Erythropoietin (EPO) increases myelin gene expression in CG4 oligodendrocyte cells through the classical EPO receptor

Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in non-hematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP)). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects

Biomarkers and prediction of myocardial triglyceride content in non-diabetic men

Background and aims: Lipid oversupply to cardiomyocytes or decreased utilization of lipids leads to cardiac steatosis. We aimed to examine the role of different circulating metabolic biomarkers as predictors of myocardial triglyceride (TG) content in non-diabetic men. Methods and results: Myocardial and hepatic TG contents were measured with 1.5 T magnetic resonance (MR) spectroscopy, and LV function, visceral adipose tissue (VAT), abdominal subcutaneous tissue (SAT), epicardial and pericardial fat by MR imaging in 76 non-diabetic men. Serum concentration of circulating metabolic biomarkers [adiponectin, leptin, adipocyte-fatty acid binding protein 4 (A-FABP 4), resistin, and lipocalin-2] including beta-hydroxybuturate (beta-OHB) were measured. Subjects were stratified by tertiles of myocardial TG into low, moderate, and high myocardial TG content groups. Concentrations of beta-OHB were lower (p = 0.003) and serum levels of A-FABP 4 were higher (p <0.001) in the group with high myocardial TG content compared with the group with low myocardial TG content. beta-OHB was negatively correlated with myocardial TG content (r = -0.316, p = 0.006), whereas A-FABP 4 was not correlated with myocardial TG content (r = 0.192, p = 0.103). In multivariable analyses beta-OHB and plasma glucose levels were the best predictors of myocardial TG content independently of VAT and hepatic TG content. The model explained 58.8% of the variance in myocardial TG content. Conclusion: Our data showed that beta-OHB and fasting glucose were the best predictors of myocardial TG content in non-diabetic men. These data suggest that hyperglycemia and alterations in lipid oxidation may be associated with cardiac steatosis in humans. (C) 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.Peer reviewe

A machine learning approach based on generative topographic mapping for disruption prevention and avoidance at JET

The need for predictive capabilities greater than 95% with very limited false alarms are demanding requirements for reliable disruption prediction systems in tokamaks such as JET or, in the near future, ITER. The prediction of an upcoming disruption must be provided sufficiently in advance in order to apply effective disruption avoidance or mitigation actions to prevent the machine from being damaged. In this paper, following the typical machine learning workflow, a generative topographic mapping (GTM) of the operational space of JET has been built using a set of disrupted and regularly terminated discharges. In order to build the predictive model, a suitable set of dimensionless, machine-independent, physics-based features have been synthesized, which make use of 1D plasma profile information, rather than simple zero-D time series. The use of such predicting features, together with the power of the GTM in fitting the model to the data, obtains, in an unsupervised way, a 2D map of the multi-dimensional parameter space of JET, where it is possible to identify a boundary separating the region free from disruption from the disruption region. In addition to helping in operational boundaries studies, the GTM map can also be used for disruption prediction exploiting the potential of the developed GTM toolbox to monitor the discharge dynamics. Following the trajectory of a discharge on the map throughout the different regions, an alarm is triggered depending on the disruption risk of these regions. The proposed approach to predict disruptions has been evaluated on a training and an independent test set and achieves very good performance with only one tardive detection and a limited number of false detections. The warning times are suitable for avoidance purposes and, more important, the detections are consistent with physical causes and mechanisms that destabilize the plasma leading to disruptions.Peer reviewe

Investigation of deuterium trapping and release in the JET divertor during the third ILW campaign using TDS

Selected set of samples from JET ITER-Like Wall (JET-ILW) divertor tiles exposed in 2015-2016 has been analysed using Thermal Desorption Spectrometry (TDS). The deuterium (D) amounts obtained with TDS were compared with Nuclear Reaction Analysis (NRA). The highest amount of D was found on the top part of inner divertor which has regions with the thickest deposited layers as for divertor tiles removed in 2014. This area resides deep in the scrape-off layer and plasma configurations for the second (ILW-2, 2013-2014) and the third (ILW-3, 2015-2016) JET-ILW campaigns were similar. Agreement between TDS and NRA is good on the apron of Tile 1 and on the upper vertical region whereas on the lower vertical region of Tile 1 the NRA results are clearly smaller than the TDS results. Inner divertor Tile 3 has somewhat less D than Tiles 0 and 1, and the D amount decreases towards the lower part of the tile. The D retention at the divertor inner and outer corner regions is not symmetric as there is more D retention poloidally at the inner than at the outer divertor corner. In most cases the TDS spectra for the ILW-3 samples are different from the corresponding ILW-2 spectra because HD and D-2 release occurs at higher temperatures than from the ILW-2 samples indicating that the low energy traps have been emptied during the plasma operations and that D is either in the energetically deep traps or located deeper in the sample.Peer reviewe

RF sheath modeling of experimentally observed plasma surface interactions with the JET ITER-Like Antenna

Waves in the Ion Cyclotron Range of Frequencies (ICRF) enhance local Plasma-Surface Interactions (PSI) near the wave launchers and magnetically-connected objects via Radio-Frequency (RF) sheath rectification. ITER will use 20MW of ICRF power over long pulses, questioning the long-term impact of RF-enhanced localized erosion on the lifetime of its Beryllium (Be) wall. Recent dedicated ICRF-heated L-mode discharges documented this process on JET for different types of ICRF antennas. Using visible spectroscopy in JET ICRF-heated L-mode discharges, poloidally-localized regions of enhanced (by similar to 2-4x) Be I and Be II light emission were observed on two outboard limiters magnetically connected to the bottom of the active ITER-Like Antenna (ILA). The observed RF-PSI induced by the ILA was qualitatively comparable to that induced by the JET standard, type-A2 antennas, for similar strap toroidal phasing and connection geometries. The Be II line emission was found more intense when powering the bottom half of the ILA rather than its top half. Conversely, more pronounced SOL density modifications were observed with only top array operation, on field lines connected to the top half of the ILA. So far the near-field modeling of the ILA with antenna code TOPICA (Torino Polytechnic Ion Cyclotron Antenna), using curved antenna model, was partially able to reproduce qualitatively the observed phenomena. A quantitative discrepancy persisted between the observed Be source amplification and the calculated, corresponding increases in E-// field at the magnetically connected locations to the ILA when changing from only top to only bottom half antenna operation. This paper revisits these current drive phased and half-ILA powered cases using for the new simulations flat model of the ILA and more realistic antenna feeding to calculate the E-// field maps with TOPICA code. Further, the Self-consistent Sheaths and Waves for Ion Cyclotron Heating Slow Wave (SSWICH-SW) code, which couples slow wave evanescence with DC Scrape-Off Layer (SOL) biasing, is used to estimate the poloidal distribution of rectified RF-sheath Direct Current (DC) potential V-DC in the private SOL between the ILA poloidal limiters. The approach so far was limited to correlating the observed, enhanced emission regions at the remote limiters to the antenna near-electric fields, as calculated by TOPICA. The present approach includes also a model for the rectification of these near-fields in the private SOL of the ILA. With the improved approach, when comparing only top and only bottom half antenna feeding, we obtained good qualitative correlation between all experimental measurements and the calculated local variations in the E-// field and V-DC potential.Peer reviewe

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 degrees 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.Peer reviewe

Comparison of the structure of the plasma-facing surface and tritium accumulation in beryllium tiles from JET ILW campaigns 2011-2012 and 2013-2014

In this study, beryllium tiles from Joint European Torus (JET) vacuum vessel wall were analysed and compared regarding their position in the vacuum vessel and differences in the exploitation conditions during two campaigns of ITER-Like-Wall (ILW) in 2011-2012 (ILW1) and 2013-2014 (ILW2) Tritium content in beryllium samples were assessed. Two methods were used to measure tritium content in the samples - dissolution under controlled conditions and tritium thermal desorption. Prior to desorption and dissolution experiments, scanning electron microscopy and energy dispersive x-ray spectroscopy were used to study structure and chemical composition of plasma-facing-surfaces of the beryllium samples. Experimental results revealed that tritium content in the samples is in range of 2.10(11)-2.10(13) tritium atoms per square centimetre of the surface area with its highest content in the samples from the outer wall of the vacuum vessel (up to 1.9.10(13) atoms/cm(2) in ILW1 campaign and 2.4.10(13) atoms/cm(2) in ILW2). The lowest content of tritium was found in the upper part of the vacuum vessel (2.0.10(12) atoms/cm(2) and 2.0.10(11) atoms/cm(2) in ILW1 and ILW2, respectively). Results obtained from scanning electron microscopy has shown that surface morphology is different within single tile, however if to compare two campaigns main tendencies remains similar.Peer reviewe

Lagrangian Views of the Pathways of the Atlantic Meridional Overturning Circulation

The Lagrangian method-where current location and intensity are determined by tracking the movement of flow along its path-is the oldest technique for measuring the ocean circulation. For centuries, mariners used compilations of ship drift data to map out the location and intensity of surface currents along major shipping routes of the global ocean. In the mid-20th century, technological advances in electronic navigation allowed oceanographers to continuously track freely drifting surface buoys throughout the ice-free oceans and begin to construct basin-scale, and eventually global-scale, maps of the surface circulation. At about the same time, development of acoustic methods to track neutrally buoyant floats below the surface led to important new discoveries regarding the deep circulation. Since then, Lagrangian observing and modeling techniques have been used to explore the structure of the general circulation and its variability throughout the global ocean, but especially in the Atlantic Ocean. In this review, Lagrangian studies that focus on pathways of the upper and lower limbs of the Atlantic Meridional Overturning Circulation (AMOC), both observational and numerical, have been gathered together to illustrate aspects of the AMOC that are uniquely captured by this technique. These include the importance of horizontal recirculation gyres and interior (as opposed to boundary) pathways, the connectivity (or lack thereof) of the AMOC across latitudes, and the role of mesoscale eddies in some regions as the primary AMOC transport mechanism. There remain vast areas of the deep ocean where there are no direct observations of the pathways of the AMOC

Modelling of tungsten erosion and deposition in the divertor of JET-ILW in comparison to experimental findings

The erosion, transport and deposition of tungsten in the outer divertor of JET-ILW has been studied for an H-Mode discharge with low frequency ELMs. For this specific case with an inter-ELM electron temperature at the strike point of about 20 eV, tungsten sputtering between ELMs is almost exclusively due to beryllium impurity and self-sputtering. However, during ELMs tungsten sputtering due to deuterium becomes important and even dominates. The amount of simulated local deposition of tungsten relative to the amount of sputtered tungsten in between ELMs is very high and reaches values of 99% for an electron density of 5E13 cm(-3) at the strike point and electron temperatures between 10 and 30 eV. Smaller deposition values are simulated with reduced electron density. The direction of the B-field significantly influences the local deposition and leads to a reduction if the E x B drift directs towards the scrape-off-layer. Also, the thermal force can reduce the tungsten deposition, however, an ion temperature gradient of about 0.1 eV/mm or larger is needed for a significant effect. The tungsten deposition simulated during ELMs reaches values of about 98% assuming ELM parameters according to free-streaming model. The measured WI emission profiles in between and within ELMs have been reproduced by the simulation. The contribution to the overall net tungsten erosion during ELMs is about 5 times larger than the one in between ELMs for the studied case. However, this is due to the rather low electron temperature in between ELMs, which leads to deuterium impact energies below the sputtering threshold for tungsten.Peer reviewe

Changes in Community Mobility in Older Men and Women. A 13-Year Prospective Study

Community mobility, defined as “moving [ones] self in the community and using public or private transportation”, has a unique ability to promote older peoples’ wellbeing by enabling independence and access to activity arenas for interaction with others. Early predictors of decreased community mobility among older men and women are useful in developing health promoting strategies. However, long-term prediction is rare, especially when it comes to including both public and private transportation. The present study describes factors associated with community mobility and decreased community mobility over time among older men and women. In total, 119 men and 147 women responded to a questionnaire in 1994 and 2007. Respondents were between 82 and 96 years old at follow-up. After 13 years, 40% of men and 43% of women had decreased community mobility, but 47% of men and 45% of women still experienced some independent community mobility. Cross-sectional independent community mobility among men was associated with higher ratings of subjective health, reporting no depression and more involvement in sport activities. Among women, cross-sectional independent community mobility was associated with better subjective health and doing more instrumental activities of daily living outside the home. Lower subjective health predicted decreased community mobility for both men and women, whereas self-reported health conditions did not. Consequently, general policies and individual interventions aiming to improve community mobility should consider older persons’ subjective health