
- Dynamic friction, sliding friction, and the stick-slip phenomenon have been studied on compacted polymer powders during high-velocity compaction. It is particularly important from a practical point of view to distinguish the stick-slip mechanism and the sliding mechanism which occur concurrently. A practical experimental system has been successfully developed to study the dry frictional force and to measure the sliding coefficient between the polymer powder particles and the die wall during high-velocity compaction. Two new components have been introduced as relaxation assists to improve the compaction process by reducing the frictional forces. It was found that the relaxation assist device leads to an improvement in the polymer powder compaction process by giving a more homogeneous opposite velocity and a better locking of the powder bed in the compacted form with less change in dimensions. The subsequent movement of the particles can be reduced and the powder bed attains a higher density with a minimum total elastic spring-back. The relative time of the stick-slip phenomenon during the compacting stage is also reduced so that the time needed to transfer from an intermittent stick-slip state to a smooth sliding state is reduced and the powder bed slides smoothly. It was found that the dynamic, dry frictional force is intermittent (stick-slip mechanism) at low compaction rates but that at high compaction rates is becomes more smooth (sliding mechanism). Both mechanisms depend on the nature of the powder and on the compaction conditions. At the beginning of the compaction stage, the sliding coefficient decreases due to an increase in the radial to axial stress ratio until the maximum pressure has been reached. During the reorganization stage, more time is needed for large particles to move, rotate and slide due to their relatively large diameter and mass. As a result, the reorganization stage is extended and the stick-slip phenomenon is observed more with increasing particle size. Much better transfer of the pressure throughout the powder bed and less loss of pressure lead to a higher sliding coefficient due to the overall friction during the compaction process. It was found that the sliding coefficient is proportional to the density. A more homogeneous density distribution in the compacted powder and a smaller pressure loss during compaction has a major influence on the sliding coefficient and on the quality of the compacted material
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| 38. |
- Azhdar, Bruska, et al.
(author)
-
Determination of springback gradient in the die on compacted polymer powders during high-velocity compaction
- 2006
-
In: Polymer testing. - : Elsevier BV. - 0142-9418 .- 1873-2348. ; 25:1, s. 114-123
-
Journal article (peer-reviewed)abstract
- A uniaxial high-velocity compaction process for polymer powder using a cylindrical, hardened steel die and a new technique with relaxation assist was tested with various heights. The influences of the relaxation assist device on the process characteristics are discussed. Two bonded strain gauges and a high-speed video camera system were used to investigate the springback phenomenon during the compaction process. It was found that the relaxation assist improves the compaction of the polymer powder by locking the powder bed in the compacted form. It is shown that the high-velocity compaction process is an interruption process and that the delay times between the pressure waves can be reduced by increasing the height of the relaxation assist device. The delay times between the pressure waves are also strongly dependent on the strain rate. If the height of the relaxation assist device is increased, the first gross instantaneous springback, and the total elastic springback, are reduced. In addition, the density of the powder bed is increased. The relative times of the compacting stage, decompacting stage and the reorganisation of the particles can be also controlled by altering the height of the relaxation assist.
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| 39. |
- Azhdar, Bruska, et al.
(author)
-
Development of a High-Velocity Compaction process for polymer powders
- 2005
-
In: Polymer testing. - : Elsevier BV. - 0142-9418 .- 1873-2348. ; 24:7, s. 909-919
-
Journal article (peer-reviewed)abstract
- The High-Velocity Compaction (HVC) process for powder polymers has been studied, with a focus on the compactibility characteristics and surface morphology of the compacted materials, with and without relaxation assists, by increasing compacting quantity and direction. The basic phenomena associated with HVC are explained and the general energy principle is introduced to explain pull-out phenomena during the decompacting stage. Polyamide-11 powders with different particle size distributions have been compacted with the application of different compaction profiles, e.g. different energies and velocities. Scanning electron microscopy (SEM) and image computer board camera, (IC-PCI Imaging Technology) have been used to the study the morphological characteristics, the limit of plastic deformation and particle bonding by plastic flow at contact points, and pull-out phenomena. The relative green density is influenced more by the pre-compacting (primary compaction step) than by the post-compacting (secondary compaction step). The pressure and density distribution differences between the upper and lower surface are not uniform. Projectile supports or 'relaxation assists' are presented as a new technique to reduce pull-out phenomenon. Experimental results for different compaction profiles are presented showing the effect of varying the opposite velocity during the decompacting stage, and how to improve the homogeneous densification between the upper and lower surface and the evenness of the upper surface of the compacted powder bed by using relaxation assists.
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| 40. |
- Azhdar, Bruska, 1965-
(author)
-
Novel Technique to Improve High-Velocity Cold Compaction : Processing of Polymer Powders and Polymer-Based Nanocomposite High Performance Components
- 2006
-
Doctoral thesis (other academic/artistic)abstract
- Compaction of polymer powders and polymer-based nanocomposites by uniaxial high-velocity cold compaction (HVC), by high-energy ball milling (HEBM) and using a novel technique, relaxation assists, was investigated with a focus on the process parameters, the compactibility characteristics, surface morphology and friction. The basic phenomena associated with HVC are explained and the general energy principle is introduced to explain the pull-out phenomenon, springback gradient, delay time, relative time of the pressure wave, and stick-slip phenomenon during the compaction process. Experimental results for different compaction profiles, different particle size distributions and different milling system for polymer-based nanocomposite are presented, showing the effect of varying the process parameters on the compacted material; the compactibility in the compacted bed, the uniformity of the compacted surface, the pull-out phenomenon, the springback gradient, the stick-slip phenomenon and the homogeneity of the dispersions of nanoparticles in the polymer powders in the solid state. It was found that the high-velocity compaction process is an interruption process and that the opposite velocity and pressure loss during the compaction process have a major influence on the quality of the compacted material. The relaxation assist device is a novel technique that has been successfully developed to improve the compaction process. The relaxation assists are parts of the piston and they are regarded as projectile supports. They are constructed of the same material as the piston, and the diameters are the same but the lengths are different. The relaxation assist device leads to an improvement in the compaction of powders, polymer powders and polymer-based nanocomposites by giving a more homogeneous opposite velocity and a better locking of the powder bed in the compacted form during the compaction process with less change in dimensions in the case of both homogeneous and heterogeneous materials. If the movement of the particles is restricted the powder bed attains a higher density and the total elastic springback is minimized. In addition, there is a more homogeneous dispersion of nanoparticles in the case of a heterogeneous material. A much better transfer of the pressure through the powder bed and a smaller loss of pressure lead to a more homogenous stick-slip of the particles and a higher sliding coefficient due to the overall friction during the compaction process.
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| 41. |
- Azhdar, Bruska, et al.
(author)
-
Polymer-nanofiller prepared by high-energy ball milling and high velocity cold compaction
- 2008
-
In: Polymer Composites. - : Wiley. - 0272-8397 .- 1548-0569. ; 29:3, s. 252-261
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Journal article (peer-reviewed)abstract
- High-energy ball milling using comilling in a solid state by low-temperature mechanical alloying to prepare nickel-ferrite (NiFe2O4) nanopowders and ultrafine poly(methyl methacrylate) (PMMA), dispersing nanoparticles in a polymer matrix, and a uniaxial high-velocity cold compaction process using a cylindrical, hardened steel die and a new technique with relaxation assists have been studied. The focus has been on the particle size distributions of the nanocomposite powder during the milling and on the surface morphology of the nanocomposite-compacted materials after compaction with and without relaxation assists. Experimental results for different milling systems are presented showing the effects of milling time and material ratio. It was found that a longer mixing time give a higher degree of dispersion of the nanopowder on the PMMA particle surfaces. Furthermore, with increasing content of NiFe2O4 nanopowder, the reduction of the particle size was more effective. Different postcompacting profiles, i.e. different energy distributions between the upper and lower parts of the compacted powder bed, lead to different movements of the various particles and particle layers. Uniformity, homogeneity, and densification on the surfaces in the compacted powder are influenced by the postcompacting magnitude and direction. It was found that the relaxation assist device leads to an improvement in the polymer powder compaction process by reducing the expansion of the compacted volume and by reducing the different opposite velocities, giving the compacted composite bed a more homogeneous opposite velocity during the decompacting stage and reducing the delay time between the successive pressure waves.
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| 42. |
- Badawy, Mona, et al.
(author)
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Hospital volume and the risk of revision in Oxford unicompartmental knee arthroplasty in the Nordic countries -an observational study of 14,496 cases
- 2017
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In: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 18:1
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Journal article (peer-reviewed)abstract
- Background: High procedure volume and dedication to unicompartmental knee arthroplasty (UKA) has been suggested to improve revision rates. This study aimed to quantify the annual hospital volume effect on revision risk in Oxfordu? nicompartmental knee arthroplasty in the Nordic countries. Methods: 14,496 cases of cemented medial Oxford III UKA were identified in 126 hospitals in the four countries included in the Nordic Arthroplasty Register Association (NARA) database from 2000 to 2012. Hospitals were divided by quartiles into 4 annual procedure volume groups (≤11, 12-23, 24-43 and ≥44). The outcome was revision risk after 2 and 10 years calculated using Kaplan Meier method. Multivariate Cox regression analysis was used to assess the Hazard Ratio (HR) of any revision due to specific reasons with 95% confidence intervals (CI). Results: The implant survival was 80% at 10 years in the volume group ≤11 procedures per year compared to 83% in other volume groups. The HR adjusted for age category, sex, year of surgery and nation was 0.87 (95% CI: 0.76-0.99, p = 0.036) for the group 12-23 procedures per year, 0.78 (95% CI: 0.68-0.91, p = 0.002) for the group 24-43 procedures per year and 0.82 (95% CI: 0.70-0.94, p = 0.006) for the group ≥44 procedures per year compared to the low volume group. Log-rank test was p = 0.003. The risk of revision for unexplained pain was 40-50% higher in the low compared with other volume groups. Conclusion: Low volume hospitals performing ≤11 Oxford III UKAs per year were associated with an increased risk of revision compared to higher volume hospitals, and unexplained pain as revision cause was more common in low volume hospitals.
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| 43. |
- Blanco, Blas, et al.
(author)
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Assessment of the influence of railway track periodicity, load speed and support modelling on the rolling noise emission
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Other publication (other academic/artistic)abstract
- The presented methodology jointly accounts for the railway track periodicity and the moving load nature at noise predictions. This modelling approaches rail and sleepers employing the Timoshenko beam theory, and it is formulated to be directly implemented into noise software based on irregularity strip technique. By means of precalculated time domain responses with an analytical track model, the periodicity and moving track dynamics are addressed. In the same way, the propagative behaviour in moving conditions of waves along the rail is characterised by comparison of the responses at several positions.Regarding track support modelling, the usual point modelling is substituted by a distributed representation in order to explore the advantages of accounting for the support length. A numerical model fulfils this task and avoids boundary effects utilising infinite elements. Distributed modelling achieves a more realistic representation of the track geometry. It prevents exaggeration of the amplitude at the `pinned-pinned' frequencies without resorting to overestimation of the steel loss factors. This improvement is especially useful when overvalued rail damping leads to predicted track decay rate (TDR) higher than the one experimentally measured.Finally, the impact of periodicity, load speed and support modelling are assessed through the sound power level (SWL) results. The predictions are performed with a software package, CRoNoS (CAF Rolling Noise Software), developed by CAF S.A. Moving conditions has a limited impact on the SWL, while modelling of the foundation as periodic is important at tracks with hard pad types, and distributed support modelling becomes significant when realistic values of the steel loss factor are used.
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| 44. |
- Blanco, Blas
(author)
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Development of new techniques for the numerical modelling of railway track dynamics. Application to rolling noise assessment
- 2019
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Doctoral thesis (other academic/artistic)abstract
- The numerical modelling is widely employed for the prediction of the railway track dynamic behaviour, which is of utmost importance for the characterisation of the undesired medium-high frequency phenomena, such as corrugation, wheel-out-of-roundness and noise emission. This study is devoted to the improvement of railway track numerical modelling, the efficient resolution of the problem in the time domain and the assessment of rolling noise for different approaches of the track modelling.Regarding the enhancement of the railway track numerical modelling, two main core ideas have led the development of this task. On the one hand, the rail modelling, and on the other hand, the characterisation of the finite length nature of track supports. The proposals of this work include two basic premises, accuracy and computational efficiency.Firstly, the study makes use of Timoshenko beam theory for the numerical description of the rail. However, the conventional Timoshenko finite element involves drawbacks for the description of the rail dynamic behaviour and the calculation of the wheel-rail interaction in the time domain. These problems are addressed by improving the finite element formulation, which is based on the description of its local displacements.Secondly, the versatility of numerical methods is exploited to develop a distributed model of support. It substitutes the usual concentrated model, which entails overestimation of the periodicity effects and disruption of the wheel-rail interaction in the time domain.Thirdly, the advantages of the formulation of numerical models in the frequency domain are explored focusing on the ability to fairly describe the sleeper dynamics, the enhancement of the model boundaries and the realistic modelling of the track components dissipative behaviour. Moreover, the frequency domain response can be used to obtain the wheel-rail interaction in the time domain efficiently, by means of the moving Green's function.Lastly, this work deals with the assessment of rolling noise, in which particular emphasis is made on the influence of track dynamics in the noise prediction. At this regard, a methodology is proposed to account for the track periodicity, load speed and finite length of supports.
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| 45. |
- Blanco, Blas, et al.
(author)
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Distributed support modelling for vertical track dynamic analysis
- 2018
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In: Vehicle System Dynamics. - : Taylor & Francis. - 0042-3114 .- 1744-5159. ; 56:4, s. 529-552
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Journal article (peer-reviewed)abstract
- The finite length nature of rail-pad supports is characterised by a Timoshenko beam element formulation over an elastic foundation, giving rise to the distributed support element. The new element is integrated into a vertical track model, which is solved in frequency and time domain. The developed formulation is obtained by solving the governing equations of a Timoshenko beam for this particular case. The interaction between sleeper and rail via the elastic connection is considered in an analytical, compact and efficient way. The modelling technique results in realistic amplitudes of the pinned-pinned' vibration mode and, additionally, it leads to a smooth evolution of the contact force temporal response and to reduced amplitudes of the rail vertical oscillation, as compared to the results from concentrated support models. Simulations are performed for both parametric and sinusoidal roughness excitation. The model of support proposed here is compared with a previous finite length model developed by other authors, coming to the conclusion that the proposed model gives accurate results at a reduced computational cost.
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| 46. |
- Blanco, Blas, et al.
(author)
-
Distributed support modelling for vertical track dynamic analysis
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Journal article (peer-reviewed)abstract
- The finite length nature of rail-pad supports is characterised by a Timoshenko beam element formulation over an elastic foundation, giving rise to the distributed support element (TEEF). The new element is integrated into a vertical track model, which is solved in frequency and time domain. The developed formulation is obtained by solving the governing equations of a Timoshenko beam for this particular case. The interaction between sleeper and rail via the elastic connection is considered in an analytical, compact and efficient way. The modelling technique results in realistic amplitudes of the ‘pin-pin’ vibration mode and, additionally, it leads to a smooth evolution of the contact force temporal response and to reduced amplitudes of the rail vertical oscillation, as compared to the results from concentrated connection support models. Simulations are performed for both parametric and sinusoidal roughness excitation. The model of support proposed here is compared with a previous finite length model developed by other authors, coming to the conclusion that the proposed model gives accurate results at a reduced computational cost.
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| 47. |
- Blanco, Blas, et al.
(author)
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Implementation of Timoshenko element local deflection for vertical track modelling
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Journal article (peer-reviewed)abstract
- A vertical track model suitable for the study of the dynamic response and the interaction between wheel and rail in the time domain is developed by using Timoshenko beam elements, and its performance is optimized by accounting for the local deflection of these type of elements. Implementation of the local system enables to obtain an accurate description of the contact force in a more computational efficient way than other numerical methods, and it leads to an almost total elimination of the discontinuities caused by the moving nature of the load and the shear incompatibilities introduced by the conventional formulation with Timoshenko beam elements. The work presented here describes both static and dynamic approaches of the local system directly obtained through the resolution of the beam governing equations. Two resolution strategies for the timedomain response are proposed, along with the local system formulation. The first is based on numerical integration of the whole system by introducing a Newmark scheme followed by a Newton–Raphson iterative process. The second resolution strategy is based on a numerical convolution integration, which is able to reduce significantly the computational cost of the simulation. This last resolution methodology together with implementation of the local system approach, join a computationally efficient routine and an accurate description of the track dynamic, which are valuable features for dynamics simulations. The results are validated by comparison with those from previous works.
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| 48. |
- Blanco, Blas, et al.
(author)
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Implementation of Timoshenko element local deflection for vertical track modelling
- 2019
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In: Vehicle System Dynamics. - : TAYLOR & FRANCIS LTD. - 0042-3114 .- 1744-5159. ; 57:10, s. 1421-1444
-
Journal article (peer-reviewed)abstract
- A vertical track model suitable for the study of the dynamic response and the interaction between wheel and rail in the time domain is developed by using Timoshenko beam elements, and its performance is optimised by accounting for the local deflection of these type of elements. Implementation of the local system enables one to obtain an accurate description of the contact force in a more computationally efficient way than other numerical methods, and it leads to an almost total elimination of the discontinuities caused by the local displacement underestimation and the shear incompatibilities introduced by the conventional formulation with Timoshenko beam elements. The work presented here describes both static and dynamic approaches of the local system directly obtained through the resolution of the beam governing equations. The dynamic approach guarantees the shear rotation continuity and describes accurately the track frequency content. The method is tested for parametric excitation, in which it ensures the smoothness of the response. Secondly, it is tested for short-pitch corrugated rails, where overestimation of the contact force is avoided with a reduced model size when compared with conventional Timoshenko element formulation. The results are validated by comparison with those from previous studies.
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| 49. |
- Blanco, Blas, et al.
(author)
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Modelling of the track supports with elements over elastic foundation together with dynamic internal degrees of freedom
- 2018
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In: Proceedings of ISMA 2018 - International Conference on Noise and Vibration Engineering and USD 2018 - International Conference on Uncertainty in Structural Dynamics2018, Pages 3255-326828th International Conference on Noise and Vibration Engineering, ISMA 2018 and 7th International Conference on Uncertainty in Structural Dynamics, USD 2018; Leuven; Belgium; 17 September 2018 through 19 September 2018. - : KU Leuven - Departement Werktuigkunde. - 9789073802995 ; , s. 3255-3268
-
Conference paper (peer-reviewed)abstract
- Formulation of the Timoshenko elements is improved with the use of internal degrees of freedom (iDOF) representing the local displacements, leading to a new finite element approach specially devoted to the numeric analysis of the track dynamics. The dynamic formulation of the local displacement is proved to correct the frequency content of the track model. Regarding time domain studies, this approach avoids the displacement underestimation and shear discontinuity between elements, which are sources of inaccuracies and irregular behaviour. Those rail sections located above the supports are modelled with Timoshenko element over elastic foundation (TEEF), and the rest with conventional Timoshenko elements (TIM4). By using TEEF prompt disruption of the contact force at support surpassing is avoided, and the frequency response of the track around the `pinned-pinned' frequency is corrected. Moreover the TEEF formulation is extended in order to account for the sleeper pitch rotation, and evaluation of its influence over the track dynamics is performed.
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| 50. |
- Blanco, B., et al.
(author)
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On the correction of rail accelerations predicted by numerical track models based on Timoshenko beam theory
- 2021
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In: Vehicle System Dynamics. - : Informa UK Limited. - 0042-3114 .- 1744-5159. ; , s. 1-25
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Journal article (peer-reviewed)abstract
- Rail accelerations can be used on the defect detection and health monitoring of railway vehicle and track components; therefore, mathematical models that predict this response are of interest for reproducing its behaviour in a wide range of situations. The numerical track models based on the Timoshenko beam theory introduce a non-physical response, which is especially noticeable in the rail accelerations. It is due to the lack of dynamic convergence of the Timoshenko finite element (FE). This paper addresses this phenomenon employing an enhanced formulation of the Timoshenko FE that includes internal degrees of freedom (iDoF). The iDoF shape functions are derived from the Timoshenko beam dynamic governing equations. Firstly, the formulation is presented, and its performance is compared with a similar Timoshenko FE formulation. Secondly, the proposal is assessed in the dynamic modelling of railway track structures. The use of iDoF efficiently corrects the non-physical response of rail accelerations by improving the FE dynamic convergence. Subsequently, a filtering criterion for accelerations is proposed, which removes the remaining non-physical response while guaranteeing the conservation of coherent frequency content. Finally, practical cases are simulated for which the proposed methodology is proved to be more efficient and reliable than the standard approach.
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