| 1. |
- Abel, I, et al.
(author)
-
Overview of the JET results with the ITER-like wall
- 2013
-
In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
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Journal article (peer-reviewed)abstract
- Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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| 2. |
- Romanelli, F, et al.
(author)
-
Overview of the JET results
- 2011
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
-
Journal article (peer-reviewed)abstract
- Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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| 3. |
- van Haarlem, M. P., et al.
(author)
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LOFAR : The LOw-Frequency ARray
- 2013
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 556, s. 1-53
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Journal article (peer-reviewed)abstract
- LOFAR, the LOw-Frequency ARray, is a new-generation radio interferometer constructed in the north of the Netherlands and across europe. Utilizing a novel phased-array design, LOFAR covers the largely unexplored low-frequency range from 10–240 MHz and provides a number of unique observing capabilities. Spreading out from a core located near the village of Exloo in the northeast of the Netherlands, a total of 40 LOFAR stations are nearing completion. A further five stations have been deployed throughout Germany, and one station has been built in each of France, Sweden, and the UK. Digital beam-forming techniques make the LOFAR system agile and allow for rapid repointing of the telescope as well as the potential for multiple simultaneous observations. With its dense core array and long interferometric baselines, LOFAR achieves unparalleled sensitivity and angular resolution in the low-frequency radio regime. The LOFAR facilities are jointly operated by the International LOFAR Telescope (ILT) foundation, as an observatory open to the global astronomical community. LOFAR is one of the first radio observatories to feature automated processing pipelines to deliver fully calibrated science products to its user community. LOFAR’s new capabilities, techniques and modus operandi make it an important pathfinder for the Square Kilometre Array (SKA). We give an overview of the LOFAR instrument, its major hardware and software components, and the core science objectives that have driven its design. In addition, we present a selection of new results from the commissioning phase of this new radio observatory.
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| 4. |
- Hermsen, W., et al.
(author)
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Synchronous X-ray and Radio Mode Switches: A Rapid Global Transformation of the Pulsar Magnetosphere
- 2013
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 339:6118, s. 436-439
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Journal article (peer-reviewed)abstract
- Pulsars emit from low-frequency radio waves up to high-energy gamma-rays, generated anywhere from the stellar surface out to the edge of the magnetosphere. Detecting correlated mode changes across the electromagnetic spectrum is therefore key to understanding the physical relationship among the emission sites. Through simultaneous observations, we detected synchronous switching in the radio and x-ray emission properties of PSR B0943+10. When the pulsar is in a sustained radio-"bright" mode, the x-rays show only an unpulsed, nonthermal component. Conversely, when the pulsar is in a radio-"quiet" mode, the x-ray luminosity more than doubles and a 100% pulsed thermal component is observed along with the nonthermal component. This indicates rapid, global changes to the conditions in the magnetosphere, which challenge all proposed pulsar emission theories.
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| 5. |
- Stappers, B. W., et al.
(author)
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Observing pulsars and fast transients with LOFAR
- 2011
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 530
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Journal article (peer-reviewed)abstract
- Low frequency radio waves, while challenging to observe, are a rich source of information about pulsars. The LOw Frequency ARray (LOFAR) is a new radio interferometer operating in the lowest 4 octaves of the ionospheric "radio window": 10-240 MHz, that will greatly facilitate observing pulsars at low radio frequencies. Through the huge collecting area, long baselines, and flexible digital hardware, it is expected that LOFAR will revolutionize radio astronomy at the lowest frequencies visible from Earth. LOFAR is a next-generation radio telescope and a pathfinder to the Square Kilometre Array (SKA), in that it incorporates advanced multi-beaming techniques between thousands of individual elements. We discuss the motivation for low-frequency pulsar observations in general and the potential of LOFAR in addressing these science goals. We present LOFAR as it is designed to perform high-time-resolution observations of pulsars and other fast transients, and outline the various relevant observing modes and data reduction pipelines that are already or will soon be implemented to facilitate these observations. A number of results obtained from commissioning observations are presented to demonstrate the exciting potential of the telescope. This paper outlines the case for low frequency pulsar observations and is also intended to serve as a reference for upcoming pulsar/fast transient science papers with LOFAR.
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| 6. |
- Coenen, T., et al.
(author)
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The LOFAR pilot surveys for pulsars and fast radio transients
- 2014
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 570, s. 1-16
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Journal article (peer-reviewed)abstract
- We have conducted two pilot surveys for radio pulsars and fast transients with the Low-Frequency Array (LOFAR) around 140 MHz and here report on the first low-frequency fast-radio burst limit and the discovery of two new pulsars. The first survey, the LOFAR Pilot Pulsar Survey (LPPS), observed a large fraction of the northern sky, ~ 1.4 × 104 deg2, with 1 h dwell times. Each observation covered ~75 deg2 using 7 independent fields formed by incoherently summing the high-band antenna fields. The second pilot survey, the LOFAR Tied-Array Survey (LOTAS), spanned ~600 deg2, with roughly a 5-fold increase in sensitivity compared with LPPS. Using a coherent sum of the 6 LOFAR “Superterp” stations, we formed 19 tied-array beams, together covering 4 deg2 per pointing. From LPPS we derive a limit on the occurrence, at 142 MHz, of dispersed radio bursts of < 150 day-1 sky-1, for bursts brighter than S> 107 Jy for the narrowest searched burst duration of 0.66 ms. In LPPS, we re-detected 65 previously known pulsars. LOTAS discovered two pulsars, the first with LOFAR or any digital aperture array. LOTAS also re-detected 27 previously known pulsars. These pilot studies show that LOFAR can efficiently carry out all-sky surveys for pulsars and fast transients, and they set the stage for further surveying efforts using LOFAR and the planned low-frequency component of the Square Kilometer Array.
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| 7. |
- Hassall, T. E., et al.
(author)
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Differential frequency-dependent delay from the pulsar magnetosphere
- 2013
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 552
-
Journal article (peer-reviewed)abstract
- Some radio pulsars show clear "drifting subpulses", in which subpulses are seen to drift in pulse longitude in a systematic pattern. Here we examine how the drifting subpulses of PSR B0809+74 evolve with time and observing frequency. We show that the subpulse period (P-3) is constant on timescales of days, months and years, and between 14-5100 MHz. Despite this, the shapes of the driftbands change radically with frequency. Previous studies have concluded that, while the subpulses appear to move through the pulse window approximately linearly at low frequencies ( 820 MHz) near to the peak of the average pulse profile. We use LOFAR, GMRT, GBT, WSRT and Effelsberg 100-m data to explore the frequency-dependence of this phase step. We show that the size of the subpulse phase step increases gradually, and is observable even at low frequencies. We attribute the subpulse phase step to the presence of two separate driftbands, whose relative arrival times vary with frequency - one driftband arriving 30 pulses earlier at 20 MHz than it does at 1380 MHz, whilst the other arrives simultaneously at all frequencies. The drifting pattern which is observed here cannot be explained by either the rotating carousel model or the surface oscillation model, and could provide new insight into the physical processes happening within the pulsar magnetosphere.
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| 8. |
- Maddison, G. P., et al.
(author)
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Contrasting H-mode behaviour with deuterium fuelling and nitrogen seeding in the all-carbon and metallic versions of JET
- 2014
-
In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 54:7, s. 073016-
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Journal article (peer-reviewed)abstract
- The former all-carbon wall on JET has been replaced with beryllium in the main torus and tungsten in the divertor to mimic the surface materials envisaged for ITER. Comparisons are presented between type I H-mode characteristics in each design by examining respective scans over deuterium fuelling and impurity seeding, required to ameliorate exhaust loads both in JET at full capability and in ITER. Attention is focused upon a common high-triangularity, single-null divertor configuration at 2.5 MA, q(95) approximate to 3.5 yielding the most robust all-C performance. Contrasting results between the alternative linings are found firstly in unseeded plasmas, for which purity is improved and intrinsic radiation reduced in the ITER-like wall (ILW) but normalized energy confinement is approximate to 30% lower than in all-C counterparts, owing to a commensurately lower (electron) pedestal temperature. Divertor recycling is also radically altered, with slower, inboard-outboard asymmetric transients at ELMs and spontaneous oscillations in between them. Secondly, nitrogen seeding elicits opposite responses in the ILW to all-C experience, tending to raise plasma density, reduce ELM frequency, and above all to recover (electron) pedestal pressure, hence global confinement, almost back to previous levels. A hitherto unrecognized role of light impurities in pedestal stability and dynamics is consequently suggested. Thirdly, while heat loads on the divertor outboard target between ELMs are successfully reduced in proportion to the radiative cooling and ELM frequency effects of N in both wall environments, more surprisingly, average power ejected by ELMs also declines in the same proportion for the ILW. Detachment between transients is simultaneously promoted. Finally, inter-ELM W sources in the ILW divertor tend to fall with N input, although core accumulation possibly due to increased particle confinement still leads to significantly less steady conditions than in all-C plasmas. This limitation of ILW H-modes so far will be readdressed in future campaigns to continue progress towards a fully integrated scenario suitable for D-T experiments on JET and for 'baseline' operation on ITER. The diverse changes in behaviour between all-C and ILW contexts demonstrate essentially the strong impact which boundary conditions and intrinsic impurities can have on tokamak-plasma states.
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| 9. |
- Diaz-Gallo, L. M., et al.
(author)
-
Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis
- 2011
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:3, s. 454-462
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Journal article (peer-reviewed)abstract
- Objective Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. Methods 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. Results The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p(FDRcorrected) = 0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p(FDRcorrected) = 0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p(FDRcorrected) = 0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p = 0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). Conclusion The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.
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| 10. |
- Giroud, C., et al.
(author)
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Impact of nitrogen seeding on confinement and power load control of a high-triangularity JET ELMy H-mode plasma with a metal wall
- 2013
-
In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:11, s. 113025-
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Journal article (peer-reviewed)abstract
- This paper reports the impact on confinement and power load of the high-shape 2.5MA ELMy H-mode scenario at JET of a change from all carbon plasma-facing components to an all metal wall. In preparation to this change, systematic studies of power load reduction and impact on confinement as a result of fuelling in combination with nitrogen seeding were carried out in JET-C and are compared with their counterpart in JET with a metallic wall. An unexpected and significant change is reported on the decrease in the pedestal confinement but is partially recovered with the injection of nitrogen.
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| 11. |
- Joffrin, E., et al.
(author)
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First scenario development with the JET new ITER-like wall
- 2014
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 54:1, s. 013011-
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Journal article (peer-reviewed)abstract
- In the recent JET experimental campaigns with the new ITER-like wall (JET-ILW), major progress has been achieved in the characterization and operation of the H-mode regime in metallic environments: (i) plasma breakdown has been achieved at the first attempt and X-point L-mode operation recovered in a few days of operation; (ii) stationary and stable type-I ELMy H-modes with beta(N) similar to 1.4 have been achieved in low and high triangularity ITER-like shape plasmas and are showing that their operational domain at H = 1 is significantly reduced with the JET-ILW mainly because of the need to inject a large amount of gas (above 10(22) Ds(-1)) to control core radiation; (iii) in contrast, the hybrid H-mode scenario has reached an H factor of 1.2-1.3 at beta(N) of 3 for 2-3 s; and, (iv) in comparison to carbon equivalent discharges, total radiation is similar but the edge radiation is lower and Z(eff) of the order of 1.3-1.4. Strong core radiation peaking is observed in H-mode discharges at a low gas fuelling rate (i. e. below 0.5 x 10(22) Ds(-1)) and low ELM frequency (typically less than 10 Hz), even when the tungsten influx from the diverter is constant. High-Z impurity transport from the plasma edge to the core appears to be the dominant factor to explain these observations. This paper reviews the major physics and operational achievements and challenges that an ITER-like wall configuration has to face to produce stable plasma scenarios with maximized performance.
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| 12. |
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| 13. |
- Neu, R., et al.
(author)
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First operation with the JET International Thermonuclear Experimental Reactor-like wall
- 2013
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In: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 20:5, s. 056111-1-056111-13
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Journal article (peer-reviewed)abstract
- To consolidate International Thermonuclear Experimental Reactor (ITER) design choices and prepare for its operation, Joint European Torus (JET) has implemented ITER's plasma facing materials, namely, Be for the main wall and W in the divertor. In addition, protection systems, diagnostics, and the vertical stability control were upgraded and the heating capability of the neutral beams was increased to over 30 MW. First results confirm the expected benefits and the limitations of all metal plasma facing components (PFCs) but also yield understanding of operational issues directly relating to ITER. H-retention is lower by at least a factor of 10 in all operational scenarios compared to that with C PFCs. The lower C content (≈ factor 10) has led to much lower radiation during the plasma burn-through phase eliminating breakdown failures. Similarly, the intrinsic radiation observed during disruptions is very low, leading to high power loads and to a slow current quench. Massive gas injection using a D2/Ar mixture restores levels of radiation and vessel forces similar to those of mitigated disruptions with the C wall. Dedicated L-H transition experiments indicate a 30% power threshold reduction, a distinct minimum density, and a pronounced shape dependence. The L-mode density limit was found to be up to 30% higher than for C allowing stable detached divertor operation over a larger density range. Stable H-modes as well as the hybrid scenario could be re-established only when using gas puff levels of a few 1021 es-1. On average, the confinement is lower with the new PFCs, but nevertheless, H factors up to 1 (H-Mode) and 1.3 (at β N ≈ 3, hybrids) have been achieved with W concentrations well below the maximum acceptable level.
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| 14. |
- Rueda, B., et al.
(author)
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BANK1 functional variants are associated with susceptibility to diffuse systemic sclerosis in Caucasians
- 2010
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:4, s. 700-705
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Journal article (peer-reviewed)abstract
- Objective To investigate the possible association of the BANK1 gene with genetic susceptibility to systemic sclerosis (SSc) and its subphenotypes. Methods A large multicentre case-control association study including 2380 patients with SSc and 3270 healthy controls from six independent case-control sets of Caucasian ancestry ( American, Spanish, Dutch, German, Swedish and Italian) was conducted. Three putative functional BANK1 polymorphisms (rs17266594 T/C, rs10516487 G/A, rs3733197 G/A) were selected as genetic markers and genotyped by Taqman 5' allelic discrimination assay. Results A significant association of the rs10516487 G and rs17266594 T alleles with SSc susceptibility was observed (pooled OR=1.12, 95% CI 1.03 to 1.22; p=0.01 and pooled OR=1.14, 95% CI 1.05 to 1.25; p=0.003, respectively), whereas the rs3733197 genetic variant showed no statistically significant deviation. Stratification for cutaneous SSc phenotype showed that the BANK1 rs10516487 G, rs17266594 T and rs3733197 G alleles were strongly associated with susceptibility to diffuse SSc (dcSSc) (pooled OR=1.20, 95% CI 1.05 to 1.37, p=0.005; pooled OR=1.23, 95% CI 1.08 to 1.41, p=0.001; pooled OR=1.15, 95% CI 1.02 to 1.31, p=0.02, respectively). Similarly, stratification for specific SSc autoantibodies showed that the association of BANK1 rs10516487, rs17266594 and rs3733197 polymorphisms was restricted to the subgroup of patients carrying anti-topoisomerase I antibodies (pooled OR=1.20, 95% CI 1.02 to 1.41, p=0.03; pooled OR=1.24, 95% CI 1.05 to 1.46, p=0.01; pooled OR=1.26, 95% CI 1.07 to 1.47, p=0.004, respectively). Conclusion The results suggest that the BANK1 gene confers susceptibility to SSc in general, and specifically to the dcSSc and anti-topoisomerase I antibody subsets.
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| 15. |
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| 16. |
- Butler, C.C., et al.
(author)
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Antibiotic prescribing for discoloured sputum in acute cough/lower respiratory tract infection
- 2011
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In: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 38:1, s. 119-125
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Journal article (peer-reviewed)abstract
- We investigated whether discoloured sputum and feeling unwell were associated with antibiotic prescription and benefit from antibiotic treatment for acute cough/lower respiratory tract infection (LTRI) in a prospective study of 3,402 adults in 13 countries. A two-level model investigated the association between producing discoloured sputum or feeling generally unwell and an antibiotic prescription. A three-level model investigated the association between an antibiotic prescription and symptom resolution. Patients producing discoloured sputum were prescribed antibiotics more frequently than those not producing sputum (OR 3.2, 95% CI 2.1-5.0), unlike those producing clear/white sputum (OR 0.95, 95% CI 0.61-1.48). Antibiotic prescription was not associated with a greater rate or magnitude of symptom score resolution (as measured by a 13-item questionnaire completed by patients each day) among those who: produced yellow (coefficient 0.00; p=0.68) or green (coefficient -0.01; p=0.11) sputum; reported any of three categories of feeling unwell; or produced discoloured sputum and felt generally unwell (coefficient -0.01; p=0.19). Adults with acute cough/LRTI presenting in primary care settings with discoloured sputum were prescribed antibiotics more often compared to those not producing sputum. Sputum colour, alone or together with feeling generally unwell, was not associated with recovery or benefit from antibiotic treatment.
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| 17. |
- Broen, J. C. A., et al.
(author)
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A rare polymorphism in the gene for Toll-like receptor 2 is associated with systemic sclerosis phenotype and increases the production of inflammatory mediators
- 2012
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In: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 64:1, s. 264-271
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Journal article (peer-reviewed)abstract
- Objective To investigate whether polymorphisms in Toll-like receptor (TLR) genes, previously reported to be associated with immune-mediated diseases, are involved in systemic sclerosis (SSc). Methods. We genotyped 14 polymorphisms in the genes for TLRs 2, 4, 7, 8, and 9 in a discovery cohort comprising 452 SSc patients and 537 controls and a replication cohort consisting of 1,170 SSc patients and 925 controls. In addition, we analyzed 15-year followup data on 964 patients to assess the potential association of TLR variants with the development of disease complications. We analyzed the functional impact of the associated polymorphism on monocyte-derived dendritic cells. Results. In the discovery cohort, we observed that a rare functional polymorphism in TLR2 (Pro631His) was associated with antitopoisomerase (antitopo) positivity (odds ratio 2.24 [95% confidence interval 1.24-4.04], P = 0.003). This observation was validated in the replication cohort (odds ratio 2.73 [95% confidence interval 1.85-4.04], P = 0.0001). In addition, in the replication cohort the TLR2 variant was associated with the diffuse subtype of the disease (P = 0.02) and with the development of pulmonary arterial hypertension (PAH) (Cox proportional hazards ratio 5.61 [95% confidence interval 1.53-20.58], P = 0.003 by log rank test). Functional analysis revealed that monocyte-derived dendritic cells carrying the Pro63His variant produced increased levels of inflammatory mediators (tumor necrosis factor alpha and interleukin-6) upon TLR-2-mediated stimulation (both P < 0.0001). Conclusion. Among patients with SSc, the rare TLR2 Pro631His variant is robustly associated with antitopoisomerase positivity, the diffuse form of the disease, and the development of PAH. In addition, this variant influences TLR-2-mediated cell responses. Further research is needed to elucidate the precise role of TLR-2 in the pathogenesis of SSc.
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| 18. |
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| 19. |
- Coenen, J. W., et al.
(author)
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Long-term evolution of the impurity composition and impurity events with the ITER-like wall at JET
- 2013
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:7, s. 073043-
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Journal article (peer-reviewed)abstract
- This paper covers aspects of long-term evolution of intrinsic impurities in the JET tokamak with respect to the newly installed ITER-like wall (ILW). At first the changes related to the change over from the JET-C to the JET-ILW with beryllium (Be) as the main wall material and tungsten (W) in the divertor are discussed. The evolution of impurity fluxes in the newly installed W divertor with respect to studying material migration is described. In addition, a statistical analysis of transient impurity events causing significant plasma contamination and radiation losses is shown. The main findings comprise a drop in carbon content (x20) (see also Brezinsek et al (2013 J. Nucl. Mater. 438 S303)), low oxygen content (x10) due to the Be first wall (Douai et al 2013 J. Nucl. Mater. 438 S1172-6) as well as the evolution of the material mix in the divertor. Initially, a short period of repetitive ohmic plasmas was carried out to study material migration (Krieger et al 2013 J. Nucl. Mater. 438 S262). After the initial 1600 plasma seconds the material surface composition is, however, still evolving. With operational time, the levels of recycled C are increasing slightly by 20% while the Be levels in the deposition-dominated inner divertor are dropping, hinting at changes in the surface layer material mix made of Be, C and W. A steady number of transient impurity events, consisting of W and constituents of inconel, is observed despite the increase in variation in machine operation and changes in magnetic configuration as well as the auxiliary power increase.
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| 20. |
- Coenen, J. W., et al.
(author)
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Tungsten erosion in the all-metal tokamaks JET and ASDEX Upgrade
- 2012
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In: 39th EPS Conference on Plasma Physics 2012, EPS 2012 and the 16th International Congress on Plasma Physics. - 9781622769810 ; , s. 253-256
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Conference paper (peer-reviewed)abstract
- The tungsten source in the all W outer divertor and Be main wall configuration has been quantified mainly during L-mode plasmas and compared to AUG Data both gained from local spectroscopy. Results so far show differences between AUG and JET based on impurities in the plasma changing the sputter behavior. This stresses the need for detailed analysis of the divertor impurity composition and detailed molding in the future analysis. The H-Mode examples indicate at ELM dominated sputtering and a rather low averaged sputtering yield in general. Nitrogen seeding can change the divertor conditions significantly either increasing W sputtering or suppressing it due to local cooling, JET and AUG behave similarly. All together it is clear that by having low divertor temperature or a beneficial impurity composition sputtering can be controlled and is rather low as expected in an all metal environment.
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| 21. |
- Coenen, Marieke J H, et al.
(author)
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Genetic Variants in Toll-Like Receptors Are Not Associated with Rheumatoid Arthritis Susceptibility or Anti-Tumour Necrosis Factor Treatment Outcome
- 2010
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:12
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Journal article (peer-reviewed)abstract
- Background: Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication. Methodology and Principal Findings: 22 single nucleotide polymorphisms (SNPs) in seven TLR genes were genotyped in a Dutch cohort consisting of 378 RA patients and 294 controls. Significantly associated variants were investigated in replication cohorts from The Netherlands, United Kingdom and Sweden (2877 RA patients and 2025 controls). 182 of the Dutch patients were treated with anti-TNF medication. Using these patients and a replication cohort (269 Swedish patients) we analysed if genetic variants in TLR genes were associated with anti-TNF outcome. In the discovery phase of the study we found a significant association of SNPs rs2072493 in TLR5 and rs3853839 in TLR7 with RA disease susceptibility. Meta-analysis of discovery and replication cohorts did not confirm these findings. SNP rs2072493 in TLR5 was associated with anti-TNF outcome in the Dutch but not in the Swedish population. Conclusion: We conclude that genetic variants in TLRs do not play a major role in susceptibility for developing RA nor in anti-TNF treatment outcome in a Caucasian population.
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| 22. |
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| 23. |
- Liang, Y., et al.
(author)
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Mitigation of type-I ELMs with n=2 fields on JET with ITER-like wall
- 2013
-
In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:7, s. 073036-
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Journal article (peer-reviewed)abstract
- Mitigation of type-I edge-localized modes (ELMs) was observed with the application of an n = 2 field in H-mode plasmas on the JET tokamak with the ITER-like wall (ILW). Several new findings with the ILW were identified and contrasted to the previous carbon wall (C-wall) results for comparable conditions. Previous results for high collisionality plasmas (nu*(e,ped) similar to 2.0) with the C-wall saw little or no influence of either n = 1 or n = 2 fields on the ELMs. However, recent observations with the ILW show large type-I ELMs with a frequency of similar to 45 Hz were replaced by high-frequency (similar to 200 Hz) small ELMs during the application of the n = 2 field. With the ILW, splitting of the outer strike point was observed for the first time during the strong mitigation of the type-I ELMs. The maximal surface temperature (T-max) on the outer divertor plate reached a stationary state and has only small variations of a few degrees due to the small mitigated ELMs. In moderate collisionality (nu*(e,ped) similar to 0.8) H-mode plasmas, similar to previous results with the C-wall, both an increase in the ELM frequency and density pump-out were observed during the application of the n = 2 field. There are two new observations compared with the C-wall results. Firstly, the effect of ELM mitigation with the n = 2 field was seen to saturate so that the ELM frequency did not further increase above a certain level of n = 2 magnetic perturbations. Secondly splitting of the outer strike point during the ELM crash was seen, resulting in mitigation of the maximal ELM peak heat fluxes on the divertor region.
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| 24. |
- McKinney, C., et al.
(author)
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Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis
- 2012
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In: Genes and Immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 13:6, s. 458-460
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Journal article (peer-reviewed)abstract
- There is increasing evidence that gene copy number (CN) variation influences clinical phenotype. The low-affinity Fc receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment of polymorphonuclear neutrophils to sites of inflammation and their activation. Given the genetic overlap between systemic lupus erythematosus and systemic sclerosis (SSc) and the strong evidence for FCGR3B CN in the pathology of SLE, we hypothesised that FCGR3B gene dosage influences susceptibility to SSc. We obtained FCGR3B deletion status in 777 European Caucasian cases and 1000 controls. There was an inverse relationship between FCGR3B CN and disease susceptibility. CN of <= 1 was a significant risk factor for SSc (OR = 1.55 (1.13-2.14), P = 0.007) relative to CN >= 2. Although requiring replication, these results suggest that impaired immune complex clearance arising from FCGR3B deficiency contributes to the pathology of SSc, and FCGR3B CN variation is a common risk factor for systemic autoimmunity.
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| 25. |
- Okada, Yukinori, et al.
(author)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Journal article (peer-reviewed)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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