Measurements Versus Predictions for the Static and Dynamic Characteristics of a Four-pad Rocker-pivot, Tilting-pad Journal Bearing

Measured and predicted static and dynamic characteristics are provided for a four-pad, rocker-pivot, tilting-pad journal bearing in the load-on-pad and load-between-pad orientations. The bearing has the following characteristics: 4 pads, .57 pad pivot offset, 0.6 L/D ratio, 60.33 mm (2.375in) pad axial length, 0.08255 mm (0.00325 in) radial clearance in the load-on-pad orientation, and 0.1189 mm (0.00468 in) radial clearance in the load-between-pad orientation. Tests were conducted on a floating test bearing design with unit loads ranging from 0 to 2903 kPa (421.1 psi) and speeds from 6.8 to 13.2 krpm. For all rotor speeds, hot-clearance measurements were taken to show the reduction in bearing clearance due to thermal expansion of the shaft and pads during testing. As the testing conditions get hotter, the rotor, pads, and bearing expand, decreasing radial bearing clearance. Hot-clearance measurements showed a 16-25% decrease in clearance compared to a clearance measurement at room temperature. For all test conditions, dynamic tests were performed over a range of excitation frequencies to obtain complex dynamic stiffness coefficients as a function of frequency. The direct real dynamic stiffness coefficients were then fitted with a quadratic function with respect to frequency. From the curve fit, the frequency dependence was captured by including a virtual-mass matrix [M] to produce a frequency independent [K][C][M] model. The direct dynamic stiffness coefficients for the load-on-pad orientation showed significant orthotropy, while the load-between-pad did not. The load-between-pad showed slight orthotropy as load increased. Experimental cross-coupled stiffness coefficients were measured in both load orientations, but were of the same sign and significantly less than direct stiffness coefficients. In both orientations the imaginary part of the measured dynamic stiffness increased linearly with increasing frequency, allowing for frequency independent direct damping coefficients. Rotordynamic coefficients presented were compared to predictions from two different Reynolds-based models. Both models showed the importance of taking into account pivot flexibility and different pad geometries (due to the reduction in bearing clearance during testing) in predicting rotordynamic coefficients. If either of these two inputs were incorrect, then predictions for the bearings impedance coefficients were very inaccurate. The main difference between prediction codes is that one of the codes incorporates pad flexibility in predicting the impedance coefficients for a tilting-pad journal bearing. To look at the effects that pad flexibility has on predicting the impedance coefficients, a series of predictions were created by changing the magnitude of the pad's bending stiffness. Increasing the bending stiffness used in predictions by a factor of 10 typically caused a 3-11% increase in predicted Kxx and Kyy, and a 10-24% increase in predicted Cxx and Cyy. In all cases, increasing the calculated bending stiffness from ten to a hundred times the calculated value caused slight if any change in Kxx, Kyy, Cxx, and Cyy. For a flexible pad an increase in bending stiffness can have a large effect on predictions; however, for a more rigid pad an increase in pad bending stiffness will have a much lesser effect. Results showed that the pad's structural bending stiffness can be an important factor in predicting impedance coefficients. Even though the pads tested in this thesis are extremely stiff, changes are still seen in predictions when the magnitude of the pad?s bending stiffness is increased, especially in Cxx, and Cyy. The code without pad flexibility predicted Kxx and Kyy much more accurately than the code with pad flexibility. The code with pad flexibility predicts Cxx more accurately, while the code without pad flexibility predicted Cyy more accurately. Regardless of prediction Code used, the Kxx and Kyy were over-predicted at low loads, but predicted more accurately as load increased. Cxx, and Cyy were modeled very well in the load-on-pad orientation, while slightly overpredicted in the load-between-pad orientation. For solid pads, like the ones tested here, both codes do a decent job at predicting impedance coefficient

Vascular miR‐181b controls tissue factor‐dependent thrombogenicity and inflammation in type 2 diabetes

BACKGROUND: Diabetes mellitus is characterized by chronic vascular inflammation leading to pathological expression of the thrombogenic full length (fl) tissue factor (TF) and its isoform alternatively-spliced (as) TF. Blood-borne TF promotes factor (F) Xa generation resulting in a pro-thrombotic state and cardiovascular complications. MicroRNA (miR)s impact gene expression on the post-transcriptional level and contribute to vascular homeostasis. Their distinct role in the control of the diabetes-related procoagulant state remains poorly understood. METHODS: In a cohort of patients with poorly controlled type 2 diabetes (n = 46) plasma levels of miR-181b were correlated with TF pathway activity and markers for vascular inflammation. In vitro, human microvascular endothelial cells (HMEC)-1 and human monocytes (THP-1) were transfected with miR-181b or anti-miR-181b and exposed to tumor necrosis factor (TNF) α or lipopolysaccharides (LPS). Expression of TF isoforms, vascular adhesion molecule (VCAM) 1 and nuclear factor (NF) κB nuclear translocation was assessed. Moreover, aortas, spleen, plasma, and bone marrow-derived macrophage (BMDM)s of mice carrying a deletion of the first miR-181b locus were analyzed with respect to TF expression and activity. RESULTS: In patients with type 2 diabetes, plasma miR-181b negatively correlated with the procoagulant state as evidenced by TF protein, TF activity, D-dimer levels as well as markers for vascular inflammation. In HMEC-1, miR-181b abrogated TNFα-induced expression of flTF, asTF, and VCAM1. These results were validated using the anti-miR-181b. Mechanistically, we confirmed a miR-181b-mediated inhibition of importin-α3 (KPNA4) leading to reduced nuclear translocation of the TF transcription factor NFκB. In THP-1, miR-181b reduced both TF isoforms and FXa generation in response to LPS due to targeting phosphatase and tensin homolog (PTEN), a principal inducer for TF in monocytes. Moreover, in miR-181-/- animals, we found that reduced levels of miR-181b were accompanied by increased TF, VCAM1, and KPNA4 expression in aortic tissue as well as increased TF and PTEN expression in spleen. Finally, BMDMs of miR-181-/- mice showed increased TF expression and FXa generation upon stimulation with LPS. CONCLUSIONS: miR-181b epigenetically controls the procoagulant state in diabetes. Reduced miR-181b levels contribute to increased thrombogenicity and may help to identify individuals at particular risk for thrombosis

Apolipoprotein A-I gene transfer exerts immunomodulatory effects and reduces vascular inflammation and fibrosis in ob/ob mice

Background Obesity is associated with vascular inflammation, fibrosis and reduced high-density lipoproteins (HDL)-cholesterol. We aimed to investigate whether adenoviral gene transfer with human apolipoprotein (apo) A-I (Ad.A-I), the main apo of HDL, could exert immunomodulatory effects and counteract vascular inflammation and fibrosis in ob/ob mice. Methods Ad.A-I transfer was performed in 8 weeks (w) old ob/ob mice, which were sacrificed 7 w later. The aorta was excised for mRNA analysis and the spleen for splenocyte isolation for subsequent flow cytometry and co-culture with murine fibroblasts. HDL was added to mononuclear cells (MNC) and fibroblasts to assess their impact on adhesion capacity and collagen deposition, respectively. Results Ad.A-I led to a 1.8-fold (p < 0.05) increase in HDL-cholesterol versus control ob/ob mice at the day of sacrifice, which was paralleled by a decrease in aortic TNF-α and VCAM-1 mRNA expression. Pre-culture of MNC with HDL decreased their adhesion to TNF-α-activated HAEC. Ad.A-I exerted immunomodulatory effects as evidenced by a downregulation of aortic NOD2 and NLRP3 mRNA expression and by a 12 %, 6.9 %, and 15 % decrease of the induced proliferation/activity of total splenic MNC, CD4+, and CD8+ cells in ob/ob Ad.A-I versus control ob/ob mice, respectively (p < 0.05). Ad.A-I further reduced aortic collagen I and III mRNA expression by 62 % and 66 %, respectively (p < 0.0005), and abrogated the potential of ob/ob splenocytes to induce the collagen content in murine fibroblasts upon co-culture. Finally, HDL decreased the TGF-ß1-induced collagen deposition of murine fibroblasts in vitro

Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment

Interstitial fibrosis plays a key role in the development and progression of heart failure. Here, we show that an enzyme that crosslinks collagen—Lysyl oxidase-like 2 (Loxl2)—is essential for interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and chamber dilatation, improving systolic and diastolic functions. Loxl2 stimulates cardiac fibroblasts through PI3K/AKT to produce TGF-β2, promoting fibroblast-to-myofibroblast transformation; Loxl2 also acts downstream of TGF-β2 to stimulate myofibroblast migration. In diseased human hearts, LOXL2 is upregulated in cardiac interstitium; its levels correlate with collagen crosslinking and cardiac dysfunction. LOXL2 is also elevated in the serum of heart failure (HF) patients, correlating with other HF biomarkers, suggesting a conserved LOXL2-mediated mechanism of human HF

MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes

Background: Diabetes mellitus is characterized by chronic vascular disorder and presents a main risk factor for cardiovascular mortality. In particular, hyperglycaemia and inflammatory cytokines induce vascular circulating tissue factor (TF) that promotes pro-thrombotic conditions in diabetes. It has recently become evident that alterations of the post-transcriptional regulation of TF via specific microRNA(miR)s, such as miR-126, contribute to the pathogenesis of diabetes and its complications. The endothelial miR-19a is involved in vascular homeostasis and atheroprotection. However, its role in diabetes-related thrombogenicity is unknown. Understanding miR-networks regulating procoagulability in diabetes may help to develop new treatment options preventing vascular complications. Methods and results: Plasma of 44 patients with known diabetes was assessed for the expression of miR-19a, TF protein, TF activity, and markers for vascular inflammation. High miR-19a expression was associated with reduced TF protein, TF-mediated procoagulability, and vascular inflammation based on expression of vascular adhesion molecule-1 and leukocyte count. We found plasma expression of miR-19a to strongly correlate with miR-126. miR-19a reduced the TF expression on mRNA and protein level in human microvascular endothelial cells (HMEC) as well as TF activity in human monocytes (THP-1), while anti-miR-19a increased the TF expression. Interestingly, miR-19a induced VCAM expression in HMEC. However, miR-19a and miR-126 co-transfection reduced total endothelial VCAM expression and exhibited additive inhibition of a luciferase reporter construct containing the F3 3′UTR. Conclusions: While both miRs have differential functions on endothelial VCAM expression, miR-19a and miR-126 cooperate to exhibit anti-thrombotic properties via regulating vascular TF expression. Modulating the post-transcriptional control of TF in diabetes may provide a future anti-thrombotic and anti-inflammatory therapy

Cardiovascular magnetic resonance findings in non‐hospitalized paediatric patients after recovery from COVID‐19

Aims: Our study aimed to investigate the cardiac involvement with sensitive tissue characterization in non-hospitalized children with coronavirus disease 2019 (COVID-19) infection using cardiovascular magnetic resonance (CMR) imaging. Methods and results: We prospectively enrolled children who recovered from mildly symptomatic COVID-19 infection between November 2020 and January 2021. Patients underwent CMR at 1.5 T (Achieva, Philips Healthcare, Best, the Netherlands) including cine images, native T1 and T2 mapping. Healthy children and paediatric patients with biopsy-proven myocarditis served as control groups. We performed CMR in 18 children with a median (25th-75th percentile) age of 12 (10-15) years, 38 (24-47) days after positive PCR test, and compared them with 7 healthy controls [15 (10-19) years] and 9 patients with myocarditis [10 (4-16) years]. The COVID-19 patients reported no cardiac symptoms. None of the COVID-19 patients showed CMR findings consistent with a myocarditis. Three patients (17%) from the COVID-19 cohort presented with minimal pericardial effusion. CMR parameters of COVID-19 patients, including volumetric and strain values as well as T1 and T2 times, were not significantly different from healthy controls, but from myocarditis patients. These had significantly reduced left ventricular (LV) ejection fraction (P = 0.035), LV global longitudinal strain, and left atrial strain values as well as elevated native T1 values compared with COVID-19 patients (P < 0.001, respectively). Conclusions There was no evidence of myocardial inflammation, fibrosis, or functional cardiac impairment in the studied cohort of children recently. CMR findings were comparable with those of healthy controls. Pericardial effusion suggests a mild pericarditis in a small subgroup. This is pointing to a minor clinical relevance of myocardial involvement in children after mildly symptomatic COVID-19 infections