GRAVITATIONAL EFFECT ON GROWTH OF InX Ga1-XSb TERNARY BULK CRYSTALS

The effect of gravity on dissolution of GaSb in InSb melt and growth of InGaSb was experimentally investigated using GaSb(seed)/InSb/GaSb(feed) sandwich samples. Two parameters were considered: (1) the inclination angle of the sample for gravity as 0°, 53° and 90°, (2) the sample diameter (D) as 9 mm and 5mm. When θ =0°, the interface was almost flat whereas the interfaces were strongly distorted when θ = 53° and 90°. The undissolved GaSb(feed) remained for \theta = 0 °. However, it dissolved completely for θ = 90°, and partially for θ = 53°. As the gravitational angle was increased, the growth length of uniform composition became long. The decrease of sample diameter reduced the dissolution area of GaSb. These facts indicated that the dissolution and growth processes were strongly influenced by gravity

犬モデルにおける ex vivo および in vivo 遺伝子治療のための代替遺伝子導入技術の開発

Introduction: Gene therapy have recently attracted much attention as a curative therapeutic option for inherited single gene disorders such as hemophilia. Hemophilia is a hereditary bleeding disorder caused by the deficiency of clotting activity of factor VIII (FVIII) or factor IX (FIX), and gene therapy for hemophilia using viral vector have been vigorously investigated worldwide. Toward further advancement of gene therapy for hemophilia, we have previously developed and validated the efficacy of novel two types of gene transfer technologies using a mouse model of hemophilia A. Here we investigated the efficacy and safety of the technologies in canine model. Especially, validations of technical procedures of the gene transfers for dogs were focused. Methods: Green fluorescence protein (GFP) gene were transduced into normal beagle dogs by ex vivo and in vivo gene transfer techniques. For ex vivo gene transfer, blood outgrowth endothelial cells (BOECs) derived from peripheral blood of normal dogs were transduced with GFP gene using lentivirus vector, propagated, fabricated as cell sheets, then implanted onto the omentum of the same dogs. For in vivo gene transfer, normal dogs were subjected to GFP gene transduction with non-viral piggyBac vector by liver-targeted hydrodynamic injections. Results: No major adverse events were observed during the gene transfers in both gene transfer systems. As for ex vivo gene transfer, histological findings from the omental biopsy performed 4 weeks after implantation revealed the tube formation by implanted GFP-positive BOECs in the sub-adipose tissue layer without any inflammatory findings, and the detected GFP signals were maintained over 6 months. Regarding in vivo gene transfer, analyses of liver biopsy samples revealed more than 90% of liver cells were positive for GFP signals in the injected liver lobes 1 week after gene transfers, then the signals gradually declined overtime. Conclusions: Two types of gene transfer techniques were successfully applied to a canine model, and the transduced gene expressions persisted for a long term. Toward clinical application for hemophilia patients, practical assessments of therapeutic efficacy of these techniques will need to be performed using a dog model of hemophilia and FVIII (or FIX) gene.博士（医学）・乙第1517号・令和3年12月21日© 2021, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/)

Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps

We previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin (POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP (P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml (P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP

Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis

Background: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. Methods: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. Results: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. Conclusions: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence

Fast Prediction of Transport Structures in the Melt by Physics Informed Neural Networks during ‘VMCz’ Crystal Growth of Silicon

Fast prediction of fluid flow and thermal fields during the growth of bulk silicon single crystals by the ‘Vertical Magnetic Field Applied Czochralski (VMCz) Method’ was successfully achieved by the application of Physics Informed Neural Networks (PINNs) without any answer-labeled training data generated by a numerical simulation. The PINNs’ results are in good agreement with those of the numerical simulation. The prediction time by PINNs was significantly reduced; to less than 0.1 seconds compared with about 30 minutes required by the numerical simulation. Moreover, being mesh-free techniques, PINNs do not require mesh reconstruction to accommodate the change in the growth melt volume during growth. This shows that PINNs have great potential, as real-time simulation techniques, for future applications in various areas

TED-AJ03-107 NUMERICAL STUDY OF THERMAL AND SOLUTAL MARANGONI CONVECTION IN A 3-DIMENSIONAL FLOATING FULL-ZONE LIQUID BRIDGE

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Sphingosylphosphorylcholine and lysosulfatide have inverse regulatory functions in monocytic cell differentiation into macrophages.

Sphingolipids act as signaling mediators that regulate a diverse range of cellular events. Although numerous sphingolipid functions have been studied, little is known about the effect of sphingolipids on monocyte differentiation into macrophages. Here, we report that two lysosphingolipids, sphingosylphosphorylcholine (SPC) and lysosulfatide (LSF), inversely affect macrophagic differentiation of monocytic cell lines, U937 and THP-1. Molecular analyses revealed that SPC enhances, whereas LSF suppresses, phorbol ester-induced classical (M1-polarized) differentiation to macrophages. The expression of CD11b, a macrophage marker, was induced in accordance with the activation status of the Raf/MEK/ERK signaling pathway in which SPC and LSF had opposite effects. Pharmacological inhibition of this pathway aborted the differentiation, indicating that this signaling pathway is required. Consistently, SPC promoted, while LSF inhibited, monocyte adhesion to fibronectin, through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. The effects of SPC on Raf/MEK/ERK and PI3K/Akt signaling were dependent on G(i/o), whereas the SPC-induced calcium influx was dependent on G(q). Thus SPC utilizes G-protein coupled receptor. In contrast, the effects of LSF were independent of G(i/o) and G(q). These results suggest that SPC enhances, whereas LSF suppresses, monocyte differentiation into macrophages through regulating the Raf/MEK/ERK and PI3K/Akt signaling pathways via distinct mechanisms

The Relative Contribution of Solutal Marangoni Convection to Thermal Marangoni Flow Instabilities in a Liquid Bridge of Smaller Aspect Ratios under Zero Gravity

The effect of solutal Marangoni convection on flow instabilities in the presence of thermal Marangoni convection in a Si-Ge liquid bridge with different aspect ratios A_s has been investigated by three-dimensional (3D) numerical simulations under zero gravity. We consider a half-zone model of a liquid bridge between a cold (top plane) and a hot (bottom plane) disks. The highest Si concentration is on the top of the liquid bridge. The aspect ratio (A_s) drastically affects the critical Marangoni numbers: the critical solutal Marangoni number (under small thermal Marangoni numbers (Ma_TA_s<_~1800)) has the same dependence on As as the critical thermal Marangoni number (under small solutal Marangoni numbers (400<_~Ma_CA_s<_~800)), i.e., it decreases with increasing A_s. The azimuthal wavenumber of the traveling wave mode increases as decreasing A_s, i.e., larger azimuthal wavenumbers (m=6,7,11,12, and 13) appear for A_s=0.25, and only m=2 appears when A_s is one and larger. The oscillatory modes of the hydro waves have been extracted as the spatiotemporal structures by using dynamic mode decomposition (DMD). The present study suggests a proper parameter region of quiescent steady flow suitable for crystal growth for smaller aspect ratios of the liquid bridge