Wall conditioning on ITER Shimada, Michiya; Pitts, Richard A.
Journal of nuclear materials,
08/2011, Letnik:
415, Številka:
1
Journal Article, Conference Proceeding
Recenzirano
Like all tokamaks, ITER will require wall conditioning systems and strategies for successful operation from the point of view of plasma-facing surface preparation. Unlike today’s devices however, ...ITER will have to manage large quantities of tritium fuel, imposing on wall conditioning a major responsibility for tritium inventory control. It will also feature the largest plasma-facing beryllium surface ever used in a tokamak and its high duty cycle and long pulse are expected to lead to the rapid formation of deposited layers in which tritium can accumulate. This paper summarises the currently planned ITER wall conditioning systems and describes the strategy for their use throughout exploitation of the device.
Interferon regulatory factor (IRF) family members impart cell-type specificity to toll-like receptor (TLR) signalling, and we recently identified a role for IRF6 in TLR2 signalling in epithelial ...cells. TLR3 has a well-characterized role in wound healing in the skin, and here, we examined TLR3-dependent IRF6 functions in human keratinocytes. Primary keratinocytes responded robustly to the TLR3 agonist poly(IC) with upregulation of mRNAs for interferon-β (IFN-β), the interleukin-12 (IL-12) family member IL-23p19 and the chemokines IL-8 and chemokine (C-C motif) ligand 5 (CCL5). Silencing of IRF6 expression enhanced poly(IC)-inducible IFN-β mRNA levels and inhibited poly(IC)-inducible IL-23p19 mRNA expression in primary keratinocytes. Consistent with these data, co-transfection of IRF6 increased poly(IC)-inducible IL-23p19 promoter activity, but inhibited poly(IC)-inducible IFN-β promoter activity in reporter assays. Surprisingly, poly(IC) did not regulate IL-12p40 expression in keratinocytes, suggesting that TLR3-inducible IL-23p19 may have an IL-23-independent function in these cells. The only other IL-12 family member that was strongly poly(IC) inducible was EBI3, which has not been shown to heterodimerize with IL-23p19. Both co-immunoprecipitation and proximity ligation assays revealed that IL-23p19 and EBI3 interact in cells. Co-expression of IL-23p19 and EBI3, as compared with IL-23p19 alone, resulted in increased levels of secreted IL-23p19, implying a functional role for this heterodimer. In summary, we report that IRF6 regulates a subset of TLR3 responses in human keratinocytes, including the production of a novel IL-12 family heterodimer (p19/EBI3). We propose that the TLR3-IRF6-p19/EBI3 axis may regulate keratinocyte and/or immune cell functions in the context of cell damage and wound healing in the skin.
ITER Pre‐Fusion Power Operation 1 (PFPO‐1) phase low‐power plasmas are simulated with the SOLEDGE3X‐EIRENE code, a multi‐fluid edge plasma solver that can describe plasma conditions up to the ...machine's first wall, including a kinetic description of neutrals. Here, SOLEDGE3X is used in 2D mean‐field mode. A throughput scan is performed, reproducing a similar scan from the ITER SOLPS simulations database. The physics assumptions for these simulations are presented, in particular the plasma–neutral interaction model where molecule charge‐exchange and ion‐molecule elastic collisions have newly been added. Challenges encountered in such up‐to‐the‐wall simulations are discussed, along with remaining open questions. Results are presented with two foci: on targets, and on the rest of the first wall. On targets, conditions transition from attached to partially detached as expected, and toroidally symmetric heat fluxes (i.e. without 3D effects) remain below 5 MW/m2, within the divertor design limits. An increase in the parallel heat flux decay length λq with throughput is also observed. On the rest of the first wall, increasing puff rate does not only spread power deposited on the target but also increases heat load on the first wall. These fluxes remain however small (<100 kW/m2).
Vascular endothelial growth factor (VEGF)-D was identified as a potential predictive biomarker for ramucirumab efficacy in second-line metastatic colorectal cancer using a research use only (RUO) ...assay. We describe results with a new assay for detecting VEGF-D in human plasma.
In RAISE (Clinical Trial Registration: NCT01183780), 1072 patients were randomized 1:1 to ramucirumab or placebo plus FOLFIRI. All patients were then randomized 1:2 to marker exploratory (ME) and marker confirmatory (MC) groups, and those with plasma samples were analyzed accordingly. A new assay validated for investigational use only (IUO) was used to measure VEGF-D levels in plasma, which were analyzed for correlation with overall and progression-free survival (OS/PFS). IUO assay data were compared with historical RUO assay data.
ME subset analyses determined the optimal cutpoint of 5.4 ng/mL for defining high/low VEGF-D subgroups. In the combined ME/MC placebo arms, OS/PFS were numerically greater for patients with low vs high VEGF-D (OS: 12.8 vs 11.1 months; PFS: 5.6 vs 4.2 months). In patients with high VEGF-D, ramucirumab vs placebo demonstrated a numerically greater improvement in OS and PFS. Differential efficacy by VEGF-D level was statistically significant for PFS, but not OS.
In patients with high VEGF-D, ramucirumab demonstrated a greater improvement in OS and PFS vs placebo; however, baseline VEGF-D level was not predictive of ramucirumab OS benefit using VEGF-D assay for IUO. The RAISE intent-to-treat results remain valid.
ERO2.0 is a recently developed Monte‐Carlo code for modelling global erosion and redeposition in fusion devices. We report here on the code's application to ITER for studying the erosion of the ...beryllium (Be) first wall armour under burning plasma steady state diverted conditions. An important goal of the study is to provide synthetic signals for the design of two key diagnostics: the main chamber visible spectroscopy and the laser in‐vessel viewing systems. The simulations are performed using toroidally symmetric plasma backgrounds obtained by combining SOLPS simulations extended to the wall using the OSM‐EIRENE‐DIVIMP edge code package. These are then further combined with a shadowing model using magnetic field line tracing to provide a three‐dimensional correction for the flux patterns. The resulting plasma wetted area, which amounts to ∼10% of the total first wall area, is in excellent agreement with shadowing calculations obtained with the SMITER field line tracing code. The simulations reveal that the main Be erosion zones are located in regions intersected by the secondary separatrix, in particular the upper Be panels, which are close to the secondary X‐point. For the particular high‐density Q = 10 background plasma case studied here, ∼80% of the eroded Be is found to re‐deposit on main chamber surfaces. The rest migrates in almost equal parts to the inner and outer divertor and is deposited close to the strike lines.
Preventable harms from medications are significant threats to patient safety in community settings, especially among ambulatory older adults on multiple prescription medications. Patients may partner ...with primary care professionals by taking on active roles in decisions, learning the basics of medication self-management, and working with community resources.
This study aims to assess the impact of a set of patient partnership tools that redesign primary care encounters to encourage and empower patients to make more effective use of those encounters to improve medication safety.
The study is a nonrandomized, cross-sectional stepped wedge cluster-controlled trial with 1 private family medicine clinic and 2 public safety-net primary care clinics each composing their own cluster. There are 2 intervention sequences with 1 cluster per sequence and 1 control sequence with 1 cluster. Cross-sectional surveys will be taken immediately at the conclusion of visits to the clinics during 6 time periods of 6 weeks each, with a transition period of no data collection during intervention implementation. The number of visits to be surveyed will vary by period and cluster. We plan to recruit patients and professionals for surveys during 405 visits. In the experimental periods, visits will be conducted with two partnership tools and associated clinic process changes: (1) a 1-page visit preparation guide given to relevant patients by clinic staff before seeing the provider, with the intention to improve communication and shared decision-making, and (2) a library of short educational videos that clinic staff encourage patients to watch on medication safety. In the control periods, visits will be conducted with usual care. The primary outcome will be patients' self-efficacy in medication use. The secondary outcomes are medication-related issues such as duplicate therapies identified by primary care providers and assessment of collaborative work during visits.
The study was funded in September 2019. Data collection started in April 2023 and ended in December 2023. Data was collected for 405 primary care encounters during that period. As of February 15, 2024, initial descriptive statistics were calculated. Full data analysis is expected to be completed and published in the summer of 2024.
This study will assess the impact of patient partnership tools and associated process changes in primary care on medication use self-efficacy and medication-related issues. The study is powered to identify types of patients who may benefit most from patient engagement tools in primary care visits.
ClinicalTrials.gov NCT05880368; https://clinicaltrials.gov/study/NCT05880368.
DERR1-10.2196/57878.
•SOLPS-ITER predictive modeling with drifts of Ne and N seeded JET high power H-mode.•Ne as efficient as N at separatrix Zeff < 1.5 decreasing target heat load by factor ~3.•Better divertor retention ...of N then Ne in deep detachment.•Beneficial impact of machine size in improving impurity retention.
A numerical study is presented, using the SOLPS-ITER plasma boundary code with full drifts and currents activated, of impurity seeded JET discharges in support of high power H-mode experimental campaigns designed to compare two ITER candidate seeding species, nitrogen (N) and neon (Ne). Fluid-kinetic edge plasma simulations are first performed at lower levels of power into the scrape-off layer (SOL) and benchmarked against existing JET experimental data. Calculations are then performed for higher levels of SOL power to examine the impact of this key parameter on the efficiency of both radiators. From the code point of view, for the chosen JET parameters, Ne can be as efficient a divertor radiator as N at the same level of upstream separatrix Zeff < 1.5 for moderate seeding, decreasing the peak power at outer target by factor ~ 3. Full detachment (state with the temperature below 5 eV along all the target) at the outer target can be obtained with both impurities at higher seeding, but in the case of Ne this leads to a higher Zeff and significant radiation in the main SOL/pedestal. The indications from this JET code modelling, in comparison with previous similar simulations for ITER and ASDEX Upgrade with drifts turned on, are that there is a beneficial impact of machine size in improving impurity retention, substantiating the claim that both N and Ne will perform well as seed impurities for divertor power dissipation in ITER.
To examine the effects of “ALL YOU NEED IS LOVE”, a novel six-week, self-directed patient education manual designed to improve chronic kidney disease knowledge/self-management, health care transition ...readiness, self-advocacy, and mindfulness skills among adolescents with chronic kidney disease.
We enrolled 49 adolescents aged 11–17 years (mean age 14.7 ± 1.9; 53.1% males) from a university hospital kidney center who had CKD stages 3 and greater, who were randomly assigned into the “ALL YOU NEED IS LOVE” patient education only group (n = 31) or the “ALL YOU NEED IS LOVE” patient education plus mindfulness training group (n = 18). Participants completed Qualtrics surveys at baseline, post-intervention, and three-month follow-up. The survey included measures of outcome variables (i.e., self-management/transition readiness, patient self-advocacy, and mindfulness), and an additional demographic questionnaire was included in the baseline survey. Multilevel model analyses were used to examine the effects of group and time on the outcome variables.
Multilevel model analyses showed an overall significant time effect across all outcome variables in both groups. However, the group effects were not statistically significant across the outcome variables.
Both interventions significantly increased participants' self-management/HCT readiness, self-advocacy, and mindfulness over time. Mindfulness training may not bring additional benefits to the “ALL YOU NEED IS LOVE” education manual.
Pediatric nurses and clinicians may utilize the self-directed “ALL YOU NEED IS LOVE” manual to increase self-management/transition readiness, self-advocacy, and mindfulness among adolescents with chronic kidney disease.
•A patient education manual for adolescents with chronic kidney disease was developed.•The manual improved self-management and health care transition readiness over time.•The manual showed additional benefits in improving self-advocacy and mindfulness.•Adding a mindfulness training did not bring additional benefits to the manual.
The compound U0126 (1,4-diamino-2,3-dicyano-1, 4-bis2-aminophenylthiobutadiene) was identified as an inhibitor of AP-1 transactivation in a cell-based reporter assay. U0126 was also shown to inhibit ...endogenous promoters containing AP-1 response elements but did not affect genes lacking an AP-1 response element in their promoters. These effects of U0126 result from direct inhibition of the mitogen-activated protein kinase kinase family members, MEK-1 and MEK-2. Inhibition is selective for MEK-1 and -2, as U0126 shows little, if any, effect on the kinase activities of protein kinase C, Abl, Raf, MEKK, ERK, JNK, MKK-3, MKK-4/SEK, MKK-6, Cdk2, or Cdk4. Comparative kinetic analysis of U0126 and the MEK inhibitor PD098059 (Dudley, D. T., Pang, L., Decker, S. J., Bridges, A. J., and Saltiel, A. R. (1995) Proc. Natl. Acad. Sci U. S. A. 92, 7686-7689) demonstrates that U0126 and PD098059 are noncompetitive inhibitors with respect to both MEK substrates, ATP and ERK. We further demonstrate that the two compounds bind to deltaN3-S218E/S222D MEK in a mutually exclusive fashion, suggesting that they may share a common or overlapping binding site(s). Quantitative evaluation of the steady state kinetics of MEK inhibition by these compounds reveals that U0126 has approximately 100-fold higher affinity for deltaN3-S218E/S222D MEK than does PD098059. We further tested the effects of these compounds on the activity of wild type MEK isolated after activation from stimulated cells. Surprisingly, we observe a significant diminution in affinity of both compounds for wild type MEK as compared with the deltaN3-S218E/S222D mutant enzyme. These results suggest that the affinity of both compounds is mediated by subtle conformational differences between the two activated MEK forms. The MEK affinity of U0126, its selectivity for MEK over other kinases, and its cellular efficacy suggest that this compound will serve as a powerful tool for in vitro and cellular investigations of mitogen-activated protein kinase-mediated signal transduction.
•Fusion reactors may experience narrow near SOL heat flux channel widths λq.•SOLPS-ITER simulation was performed for ITER with λq ∼ 1 mm.•Operational window for divertor pressure with λq∼1mm is ...rather narrow.•The inclusion of drifts increases outer target heat fluxes.
SOLPS-ITER code simulations with fluid drifts activated are used to examine the consequences for divertor performance, under burning plasma conditions, of a reduction in scrape-off layer (SOL) cross-field transport such that the outboard midplane SOL parallel heat flux width, λq is reduced to the very low values predicted by the experimental scaling in T. Eich et al., Nucl. Fusion 53 (2013) 093031 for high plasma current operation on ITER. The decrease of λq from the standard value (~3.5 mm) used in the ITER SOLPS modeling database, to λq ~ 1–2 mm expected from the scaling, leads to a strong narrowing of the operational window in terms of divertor heat loading limits. To maintain similar levels of sub-divertor neutral pressure, pn (one of the key divertor operational parameters) as those obtained with standard transport, higher levels of neon impurity seeding are required when transport is reduced, yielding higher Zeff at the upstream separatrix and requiring further integrated modelling to assess the impact on confinement. The simulations also demonstrate that the strong increase in in-out target peak power loading asymmetry at low pn seen for standard transport when drifts are switched on in the code is preserved, and in fact worsens, for low transport. This significantly reduces margins for power handling control at lower pn if heat flux channels will be narrow on ITER.
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