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

The role of zinc in the anti-tumour and anti-cachectic activity of D-myo-inositol 1,2,6-triphosphate

Background: D-myo-inositol-1,2,6-triphosphate (a-trinositol, AT) is a polyanionic molecule capable of chelating divalent metal ions with anti-tumour and anti-cachectic activity in a murine model. Methods: To investigate the role of zinc in this process, mice bearing cachexia-inducing MAC16 tumour were treated with AT, with or without concomitant administration of ZnSO4. Results: At a dose of 40mgkg-1, AT effectively attenuated both weight loss and growth of the MAC16 tumour, and both effects were attenuated by co-administration of Zn2+. The concentration of zinc in gastrocnemius muscle increased with increasing weight loss, whereas administration of AT decreased the levels of zinc in plasma, skeletal muscle and tumour, which were restored back to control values after administration of ZnSO4. Conclusion: These results suggest that zinc is important in both tumour growth and cachexia in this animal model

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

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

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

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 the W 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.Peer reviewe

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

Dynamic modelling of local fuel inventory and desorption in the whole tokamak vacuum vessel for auto-consistent plasma-wall interaction simulations

An extension of the SolEdge2D-EIRENE code package, named D-WEE, has been developed to add the dynamics of thermal desorption of hydrogen isotopes from the surface of plasma facing materials. To achieve this purpose, D-WEE models hydrogen isotopes implantation, transport and retention in those materials. Before launching autoconsistent simulation (with feedback of D-WEE on SolEdge2D-EIRENE), D-WEE has to be initialised to ensure a realistic wall behaviour in terms of dynamics (pumping or fuelling areas) and fuel content. A methodology based on modelling is introduced to perform such initialisation. A synthetic plasma pulse is built from consecutive SolEdge2D-EIRENE simulations. This synthetic pulse is used as a plasma background for the D-WEE module. A sequence of plasma pulses is simulated with D-WEE to model a tokamak operation. This simulation enables to extract at a desired time during a pulse the local fuel inventory and the local desorption flux density which could be used as initial condition for coupled plasma-wall simulations. To assess the relevance of the dynamic retention behaviour obtained in the simulation, a confrontation to post-pulse experimental pressure measurement is performed. Such confrontation reveals a qualitative agreement between the temporal pressure drop obtained in the simulation and the one observed experimentally. The simulated dynamic retention during the consecutive pulses is also studied.Peer reviewe

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.Peer reviewe

Mixing and Circulation in the Tropical Atlantic Cruise No. M98

July 01 – July 28, 2013 Fortaleza (Brazil) – Walvis Bay (Namibia