Transdifferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocytes

Background - Further to promoting angiogenesis, cell therapy may be an approach for cardiac regeneration. Recent studies suggest that progenitor cells can transdifferentiate into other lineages. However, the transdifferentiation potential of endothelial progenitor cells (EPCs) is unknown

Nitric Oxide-Induced Activation of the AMP-Activated Protein Kinase α2 Subunit Attenuates IκB Kinase Activity and Inflammatory Responses in Endothelial Cells

BACKGROUND: In endothelial cells, activation of the AMP-activated protein kinase (AMPK) has been linked with anti-inflammatory actions but the events downstream of kinase activation are not well understood. Here, we addressed the effects of AMPK activation/deletion on the activation of NFκB and determined whether the AMPK could contribute to the anti-inflammatory actions of nitric oxide (NO). METHODOLOGY/PRINCIPAL FINDINGS: Overexpression of a dominant negative AMPKα2 mutant in tumor necrosis factor-α-stimulated human endothelial cells resulted in increased NFκB activity, E-selectin expression and monocyte adhesion. In endothelial cells from AMPKα2(-/-) mice the interleukin (IL)-1β induced expression of E-selectin was significantly increased. DETA-NO activated the AMPK and attenuated NFκB activation/E-selectin expression, effects not observed in human endothelial cells in the presence of the dominant negative AMPK, or in endothelial cells from AMPKα2(-/-) mice. Mechanistically, overexpression of constitutively active AMPK decreased the phosphorylation of IκB and p65, indicating a link between AMPK and the IκB kinase (IKK). Indeed, IKK (more specifically residues Ser177 and Ser181) was found to be a direct substrate of AMPKα2 in vitro. The hyper-phosphorylation of the IKK, which is known to result in its inhibition, was also apparent in endothelial cells from AMPKα2(+/+) versus AMPKα2(-/-) mice. CONCLUSIONS: These results demonstrate that the IKK is a direct substrate of AMPKα2 and that its phosphorylation on Ser177 and Ser181 results in the inhibition of the kinase and decreased NFκB activation. Moreover, as NO potently activates AMPK in endothelial cells, a portion of the anti-inflammatory effects of NO are mediated by AMPK

Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate

The effect of beryllium oxide on retention in JET ITER-like wall tiles

Preliminary results investigating the microstructure, bonding and effect of beryllium oxide formation on retention in the JET ITER-like wall beryllium tiles, are presented. The tiles have been investigated by several techniques: Scanning Electron Microscopy (SEM) equipped with Energy Dispersive X-ray (EDX), Transmission Electron microscopy (TEM) equipped with EDX and Electron Energy Loss Spectroscopy (EELS), Raman Spectroscopy and Thermal Desorption Spectroscopy (TDS). This paper focuses on results from melted materials of the dump plate tiles in JET. From our results and the literature, it is concluded, beryllium can form micron deep oxide islands contrary to the nanometric oxides predicted under vacuum conditions. The deepest oxides analyzed were up to 2-micron thicknesses. The beryllium Deuteroxide (BeOxDy) bond was found with Raman Spectroscopy. Application of EELS confirmed the oxide presence and stoichiometry. Literature suggests these oxides form at temperatures greater than 700 °C where self-diffusion of beryllium ions through the surface oxide layer can occur. Further oxidation is made possible between oxygen plasma impurities and the beryllium ions now present at the wall surface. Under Ultra High Vacuum (UHV) nanometric Beryllium oxide layers are formed and passivate at room temperature. After continual cyclic heating (to the point of melt formation) in the presence of oxygen impurities from the plasma, oxide growth to the levels seen experimentally (approximately two microns) is proposed. This retention mechanism is not considered to contribute dramatically to overall retention in JET, due to low levels of melt formation. However, this mechanism, thought the result of operation environment and melt formation, could be of wider concern to ITER, dependent on wall temperatures

Impact of ICRF on the scrape-off layer and on plasma wall interactions: From present experiments to fusion reactor

Recent achievements in studies of the effects of ICRF (Ion Cyclotron Range of Frequencies) power on the SOL (Scrape-Off Layer) and PWI (Plasma Wall Interactions) in ASDEX Upgrade (AUG), Alcator C-Mod, and JET-ILW are reviewed. Capabilities to diagnose and model the effect of DC biasing and associated impurity production at active antennas and on magnetic field connections to antennas are described. The experiments show that ICRF near-fields can lead not only to E×B convection, but also to modifications of the SOL density, which for Alcator C-Mod are limited to a narrow region near antenna. On the other hand, the SOL density distribution along with impurity sources can be tailored using local gas injection in AUG and JET-ILW with a positive effect on reduction of impurity sources. The technique of RF image current cancellation at antenna limiters was successfully applied in AUG using the 3-strap AUG antenna and extended to the 4-strap Alcator C-Mod field-aligned antenna. Multiple observations confirmed the reduction of the impact of ICRF on the SOL and on total impurity production when the ratio of the power of the central straps to the total antenna power is in the range 0.6<P$_{cen}$/P$_{total}$<0.8. Near-field calculations indicate that this fairly robust technique can be applied to the ITER ICRF antenna, enabling the mode of operation with reduced PWI. On the contrary, for the A2 antenna in JET-ILW the technique is hindered by RF sheaths excited at the antenna septum. Thus, in order to reduce the effect of ICRF power on PWI in a future fusion reactor, the antenna design has to be optimized along with design of plasmafacing components

Determination of tungsten sources in the JET-ILW divertor by spectroscopic imaging in the presence of a strong plasma continuum

The identification of the sources of atomic tungsten and the measurement of their radiation distribution in front of all plasma-facing components has been performed in JET with the help of two digital cameras with the same two-dimensional view, equipped with interference filters of different bandwidths centred on theW I (400.88 nm) emission line. A new algorithm for the subtraction of the continuum radiation was successfully developed and is now used to evaluate the W erosion even in the inner divertor region where the strong recombination emission is dominating over the tungsten emission. Analysis of W sputtering and W redistribution in the divertor by video imaging spectroscopy with high spatial resolution for three different magnetic configurations was performed. A strong variation of the emission of the neutral tungsten in toroidal direction and corresponding W erosion has been observed. It correlates strongly with the wetted area with a maximal W erosion at the edge of the divertor tile

Improved ERO modelling of beryllium erosion at ITER upper first wall panel using JET-ILW and PISCES-B experience

ERO is a 3D Monte-Carlo impurity transport and plasma-surface interaction code. In 2011 it was applied for the ITER first wall (FW) life time predictions [1] (critical blanket module BM11). After that the same code was significantly improved during its application to existing fusion-relevant plasma devices: the tokamak JET equipped with an ITER-like wall and linear plasma device PISCES-B. This has allowed testing the sputtering data for beryllium (Be) and showing that the “ERO-min” fit based on the large (50%) deuterium (D) surface content is well suitable for plasma-wetted areas (D plasma). The improved procedure for calculating of the effective sputtering yields for each location along the plasma-facing surface using the recently developed semi-analytical sheath approach was validated. The re-evaluation of the effective yields for BM11 following the similar revisit of the JET data has indicated significant increase of erosion and motivated the current re-visit of ERO simulations