National Institutes for Quantum and Radiological Science and Technology
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Lack of XRCC4 Remarkably Enhances Radiosensitivity of Human Colon Cancer Stem Cells
No full textPurpose: The X-ray cross-complementing group 4 (XRCC4) is a key gene for DNA double-strand breaks (DSB) in the nonhomologous DNA end-joining (NHEJ) pathway (1, 2). In this study, we investigate the relationship between XRCC4 and cancer stem cell (CSC) properties and the contribution of XRCC4 to radiosensitivity. Methods: Putative CSCs sorted from HCT116-wild type (WT) and XRCC4-knock out (KO) cells were treated with or without carbon-ion beam or X-ray irradiation (IR), then the colony and spheroid formation analysis, fluorescence activated cell sorting (FACS) analysis, gammaH2AX foci immunofluorescence staining and real-time PCR assay were performed. Results: FACS analysis showed that the proportion of CSC markers CD44+ and ESA+ cells was significantly increased but CD133+ cells decreased in XRCC4 KO cells compared to that of HCT116-WT cells. The colony and spheroid formation ability of CSCs from XRCC4-KO cells were markedly decreased compared with those from HCT116-WT cells. The clonogenic assay showed that the doses at D10 for CSCs sorted from XRCC4-KO and HCT116-WT cells were 1.4 and 4.2 Gy for X-ray and 1.0 and 1.9 Gy for carbon ion beam IR, respectively. A much larger number and large-sized gamma H2AX foci were observed in CSCs sorted from XRCC4 KO cells compared to those from HCT116-WT cells, after 24 h of carbon ion beam IR compared with X-ray. Real-time PCR assay showed carbon-ion beam IR enhanced apoptosis- and autophagy-related gene expression in XRCC4 KO cells compared to HCT116-WT cells. Conclusion: Loss of XRCC4 significantly altered the properties of CSCs, rendering them radiosensitive to both carbon ion beams and X-rays, suggesting that XRCC4 may play an important role in regulating the radiosensitivity of CSCs.第54回 内藤コンファレンスconference poste
Status of Lithium-6 Enrichment using Electrodialysis with Ionic Conductor Membrane
No full textIn fusion power generation, the isotope ratio of lithium-6 in breeding blanket materials is crucial for achieving the tritium self-sufficiency. Lithium-6 is an abundant resource in nature, but it constitutes only 7.6% of natural lithium. Therefore, isotope separation technology is essential to meet the lithium-6 ratio required in a fusion reactor. The amalgam method using mercury has been the only lithium isotope separation technology put into practical use so far. However, it is desirable to use another technology considering the impact of environmental pollution.At QST, we are conducting research and development on the extraction of high-purity lithium and the separation and enrichment of lithium-6 by electrodialysis using a lithium-ion conductor as a separator membrane. This technology utilizes the difference in diffusion rates of lithium ions in the ion conductor due to their mass. The ratio of diffusion coefficients between lithium-6 and lithium-7 is given by the square root of the inverse mass ratio, which is 1.08, and the separation factor characterizing the actual separation and enrichment performance is slightly lower than this value.In this presentation, we will discuss how the applied voltage affects the separation factor and the migration rate of lithium, and describe the trade-off tendency between them. Furthermore, we will discuss the scale of the production facility when the cascade theory is applied to the results.22nd International Conference on Fusion Reactor Materials (ICFRM22)への参加conference poste
Total-Body Small-Animal PET with 4-Layer DOI Detectors Enabled for Sub-Second Dynamic Imaging
No full textSub-second dynamic PET imaging is important for preclinical research as cardiac, or brain functions change in sub-second scale order. However, the temporal resolution of conventional small animal PET scanners has been limited to the order of a few seconds at best due to low sensitivity. Here, we present an ultrasensitive small-animal PET scanner with total-body coverage of a rat for sub-second dynamic imaging. The developed total-body small-animal (TBS) PET scanner has a 155 mm inner diameter and 325.6 mm axial coverage. The PET scanner has 6 rings, each of which has 10 depth-of-interaction (DOI) detectors. Each DOI detector consists of a 4-layer Zr-doped gadolinium oxyorthosilicate crystal array (2.85 mm pitch, 30 mm total thickness) and 8×8 multi-anode photomultiplier tubes. The physical PET performance was evaluated based on the National Electrical Manufacturers Association NU4 protocol. The peak absolute sensitivity was 20.2% with an energy window of 400-600 keV. The 2.2 mm rod structure of the resolution phantom was resolved using an iterative algorithm. Total-body images of a rat were obtained with a single bed position. The cardiac function of a rat was visualized with 0.25 s temporal resolution, which was hardly possible with conventional small animal PET scanners. In conclusion, the developed TBS-PET enabled sub-second dynamic PET imaging in rodent models with total-body coverage.2025 IEEE NSS MIC RTSDconference presentatio
Proposal of a new model for x-ray ablation
No full textThis study proposes a new simulation model and hypothesis to explain the unusual trends in the ablated crater depth produced by X-ray irradiation. Photoelectrons and Auger electrons are expected to be trapped by the electric field formed by the positively charged lattice in the region irradiated by X-rays. This positively charged lattice was produced by X-ray absorption. These trapped electrons are expected to increase the electron density and lattice temperature, which are important parameter for X-ray ablation. Furthermore, photoelectrons and Auger electrons start to be trapped at different X-ray fluences; that is, these electrons are expected to suddenly increase the electron density and lattice temperature at these different X-ray fluences. Owing to this difference, we expected that photoelectrons and Auger electrons would generate the unusual trend of the crater depth mentioned previously.QST International Conference on “Future Prospects of Quantum Science and Technology Using Laser-based Soft X-ray and Synchrotron Radiation”conference poste
Engineering Validation of the IFMIF Accelerator: LIPAc Achievements and Future Outlook
No full textThe IFMIF/EVEDA Project (International Fusion Materials Irradiation Facility / Engineering Design and Engineering Validation Activities) is conducted under the Broader Approach agreement between EURATOM and Japan. Its primary goal is to deliver a comprehensive and fully integrated engineering design of the IFMIF facility, along with all data necessary for decisions on construction, operation, maintenance, as well as decommissioning, and it served as a basis for the IFMIF/DONES (Demo Oriented NEutron Source) Project. Among the original activities of IFMIF/EVEDA, the engineering validation of the IFMIF accelerator concept—conducted through the Linear IFMIF Prototype Accelerator (LIPAc)—remains the only activity still ongoing.Developed as a 1:1-scale prototype up to the first cryomodule, LIPAc aims to demonstrate the feasibility of an accelerator-based deuterium-lithium neutron source capable of delivering high-intensity neutron fluxes with an energy spectrum optimized for testing materials intended for future fusion reactors. Achieving this objective requires the IFMIF accelerator to meet unprecedented performance, verified through the design, manufacturing, installation, commissioning, and testing of key components such as the injector, first cryomodule, High Energy Beam Transport line, and High-Power Beam Dump.Following major achievements in 2019 and 2024, the LIPAc project has entered its fourth commissioning phase, focusing on validating the accelerator in its final configuration. The cryomodule assembly, currently in an advanced stage, will enable testing at the nominal energy of 9 MeV. Meanwhile, operational feedback allows to develop and manufacturing improved subsystems, such as the injector, RF power supplies, and Machine Protection Systems that will be tested in a later stage.This paper addresses the milestones reached so far and the future LIPAc developments, including commissioning phases planned for 2026 and beyond, aimed at supporting the next-generation fusion neutron sources, particularly (A-FNS) Advanced Fusion Neutrons Source in Japan and IFMIF/DONES whose construction phase has started in Granada, Spain.The 16th International Symposium on Fusion Nuclear Technologyconference presentatio
Modernizing Information Management for LIPAc Operations
No full textThe Linear IFMIF Prototype Accelerator (LIPAc), a prototype of high-current deuteron accelerators for fusion neutron source applications, requires comprehensive management of operational logs, maintenance records, spare parts inventory, source code, and troubleshooting history. Traditionally, these records were manually maintained using legacy web tools, custom scripts, Excel spreadsheets—adding entries row by row—and Word templates. As the number and complexity of records increased, this approach became increasingly cumbersome, making it difficult to search, aggregate, and analyze data consistently.To overcome these limitations, LIPAc is transitioning to more structured and purpose-specific systems, primarily web-based tools tailored to distinct operational domains. Redmine has been introduced to improve traceability and task management; OpenNMS now supports real-time network monitoring and alerting; Grafana enables unified log aggregation and visualization; GitLab pipelines streamline source code deployment and version control. For network asset documentation and IP address management, phpIPAM and Netbox have been trialed to replace manual tracking.Each tool presents unique benefits and implementation challenges. Through a comparative evaluation and trial implementations, LIPAc is refining its approach to scalable, maintainable, and efficient operational support. This presentation will share the evolution of information management practices at LIPAc, discuss the rationale behind tool selection, and highlight lessons learned in the pursuit of more efficient and scalable operational support.The 14th Workshop on Accelerator Operations (WAO2025)conference poste
清酒酵母のピルビン酸低生産性化に向けた研究の紹介
No full text清酒の高品質化、多様化に伴い、低アルコール清酒のジャンルが開拓されてきている。その製造方法としては、18%程度の高アルコールのもろみを上槽後、できた製成酒に加水して12%以下に下げる方法と、12%以下の低アルコールのもろみを上槽して原酒として出すという方法がある。加水して下げる方法では、香味のバランスが崩れやすいため、大手の酒造会社しか行っていない。一方、もろみで低アルコールの状態とは、酵母の発酵が盛んな時期であり、酵母がもろみ中にピルビン酸を多く排出している。このピルビン酸が高濃度の状態で上槽されると、生化学的にα-アセト乳酸となり、さらにオフフレーバーのジアセチルに変換されてしまう。これまでに我々は、イオンビーム照射による突然変異誘発処理とβ-フルオロピルビン酸耐性化によって、ピルビン酸生産性が低下した清酒酵母を開発した。今回の報告では、その研究の概要と全ゲノム解析の結果、およびピルビン酸低生産性化となった要因の遺伝子解析結果について紹介する。令和7年度愛知県農学系4機関による研究交流会conference poste
Neutron and high-resolution X-ray structural studies of copper-containing nitrite reductase and its physiological electron donor, pseudoazurin
No full textMetalloproteins play fundamental roles in organisms. Knowing strategies of metalloproteins, by which they exquisitely tune their activities, will not only lead to the understanding of biochemical phenomena but also contribute to various applications. Obtaining precise enzyme structures that include all the H atoms, account for about half the atoms in biomacromolecules, allows a deeper understanding of their structure-function relationships.Copper-containing nitrite reductases (CuNIRs) catalyze transformation of nitrite to nitric oxide, which has impacts on geochemical, agricultural, and medical health fields. Despite intense research efforts, the dynamics of H atoms during the enzymatic reaction of CuNIRs are unknown and hence the catalytic mechanism remains unclear. We performed neutron crystallography to shoot a single H-atom resolution picture of a CuNIR in complex with nitrite. We found that nitrite binds on the catalytic Cu center as NO2- and not as protonated HNO2. Our X-ray data and quantum chemical calculation show that NO2- is in an electron-localized state that can facilitate N-O bond cleavage after receiving an electron. The catalytic residues, AspCAT and HisCAT, are deprotonated and protonated, respectively, suggesting that HisCAT is the point of departure of the proton transfer sequence. Subatomic resolution X-ray structures of the AspCAT-to-Asn mutants, which mimic the protonated state of AspCAT, were also determined to investigate the involvement of protonated AspCAT in the reaction. Our crystallographic data and quantum chemical calculations reveal in detail the first step of the CuNIR reaction.Pseudoazurin (Paz), a blue copper protein, mediates electron transfer in the bacterial anaerobic respiratory chain. Its redox potential is finely tuned by hydrogen (H) bond networks; however, difficulty in visualizing H atom positions in the protein hinders the de-tailed understanding of the protein's structure-function relationship. We here used neutron and sub-ångström resolution X-ray crystallography to directly observe H atoms in Paz. The 0.86-Å-resolution X-ray structure shows that the peptide bond between Pro80 and the His81 Cu ligand deviates from the ideal planar structure. The 1.9-Å-resolution neutron structure confirms a long-overlooked H bond formed by the amide of His81 and the S atom of another Cu ligand Cys78. Quantum mechanics/molecular mechanics calculations show that this H bond increases the redox potential of the Cu site and explains experimental results well. Our study demonstrates the potential of neutron and sub-ångström resolution X-ray crystallography to understand the chemistry of metalloproteins at atomic and quantum levels.the 19th Conference of AsCA (AsCA 2025)conference poste
微生物由来プラスチック分解酵素の結晶構造解析
No full textポリエチレンテレフタレート（PET）は年間数千トン生産されているが、リサイクル率は数％に過ぎない。また、マイクロプラスチックによる環境汚染は大きな社会問題である。したがって、PETを効率的に分解するシステムが環境・エネルギーの両面で求められている。本研究では、PETを効率的に分解する細菌Ideonella sakaiensis 201-F6株由来の酵素PETaseに注目し、結晶構造解析を通じて、その機能を原子レベルで理解することを目的としている。 大腸菌を用いて発現させたPETaseを精製後、X線結晶構造解析を行った。生成物類似体である安息香酸との複合体構造から、安息香酸の芳香環近傍に疎水性残基が多く存在し、PETaseは主に疎水性相互作用で安息香酸を認識すると考えられた。また、酵素単体と安息香酸複合体の主鎖構造の差異は小さかった（Cα原子rmsd値：0.186Å）。一方、酵素単体ではトリプトファン（Trp185）の側鎖に2つのコンフォメーションが確認されたのに対し(図1.)、安息香酸複合体では片方のコンフォメーションのみが許容された(図2.)。この結果から、側鎖の微細な構造変化が酵素活性に関与する可能性が示唆された。第8回 次世代生物研究会conference poste
Development of hyperpolarization platform and technology for cancer treatment evaluation using triplet DNP
No full textCurrent research and development on triplet-DNP and dissolution-DNP in iqls/QST is presented, introducing the organizational structure, aims, and progress of our project in quantum sensing in the third SIP. This opportunity is expected to strengthen the relationship between DK and JPN in both academic research and business matching.Danish - Japanese (SiP3) Quantum sensing event -EQTC side event-conference presentatio