Model-Free Detection of Cyberattacks on Voltage Control in Distribution Grids

Incorporating information and communication technology in the operation of the electricity grid is undoubtedly contributing to a more cost-efficient, controllable, and flexible power grid. Although this technology is promoting flexibility and convenience, its integration with the electricity grid is rendering this critical infrastructure inherently vulnerable to cyberattacks that have potential to cause large-scale and far-reaching damage. In light of the growing need for a resilient smart grid, developing suitable security mechanisms has become a pressing matter. In this work, we investigate the effectiveness of a model-free state-of-the-art attack-detection method recently proposed by the cybersecurity community in detecting common types of cyberattacks on voltage control in distribution grids. Experimental results show that, by monitoring raw controller and smart-meter data in real time, it is possible to detect denial of service, replay, and integrity attacks, thus contributing to a resilient and more secure grid

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

Polymorphism in the MHC2TA Gene Is Associated with Features of the Metabolic Syndrome and Cardiovascular Mortality

BACKGROUND: Recently, a -168A→G polymorphism in the MHC class II transactivator gene (MHC2TA) was shown to be associated with increased susceptibility to myocardial infarction (MI). AIM: To confirm the association between the MHC2TA -168A→G polymorphism and MI and to study its putative role for microalbuminuria, the metabolic syndrome (MetS) and cardiovascular mortality. MATERIALS AND METHODS: Using an allelic discrimination method we genotyped 11,064 individuals from three study populations: 1) 4,432 individuals from the Botnia type 2 diabetes (T2D) study, 2) 1,222 patients with MI and 2,345 control subjects participating in the Malmö Diet and Cancer study and comprising an MI case-control sample, and 3) 3,065 T2D patients from the Local Swedish Diabetes registry. RESULTS: No association between the -168A→G polymorphism in MHC2TA and MI was observed. However, in the Botnia cohort the AG/GG genotypes were associated with cardiovascular mortality after MI (1.78 [1.09–2.92], p = 0.02). In addition, the AG/GG genotypes were more common in subjects with MetS (40.1% vs. 36.9%, p = 0.03) and in non-diabetic subjects with microalbuminuria (45.4% vs. 36.5%, p = 0.003) compared to control subjects. CONCLUSIONS: A polymorphism in MHC2TA was associated with cardiovascular mortality and predictors of cardiovascular mortality, microalbuminuria and MetS

Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus

Aims: To examine whether genetic variants that predispose individuals to type 2 diabetes (T2D) could predict the development of diabetes after gestational diabetes mellitus (GDM). Methods: 13 SNPs (FTO rs8050136, CDKAL1 rs7754840 and rs7756992, CDKN2A/2B rs10811661, HHEX rs1111875, IGF2BP2 rs1470579 and rs4402960, SLC30A8 rs13266634, TCF7L2 rs7903146, PPARG rs1801282, GCK rs1799884, HNF1A rs1169288, and KCNJ11 rs5219) were genotyped in 793 women with GDM after a median follow-up of 57 months. Results: After adjustment for age and ethnicity, the TCF7L2 rs7903146 and the FTO rs8050136 variants significantly predicted postpartum diabetes; hazard ratio (95% confidence interval 1.29 (1.01-1.66) and 1.36 (1.06-1.74), respectively (additive model) versus 1.45 (1.01-2.08) and 1.56 (1.06-2.29) (dominant model)). Adjusting for BMI attenuated the effect of the FTO variant, suggesting that the effect was mediated through its effect on BMI. Combining all risk alleles to a weighted risk score was significantly associated with the risk of postpartum diabetes (hazard ratio 1.11, 95% confidence interval 1.05-1.18, p = 0.00016 after adjustment for age and ethnicity). Conclusions: The TCF7L2 rs7903146 and FTO rs8050136 polymorphisms, and particularly a weighted risk score of T2D risk alleles, predict diabetes after GDM. Further studies in other populations are needed to confirm our results. (C) 2012 Elsevier Ireland Ltd. All rights reserved

The Triglyceride Content in Skeletal Muscle Is Associated with Hepatic But Not Peripheral Insulin Resistance in Elderly Twins.

Context and Objective:Total muscle triglyceride (MT) content has been associated with insulin resistance. We investigated the predictors and impact of MT on relevant metabolic parameters including peripheral and hepatic insulin resistance in elderly twins.Design and Participants:Seventy-four elderly same-sex twins underwent hyperinsulinemic euglycemic clamps preceded by an iv glucose tolerance test. Aerobic capacity (VO(2max)) and body composition (dual-energy x-ray absorptiometry scan) were determined in all twins. A biopsy from the vastus lateralis muscle was excised in the fasting state. The muscle triacylglycerol content was analyzed by biochemical extraction from these biopsies.Results:The percentage of total body fat was the only independent predictor of MT content. After adjustment for trunk fat percentages and sex, MT level was significantly associated to fasting plasma levels of glucose and insulin as well as hepatic insulin resistance. However, the association was weakened after adjustment for total fat percentages. A 1 sd (34.5 mmol/kg dry weight) increase in MT content was associated with a 24% increase of hepatic insulin resistance. No association between MT content and peripheral insulin sensitivity was observed.Conclusion:MT content is associated with hepatic but not peripheral insulin resistance in elderly twins. We speculate that MT content may reflect the general ectopic accumulation of triglycerides, including fat in the liver

Prediction of Blood Pressure Changes Over Time and Incidence of Hypertension by a Genetic Risk Score in Swedes.

Recent Genome-Wide Association Studies (GWAS) have pinpointed different single nucleotide polymorphisms consistently associated with blood pressure (BP) and hypertension prevalence. However, little data exist regarding single nucleotide polymorphisms predicting BP variation over time and hypertension incidence. The aim of this study was to confirm the association of a genetic risk score (GRS), based on 29 independent single nucleotide polymorphisms, with cross-sectional BP and hypertension prevalence and to challenge its prediction of BP change over time and hypertension incidence in >17 000 middle-aged Swedes participating in a prospective study, the Malmö Preventive Project, investigated at baseline and over a 23-year average period of follow-up. The GRS was associated with higher systolic and diastolic BP values both at baseline (β±SEM, 0.968±0.102 mm Hg and 0.585±0.064 mm Hg; P<1E-19 for both) and at reinvestigation (β±SEM, 1.333±0.161 mm Hg and 0.724±0.086 mm Hg; P<1E-15 for both) and with increased hypertension prevalence (odds ratio [95% CI], 1.192 [1.140-1.245] and 1.144 [1.107-1.183]; P<1E-15 for both). The GRS was positively associated with change (Δ) in BP (β±SEM, 0.033±0.008 mm Hg/y and 0.023±0.004 mm Hg/y; P<1E-04 for both) and hypertension incidence (odds ratio [95% CI], 1.110 [1.065-1.156]; P=6.7 E-07), independently from traditional risk factors. The relative weight of the GRS was lower in magnitude than obesity or prehypertension, but comparable with diabetes mellitus or a positive family history of hypertension. A C-statistics analysis does not show any improvement in the prediction of incident hypertension on top of traditional risk factors. Our data from a large cohort study show that a GRS is independently associated with BP increase and incidence of hypertension

A truncated Kv1.1 protein in the brain of the megencephaly mouse: expression and interaction

BACKGROUND: The megencephaly mouse, mceph/mceph, is epileptic and displays a dramatically increased brain volume and neuronal count. The responsible mutation was recently revealed to be an eleven base pair deletion, leading to a frame shift, in the gene encoding the potassium channel Kv1.1. The predicted MCEPH protein is truncated at amino acid 230 out of 495. Truncated proteins are usually not expressed since nonsense mRNAs are most often degraded. However, high Kv1.1 mRNA levels in mceph/mceph brain indicated that it escaped this control mechanism. Therefore, we hypothesized that the truncated Kv1.1 would be expressed and dysregulate other Kv1 subunits in the mceph/mceph mice. RESULTS: We found that the MCEPH protein is expressed in the brain of mceph/mceph mice. MCEPH was found to lack mature (Golgi) glycosylation, but to be core glycosylated and trapped in the endoplasmic reticulum (ER). Interactions between MCEPH and other Kv1 subunits were studied in cell culture, Xenopus oocytes and the brain. MCEPH can form tetramers with Kv1.1 in cell culture and has a dominant negative effect on Kv1.2 and Kv1.3 currents in oocytes. However, it does not retain Kv1.2 in the ER of neurons. CONCLUSION: The megencephaly mice express a truncated Kv1.1 in the brain, and constitute a unique tool to study Kv1.1 trafficking relevant for understanding epilepsy, ataxia and pathologic brain overgrowth

Plasma lipid composition and risk of developing cardiovascular disease.

We tested whether characteristic changes of the plasma lipidome in individuals with comparable total lipids level associate with future cardiovascular disease (CVD) outcome and whether 23 validated gene variants associated with coronary artery disease (CAD) affect CVD associated lipid species

The Renalase Asp37Glu polymorphism is not associated with hypertension and cardiovascular events in an urban-based prospective cohort: the Malmo Diet and cancer study

Background: Renalase (gene name RNLS), a recently discovered enzyme with monoamine oxidase activity, is implicated in the degradation of catecholamines. Recent studies delineate a possible role of this enzyme in blood pressure (BP) maintenance and cardiac protection and two single nucleotide polymorphisms, RNLS rs2576178 A > G and rs2296545 C > G have been associated with hypertension. The latter SNP leads to a non synonymous Asp to Glu substitution deleting a flavin adenine dinucleotide (FAD) binding site with possible impaired functionality. We tested the hypothesis that these polymorphisms could affect BP levels, hypertension prevalence, and risk of incident cardiovascular events in middle-aged Swedes. Methods: The polymorphisms were genotyped in 5696 participants of the population-based Cardiovascular Cohort of the "Malmo Diet and Cancer" (MDC-CC). The incidence of cardiovascular events (coronary events [n = 408], strokes [n = 330], heart failure [n = 190] and atrial fibrillation/flutter [n = 406]) was monitored for an average of approximately 15 years of follow-up. Results: Both before and after adjustment for sex, age and BMI the polymorphisms did not show any effect on BP level and hypertension prevalence. Before and after adjustment for major cardiovascular risk factors, the hazard ratio for cardiac and cerebrovascular events was not significantly different in carriers of different genotypes. A significant interaction was found between the rs2296545 C > G and age with respect to BP/hypertension. Conclusions: Our data do not support a major role for these RNLS polymorphisms in determining BP level and incident events at population level. The positive interaction with age suggest that the effect of the rs2296545 C > G polymorphism, if any, could vary between different ages