| 1. |
- Lerche, E., et al.
(author)
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Optimizing ion-cyclotron resonance frequency heating for ITER : dedicated JET experiments
- 2011
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In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 53:12, s. 124019-
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Journal article (peer-reviewed)abstract
- In the past years, one of the focal points of the JET experimental programme was on ion-cyclotron resonance heating (ICRH) studies in view of the design and exploitation of the ICRH system being developed for ITER. In this brief review, some of the main achievements obtained in JET in this field during the last 5 years will be summarized. The results reported here include important aspects of a more engineering nature, such as (i) the appropriate design of the RF feeding circuits for optimal load resilient operation and (ii) the test of a compact high-power density antenna array, as well as RF physics oriented studies aiming at refining the numerical models used for predicting the performance of the ICRH system in ITER. The latter include (i) experiments designed for improving the modelling of the antenna coupling resistance under various plasma conditions and (ii) the assessment of the heating performance of ICRH scenarios to be used in the non-active operation phase of ITER.
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| 2. |
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| 5. |
- Mayoral, M. -L, et al.
(author)
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Overview of Recent Results on Heating and Current Drive in the JET tokamak
- 2009
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In: RADIO FREQUENCY POWER IN PLASMAS. - : AIP. - 9780735407534 ; , s. 39-46
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Conference paper (peer-reviewed)abstract
- In this paper, significant results in the heating and current drive domains obtained at JET in the past few years following systems upgrade and dedicated experimental time, will be reviewed. Firstly, an overview of the new Ion Cyclotron Resonance Frequency (ICRF) heating capabilities will be presented i.e. results from the ITER-Like ICRF antenna (ILA), the use of External Conjugate-T and 3dB hybrid couplers to increase the ICRF power during ELMy H-mode, Furthermore, experiments to study the influence of the phasing of the ICRF antenna on power absorption and coupling will be described. Looking at Low Hybrid (I-H) issues for ITER, the effect of the location of gas injection on the LH coupling improvement at large launcher-separatrix distances will be discussed as the possibility to operate at ITER-relevant power densities. Experiments to characterise the LH power losses in the Scrape-Off-Layer (SOL) and to determine the LH wave absorption and current drive using power modulation will be shown. Finally, plasma rotation studies in the presence of ICRF heating with standard and enhanced JET toroidal field ripple will be presented.
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| 6. |
- Van Eester, D., et al.
(author)
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Enhancing the mode conversion efficiency in JET plasmas with multiple mode conversion layers
- 2011
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In: AIP Conf. Proc.. - : AIP. - 1551-7616 .- 0094-243X. - 9780735409781 ; , s. 301-308
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Conference paper (peer-reviewed)abstract
- The constructive interference effect described by Fuchs et al. [1] shows that the mode conversion and thereby the overall heating efficiency can be enhanced significantly when an integer number of fast wave wavelengths can be folded in between the high field side fast wave cutoff and the ion-ion hybrid layer(s) at which the ion Bernstein or ion cyclotron waves are excited. This effect was already experimentally identified in ( 3He)-D plasmas [2] and was recently tested in ( 3He)-H JET plasmas. The latter is an 'inverted' scenario, which differs significantly from the ( 3He)-D scenarios since the mode-conversion layer is positioned between the low field side edge of the plasma and the ion-cyclotron layer of the minority 3He ions (whereas the order in which a wave entering the plasma from the low field side encounters these layers is inverted in a 'regular' scenario), and because much lower 3He concentrations are needed to achieve the mode-conversion heating regime. The presence of small amounts of 4He and D in the discharges gave rise to an additional mode conversion layer on top of the expected one associated with 3He-H, which made the interpretation of the results more complex but also more interesting: Three different regimes could be distinguished as a function of X[ 3He], and the differing dynamics at the various concentrations could be traced back to the presence of these two mode conversion layers and their associated fast wave cutoffs. Whereas (1-D and 2-D) numerical modeling yields quantitative information on the RF absorptivity, recent analytical work by Kazakov [3] permits to grasp the dominant underlying wave interaction physics.
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| 7. |
- Van Eester, D., et al.
(author)
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Minority and mode conversion heating in (He-3)-H JET plasmas
- 2012
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In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 54:7, s. 074009-
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Journal article (peer-reviewed)abstract
- Radio frequency (RF) heating experiments have recently been conducted in JET (He-3)-H plasmas. This type of plasmas will be used in ITER's non-activated operation phase. Whereas a companion paper in this same PPCF issue will discuss the RF heating scenario's at half the nominal magnetic field, this paper documents the heating performance in (He-3)-H plasmas at full field, with fundamental cyclotron heating of He-3 as the only possible ion heating scheme in view of the foreseen ITER antenna frequency bandwidth. Dominant electron heating with global heating efficiencies between 30% and 70% depending on the He-3 concentration were observed and mode conversion (MC) heating proved to be as efficient as He-3 minority heating. The unwanted presence of both He-4 and D in the discharges gave rise to 2 MC layers rather than a single one. This together with the fact that the location of the high-field side fast wave (FW) cutoff is a sensitive function of the parallel wave number and that one of the locations of the wave confluences critically depends on the He-3 concentration made the interpretation of the results, although more complex, very interesting: three regimes could be distinguished as a function of X[He-3]: (i) a regime at low concentration (X[He-3] < 1.8%) at which ion cyclotron resonance frequency (ICRF) heating is efficient, (ii) a regime at intermediate concentrations (1.8 < X[He-3] < 5%) in which the RF performance is degrading and ultimately becoming very poor, and finally (iii) a good heating regime at He-3 concentrations beyond 6%. In this latter regime, the heating efficiency did not critically depend on the actual concentration while at lower concentrations (X[He-3] < 4%) a bigger excursion in heating efficiency is observed and the estimates differ somewhat from shot to shot, also depending on whether local or global signals are chosen for the analysis. The different dynamics at the various concentrations can be traced back to the presence of 2 MC layers and their associated FW cutoffs residing inside the plasma at low He-3 concentration. One of these layers is approaching and crossing the low-field side plasma edge when 1.8 < X[He-3] < 5%. Adopting a minimization procedure to correlate the MC positions with the plasma composition reveals that the different behaviors observed are due to contamination of the plasma. Wave modeling not only supports this interpretation but also shows that moderate concentrations of D-like species significantly alter the overall wave behavior in He-3-H plasmas. Whereas numerical modeling yields quantitative information on the heating efficiency, analytical work gives a good description of the dominant underlying wave interaction physics.
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| 8. |
- Hillier, J. K., et al.
(author)
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Manual mapping of drumlins in synthetic landscapes to assess operator effectiveness
- 2015
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In: Journal of Maps. - : Informa UK Limited. - 1744-5647. ; 11:5, s. 719-729
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Journal article (peer-reviewed)abstract
- Mapped topographic features are important for understanding processes that sculpt the Earth's surface. This paper presents maps that are the primary product of an exercise that brought together 27 researchers with an interest in landform mapping wherein the efficacy and causes of variation in mapping were tested using novel synthetic DEMs containing drumlins. The variation between interpreters (e.g. mapping philosophy, experience) and across the study region (e.g. woodland prevalence) opens these factors up to assessment. A priori known answers in the synthetics increase the number and strength of conclusions that may be drawn with respect to a traditional comparative study. Initial results suggest that overall detection rates are relatively low (34-40%), but reliability of mapping is higher (72-86%). The maps form a reference dataset.
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| 9. |
- Lerche, E., et al.
(author)
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Experimental investigation of ion cyclotron range of frequencies heating scenarios for ITER's half-field hydrogen phase performed in JET
- 2012
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In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 54:7, s. 074008-
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Journal article (peer-reviewed)abstract
- Two ion cyclotron range of frequencies ( ICRF) heating schemes proposed for the half-field operation phase of ITER in hydrogen plasmas-fundamental H majority and second harmonic He-3 ICRF heating-were recently investigated in JET. Although the same magnetic field and RF frequencies (f approximate to 42 MHz and f approximate to 52 MHz, respectively) were used, the density and particularly the plasma temperature were lower than those expected in the initial phase of ITER. Unlike for the well-performing H minority heating scheme to be used in He-4 plasmas, modest heating efficiencies (n = P-absorbed/P-launched < 40%) with dominant electron heating were found in both H plasma scenarios studied, and enhanced plasma-wall interaction manifested by high radiation losses and relatively large impurity content in the plasma was observed. This effect was stronger in the He-3 ICRF heating case than in the H majority heating experiments and it was verified that concentrations as high as similar to 20% are necessary to observe significant ion heating in this case. The RF acceleration of the heated ions was modest in both cases, although a small fraction of the 3He ions reached about 260 keV in the second harmonic He-3 heating experiments when 5MW of ICRF power was applied. Considerable RF acceleration of deuterium beam ions was also observed in some discharges of the He-3 heating experiments (where both the second and third harmonic ion cyclotron resonance layers of the D ions are inside the plasma) whilst it was practically absent in the majority hydrogen heating scenario. While hints of improved RF heating efficiency as a function of the plasma temperature and plasma dilution (with He-4) were confirmed in the H majority case, the He-3 concentration was the main handle on the heating efficiency in the second harmonic He-3 heating scenario.
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| 13. |
- Loth, Eva, et al.
(author)
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The EU-AIMS Longitudinal European Autism Project (LEAP) : design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders.
- 2017
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In: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
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Journal article (peer-reviewed)abstract
- BACKGROUND: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD.METHODS: LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability.RESULTS: Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted).CONCLUSION: We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies.
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| 16. |
- Charman, Tony, et al.
(author)
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The EU-AIMS Longitudinal European Autism Project (LEAP) : clinical characterisation.
- 2017
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In: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
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Journal article (peer-reviewed)abstract
- BACKGROUND: The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study on biomarkers for autism spectrum disorder (ASD). The current paper describes the clinical characteristics of the LEAP cohort and examines age, sex and IQ differences in ASD core symptoms and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers.METHODS: From six research centres in four European countries, we recruited 437 children and adults with ASD and 300 controls between the ages of 6 and 30 years with IQs varying between 50 and 148. We conducted in-depth clinical characterisation including a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms.RESULTS: The cohort showed heterogeneity in ASD symptom presentation, with only minimal to moderate site differences on core clinical and cognitive measures. On both parent-report interview and questionnaire measures, ASD symptom severity was lower in adults compared to children and adolescents. The precise pattern of differences varied across measures, but there was some evidence of both lower social symptoms and lower repetitive behaviour severity in adults. Males had higher ASD symptom scores than females on clinician-rated and parent interview diagnostic measures but not on parent-reported dimensional measures of ASD symptoms. In contrast, self-reported ASD symptom severity was higher in adults compared to adolescents, and in adult females compared to males. Higher scores on ASD symptom measures were moderately associated with lower IQ. Both inattentive and hyperactive/impulsive ADHD symptoms were lower in adults than in children and adolescents, and males with ASD had higher levels of inattentive and hyperactive/impulsive ADHD symptoms than females.CONCLUSIONS: The established phenotypic heterogeneity in ASD is well captured in the LEAP cohort. Variation both in core ASD symptom severity and in commonly co-occurring psychiatric symptoms were systematically associated with sex, age and IQ. The pattern of ASD symptom differences with age and sex also varied by whether these were clinician ratings or parent- or self-reported which has important implications for establishing stratification biomarkers and for their potential use as outcome measures in clinical trials.
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| 17. |
- Gutierrez, J, et al.
(author)
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Equilibrium design for concurrent games
- 2019
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In: Leibniz International Proceedings in Informatics, LIPIcs. - 1868-8969.
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Conference paper (peer-reviewed)abstract
- In game theory, mechanism design is concerned with the design of incentives so that a desired outcome of the game can be achieved. In this paper, we study the design of incentives so that a desirable equilibrium is obtained, for instance, an equilibrium satisfying a given temporal logic property – a problem that we call equilibrium design. We base our study on a framework where system specifications are represented as temporal logic formulae, games as quantitative concurrent game structures, and players’ goals as mean-payoff objectives. In particular, we consider system specifications given by LTL and GR(1) formulae, and show that implementing a mechanism to ensure that a given temporal logic property is satisfied on some/every Nash equilibrium of the game, whenever such a mechanism exists, can be done in PSPACE for LTL properties and in NP/ΣP2 for GR(1) specifications. We also study the complexity of various related decision and optimisation problems, such as optimality and uniqueness of solutions, and show that the complexities of all such problems lie within the polynomial hierarchy. As an application, equilibrium design can be used as an alternative solution to the rational synthesis and verification problems for concurrent games with mean-payoff objectives whenever no solution exists, or as a technique to repair, whenever possible, concurrent games with undesirable rational outcomes (Nash equilibria) in an optimal way.
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| 18. |
- Mason, L., et al.
(author)
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Preference for biological motion is reduced in ASD : implications for clinical trials and the search for biomarkers
- 2021
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In: Molecular Autism. - : Springer Nature. - 2040-2392. ; 12
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Journal article (peer-reviewed)abstract
- Background: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology.Methods: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N = 282) and non-autistic control (N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL).Results: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline.Limitations: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons.Conclusions: Biological motion preference elicits small-to-medium-sized case–control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear.
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| 19. |
- Khairalla, Ahmed S., et al.
(author)
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Nuclear trafficking, histone cleavage and induction of apoptosis by the meningococcal App and MspA autotransporters
- 2015
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In: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 17:7, s. 1008-1020
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Journal article (peer-reviewed)abstract
- Neisseria meningitidis, a major cause of bacterial meningitis and septicaemia, secretes multiple virulence factors, including the adhesion and penetration protein (App) and meningococcal serine protease A (MspA). Both are conserved, immunogenic, type Va autotransporters harbouring S6-family serine endopeptidase domains. Previous work suggested that both could mediate adherence to human cells, but their precise contribution to meningococcal pathogenesis was unclear. Here, we confirm that App and MspA are in vivo virulence factors since human CD46-expressing transgenic mice infected with meningococcal mutants lacking App, MspA or both had improved survival rates compared with mice infected with wild type. Confocal imaging showed that App and MspA were internalized by human cells and trafficked to the nucleus. Cross-linking and enzyme-linked immuno assay (ELISA) confirmed that mannose receptor (MR), transferrin receptor 1 (TfR1) and histones interact with MspA and App. Dendritic cell (DC) uptake could be blocked using mannan and transferrin, the specific physiological ligands for MR and TfR1, whereas in vitro clipping assays confirmed the ability of both proteins to proteolytically cleave the core histone H3. Finally, we show that App and MspA induce a dose-dependent increase in DC death via caspase-dependent apoptosis. Our data provide novel insights into the roles of App and MspA in meningococcal infection.
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| 20. |
- Vassey, Matthew, et al.
(author)
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G1 Cell Cycle Arrest Is Induced by the Fourth Extracellular Loop of Meningococcal PorA in Epithelial and Endothelial Cells
- 2023
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In: Cellular Microbiology. - 1462-5814 .- 1462-5822. ; 2023
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Journal article (peer-reviewed)abstract
- Neisseria meningitidis is the most frequent cause of bacterial meningitis and is one of the few bacterial pathogens that can breach the blood-brain barrier (BBB). The 37/67 kDa laminin receptor (LamR) was previously identified as a receptor mediating meningococcal binding to rodent and human brain microvascular endothelial cells, which form part of the BBB. The meningococcal surface proteins PorA and PilQ were identified as ligands for this receptor. Subsequently, the fourth extracellular loop of PorA (PorA-Loop4) was identified as the LamR-binding moiety. Here, we show that PorA-Loop4 targets the 37 kDa laminin receptor precursor (37LRP) on the cell surface by demonstrating that deletion of this loop abrogates the recruitment of 37LRP under meningococcal colonies. Using a circularized peptide corresponding to PorA-Loop4, as well as defined meningococcal mutants, we demonstrate that host cell interaction with PorA-Loop4 results in perturbation of p-CDK4 and Cyclin D1. These changes in cell cycle control proteins are coincident with cellular responses including inhibition of cell migration and a G1 cell cycle arrest. Modulation of the cell cycle of host cells is likely to contribute to the pathogenesis of meningococcal disease.
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