Design and Calibration of a Full Scale Active Magnetic Bearing Based Test Facility for Investigating Rotordynamic Properties of Turbomachinery Seals in Multiphase Flow

The recent move toward subsea oil and gas production brings about a requirement to locate process equipment in deepwater installations. Furthermore, there is a drive toward omitting well stream separation functionality, as this adds complexity and cost to the subsea installation. This in turn leads to technical challenges for the subsea installed pumps and compressors that are now required to handle multiphase flow of varying gas to liquid ratios. This highlights the necessity for a strong research focus on multiphase flow impact on rotordynamic properties and thereby operational stability of the subsea installed rotating machinery. It is well known that careful design of turbomachinery seals, such as interstage and balance piston seals, is pivotal for the performance of pumps and compressors. Consequently, the ability to predict the complex interaction between fluid dynamics and rotordynamics within these seals is key. Numerical tools offering predictive capabilities for turbomachinery seals in multiphase flow are currently being developed and refined, however the lack of experimental data for multiphase seals renders benchmarking and validation impossible. To this end, the Technical University of Denmark and Lloyd's Register Consulting are currently establishing a purpose built state of the art multiphase seal test facility, which is divided into three modules. Module I consists of a full scale active magnetic bearing (AMB) based rotordynamic test bench. The internally designed custom AMBs are equipped with an embedded Hall sensor system enabling high-precision noncontact seal force quantification. Module II is a fully automatized calibration facility for the Hall sensor based force quantification system. Module III consists of the test seal housing assembly. This paper provides details on the design of the novel test facility and the calibration of the Hall sensor system employed to measure AMB forces. Calibration and validation results are presented, along with an uncertainty analysis on the force quantification capabilities.</jats:p

Celebrities in the heart, strangers in the pancreatic beta cell:Voltage-gated potassium channels K_v7.1 and K_v11.1 bridge long QT syndrome with hyperinsulinaemia as well as type 2 diabetes

Voltage‐gated potassium (K(v)) channels play an important role in the repolarization of a variety of excitable tissues, including in the cardiomyocyte and the pancreatic beta cell. Recently, individuals carrying loss‐of‐function (LoF) mutations in KCNQ1, encoding K(v)7.1, and KCNH2 (hERG), encoding K(v)11.1, were found to exhibit post‐prandial hyperinsulinaemia and episodes of hypoglycaemia. These LoF mutations also cause the cardiac disorder long QT syndrome (LQTS), which can be aggravated by hypoglycaemia. Interestingly, patients with LQTS also have a higher burden of diabetes compared to the background population, an apparent paradox in relation to the hyperinsulinaemic phenotype, and KCNQ1 has been identified as a type 2 diabetes risk gene. This review article summarizes the involvement of delayed rectifier K(+) channels in pancreatic beta cell function, with emphasis on K(v)7.1 and K(v)11.1, using the cardiomyocyte for context. The functional and clinical consequences of LoF mutations and polymorphisms in these channels on blood glucose homeostasis are explored using evidence from pre‐clinical, clinical and genome‐wide association studies, thereby evaluating the link between LQTS, hyperinsulinaemia and type 2 diabetes

Cardiovascular and All-Cause Mortality Risk Associated With Urinary Excretion of 8-oxoGuo, a Biomarker for RNA Oxidation, in Patients With Type 2 Diabetes:A Prospective Cohort Study

OBJECTIVE Cardiovascular mortality risk remains high among patients with type 2 diabetes. Oxidative stress indicated by high urinary excretion of the biomarker for RNA oxidation, 8-oxo-7,8-dihydroguanosine (8-oxoGuo), is associated with an increased risk of death in newly diagnosed and treated patients. We assessed whether 8-oxoGuo is associated with specific cardiovascular and all-cause mortality risk. RESEARCH DESIGN AND METHODS Urinary biomarkers for nucleic acid oxidation were measured in a cohort of patients with type 2 diabetes aged ≥60 years (n = 1,863), along with biochemical measurements, questionnaire findings, and Central Person Registry information to estimate the hazard ratios (HRs) for log2-transformed RNA oxidation using Cox regression. RESULTS During the 5-year follow-up, 173 of 1,863 patients had died (9.3%), including 73 patients who died of cardiovascular disease (42.2%). Doubling of RNA oxidation was associated with an HR of all-cause mortality of 2.10 (95% CI 1.63–2.71; P &amp;lt; 0.001) and an HR of cardiovascular death of 1.82 (95% CI 1.20–2.77; P = 0.005) after multiple adjustments. The 5-year absolute risks (ARs) of all-cause mortality (AR 13.9 [95% CI 10.8–17.0] vs. AR 6.10 [95% CI 4.00–8.30]) and cardiovascular mortality (AR 5.49 [95% CI 3.44–7.55] vs. AR 3.16 [95% CI 1.59–4.73]) were approximately two times higher in the highest quartile of RNA oxidation than in the lowest quartile. CONCLUSIONS We conclude that high RNA oxidation is associated with all-cause and cardiovascular mortality risk in patients with type 2 diabetes. Targeting oxidative stress via interventions with long-term follow-up may reveal the predictive potential of the biomarker 8-oxoGuo. </jats:sec

Enhancer of Zeste Homolog 2 (EZH2) Mediates Glucolipotoxicity-Induced Apoptosis in beta-Cells

Selective inhibition of histone deacetylase 3 (HDAC3) prevents glucolipotoxicity-induced &beta;-cell dysfunction and apoptosis by alleviation of proapoptotic endoplasmic reticulum (ER) stress-signaling, but the precise molecular mechanisms of alleviation are unexplored. By unbiased microarray analysis of the &beta;-cell gene expression profile of insulin-producing cells exposed to glucolipotoxicity in the presence or absence of a selective HDAC3 inhibitor, we identified Enhancer of zeste homolog 2 (EZH2) as the sole target candidate. &beta;-Cells were protected against glucolipotoxicity-induced ER stress and apoptosis by EZH2 attenuation. Small molecule inhibitors of EZH2 histone methyltransferase activity rescued human islets from glucolipotoxicity-induced apoptosis. Moreover, EZH2 knockdown cells were protected against glucolipotoxicity-induced downregulation of the protective non-canonical Nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF&kappa;B) pathway. We conclude that EZH2 deficiency protects from glucolipotoxicity-induced ER stress, apoptosis and downregulation of the non-canonical NF&kappa;B pathway, but not from insulin secretory dysfunction. The mechanism likely involves transcriptional regulation via EZH2 functioning as a methyltransferase and/or as a methylation-dependent transcription factor