Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis

Library 2.0: the effectiveness of social media as a marketing tool for libraries in educational institutions

In an attempt to market their services and connect with potential users, and particularly young people, many libraries are opening accounts on social media platforms. Research suggests a contradiction between the advice relating to marketing and that regarding the use of social media in libraries, with the former emphasising the importance of the user at the centre of all considerations and the latter placing library staff as central to decisions. In this work we attempt to re-address this imbalance by surveying the current state of library activity on Twitter and, by means of questionnaires, investigate the experiences and motivations of librarians (n=58) in using social media and whether students (n=498) are willing to engage with the library in this manner and why. Our findings confirm that libraries in the sector are indeed struggling to foster interest in their social media activities and go some way to understanding why this is so, leading to a number of conclusions and recommendations for practitioners

Toward a multiscale modeling framework for understanding serotonergic function

Despite its importance in regulating emotion and mental wellbeing, the complex structure and function of the serotonergic system present formidable challenges toward understanding its mechanisms. In this paper, we review studies investigating the interactions between serotonergic and related brain systems and their behavior at multiple scales, with a focus on biologically-based computational modeling. We first discuss serotonergic intracellular signaling and neuronal excitability, followed by neuronal circuit and systems levels. At each level of organization, we will discuss the experimental work accompanied by related computational modeling work. We then suggest that a multiscale modeling approach that integrates the various levels of neurobiological organization could potentially transform the way we understand the complex functions associated with serotonin

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

Tritium distributions on W-coated divertor tiles used in the third JET ITER-like wall campaign

Tritium (T) distributions on tungsten (W)-coated plasma-facing tiles used in the third ITER-like wall campaign (2015–2016) of the Joint European Torus (JET) were examined by means of an imaging plate technique and β-ray induced x-ray spectrometry, and they were compared with the distributions after the second (2013–2014) campaign. Strong enrichment of T in beryllium (Be) deposition layers was observed after the second campaign. In contrast, T distributions after the third campaign was more uniform though Be deposition layers were visually recognized. The one of the possible explanations is enhanced desorption of T from Be deposition layers due to higher tile temperatures caused by higher energy input in the third campaign

Impact of fast ions on density peaking in JET : fluid and gyrokinetic modeling

The effect of fast ions on turbulent particle transport, driven by ion temperature gradient (ITG)/trapped electron mode turbulence, is studied. Two neutral beam injection (NBI) heated JET discharges in different regimes are analyzed at the radial position rho(t) = 0.6, one of them an L-mode and the other one an H-mode discharge. Results obtained from the computationally efficient fluid model EDWM and the gyro-fluid model TGLF are compared to linear and nonlinear gyrokinetic GENE simulations as well as the experimentally obtained density peaking. In these models, the fast ions are treated as a dynamic species with a Maxwellian background distribution. The dependence of the zero particle flux density gradient (peaking factor) on fast ion density, temperature and corresponding gradients, is investigated. The simulations show that the inclusion of a fast ion species has a stabilizing influence on the ITG mode and reduces the peaking of the main ion and electron density profiles in the absence of sources. The models mostly reproduce the experimentally obtained density peaking for the L-mode discharge whereas the H-mode density peaking is significantly underpredicted, indicating the importance of the NBI particle source for the H-mode density profile

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

Interpretative and predictive modelling of Joint European Torus collisionality scans

Transport modelling of Joint European Torus (JET) dimensionless collisionality scaling experiments in various operational scenarios is presented. Interpretative simulations at a fixed radial position are combined with predictive JETTO simulations of temperatures and densities, using the TGLF transport model. The model includes electromagnetic effects and collisions as well as □(→┬E ) X □(→┬B ) shear in Miller geometry. Focus is on particle transport and the role of the neutral beam injection (NBI) particle source for the density peaking. The experimental 3-point collisionality scans include L-mode, and H-mode (D and H and higher beta D plasma) plasmas in a total of 12 discharges. Experimental results presented in (Tala et al 2017 44th EPS Conf.) indicate that for the H-mode scans, the NBI particle source plays an important role for the density peaking, whereas for the L-mode scan, the influence of the particle source is small. In general, both the interpretative and predictive transport simulations support the experimental conclusions on the role of the NBI particle source for the 12 JET discharges

Impact of fast ions on density peaking in JET: fluid and gyrokinetic modeling

The effect of fast ions on turbulent particle transport, driven by ion temperature gradient (ITG)/ trapped electron mode turbulence, is studied. Two neutral beam injection (NBI) heated JET discharges in different regimes are analyzed at the radial position ρ$_{t}$=0.6, one of them an L-mode and the other one an H-mode discharge. Results obtained from the computationally efficient fluid model EDWM and the gyro-fluid model TGLF are compared to linear and nonlinear gyrokinetic GENE simulations as well as the experimentally obtained density peaking. In these models, the fast ions are treated as a dynamic species with a Maxwellian background distribution. The dependence of the zero particle flux density gradient (peaking factor) on fast ion density, temperature and corresponding gradients, is investigated. The simulations show that the inclusion of a fast ion species has a stabilizing influence on the ITG mode and reduces the peaking of the main ion and electron density profiles in the absence of sources. The models mostly reproduce the experimentally obtained density peaking for the L-mode discharge whereas the H-mode density peaking is significantly underpredicted, indicating the importance of the NBI particle source for the H-mode density profile