Suzaku Observations of M82 X-1 : Detection of a Curved Hard X-ray Spectrum

A report is presented on Suzaku observations of the ultra-luminous X-ray source X-1 in the starburst galaxy M82, made three time in 2005 October for an exposure of ~ 30 ks each. The XIS signals from a region of radius 3 around the nucleus defined a 2-10 keV flux of 2.1 x 10^-11 erg s-1 cm-2 attributable to point sources. The 3.2-10 keV spectrum was slightly more convex than a power-law with a photon index of 1.7. In all observations, the HXD also detected signals from M82 up to ~ 20 keV, at a 12-20 keV flux of 4.4 x 10^-12 erg s-1 cm-2 . The HXD spectrum was steeper than that of the XIS. The XIS and HXD spectra can be jointly reproduced by a cutoff power-law model, or similar curved models. Of the detected wide-band signals, 1/3 to 2/3 are attributable to X-1, while the remainder to other discrete sources in M82. Regardless of the modeling of these contaminants, the spectrum attributable to X-1 is more curved than a power-law, with a bolometric luminosity of (1.5 -3) x 10 ^40 erg s-1. These results are interpreted as Comptonized emission from a black hole of 100-200 solar masses, radiating roughly at the Eddington luminosity.Comment: 19 pages, 9 figures, accepted in Publications of the Astronomical Society of Japa

Image‐Guided Adaptive Brachytherapy for Cervical Cancer Using Magnetic Resonance Imaging: Overview and Experience

Image-guided adaptive brachytherapy (IGABT) using magnetic resonance imaging (MRI) has been accepted as a novel treatment technique for cervical cancer. During the development of MRI-based IGABT, a very important concept called “High-risk clinical target volume (HR-CTV)” was introduced. However, computed tomography (CT)-based IGABT is the most common modality in Japan

New Paradigms of Radiotherapy for Bone Metastasis

Proper care of patients with bone metastasis requires interdisciplinary treatments. Radiotherapy (RT) plays a central role in the management of painful bone metastasis. External beam RT can provide rapid successful palliation of painful bone metastasis in 50–80% of patients, is associated with very few adverse effects and leads to complete pain relief at the treated site in up to one‐third of patients. Intensity‐modulated RT (IMRT) or stereotactic body RT (SBRT) enables the delivery of higher doses to the target tumor while minimizing the dose to adjacent organs. Reirradiation using IMRT or SBRT is a valuable option for the management of bone metastases. A multidisciplinary team, especially one consisting of a spinal surgeon and rehabilitation physician, is particularly useful for treating patients with spinal bone metastases characterized by spinal instability. Rehabilitation intervention which increases the physical activity level and prevents deconditioning is important. Future developments in surgical procedures and RT will likely improve the management protocols for bone metastases and technology to reduce metal artifacts in radiation planning might improve the efficacy and safety of combination therapy

Evaluation of flight efficiency for Stockholm Arlanda Airport arrivals

Analysis of punctuality of airport arrivals, as well as identification of causes of the delays within transition airspace, is an important step in evaluating performance of the Terminal Maneuvering Area (TMA) Air Navigation Services: without knowing the current performance levels, it is difficult to identify which areas could be improved. Deviations from the flight plans is one of the major reasons for arrival delays. In this work, we quantified the impact of the deviations from the flight plans on the fuel burn. One of the main reasons of fuel waste is non- optimal vertical profiles during the descent phase. We calculated how much extra fuel is wasted due to vertical flight inefficiency within Stockholm TMA.Peer ReviewedPostprint (published version

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

Exosome-mediated radiosensitizing effect on neighboring cancer cells via increase in intracellular levels of reactive oxygen species

The precise mechanism of intercellular communication between cancer cells following radiation exposure is unclear. Exosomes are membrane-enclosed small vesicles comprising lipid bilayers and are mediators of intercellular communication that transport a variety of intracellular components, including microRNAs (miRNAs or miRs). The present study aimed to identify novel roles of exosomes released from irradiated cells to neighboring cancer cells. In order to confirm the presence of exosomes in the human pancreatic cancer cell line MIAPaCa-2, ultracentrifugation was performed followed by transmission electron microscopy and nanoparticle tracking analysis (NanoSight) using the exosome-specific surface markers CD9 and CD63. Subsequent endocytosis of exosomes was confirmed by fluorescent microscopy. Cell survival following irradiation and the addition of exosomes was evaluated by colony forming assay. Expression levels of miRNAs in exosomes were then quantified by microarray analysis, while protein expression levels of Cu/Zn- and Mn-superoxide dismutase (SOD1 and 2, respectively) enzymes in MIAPaCa-2 cells were evaluated by western blotting. Results showed that the uptake of irradiated exosomes was significantly higher than that of non-irradiated exosomes. Notably, irradiated exosomes induced higher intracellular levels of reactive oxygen species (ROS) and a higher frequency of DNA damage in MIAPaCa-2 cells, as determined by fluorescent microscopy and immunocytochemistry, respectively. Moreover, six up- and five downregulated miRNAs were identified in 5 and 8 Gy-irradiated cells using miRNA microarray analyses. Further analysis using miRNA mimics and reverse transcription-quantitative PCR identified miR-6823-5p as a potential candidate to inhibit SOD1, leading to increased intracellular ROS levels and DNA damage. To the best of our knowledge, the present study is the first to demonstrate that irradiated exosomes enhance the radiation effect via increasing intracellular ROS levels in cancer cells. This contributes to improved understanding of the bystander effect of neighboring cancer cells

New proposal to revise the classification for squamous cell carcinoma of the external auditory canal and middle ear

Background The prognosis of patients with advanced squamous cell carcinoma of the external auditory canal and middle ear has been improved by advances in skull base surgery and multidrug chemoradiotherapy during the last two decades. Methods Ninety-five patients with squamous cell carcinoma of the external auditory canal and middle ear who were treated between 1998 and 2017 were enrolled. The number of patients with tumour stages T1, T2, T3 and T4 was 15, 22, 24 and 34, respectively. Oncological outcomes and prognostic factors were retrospectively investigated. Results Among patients with T4 disease, invasion of the brain (p = 0.024), carotid artery (p = 0.049) and/or jugular vein (p = 0.040) were significant predictors of poor prognosis. The five-year overall survival rate of patients with at least one of these factors (T4b) was significantly lower than that of patients without these factors (T4a) (25.5 vs 65.5 per cent, p = 0.049). Conclusion It is proposed that stage T4 be subclassified into T4a and T4b according to the prognostic factors