National Institutes for Quantum and Radiological Science and Technology
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Beam halo losses reduction with simulation constrained Bayesian Optimization
No full textThe Linear IFMIF Prototype Accelerator (LIPAc) is designedto demonstrate continuous wave (CW) accelerationof a 125 mA deuteron beam up to 9 MeV using a radiofrequencyquadrupole (RFQ) and a superconducting radiofrequency(SRF) linac. Prior to SRF linac installation, beamcommissioning was conducted with a 5 MeV deuteron beam.Attempts to increase the duty cycle revealed a significant risein vacuum pressure, as detected by sensors, thus limitingthe operational duty cycle to about 3%. Simulation studiesindicated that the pressure increase was likely attributable tobeam halo formation. To address this issue, Bayesian optimizationwas applied to the beam optics—specifically, fourquadrupole magnets and four steerers—with the objectiveof minimizing halo-induced losses by monitoring vacuumpressure while constraining core beam losses. This approachsuccessfully reduced the sector vacuum pressure by approximately67%. Further simulations verified that beam haloformation driven by nonlinear space-charge forces was effectivelymitigated by relaxing beam focusing in specificregions, consistent with theoretical predictions. As a result,the duty cycle was increased to 8.7%. These findings demonstratethat machine learning techniques, such as Bayesianoptimization, can effectively support beam optics tuningin high-current accelerator systems. This paper presents acomparative analysis of the beam optics before and afteroptimization, highlighting the improvements in halo suppression.conference pape
Heavy water toxicity via isotope effects: Stronger than high-dose radiation, neutralized by light water
No full textNumerous enzymatic reactions involve hydrolysis, making water indispensable for sustaining life. Some water includes hydrogen isotopes, deuterium or tritium, with larger atomic weights. Heavy water consisting of deuterium is toxic to living organisms and induces cell death; however, the extent and underlying mechanisms of this toxicity remained elusive. Herein, we demonstrate that 100% heavy water triggers a remarkably heightened apoptotic response in human cells, compared to exposure to high-dose ionizing radiation. This pronounced effect of heavy water on cellular function may stem from the quantum-level mechanisms of kinetic isotope effects inherent to water isotopes, leading to a deceleration in enzymatic hydrolysis reactions. Notably, dilution of heavy water by approximately ten-fold with ordinary light water abolishes its isotope effect on enzymatic hydrolysis reactions, concomitant with the disappearance of DNA repair inhibition and cell death induction in human cells. These findings reveal that high concentrations of water isotopes containing heavier hydrogen have extreme cell death-inducing toxicity, yet this toxicity disappears upon dilution, thereby offering crucial insights into environmental considerations.journal articl
Effects of whole-body carbon-ion beam irradiation on bone marrow death in mice and an examination of candidates for protectors or mitigators against carbon-ion beam-induced bone marrow death
No full textThe present study examined the effects of whole-body carbon-ion beam irradiation on bone marrow death in mice and investigated whether compounds/materials, which were identified as efficient radio-protectors or mitigators against X-ray irradiation-induced bone marrow death, were also effective against the carbon-ion beam-induced death of mice. Amifostine and cysteamine were used as radio-protectors and zinc-containing heat-killed yeast (Zn-yeast) and γ-tocopherol-N,N-dimethylglycine ester (γTDMG) as radio-mitigators. Amifostine or cysteamine was intraperitoneally administered in a single injection of 1.95 mmol/kg body weight 30 min before whole-body carbon-ion beam irradiation. Zn-yeast or γTDMG was administered in a single intraperitoneal injection of 100 mg/kg body weight immediately after whole-body carbon-ion beam irradiation. The absorbed dose dependence of the 30-day survival rate after carbon-ion beam irradiation was analyzed. The biological effectiveness of carbon-ion beam irradiation (LD50/30 = 5.54 Gy) was estimated as 1.2 relative to X-ray irradiation (LD50/30 = 6.62 Gy). The dose reduction factors (DRF) of amifostine, cysteamine, Zn-yeast, and γTDMG estimated for carbon-ion beam irradiation were 1.75, 1.53, 1.16, and 1.15, respectively. Radio-protectors and -mitigators that were effective against photon irradiation also exhibited efficacy against carbon-ion beam irradiation; however, the DRF for carbon-ion beam irradiation was slightly smaller than that for photon irradiation. Based on the radio-protective effects of amifostine and cysteamine, the contribution of ROS/free radicals to carbon-ion beam-induced bone marrow death was 70?90% of that to photon irradiation. Since the suppression of tumor growth by carbon-ion beam irradiation was not inhibited by the treatment with γTDMG or Zn-yeast, both mitigators have potential as normal tissue-selective protectors in carbon-ion radiation therapy.journal articl
Quantification of Oxygenation and Oxygen Consumption Rates in the Mouse Brain based on Tissue Oxygen Level-Dependent (TOLD) MRI
Get PDFA non-invasive method to estimate oxygenation and oxygen (O2) consumption rates in mouse brain tissue based on T1-weighted tissue oxygen level-dependent (TOLD) MRI was developed. The aim of the present study was to estimate the kinetics of O2 in tissue in order to facilitate the planning of radiation therapy.
The relationship between the proton T1 relaxation rate and O2 concentrations was examined in water and corn oil samples, which are models of the aqueous and lipidic phases of cell components. T1 maps of the mouse brain were obtained under breathing high oxygen concentration gas, carbogen (95% O2 + 5% CO2), or 100% O2, and shifts in the concentration of O2 from the physiological state in the brain were then estimated. Pseudo-TOLD signals in blood samples, hemoglobin, and myoglobin aqueous solutions under oxygenation were measured to examine the effects of heme iron on T1. O2 metabolism in mouse brains was evaluated by the enhancement/diminishment rates of the TOLD signal when the breathing gas was switched from air to carbogen or 100% O2 and when it was switched back to air.
Carbogen or 100% O2 inhalation increased cortical O2 levels by 0.28 or 0.26 mmol/L, respectively. By analyzing the time course profile of the TOLD signal, the oxygenation rate, oxygenation level, and O2 consumption rate were successfully estimated. TOLD MRI has potential as a useful tool to estimate the quantitative indices of oxygenation and O2 consumption rates in brain tissue.journal articl
Designer Catalyst-Enabled Regiodivergent Histone Acetylation
No full textThe “histone code,” defined by the combinatorial patterns of post-translational modifications (PTMs) on histones, plays a pivotal role in chromatin structure and gene expression. Tools for the regioselective introduction of histone PTMs in living cells are critical for dissecting the functions of these epigenetic marks. Here, we report the design and development of three regioselective catalysts that acetylate distinct lysine residues (K43, K108, and K120) on histone H2B. Using a combination of molecular dynamics simulations of catalyst-nucleosome complexes and systematic experimental optimization of catalyst structures, we identified key design principles for achieving regioselectivity. Specifically, excluding highly reactive off-target lysine residues from the catalyst effective region (CER) while maintaining proximity to a target lysine residue proved crucial. Biochemical and cellular analyses of the catalytic histone acetylation revealed that each lysine acetylation elicited unique effects on the binding affinity and activity of nucleosome-interacting molecules, as well as on transcriptional programs and cellular phenotypes. These findings establish a framework for designing regioselective histone acetylation catalysts and advance our understanding of the regulatory mechanisms underlying histone PTMs.journal articl
An efficient output coupler for a terahertz generation device by stacking parallel plates with different refractive indices
No full textIn terahertz (THz) wave generation by MgO:LiNbO3 (LN) crystals, low extraction efficiency due to high refractive index (n = 4.93) in THz region is problematic. We propose and demonstrate an output coupler which consists of parallel plates with different refractive indices to couple out a THz wave to the air (n ~ 1) more efficiently than without plates. Without any complicated processing on the surface of LN crystals, 1.8 times increase in the transmitted THz power was obtained.journal articl
Primary cilium restricts TGF-β/SMAD signaling induced RIBEs in the co-culture model
No full textTransforming growth factor β (TGF-β) is one of the most common cytokines that respond to ionizing radiation and participates in radiation induced bystander effects (RIBEs). Primary cilium (PC) coordinates several signaling pathways, including TGF-β signaling, to regulate diverse cellular processes. In our previous study, by using a medium transfer system, we uncovered the regulatory role of PC during RIBE by restricting TGF-β signaling. Here, to further study the function of PC during RIBE and to explore the potential mechanisms underlying the process, proton microbeam radiation (MR) and cell partial radiation were used to arrange the co-culture bystander system, siRNAs were used to switch PC formation rate and the activation and expression of ATM, ATR or DNApk, γH2AX foci and cell proliferation were detected to reflect cellular damage. The results showed that, firstly, under both partial radiation model and MR model, PC inhibition upregulated γH2AX foci and protein level in 12 h and downregulated cell proliferation ability, which were reversed by TGF-β signaling inhibition. Secondly, ATM, ATR or DNApk inhibition will decrease the foci formation but resulted in decrease of proliferation rate, also the clearance of ROS or NO reduced the foci level and promoted cell survival. Thirdly, inhibition of SMAD2/3 complex in PC defective bystander cells suppressed expression of ATM and ATR and resulted in the decrease of cellular NO levels and ROS levels. In conclusion, through canonical p-SMAD2/3 pathway, TGF-β1 promoted the production of inducible ROS/NO and overactivation of ATM, ATR, or DNA-Pkcs, leading to the DNA damages in bystander cells, which process is restricted by PC and constitutes the mechanism for PC regulated RIBEs.journal articl
Plasma structure measurements with scattered intense laser beam
No full textShort-pulse intense lasers have the potential to model extreme astrophysical environments in laboratories. Although there are diagnostics for energetic electrons and ions resulting from laser-plasma interactions, the diagnostics to measure the interaction region of laser and plasma are limited. We have been developing the diagnostics of the interaction between intense laser and plasma using scattered intense laser. We performed experiments to observe the spatial distributions and polarization of the scattered drive laser beam interacting with a gas-like target using optical imaging. The observed light has a polarization consistent with the drive laser beam indicating the observed light originates from the drive laser. Imaging of the scattered light shows the structure of electrons interacting with the intense laser. We observed the change of plasma structure due to the laser pre-pulse that destroys the target before the arrival of the main pulse.journal articl
Prognostic Significance of Plasma Soluble IL-6 Receptor in Carbon-ion Radiotherapy for Pancreatic Cancer
No full textBackground/Aim: For patients with unresectable locally advanced pancreatic cancer (LAPC), carbon-ion radiotherapy (C-ion RT) can safely deliver higher doses than conventional photon therapy, increasing the potential for long-term survival. However, achieving meaningful improvements in survival rates requires reliable prognostic biomarkers to identify patients likely to benefit from treatment. Patients and Methods: In this study, we measured plasma levels of soluble interleukin-6 receptor (sIL-6R) before C-ion RT and examined their association with the risk of distant metastasis (DM), local recurrence (LR), and overall survival (OS). Results: Results showed that patients with higher plasma sIL-6R levels had a lower risk of DM [hazard ratio (HR)=0.53; p=0.033] and improved OS (HR=0.55; p=0.037). No significant association was observed between LR and plasma sIL-6R levels (HR=1.47; p=0.273). Conclusion: These findings suggest that pretreatment plasma sIL-6R levels may serve as a prognostic marker for C-ion RT in LAPC.journal articl
Physical parameters and biological factors affect the abscopal effect of combining radiotherapy with immunotherapy: an update on preclinical works
No full textIn the process of radiotherapy for cancer patients, there is an extremely low probability phenomenon that the distal tumor/metastasis away from the irradiation field undergoes regression after localized radiation therapy, which is called the abscopal effect. Enhancing the incidence of this phenomenon possesses profound significance for the investigation of metastatic cancer treatment. Currently, the underlying mechanisms of the abscopal effect remain unclear. Radiation-induced immunogenic cell death is considered one of the potential mechanisms for the abscopal effect. From this perspective, we explored how physical parameters and biological factors influence this process. Differences between patients with respect to physical factors and intrinsic biological factors that activate the immune response (acquired factors) may affect the induction of the abscopal effect.journal articl