Approximate boundary conditions for a fluid-loaded elastic plate

Approximate boundary conditions for an infinite elastic layer immersed in a fluid are derived. By using series expansions in the thickness coordinate of the plate fields, the displacements fields are eliminated, adopting the three-dimensional equations of motion. The sums and differences of the boundary pressure fields and their normal derivatives are related through a set of approximate boundary conditions, one symmetric and one antisymmetric. These equations involve powers in the layer thickness together with partial derivatives with respect to time as well as the spatial variables in the plate plane. The approximate boundary conditions can be truncated to an arbitrary order, and explicit relations are presented including terms of order five. Comparisons are made with effective boundary conditions using classical plate theories. The numerical examples involve reflection and transmission of plane waves incident on the plate at different angles, as well as the pressure fields due to a line force. Three fluid-loading cases are studied: modest, heavy, and light loadings. The results using truncated approximate boundary conditions are compared to exact and classical plate solutions. The examples show that the accuracies of the power series approximations of order three and higher are very good in the frequency interval considered

Identification of CpG-SNPs associated with type 2 diabetes and differential DNA methylation in human pancreatic islets.

AIMS/HYPOTHESIS: To date, the molecular function of most of the reported type 2 diabetes-associated loci remains unknown. The introduction or removal of cytosine-phosphate-guanine (CpG) dinucleotides, which are possible sites of DNA methylation, has been suggested as a potential mechanism through which single-nucleotide polymorphisms (SNPs) can affect gene function via epigenetics. The aim of this study was to examine if any of 40 SNPs previously associated with type 2 diabetes introduce or remove a CpG site and if these CpG-SNPs are associated with differential DNA methylation in pancreatic islets of 84 human donors. METHODS: DNA methylation was analysed using pyrosequencing. RESULTS: We found that 19 of 40 (48%) type 2 diabetes-associated SNPs introduce or remove a CpG site. Successful DNA methylation data were generated for 16 of these 19 CpG-SNP loci, representing the candidate genes TCF7L2, KCNQ1, PPARG, HHEX, CDKN2A, SLC30A8, DUSP9, CDKAL1, ADCY5, SRR, WFS1, IRS1, DUSP8, HMGA2, TSPAN8 and CHCHD9. All analysed CpG-SNPs were associated with differential DNA methylation of the CpG-SNP site in human islets. Moreover, six CpG-SNPs, representing TCF7L2, KCNQ1, CDKN2A, ADCY5, WFS1 and HMGA2, were also associated with DNA methylation of surrounding CpG sites. Some of the type 2 diabetes CpG-SNP sites that exhibit differential DNA methylation were further associated with gene expression, alternative splicing events determined by splice index, and hormone secretion in the human islets. The 19 type 2 diabetes-associated CpG-SNPs are in strong linkage disequilibrium (r (2) > 0.8) with a total of 295 SNPs, including 91 CpG-SNPs. CONCLUSIONS/INTERPRETATION: Our results suggest that the introduction or removal of a CpG site may be a molecular mechanism through which some of the type 2 diabetes SNPs affect gene function via differential DNA methylation and consequently contributes to the phenotype of the disease

Two common genetic variants near nuclear-encoded OXPHOS genes are associated with insulin secretion in vivo

Context Mitochondrial ATP production is important in the regulation of glucose-stimulated insulin secretion. Genetic factors may modulate the capacity of the β-cells to secrete insulin and thereby contribute to the risk of type 2 diabetes. OBJECTIVE: The aim of this study was to identify genetic loci in or adjacent to nuclear encoded genes of the oxidative phosphorylation (OXPHOS) pathway that are associated with insulin secretion in vivo. DESIGN AND METHODS: To find polymorphisms associated with glucose-stimulated insulin secretion, data from a genome-wide association study (GWAS) of 1467 non-diabetic individuals, the Diabetes Genetic Initiative (DGI), was examined. 413 single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) ≥0.05 located in or adjacent to 76 OXPHOS genes were included in the DGI GWAS. A more extensive population based study of 4323 non-diabetics, the PPP-Botnia, was used as a replication cohort. Insulinogenic index during an oral glucose tolerance test (OGTT) was used as a surrogate marker of glucose-stimulated insulin secretion. Multivariate linear regression analyses were used to test genotype-phenotype associations. RESULTS: Two common variants were indentified in the DGI, where the major C-allele of rs606164, adjacent to NDUFC2 (NADH dehyrogenase (ubiqinone) 1 subunit C2), and the minor G-allele of rs1323070, adjacent to COX7A2 (cythochrome c oxidase subunit VIIa polypeptide 2), showed nominal associations with decreased glucose-stimulated insulin secretion (p=0.0009 respective p=0.003). These associations were replicated in PPP-Botnia (p=0.002 and p=0.05). CONCLUSION: Our study shows that genetic variation near genes involved in oxidative phosphorylation may influence glucose-stimulated insulin secretion in vivo

Decreased expression of genes involved in oxidative phosphorylation in human pancreatic islets from patients with type 2 diabetes

Objective: Gene expression alterations, especially in target tissues of insulin, have been associated with type 2 diabetes (T2D). In this study, we examined if genes involved in oxidative phosphorylation (OXPHOS) show differential gene expression and DNA methylation in pancreatic islets from patients with T2D compared with non-diabetic donors. Design and methods: Gene expression was analyzed in human pancreatic islets from 55 non-diabetic donors and nine T2D donors using microarray. Results: While the expected number of OXPHOS genes with reduced gene expression is 7.21, we identified 21 downregulated OXPHOS genes in pancreatic islets from patients with T2D using microarray analysis. This gives a ratio of observed over expected OXPHOS genes of 26.37 by a χ-test with P=2.81 × 10. The microarray data was validated by qRT-PCR for four selected OXPHOS genes: NDUFA5, NDUFA10, COX11, and ATP6V1H. All four OXPHOS genes were significantly downregulated in islets from patients with T2D compared with non-diabetic donors using qRT-PCR (P≤0.01). Furthermore, HbAlc levels correlated negatively with gene expression of NDUFA5, COX11, and ATP6V1H (

Synchrotron XRF Analysis Identifies Cerium Accumulation Colocalized with Pharyngeal Deformities in CeO2 NP-Exposed Caenorhabditis elegans

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Vortex glass transition in a random pinning model

We study the vortex glass transition in disordered high temperature superconductors using Monte Carlo simulations. We use a random pinning model with strong point-correlated quenched disorder, a net applied magnetic field, longrange vortex interactions, and periodic boundary conditions. From a finite size scaling study of the helicity modulus, the RMS current, and the resistivity, we obtain critical exponents at the phase transition. The new exponents differ substantially from those of the gauge glass model, but are consistent with those of the pure three-dimensional XY model.Comment: 7 pages RevTeX, 4 eps figure

Impact of national holidays and weekends on incidence of acute type A aortic dissection repair

Publisher Copyright: © 2022, The Author(s).Previous studies have demonstrated that environmental and temporal factors may affect the incidence of acute type A aortic dissection (ATAAD). Here, we aimed to investigate the hypothesis that national holidays and weekends influence the incidence of surgery for ATAAD. For the period 1st of January 2005 until 31st of December 2019, we investigated a hypothesised effect of (country-specific) national holidays and weekends on the frequency of 2995 surgical repairs for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Compared to other days, the number of ATAAD repairs were 29% (RR 0.71; 95% CI 0.54–0.94) lower on national holidays and 26% (RR 0.74; 95% CI 0.68–0.82) lower on weekends. As day of week patterns of symptom duration were assessed and the primary analyses were adjusted for period of year, our findings suggest that the reduced surgical incidence on national holidays and weekends does not seem to correspond to seasonal effects or surgery being delayed and performed on regular working days.Peer reviewe

Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes.

Reduced insulin release has been linked to defect exocytosis in β-cells. However, whether expression of genes suggested to be involved in the exocytotic process (exocytotic genes) is altered in pancreatic islets from patients with type 2 diabetes (T2D), and correlate to insulin secretion, needs to be further investigated. Analysing expression levels of 23 exocytotic genes using microarray revealed reduced expression of five genes in human T2D islets (χ(2)=13.25; p<0.001). Gene expression of STX1A, SYT4, SYT7, SYT11, SYT13, SNAP25 and STXBP1 correlated negatively to in vivo measurements of HbA1c levels and positively to glucose stimulated insulin secretion (GSIS) in vitro in human islets. STX1A, SYT4 and SYT11 protein levels correspondingly decreased in human T2D islets. Moreover, silencing of SYT4 and SYT13 reduced GSIS in INS1-832/13 cells. Our data support that reduced expression of exocytotic genes contributes to impaired insulin secretion, and suggest decreased expression of these genes as part of T2D pathogenesis

Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes

Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in beta-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D.Peer reviewe