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Topography simulation of chemical-vapordeposition (CVD) trench filling has been advanced as a tool for designing fabrication processes of high-voltage 4H-SiC superjunction devices. In the longitudinal section of filled stripe trenches, an experimentally observed dip, which had not been well reproduced with a previous technique using a fixed surface free energy $\gamma$, came to be qualitatively reproduced by including an orientation dependence of $\gamma$.

Notch signaling regulates multiple helper CD4+ T cell programs. We have recently demonstrated that dendritic cells (DCs) expressing the Notch ligand DLL4 are critical for eliciting alloreactive T cell responses and induction of graft-versus-host disease in mice. However, the human counterpart of murine DLL4+ DCs has yet to be examined. We report the identification of human DLL4+ DCs and their critical role in regulating Th1 and Th17 differentiation. CD1c+ DCs and plasmacytoid DCs (pDCs) from the peripheral blood (PB) of healthy donors did not express DLL4. In contrast, patients undergoing allogeneic hematopoietic stem cell transplantation had a 16-fold more DLL4+CD1c+ DCs than healthy donors. Upon activation of TLR signaling, healthy donor-derived CD1c+ DCs dramatically upregulated DLL4, as did pDCs to a lesser extent. Activated DLL4+ DCs were better able to promote Th1 and Th17 differentiation than unstimulated PB DCs. Blocking DLL4 using a neutralizing Ab decreased Notch signaling in T cells stimulated with DLL4+ DCs, and it reduced the generation of Th1 and Th17 cells. Both NF-κB and STAT3 were crucial for inducing DLL4 in human DCs. Interestingly, STAT3 directly activated DLL4 transcription and inhibiting STAT3 alone was sufficient to reduce DLL4 in activated PB DCs. Thus, DLL4 is a unique functional molecule of human circulating DCs critical for directing Th1 and Th17 differentiation. These findings identify a pathway for therapeutic intervention for inflammatory disorders in humans, such as graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, autoimmunity, and tumor immunity.

Conventional floating-field rings, which are used to reduce the peak electric field at the periphery of power devices, cause nonuniform avalanche multiplication when applied to planar junctions formed on 4H-SiC substrates misoriented from (0001) toward $[{ 11}{\overline {2}}0]$ . Accordingly, a novel asymmetrically spaced floating-field ring (AS-FFR) was applied to 4H-SiC 4°-off (0001) p–n diodes and found to be effective against such nonuniform avalanche multiplication; that is, luminescence at breakdown was nearly uniform when the spacing between the edge of the anode and the inner edge of the AS-FFR was 2.0 ${{\mu }}\text{m}$ in the [ $\overline { 1}{\,}\overline {1}20$ ] direction and 1.5 ${{\mu }}\text{m}$ in the $[{11}{\overline {2}}0]$ direction. This result should contribute to exploring the possibility of 4H-SiC power devices with higher avalanche ruggedness.

A commercial-simulator-based numerical-analysis methodology for 4H-SiC power devices formed on misoriented (0001) substrates is proposed and applied for analyzing avalanche breakdown of floating-field-ring-terminated p-n diodes. Due to the inexpedience of a fixed orientation of the (0001) surface in current commercial device simulators, 4H-SiC (0001) surface is etched to form a miscut to separate the known effects of asymmetric nature of impact ionization and asymmetric aluminum concentration contours. 2-D process simulation of etching a 4H-SiC (0001) surface to expose a sloped surface, patterning the sloped surface with a mask, vertically implanting aluminum ions into the masked surface, removing the mask, and forming electrodes and a SiO2 passivation film was carried out. This process simulation revealed asymmetric lateral straggling of implanted aluminum acceptors. The subsequent device simulation, which assumed fixed charge at the SiO2/4H-SiC interface, revealed asymmetric avalanche breakdown voltage in the misoriented direction and the opposite direction. This asymmetric breakdown qualitatively explains the previously reported nonuniform luminescence at breakdown. The proposed methodology is considered to be applicable to other power devices with other termination structures formed on misoriented 4H-SiC (0001) substrates.

4H-SiC (0001) p-n diodes terminated with a floating-field ring were found to emit light at breakdown in the opposite direction to that of substrate misorientation when the diodes were fabricated by aluminum implantation and dry-oxidation passivation. Two-dimensional simulation revealed that such non-uniform breakdown was mainly attributable to the asymmetric lateral straggling of implanted aluminum acceptors, rather than the anisotropic nature of the impact ionization coefficient.

A novel method for analyzing a decrease in breakdown voltage (VBD) in the termination of 4H-SiC power devices after reverse-bias stressing on the basis of change in depletion-layer capacitance is proposed. Test PN diodes terminated with a junction-termination extension (JTE) were fabricated on n-type 4H-SiC and analyzed by I-V and C-V measurements. According to the results of the measurements, VBD after stressing decreases, and the capacitance of the test devices decreases after stressing. Measurements with different chip sizes but the same termination width show that the capacitance decrease occurs in the termination area. The simulated capacitance change, on the supposition that positive charge accumulated at the SiO2/SiC interface, and the measured capacitance change show the same tendency. These results indicate that the origin of VBD decrease is positive charge accumulated at the SiO2/SiC interface of the termination after reverse-bias stressing.

A technology-computer-aided-design (TCAD)-based topography-simulation model is proposed to simulate chemical-vapor-deposition (CVD) trench filling for SiC superjunction (SJ) devices. Experimental observations, concerning void formation and mesa overetching, are reproduced for the first time by including the Gibbs-Thomson (GT) effect (i.e., the effect of curvature of a growing surface on equilibrium vapor-phase concentration of growing species).

GF is one of the fatal complications of allogeneic HSCT. To rescue patients with primary GF, a second HSCT should be conducted as soon as possible, but the optimal donor source and technique have yet to be established. In this study, we retrospectively analyzed six children with hematologic malignancies who received TCR-haploidentical second HSCT for primary GF. The median interval between the prior HSCT and the second HSCT was 37.5 days. All patients received fludarabine and ATG containing reduced-intensity re-conditioning before the second HSCT. All patients, except one who died early, achieved both neutrophil and Plt engraftment at a median time of 15 and 33 days, respectively. Chimerism analysis showed that all engrafted patients achieved complete donor chimerism within 3 weeks. Four patients developed acute GVHD, and three patients developed chronic GVHD. TRM occurred in two patients. Median follow-up of the four survivors was 6.8 years, and all remained in sustained remission until the last follow-up. These results suggested that a TCR-haploidentical second HSCT for pediatric patients is feasible, and this approach may provide a potent option for children with primary GF.

We have investigated the possibility of being able to create gallium nitride bipolar junction transistors (GaN BJTs) whose n-type emitter region is formed using a conventional Si-ion implantation technology. The thermal stability of the p-GaN layer, which was the most important technique in creating GaN BJTs, was found to be maintained even after annealing at 1100 °C. A Hall-effect measurement revealed that the n-type emitter region, which was formed using 2.0 × 10 15 cm -2 Si-ion implantation within the p-GaN base layer, has a sheet carrier density of 1.59 × 10 14 cm -2 (i.e., a carrier activation ratio of 8%), an electron mobility of 41.0 cm 2 /Vs, and a sheet resistance of 958 Q/sq. The fabricated GaN BJTs had a maximum dc current gain of 160 and a maximum differential current gain of 238. These results show that Si-ion implantation is a promising technique for forming an n-type emitter of GaN BJTs. However, some of the transistor characteristics were found to be limited possibly by the Si-ion implantation-induced large base resistance.

Malignant peritoneal mesothelioma in children is a very rare disease and has a poor prognosis. Unlike malignant mesothelioma in adults, there is no clear causal association between this very rare malignancy in children and asbestos exposure. We report a case of peritoneal mesothelioma in an 11-year-old boy who presented with ascites. He was diagnosed with malignant mesothelioma on the basis of histopathological findings. His disease showed resistance to pemetrexed, but was treated successfully with platinum-based therapy with gemcitabine. He has achieved long-term survival in partial remission with stable disease.

SUMMARY Background: Despite improvements in first-line therapies, the outcomes of relapsed or refractory childhood acute leukaemia that has not achieved complete remission after relapse, has relapsed after stem cell transplantation (SCT), has primary induction failure and has relapsed with a very unfavourable cytogenetic risk profile, are dismal. Objectives and Methods: We evaluated the feasibility and efficacy of T-cell-replete haploidentical peripheral blood stem cell transplantation (haplo-SCT) with low-dose anti-human thymocyte immunoglobulin (ATG), tacrolimus, methotrexate and prednisolone (PSL) in 14 paediatric patients with high-risk childhood acute leukaemia. Results: All patients achieved complete engraftment. The median time to reaching an absolute neutrophil count of more than 0.5 × 10 9 L −1 was 14 days. Acute graft-vs-host disease (aGVHD) of grades II–IV and III–IV developed in 10 (71%) and 2 (14%) patients, respectively. Treatment-related mortality and relapse occurred in one (7%) patient and six (43%) patients, respectively. Eleven patients were alive and seven of them were disease-free with a median follow-up of 36 months (range: 30–159 months). The probability of event-free survival after 2 years was 50%. Conclusion: These findings indicate that T-cell-replete haplo-SCT, with low-dose ATG and PSL, provides sustained remission with an acceptable risk of GVHD in paediatric patients with advanced haematologic malignancies.

Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndrome. IFN-γ–producing Th1 CD4+ T cells mediate the immune destruction of hematopoietic cells, and they are central to the pathogenesis. However, the molecular events that control the development of BM-destructive Th1 cells remain largely unknown. Ezh2 is a chromatin-modifying enzyme that regulates multiple cellular processes primarily by silencing gene expression. We recently reported that Ezh2 is crucial for inflammatory T cell responses after allogeneic BM transplantation. To elucidate whether Ezh2 mediates pathogenic Th1 responses in AA and the mechanism of Ezh2 action in regulating Th1 cells, we studied the effects of Ezh2 inhibition in CD4+ T cells using a mouse model of human AA. Conditionally deleting Ezh2 in mature T cells dramatically reduced the production of BM-destructive Th1 cells in vivo, decreased BM-infiltrating Th1 cells, and rescued mice from BM failure. Ezh2 inhibition resulted in significant decrease in the expression of Tbx21 and Stat4, which encode transcription factors T-bet and STAT4, respectively. Introduction of T-bet but not STAT4 into Ezh2-deficient T cells fully rescued their differentiation into Th1 cells mediating AA. Ezh2 bound to the Tbx21 promoter in Th1 cells and directly activated Tbx21 transcription. Unexpectedly, Ezh2 was also required to prevent proteasome-mediated degradation of T-bet protein in Th1 cells. Our results demonstrate that Ezh2 promotes the generation of BM-destructive Th1 cells through a mechanism of transcriptional and posttranscriptional regulation of T-bet. These results also highlight the therapeutic potential of Ezh2 inhibition in reducing AA and other autoimmune diseases.

Diffusion equations were solved to examine how the aluminum concentration in 4H-SiC grown on a trenched substrate is influenced by the Gibbs−Thomson (GT) effect. The GT effect increases or decreases the equilibrium gas-phase concentration of growing species in the vicinity of the top or bottom of the trench, respectively, which results in a part of the incident growing species, excluding the central area of the trench, diffusing inward. After fitting activity coefficient of a conditional constituent AlC in solid solution AlSiC and surface free energy of 4H-SiC, we determined the aluminum fluxes toward the top and bottom in such a way that the flux ratio of aluminum to silicon equals the AlC mole fraction at the top () and bottom (), respectively. Calculated was lower than and almost agreed with the measured in filled trenches, showing the GT effect on AlC being weaker than that on SiC.

Discrepancies in reported electronic stopping cross sections and simulated concentration-depth profiles in 4H-SiC for low-velocity ions have made it difficult to select ion species suited for channeled implantation to be used in multi-epitaxial growth for superjunction devices. In this study, a parallel-scanning system was used to vertically implant 9 × 107-cm s−1 ions into a nominal (0001) wafer at RT. Among the possible channeled implantations of nitrogen or phosphorus ions into p-type 4H-SiC and boron or aluminum ions into n-type 4H-SiC, aluminum-ion implantation into n-type 4H-SiC was concluded to be the best for minimizing repetition of the epitaxial growth/ion implantation steps.

An effective acceptor level (EAeff) for representing the increased ionization ratio in extrinsically photon-recycled p-type GaN is proposed.EAeffat 300 K in the range of 0.1360.145 eV is found to reproduce current/voltage characteristics of transmission-line-model patterns formed with GaN p-n junction epitaxial layers and electrode spacing of 320 μm when the p-n diode current flowing through an 80×100-μm electrode is 90 mA. WhenEAeffis decreased from 0.160 eV to 0.145 eV, the on-resistance of 18×100-μm GaN bipolar transistors is predicted to be reduced by more than 50%.

Graft-versus-host disease (GVHD) reflects an exaggerated inflammatory allogeneic T cell response in hosts receiving allogeneic hematopoietic stem cell transplantation (HSCT). Inhibition of pan-Notch receptor signaling in donor T cells causes reduction of GVHD. However, which Notch ligand(s) in what APCs is important for priming graft-versus-host reaction remains unknown. We demonstrate that δ-like ligand-4 (Dll4) and Dll4-positive (Dll4high) inflammatory dendritic cells (i-DCs) play important roles in eliciting allogeneic T cell responses. Host-type Dll4high i-DCs occurred in the spleen and intestine of HSCT mice during GVHD induction phase. These Dll4high i-DCs were CD11c+B220+PDCA-1+, resembling plasmacytoid dentritic cells (pDCs) of naive mice. However, as compared with unstimulated pDCs, Dll4high i-DCs expressed higher levels of costimulatory molecules, Notch ligands Jagged1 and Jagged2, and CD11b, and produced more Ifnb and Il23 but less Il12. In contrast, Dll4-negative (Dll4low) i-DCs were CD11c+B220−PDCA-1−, and had low levels of Jagged1. In vitro assays showed that Dll4high i-DCs induced significantly more IFN-γ– and IL-17–producing effector T cells (3- and 10-fold, respectively) than Dll4low i-DCs. This effect could be blocked by anti-Dll4 Ab. In vivo administration of Dll4 Ab reduced donor-alloreactive effector T cells producing IFN-γ and IL-17 in GVHD target organs, leading to reduction of GVHD and improved survival of mice after allogeneic HSCT. Our findings indicate that Dll4high i-DCs represent a previously uncharacterized i-DC population distinctive from steady state DCs and Dll4low i-DCs. Furthermore, Dll4 and Dll4high i-DCs may be beneficial targets for modulating allogeneic T cell responses, and could facilitate the discovery of human counterparts of mouse Dll4high i-DCs.

Background Epstein-Barr virus-related post-transplantation lymphoproliferative disorder (EBV-PTLD) is a serious complication in hematopoietic stem cell transplantation (HSCT) recipients. Methods We conducted a retrospective study to investigate the incidence and potential risk factors for EBV reactivation and to assess the efficacy of the management of EBV reactivation with preemptive rituximab in children who had T-cell-replete haploidentical HSCT (TCR-haplo-SCT) with low-dose anti-thymocyte globulin (ATG). EBV-DNA level in peripheral blood (PB) was determined when suspicious symptoms of EBV reactivation were observed. When the EBV-DNA level in PB increased to >1,000 copies/106 peripheral blood mononuclear cells (PBMCs), patients were preemptively treated with rituximab (375 mg/m2/dose). Results A total of 19 (50%) of 38 patients received rituximab infusion at a median time of 56 days after HSCT (range, 17–270). The median viral load at initiation of therapy was 2900 copies/106 PBMCs (range: 1000–650000). Preemptive therapy was started after a median of 2 (range, 0–7) days. The median number of weekly treatment cycles was 2 (range, 1–3). None of the patients developed PTLD or other EBV-associated diseases. Conclusion We conclude that preemptive rituximab therapy could be a useful strategy for EBV-PTLD in TCR-haplo-SCT recipients with low-dose ATG. This article is protected by copyright. All rights reserved.

Background The objective of this study was to evaluate the efficacy and safety of our combination therapy in febrile neutropenic children with cancer. Methods A total of 109 patients with 251 episodes of febrile neutropenia received antibiotic therapy between January 2003 and December 2008 at a single institution. Results Blood cultures were positive in 35 episodes (14%). Gram-positive organisms predominated (23/38 organisms isolated). There were 15 gram-negative isolates and no fungal isolates. The recommended empirical first-line antibiotics (cefepime or cefozopran + piperacillin + amikacin) were used in 206 (82%), second-line antibiotics (piperacillin-tazobactam + carbapenem + amikacin + micafungin) in 73 (29%), and third-line antibiotics (meropenem + glycopeptides + micafungin) in 24 (10%) episodes. The overall response rates were 71.4%, 50.7%, and 62.5% for the first-, second-, and third-line antibiotic therapies, respectively. Granulocyte transfusion was performed in seven patients, and the response rate was 57%. Four deaths were recorded. Conclusions Although a significant improvement of mortality was not observed, our regimen of empirical antibiotic therapies led to a significant and clinically relevant decrease in glycopeptide use, and it is safe and well tolerated by pediatric neutropenic patients.

The reduction of reverse leakage currents was attempted to fabricate 4H-SiC diodes with large current capacity for high voltage applications. Firstly diodes with Schottky metal of titanium (Ti) with active areas of 2.6 mm2 were fabricated to investigate the mechanisms of reverse leakage currents. The reverse current of a Ti Schottky barrier diode (SBD) is well explained by the tunneling current through the Schottky barrier. Then, the effects of Schottky barrier height and electric field on the reverse currents were investigated. The high Schottky barrier metal of nickel (Ni) effectively reduced the reverse leakage current to 2 x 10-3 times that of the Ti SBD. The suppression of the electric field at the Schottky junction by applying a junction barrier Schottky (JBS) structure reduced the reverse leakage current to 10-2 times that of the Ni SBD. JBS structure with high Schottky barrier metal of Ni was applied to fabricate large chip-size SiC diodes and we achieved 30 A- and 75 A-diodes with low leakage current and high breakdown voltage of 4 kV.

Alloreactive T cells play a critical role in eliminating hematopoietic malignant cells but are also the mediators of graft-versus-host disease (GVHD), a major complication that subverts the success of allogeneic hematopoietic stem cell transplantation (HSCT). However, induction of alloreactive T cells does not necessarily lead to GVHD. Here we report the development of a cellular programming approach to render alloreactive T cells incapable of causing severe GVHD in both major histocompatibility complex (MHC)-mismatched and MHC-identical but minor histocompatibility antigen-mismatched mouse models. We established a novel platform that produced δ-like ligand 4-positive dendritic cells (Dll4(hi)DCs) from murine bone marrow using Flt3 ligand and Toll-like receptor agonists. Upon allogeneic Dll4(hi)DC stimulation, CD4(+) naive T cells underwent effector differentiation and produced high levels of interferon γ (IFN-γ) and interleukin-17 in vitro, depending on Dll4 activation of Notch signaling. Following transfer, allogeneic Dll4(hi)DC-induced T cells were unable to mediate severe GVHD but preserved antileukemic activity, significantly improving the survival of leukemic mice undergoing allogeneic HSCT. This effect of Dll4(hi)DC-induced T cells was associated with their impaired expansion in GVHD target tissues. IFN-γ was important for Dll4(hi)DC programming to reduce GVHD toxicities of alloreactive T cells. Absence of T-cell IFN-γ led to improved survival and expansion of Dll4(hi)DC-induced CD4(+) T cells in transplant recipients and caused lethal GVHD. Our findings demonstrate that Dll4(hi)DC programming can overcome GVHD toxicity of donor T cells and produce leukemia-reactive T cells for effective immunotherapy.

Intensive chemotherapy with tyrosine kinase inhibitor (TKI) improves the prognosis of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). However, the prognosis of cases of relapsed or refractory Ph-ALL remains poor. Here, we aimed to assess the efficacy of T-cell-rich HLA-haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) in eight patients with relapsed or refractory pediatric Ph-ALL. Transplant-related mortality was observed in two patients. All patients discontinued TKI after receiving TCR-haplo-HSCT. The 3-year probability of overall survival and event-free survival was 75.0 and 62.5%, respectively. These results indicate the efficacy of TCR-haplo-HSCT for relapsed/refractory pediatric Ph-ALL.

Background Pediatric apheresis for peripheral blood stem cell transplantation should be carried out with due concern for low corporeal blood volume and vulnerability to hypocalcemia-related complications, hypovolemic shock, and hypervolemic cardiac overload. Study Design And Methods We retrospectively investigated a total of 267 apheresis procedures from 1990 to 2013 on 93 children between 0 and 10 years old, including 89 patients and 4 healthy donors, with body weights of 6.3 to 44.0 kg. Results The median CD34+ cell yield per apheresis procedure was 2.3 × 10 6 CD34+ cells/kg (0.2–77.9 × 10 6 CD34+ cells/kg). Adverse events occurred in 11.6% of procedures (n = 31), including mild perivascular pain (n = 12), emesis (n = 9), hypotension (n = 3), urticaria (n = 2), numbness (n = 2), chest pain (n = 1), facial flush (n = 1), and abdominal pain (n = 1). Among hypotensive events, shock in a 9.6 kg one-year-old boy required emergency treatment in 1996. Thereafter, we adopted continuous injection of calcium gluconate, ionized calcium monitoring, central venous catheter access and circuit priming with albumin in addition to concentrated red cells. Since then we have had fewer complications: 16.4% per apheresis during 1990–1997 versus 5.8% during 1998–2013. No healthy pediatric donors suffered from any late-onset complications related to apheresis or G-CSF administration. Conclusion By employing appropriate measures, peripheral blood stem cell apheresis for small children can have an improved safety profile, even for children weighing

The influence of surface recombination on forward current-voltage (IF-VF) characteristics of gallium nitride (GaN) p+n diodes formed on GaN free-standing substrates was both experimentally and computationally investigated. In the temperature range of 373-273 K, the surface-recombination velocity 5 of 0.5-μm n GaN overetched circular-mesa diodes was derived, respectively, as 2-10 × 107 and 1 × 107 cm/s for diodes with and without a mesa-field-plate termination structure consisting of dielectric and metal layers. It was shown that IF (VF

Abstract 820 Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with hematological malignancies. However, its success is limited by life-threatening graft-versus-host disease (GVHD). Novel approaches are needed to control GVHD. Recent studies have shown the importance of histone methylation in regulating the expression of genes associated with effector T cell differentiation and proliferation. Using several mouse models of allo-HSCT, we report that in vivo administration of the histone methylation inhibitor 3-Deazaneplanocin A (DZNep) arrested ongoing GVHD while preserving graft-versus-leukemia activity (GVL). To assess the therapeutic effect of pharmacologic modulation of histone methylation on GVHD, we administered DZNep to BALB/c mice receiving major histocompatibility-mismatched C57BL/6 mouse T cells 7 days after transplantation, in which GVHD had been fully established. Notably, injection of 12 doses of DZNep controlled the disease in these recipients, with approximately 80% of them surviving long-term without significant clinical signs of GVHD. We found that in vivo administration of DZNep caused selective apoptosis in alloantigen-activated T cells, but did not impair the generation of effector T cells that produced inflammatory cytokines (e.g., TNF-α, IFN-γ and IL-17) and cytotoxic molecules (e.g., granzyme B and Fas ligand). As a result, alloreactive T cells retained potent GVL activity, leading to improved overall survival of the recipients challenged by leukemic cells. These data suggest that DZNep-mediated inhibition of GVHD may be accounted for by reduced number of alloreactive effector T cells. In vitro culture assays showed that DZNep treatment induced apoptosis in T cells activated by anti-CD3/CD28 antibodies but not in naive T cells stimulated by IL-2 or IL-7. This effect was associated with DZNep's ability to selectively reduce trimethylation of histone H3 lysine 27 (H3K27), deplete the histone methyltranferase Ezh2 that specifically catalyzes trimethylation of H3K27, and activate Ezh2-repressed pro-apoptotic gene Bim. Inactivation of Bim partially protected alloreactive T cells from DZNep-mediated apoptosis. Importantly, unlike DNA methylation inhibitors, inhibition of histone methylation by DZNep had no toxicities to hematopoietic cells or impairment on the reconstitution of hematopoiesis and thymopoiesis. Our findings indicate that modulation of histone methylation may have significant implications in the development of novel approaches to treat established GVHD and other T cell-mediated inflammatory disorders in a broad context. Disclosures: No relevant conflicts of interest to declare.

Lithium orthosilicate and lithium aluminate are the candidates of the breeder material of the tritium-breeding blanket. To enhance the rate of tritium release from these breeder materials, 0.2 wt.% of palladium was impregnated into the breeder materials by the incipient wet impregnation method. The lithium orthosilicate and the lithium aluminate pebbles with or without Pd were irradiated in the Kyoto university research reactor, and out-of-pile annealing experiments were performed. When the breeder materials were deposited with a catalytic additive, such as Pd the ratio of the tritium discharged in the molecular form of tritium (HT) increased. It was also found that the amount of the tritium discharged from the lithium orthosilicate pebbles with a catalytic additive at the low temperatures is greater compared with lithium aluminate.

Recovery of tritium released into working areas in nuclear fusion plants is a key issue of safety. A large volume of air from tritium fuel cycle or vacuum vessel should be processed by air cleanup system (ACS). In ACS, tritium gas is oxidized by catalysts, and then tritiated water vapor is collected by adsorbents. This method can remove tritium effectively, whereas high throughput of air causes high-pressure drop in catalyst and adsorbent beds. In this study, the applicability of honeycomb-type adsorbents, which offers a useful advantage in terms of their low-pressure drop, to ACS was examined, in comparison with conventional pebble-type adsorbent. Honeycomb-type adsorbent causes far less pressure drop than pebble-type adsorbent beds. Adsorption capacity of water vapor on a honeycomb-type adsorbent is slightly lower than that on a pebble-type adsorbent, while adsorption rate of water vapor on honeycomb-type adsorbent is much higher than that of pebble-type adsorbent.

In the process of development of D–T fusion power reactors, recovery of tritium released into the last confinement system would be a key issue related to safety. If an accidental leakage of tritium takes place in a fusion power plant, a large volume of air should be detritiated with an air cleanup system (ACS). In ACS, tritium gas is converted to tritiated water vapor with a catalyst bed, and then which is recovered with an adsorption bed. In this study, the authors examined the applicability of honeycomb-type catalysts to ACS. A screening test of catalysts for oxidation of hydrogen and deuterium was performed using various honeycomb-type and pebble-type catalysts. Experimental results reveal that a honeycomb-type catalyst possesses a high oxidation performance for oxidation of hydrogen isotopes. Furthermore, the isotope effect on the oxidation of hydrogen isotopes over the honeycomb-type catalyst was thoroughly examined and quantified using tritium.

A novel bioethanol separation process was proposed in this study employing molecular sieving carbon (MSC) as an adsorbent, whose pore diameter is close to molecular size of ethanol. In the proposed process, fermentation broth is first introduced to the adsorption bed packed with MSC. In this step, ethanol is selectively adsorbed onto MSC, with highly enriching ethanol in the micropore of MSC. Subsequently, the concentrated ethanol is desorbed from MSC to gaseous phase, resulting in further purification of ethanol owing to a considerable difference in desorption rate between water and ethanol; Because of molecular sieving effect of MSC, the desorption rate of ethanol is much smaller than that of water. To establish this process, adsorption equilibrium and kinetics of ethanol on various MSCs were investigated in aqueous phase as the first step. Also, desorption kinetics of ethanol and water in gaseous phase were investigated. As a result, it was suggested that highly concentrated ethanol could be obtained with high recovery ratio through these simple operations, meaning the proposed process is quite promising.

A two-dimensional model of aluminum-ion implantation into 4H-SiC at moderate doses (1011 to 1013 cm-2) has been developed. The model is based on a Monte-Carlo simulation using a binary-collision approximation. This simulation reveals that iso-concentration contours are independent of the orientation of the masking edge. Lateral range straggling is extracted by expressing the lateral-concentration profiles as a one-dimensional dual-Pearson-distribution function multiplied by a Gauss-distribution function. Compared to vertical straggling, the lateral straggling is found to be more weakly dependent on projected range.

For large volume air clean-up in nuclear fusion facilities, honeycomb-type adsorbents offer a useful advantage in terms of their low-pressure drop. In this study, two different honeycomb-type adsorbents (honeycomb-K and honeycomb-N) and pebble-type adsorbents were used as samples and the water vapor adsorption performance of each adsorbent was examined by changing temperature, concentration of water vapor and flow rate. The honeycomb-K and honeycomb-N adsorbents included zeolite-4A or zeolite-5A with a 50% clay binder and with a 15% sepiolite binder, respectively. The shapes of cells in honeycomb-K and honeycomb-N are triangles with 1 mm sides and squares with 1 mm sides, respectively, and the cell densities of the both adsorbents were 200 CPSI (cells/in.2). The adsorption capacity for water vapor on the honeycomb-K adsorbent was comparable to that on the pebble-type adsorbent, while the adsorption capacity on the honeycomb-N adsorbent was lower. The adsorption rates of honeycomb-K and honeycomb-N adsorbents were higher than that of the pebble-type adsorbent. The honeycomb-K adsorbent containing zeolite-5A showed a higher adsorption rate than that containing zeolite-4A. Thus, honeycomb-K containing zeolite-5A adsorbent could be applicable to air cleanup systems in terms of both adsorption capacity and rate.

In this study, we evaluated the feasibility of our graft-versus-host disease (GVHD) prophylaxis with tacrolimus, methotrexate, and prednisolone in non-T-cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT) for children. Twenty-one consecutive patients including those with hematological malignancies (n = 11), solid tumors (n = 7), and non-malignancies (n = 3) were analyzed. Myeloablative and reduced intensity conditionings were carried out in 5 and 16 patients, respectively, and both of the regimens contained anti-human T-lymphocyte immunoglobulin. Twenty (95%) of the 21 patients achieved primary engraftment. Acute GVHD of grades II-IV and III-IV were observed in nine (47%) and one (5%) patient, respectively, all of which were controllable by steroids. Chronic GVHD was observed in eight (51%) of the 17 evaluable patients, and one of them developed steroid refractory chronic GVHD. Treatment-related mortality occurred in three patients (15%), as a result of acute pancreatitis, chronic GVHD, and EB virus associated lymphoproliferative disease. The median follow-up of the 13 survivors was 24 months, and the two-yr probability of overall survival was 68%. The Karnofsky performance scale score of the 13 survivors was 100%. These results indicated the feasibility of our GVHD prophylaxis in non-T-cell-depleted haploidentical HSCT for children.

10544Background: Despite the significant improvements of long-term survival rates for pediatric cancers, prognosis of refractory/relapsed solid tumors are extremely poor, and novel strategies are d...

Boron diffusion in boron-doped poly-Si/nitrogen-doped 4H-SiC structure was investigated by combining a reported model of poly-Si diffusion sources with the authors’ model of boron diffusion in 4H-SiC. By taking the limited supply of carbon interstitials at heterointerfaces into account, we determined a segregation coefficient of 4 to 8 and an activation energy of 0.20 eV in the temperature range of 650 to 1000°C.

Forward current density (JF)-forward voltage (VF) characteristics are experimentally and computationally investigated for 4H-silicon carbide junction barrier Schottky (JBS) diodes with a lightly doped (3 - 5 times1015 cm-3) drift layer and 2-mum-wide p+ stripe regions separated by 1 mum. The JF-VF characteristics of fabricated JBS diodes are compared with those of Schottky barrier diodes simultaneously fabricated on the same epitaxial wafers. These JF-VF characteristics are also compared with those of simulated JBS diodes, assuming boxlike and Monte Carlo-simulated profiles of aluminum. In the simulation of aluminum ion implantation, concentration contours of created interstitials and vacancies are calculated, and their influence on the JF-VF characteristics of JBS diodes is discussed in terms of degradation of electron mobility in the surface region of the drift layer.

We demonstrate a Dual-Pearson approach to model ion-implanted Al concentration profiles in 4H-SiC for high-precision design of high-voltage power devices. Based on the Monte Carlo simulated data for 35-400 keV implantation, we determine the nine Dual-Pearson parameters and confirm precise reproduction of profiles of 1015-1021 cm-3 Al with sufficient smoothness. This leads to a direct incorporation of implanted Al profiles into a device simulator. The influence of dose and energy on channeling is also discussed from the view point of implantation-induced disorder in 4H-SiC.

This paper presents a detailed analysis and precise modeling of multiple-energy Al implantations necessary for boxlike profiles in the p+-region of 4H-SiC power devices. To demonstrate the balance between "scatter-in channeling" and "amorphization-suppressed channeling," a thin-surface SiO2 layer is formed on 4H-SiC substrates misoriented by 8deg from (0001) toward [112 macr0]. Experimental, as well as Monte-Carlo-simulated, as-implanted concentration profiles of Al normally incident to the surface suggest that the least ion channeling is realized for implantations without SiO2 in a decreasing energy order. To understand this mechanism, concentration profiles of Al implantations at a single energy with and without SiO2 are modeled using the dual-Pearson approach. Based on the developed model, the Al ion channeling in 4H-SiC is discussed in terms of effects of surface SiO2 layers and the sequence of multiple-energy implantations.

The aim of this study was to examine the extended storage of granulocyte concentrates mobilized by granulocyte-colony-stimulating factor (G-CSF) with/without dexamethasone (DEX) and collected by a bag separation method. Ten healthy adult volunteers donated blood three times: twice after granulocyte mobilization by (1) injecting G-CSF at 3 microg kg(-1) subcutaneously (s.c.) and (2) injecting G-CSF at 3 microg kg(-1) s.c. + DEX at 8 mg per oral and once (3) for a baseline control without any forms of mobilization. Granulocytes were collected by a bag separation method. The functions (phagocytosis and oxidative killing levels), viability and levels of interleukin (IL)-1beta, IL-8, IL-6 and tumour necrosis factor-alpha of granulocytes were measured. The average numbers of granulocytes collected from 200-mL samples of whole blood from the G-CSF and G-CSF + DEX groups were 35.1 x 10(8) and 49.4 x 10(8), respectively. Phagocytosis level, oxidative killing level and the viability of the granulocytes mobilized by G-CSF with/without DEX were well maintained for up to 72 h of storage after collection. The levels of the cytokines increased in a time-dependent manner. The in vitro phagocytosis level, oxidative killing level and the viability of granulocytes mobilized by G-CSF with/without DEX and collected by bag separation method can be maintained for as long as 72 h after collection.

Ewing sarcoma family of tumors (ESFT) comprise common sarcomas in children and young adults. Such tumors usually occur in the medullary cavity of long bones and directly invade cortical bone and circumferential soft tissue, including periosteum. Periosteal ESFT is extremely rare and only a small numbers of cases, including cases not confirmed by molecular detection of chimeric fusion gene, have been reported. We describe herein a case of periosteal ESFT of the femur in a 13-year-old boy harboring EWS-FLI1 chimeric fusion gene transcripts detected by reverse transcription-polymerase chain reaction analysis. This report may provide an opportunity for further evaluation of the EWS-FLI1 type 1 fusion gene and detection of prognostic significance in periosteal ESFT.

The catalytic activities of propylene oxidation on different aluminum silicates with the mayenite structure [Ca 12 Al 14-x Si x O 33+0.5x (x=0,4)] formed at 500, 800 and 100°C were investigated. The aluminum silicates were prepared by the hydrothermal and solid-state reactions of a stoichiometirc mixture of calcium oxide, alumina sol and silica. The XRD results of the aluminum silicates obtained by the solid-state reaction showed that the peak intensities of the mayenite phases became larger as the calcination temperature increased. The aluminum silicates included two kinds of active oxygen species (O 2- 2 , O - 2 ) related to Raman shifts around 887 and 1092cm -1 , respectively. As a result, the aluminum silicates exhibited oxidation activities based on the easily reducible active oxygen species. Notably, the Ca 12 Al 10 Si 4 O 35 calcined at 1000°C without the hydrothermal treatment showed the highest activity of all catalysts, indicating that the crystal structures play an important role in determining the catalytic activity.

Hematopoietic stem cell transplantation (HSCT)-related nephrotic syndrome (NS) is a rare event and has been described as a clinical form of chronic graft-versus-host disease (GVHD). Although immunological mechanisms are thought to play important roles in NS after HSCT, the exact mechanisms have not been clarified.We report a 4-year-old boy with acute lymphoblastic leukemia (ALL) who developed NS during the tapering of immunosuppressants 5 months after an allogeneic HSCT (allo-HSCT). A renal biopsy was performed, and light and electron microscopy revealed minimal change disease (MCD). Although the response to treatment with steroids and tacrolimus was favorable, the child experienced two relapses of NS within the first 9 months after the initial response. A second allo-HSCT was performed to treat the relapse of ALL. After the second allo-HSCT, the remission of NS was maintained without recurrence for 5 years, even after the cessation of immunosuppressants.Our patient who had ALL and developed NS after his first allo-HSCT, maintained remission from NS after a second allo-HSCT. This suggests that the immune cells from the first donor origin were associated with the pathogenesis of NS.

Calcium ferrite oxides were prepared by calcining a mixture powder of iron- and calcium oxide. The 57Fe-Mossbauer spectra of the calcium ferrites oxides were measured, revealing that the products should be Ca2Fe2O5 and CaFe2O4, the ratio of which was dependent of the Fe/Ca atomic ratio of the mixture powder.

Several types of calcium ferrite base catalysts (Ca/Fe = 0.33–3) for propylene (C3H6) combustion were prepared. Calcium ferrite catalyst with brownmillerite crystal structure provided catalytic activity for C3H6 combustion in the temperature range of 250–450 °C. The brownmillerite phase (Ca2Fe2O5) was responsible for the formation of oxygen adspecies (O2−) in the surface layer below 450 °C.

In this paper, thermal stability in the multifinger GaInP/GaAs collector-up tunneling-collector heterojunction bipolar transistors (C-up TC-HBTs) has been investigated. Two unique structures in these C-up TC-HBTs are provided for thermal management for a stable operation. One is the base layer that is incorporated with highly resistive regions, which serves as a ballast resistor, due to the boron-ion implantation. The other is the backside via-hole structure constructed underneath the transistors called "the subtransistor via-hole structure", leading to a superior thermal conduction. In this paper, as a result, it was revealed that the effect of the via hole on the thermal stability depends on the effect of the base resistance on the thermal stability. The thermal stability in the C-up TC-HBTs, with a relatively lower base resistance due to the boron-ion implantation of 1times10 12 cm-2, is attributed to the decrease in the thermal resistance due to the via hole, while that in the C-up TC-HBTs, with a boron-ion implantation of 2times1012 cm-2, is dominated by a relatively large base resistance. Moreover, with a reduction in the finger space in the four-finger C-up TC-HBTs with a low base resistance, the range of a thermally stable operation is found to become narrower. This can be explained by the dependence of the thermal resistance on the finger space in the four-finger C-up TC-HBTs. These results are useful for the device design, so as to obtain the thermal stability in the C-up TC-HBTs with a subtransistor via-hole structure, for application in the small and high-power amplifiers

Myeloid/natural killer cell precursor acute leukemia (MNKL) is an aggressive disease with a high relapse rate even after allogeneic hematopoietic stem cell transplantation (SCT). We report a patient with MNKL who had a donor lymphocyte infusion (DLI) for relapse after T cell-replete human leukocyte antigen (HLA)-haploidentical SCT, but relapsed again 20 months later with loss of mismatched HLA. This case suggests that a strong graft-versus-leukemia effect of haploidentical SCT can be expected in MNKL patients. In the haploidentical setting, DLI should be considered for patients with relapsed leukemia whose leukemic cells have not lost HLA cell surface expression.

To characterize and model the degradation of collector-up (C-up) heterojunction bipolar transistors (HBTs), we bias stress InGaP/GaAs C-up tunneling-collector HBTs (TC-HBTs) fabricated under various conditions for etching the collector mesas and of implanting boron ions into the extrinsic emitter. Contrary to the previous reports on reduction in collector current I/sub C/ of bias-stressed emitter-up HBTs fabricated with ion implantation, no I/sub C/ Gummel shift is observed in the case of C-up TC-HBTs, probably due to the lower damage resulting from the lower ion dosage. On the other hand, the base current of the bias-stressed C-up TC-HBTs increases with the decrease of the ion dose and with the increase of the collector mesa undercut under the collector electrode that is also used as an implant mask. We attribute the increased base current to the increased carrier recombination at the extrinsic base surface. Making the area of the emitter-base junction smaller than that of the base-collector junction-using electron-cyclotron resonance plasma etching together with lateral spreading of heavily implanted boron ions-results in a stable current gain even after a 1030-h testing at a junction temperature of 210/spl deg/C and a collector current density of 40/sup 2/kA/cm.

AlGaAs/GaAs/GaAs and GaInP/GaAs/GaAs n-p-n heterojunction bipolar transistors (HBTs) are now in widespread use in microwave power amplifiers. In this paper, improved HBT structures are presented to address issues currently problematic for these devices: high offset and knee voltages and saturation charge storage. Reduced HBT offset and knee voltages (V/sub CE,os/ and V/sub k/) are important to improve the power amplifier efficiency. Reduced saturation charge storage is desirable to increase gain under conditions when the transistor saturates (such as in over-driven Class AB amplifiers and switching mode amplifiers). It is shown in this paper that HBT structures using a 100-/spl Aring/-thick layer of GaInP between the GaAs base, and collector layers are effective in reducing V/sub CE,os/ to 30 mV and V/sub k/ measured at a collector current density of 2/spl times/10/sup 4/ A/cm/sup 2/ to 0.3 V (while for conventional HBTs V/sub CE,os/=0.2 V and V/sub k/=0.5 V are typical). A five-fold reduction in saturation charge storage is simultaneously obtained.

本報告は, RTK-GPSを用いた大規模な地盤変状の計測の可能性を検討したものである. これは, 地震時の液状化時等に発生しうる広範囲な地盤の大変状に対し, リアルタイム性と十分な計測精度を確保して計測する手法の候補である. 人工的に引き起こされた液状化による地盤変状を10台のGPS受信機を用いて計測し, トータルステーションや画像解析による計測結果の比較によって計測精度を評価した. 堅牢性には大きな問題はなく, 残留変位を測る静的計測精度や, 変状中の変位を測る動的計測精度も, 地盤大変状の検知には十分であった. 検討結果はRTK-GPSを用いた地盤大変状の計測の実用性を示すものである.

Effector T cell migration into inflamed sites greatly exacerbates tissue destruction and disease severity in inflammatory diseases, including graft-versus-host disease (GVHD). T cell migration into such sites depends heavily on regulated adhesion and migration, but the signaling pathways that coordinate these functions downstream of chemokine receptors are largely unknown. Using conditional knockout mice, we found that T cells lacking the adaptor proteins CRK and CRK-like (CRKL) exhibit reduced integrin-dependent adhesion, chemotaxis, and diapedesis. Moreover, these two closely related proteins exhibited substantial functional redundancy, as ectopic expression of either protein rescued defects in T cells lacking both CRK and CRKL. We determined that CRK proteins coordinate with the RAP guanine nucleotide exchange factor C3G and the adhesion docking molecule CASL to activate the integrin regulatory GTPase RAP1. CRK proteins were required for effector T cell trafficking into sites of inflammation, but not for migration to lymphoid organs. In a murine bone marrow transplantation model, the differential migration of CRK/CRKL-deficient T cells resulted in efficient graft-versus-leukemia responses with minimal GVHD. Together, the results from our studies show that CRK family proteins selectively regulate T cell adhesion and migration at effector sites and suggest that these proteins have potential as therapeutic targets for preventing GVHD.