Improved profile fitting and quantification of uncertainty in experimental measurements of impurity transport coefficients using Gaussian process regression

The need to fit smooth temperature and density profiles to discrete observations is ubiquitous in plasma physics, but the prevailing techniques for this have many shortcomings that cast doubt on the statistical validity of the results. This issue is amplified in the context of validation of gyrokinetic transport models (Holland et al 2009 Phys. Plasmas 16 052301), where the strong sensitivity of the code outputs to input gradients means that inadequacies in the profile fitting technique can easily lead to an incorrect assessment of the degree of agreement with experimental measurements. In order to rectify the shortcomings of standard approaches to profile fitting, we have applied Gaussian process regression (GPR), a powerful non-parametric regression technique, to analyse an Alcator C-Mod L-mode discharge used for past gyrokinetic validation work (Howard et al 2012 Nucl. Fusion 52 063002). We show that the GPR techniques can reproduce the previous results while delivering more statistically rigorous fits and uncertainty estimates for both the value and the gradient of plasma profiles with an improved level of automation. We also discuss how the use of GPR can allow for dramatic increases in the rate of convergence of uncertainty propagation for any code that takes experimental profiles as inputs. The new GPR techniques for profile fitting and uncertainty propagation are quite useful and general, and we describe the steps to implementation in detail in this paper. These techniques have the potential to substantially improve the quality of uncertainty estimates on profile fits and the rate of convergence of uncertainty propagation, making them of great interest for wider use in fusion experiments and modelling efforts.United States. Dept. of Energy. Office of Fusion Energy Sciences (Award DE-FC02-99ER54512)United States. Dept. of Energy. Office of Science (Contract DE-AC05-06OR23177)United States. Dept. of Energy. Office of Advanced Scientific Computing Research (Award DE-SC0007099

Six-minute walking test performance relates to neurocognitive abilities in preschoolers

This study investigated the relationship between six-minute walking test (6MWT) distance walked and preschool-aged children\u27s academic abilities, and behavioral and event-related potentials (ERP) indices of cognitive control. There were 59 children (25 females; age: 5.0 ± 0.6 years) who completed a 6MWT (mean distance: 449.6 ± 82.0 m) to estimate cardiorespiratory fitness. The Woodcock Johnson Early Cognitive and Academic Development Test evaluated academic abilities. A modified Eriksen flanker, hearts and flowers task, and auditory oddball task eliciting ERPs (N2, P3) assessed cognitive control. After adjusting for adiposity, diet, and demographics, linear regressions resulted in positive relationships between 6MWT distance and General Intellectual Ability (β = 0.25, Adj

Nonlinear gyrokinetic simulations of the I-mode high confinement regime and comparisons with experimenta)

For the first time, nonlinear gyrokinetic simulations of I-mode plasmas are performed and compared with experiment. I-mode is a high confinement regime, featuring energy confinement similar to H-mode, but without enhanced particle and impurity particle confinement [D. G. Whyte et al., Nucl. Fusion 50, 105005 (2010)]. As a consequence of the separation between heat and particle transport, I-mode exhibits several favorable characteristics compared to H-mode. The nonlinear gyrokinetic code GYRO [J. Candy and R. E. Waltz, J Comput. Phys. 186, 545 (2003)] is used to explore the effects of E × B shear and profile stiffness in I-mode and compare with L-mode. The nonlinear GYRO simulations show that I-mode core ion temperature and electron temperature profiles are more stiff than L-mode core plasmas. Scans of the input E × B shear in GYRO simulations show that E × B shearing of turbulence is a stronger effect in the core of I-mode than L-mode. The nonlinear simulations match the observed reductions in long wavelength density fluctuation levels across the L-I transition but underestimate the reduction of long wavelength electron temperature fluctuation levels. The comparisons between experiment and gyrokinetic simulations for I-mode suggest that increased E × B shearing of turbulence combined with increased profile stiffness are responsible for the reductions in core turbulence observed in the experiment, and that I-mode resembles H-mode plasmas more than L-mode plasmas with regards to marginal stability and temperature profile stiffness.United States. Department of Energy (Contract No. DE-FC02-99ER54512-CMOD)United States. Department of Energy. Office of Science (Contract No. DE-AC02- 05CH11231

Non-local heat transport in Alcator C-Mod ohmic L-mode plasmas

Non-local heat transport experiments were performed in Alcator C-Mod ohmic L-mode plasmas by inducing edge cooling with laser blow-off impurity (CaF2) injection. The non-local effect, a cooling of the edge electron temperature with a rapid rise of the central electron temperature, which contradicts the assumption of 'local' transport, was observed in low collisionality linear ohmic confinement (LOC) regime plasmas. Transport analysis shows this phenomenon can be explained either by a fast drop of the core diffusivity, or the sudden appearance of a heat pinch. In high collisionality saturated ohmic confinement (SOC) regime plasmas, the thermal transport becomes 'local': the central electron temperature drops on the energy confinement time scale in response to the edge cooling. Measurements from a high resolution imaging x-ray spectrometer show that the ion temperature has a similar behaviour as the electron temperature in response to edge cooling, and that the transition density of non-locality correlates with the rotation reversal critical density. This connection may indicate the possible connection between thermal and momentum transport, which is also linked to a transition in turbulence dominance between trapped electron modes (TEMs) and ion temperature gradient (ITG) modes. Experiments with repetitive cold pulses in one discharge were also performed to allow Fourier analysis and to provide details of cold front propagation. These modulation experiments showed in LOC plasmas that the electron thermal transport is not purely diffusive, while in SOC the electron thermal transport is more diffusive like. Linear gyrokinetic simulations suggest the turbulence outside r/a = 0.75 changes from TEM dominance in LOC plasmas to ITG mode dominance in SOC plasmas.United States. Dept. of Energy (DoE Contract No DE-FC02-99ER54512)Oak Ridge Institute for Science and Education (DOE Fusion Energy Postdoctoral Research Program

Retinal Morphometric Markers of Crystallized and Fluid Intelligence Among Adults With Overweight and Obesity

Objective: To investigate the relationship between retinal morphometric measures and intellectual abilities among adults with overweight and obesity.Methods: Adults between 25 and 45 years (N = 55, 38 females) with overweight or obesity (BMI ≥ 25.0 kg/m2) underwent an optical coherence tomography (OCT) scan to assess retinal nerve fiber layer (RNFL) volume, ganglion cell layer (GCL) volume, macular volume, and central foveal thickness. Dual-Energy X-ray absorptiometry was used to assess whole-body adiposity (% Fat). The Kaufman Brief Intelligence Test-2 was used to assess general intelligence (IQ), fluid, and crystallized intelligence. Hierarchical linear regression analyses were performed to examine relationships between adiposity and intelligence measures following adjustment of relevant demographic characteristics and degree of adiposity (i.e., % Fat).Results: Although initial bivariate correlations indicated that % Fat was inversely related to fluid intelligence, this relationship was mitigated by inclusion of other demographic factors, including age, sex, and education level. Regression analyses for primary outcomes revealed that RNFL was positively related to IQ and fluid intelligence. However, only GCL was positively related to crystallized intelligence.Conclusion: This work provides novel data linking specific retinal morphometric measures – assessed using OCT – to intellectual abilities among adults with overweight and obesity.Clinical Trial Registration:www.clinicaltrials.gov, identifier NCT02740439

Gene Regulation of Intestinal Porcine Epithelial Cells IPEC-J2 Is Dependent on the Site of Deoxynivalenol Toxicological Action

The intestinal epithelial cell layer represents the border between the luminal and systemic side of the gut. The decision between absorption and exclusion of substances is the quintessential function of the gut and varies along the gut axis. Consequently, potentially toxic substances may reach the basolateral domain of the epithelial cell layer via blood stream. The mycotoxin deoxynivalenol (DON) is a Fusarium derived secondary metabolite known to enter the blood stream and displaying a striking toxicity on the basolateral side of polarised epithelial cell layers in vitro. Here we analysed potential mechanisms of apical and basolateral DON toxicity reflected in the gene expression. We used the jejunum-derived, polarised intestinal porcine epithelial cell line IPEC-J2 as an in vitro cell culture model. Luminal and systemic DON challenge of the epithelial cell layer was mimicked by a DON application from the apical or basolateral compartment of membrane inserts for 72 h. We compared the genome-wide gene expression of untreated and DON-treated IPEC-J2 cells with the GeneChip® Porcine Genome Array of Affymetrix. Low basolateral DON (200 ng/mL) application triggered 10 times more gene transcripts in comparison to the corresponding apical application (2539 versus 267) despite the intactness of the challenged cell layer as measured by transepithelial electrical resistance. Analysis of the regulated genes by bioinformatic resource DAVID identified several groups of biochemical pathways modulated by concentration and orientation of DON application. Selected genes representing pathways of the cellular metabolism, information processing and structural design were analysed in detail by quantitative PCR. Our findings clearly show that apical and basolateral challenge of epithelial cell layers trigger different gene response profiles paralleled with a higher susceptibility towards basolateral challenge. The evaluation of toxicological potentials of mycotoxins should take this difference in gene regulation dependent on route of application into account

20 years of research on the Alcator C-Mod tokamak

The object of this review is to summarize the achievements of research on the Alcator C-Mod tokamak [Hutchinson et al., Phys. Plasmas 1, 1511 (1994) and Marmar, Fusion Sci. Technol. 51, 261 (2007)] and to place that research in the context of the quest for practical fusion energy. C-Mod is a compact, high-field tokamak, whose unique design and operating parameters have produced a wealth of new and important results since it began operation in 1993, contributing data that extends tests of critical physical models into new parameter ranges and into new regimes. Using only high-power radio frequency (RF) waves for heating and current drive with innovative launching structures, C-Mod operates routinely at reactor level power densities and achieves plasma pressures higher than any other toroidal confinement device. C-Mod spearheaded the development of the vertical-target divertor and has always operated with high-Z metal plasma facing components—approaches subsequently adopted for ITER. C-Mod has made ground-breaking discoveries in divertor physics and plasma-material interactions at reactor-like power and particle fluxes and elucidated the critical role of cross-field transport in divertor operation, edge flows and the tokamak density limit. C-Mod developed the I-mode and the Enhanced Dα H-mode regimes, which have high performance without large edge localized modes and with pedestal transport self-regulated by short-wavelength electromagnetic waves. C-Mod has carried out pioneering studies of intrinsic rotation and demonstrated that self-generated flow shear can be strong enough in some cases to significantly modify transport. C-Mod made the first quantitative link between the pedestal temperature and the H-mode's performance, showing that the observed self-similar temperature profiles were consistent with critical-gradient-length theories and followed up with quantitative tests of nonlinear gyrokinetic models. RF research highlights include direct experimental observation of ion cyclotron range of frequency (ICRF) mode-conversion, ICRF flow drive, demonstration of lower-hybrid current drive at ITER-like densities and fields and, using a set of novel diagnostics, extensive validation of advanced RF codes. Disruption studies on C-Mod provided the first observation of non-axisymmetric halo currents and non-axisymmetric radiation in mitigated disruptions. A summary of important achievements and discoveries are included.United States. Dept. of Energy (Cooperative Agreement DE-FC02-99ER54512)United States. Dept. of Energy (Cooperative Agreement DE-FG03-94ER-54241)United States. Dept. of Energy (Cooperative Agreement DE-AC02-78ET- 51013)United States. Dept. of Energy (Cooperative Agreement DE-AC02-09CH11466)United States. Dept. of Energy (Cooperative Agreement DE-FG02-95ER54309)United States. Dept. of Energy (Cooperative Agreement DE-AC02-05CH11231)United States. Dept. of Energy (Cooperative Agreement DE-AC52-07NA27344)United States. Dept. of Energy (Cooperative Agreement DE-FG02- 97ER54392)United States. Dept. of Energy (Cooperative Agreement DE-SC00-02060

Vulnerability of Polarised Intestinal Porcine Epithelial Cells to Mycotoxin Deoxynivalenol Depends on the Route of Application

BACKGROUND AND AIMS: Deoxynivalenol (DON) is a Fusarium derived mycotoxin, often occurring on cereals used for human and animal nutrition. The intestine, as prominent barrier for nutritional toxins, has to handle the mycotoxin from the mucosa protected luminal side (apical exposure), as well as already absorbed toxin, reaching the cells from basolateral side via the blood stream. In the present study, the impact of the direction of DON exposure on epithelial cell behaviour and intestinal barrier integrity was elucidated. METHODS: A non-transformed intestinal porcine epithelial cell line (IPEC-J2), cultured in membrane inserts, serving as a polarised in vitro model to determine the effects of deoxynivalenol (DON) on cellular viability and tight junction integrity. RESULTS: Application of DON in concentrations up to 4000 ng/mL for 24, 48 and 72 hours on the basolateral side of membrane cultured polarised IPEC-J2 cells resulted in a breakdown of the integrity of cell connections measured by transepithelial electrical resistance (TEER), as well as a reduced expression of the tight junction proteins ZO-1 and claudin 3. Epithelial cell number decreased and nuclei size was enlarged after 72 h incubation of 4000 ng/mL DON from basolateral. Although necrosis or caspase 3 mediated apoptosis was not detectable after basolateral DON application, cell cycle analysis revealed a significant increase in DNA fragmentation, decrease in G0/G1 phase and slight increase in G2/M phase after 72 hours incubation with DON 2000 ng/mL. CONCLUSIONS: Severity of impact of the mycotoxin deoxynivalenol on the intestinal epithelial barrier is dependent on route of application. The epithelium appears to be rather resistant towards apical (luminal) DON application whereas the same toxin dose from basolateral severely undermines barrier integrity

Alcator C-Mod: research in support of ITER and steps beyond

This paper presents an overview of recent highlights from research on Alcator C-Mod. Significant progress has been made across all research areas over the last two years, with particular emphasis on divertor physics and power handling, plasma–material interaction studies, edge localized mode-suppressed pedestal dynamics, core transport and turbulence, and RF heating and current drive utilizing ion cyclotron and lower hybrid tools. Specific results of particular relevance to ITER include: inner wall SOL transport studies that have led, together with results from other experiments, to the change of the detailed shape of the inner wall in ITER; runaway electron studies showing that the critical electric field required for runaway generation is much higher than predicted from collisional theory; core tungsten impurity transport studies reveal that tungsten accumulation is naturally avoided in typical C-Mod conditions.United States. Department of Energy (DE-FC02-99ER54512-CMOD)United States. Department of Energy (DE-AC02-09CH11466)United States. Department of Energy (DE-FG02-96ER-54373)United States. Department of Energy (DE-FG02-94ER54235

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe