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Impurity incorporation during vapor-phase epitaxy on stepped surfaces was modeled by classifying rate-limiting processes into i) surface diffusion, ii) step kinetics, and iii) segregation. Examples were shown for i) desorption-limited Al incorporation during chemical vapor deposition (CVD) of (0001) SiC, ii) preferential desorption of C atoms from kinks during CVD of Al-doped (000-1) SiC, and iii) segregation-limited C incorporation during metalorganic vapor-phase epitaxy of (0001), (000-1), and (10-10) GaN.

Background Cancer vaccines that induce endogenous antitumor immunity represent an ideal strategy to overcome intractable cancers. However, doing this against a pre-established cancer using autologous immune cells has proven to be challenging. “Allogeneic effects” refers to the induction of an endogenous immune response upon adoptive transfer of allogeneic lymphocytes without utilizing hematopoietic stem cell transplantation. While allogeneic lymphocytes have a potent ability to activate host immunity as a cell adjuvant, novel strategies that can activate endogenous antitumor activity in cancer patients remain an unmet need. In this study, we established a new method to destroy pre-developed tumors and confer potent antitumor immunity in mice using alloantigen-activated CD4+ (named AAA-CD4+) T cells. Methods AAA-CD4+ T cells were generated from CD4+ T cells isolated from BALB/c mice in cultures with dendritic cells (DCs) induced from C57BL/6 (B6) mice. In this culture, allogeneic CD4+ T cells that recognize and react to B6 mouse-derived alloantigens are preferentially activated. These AAA-CD4+ T cells were directly injected into the pre-established melanoma in B6 mice to assess their ability to elicit antitumor immunity in vivo. Results Upon intratumoral injection, these AAA-CD4+ T cells underwent a dramatic expansion in the tumor and secreted high levels of IFN-γ and IL-2. This was accompanied by markedly increased infiltration of host-derived CD8+ T cells, CD4+ T cells, natural killer (NK) cells, DCs, and type-1 like macrophages. Selective depletion of host CD8+ T cells, rather than NK cells, abrogated this therapeutic effect. Thus, intratumoral administration of AAA-CD4+ T cells results in a robust endogenous CD8+ T cell response that destroys pre-established melanoma. This locally induced antitumor immunity elicited systemic protection to eliminate tumors at distal sites, persisted over 6 months in vivo, and protected the animals from tumor re-challenge. Notably, the injected AAA-CD4+ T cells disappeared within 7 days and caused no adverse reactions. Conclusions Our findings indicate that AAA-CD4+ T cells reinvigorate endogenous cytotoxic T cells to eradicate pre-established melanoma and induce long-term protective antitumor immunity. This approach can be immediately applied to patients with advanced melanoma and may have broad implications in the treatment of other types of solid tumors.

Background Haploidentical hematopoietic stem cell transplantation (HSCT) is a useful therapy for relapsed/refractory acute leukemia or lymphoma because of the strong graft-versus-leukemia (GvL) effect. However, it is often accompanied by severe acute graft-versus-host disease (GvHD), which is the most serious complication after haploidentical HSCT. Thus, it is important to control the severity of acute GvHD while maintaining the GvL effect. In our experiences of pediatric haploidentical HSCT, it takes several days for acute GvHD to become severe after the appearance of initial symptoms, mostly skin rashes. In this study, we aimed to identify useful biomarkers at the onset of acute GvHD that predict subsequent development of severe acute GvHD. Methods Forty-five consecutive children with relapsed/refractory acute leukemia or lymphoma who developed acute GvHD after haploidentical HSCT were enrolled. We analyzed possible biomarkers from samples collected at the onset of acute GvHD. Results Nineteen patients developed grade 1-2 acute GvHD, and 26 patients developed grade 3-4 acute GvHD. There was no significant difference in patient characteristics between the two groups. Transplant-related mortality occurred only in the grade 3-4 acute GvHD group (34.5%). Multivariate analysis revealed that serum albumin was an independent biomarker for predicting the severity of acute GvHD (p=0.009). The area under the receiver operating characteristic curve of serum albumin was 0.864. Conclusions The serum albumin level at the onset of acute GvHD could be a useful biomarker for the development of subsequent severe acute GvHD in pediatric patients after haploidentical HSCT.

Chronic myeloid leukemia (CML) is an uncommon entity in pediatric patients. CML in chronic phase (CML-CP) has a relatively favorable outcome. Leukostasis occurs in 9.7% of patients with CML. One of the most serious leukostasis-related complications is intracranial hemorrhage (ICH). However, this is very rare in patients with CML-CP, and few early mortalities have been reported in CML patients with leukostasis. We report the case of a 14-year-old female patient with CML-CP who developed ICH 8 days after admission. A 14-year-old girl developed symptoms of fatigue and slight fever and was diagnosed with CML-CP. She was treated with imatinib and received low-molecular-weight heparin owing to coagulation abnormalities. However, 6 days later, she developed sensorineural hearing loss, which is a symptom of leukostasis. She received hydroxyurea to reduce her white blood cell (WBC) count, and her treatment was changed from imatinib to nilotinib. The WBC and platelet counts remained unchanged, blast counts did not increase, and mild coagulation abnormality persisted. Eight days after admission, she suddenly lost consciousness and experienced respiratory arrest. Cranial computed tomography revealed multiple ICH lesions and brain hernia. She received intensive care but was diagnosed with brain death by electroencephalography and died 14 days after hospitalization. ICH is very rare in patients with CML-CP; however, patients with leukostasis and coagulation abnormalities can develop severe hemorrhage, even in the chronic phase. Thus, it is necessary to accurately estimate the cause and provide appropriate treatment for these patients.

TCF3-HLF-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has an extremely poor prognosis. A 2-year-old boy with TCF3-HLF-positive BCP-ALL had an isolated extramedullary relapse in multiple bones after allogeneic hematopoietic stem cells transplantation (HSCT) from a human leukocyte antigen-matched unrelated donor. In this study, he received a T-cell-replete haploidentical HSCT (TCR-haplo-HSCT) from his father when in nonremission state, which resulted in a sustained complete remission for over 3 years. Immune therapies for patients with an extramedullary relapse of TCF3-HLF-positive BCP-ALL have been attempted; however, long-term efficacies of these therapies remain unknown. Our TCR-haplo-HSCT may be an effective therapeutic option for such patients.

Background: The prognosis of refractory/relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains dismal owing to acquired resistance to chemotherapeutic agents. This study aimed to evaluate the efficacy of T-cell replete HLA haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) for pediatric refractory/relapsed BCP-ALL (RR-BCP-ALL).Methods: Nineteen pediatric patients with RR-BCP-ALL underwent TCR-haplo-HSCT between 2010 and 2019 at the Fukushima Medical University Hospital. The disease status at TCR-haplo-HSCT included complete remission (CR) in eight patients and non-CR with active disease in 11 patients. Total body irradiation-based, busulfan-based, and reduced-intensity conditioning regimens were employed in 11, 6, and 2 patients, respectively. Low-dose anti-thymocyte globulin (thymoglobulin, 2.5 mg/kg) was used in all patients. Graft-vs.-host disease (GVHD) prophylaxis was administered with tacrolimus, methotrexate, and prednisolone.Results: All patients received peripheral blood stem cells as the stem cell source. The HLA disparities in graft vs. host directions were 2/8 in one, 3/8 in five, and 4/8 in 13 patients. Among 18 patients who achieved primary engraftment, acute GVHD occurred in all 18 evaluable patients (grade II, 9; grade III, 8; grade IV, 1), and chronic GVHD was observed in 10 out of 15 evaluable patients. Three patients died because of transplant-related mortality. The 3-year overall survival (OS) and leukemia-free survival rates were 57.4 and 42.1%, respectively. Compared to patients older than 10 years in age (N = 10), those younger than 10 years in age (N = 9) showed an excellent OS rate (3-year OS rate: patients < 10 years old, 100%; patients > 10 years old, 20% [95% confidence interval, 3.1–47.5]; p = 0.002).Conclusions: We suggest that TCR haplo-HSCT with low-dose ATG conditioning has the potential to improve the transplantation outcomes in patients with RR-BCP.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the preferred treatment for children with high-risk hematologic malignancies, but post-allo-HSCT relapse has a poor prognosis and limited treatment options. We evaluated the feasibility, outcome, and risk factors influencing survival after T-cell-replete haploidentical HSCT with low-dose anti-thymocyte globulin (ATG) in 30 patients with post-allo-HSCT relapse of acute lymphoblastic leukemia and acute myeloid leukemia. Overall, 50% of the patients had complete remission (CR) before the second transplant and the overall survival (OS) rate was 52%. In surviving patients (median follow-up 614 days), Kaplan-Meier analysis revealed estimated 2-year leukemia-free survival and OS rates of 48.1% and 61.1%, respectively. Cumulative incidences of 2-year non-relapse mortality and relapse were 24.7% and 36.3%, respectively. Achieving CR before the second allo-HSCT was a predominant independent prognostic factor identified in the multivariate analysis, with a significantly improved 2-year OS rate of 86.7%. T-cell-replete haplo-HSCT with low-dose ATG for second allo-HSCT may benefit a selected patient population.

Pneumorrhachis refers to the clinical presentation of air within the spinal canal, and it is rarely associated with pneumomediastinum, particularly in young children. Pneumorrhachis associated with pneumomediastinum is generally asymptomatic. Here we report 2 unusual cases involving very young children with pneumorrhachis secondary to pneumomediastinum and present a review of the relevant literature. Case 1 involved a 4-year-old girl who presented with wheezing, violent coughing, and dyspnea associated with bronchiolitis. Case 2 involved a 3-year-old boy who presented with wheezing, violent coughing, and dyspnea associated with interstitial pneumonia possibly caused by graft-versus-host disease with human herpesvirus 6 infection after allogeneic hematopoietic stem cell transplantation. In both cases, pneumorrhachis improved with oxygen inhalation therapy and treatment of the underlying disease. Pneumorrhachis is rarely associated with neurological problems; however, decompressive laminectomy may be indicated to relieve the air block. Because pneumorrhachis is rare in children and neurological sequelae may be difficult to identify, close clinical, and radiographic observations are necessary. Plain radiography is not sufficient, and computed tomography should be performed to rule out intraspinal air. Keywords: Pneumorrhachis, Pneumomediastinum, Children

Trench-filling epitaxial growth of 4H-SiC by chemical vapor deposition (CVD) with and without HCl was analyzed based on a continuum-diffusion model including the Gibbs–Thomson effect. Qualitative reproduction of the reported observation showed that the effective surface free energy of SiC during CVD can be doubled by the addition of HCl

Ranges for Al implantations into 4H-SiC (0001) were compared between channeled-ion implantation (without using a MeV implanter) and non-channeled ion implantation using an ion energy E0 in the Bethe–Bloch region (IIBB). Since the latter (i.e., projected range of 7.5 μm at E0 = 26 MeV) was larger than the former (i.e., maximum channeled range of 3.4 μm at E0 = 900 keV), IIBB was concluded to be suitable to minimize the repeat count of epitaxial growth/ion implantation steps used in the fabrication of 4H-SiC superjunction power devices.

By inspecting the CVD growth parameters, such as the flow rates of HCl and H2 carrier gases, the pressure and the C/Si ratio, the trench filling in a high-rate mode with a high growth rate on the bottom and a relatively low growth rate on the mesa top was carried out. 4H-SiC trenches with the depths of 48 and 55 μm have been completely filled at the rates of 6.2 and 5.5 μm/h, respectively.

To apply channeled-ion implantation to cost-effective multi-epitaxial growth for 4H-SiC superjunction devices, we re-evaluated the Al-ion energy (E) dependence of the electronic stopping cross section (S e) in 4H-SiC based on the recently reported secondary-ion mass spectrometry measured depth profiles. By including the effect of stripping of the ion electrons on the E dependence of S e, we successfully reproduced the reported maximum channeled ranges of Al into 4H-SiC (0001), ranging from 0.6 μm at the implantation-energy (E 0) of 60 keV to 7.2 μm at E 0 of 8 MeV.

Based on the Burton–Cabrera–Frank (BCF) and Cabrera–Levine theories, supersaturation at steps (σ step) during chemical vapor deposition of 4H-SiC (0001̄) at 1570 °C under the condition of C/Si ratio of unity was estimated from the reported growth rate and cross-sectional profile of a spiral hillock, as a function of surface diffusion length of C2H2 molecules (λC2H2). The previously assumed zero σ step in the BCF theory was found to be a possible source of error in the case λC2H2 > 0.63 μm because of the estimated ratio of σ step to the surface supersaturation exceeding 0.1.

Anode-size-independent forward current–density/voltage (V) characteristics of circular GaN p+n diodes were extracted (in the V range of 2.7−3.0 V) from measured ones by an estimation technique of the effective anode radius, followed by the least-squares fitting technique of peripheral-to-area ratio analysis. It was found that the extracted diffusion current of diodes with a higher p-type doping level is lower than that of diodes with a lower one and that both currents have an ideality factor of unity. Since these findings agree with the diffusion theory, the demonstrated method should be useful for theoretical analysis of GaN p+n diodes.

Reported experimental results on homoepitaxially grown nitrogen-doped 4H-SiC on (03 3 ¯ 8) and misoriented (0001) substrates under carbon-rich conditions in a SiH4–C3H8–N2–H2 system were analyzed according to surface diffusion theory dealing with step kinetics. On misoriented (0001) surfaces at 1723–1873 K, the relaxation time for a silicon adatom to enter a step was negligibly small. This finding, however, was not the case with the relaxation time for nitrogen-containing species (τ k N). The ratio of τ k N to the residence time of the nitrogen-containing species on the surfaces was estimated to be 0.1–0.2 at 1723–1823 K and 0.04 at 1873 K.

Aluminum doping during 4H-SiC chemical-vapor-deposition (CVD) trench filling was numerically modeled toward precise design of high-voltage superjunction devices. As a first-order approximation, growth-rate- and surface-normal-scaling functions were determined based on the reported experimental results. Simulated isoconcentration contours of aluminum were confirmed to qualitatively agree with the reported imaging of doping in SiC by scanning spreading resistance microscopy. Improvement of the proposed models based on additional experiments should contribute to reducing the development time for 4H-SiC superjunction devices fabricated using CVD trench filling.

The characteristics of p-n junction diodes on heavily Ge-doped substrates were compared with those on conventional Si-doped substrates. A large decrease in on-resistance was observed which greatly exceeded the component due to the lower resistance of the Ge-doped substrate. This result implied an occurrence of a strong conductivity modulation by the heavily doped substrate. Current-density dependence on the anode-electrode diameter could be minimized by the use of the substrate. No significant difference was observed in the breakdown voltage even when the doping concentration in the substrate was increased. It has been clarified that the heavily Ge-doped GaN substrate is essential for low on-resistance and large size GaN power devices.

Influences of hole traps on large forward current (I F) of GaN p+n diodes on low-dislocation-density (≤4 × 105 cm−2) GaN substrates were numerically investigated. As with the reported simulation of GaAs p+n diodes, hole traps were found to increase the electron concentration in the drift layer when forward voltage V F was increased. To reproduce the measured I F/V F characteristics, however, we had to assume an unrealistic electron mobility increasing with the electric field. We, therefore, concluded that sources other than hole traps were responsible for the reported enhancement of conductivity modulation in GaN p+n diodes.

By mapping the source and HCl flow rates dependent growth rates, the evolving trend of a quasi-selective epitaxial growth (quasi-SEG) that growing very thin epilayer on mesa top and ensuring an extremely low risk of voids defect generation was firstly figured out on a 5-μm 4H-SiC trench. Then, basing on the acquired knowledge, a 25-μm 4H-SiC trench with an aspect ratio up to ~10 was completely filled in the quasi-SEG mode.

Based on Burton−Cabrera−Frank theory and the step-edge segregation model, we analyzed the reported difference in the sheet concentration of doped magnesium under naturally formed surface stripes on homo-epitaxially grown layers on a freestanding GaN substrate misoriented from a c-plane by 0.3°. By assuming the step height being equal to the peak-to-valley height of the surface stripes, we considered the growth steps on gently and sharply sloped surfaces to be supplied, respectively, from mixed dislocations and the misorientation from the c-plane. The step-velocity dependence of the magnesium concentration was reproduced with the reported magnesium diffusivity of 3 × 10−14 cm2 s−1.

Trench-filling epitaxial growth of 4H-SiC was analyzed based on a simulation model for continuous fluid approximation including the Gibbs-Thomson effect. With the use of the radii of curvature at the top and bottom of the trenches, the proposed model well reproduced the measured dependence of the growth rate on the trench pitch (L) in the case of narrow (L ≤ 6.0 μm) trenches.

Predictors of peripheral blood stem cell (PBSC) yield can potentially improve the comfort, safety, and efficacy of CD34+ cell collection from donors treated with recombinant human granulocyte colony-stimulating factor (G-CSF). We investigated 181 apheresis procedures on 109 healthy allogeneic donors to identify factors correlating with efficient PBSC collection. Apheresis started on Day 4 or 5 and continued up to Day 6 of G-CSF administration. CD34+ cell yields on Days 4 and 5 were comparable, and significantly higher than on Day 6. This suggests that starting apheresis on Day 4 rather than Day 5 may be preferable, to reduce G-CSF exposure and optimize yield, even if multi-day collection is required. More CD34+ cells were collected from male and cytomegalovirus (CMV)-seronegative donors than from female and CMV-seropositive donors, respectively. The yields of CD34+ cells were similarly high in both male and female donors aged 20–29 years; yields decreased in female donors in their thirties, and were comparably low in both male and female donors in their forties and thereafter. These findings should guide decision-making about when to begin apheresis, and encourage careful consideration of donor factors such as gender, age, and CMV serostatus when collecting PBSCs.

A super-junction (SJ) device has been developed to improve the trade-off relationship between the breakdown voltage ( $V_{\text{BD}}$ ) and specific on-resistance ( $\boldsymbol{R}_{\mathbf{onA}}$ ). A multi-epitaxial (ME) growth method had been used for fundamental demonstrations, but this method needs a lot of repetitions of epitaxial growth and implantation in the case of SiC material. A trench-filling epitaxial (TFE) growth method is expected as a promising alternative, especially for high-voltage devices. In this study, we have established critical fabrication processes for a thick ( $> 20\ \boldsymbol{\mu} \mathbf{m}$ ) and high-aspect-ratio SJ structure. The measured $\boldsymbol{R}_{\mathbf{onA}}$ of a 7.8 kV SJ MOSFET was $17.8\ \mathbf{m}\mathbf{\Omega}\cdot \mathbf{cm}^{2}$ , which is less than half the $\boldsymbol{R}_{\mathbf{onA}}$ of the state-of-the-art 6.5 kV-class SiC MOSFET with an n-type drift layer. Improvement of trade-off relationship exceeding the 4H-SiC theoretical limit was experimentally demonstrated for the first time.

Long-term survival rates for pediatric patients with cancer have significantly improved, but novel approaches are desired for those with refractory/relapsed solid tumors. Recently, programed cell death-1/programed cell death-ligand-1 blockade has emerged as an effective option for many intractable cancers. However, not all patients show objective response to such therapy. On the other hand, several other checkpoint pathways, including Herpes virus entry mediator (HVEM)/B- and T-lymphocyte attenuator (BTLA), galectin-9 (GAL9)/T-cell immunoglobulin and mucin domain-3 (TIM3), and major histocompatibility complex class II (MHC-II)/lymphocyte activation gene-3 (LAG3), also regulate immune responses in the tumor microenvironment and may be alternative targets for novel immune therapies. In this study, we examined 65 common pediatric solid tumors and characterized the expression of Herpes virus entry mediator, GAL9, and MHC-II on tumor cells and their corresponding receptors B- and T-lymphocyte attenuator, TIM3, and LAG3, respectively, on tumor-infiltrating lymphocytes (TILs) with immunohistochemistry. Whereas the expression of GAL9 and MHC-II was limited, 73% of rhabdomyosarcomas and 100% of osteosarcomas expressed moderate to high levels of Herpes virus entry mediator on the tumor. TILs were detected in all tumor samples except one osteosarcoma. Interestingly, 45% of rhabdomyosarcomas, and 45% of osteosarcomas expressed moderate to high levels of both Herpes virus entry mediator on the tumor cells and B- and T-lymphocyte attenuator on the TILs. Results showed that a subset of pediatric solid tumors expressed tumor-associated checkpoint molecules, and TILs expressed corresponding receptors for these checkpoint molecules. Thus, immunogenic environments may be created, and checkpoint blockade may induce favorable immune responses.

A 3.3-kV SiC-Si hybrid module, composed of a low-forward-voltage (VF) SiC junction-barrier-Schottky (JBS) diode and a low-saturation-voltage VCE(sat) Si trench IGBT was fabricated and demonstrated highly efficient operation.

Reported experimental results on homoepitaxial 4H-SiC grown by chemical vapor deposition on 1°- and 4°-off (0001) surfaces under silicon-rich conditions in a SiH4−C3H8−N2−H2 system are quantitatively analyzed according to surface diffusion theory dealing with step dynamics. The surface-diffusion lengths of carbon- and nitrogen-containing molecules are, respectively, estimated to be λ C = 25 nm and λ N ≥ λ C at 1773 K. This magnitude relationship agrees with the reported assumption made for the variation in nitrogen concentration on (000 1 – ) facets of 4H-SiC grown by physical vapor transport.

4H-SiC trenches with depths of approximately 25 μm were filled under a special condition called the quasi-selective epitaxial growth mode that showed a refill-rate of 2.1 μm/h within 12 h, using a hot-wall chemical vapor deposition (CVD) method with the assistance of HCl gas. To develop a high-rate growth mode for the 4H-SiC trench filling process, several CVD growth parameters, such as the flow rates of source gases, HCl and H2 carrier gases, their pressures, and the applied C/Si ratio, were regulated and optimized, to enhance the partial pressures of the source species in the gas phase of the CVD reactor. A refill-rate of 11.4 μm/h in 2 h was achieved, which is nearly five times faster than the initial growth.

Mismatched HLA loss is a cause of leukemia relapse after HLA-haploidentical stem cell transplantation (haplo-SCT). We report a patient with a history of 2 occurrences of leukemia relapse due to mismatched HLA loss after haplo-SCT. He received haplo-SCT from his father but showed leukemia relapse with loss of the maternal HLA haplotype. He then underwent haplo-SCT from his mother, and developed relapse with loss of the paternal HLA haplotype. Both donors had killer cell immunoglobulin-like receptor-ligand mismatch but alloreactive natural killer cells could not prevent relapse. Second haplo-SCT should be conducted carefully for patients with relapse due to mismatched HLA loss.

Correlation between step velocity and carbon incorporation during step-flow growth of GaN were analyzed from standpoints of the mean time till a carbon atom incorporated at the kink site escapes from the step-edge site, τ, and the length of time before the carbon concentration at the step-edge site reaches its equilibrium value, τstep. Reported step-velocity dependencies of carbon concentration in GaN were successfully reproduced with assumptions τ >> τstep (step-edge segregation) and τ < τstep (kink segregation). Due to the difficulty in estimating τ and τstep, additional experiments are needed to tell which segregation is dominant for carbon in GaN.