| 41. |
- Rönn, Tina, et al.
(författare)
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Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle.
- 2008
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 51:7, s. 1159-1168
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Reduced oxidative capacity of the mitochondria in skeletal muscle has been suggested to contribute to insulin resistance and type 2 diabetes. Moreover, a set of genes influencing oxidative phosphorylation (OXPHOS) is downregulated in diabetic muscle. Here we studied whether genetic, epigenetic and non-genetic factors influence a component of the respiratory chain, COX7A1, previously shown to be downregulated in skeletal muscle from patients with type 2 diabetes. The specific aims were to: (1) evaluate the impact of genetic (single nucleotide polymorphisms [SNPs]), epigenetic (DNA methylation) and non-genetic (age) factors on the expression of COX7A1 in human skeletal muscle; and (2) investigate whether common variants in the COX7A1 gene are associated with increased risk of type 2 diabetes. METHODS: COX7A1 mRNA expression was analysed in muscle biopsies from young (n = 110) and elderly (n = 86) non-diabetic twins and related to measures of in vivo metabolism. Genetic variants (three SNPs) from the COX7A1 locus were genotyped in the twins and in two independent type 2 diabetes case-control cohorts (n = 1466 and 6380, respectively). DNA methylation of the COX7A1 promoter was analysed in a subset of twins (ten young, ten elderly) using bisulphite sequencing. RESULTS: While DNA methylation of the COX7A1 promoter was increased in muscle from elderly compared with young twins (19.9 +/- 8.3% vs 1.8 +/- 2.7%; p = 0.035), the opposite was found for COX7A1 mRNA expression (elderly 1.00 +/- 0.05 vs young 1.68 +/- 0.06; p = 0.0005). The heritability of COX7A1 expression was estimated to be 50% in young and 72% in elderly twins. One of the polymorphisms investigated, rs753420, influenced basal COX7A1 expression in muscle of young (p = 0.0001) but not of elderly twins. The transcript level of COX7A1 was associated with increased in vivo glucose uptake and [Formula: see text] (p = 0.009 and p = 0.001, respectively). We did not observe any genetic association between COX7A1 polymorphisms and type 2 diabetes after correcting for multiple testing. CONCLUSIONS/INTERPRETATION: Our results provide further evidence for age as a factor influencing DNA methylation and expression of OXPHOS genes, and thereby in vivo metabolism.
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| 42. |
- Scott, Robert A., et al.
(författare)
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An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:11, s. 2888-2902
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Tidskriftsartikel (refereegranskat)abstract
- To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
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| 43. |
- Tagetti, A., et al.
(författare)
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A genetic risk score for hypertension is associated with risk of thoracic aortic aneurysm
- 2019
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Ingår i: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 0950-9240 .- 1476-5527. ; 33:9, s. 658-663
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Tidskriftsartikel (refereegranskat)abstract
- A genetic risk score (GRS) based on 29 single nucleotide polymorpysms (SNPs) associated with high blood pressure (BP) was prospectively associated with development of hypertension, stroke and cardiovascular events. The aim of the present study was to evaluate the impact of this GRS on the incidence of aortic disease, including aortic dissection (AD), rupture or surgery of a thoracic (TAA) or abdominal (AAA) aortic aneurysm. More than 25,000 people from the Swedish Malmo Diet and Cancer Study had information on at least 24 SNPs and were followed up for a median ≥ 18 years. The number of BP elevating alleles of each SNPs, weighted by their effect size in the discovery studies, was summed into a BP-GRS. In Cox regression models, adjusted for traditional cardiovascular risk factors including hypertension, we found significant associations of the BP-GRS, prospectively, with incident TAA (hazard ratio (HR) 1.64 (95% confidence interval (CI) 1.081–2.475 comparing the third vs. the first tertile; p = 0.020) but not with either AAA or aortic dissection. Calibration, discrimination and reclassification analyses show modest improvement in prediction using the BP-GRS in addition to the model which used only traditional risk factors. A GRS for hypertension associates with TAA suggesting a link between genetic determinants of BP and aortic disease. The effect size is small but the addition of more SNPs to the GRS might improve its discriminatory capability.
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| 44. |
- Willer, Cristen J., et al.
(författare)
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Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
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| 45. |
- Winckler, W, et al.
(författare)
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Association of common variation in the HNF1 alpha gene region with risk of type 2 diabetes
- 2005
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Ingår i: Diabetes. - 1939-327X. ; 54:8, s. 2336-2342
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Tidskriftsartikel (refereegranskat)abstract
- It is currently unclear how often genes that are mutated to cause rare, early-onset monogenic forms of disease also harbor common variants that contribute to the more typical polygenic form of each disease. The gene for MODY3 diabetes, HNF1 alpha, lies in a region that has shown linkage to late-onset type 2 diabetes (12q24, NIDDM2), and previous association studies have suggested a weak trend toward association for common missense variants in HNF1a with glucose-related traits. Based on genotyping of 79 common SNPs in the 118 kb spanning HNF1 alpha, we selected 21 haplotype tag single nucleotide polymorphisms (SNPs) and genotyped them in > 4,000 diabetic patients and control subjects from Sweden, Finland, and Canada. Several SNPs from the coding region and 5' of the gene demonstrated nominal association with type 2 diabetes, with the most significant marker (rs1920792) having an odds ratio of 1.17 and a P value of 0.002. We then genotyped three SNPs with the strongest evidence for association to type 2 diabetes (rs1920792, I27L, and A98V) in an additional 4,400 type 2 diabetic and control subjects from North America and Poland and compared our results with those of the original sample and of Weedon et al. None of the results were consistently observed across all samples, with the possible exception of a modest association of the rare (3-5%) A98V variant. These results indicate that common variants in HNF1 alpha either play no role in type 2 diabetes, a very small role, or a role that cannot be consistently observed without consideration of as yet unmeasured genetic or environmental modifiers.
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| 46. |
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| 47. |
- Almgren, Karin, et al.
(författare)
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Role of fibre-fibre and fibre-matrix adhesion in stress transfer in composites made from resin-impregnated paper sheets.
- 2009
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Ingår i: International Journal of Adhesion and Adhesives. - : Elsevier BV. - 0143-7496 .- 1879-0127. ; 29:5, s. 551-557
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Tidskriftsartikel (refereegranskat)abstract
- Paper-reinforced plastics are gaining increased interest as packaging materials, where mechanical properties are of great importance. Strength and stress transfer in paper sheets are controlled by fibre-fibre bonds. In paper-reinforced plastics, where the sheet is impregnated with a polymer resin, other stress-transfer mechanisms may be more important. The influence of fibre-fibre bonds on the strength of paper-reinforced plastics was therefore investigated. Paper sheets with different degrees of fibre-fibre bonding were manufactured and used as reinforcement in a polymeric matrix. Image analysis tools were used to verify that the difference in the degree of fibre-fibre bonding had been preserved in the composite materials. Strength and stiffness of the composites were experimentally determined and showed no correlation to the degree of fibre-fibre bonding, in contrast to the behaviour of unimpregnated paper sheets. The degree of fibre-fibre bonding is therefore believed to have little importance in this type of material, where stress is mainly transferred through the fibre-matrix interface.
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| 48. |
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| 49. |
- Almgren, Magnus, 1972, et al.
(författare)
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RICS-el : Building a national testbed for research and training on SCADA security (short paper)
- 2019
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Ingår i: Lect. Notes Comput. Sci.. - Cham : Springer Nature. ; 11260 LNCS, s. 219-225, s. 219-225
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Konferensbidrag (refereegranskat)abstract
- Trends show that cyber attacks targeting critical infrastructures are increasing, but security research for protecting such systems are challenging. There is a gap between the somewhat simplified models researchers at universities can sustain contra the complex systems at infrastructure owners that seldom can be used for direct research. There is also a lack of common datasets for research benchmarking. This paper presents a national experimental testbed for security research within supervisory control and data acquisition systems (SCADA), accessible for both research training and experiments. The virtualized testbed has been designed and implemented with both vendor experts and security researchers to balance the goals of realism with specific research needs. It includes a real SCADA product for energy management, a number of network zones, substation nodes, and a simulated power system. This environment enables creation of scenarios similar to real world utility scenarios, attack generation, development of defence mechanisms, and perhaps just as important: generating open datasets for comparative research evaluation.
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| 50. |
- Almgren, P
(författare)
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Tvärkraftsbelastade spikar i ändträ provningsrapport
- 1987
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Provningar för dimensionering av olika konstruktioner kräver tid och omtanke. I dagens byggnorm, SBN 1980, finns inga angivna tillåtna värden för spikar i ändträ, varken när det gäller utdragskraft eller tvärkraft. I praktiken utnyttjas ofta spikar i ändträ för att ta upp tvärkraften. Man vet av erfarenhet att det ger en avsevärd hållfasthet åt förbanden. Ingen riktig dokumentation av hur stor hållkraften är har dock funnits. En inledande studie har nu gjorts av spikars hållkraft i ändträ. Det karakteristiska värdet (ett av hållfasthetsspridningen påverkat fraktilvärde, lägre än medelvärdet) för spik i ändträ visade sig kunna sättas till ca 60 % av motsvarande värde för spik slagen vinkelrätt fibrerna. Värdet kan dock inte anges utan förbehåll innan ytterligare studier gjorts och regler för hur provningen skall utföras utarbetats.
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