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Cardiac cell lines and primary cells are widely used in cardiovascular research. Despite increasing number of publications using these models, comparative characterization of these cell lines has not been performed, therefore, their limitations are undetermined. We aimed to compare cardiac cell lines to primary cardiomyocytes and to mature cardiac tissues in a systematic manner.Cardiac cell lines (H9C2, AC16, HL-1) were differentiated with widely used protocols. Left ventricular tissue, neonatal primary cardiomyocytes, and human induced pluripotent stem cell-derived cardiomyocytes served as reference tissue or cells. RNA expression of cardiac markers (e.g. Tnnt2, Ryr2) was markedly lower in cell lines compared to references. Differentiation induced increase in cardiac- and decrease in embryonic markers however, the overall transcriptomic profile and annotation to relevant biological processes showed consistently less pronounced cardiac phenotype in all cell lines in comparison to the corresponding references. Immunocytochemistry confirmed low expressions of structural protein sarcomeric alpha-actinin, troponin I and caveolin-3 in cell lines. Susceptibility of cell lines to sI/R injury in terms of viability as well as mitochondrial polarization differed from the primary cells irrespective of their degree of differentiation.Expression patterns of cardiomyocyte markers and whole transcriptomic profile, as well as response to sI/R, and to hypertrophic stimuli indicate low-to-moderate similarity of cell lines to primary cells/cardiac tissues regardless their differentiation. Low resemblance of cell lines to mature adult cardiac tissue limits their potential use. Low translational value should be taken into account while choosing a particular cell line to model cardiomyocytes.

Cardiometabolic diseases (CMDs) are metabolic diseases (e.g., obesity, diabetes, atherosclerosis, rare genetic metabolic diseases, etc.) associated with cardiac pathologies. Pathophysiology of most CMDs involves increased production of reactive oxygen species and impaired antioxidant defense systems, resulting in cardiac oxidative stress (OxS). To alleviate OxS, various antioxidants have been investigated in several diseases with conflicting results. Here we review the effect of CMDs on cardiac redox homeostasis, the role of OxS in cardiac pathologies, as well as experimental and clinical data on the therapeutic potential of natural antioxidants (including resveratrol, quercetin, curcumin, vitamins A, C, and E, coenzyme Q10, etc.), synthetic antioxidants (including N-acetylcysteine, SOD mimetics, mitoTEMPO, SkQ1, etc.), and promoters of antioxidant enzymes in CMDs. As no antioxidant indicated for the prevention and/or treatment of CMDs has reached the market despite the large number of preclinical and clinical studies, a sizeable translational gap is evident in this field. Thus, we also highlight potential underlying factors that may contribute to the failure of translation of antioxidant therapies in CMDs.

The regioselective Cu(I)-catalyzed 1,3-dipolar cycloaddition of 17α- and 17β-azidoandrost-5-en-3β-ol epimers (3b and 5b) with different terminal alkynes afforded novel 1,4-substituted triazolyl derivatives (8a–k and 9a–k). For the preparation of 5′-iodo-1′,2′,3′-triazoles (8m–n and 9m–n), an improved method was developed, directly from steroidal azides and terminal alkynes, in reaction mediated by CuI and ICl as iodinating agents. Acetolysis and subsequent hydrolysis of 8n and 9n yielded 5′-hydroxy-1′,2′,3′-triazoles 8o and 9o. The inhibitory effect of 8a–o, 9a–o, 3, and 5 on rat testicular C17,20-lyase was investigated by means of an in vitro radioincubation technique. The results revealed that the C-17 epimers of steroidal triazoles influence the C17,20-lyase effect. Inhibitors were found only in the 17α-triazolyl series (8a–o), whereas in the C-17 azide pair the 17β compound (5b) was more potent.

We complete the recent derivation of a Ruijsenaars type system that arises as a reduction of the natural free system on the Heisenberg double of SU(n,n). The previous analysis by Marshall focused on a dense open submanifold of the reduced phase space, and here we describe the full phase space wherein Liouville integrability of the system holds by construction., Comment: 15 pages, submitted to JGP special issue "Finite dimensional integrable systems 2"

Voltage unbalance is a major yet often overlooked power quality problem in low voltage residential feeders due to the random location and rating of single-phase renewable sources and uneven distribution of household loads. This paper proposes a new indicator of voltage deviation that may serve as a basis of analysis and compensation methods in this dimension of power quality. The paper proposes three main results. First of all a novel voltage norm capable of jointly indicating unbalance and under-voltage in a single value, afterwards a three phase unbalance reduction controller structure is given. As the third main result, the proposed controller structure is integrated with an optimization based control algorithm that uses asynchronous parallel pattern search as its engine. The suggested structure and the underlying three phase power grid model has been implemented in a dynamical simulation environment and tested against engineering expectations. The simulation based experiments served as a proof of concept for the proposed complex control structure. The experiments included performance and robustness analysis, both of them concluded that the proposed control and inverter structure is promising. The proposed three phase inverter structure together with the control algorithm connected with a renewable source (photovoltaic panel or wind turbine) is capable of an asymmetric power injection or rerouting the energy flow to the grid so that the voltage unbalance decrease. This is also important from the environmental point of view since the achieved power loss reduction can easily be translated to CO2 emission reduction and carbon footprint - these indicators has also been calculated.

Aims Exogenously administered biglycan (core protein with high-molecular weight glycosaminoglycan chains) has been shown to protect neonatal cardiomyocytes against simulated ischemia/reperfusion injury (SI/R), however, the mechanism of action is not clear. In this study we aimed to investigate, which structural component of biglycan is responsible for its cardiocytoprotective effect and to further explore the molecular mechanisms involved in the cytoprotection. Methods and results A pilot study was conducted to demonstrate that both native (glycanated) and deglycanated biglycan can attenuate cell death induced by SI/R in a dose-dependent manner in primary neonatal cardiomyocytes isolated from Wistar rats. In separate experiments, we have shown that similarly to glycanated biglycan, recombinant human biglycan core protein (rhBGNc) protects cardiomyocytes against SI/R injury. In contrast, the glycosaminoglycan component dermatan sulfate had no significant effect on cell viability, while chondroitin sulfate further enhanced cell death induced by SI/R. Treatment of cardiomyocytes with rhBGNc reverses the effect of SI/R upon markers of necrosis, apoptosis, mitochondrial membrane potential, and autophagy. We have also shown that pharmacological blockade of Toll-like receptor 4 (TLR4) signaling or its downstream mediators (IRAK1/4, ERK, JNK and p38 MAP kinases) abolished the cytoprotective effect of rhBGNc against SI/R injury. Pretreatment of cardiomyocytes with rhBGNc for 20 h resulted in increased Akt phosphorylation and NO production without having significant effect on phosphorylation of ERK1/2, STAT3, and on the production of superoxide. Treatment over 10 min and 1 h with rhBGNc increased ERK1 phosphorylation, while the SI/R-induced increase in superoxide production was attenuated by rhBGNc. Blockade of NO synthesis also prevented the cardiocytoprotective effect of rhBGNc. Conclusions The core protein of exogenous biglycan protects myocardial cells from SI/R injury via TLR4-mediated mechanisms involving activation of ERK, JNK and p38 MAP kinases and increased NO production. The cytoprotective effect of rhBGNc is due to modulation of SI/R-induced changes in necrosis, apoptosis and autophagy.

Despite the great clinical significance of radiation-induced cardiac damage, experimental investigation of its mechanisms is an unmet need in medicine. Beneficial effects of growth hormone-releasing hormone (GHRH) agonists in regeneration of the heart have been demonstrated. The aim of this study was the evaluation of the potential of modern GHRH agonistic analogs in prevention of radiation damage in an in vitro cardiac myocyte-based model. Cultures of cardiac myocytes isolated from newborn rats (NRVM) were exposed to a radiation dose of 10Gy. The effects of the agonistic analogs, JI-34 and MR-356, of human GHRH on cell viability, proliferation, their mechanism of action and the protein expression of the GHRH/SV1 receptors were studied. JI-34 and MR-356, had no effect on cell viability or proliferation in unirradiated cultures. However, in irradiated cells JI-34 showed protective effects on cell viability at concentrations of 10 and 100nM, and MR-356 at 500nM; but no such protective effect was detected on cell proliferation. Both agonistic analogs decreased radiation-induced ROS level and JI-34 interfered with the activation of SAFE/RISK pathways. Using Western blot analysis, a 52kDa protein isoform of GHRHR was detected in the samples in both irradiated and unirradiated cells. Since GHRH agonistic analogs, JI-34 and MR-356 alleviated radiation-induced damage of cardiac myocytes, they should be tested in vivo as potential protective agents against radiogenic heart damage.

A measurement based model of hydrogen generating cell for simulation of complex energy system is described in this paper. The model parameter estimation has been performed based on measurement data obtained during the detailed examination of a demonstration cell. A series of experiments has been carried out on a HHO (Oxyhydrogen) gas producing dry cell in order to find its optimal electrochemical, (e.g. electrolyte concentration, current value, etc.) and geometric (distance between the plates) parameters. The novel element is the current and concentration dependent Matlab Simulink model of the hydrogen generation cell. Hydrogen generation enables the long range storage of spare electric energy collected but not consumed or injected into the low voltage grid. The generated hydrogen can be consumed by vehicles for transportation purposes or it can be applied in fuel cells generating direct electrical energy for energy-deficient low voltage network situations. The potentially occurring energetic situations were simulated in a complex energetic system model. The simulations showed that the presented hydrogen generating cell model met the engineering expectations.

The equivalence of two complete sets of Poisson commuting Hamiltonians of the (super)integrable rational BCn Ruijsenaars–Schneider–van Diejen system is established. Specifically, the commuting Hamiltonians constructed by van Diejen are shown to be linear combinations of the Hamiltonians generated by the characteristic polynomial of the Lax matrix obtained recently by Pusztai, and the explicit formula of this invertible linear transformation is found.

Connexins are widely distributed proteins in the body that are crucially important for heart and brain functions. Six connexin subunits form a connexon or hemichannel in the plasma membrane. Interactions between two hemichannels in a head-to-head arrangement result in the formation of a gap junction channel. Gap junctions are necessary to coordinate cell function by passing electrical current flow between heart and nerve cells or by allowing exchange of chemical signals and energy substrates. Apart from its localization at the sarcolemma of cardiomyocytes and brain cells, connexins are also found in the mitochondria where they are involved in the regulation of mitochondrial matrix ion fluxes and respiration. Connexin expression is affected by age and gender as well as several pathophysiological alterations such as hypertension, hypertrophy, diabetes, hypercholesterolemia, ischemia, post-myocardial infarction remodeling or heart failure, and post-translationally connexins are modified by phosphorylation/de-phosphorylation and nitros(yl)ation which can modulate channel activity. Using knockout/knockin technology as well as pharmacological approaches, one of the connexins, namely connexin 43, has been identified to be important for cardiac and brain ischemia/reperfusion injuries as well as protection from it. Therefore, the current review will focus on the importance of connexin 43 for irreversible injury of heart and brain tissues following ischemia/reperfusion and will highlight the importance of connexin 43 as an emerging therapeutic target in cardio- and neuroprotection.

An experimental study is presented in this work, where the distortion effect of a 4 kW photovoltaic domestic power plant, located in Hungary, has been examined. The power plant is connected to a low voltage grid by using a standard grid synchronized inverter. Based on the measured voltage and current signals we examined the frequency domain behavior of the power plant, and the effect of the power plant on the power quality, mainly the total harmonic distortion. The measurement database shows that the synchronous power injection of the photovoltaic domestic power plant has serious effect on the voltage distortion of the low voltage grid, and this effect highly depends on the actual generated power. Based on the experimental results, suggestions on how to operate the photovoltaic domestic power plant are formulated that enable its energy-efficient operation with minimal distortion effect.

Diet-induced hypercholesterolemia leads to oxidative/nitrative stress and subsequent myocardial dysfunction. However, the regulatory role of microRNAs in this phenomenon is unknown. We aimed to investigate, whether hypercholesterolemia-induced myocardial microRNA alterations play a role in the development of oxidative/nitrative stress and in subsequent cardiac dysfunction. Male Wistar rats were fed with 2% cholesterol/0.25% cholate-enriched or standard diet for 12weeks. Serum and tissue cholesterol levels were significantly elevated by cholesterol-enriched diet. Left ventricular end-diastolic pressure was significantly increased in cholesterol-fed rats both in vivo and in isolated perfused hearts, indicating diastolic dysfunction. Myocardial expression of microRNAs was affected by cholesterol-enriched diet as assessed by microarray analysis. MicroRNA-25 showed a significant down-regulation as detected by microarray analysis and QRT-PCR. In silico target prediction revealed NADPH oxidase 4 (NOX4) as a putative target of microRNA-25. NOX4 protein showed significant up-regulation in the hearts of cholesterol-fed rats, while NOX1 and NOX2 remained unaffected. Cholesterol-feeding significantly increased myocardial oxidative/nitrative stress as assessed by dihydroethidium staining, protein oxidation assay, and nitro-tyrosine ELISA, respectively. Direct binding of microRNA-25 mimic to the 3' UTR region of NOX4 was demonstrated using a luciferase reporter assay. Transfection of a microRNA-25 mimic into primary cardiomyocytes decreased superoxide production, while a microRNA-25 inhibitor resulted in an up-regulation of NOX4 protein and an increase in oxidative stress that was attenuated by the NADPH oxidase inhibitor diphenyleneiodonium. Here we demonstrated for the first time that hypercholesterolemia affects myocardial microRNA expression, and by down-regulating microRNA-25 increases NOX4 expression and consequently oxidative/nitrative stress in the heart. We conclude that hypercholesterolemia-induced microRNA alterations play an important role in the regulation of oxidative/nitrative stress and in consequent myocardial dysfunction.

The paper presents a general temperature-dependent model for a family of batteries developed for electrical vehicle (EV) use. In addition to the model’s derivation, the methodology and instruments developed to accurately measure the temperature-dependent parameters are also presented together with a Matlab/Simulink block for a temperature-dependent battery. This information is very important for simulating the behavior of an EV in real-life weather and temperature conditions and for simulating the quick charging process, which are key issues for spreading EVs. The battery model has been verified in a complex energetic structure consisting of a harmonic controller that minimizes the amplitudes of the 3rd, 5th, 7th, 9th, and 11th higher order components of the output voltage and that of the connection voltage controller, which controls the energy flow between the low voltage network and the renewable energy source, thereby reducing the power loss of the whole low voltage transformer area and reducing the CO2 emission of the average household.

This paper describes a low-voltage grid composed of small, domestic power plants fueled by clean and renewable energy sources and augmented with electric vehicle batteries as power storage devices. We propose that this grid could utilize a complex multifunctional control unit capable of optimizing the working point and charging current of the system, while also implementing active power factor correction, lowering extant harmonic distortion and controlling the voltage level in the low-voltage power lines. The complex controller structure proposed in this paper contains the following novel components: an upper harmonic controller which (together with the connection voltage controller) minimizes the amplitudes of the 3rd, 5th, 7th, 9th, and 11th high order components in the output voltage; and a connection voltage controller which controls the energy flow between the low-voltage network, its renewable energy sources and the electrical vehicle batteries. Unlike other similar approaches, the harmonic controller proposed in this paper does not rely on a measured current signal but rather optimizes the voltage shape, the latter of which depends on the nonlinear distortion of the whole low-voltage transformer area and determines additional power losses. We analyzed the proposed controller via simulations in a Matlab environment and as a result, achieved substantial improvements to the output voltage, current waveform and energy flow of the system’s low-voltage conditions. Our calculations show that the implementation of substantial reductions in CO2 emissions could be achieved for an average household. The robustness of the method against nonlinear loads and fluctuations in overloads and overproductions was also tested.

Biglycan, a proteoglycan component of extracellular matrix, has been suspected to contribute to the development of atherosclerosis, but overexpression of biglycan in transgenic mice has been shown to induce cardioprotective genes including nitric oxide (NO) synthases in the heart. Therefore, here we hypothesized if exogenous administration of biglycan exerts cytoprotection. Primary cardiomyocytes from neonatal rats were subjected to 150 min hypoxia and 2 h reoxygenation. Mortality of cardiomyocytes was dose-dependently attenuated by pretreatment with 1-100 nM biglycan. Biglycan enhanced eNOS mRNA and protein, and significantly increased NO content of cardiomyocytes. The NO synthase inhibitor L-nitro-arginine-methyl-ester significantly attenuated the cytoprotective effect of biglycan. This is the first demonstration that biglycan leads to cytoprotection against hypoxia/reoxygenation injury, and that this phenomenon is partially mediated by an NO-dependent mechanism. (c) 2010 Elsevier Ltd. All rights reserved.

Plasmonic structures are prepared on bimetal films evaporated onto glass substrates applying a multi-step process, and atomic force microscopy is utilized to study the structures after each step. Sub-micrometer gratings are generated on polycarbonate films spin-coated onto silver-gold bimetal layers by interference lithography (IL) applying the fourth harmonics of a Nd:YAG laser. These polymer gratings are used as prepatterned templates in order to deposit silica colloid spheres by spin-coating. It is shown that the conditions of periodic silica sphere-array formation along the template valleys are sufficiently large grating modulation depth, appropriate ratio of silica sphere diameter to grating period, and optimized speed of spinning. The periodic silica sphere arrays are illuminated by a homogeneous KrF excimer laser beam, and periodically arrayed sub-wavelength holes are drilled into bimetal films via colloid sphere lithography (CSL). The characteristic dimensions of the resulted plasmonic structures are defined by the polymer grating period and by the silica colloid sphere diameter. Attenuated total reflection spectroscopy is performed exciting plasmons on different metal-dielectric interfacial structures by the second harmonic of a continuous Nd:YAG laser. The polar and azimuthal angle dependent grating-coupling and scattering effects of the complex periodic structures on the resonance characteristic of plasmons is demonstrated.

Muscles are formed by fusion of individual postmitotic myoblasts to form multinucleated syncytial myotubes. The process requires a well-coordinated transition from proliferation, through migratory alignment and cycle exit, to breakdown of apposed membranes. Connexin43 protein and cell-cycle inhibitor levels are correlated, and gap junction blockers can delay muscle regeneration, so a coordinating role for gap junctions has been proposed. Here, wild-type and dominant-negative connexin43 variants (wtCx43, dnCx43) were introduced into rat myoblasts in primary culture through pIRES-eGFP constructs that made transfected cells fluoresce. GFP-positive cells and vitally-stained nuclei were counted on successive days to reveal differences in proliferation, and myotubes were counted to reveal differences in fusion. Individual transfected cells were injected with Cascade Blue, which permeates gap junctions, mixed with FITC-dextran, which requires cytoplasmic continuity to enter neighbouring cells. Myoblasts transfected with wtCx43 showed more gap-junctional coupling than GFP-only controls, began fusion sooner as judged by the incidence of cytoplasmic coupling, and formed more myotubes. Myoblasts transfected with dnCx43 remained proliferative for longer than either GFP-only or wtCx43 myoblasts, showed less coupling, and underwent little fusion into myotubes. These results highlight the critical role of gap-junctional coupling in myotube formation.