National Institutes for Quantum and Radiological Science and Technology
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Effect of residual stress on the electromagnetic non-destructive testing signals from components made of F82H steel
No full textThis study investigates the magnetic properties of F82H steel under weak magnetic fields to assess the applicability of eddy current testing to the non-destructive inspection of blanket cooling paths made of F82H steel. Sample plates made of F82H steel and three other types of steel were prepared and subjected to cold rolling to induce residual stress. Eddy current tests were performed to gather signals from the samples using a pancake-type eddy current testing probe. While cold rolling altered the eddy current signals for F82H plates, the changes were less pronounced than those observed in the other steels. Subsequently, the B-H curves of the samples were measured using a vibrating sample magnetometer. The results of the measurement clearly showed that the residual stress changes the magnetic properties of F82H steel. Change in relative permeability correlated with variations in the eddy current signal. The findings indicate that residual magnetization, rather than magnetic property changes induced by residual stress, is the primary source of noise in the eddy current signals.journal articl
Evaluation of in vivo and in vitro binding property of a novel candidate PET tracer for CSF1R imaging and comparison with two currently-used CSF1R-PET tracers
No full textBackground Colony-stimulating factor 1 receptor (CSF1R) is a promising imaging biomarker for neuroinflammation and tumor-associated macrophages. However, existing positron emission tomography (PET) tracers for CSF1R imaging often suffer from limited specificity or sensitivity.Results We have performed 11C-labeled radiosynthesis of compound FJRD(3-((2-amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)ethynyl)-N-(4-methoxyphenyl)-4-methylbenzamide), which exhibits excellent affinity for CSF1R, and evaluated its in vivo and in vitro binding properties. PET images of [11C]FJRD show low brain uptake and specific binding in the living organs, except the kidneys in both normal mice and rats. In vitro autoradiographs demonstrate high levels of specific binding in all investigated organs, including the brain, spleen, liver, kidneys and lungs, when selfblocking was used. The addition of CPPC partially blocked in vitro [11C]FJRD binding in these organs, with blocking effects ranging from 9 to 67%. In contrast, the other two CSF1R inhibitors, GW2580 and BLZ945, showed minimal blocking effects, suggesting unignorable off-target binding in these organs. Furthermore, specific binding of [11C] CPPC and [11C]GW2580 was faint in the mouse organs, with [11C]CPPC demonstrating detectable binding only in the spleen.Conclusions These results suggest that [11C]FJRD is a potential CSF1R-PET tracer for more sensitive detection of CSF1R, compared to [11C]CPPC and [11C]GW2580. However, the high level off-target binding necessitates further improvements in specificity for CSF1R imaging.journal articl
Precise PEGylation Modulates the in Vivo Fate of Peptide Radiopharmaceuticals
No full textPEGylation has emerged as a promising approach to addressing stability issues and tumor retention challenges in radiopharmaceutical development. Herein, how PEGylation affects the in vivo behavior of peptide radiopharmaceuticals is investigated, focusing on the length and topological structure of the PEG molecules. A peptide ligand that targets CD133 is used and modified with different lengths of PEG (PEG3, PEG10, and PEG20) to study the impact of PEG length. Additionally, a peptide ligand targeting PD-L1 is modified with single-arm PEG, 4-arm PEG, and 8-arm PEG to examine the effects of PEG polyvalency. Through quantitative PET/CT imaging for long-term tracking, the in vivo behavior of the synthesized peptide radioligands is compared. Interestingly, PEG10 is the optimal spacer for achieving maximum tumor retention for the CD133-targeting peptide. However, the PD-L1 peptide derivatives modified with different armed PEG molecules showed complex results, with increased PEG arms leading to a higher tumor therapeutic index but compromising the pharmacokinetic properties. The findings highlight the dual nature of PEGylation in peptide radiopharmaceutical development, emphasizing the importance of considering PEG size, structure, and attachment point in drug design process. This study shed light on the diverse effects of PEGylation and aids in discovering PEGylated radiopharmaceuticals.journal articl
Guidance on the short hydration method for cisplatin administration.
No full textCisplatin is currently used as the central agent in several cancer chemotherapy protocols because of its broad antitumor spectrum and potent antitumor effects; however, preventing cisplatin-induced renal damage and other adverse events is challenging. Recently, several clinical studies have shown that a short hydration method could prevent cisplatin-induced renal damage. In addition, appropriate magnesium supplementation and administration of forced diuretics have been shown to be renoprotective. The Japanese Lung Cancer Society Guidelines Committee has summarized the evidence of renal protection regarding cisplatin administration to provide optimal administration guidance for the cisplatin short hydration method.journal articl
Modification of the MSD-AFLP Method for Detection of 5-Hydroxymethylcytosine and Its Application to NGS
No full text5-Hydroxymethylcytosine (5hmC) is beginning to be expected to play a role as a diagnostic and prognostic marker of diseases. On the other hand, we developed the methylated-site display-amplified fragment length polymorphism (MSD-AFLP), an affordable, large-scale (approximately 40,000-50,000 CpG sites), highly sensitive methylation profiling method, and applied it to environmental health and disease biomarker discovery research. Herein, we attempted to modify the MSD-AFLP method to detect 5hmC. To validate this method, we compared hydroxymethylation levels among tissues using mouse samples to determine whether this method could detect tissue-specific differential 5hmC. We also considered combining this method with next generation sequencing (NGS). Comparisons using AFLP revealed that in some sites, the variation in hydroxymethylated DNA was greater than that in methylated DNA between tissues. Therefore, we determined the hydroxymethylation levels at these sites using Glucosylation-mediated restriction enzyme sensitive qPCR (gRES-qPCR) to confirm the accuracy of the AFLP analysis. The differences in hydroxymethylation levels between tissues were similar between the two methods. The protocol for combination with NGS was evaluated by comparing the AFLP data with 11 DNA fragments. The differences in hydroxymethylation levels between tissues were similar between the two methods. Cluster analysis demonstrated that NGS data were comparable to AFLP data in detecting differential and contrasting hydroxymethylation patterns across tissues. This method, based on the MSD-AFLP technique, will contribute to various epigenetics-based research, including the discovery of biomarkers and therapeutic drug targets.journal articl
Determination of binding energy of hydrogen atom to vacancy–carbon complexes in α-iron under uniaxial compressive and hydrostatic strains using density functional theory calculations
No full textElastic strain (change in atomic distance) is observed in dislocation cores and coherent interfaces in industrial materials. To better understand the interaction between defects and gas atoms under elastic strain, density functional theory calculations are performed in this study for obtaining the solution energies of hydrogen and carbon and the binding energy of a hydrogen atom to vacancy–carbon complexes under uniaxial compressive and hydrostatic strains (results under uniaxial tensile strains have already been reported). The solution energies of the hydrogen and carbon atoms increase with uniaxial and hydrostatic compressive strains and decrease with hydrostatic tensile strain. The binding energy of a hydrogen atom to vacancies or vacancy–carbon complexes increases with increasing uniaxial and hydrostatic compressive strains and decreases with increasing hydrostatic tensile strain. The binding energy of a hydrogen atom to vacancy–carbon complexes decreases with an increasing uniaxial tensile strain, which does not correspond to the results of a previous study. Further, the elastic dipole tensor is compared with the change in the formation energy of vacancies or vacancy–carbon–hydrogen complexes. The number of hydrogen atoms trapped in the vacancies tend to change based on hydrogen concentration. This study is useful for estimating hydrogen retention in fractured tips under a hydrogen atmosphere.journal articl
Late fluid flow in a primitive asteroid revealed by Lu–Hf isotopes in Ryugu
No full textCarbonaceous asteroids are the most primitive remnants of planetary formation. Their fragments, delivered as chondritic meteorites and recently returned from the asteroid Ryugu, contain evidence of aqueous alteration early in Solar System history. However, the fate of water on carbonaceous asteroids remains unknown. We show that Ryugu fragments have excess radiogenic hafnium-176 unsupported by parent lutetium-176 present in the samples, which can be explained only by lutetium loss through aqueous fluid escape more than 1 billion years after the parent body accretion. The late fluid escape likely resulted from an impact that generated heat for ice melting and rock fractures for fluid pathways. The long-term retention of ice in a carbonaceous asteroid implies that the Earth’s building blocks contained more water than previously thought.journal articl
Mutational Signatures in Radiation-Induced Cancer: A Review of Experimental Animal and Human Studies
No full textIonizing radiation can damage DNA, leading to mutations, and is a risk factor for cancer. Based on the assumption that all radiation exposure poses a risk in linear proportion to its dose, ionizing radiation is considered a non-threshold carcinogen. However, most epidemiological studies have had insufficient statistical power to detect excess cancer risks from low-dose radiation exposure. Therefore, research is needed to identify radiation signatures that distinguish radiation-induced cancers from spontaneously developed cancers. In rodent cancer models, interstitial chromosomal deletions of specific tumor-suppressor gene loci are characteristically found in cancers from irradiated animals. In humans, a high frequency of small deletions and chromosome rearrangements, such as large deletions, inversions, and translocations, has also been reported in second cancers that develop in patients who received radiotherapy and in thyroid cancers diagnosed in residents after the Chornobyl accident. These genomic alterations are likely to be generated as a consequence of the processing of radiation-induced DNA double-strand breaks. Particularly, chromosome rearrangements that occur at loci directly linked to tumor formation after ionizing-radiation exposure are potentially useful as biomarkers and as therapeutic targets for radiation-induced cancer. Here we provide an overview of the radiation-induced mutational signatures observed in animal and human cancers.journal articl
〈前向き〉概念とその哲学的含意：逆境に駆動された肯定性のダイナミクス
No full text「前向き」という日常的な語の用法を精査することから出発し、そこに「逆境」との明示的・暗黙的な関係が特徴的なものとして含まれることを指摘した上で、「逆境」と「前向き」との複合的・重層的な媒介関係を様々な局面に即して哲学的に分析する。journal articl
Influence of age and sex on the relative biological effectiveness of 13-keV/μm carbon ions for lifespan shortening of B6C3F1 Mice
No full textEpidemiological studies of Japanese atomic bomb survivors indicate that the risk of cancer from radiation exposure is higher in individuals who are relatively young at the time of exposure, with women facing a more significant risk compared to men. However, this type of data is limited for other radiation types, such as particle radiations. Low linear energy transfer (LET) carbon ions are a type of particle radiation to which humans may be exposed as cosmic radiation during long-duration space missions and as radiation passing through healthy tissue during carbon ion radiotherapy. This raises concerns about the risk of late complications, including cancer development. To address these issues, we examined the lifespan of mice after exposure to γ rays or low-LET carbon-ion beams, assessed the effects of sex and age at the time of exposure, and calculated the RBE. Male and female B6C3F1 mice of various ages (embryonic days 3, 13, and 17, and postnatal weeks 1, 3, 7, and 15) were whole-body irradiated a single time with 137Cs γ rays (662 keV) or 290-MeV/u monoenergetic carbon ions (LET, ~13 keV/µm), and their lifespan was analyzed. For both γ rays and carbon ions, the hazard ratio for mortality increased in a dose-dependent manner, was higher for females than for males, and peaked at 1 week of age at the time of exposure. The RBE of low-LET carbon ions for lifespan shortening was 0.9–1.8 for females and 1.2–2.0 for males, regardless of the age at exposure. Thus, the risk associated with low-LET carbon ion exposure varied with age and sex, but RBE did not. These findings provide essential data for assessing the impacts of low-LET carbon ion exposure.journal articl