Asymmetrical normal-zone propagation observed in the aluminum-stabilized superconductor for the LHD helical coils

Transient normal-transitions have been observed in the superconducting helical coils of the Large Helical Device (LHD). Stability tests have been performed for an R&D coil as an upgrading program of LHD, and we observed asymmetrical propagation of an initiated normal-zone. In some conditions, a normal-zone propagates only in one direction along the conductor and it hence forms a traveling normal-zone. The Hall electric field generated in the longitudinal direction in the aluminum stabilizer is a plausible candidate to explain the observed asymmetrical normal-zone propagation

Stability and safety estimates and tests of a superconducting bus-line for large-scale superconducting coils

We have been developing a flexible superconducting bus-line as a unit electrical feeder between large-scale superconducting coils and their power supplies away from the coils. The designed superconducting bus-line consists of a pair of +/- aluminum stabilized NbTi/Cu compacted strand cables and a coaxial four-channel transfer line. A full-scale model of the SC bus-line (20 m long) has been constructed and tested successfully up to 40 kA without a quench under the short-circuit condition. Stability tests were also done by inducing a forced quench with heaters. A minimum propagation current larger than 32.5 kA was confirmed. Thus, the bus-line was cryogenically stabilized at the rated current of 30 kA. We have examined the test results and evaluated the stability and safety margins of this bus-line. The design criteria for a superconducting bus-line are also shown for large-scale superconducting coils with operating current as a parameter

Antitumor activity of α-pinene in T-cell tumors

T-cell acute leukemia and lymphoma have a poor prognosis. Although new therapeu-tic agents have been developed, their therapeutic effects are suboptimal. α- Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic ma-lignancies. This report provides a comprehensive analysis of the potential benefits of using α- pinene as an antitumor agent for the treatment of T-cell tumors. We found that α- pinene inhibited the proliferation of hematologic malignancies, especially in T- cell tumor cell lines EL-4 and Molt-4, induced mitochondrial dysfunction and re-active oxygen species accumulation, and inhibited NF-κB p65 translocation into the nucleus, leading to robust apoptosis in EL-4 cells. Collectively, these findings suggest that α- pinene has potential as a therapeutic agent for T-cell malignancies, and further investigation is warranted

First Cool-Down Performance of the LHD

The first cool-down test of the Large Helical Device (LHD) and the performance of the LHD cryogenic system during the first cycle operation are described. The first cool-down started on Feb. 23, 1998 and finished on Mar. 22. After the cool-down, the excitation tests of the SC coils up to 1.5 T and the first cycle operations for plasma physics experiments were conducted until May 18. The first cycle operation was successfully completed after the warm-up process to room temperature from May 19 to Jun. 15. The cooling characteristics of the LHD, such as temperature distribution during cool-down, heat loads under steady state condition, reliability during long-term operation, are reporte

Research Activities in the Department of Physical Therapy

[Introduction] It is already fifty years since the Japanese law of physical therapists and occupational therapists has been effective. The physical therapist is referred by the law as "the professionals who implements the physical therapy to persons with disabilities under the prescription of medical doctors". In fifty years, however, the target of physical therapy has been significantly expanded. The subject for physical therapy now includes the patients in acute disease just after the surgical operation in addition to those in rehabilitation stage. In other words, the physical therapy is now recognized as the indispensable intervention to the subject with acute as well as chronic disorders. On the other hand, due to a rapid transition of the society into the aged society, prevention of diseases, and decline of activity capacity due to the aging have become major issues for the physical therapy

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

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

Promoter Hypermethylation of p16 during Neoplastic Transformation of Rat Respiratory Tract Epithelial Cells.

To investigate whether p16 hypermethylation is involved in the silencing of p16 expression and the development of rat lung tumors, p16 status and neoplastic transformation of several respiratory tract epithelial cell lines were examined. Analysis utilizing methylation specific PCR (MSP) method revealed that virus-immortalized SV40T2 cells had unmethylated status and that benzo [a] pyrene-induced BP cells displayed heterogeneous methylation status of the p16 promoter region. On the other hand, BP130, BP270 and BP(P)Tu cells derived from BP cells, and gamma ray-transformed RTiv3 cells displayed complete methylation of the gene. The MSP and PCR of genomic DNA in the p16 region did not amplify product in PuD2 cells established from the plutonium-induced lung tumor. Expression analysis of p16 mRNA by RT-PCR demonstrated that SV40T2 and BP cells expressed the p16 transcript. Demethylating agent, 5AzaC demethylated partially the p16 promoter region of BP(P)Tu and BP cells and increased expression of the p16 transcript. Tumorigenicity assay utilizing inoculation of the cells into nude mouse revealed that SV40T2 and RTiv3 cells had no tumorigenicity. Treatment of BP(P)Tu and BP cells with 5AzaC decreased the cell growth in nude mouse. These results indicate that the hypermethylation of p16 promoter region occurs at the early stage of neoplastic transformation processes and the gene silencing following the methylation is partially concerned with the tumorigenicity of rat respiratory tract cells. Homozygous deletion and lack of expression of the p16 may also account for the mechanisms of tumorigenicity.The 6th Japan-France Workshop on Radiobiology and Isotopic Imagin

Comparison of radiation sensitivity of rat respiratory tract epithelial cells

Lung model of ICRP publication 66 describes that cells at risk in respiratory tract tissues are secretory and basal cells in bronchial airways, and Clara and Type II cells in alveolar interstitial region. It is, however, unclear whether there is a difference in radiation sensitivities between the target cells. The purpose of this study is to compare the dose-response relationships of radiation-induced cell death and transformation in primarily cultured rat tracheal epithelial (RTE) and rat lung epithelial (RLE) cells. The RLE cells were isolated from lung of female Wistar rats (4-6-week-old) by enzyme digestion and gradient centrifugation. Tracheae were filled with enzyme solution, and then the RTE cells were rinsed from inside the tracheae. The RLE and RTE cells were cultured in serum free medium including epidermal growth factor and other necessary factors. The cells were irradiated using an alpha source of 238Pu (3.6MeV, 0.8Gy/min) or a gamma source of 137Cs (8.2Gy/min). The cytotoxic responses of the cells to irradiations were determined in colony formation assay. Transformants formed dense colonies in 2% serum containing and growth factor-free selective medium, and transformation frequencies (TF) were calculated from number of the colonies.The irradiation caused similarly an exponential decrease in survival in the RLE and RTE cells, and D37 of alpha particle and gamma ray were 0.65 Gy and 3.6 Gy, respectively. Relative biological effectiveness (RBE) for cell killing was 5.5 in the both types of cell. TF for the RLE and RTE were 3.7x10-3E and 2.4x10-3E at 2 Gy of alpha particle, respectively. At 7.5 Gy of gamma ray, TF for the RLE and RTE increased to 8.0x10-3E and 7.1x10-3E, respectively. The RBE for transformation of RLE was 1.7, and that of RTE was 1.3. These results indicate that there is no difference between the radiation sensitivities of the RLE and the RTE cells in culture condition. This primary epithelial cell culture system of rat lung will be useful for analysis of radiation sensitivity among the different target cells and mechanistic studies of early changes in radiation-induced carcinogenesis.13th international Congress of Radiation Researc