Switching Behaviour of a Series Connection of a Vacuum Interrupter and a Gas Circuit Breaker

After being in the focus of sciences' and industry's research and development activities for many years, the investigation of possible SF6 gas-alternatives has been even more intensified after the revision of the European F-Gas regulation 517/2014. As natural gases yield a significantly lower dielectric strength in comparison to SF6, new challenges arise for the design of high voltage switchgear. Vacuum interrupters are environmentally friendly, reliable and able to withstand steep rising transient recovery voltages. In the last years, first installations of switchgear based on vacuum switching technology in sub-transmission level are in operation. One option for the realization of a SF6 free high voltage switchgear for transmission level is the combination of a gas circuit breaker filled with an atmospheric gas with a vacuum interrupter in a hybrid switchgear. In this contribution the voltage distribution and switching behavior of a hybrid circuit breaker is experimentally investigated

Reversing Blood Flows Act through klf2a to Ensure Normal Valvulogenesis in the Developing Heart

Heart valve anomalies are some of the most common congenital heart defects, yet neither the genetic nor the epigenetic forces guiding heart valve development are well understood. When functioning normally, mature heart valves prevent intracardiac retrograde blood flow; before valves develop, there is considerable regurgitation, resulting in reversing (or oscillatory) flows between the atrium and ventricle. As reversing flows are particularly strong stimuli to endothelial cells in culture, an attractive hypothesis is that heart valves form as a developmental response to retrograde blood flows through the maturing heart. Here, we exploit the relationship between oscillatory flow and heart rate to manipulate the amount of retrograde flow in the atrioventricular (AV) canal before and during valvulogenesis, and find that this leads to arrested valve growth. Using this manipulation, we determined that klf2a is normally expressed in the valve precursors in response to reversing flows, and is dramatically reduced by treatments that decrease such flows. Experimentally knocking down the expression of this shear-responsive gene with morpholine antisense oligonucleotides (MOs) results in dysfunctional valves. Thus, klf2a expression appears to be necessary for normal valve formation. This, together with its dependence on intracardiac hemodynamic forces, makes klf2a expression an early and reliable indicator of proper valve development. Together, these results demonstrate a critical role for reversing flows during valvulogenesis and show how relatively subtle perturbations of normal hemodynamic patterns can lead to both major alterations in gene expression and severe valve dysgenesis

Significance of Thymosin β4 and Implication of PINCH-1-ILK-α-Parvin (PIP) Complex in Human Dilated Cardiomyopathy

Myocardial remodeling is a major contributor in the development of heart failure (HF) after myocardial infarction (MI). Integrin-linked kinase (ILK), LIM-only adaptor PINCH-1, and α-parvin are essential components of focal adhesions (FAs), which are highly expressed in the heart. ILK binds tightly to PINCH-1 and α-parvin, which regulates FA assembly and promotes cell survival via the activation of the kinase Akt. Mice lacking ILK, PINCH or α-parvin have been shown to develop severe defects in the heart, suggesting that these proteins play a critical role in heart function. Utilizing failing human heart tissues (dilated cardiomyopathy, DCM), we found a 2.27-fold (p<0.001) enhanced expression of PINCH, 4 fold for α-parvin, and 10.5 fold (p<0.001) for ILK as compared to non-failing (NF) counterparts. No significant enhancements were found for the PINCH isoform PINCH-2 and parvin isoform β-parvin. Using a co-immunoprecipitation method, we also found that the PINCH-1-ILK-α-parvin (PIP) complex and Akt activation were significantly up-regulated. These observations were further corroborated with the mouse myocardial infarction (MI) and transaortic constriction (TAC) model. Thymosin beta4 (Tβ4), an effective cell penetrating peptide for treating MI, was found to further enhance the level of PIP components and Akt activation, while substantially suppressing NF-κB activation and collagen expression—the hallmarks of cardiac fibrosis. In the presence of an Akt inhibitor, wortmannin, we show that Tβ4 had a decreased effect in protecting the heart from MI. These data suggest that the PIP complex and activation of Akt play critical roles in HF development. Tβ4 treatment likely improves cardiac function by enhancing PIP mediated Akt activation and suppressing NF-κB activation and collagen-mediated fibrosis. These data provide significant insight into the role of the PIP-Akt pathway and its regulation by Tβ4 treatment in post-MI

Increased Expression of Integrin-Linked Kinase Improves Cardiac Function and Decreases Mortality in Dilated Cardiomyopathy Model of Rats

AIMS: Integrin-linked kinase (ILK) is a multifunctional kinase linking the extracellular matrix to intracellular signaling pathways, whose activation in the heart gives rise to a number of functional consequences. The aim of this study is to demonstrate the therapeutic and survival benefit of cardiac ILK overexpression in a rat model of dilated cardiomyopathy. METHODS AND RESULTS: The dilated cardiomyopathy model was generated in rats by intraperitoneal administration of six equal doses of doxorubicin over a 2 week period. Five weeks after the first injection, echocardiographic analysis demonstrated impaired cardiac function and, at that point, recombinant adenoviral vector harboring ILK cDNA or vehicle was injected into the myocardium, and the rats re-studied 4 weeks later. Compared with vehicle injection, ILK treatment ameliorated inflammatory cell infiltration and cardiomyocyte degeneration, as well as left ventricular dilation and dysfunction. ILK treatment was also associated with a reduction in apoptosis and an increase in proliferation of cardiomyocytes, as well as decreased oxidative stress and autophagic vacuole accumulation. Importantly, mortality was lower in rats following ILK treatment than in those following vehicle injection. In cultured neonatal rat cardiomyocytes, we also found that ILK overexpression protected against doxorubicin-induced apoptosis, giving rise to an increase in their proliferation. CONCLUSIONS: These data demonstrate for the first time that ILK gene therapy improves cardiac function and survival in a model of dilated cardiomyopathy, and this may be mediated through suppression of inflammation, prevention of ventricular remodeling, inhibition of cardiomyocyte apoptosis and autophagy, and stimulation of cardiomyocyte proliferation

ILK Induces Cardiomyogenesis in the Human Heart

Integrin-linked kinase (ILK) is a widely conserved serine/threonine kinase that regulates diverse signal transduction pathways implicated in cardiac hypertrophy and contractility. In this study we explored whether experimental overexpression of ILK would up-regulate morphogenesis in the human fetal heart.Primary cultures of human fetal myocardial cells (19-22 weeks gestation) yielded scattered aggregates of cardioblasts positive for the early cardiac lineage marker nk × 2.5 and containing nascent sarcomeres. Cardiac cells in colonies uniformly expressed the gap junction protein connexin 43 (C × 43) and displayed a spectrum of differentiation with only a subset of cells exhibiting the late cardiomyogenic marker troponin T (cTnT) and evidence of electrical excitability. Adenovirus-mediated overexpression of ILK potently increased the number of new aggregates of primitive cardioblasts (p<0.001). The number of cardioblast colonies was significantly decreased (p<0.05) when ILK expression was knocked down with ILK targeted siRNA. Interestingly, overexpression of the activation resistant ILK mutant (ILK(R211A)) resulted in much greater increase in the number of new cell aggregates as compared to overexpression of wild-type ILK (ILK(WT)). The cardiomyogenic effects of ILK(R211A) and ILK(WT) were accompanied by concurrent activation of β-catenin (p<0.001) and increase expression of progenitor cell marker islet-1, which was also observed in lysates of transgenic mice with cardiac-specific over-expression of ILK(R211A) and ILK(WT). Finally, endogenous ILK expression was shown to increase in concert with those of cardiomyogenic markers during directed cardiomyogenic differentiation in human embryonic stem cells (hESCs).In the human fetal heart ILK activation is instructive to the specification of mesodermal precursor cells towards a cardiomyogenic lineage. Induction of cardiomyogenesis by ILK overexpression bypasses the requirement of proximal PI3K activation for transduction of growth factor- and β1-integrin-mediated differentiation signals. Altogether, our data indicate that ILK represents a novel regulatory checkpoint during human cardiomyogenesis

Chemical Diversity and Complexity of Scotch Whisky as Revealed by High-Resolution Mass Spectrometry

Scotch Whisky is an important product, both culturally and economically. Chemically, Scotch Whisky is a complex mixture, which comprises thousands of compounds, the nature of which are largely unknown. Here, we present a thorough overview of the chemistry of Scotch Whisky as observed by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Eighty-five whiskies, representing the majority of Scotch Whisky produced and sold, were analyzed by untargeted high-resolution mass spectrometry. Thousands of chemical formulae were assigned for each sample based on parts-per-billion mass accuracy of FT-ICR MS spectra. For the first time, isotopic fine structure analysis was used to confirm the assignment of high molecular weight CHOS species in Scotch Whisky. The assigned spectra were compared using a number of visualization techniques, including van Krevelen diagrams, double bond equivalence (DBE) plots, as well as heteroatomic compound class distributions. Additionally, multivariate analysis, including PCA and OPLS-DA, was used to interpret the data, with key compounds identified for discriminating between types of whisky (blend or malt) or maturation wood type. FT-ICR MS analysis of Scotch Whisky was shown to be of significant potential in further understanding of the complexity of mature spirit drinks and as a tool for investigating the chemistry of the maturation processes. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13361-016-1513-y) contains supplementary material, which is available to authorized users

Principal variable selection to explain grain yield variation in winter wheat from features extracted from UAV imagery

Background: Automated phenotyping technologies are continually advancing the breeding process. However, collecting various secondary traits throughout the growing season and processing massive amounts of data still take great efforts and time. Selecting a minimum number of secondary traits that have the maximum predictive power has the potential to reduce phenotyping efforts. The objective of this study was to select principal features extracted from UAV imagery and critical growth stages that contributed the most in explaining winter wheat grain yield. Five dates of multispectral images and seven dates of RGB images were collected by a UAV system during the spring growing season in 2018. Two classes of features (variables), totaling to 172 variables, were extracted for each plot from the vegetation index and plant height maps, including pixel statistics and dynamic growth rates. A parametric algorithm, LASSO regression (the least angle and shrinkage selection operator), and a non-parametric algorithm, random forest, were applied for variable selection. The regression coefficients estimated by LASSO and the permutation importance scores provided by random forest were used to determine the ten most important variables influencing grain yield from each algorithm. Results: Both selection algorithms assigned the highest importance score to the variables related with plant height around the grain filling stage. Some vegetation indices related variables were also selected by the algorithms mainly at earlier to mid growth stages and during the senescence. Compared with the yield prediction using all 172 variables derived from measured phenotypes, using the selected variables performed comparable or even better. We also noticed that the prediction accuracy on the adapted NE lines (r = 0.58–0.81) was higher than the other lines (r = 0.21–0.59) included in this study with different genetic backgrounds. Conclusions: With the ultra-high resolution plot imagery obtained by the UAS-based phenotyping we are now able to derive more features, such as the variation of plant height or vegetation indices within a plot other than just an averaged number, that are potentially very useful for the breeding purpose. However, too many features or variables can be derived in this way. The promising results from this study suggests that the selected set from those variables can have comparable prediction accuracies on the grain yield prediction than the full set of them but possibly resulting in a better allocation of efforts and resources on phenotypic data collection and processing

Thrombospondins in the heart: potential functions in cardiac remodeling

Cardiac remodeling after myocardial injury involves inflammation, angiogenesis, left ventricular hypertrophy and matrix remodeling. Thrombospondins (TSPs) belong to the group of matricellular proteins, which are non-structural extracellular matrix proteins that modulate cell–matrix interactions and cell function in injured tissues or tumors. They interact with different matrix and membrane-bound proteins due to their diverse functional domains. That the expression of TSPs strongly increases during cardiac stress or injury indicates an important role for them during cardiac remodeling. Recently, the protective properties of TSP expression against heart failure have been acknowledged. The current review will focus on the biological role of TSPs in the ischemic and hypertensive heart, and will describe the functional consequences of TSP polymorphisms in cardiac disease