A Novel Diagnostic Feature for a Wind Turbine Imbalance Under Variable Speed Conditions.

Dependency between the conventional imbalance diagnostic feature and the shaft rotational speed makes imbalance diagnosis challenging for variable-speed machines. This paper focuses on an investigation of this dependency and on a proposal for a novel imbalance diagnostic feature and a novel simplified version for this feature, which are independent of shaft rotational speed. An equivalent mass-spring-damper system is investigated to find a closed-form expression describing this dependency.

"Tis Better to Give Than to Receive?" Health-related Benefits of Delivering Peer Support in Type 2 Diabetes: An Explanatory Sequential Mixed-methods Study.

Objectives: Existing peer support literature in diabetes has focussed predominantly on the health impact it has on the beneficiaries rather than the benefactors. In this mixed-methods study, we examined the effect of delivering peer support (vs receiving) on glycated hemoglobin (A1C) and diabetes distress (DD) at 3 and 12 months as part of a larger diabetes self-management support randomized controlled trial. Maintenance or improvement of outcomes was expected.

Predicting the role of coping factors on pandemic-related anxiety.

The year 2020 saw the emergence of a worldwide pandemic caused by the novel coronavirus COVID-19. Measures against further spread of the virus were taken nearly everywhere in the world. Many countries also imposed social distancing rules and lockdowns on their population.

Profiling "Success": Demographic and Personality Predictors of Effective Peer Leaders in a Diabetes Self-management Intervention.

Background: The sociodemographic and personality profiles of effective peer leaders in the context of diabetes self-management interventions are poorly understood. In this study, we explored the demographic and personality characteristics of peer leaders participating in a 12-month, telephone-based type 2 diabetes self-management intervention.

Methods: We used a sequential explanatory mixed-methods research design and recruited 52 peer leaders.

Out of the mouths of Peer Leaders: Perspectives on how to improve a telephone-based peer support intervention in type 2 diabetes.

Objective: To explore the experiences of peer leaders with respect to delivering core components of a 12-month, telephone-based peer support intervention in type 2 diabetes within a tertiary-care setting.

Methods: Seventeen peer leaders were recruited and interviewed. Interviews lasted approximately 20 to 45 min, were audio-taped, and transcribed verbatim.

Masson's Tumor of the Hand: An Uncommon Histopathological Entity.

Masson's tumor or Masson's hemangioma, more precisely termed intravascular papillary endothelial hyperplasia (IPEH), is an uncommon benign vascular lesion of the skin and subcutaneous tissues which can be frequently confused with angiosarcoma. Although relatively rare, its accurate diagnosis is essential since it can clinically be similar to both benign and malignant lesions. We present a 39-year-old man with a round bulging arising from the left palm side of the hand with gradual growth in the last 5 months and on and off tenderness.

The other functions of the sodium pump.

Na/K-ATPase (the sodium pump) was discovered in the 1950s as the plasma membrane enzyme that carries out the coupled active transports of Na and K across the membranes of nearly all eukaryotic cells. It was not until the 1990s when it was shown that besides pumping ions, Na/K-ATPase is also capable of stimulus-induced interactions with neighboring proteins that lead to activations of signal transduction pathways causing cell growth. This article is an attempt to review the progress of the research on these signaling functions of sodium pump during the past 2-3 decades.

Peer support interventions in type 2 diabetes: Review of components and process outcomes.

Background: This review seeks to identify (a) the various components and process outcomes of type 2 diabetes peer support (PS) interventions and (b) the measures implemented to monitor intervention fidelity and evaluate outcomes in these studies.

Methods: The MEDLINE, PubMed, EMBASE (Excerpta Medica Database), CENTRAL (Cochrane Central Register of Controlled Trials), CINAHL (Cumulative Index to Nursing and Allied Health Literature), and PsycINFO databases were searched from inception to May 2019. Two reviewers independently screened and extracted data from eligible articles via the Template for Intervention Description and Replication (TIDieR) checklist (why, what, who provided, how, where, when and how much, tailoring, modifications, and how well).

The sodium pump and digitalis drugs: Dogmas and fallacies.

The sodium pump (Na/K-ATPase) is a plasma membrane enzyme that transports Na and K against their physiological gradients in most eukaryotic cells. Besides pumping ions, the enzyme may also interact with neighboring proteins to activate cell signaling pathways that regulate cell growth. Digitalis drugs, useful for the treatment of heart failure and atrial arrhythmias, inhibit the pumping function of Na/K-ATPase and stimulate its signaling function.

Comparison of Digitalis Sensitivities of Na/K-ATPases from Human and Pig Kidneys.

Digitalis drugs are selective inhibitors of the plasma membrane Na/K-ATPase. There are many studies on molecular mechanisms of digitalis interaction with purified pig kidney enzyme, with the tacit assumption that it is a good model of human kidney enzyme. However, previous studies on crude or recombinant human kidney enzymes are limited, and have not resulted in consistent findings on their digitalis sensitivities.

Evolution of the α-Subunit of Na/K-ATPase from Paramecium to Homo sapiens: Invariance of Transmembrane Helix Topology.

Na/K-ATPase is a key plasma membrane enzyme involved in cell signaling, volume regulation, and maintenance of electrochemical gradients. The α-subunit, central to these functions, belongs to a large family of P-type ATPases. Differences in transmembrane (TM) helix topology, sequence homology, helix-helix contacts, cell signaling, and protein domains of Na/K-ATPase α-subunit were compared in fungi (Beauveria), unicellular organisms (Paramecia), primitive multicellular organisms (Hydra), and vertebrates (Xenopus, Homo sapiens), and correlated with evolution of physiological functions in the α-subunit.

Ouabain prevents pathological cardiac hypertrophy and heart failure through activation of phosphoinositide 3-kinase α in mouse.

Background: Use of low doses of digitalis to prevent the development of heart failure was advocated decades ago, but conflicting results of early animal studies dissuaded further research on this issue. Recent discoveries of digitalis effects on cell signal pathways prompted us to reexamine the possibility of this prophylactic action of digitalis. The specific aim of the present study was to determine if subinotropic doses of ouabain would prevent pressure overload-induced cardiac remodeling in the mouse by activating phosphoinositide 3-kinase α (PI3Kα).

Digitalis-induced cell signaling by the sodium pump: on the relation of Src to Na(+)/K(+)-ATPase.

In addition to performing its essential transport function, the sodium pump also activates multiple cell signaling pathways in response to digitalis drugs such as ouabain. Based mainly on cell-free studies with mixtures of purified Src kinase and Na(+)/K(+)-ATPase, a well-advocated hypothesis on how ouabain initiates the activation of signaling pathways is that there is a preexisting physiological complex of inactive Src bound to the α-subunit of Na(+)/K(+)-ATPase, and that ouabain binding to this subunit disrupts the bound Src and activates it. Because of the published disagreements of the results of such cell-free experiments of two other laboratories, our aim was to attempt the resolution of these discrepancies.

Cell signaling associated with Na(+)/K(+)-ATPase: activation of phosphatidylinositide 3-kinase IA/Akt by ouabain is independent of Src.

Exposure of intact cells to selective inhibitors of Na(+)/K(+)-ATPase such as ouabain activates several growth-related cell signaling pathways. It has been suggested that the initial event of these pathways is the binding of ouabain to a preexisting complex of Src with Na(+)/K(+)-ATPase of the plasma membrane. The aim of this work was to evaluate the role of Src in the ouabain-induced activation of phosphatidylinositide 3-kinase 1A (PI3K1A) and its downstream consequences.

Different roles of the cardiac Na+/Ca2+-exchanger in ouabain-induced inotropy, cell signaling, and hypertrophy.

Previous studies have shown that digitalis drugs, acting as specific inhibitors of cardiac Na(+)/K(+)-ATPase, not only cause positive inotropic effects, but also activate cell signaling pathways that lead to cardiac myocyte hypertrophy. A major aim of this work was to assess the role of Na(+)/Ca(2+)-exchanger, NCX1, in the above two seemingly related drug effects. Using a mouse with ventricular-specific knockout (KO) of NCX1, ouabain-induced positive inotropy that was evident in isolated wild-type (Wt) hearts was clearly reduced in KO hearts.

Caveolin-Na/K-ATPase interactions: role of transmembrane topology in non-genomic steroid signal transduction.

Progesterone and its polar metabolite(s) trigger the meiotic divisions in the amphibian oocyte through a non-genomic signaling system at the plasma membrane. Published site-directed mutagenesis studies of ouabain binding and progesterone-ouabain competition studies indicate that progesterone binds to a 23 amino acid extracellular loop of the plasma membrane α-subunit of Na/K-ATPase. Integral membrane proteins such as caveolins are reported to form Na/K-ATPase-peptide complexes essential for signal transduction.

Comparative properties of caveolar and noncaveolar preparations of kidney Na+/K+-ATPase.

To evaluate previously proposed functions of renal caveolar Na(+)/K(+)-ATPase, we modified the standard procedures for the preparation of the purified membrane-bound kidney enzyme, separated the caveolar and noncaveolar pools, and compared their properties. While the subunits of Na(+)/K(+)-ATPase (α,β,γ) constituted most of the protein content of the noncaveolar pool, the caveolar pool also contained caveolins and major caveolar proteins annexin-2 tetramer and E-cadherin. Ouabain-sensitive Na(+)/K(+)-ATPase activities of the two pools had similar properties and equal molar activities, indicating that the caveolar enzyme retains its ion transport function and does not contain nonpumping enzyme.

Progesterone modulation of transmembrane helix-helix interactions between the alpha-subunit of Na/K-ATPase and phospholipid N-methyltransferase in the oocyte plasma membrane.

Background: Progesterone binding to the surface of the amphibian oocyte initiates the meiotic divisions. Our previous studies with Rana pipiens oocytes indicate that progesterone binds to a plasma membrane site within the external loop between the M1 and M2 helices of the alpha-subunit of Na/K-ATPase, triggering a cascade of lipid second messengers and the release of the block at meiotic prophase. We have characterized this site, using a low affinity ouabain binding isoform of the alpha1-subunit.

Progesterone binding to the alpha1-subunit of the Na/K-ATPase on the cell surface: insights from computational modeling.

Progesterone triggers the resumption of meiosis in the amphibian oocyte through a signaling system at the plasma membrane. Analysis of [(3)H]ouabain and [(3)H]progesterone binding to the plasma membrane of the Rana pipiens oocyte indicates that progesterone competes with ouabain for a low affinity ouabain binding site on a 112kDa alpha1-subunit of the membrane Na/K-ATPase. Published amino acid sequences from both low and high affinity ouabain binding alpha1-subunits are compared, together with published site-directed mutagenesis studies of ouabain binding.

Association of PI3K-Akt signaling pathway with digitalis-induced hypertrophy of cardiac myocytes.

Our previous studies on cardiac myocytes showed that positive inotropic concentrations of the digitalis drug ouabain activated signaling pathways linked to Na(+)-K(+)-ATPase through Src and epidermal growth factor receptor (EGFR) and led to myocyte hypertrophy. In view of the known involvement of phosphatidylinositol 3-kinase (PI3K)-Akt pathways in cardiac hypertrophy, the aim of the present study was to determine whether these pathways are also linked to cardiac Na(+)-K(+)-ATPase and, if so, to assess their role in ouabain-induced myocyte growth. In a dose- and time-dependent manner, ouabain activated Akt and phosphorylation of its substrates mammalian target of rapamycin and glycogen synthase kinase in neonatal rat cardiac myocytes.

Interactions of K+ATP channel blockers with Na+/K+-ATPase.

Two K(+) (ATP) channel blockers, 5-hydroxydecanoate (5-HD) and glyburide, are often used to study cross-talk between Na(+)/K(+)-ATPase and these channels. The aim of this work was to characterize the effects of these blockers on purified Na(+)/K(+)-ATPase as an aid to appropriate use of these drugs in studies on this cross-talk. In contrast to known dual effects (activating and inhibitory) of other fatty acids on Na(+)/K(+)-ATPase, 5-HD only inhibited the enzyme at concentrations exceeding those that block mitochondrial K(+) (ATP) channels.

On the importance and mechanism of amplification of digitalis signal through Na+/K+-ATPase.

Therapeutic concentrations of digitalis drugs inhibit the proliferation of breast cancer cells by inducing the interaction of Na+/K+-ATPase with Src/EGFR, activation of ERK1/2, and the resulting upregulation of cell cycle inhibitor p21Cip1. Quantitative comparison of ouabain dose-response curves for growth arrest and pump inhibition shows that ratio of Ki (pump)/Ki (proliferation) = 7.2.

Beta-subunit of cardiac Na+-K+-ATPase dictates the concentration of the functional enzyme in caveolae.

Previous studies showed the presence of a significant fraction of Na(+)-K(+)-ATPase alpha-subunits in cardiac myocyte caveolae, suggesting the caveolar interactions of Na(+)-K(+)-ATPase with its signaling partners. Because both alpha- and beta-subunits are required for ATPase activity, to clarify the status of the pumping function of caveolar Na(+)-K(+)-ATPase, we have examined the relative distribution of two major subunit isoforms (alpha(1) and beta(1)) in caveolar and noncaveolar membranes of adult rat cardiac myocytes. When cell lysates treated with high salt (Na(2)CO(3) or KCl) concentrations were fractionated by a standard density gradient procedure, the resulting light caveolar membranes contained 30-40% of alpha(1)-subunits and 80-90% of beta(1)-subunits.

Digitalis-induced signaling by Na+/K+-ATPase in human breast cancer cells.

Because beneficial effects of digitalis treatment in breast cancer patients have been suggested by epidemiological studies, we explored the mechanism of the growth inhibitory effects of these drugs on the estrogen receptor-negative human breast cancer cell line MDA-MB-435 s. Ouabain concentrations (100 nM or lower) that caused less than 25% inhibition of the pumping function of Na+/K+-ATPase had no effect on cell viability but inhibited proliferation. At the same concentrations, ouabain 1) activated Src kinase and stimulated the interaction of Src and Na+/K+-ATPase with epidermal growth factor receptor (EGFR); 2) caused a transient and then a sustained activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2); 3) increased the expression of p21Cip1 but decreased that of p53; and 4) activated c-Jun NH2-terminal kinase (JNK) but not p38 kinase.

Role of caveolae in ouabain-induced proliferation of cultured vascular smooth muscle cells of the synthetic phenotype.

We have shown earlier that low concentrations of ouabain that do not perturb the ionic milieu can initiate proliferation of vascular smooth muscle cells (VSMCs) in the synthetic phenotype from three different species: canine, rodent, and human. This effect occurs by activation of Src and the epidermal growth factor receptor (EGFR), and thus supports the concept of an additional, nonionic, transducing function of the Na pump. The present study presents data suggesting that such activation occurs through specific Na pump sites localized to the caveolae, and subsequent interactions with selected signaling proteins resident within the same membrane microdomain.