Analysis of the cesium distribution in the JT-60SA negative ion sources for steady long-pulse operation.

To realize stable negative ion beams for 100 s required in the neutral beam injector of JT-60SA, a physical model to control cesium (Cs) distribution inside the negative ion source has been developed in order to maintain the stable negative ion production at the plasma grid (PG) surface with Cs. In this work, to quantitatively evaluate Cs coverage on the PG, a three-dimensional Cs transportation code was introduced to consider the spatial Cs distribution in the source. The spatial temperature distribution of the chamber wall was also introduced in this model. As a result, the reasonable variation of the Cs coverage for 100 s was obtained, compared to that in the initial model. Based on the modified model, the operational temperature of the chamber wall was proposed to be less than 60 °C to suppress the desorption of Cs in the chamber wall and to sustain the stable negative ion production. In addition, it was also suggested that a slightly higher wall temperature before the operation leads to a decrease in the amount of Cs stored at the chamber wall, resulting in suppression of Cs consumption in the ion source.

Achievement of high power and long pulse negative ion beam acceleration for JT-60SA NBI.

Long pulse acceleration of hydrogen negative ion beams with the power density over 70 MW/m2 and the pulse length over 100 s has been demonstrated for the first time by using a multi-aperture 3-stage accelerator. Such long pulse acceleration was achieved by integrating the design of beam optics and voltage holding capability to meet the requirements of JT-60SA. By using the newly designed accelerator for JT-60SA, voltage holding at 500 kV with beam acceleration was stably sustained even after 5 g of cesium was seeded, and heat load on each acceleration grid was reduced below the allowable level for long pulse, less than 5% of total acceleration power. As a result, 500 keV, 154 A/m2 for 118 s beam acceleration was achieved, which satisfies the requirement of the negative ion source for JT-60SA. This pulse length of such high-power density beams is longest in the world. In addition, the result contributes to the long pulse acceleration of multi-stage electrostatic accelerators, such as 1 MeV negative ion accelerator for ITER.

Time evolution of negative ion profile in a large cesiated negative ion source applicable to fusion reactors.

To understand the physics of the cesium (Cs) recycling in the large Cs-seeded negative ion sources relevant to ITER and JT-60SA with ion extraction area of 45-60 cm × 110-120 cm, the time evolution of the negative ion profile was precisely measured in JT-60SA where the ion extraction area is longitudinally segmented into 5. The Cs was seeded from the oven at 180 °C to the ion source. After 1 g of Cs input, surface production of the negative ions appeared only in the central segment where a Cs nozzle was located. Up to 2 g of Cs, the negative ion profile was longitudinally expanded over full ion extraction area. The measured time evolution of the negative ion profile has the similar tendency of distribution of the Cs atoms that is calculated. From the results, it is suggested that Cs atom distribution is correlated with the formation of the negative ion profile.

Development of design technique for vacuum insulation in large size multi-aperture multi-grid accelerator for nuclear fusion.

Design techniques for the vacuum insulation have been developed in order to realize a reliable voltage holding capability of multi-aperture multi-grid (MAMuG) accelerators for fusion application. In this method, the nested multi-stage configuration of the MAMuG accelerator can be uniquely designed to satisfy the target voltage within given boundary conditions. The evaluation of the voltage holding capabilities of each acceleration stages was based on the previous experimental results about the area effect and the multi-aperture effect. Since the multi-grid effect was found to be the extension of the area effect by the total facing area this time, the total voltage holding capability of the multi-stage can be estimated from that per single stage by assuming the stage with the highest electric field, the total facing area, and the total apertures. By applying these consideration, the analysis on the 3-stage MAMuG accelerator for JT-60SA agreed well with the past gap-scan experiments with an accuracy of less than 10% variation, which demonstrated the high reliability to design MAMuG accelerators and also multi-stage high voltage bushings.

Development of the negative ion beams relevant to ITER and JT-60SA at Japan Atomic Energy Agency.

In order to realize negative ion sources and accelerators to be applicable to International Thermonuclear Experimental Reactor and JT-60 Super Advanced, a large cesium (Cs)-seeded negative ion source and a multi-aperture and multi-stage electric acceleration have been developed at Japan Atomic Energy Agency (JAEA). Long pulse production and acceleration of the negative ion beams have been independently carried out. The long pulse production of the high current beams has achieved 100 s at the beam current of 15 A by modifying the JT-60 negative ion source. The pulse duration time is increased three times longer than that before the modification. As for the acceleration, a pulse duration time has been also extended two orders of magnitudes from 0.4 s to 60 s. The developments of the negative ion source and acceleration at JAEA are well in progress towards the realization of the negative ion sources and accelerators for fusion applications.

Specific overexpression of tumour necrosis factor-α-induced protein (TNFAIP)9 in CD14(+) CD16(-) monocytes in patients with rheumatoid arthritis: comparative analysis with TNFAIP3.

The tumour necrosis factor (TNF)-α-induced proteins (TNFAIP)9 and TNFAIP3 play an important pathogenic role in murine arthritis. To clarify their pathophysiological roles in patients with rheumatoid arthritis (RA), we examined their expression and localization in peripheral blood mononuclear cells (PBMC). TNFAIP9 and TNFAIP3 mRNA expression was determined in PBMC of RA patients and healthy subjects (control). Flow cytometry was used to analyse the main TNFAIP9- and TNFAIP3-expressing cell populations. TNFAIP9 and TNFAIP3 mRNA expression levels were examined in vitro on CD14(+) cells stimulated with TNF-α and lipopolysaccharide (LPS). The expression levels of TNFAIP9 and TNFAIP3 mRNA were also measured before and 12 weeks after treatment with tocilizumab and abatacept. TNFAIP9 expression was significantly higher, while TNFAIP3 expression was lower in PBMC of RA (n=36) than the control (n=24) (each P < 0.05). TNFAIP9 was expressed on CD14(+) cells, especially in human leucocyte antigen D-related (HLA-DR)(+) CD14(bright) CD16(-) cells, while TNFAIP3 was expressed mainly on CD3(+) T cells. TNF-α and LPS induced TNFAIP9 and TNFAIP3 in human CD14(+) monocytes in vitro. Treatment with tocilizumab (n=13), but not abatacept (n=11), significantly reduced TNFAIP9 mRNA expression in PBMC, which was associated with reduction in the number of circulating CD14(bright) monocytes. The expression of TNFAIP9 in CD14(+) cells was specifically elevated in patients with RA, regulated by TNF-α and LPS, and suppressed by tocilizumab, while TNFAIP3 in PBMC showed different localization and induction patterns.

Predictors of the response to treatment in acute lupus hemophagocytic syndrome.

OBJECTIVE: The objective of this paper is to identify predictors for the response to treatment of acute lupus hemophagocytic syndrome (ALHS). METHODS: We reviewed seven cases with ALHS admitted to our hospital and published ALHS cases identified in the 2001-2014 Medline database, and then conducted univariate and multivariate analyses to identify predictors for the response to treatment. RESULTS: Review of our cases showed a significant and negative correlation between serum ferritin and anti-DNA antibody (p = 0.0025). All three patients treated with cyclosporine A (CsA) were considered responders despite high serum ferritin and corticosteroid resistance. We also reviewed 93 patients with ALHS identified in 46 articles. Multiple logistic regression analysis identified C-reactive protein (CRP) (OR 0.83, p = 0.042) and hemoglobin (OR 1.53, p = 0.026) measured at diagnosis of ALHS as significant predictors of the response to corticosteroid monotherapy. Moreover, among 32 patients treated with CsA, serum ferritin was significantly higher in CsA responders (12163 ± 16864 µg/l, n = 22) than in non-responders (3456 ± 6267/µg/l, p = 0.020, n = 10). Leukocyte count was significantly lower in the CsA responders (1940.0 ± 972.3/µl) than in the non-responders (3253 ± 2198/µl, p = 0.034). CONCLUSION: Low CRP and high hemoglobin can predict a positive response to corticosteroid monotherapy while high serum ferritin and low leukocyte count can predict a positive response to CsA in patients with ALHS and therefore, when corticosteroid monotherapy is not effective in such cases, CsA could be the first choice of an additional immunosuppressive agent.

Antigen-specific over-expression of human cartilage glycoprotein 39 on CD4+ CD25+ forkhead box protein 3+ regulatory T cells in the generation of glucose-6-phosphate isomerase-induced arthritis.

Human cartilage gp-39 (HC gp-39) is a well-known autoantigen in rheumatoid arthritis (RA). However, the exact localization, fluctuation and function of HC gp-39 in RA are unknown. Therefore, using a glucose-6-phosphate isomerase (GPI)-induced model of arthritis, we investigated these aspects of HC gp-39 in arthritis. The rise in serum HC gp-39 levels was detected on the early phase of GPI-induced arthritis (day 7) and the HC gp-39 mRNA was increased significantly on splenic CD4(+) T cells on day7, but not on CD11b(+) cells. Moreover, to identify the characterization of HC gp-39(+) CD4(+) T cells, we assessed the analysis of T helper (Th) subsets. As a result, HC gp-39 was expressed dominantly in CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) refulatory T cells (T(reg)), but not in Th1, Th2 or Th17 cells. Furthermore, to investigate the effect of HC gp-39 to CD4(+) T cells, T cell proliferation assay and cytokine production from CD4(+) T cells using recombinant HC gp-39 was assessed. We found that GPI-specific T cell proliferation and interferon (IFN)-γ or interleukin (IL)-17 production were clearly suppressed by addition of recombinant HC gp-39. Antigen-specific over-expression of HC gp-39 in splenic CD4(+) CD25(+) FoxP3(+) T(reg) cells occurs in the induction phase of GPI-induced arthritis, and addition of recombinant HC gp-39 suppresses antigen-specific T-cell proliferation and cytokine production, suggesting that HC gp-39 in CD4(+) T cells might play a regulatory role in arthritis.

Long-pulse beam acceleration of MeV-class H(-) ion beams for ITER NB accelerator.

In order to realize neutral beam systems in International Thermonuclear Experimental Reactor whose target is to produce a 1 MeV, 200 A/m(2) during 3600 s D(-) ion beam, the electrostatic five-stages negative ion accelerator so-called "MeV accelerator" has been developed at Japan Atomic Energy Agency. To extend pulse length, heat load of the acceleration grids was reduced by controlling the ion beam trajectory. Namely, the beam deflection due to the residual magnetic field of filter magnet was suppressed with the newly developed extractor with a 0.5 mm off-set aperture displacement. The new extractor improved the deflection angle from 6 mrad to 1 mrad, resulting in the reduction of direct interception of negative ions from 23% to 15% of the total acceleration power, respectively. As a result, the pulse length of 130 A/m(2), 881 keV H(-) ion beam has been successfully extended from a previous value of 0.4 s to 8.7 s. This is the first long pulse negative ion beam acceleration over 100 MW/m(2).

100 s extraction of negative ion beams by using actively temperature-controlled plasma grid.

Long pulse beam extraction with a current density of 120 A/m(2) for 100 s has been achieved with a newly developed plasma grid (PG) for the JT-60SA negative ion source which is designed to produce high power and long pulse beams with a negative ion current of 130 A/m(2) (22 A) and a pulse length of 100 s. The PG temperature is regulated by fluorinated fluids in order to keep the high PG temperature for the cesium-seeded negative ion production. The time constant for temperature controllability of the PG was measured to be below 10 s, which was mainly determined by the heat transfer coefficient of the fluorinated fluid. The measured decay time of the negative ion current extracted from the actively temperature-controlled PG was 430 s which was sufficient for the JT-60SA requirement, and much longer than that by inertial-cooling PG of 60 s. Obtained results of the long pulse capability are utilized to design the full size PG for the JT-60SA negative ion source.

Development of negative ion extractor in the high-power and long-pulse negative ion source for fusion application.

High power and long-pulse negative ion extractor, which is composed of the plasma grid (PG) and the extraction grid (EXG), is newly developed toward the neutral beam injector for heating and current drive of future fusion machines such as ITER, JT-60 Super Advanced and DEMO reactor. The PG is designed to enhance surface production of negative ions efficiently by applying the chamfered aperture. The efficiency of the negative ion production for the discharge power increased by a factor of 1.3 against that of the conventional PG. The EXG is also designed with the thermal analysis to upgrade the cooling capability for the long pulse operation of >1000 s required in ITER. Though the magnetic field for electron suppression is reduced to 0.75 of that in the conventional EXG due to this upgrade, it was experimentally confirmed that the extracted electron current can be suppressed to the allowable level for the long pulse operation. These results show that newly developed extractor has the high potential for the long pulse extraction of the negative ions.

Anti-citrullinated glucose-6-phosphate isomerase peptide antibodies in patients with rheumatoid arthritis are associated with HLA-DRB1 shared epitope alleles and disease activity.

To identify and characterize anti-citrullinated glucose-6-phosphate isomerase (GPI) peptide antibodies in patients with rheumatoid arthritis (RA). Nine GPI arginine-bearing peptides in human GPI protein were selected and cyclic citrullinated GPI peptides (CCG-1-9) were constructed. Samples were obtained from RA (n = 208), systemic lupus erythematosus (SLE) (n = 101), Sjögren's syndrome (SS; n = 101) and healthy controls (n = 174). Antibodies against CCG-1-9 were measured, and anti-citrullinated α-enolase-1 (CEP-1), -cyclic citrullinated peptides (CCP) and -GPI proteins antibodies were also examined. Patients with RA were genotyped for HLA-DRB1. The numbers of shared epitope (SE) alleles were counted and compared with those of the autoantibodies. Rabbit GPI was citrullinated with rabbit peptidylarginine deiminase and immunoblot analysis of RA sera performed. The levels of autoantibodies were compared before and after treatment with TNF antagonists in 58 RA patients. Anti-CCG-2, -4 and -7 antibodies were detected in 25·5, 33·2 and 37·0% patients with RA, respectively, and these antibodies were very specific for RA (specificity, 98·1-99·7%). Altogether, 44·2, 86·1 and 13·9% of RA sera were positive for anti-CEP-1, -CCP and -GPI protein antibodies, respectively. Anti-CCG-2, -4 and -7 antibodies were correlated with anti-CCP and anti-CEP-1 antibodies and with the presence of HLA-DRB1 SE alleles. Citrullinated GPI protein was detected using RA sera. Treatment with tumour necrosis factor antagonists reduced significantly the levels of anti-CCG-2 and -7 but not of anti-CEP-1 antibodies. This is the first report documenting the presence of anti-CCG antibodies in RA. Anti-CCG-2 and -7 antibodies could be considered as markers for the diagnosis of RA and its disease activity.

Effect of non-uniform electron energy distribution function on plasma production in large arc driven negative ion source.

Spatially non-uniform electron energy distribution function (EEDF) in an arc driven negative ion source (JAEA 10A negative ion source: 10 A NIS) is calculated numerically by a three-dimensional Monte Carlo kinetic model for electrons to understand spatial distribution of plasma production (such as atomic and ionic hydrogen (H(0)∕H(+)) production) in source chamber. The local EEDFs were directly calculated from electron orbits including electromagnetic effects and elastic∕inelastic collision forces. From the EEDF, spatial distributions of H(0)∕H(+) production rate were obtained. The results suggest that spatial non-uniformity of H(0)∕H(+) productions is enhanced by high energy component of EEDF.

Vacuum insulation of the high energy negative ion source for fusion application.

Vacuum insulation on a large size negative ion accelerator with multiple extraction apertures and acceleration grids for fusion application was experimentally examined and designed. In the experiment, vacuum insulation characteristics were investigated in the JT-60 negative ion source with >1000 apertures on the grid with the surface area of ∼2 m(2). The sustainable voltages varied with a square root of the gap lengths between the grids, and decreased with number of the apertures and with the surface area of the grids. Based on the obtained results, the JT-60SA (super advanced) negative ion source is designed to produce 22 A, 500 keV D(-) ion beams for 100 s.

Beam optics in a MeV-class multi-aperture multi-grid accelerator for the ITER neutral beam injector.

In a multi-aperture multi-grid accelerator of the ITER neutral beam injector, the beamlets are deflected due to space charge repulsion between beamlets and beam groups, and also due to magnetic field. Moreover, the beamlet deflection is influenced by electric field distortion generated by grid support structure. Such complicated beamlet deflections and the compensations have been examined utilizing a three-dimensional beam analysis. The space charge repulsion and the influence by the grid support structure were studied in a 1∕4 model of the accelerator including 320 beamlets. Beamlet deflection due to the magnetic field was studied by a single beamlet model. As the results, compensation methods of the beamlet deflection were designed, so as to utilize a metal bar (so-called field shaping plate) of 1 mm thick beneath the electron suppression grid (ESG), and an aperture offset of 1 mm in the ESG.

Voltage holding study of 1 MeV accelerator for ITER neutral beam injector.

Voltage holding test on MeV accelerator indicated that sustainable voltage was a half of that of ideal quasi-Rogowski electrode. It was suggested that the emission of the clumps is enhanced by a local electric field concentration, which leads to discharge initiation at lower voltage. To reduce the electric field concentration in the MeV accelerator, gaps between the grid supports were expanded and curvature radii at the support corners were increased. After the modifications, the accelerator succeeded in sustaining -1 MV in vacuum without beam acceleration. However, the beam energy was still limited at a level of 900 keV with a beam current density of 150 A∕m(2) (346 mA) where the 3 × 5 apertures were used. Measurement of the beam profile revealed that deflection of the H(-) ions was large and a part of the H(-) ions was intercepted at the acceleration grid. This causes high heat load on the grids and the breakdowns during beam acceleration. To suppress the direct interception, new grid system was designed with proper aperture displacement based on a 3D beam trajectory analysis. As the result, the beam deflection was compensated and the voltage holding during the beam acceleration was improved. Beam parameter of the MeV accelerator was increased to 980 keV, 185 A∕m(2) (427 mA), which is close to the requirement of ITER accelerator (1 MeV, 200 A∕m(2)).

Six-transmembrane epithelial antigen of prostate 4 (STEAP4) is expressed on monocytes/neutrophils, and is regulated by TNF antagonist in patients with rheumatoid arthritis.

OBJECTIVES: Human six-transmembrane epithelial antigen of prostate 4 (STEAP4) is one of the STEAP family as a homologue of mouse tumour necrosis factor-α-induced adipose-related protein (TIARP). Recently, we reported that the TIARP gene expression was remarkably increased in spleen and joints of glucose-6-phosphate isomerise (GPI)-induced arthritis model, suggesting pivotal association to arthritis. The aim of the present study was to assess the expression, localisation and function of STEAP4 in peripheral blood of patients with rheumatoid arthritis (RA). METHODS: Peripheral blood was obtained from seven patients with RA, the surface expression of STEAP4 was detected by flow cytometry. The number of neutrophils was compared with the expression of STEAP4 mRNA derived from peripheral blood of patients with RA. Neutrophils were introduced by HL60 with retinoic acid, and were transfected with GFP-STEAP4 plasmid DNA, then the migration of neutrophil-like HL60 was determined by transwell assay. In addition, the fluctuation of STEAP4 mRNA was analysed before and after treatment with infliximab in 40 patients with RA. RESULTS: STEAP4 was expressed on monocytes and neutrophils in peripheral blood in RA. The number of neutrophils and expression of STEAP4 mRNA was positively correlated. Migration of neutrophil-like HL60 was down-regulated by over-expression of STEAP4. Expression of STEAP4 Mrna was significantly decreased after infliximab treatment in patients with RA, especially in good responders. CONCLUSIONS: STEAP4 is expressed on monocytes and neutrophils in peripheral blood, regulates cell migration, is down-regulated by TNF antagonist, and might be a possible predictor of response to TNF antagonist.

Bio rapid prototyping by extruding/aspirating/refilling thermoreversible hydrogel.

This paper reports a method for rapid prototyping of cell tissues, which is based on a system that extrudes, aspirates and refills a mixture of cells and thermoreversible hydrogel as a scaffold. In the extruding mode, a cell-mixed scaffold solution in the sol state is extruded from a cooled micronozzle into a temperature-controlled substrate, which keeps the scaffold in the gel state. In the aspiration mode, the opposite process is performed by Bernoulli suction. In the refilling mode, the solution is extruded into a groove created in the aspiration mode. The minimum width of extruded hydrogel pattern is 114 +/- 15 microm by employing a nozzle of diameter 100 microm, and that of aspirated groove was 355 +/- 10 microm using a 500 microm-diameter nozzle. Gum arabic is mixed with the scaffold solution to avoid peeling-off of the gel pattern from the substrate. Patterning of Sf-9 cell tissue is demonstrated, and the stability of the patterned cell is investigated. This system offers a procedure for rapid prototyping and local modification of cell scaffolds for tissue engineering.

Improvement of voltage holding capability in the 500 keV negative ion source for JT-60SA.

Voltage holding capability of JT-60 negative ion source that has a large electrostatic negative ion accelerator with 45 cm x 1.1 m acceleration grids was experimentally examined and improved to realize 500 keV, 22 A, and 100 s D- ion beams for JT-60 Super Advanced. The gap lengths in the acceleration stages were extended to reduce electric fields in a gap between the large grids and at the corner of the support flanges from the original 4-5 to 3-4 kV/mm. As a result, the voltage holding capability without beam acceleration has been successfully improved from 400 to 500 kV. The pulse duration to hold 500 kV reached 40 s of the power supply limitation.