Observations of hard X-rays of auroral origin with Polar Patrol Balloons No. 8 and 10

In the Polar Patrol Balloon (PPB) project, two balloons named PPB-8 and -10 were launched in rapid succession to form a cluster of balloons during their flight on January 13, 2003, from Syowa Station, Antarctica. In order to make the two-dimensional images for auroral X-rays and to obtain the energy spectra of auroras with energy range from 30 keV to 778 keV, the same instruments for hard X-rays were installed on PPB-8 and -10, respectively. These detection systems observed several auroral X-ray events during the flight. In particularly on January 25, 2003, strong auroral events were detected at about 0919 UT by PPB-10 and at 0927 UT by PPB-8. The aurora observed by PPB-10 was observed after about 8 min by PPB-8 located a 650 km west of PPB-10. The energy spectra of the bright aurora at 0919 UT and 0927 UT for PPB-10 and -8 is obtained as E0 = (78+-5) keV and (70+-5) keV, respectively

Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors

AK2 is an adenylate phosphotransferase that localizes at the intermembrane spaces of the mitochondria, and its mutations cause a severe combined immunodeficiency with neutrophil maturation arrest named reticular dysgenesis (RD). Although the dysfunction of hematopoietic stem cells (HSCs) has been implicated, earlier developmental events that affect the fate of HSCs and/or hematopoietic progenitors have not been reported. Here, we used RD-patient-derived induced pluripotent stem cells (iPSCs) as a model of AK2-deficient human cells. Hematopoietic differentiation from RD-iPSCs was profoundly impaired. RD-iPSC-derived hemoangiogenic progenitor cells (HAPCs) showed decreased ATP distribution in the nucleus and altered global transcriptional profiles. Thus, AK2 has a stage-specific role in maintaining the ATP supply to the nucleus during hematopoietic differentiation, which affects the transcriptional profiles necessary for controlling the fate of multipotential HAPCs. Our data suggest that maintaining the appropriate energy level of each organelle by the intracellular redistribution of ATP is important for controlling the fate of progenitor cells

Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model

Whole-organ regeneration has great potential for the replacement of dysfunctional organs through the reconstruction of a fully functional bioengineered organ using three-dimensional cell manipulation in vitro. Recently, many basic studies of whole-tooth replacement using three-dimensional cell manipulation have been conducted in a mouse model. Further evidence of the practical application to human medicine is required to demonstrate tooth restoration by reconstructing bioengineered tooth germ using a postnatal large-animal model. Herein, we demonstrate functional tooth restoration through the autologous transplantation of bioengineered tooth germ in a postnatal canine model. The bioengineered tooth, which was reconstructed using permanent tooth germ cells, erupted into the jawbone after autologous transplantation and achieved physiological function equivalent to that of a natural tooth. This study represents a substantial advancement in whole-organ replacement therapy through the transplantation of bioengineered organ germ as a practical model for future clinical regenerative medicine

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

A Mixed-Methods Approach to Analyze Shared Epistemic Agency in Jigsaw Instruction at Multiple Scales of Temporality

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Analysis of Heat Transfer Behaviors in EAGLE ID1 Test Using Particle-Based Simulation Method

In the EAGLE in-pile ID1 test, which has been performed by Japan Atomic Energy Agency (JAEA) to demonstrate early fuel discharge from a fuel subassembly with an inner duct structure (FAIDUS), it was deduced that observed early duct wall failure was initiated by high heat flux from the molten pool of fuel and steel mixture. The posttest analyses suggest that pool-to-duct wall heat transfer might be enhanced effectively by the molten steel in the pool without the presence of fuel crust on the duct wall. In the present study, mechanisms of effective heat transfer from the molten pool to the duct wall was analyzed using a fully Lagrangian approach based on the finite volume particle (FVP) method for multi-component, multi-phase flows. Material distribution as well as steel droplet size in the molten pool after its formation was considered as parametric simulations. The present 2D particle-based simulations demonstrated that large thermal load that leads to early duct wall failure can be caused by local contact of molten steel to the duct wall as well as discrete formation of fuel crust on the duct wall

Analysis of Heat Transfer Behaviors in EAGLE ID1 Test Using Particle-Based Simulation Method

In the EAGLE in-pile ID1 test, which has been performed by Japan Atomic Energy Agency (JAEA) to demonstrate early fuel discharge from a fuel subassembly with an inner duct structure (FAIDUS), it was deduced that observed early duct wall failure was initiated by high heat flux from the molten pool of fuel and steel mixture. The posttest analyses suggest that pool-to-duct wall heat transfer might be enhanced effectively by the molten steel in the pool without the presence of fuel crust on the duct wall. In the present study, mechanisms of effective heat transfer from the molten pool to the duct wall was analyzed using a fully Lagrangian approach based on the finite volume particle (FVP) method for multi-component, multi-phase flows. Material distribution as well as steel droplet size in the molten pool after its formation was considered as parametric simulations. The present 2D particle-based simulations demonstrated that large thermal load that leads to early duct wall failure can be caused by local contact of molten steel to the duct wall as well as discrete formation of fuel crust on the duct wall