Inflammatory Stratification in Primary Sjögren’s Syndrome Reveals Novel Immune Cell Alterations in Patients’ Minor Salivary Glands

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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

Health benefit for the child and promotion of the common good were the two most important reasons for participation in the FinIP vaccine trial

Background and aims: The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was a nationwide cluster-randomised double-blind trial designed to demonstrate the effectiveness of pneumococcal conjugate vaccine in vaccinated children and indirect effects in unvaccinated populations. Together with the parallel carriage/AOM trial, over 47,000 children were enrolled, 52% of the initial target. We conducted a questionnaire study to find out which factors affected parents’ decision on their child’s study participation. Methods: A questionnaire designed to evaluate parents’ attitudes to vaccine trial participation in general and the FinIP trial in particular was mailed after the trial enrolment period had ended to parents of randomly selected children: 1,484 who participated in the trial and 1,485 who did not participate. Results: Altogether 1,438 parents (48%) responded to the questionnaire. The response rate was higher among FinIP participants (65%, 965/1,484) than among FinIP non-participants (32%, 473/1,485). The two most important reasons for giving consent to the FinIP trial were the potential benefit of immunisation against pneumococcal diseases (75% of consenters) and the promotion of the common good and public health (11%). The reasons reported as most important for declining consent were suspicions of vaccine safety (36%) and the double-blind trial design (12%). Up to 65% of the non-consenters declared that drug and vaccine trials should not be conducted in children at all. Conclusions: The expected health benefit for the child was by far the most important reason for consenting to the vaccine trial. Safety concern was the main reason for decline. Importance and necessity of clinical drug and vaccine trials among children and the rationale of the blinded studies should be thoroughly explained to the public. This may increase participation in future vaccine trials

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

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

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

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