National Institutes for Quantum and Radiological Science and Technology
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Beam Characterization and Lessons Learned from Beam Commissioning Prior to SRF Linac Integration
No full textThe Linear IFMIF Prototype Accelerator (LIPAc) is a deuteron linear accelerator (linac) designed to validate the acceleration of a 125-mA beam up to 9 MeV in continuous wave (CW) operation, contributing to the realization of the IFMIF project. The 125-mA deuteron beam is initially accelerated to 5 MeV by a radio-frequency quadrupole (RFQ) and subsequently to 9 MeV by a superconducting radio-frequency (SRF) linac. In LIPAc, even slight particle losses can lead to SRF linac quenching, component damage, and radioactivation. Therefore, ensuring stable beam transport with minimal particle losses is crucial to the success of this project. LIPAc is assembled and commissioned in phases, and the installation of the SRF linac into the beamline is underway. The validation of the functionality of the beam diagnostic devices and the characterization of the beam properties were conducted during phase B+ beam commissioning prior to operating with the SRF linac. Particle losses and discrepancies were observed between the measured and simulated beam sizes. However, through iterative optimization, these particle losses were minimized achieving a matched beam. In this conference, the details of the beam characterization and lessons learned from Phase-B+ will be presented, as well as the beam optics for commissioning with the SRF linac.conference pape
Accomplishment of high duty cycle beam commissioning of Linear IFMIF Prototype Accelerator (LIPAc) at 5 MeV, 125 mA D+
No full textThe Linear IFMIF Prototype Accelerator (LIPAc) is being commissioned under the Broader Approach agreement between Europe and Japan, with the aim of validating the low-energy section of the accelerator for the International Fusion Materials Irradiation Facility (IFMIF). LIPAc is designed to accelerate a 125 mA deuteron beam up to 9 MeV in continuous-wave (CW) operation. This paper reports the outcomes of high-duty cycle beam commissioning at 5 MeV using the RFQ referred to as Phase B+. In this phase, a maximum duty cycle of 8.75% and a beam current of 119 mA were achieved. This corresponds to an average beam power of 40–45 kW, which is the highest beam power among operational RFQs. It was also identified that the RFQ RF couplers are a bottleneck for further duty cycle increases, leading to the preparation of brazed high-duty couplers. These achievements establish a solid foundation for the next commissioning phase, which will include SRF Linac commissioning and aim for CW operation to demonstrate the IFMIF accelerator concept.conference pape
自由エネルギー摂動法によるタンパク質安定化・リガンド改変
No full text自由エネルギー摂動法(free-energy perturbation; FEP)は分子の一部構造を変更した場合の自由エネルギー差を求める事ができる手法であり、主に分子動力学シミュレーションなどと組み合わせて利用される。FEPを用いることで小分子-タンパク質の相互作用自由エネルギー、すなわち結合安定性を推定することが可能であるほか、タンパク質に変異を入れた際の安定性の変化、タンパク質-タンパク質の結合安定性の推定などにも適用でき、使用法によって様々な応用が可能である。当研究室ではFEP-suiteというFEPを実施するためのソフトウェアパッケージを開発し、ユーザーが自由に使えるようオープンソースソフトウェアとして公開している。FEP-suiteはMDソフトウェアパッケージに修正を加え、特にサンプリング法であるReplica-exchange with solute tempering(REST)法を組み込むことでシミュレーションの精度を稼ぐなど、他のソフトウェアパッケージをそのまま用いるだけでは難しい計算を可能にしている。本発表ではFEP-suiteの紹介を行う。リガンド-タンパク質間相互作用やタンパク質の安定化等ベンチマーク例を示すとともに、実応用例を紹介する。第25回日本蛋白質科学会年会conference poste
Activity-dependent organization of prefrontal hub-networks for associative learning and signal transformation
No full textAssociative learning is crucial for adapting to environmental changes. Interactions among neuronal populations involving the dorso-medial prefrontal cortex (dmPFC) in rodents are proposed to regulate associative memory. However, how these neuronal populations store and process information about the association remains unclear. Here we developed a pipeline for longitudinal two-photon imaging and computational dissection of neural population activities in male mouse dmPFC during fear-conditioning procedures, enabling us to detect learning-dependent changes in the dmPFC network topology. After confirming that the dmPFC contributes to the expression of the conditioned responses (CR) by chemogenetic silencing, we analyzed neural population activities by regularized regression methods and graphical modeling. We found that fear conditioning drove dmPFC reorganization to generate a neuronal ensemble encoding CR, which was characterized by enhanced internal coactivity and functional connectivity. Importantly, neurons strongly responding to unconditioned stimuli during fear conditioning subsequently became hubs of this novel network and revealed enhanced association with conditioned stimuli (CS), which may work as an information-processing neural network implementing CS-triggered CR (i.e., a neural network for the CS-to-CR transformation). Altogether, we demonstrate learning-dependent dynamic modulation of population coding structured on the activity-dependent formation of the hub network within the dmPFC.Currently, we are developing a new imaging method to enhance brightness and spatial resolution in the deep mPFC, enabling simultaneous imaging across broader regions and multiple layers to further investigate the neural mechanisms underlying long-term memory and extinction.Optical Interrogation of Neural Structure and Dynamics Underlying Behaviorconference presentatio
Reaction of N-[11C/18F]alkylagents with aryl and heteroaryl amines in the presence of tBu-P4
No full textObjectives: [11C/18F]Alkylation of phenol derivatives is a useful method for introduction of 11C or 18F into molecules. However, introduction of 11C or 18F into aromatic amine derivatives has remained a significant challenge [1,2]. Because of its weak nucleophilicity the amino group in these amines is difficult to react with alkylating agents. To solve this problem, we focused on the tBu-P4 base for deprotonation of aromatic amine in situ. tBu-P4 which is known to have low nucleophilicity and basicity comparable to n-butyllithium has been used for a variety of deprotonation reactions. In addition, the large size of the protonated tBu-P4 cation enhances the nucleophilicity of its counter anion. In this study, we developed a simple method for introducing [11C/18F]alkyl motif into aromatic amines in the presence of tBu-P4.Methods: The reaction conditions for the methylation of 2-aminopyridine as a model compound with unlabeled CH3I were optimized at 60 oC for 30 min. Under the optimized conditions, the methylation of various aryl amines was performed. [11C]CH3I, [18F]FEtBr, or [18F]epifluorohydrin (EPIF) [3] was used as an alkylating agent. [11C]Methylation of heteroaryl amine was performed by the reaction of [11C]CH3I with precursor (1 mg) in DMF (150 L) with tBu-P4 at 60 oC for 5 min. [18F]Fluoroalkylation of heteroaryl amine was performed by the reaction of [18F]FEtBr or [18F]EPIF with precursor (1 mg) in DMF (150 L) with tBu-P4 at 60 oC or room temperature for 5 min. Radiochemical conversions (RCCs) were determined by radio-HPLC for these reaction mixtures. Results: The methylation of 2-aminopyridine with unlabeled CH3I in DMF or THF using tBu-P4 gave 2-methylaminopyridine in 21% and 31%, respectively. Compared to other solvents, DMF and THF were found to be suitable for the methylation. At the same time, 2-dimethylaminopyridine was obtained as a byproduct with 30% yield in each solvent. On the other hand, the methylation did not proceed effectively under 1 M NaOH, KOH, Et-P2 (phosphazene base), and NaH in DMF. Based on these conditions, starting from 29.6 GBq of [11C]CO2, [11C]1a–n were synthesized by the reaction of aryl amine with [11C]CH3I and tBu-P4 in DMF under an automated synthesis system developed in house. By purification for the reaction mixture with semi-preparative HPLC, [11C]1a–n were obtained with a synthesis time of 20 ± 5 min and 3–41% radiochemical yield (decay-corrected). To extend application of this method, synthesis of [18F]2–4 with [18F]fluoroalkylating agents was examined. In the synthesis of [18F]2, it was observed that [18F]fluoride was mainly liberated because of degradation of [18F]2. On the other hand, [18F]3 and [18F]4 were also obtained in 20% and 14% RCCs, respectively.Conclusions: We have successively synthesized [11C]1a–n and [18F]2–4 using [11C/18F]alkylagents in the presence of tBu-P4. We are currently optimizing reaction condition to increase the radiochemical yield of [18F]2 and [18F]fluoroethylating efficiency of other aryl amines.iSRS2025conference poste
Development of a convenient synthesis method for [18F]fluoroform via difluorocarbene
No full textObjectives: Fluoroform (HCF3) is used as a precursor for the synthesis of various CF3-containing compounds. In recent years, several studies have reported the reactivity of HCF3 and development of [11C/18F]HCF3 as radiolabeling agents [1-3]. However, the studies have remained some challenging issues, such as handling of precursor for radiolabeling agent and complexity of automated synthetic equipment. To solve these problems, we hypothesized that use of a difluorocarbene source would enable the synthesis of [18F]HCF3 using a two-pot automated synthesis system for [18F]fluoroalkylation reaction, like the use of BrCH2CH2OTf or glycidyl tosylate to produce gaseous [18F]FEtBr or [18F]EPIF. In this study, we developed a convenient method for synthesizing [18F]HCF3 via difluorocarbene produced in situ.Methods: The difluorocarbene source was determined for the difluoromethylation of 4-phenylphenol at 130 oC for 20 min in the presence of tBuOK. [18F]HCF3 was synthesized by the reaction of the optimal difluorocarbene source and [18F]KF/K2.2.2 in 1,2-dichlorobenzene at 130 oC for 2 min and immediately transferred by distillation into a reaction vial 2 containing benzophenone (1.5 mg) in DMF (500 L) and tBuOK, under an automated synthesis system developed in house. The [18F]trifluoromethylation of benzophenone was performed at 50 oC for 5 min as a model reaction. After the reaction, the reaction mixture was purified by the semi-preparative HPLC column.Results: To determine the optimal difluorocarbene source, the difluoromethylation of 4-phenylphenol as a model reaction was investigated. When ClCF2CO2Me, ClCF2CO2Na, and BrCF2CO2K were used and converted to difluorocarbene sources in situ, the difluoromethylated compounds were obtained in 13%, 3%, and 19% yields, respectively. Because BrCF2CO2K showed poor solubility in 1,2-dichrolobenzene, ClCF2CO2Me was selected as the optimal difluorocarbene source. The formation of [18F]HCF3 was confirmed by the reaction of ClCF2CO2Me and [18F]KF at 130 oC for 2 min without addition of proton source. As [18F]HCF3 has no significant UV signal, we performed a model reaction of [18F]HCF3 with benzophenone to determine the molar activity. The trifluoromethyl carbinol was obtained in 10 ± 2% radiochemical yield (isolated-yield based on the cyclotron-produced [18F]fluoride) and 0.61 ± 0.30 GBq/μmol molar activity. Reduction of the used amounts of ClCF2CO2Me and K2CO3 improved the molar activity to 12 GBq/μmol. Conclusions: We have successively synthesized [18F]HCF3 by applying the two-pot automated synthesis system for [18F]fluoroalkylation reaction and will continue to improve the molar activity of [18F]HCF3. In addition, this method is now applied to the synthesis of other CF3-containing radiolabeling agentsiSRS2025conference poste
2-Nitroimidazole-Functionalized Superparamagnetic Iron Oxide Nanoparticles Detect Hypoxic Regions of Glioblastomas on MRI and Improve Radiotherapy Efficacy.
No full textThe presence of hypoxic regions in tumors is associated with malignancy and is an important target for the high-precision diagnosis and treatment of tumors. Radioresistant hypoxic regions can be precisely identified and treated without the use of high doses of radiation if hypoxic region-specific contrast agents have a therapeutic effect. In this study, we synthesized a therapeutic-diagnostic complex agent (SPION-PG-NI) by combining polyglycerol-functionalized superparamagnetic iron oxide nanoparticles (SPION-PG, core diameter of 8.8 ± 1.9 nm) as an MRI contrast agent and 2-nitroimidazole (NI, a pimonidazole derivative) as a hypoxia-targeted ligand to visually evaluate hypoxic regions using MRI and improve radiotherapy efficacy at those sites. SPION-PG-NI showed a concentration-dependent contrast effect and had significantly higher accumulation in subcutaneous glioblastomas than the control agent, SPION-PG, 24 h after administration. Immunohistological evaluations showed that the SPION-PG-NI-accumulated regions corresponded well to hypoxic regions. SPION-PG-NI showed neither migration into the brain parenchyma nor neurotoxicity. Both SPION-PG and SPION-PG-NI decrease reactive oxygen species (ROS); however, they improve radiotherapy efficacy in hypoxic glioblastoma cells due to cytotoxicity. This effect of SPION-PG-NI was significantly higher than that of SPION-PG ( < 0.01). After 12 Gy irradiation, the mean normalized glioblastoma tumor volume on day 38 in the SPION-PG-NI group (288%) was significantly lower than that in the control group (882%) ( < 0.05). Collectively, these findings suggest the potential of SPION-PG-NI as a useful and safe tumor theranostic nanodevice for hypoxic imaging and improving radiotherapy efficacy.journal articl
Designing a two-stage acceleration lens for a 100 keV single-ion implantation system
No full textAn array of color centers, each known as an NV center formed by a single-nitrogen atom and a vacancy, spaced at intervals of several tens of nanometers in a diamond exhibits quantum entanglement effects and indicates potential for quantum device applications. To fabricate such an array by implanting single-nitrogen ions into a diamond, a 100 keV single-ion implantation system (SIIS) has been developed by combining a linear Paul-trap laser-cooling ion source (LPTLC-IS) with a sympathetically cooled ion technique and a two-stage acceleration lens. So far, the LPTLC-IS and the two-stage acceleration lens have been refined as individual elemental technologies. However, for deterministic single-ion implantation, the SIIS must meet the following ion beam conditions: implantation with nanometer accuracy, a long working distance exceeding 100 mm to accommodate a quantum effect detector, and a penetration depth of approximately 100 nm in a diamond. These requirements necessitate the development of a two-stage acceleration lens capable of focusing the ion beam to a width of < 50 nm without a collimator when using a 100 keV ion beam. In this study, the two-stage acceleration lens, comprising 1st and 2nd acceleration lenses, was redesigned using numerical simulations to optimize lens parameters. Our primary redesign focus was the 2nd acceleration lens, which was redesigned based on the configuration of the previously developed lens. The resulting two-stage acceleration lens successfully met the target beam conditions for the SIIS.journal articl
Origin of entanglement in an H(2) atom pair produced through the photodissociation of an H2 molecule
No full textIn this paper, as a continuation of our recent article demonstrating that the 2p atom pair is entangled in the H2 photodissociation [Phys. Rev. A 111, 023116 (2025)], we have discovered the origins of the entanglement for the 2p atom-pair state and obtained the entanglement entropies by origins. The same investigation has been carried out for the precursor molecular state of the 2p atom pair. The reason for the increase of the entanglement entropy during the dissociation from the precursor molecule into the H(2p) + H(2p) atom pair has been made clear.journal articl
Hybrid nanosensors of carbon quantum dots and fluorescent nanodiamonds: Ratiometric thermometry and multicolor sensing
No full textHybridization of carbon-based materials opens new frontiers in creating multifunctional nanosensors for biomedical and quantum sensing applications. Here, we present a novel nanosensor, CQD-FND, integrating carbon quantum dots (CQDs) and fluorescent nanodiamonds (FNDs). By utilizing a silica coating to facilitate the conjugation of FNDs and CQDs, we developed a design that effectively suppresses fluorescence quenching of CQDs caused by dangling bonds on the FND surface, enabling sufficient fluorescence measurement from both FNDs and CQDs in the hybrids. This sensor achieves ratiometric thermometry, overcoming the limitations associated with using FNDs or CQDs individually for temperature measurements. The CQD-FND sensor exhibits remarkable stability under varying environmental conditions such as ionic strength, viscosity, and pH, demonstrating robust performance in biological systems and enabling accurate temperature measurements. Moreover, we labeled FNDs with blue- or green-fluorescent CQDs, enabling multicolor labeling for magnetic resonance measurements. We successfully measured the magnetic resonance signal of CQD-FND in cells and nematode C. elegans, demonstrating its potential for multi-parameter quantum biosensing applications. These results establish CQD-FND as a versatile tool for applications ranging from bioimaging to biosensing.journal articl