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Background: In carbon ion radiotherapy, accurate measurement of the three‐dimensional (3D) absorbed dose distribution is critical for effectively targeting tumors. Although micellar gel dosimeters exhibit considerable potential for measuring 3D absorbed dose distributions, few studies have focused on radiotherapy using carbon ion beams. Purpose: This study investigated the applicability of the surfactant hydrogel dosimeter (SHD), a micellar gel dosimeter, to measuring a 3D dose absorbed through carbon ion beam irradiation. Methods: A cubic target region of 34 mm per side was established at a depth of 46 mm below the upper surface of an SHD specimen. Scanning irradiation was performed using a pencil beam of carbon ions at the Ion‐beam Radiation Oncology Center in Kanagawa ("i‐ROCK"), Japan, under irradiation conditions set by the treatment planning system ("Monaco for Carbon", Ver. 5.20, Elekta AB, Sweden) to create a spread‐out Bragg peak within the target. The physical dose was set to 10 Gy at the isocenter, situated at the center of the target. The SHD responsiveness was measured twice using optical computed tomography (CT) ("Vista 15", Modus Medical Devices, Canada) for three irradiated specimens, and six types of measured optical attenuation coefficient (OAC) were obtained. To assess whether the OAC represented the absorbed dose expected in the treatment plan, we compared the relative distribution of the OAC and that of the absorbed dose. Relative fraction (RF) was used to measure the difference between the relative value of the OAC and that of the absorbed dose. Moreover, the distribution of OH radical (•OH) concentration obtained by Monte Carlo simulation ("PHITS" ver. 3.24 JAEA, Japan) and that of the OAC were compared. Results: In the direction of beam travel, the relative distribution of the OAC was lower than that of the absorbed dose. This discrepancy could be attributed to a decrease in the concentration of •OH produced by irradiation owing to the recombination reaction, which does not accurately reflect the absorbed dose. By contrast, the distributions in the plane perpendicular to the beam travel were consistent. The RF increased from ± 3% to ± 13% along the beam travel direction. The small RF in the plane perpendicular to the beam travel could be attributed to the constant distribution of linear energy transfer, regardless of the irradiation position, and the generation of radicals proportionally to the absorbed dose. The increase in RF along the beam travel direction was ascribed to ring artifacts in the irradiated region. Conclusion: The measurement of the absorbed dose distribution in the beam travel direction should be improved. The observed discrepancy is attributed to the reduced reactivity of the SHD due to a high liner energy transfer near the Bragg peak. However, the absorbed dose distribution can be effectively evaluated in the plane perpendicular to the direction of beam travel. [ABSTRACT FROM AUTHOR]

Recently, ultra-high dose rate (> 40 Gy/s, uHDR; FLASH) radiation therapy (RT) has attracted interest, because the FLASH effect that is, while a cell-killing effect on cancer cells remains, the damage to normal tissue could be spared has been reported. This study aimed to compare the immune-related protein expression on cancer cells after γ-ray, conventionally used dose rate (Conv) carbon ion (C-ion), and uHDR C-ion. B16F10 murine melanoma and Pan02 murine pancreas cancer were irradiated with γ-ray at Osaka University and with C-ion at Osaka HIMAK. The dose rates at 1.16 Gy/s for Conv and 380 Gy/s for uHDR irradiation. The expressed calreticulin (CRT), major histocompatibility complex class (MHC)-I, and programmed cell death 1 ligand (PD-L1) were evaluated by flow cytometry. Western blotting and PCR were utilized to evaluate endoplasmic reticulum (ER) stress, DNA damage, and its repair pathway. CRT, MHC-I on B16F10 was also increased by irradiation, while only C-ion increased MHC-I on Pan02. Notably, PD-L1 on B16F10 was increased after irradiation with both γ-ray and C-ion, while uHDR C-ion suppressed the expression of PD-L1 on Pan02. The present study indicated that uHDR C-ion has a different impact on the repair pathway of DNA damage and ER than the Conv C-ion. This is the first study to show the immune-related protein expressions on cancer cells after uHDR C-ion irradiation. [ABSTRACT FROM AUTHOR]

Carbon ion beam irradiation (CIBI) is a highly efficient mutagenesis for generating mutations that can be used to expand germplasm resources and create superior new germplasm. The study investigated the effects of different doses of CIBI (50 Gy, 100 Gy, 150 Gy, 200 Gy and 300 Gy) on seed germination and seedling survival, seedling morphological and physiological traits of an elite centipedegrass cultivar Ganbei. The results showed that irradiation greater than 50 Gy cause inhibition of seed germination, and the semi-lethal dose (LD50) is around 90 Gy for CIBI treated seeds of Ganbei. A carbon ion beam-mutagenized centipedegrass population was generated from Ganbei, with irradiation dosages from 50 Gy to 200 Gy. More than ten types of phenotypic variations and novel mutants with heritable tendencies mainly including putative mutants of stolon number, length and diameter, of internode length, of leaf length and width, of leaf chlorophyll content, of stolon growth rate, of aboveground tissue dry weight, of sward height were identified. While the total sugar content of the plants from irradiated seeds showed no obvious change in all treatments as compared to the control, the crude protein content displayed significant reduction at a high-dose treatment of 200 Gy. Genetic polymorphism was detected in mutagenized centipedegrass population using SSR-PCR analysis, suggesting that CIBI caused alteration of larger fragments of the DNA sequence. As a result, a preliminary batch of mutants was screened in this study. In summary, carbon ion beam mutagenesis is an effective way for developing centipedegrass germplasm with wider variation, and treating seeds with CIBI at a dosage of ~100 Gy could be effective in centipedegrass mutation breeding. [ABSTRACT FROM AUTHOR]

Cannabis fructus (Cannabis sativa L.) belongs to the mulberry family, which is one of the earliest cultivated crops by humans and has industrial, agricultural, and medicinal values. In this study, the effect of carbon ion beam irradiation on the physiological and biochemical pathways of cannabis fructus was analyzed by multi-omics. Compared to the unirradiated cannabis fructus stem, 2,891 differentially-expressed genes, 1,145 differentially-expressed proteins, and 954 altered ubiquitination modification sites were identified in cannabis fructus irradiated by carbon ion beam irradiation (60 Gy dosage). Correlation analyses between proteomic, transcriptomic, and ubiquitin modification groups were carried out, and we found that the carbon fixation pathway, fatty acid synthesis pathway, JA synthesis, and glutathione metabolism pathway were enriched in relevant protein levels, and activates the MAPK signaling pathway regulated by gene expression. Further analysis found that the content of some proteins (LOX, AOC, and MDR) was correlated with their respective transcriptional levels, and the content of some proteins (APX, G-6-PD, GST, GAPHD, FBA, AOS, PR1, and ChiB) was correlated with their ubiquitination levels. In addition, M2 generation cannabis fructus seeds exhibited a larger volume, higher thousand-grain weight, and increased linolenic acid content compared to the control group, which was consistent with the trends of our multi-omics analyses. In summary, we demonstrated that 60 Gy carbon ion beam irradiation can enhance the carbon fixation pathway in cannabis fructus and enhance linolenic acid synthesis. Taken together, our multi-omics analysis of the response of cannabis fructus to carbon ion beam irradiation provides a theoretical foundation for readily producing cannabis fructus varieties with advantageous traits in the future.

Chimeras are universal phenomena in the M1-generation plants obtained following radiation-induced mutagenesis; however, the mutational effects and variant inheritance mechanisms of related rice chimeras have yet to be sufficiently clarified. In this study, we used target capture-seq technology to obtain OsNramp5 mutant chimeras via carbon ion beam irradiation, and used a 10 kb liquid chip to determine the SNP/InDel mutational occurrence and genetic isolation characteristics of the chimeric M1 generation and mutational M2 genomes. The results revealed that the mutation detected in the OsNramp5 gene of M1 chimeric rice was not inherited by the M2 generation; that is, the mutation detected in somatic cells of the M1 population was not passed to the subsequent generation via the germ cells. In addition, conversion was established to be twice as common as transversion among the M1 genomic mutation types, although more than half of the variant sites were inherited by the M2 generation. However, these sites were rarely located within the functional coding regions of genes. Our findings in this study revealed the genomic variation characteristics of somatic M1-generation chimeras induced by carbon ion beam irradiation and their genetic characteristics in the M2 generation. These findings will provide a reference for further studies that seek to elucidate the mechanisms underlying chimeric mutation effects and for selecting appropriate procedures for mutagenesis breeding following carbon ion beam irradiation.

The molecular nature of mutations induced by ionizing radiation and chemical mutagens in plants is becoming clearer owing to the availability of highthroughput DNA sequencing technology. However, few studies have compared the induced mutations between different radiation qualities and between different irradiated materials with the same analysis method. To compare mutation induction between dry-seeds and seedlings irradiated with carbon ions and gamma rays in Arabidopsis, in this study we detected the mutations induced by seedling irradiation with gamma rays and analyzed the data together with data previously obtained for the other irradiation treatments. Mutation frequency at the equivalent dose for survival reduction was higher with gamma rays than with carbon ions, and was higher with dry-seed irradiation than with seedling irradiation. Carbon ions induced a higher frequency of deletions (2 −99 bp) than gamma rays in the case of dry-seed irradiation, but this difference was less evident in the case of seedling irradiation. This result supported the inference that dry-seed irradiation under a lower water content more clearly reflects the difference in radiation quality. However, the ratio of rearrangements (inversions, translocations, and deletions larger than 100 bp), which are considered to be derived from the rejoining of two distantly located DNA breaks, was significantly higher with carbon ions than gamma rays irrespective of the irradiated material. This finding suggested that high-linear energy transfer radiation induced closely located DNA damage, irrespective of the water content of the material, that could lead to the generation of rearrangements. Taken together, the results provide an overall picture of radiation-induced mutation in Arabidopsis and will be useful for selection of a suitable radiation treatment for mutagenesis. [ABSTRACT FROM AUTHOR]

Heat stress has become a major threat to plant growth and development. The objective of the present study was to investigate any changes in physio-biochemical and transcriptional seedling responses to heat stress caused by pre-stress irradiation of Arabidopsis seeds with a carbon ion beam. The seeds were exposed to a series of doses (0, 50, 100, 150, and 200 Gray [Gy]) before being exposed to heat stress (40 °C). The results showed that 50-Gy carbon ion beam irradiation exhibited stimulatory effects, compared with seedlings grown from non-irradiated seeds, on germination index, root length, and fresh weight in heat-stressed Arabidopsis seedlings. Moreover, the accumulation rates of superoxide anion radicals, hydroxyl radicals, hydrogen peroxide, and malondialdehyde concentrations were significantly lower in stressed seedlings grown from irradiated seeds. Furthermore, antioxidant enzyme activities and non-enzymatic antioxidant concentrations in heat-stressed seedlings grown from irradiated seed were significantly higher than in the control seedlings grown from non-irradiated seedlings. Notably, the transcription levels of several genes related to heat stress response were differentially regulated in response to heat stress in seedlings grown from seed irradiated with low-dose carbon ion beams. Collectively, this study suggests that low-dose carbon ion beam irradiation can modulate the physiological responses and regulate heat-signaling genes involved in mitigating heat stress during Arabidopsis seedling growth. [ABSTRACT FROM AUTHOR]

Abstract Aim With the increased use of particle therapy for liver cancer, local recurrence after particle therapy increased. Salvage hepatectomy is an acceptable treatment option for local recurrence following particle therapy; however, its safety and effectiveness remain unclear. Therefore, this multi‐center study aimed to verify the feasibility and efficacy of salvage hepatectomy and assess clinical issues associated with its application. Methods We retrospectively assessed the perioperative outcomes, prognosis, and pathological characteristics of 15 patients who underwent salvage hepatectomy for local recurrence after particle therapy between 2006 and 2019. Results Hepatocellular carcinoma and metastatic liver tumors were noted in eight and seven patients, respectively. The mean total dose and number of fractions were 66.5 Gy and 12, respectively, and the mean interval between particle therapy and surgery was 30.1 months. Major hepatectomy was performed in seven cases. Moreover, the mortality rate was 0%, and surgical complications of Clavien‐Dindo grade IIIa or higher were observed in four cases (27%)—two bile leakages, one pleural effusion, and one refractory skin fistula. The median overall survival time and 5‐year overall survival rate after salvage hepatectomy were 29.9 months and 43.1%, respectively. Histological examination of the irradiated liver tissue surrounding the tumor showed sinusoidal dilatation, loss of hepatocyte, and fibrosis in most cases. Conclusion Salvage hepatectomy after particle therapy is a feasible therapy; however, the risk of refractory complications associated with particle therapy is relatively high. Therefore, the first‐line treatment for resectable liver cancer should be carefully determined considering second‐line treatment after local recurrence.

Aim: With the increased use of particle therapy for liver cancer, local recurrence after particle therapy increased. Salvage hepatectomy is an acceptable treatment option for local recurrence following particle therapy; however, its safety and effectiveness remain unclear. Therefore, this multi‐center study aimed to verify the feasibility and efficacy of salvage hepatectomy and assess clinical issues associated with its application. Methods: We retrospectively assessed the perioperative outcomes, prognosis, and pathological characteristics of 15 patients who underwent salvage hepatectomy for local recurrence after particle therapy between 2006 and 2019. Results: Hepatocellular carcinoma and metastatic liver tumors were noted in eight and seven patients, respectively. The mean total dose and number of fractions were 66.5 Gy and 12, respectively, and the mean interval between particle therapy and surgery was 30.1 months. Major hepatectomy was performed in seven cases. Moreover, the mortality rate was 0%, and surgical complications of Clavien‐Dindo grade IIIa or higher were observed in four cases (27%)—two bile leakages, one pleural effusion, and one refractory skin fistula. The median overall survival time and 5‐year overall survival rate after salvage hepatectomy were 29.9 months and 43.1%, respectively. Histological examination of the irradiated liver tissue surrounding the tumor showed sinusoidal dilatation, loss of hepatocyte, and fibrosis in most cases. Conclusion: Salvage hepatectomy after particle therapy is a feasible therapy; however, the risk of refractory complications associated with particle therapy is relatively high. Therefore, the first‐line treatment for resectable liver cancer should be carefully determined considering second‐line treatment after local recurrence. [ABSTRACT FROM AUTHOR]

Background Medium‐dose (25 gray) x‐ray radiation therapy has recently been performed on patients with refractory ventricular tachyarrhythmias. Unlike x‐ray, carbon ion and proton beam radiation can deliver most of their energy to the target tissues. This study investigated the electrophysiological and pathological changes caused by medium‐dose carbon ion and proton beam radiation in the left ventricle (LV). Methods and Results External beam radiation in the whole LV was performed in 32 rabbits. A total of 9 rabbits were not irradiated (control). At the 3‐month or 6‐month follow‐up, the animals underwent an open‐chest electrophysiological study and were euthanized for histological analyses. No acute death occurred. Significant LV dysfunction was not seen. The surface ECG revealed a significant reduction in the P and QRS wave voltages in the radiation groups. The electrophysiological study showed that the local conduction times in each LV site were significantly longer and that the local LV bipolar voltages were significantly lower in the radiation groups than in the control rabbits. Histologically, apoptosis, fibrotic changes, and a decrease in the expression of the connexin 43 protein were seen in the LV myocardium. These changes were obvious at 3 months, and the effects were sustained 6 months after radiation. No histological changes were seen in the coronary artery and esophagus, but partial radiation pneumonitis was observed. Conclusions Medium‐dose carbon ion and proton beam radiation in the whole LV resulted in a significant electrophysiological disturbance and pathological changes in the myocardium. Radiation of the arrhythmogenic substrate would modify the electrical status and potentially induce the antiarrhythmic effect.

Radiation therapy is an important component of the comprehensive treatment of esophageal cancer. However, conventional radiation resistance is one of the main reasons for treatment failure. The superiority of heavy ion radiation in physics and biology has been increasingly highlighted in radiation therapy research. The Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway plays an important role in the occurrence, development and metastasis of esophageal squamous cell carcinoma (ESCC) and is related to the development of resistance to ionizing radiation in ESCC. Therefore, the aim of the present study was to investigate the relationship between carbon ion inhibition of the proliferation and metastasis of esophageal carcinoma cells and the JAK2/STAT3 signaling pathway. The results demonstrated that carbon ion beams significantly reduced cell viability and stimulated apoptosis in human ESCC cells in a dose-dependent manner. In addition, carbon ion beams induced G2/M phase cell cycle arrest in ESCC cells and inhibited tumor metastasis in a dose-dependent manner. Additionally, poorly differentiated KYSE150 cells were more sensitive to the same carbon ion beam dose than moderately differentiated ECA109 cells. Carbon ion beam exposure regulated the relative expression of metastasis-related molecules at the transcriptional and translational levels in ESCC cells. Carbon ion beams also regulated CDH1 and MMP2 downstream of the STAT3 pathway and inhibited ESCC cell metastasis, which activated the STAT3 signaling pathway. This study confirmed the inhibition of cell proliferation and the metastatic effect of carbon ion beam therapy in ESCC cells.

We have measured the energy of each charged particle in carbon ion beam using a transition edge sensor (TES). The TES was irradiated by carbon ion beam of 100 MeV/u in Heavy Ion Medical Accelerator in Chiba. We have measured the energy of each charged particle in the carbon ion beam. This will contribute to the establishment of a new dosimetry method of carbon ion beam for radiotherapy. [ABSTRACT FROM AUTHOR]

• PSP can broaden the Bragg-peak width while maintaining sharp distal falloff width. • PSP possesses a high modulation power and a good modulation effect. • The PSP-modulated fluence showed a better homogeneity than using RiFis. The present study aimed to develop a porous structure with plug-ins (PSP) to broaden the Bragg peak width (BPW, defined as the distance in water between the proximal and distal 80% dose) of the carbon ion beam while maintaining a sharp distal falloff width (DFW, defined as the distance along the beam axis where the dose in water reduces from 80% to 20%). The binary voxel models of porous structure (PS) and PSP were established in the Monte Carlo code FLUKA and the corresponding physical models were manufactured by 3D printing. Both experiment and simulation were performed for evaluating the modulation capacity of PS and PSP. BPWs and DFWs derived from each integral depth dose curves were compared. Fluence homogeneity of 430 MeV/u carbon-ion beam passing through the PSP was recorded by analyzing radiochromic films at six different locations downstream the PSP in the experiment. Additionally, by changing the beam spot size and incident position on the PSP, totally 48 different carbon-ion beams were simulated and corresponding deviations of beam metrics were evaluated to test the modulating stability of PSP. According to the measurement data, the use of PSP resulted in an average increase of 0.63 mm in BPW and a decrease of 0.74 mm in DFW compared to PS. The 2D radiation field inhomogeneities were lower than 3 % when the beam passing through a ≥ 10 cm PMMA medium. Furthermore, employing a spot size of ≥ 6 mm ensures that beam metric deviations, including BPW, DFW, and range, remain within a deviation of 0.1 mm across various incident positions. The developed PSP demonstrated its capability to effectively broaden the BPW of carbon ion beams while maintaining a sharp DFW comparing to PS. The superior performance of PSP, indicates its potential for clinical use in the future. [ABSTRACT FROM AUTHOR]

SUMMARY: Undaria pinnatifida, the brown macroalga, is a major commercial edible seaweed, and there is increasing interest in breeding new, improved cultivars for market expansion. In this study, we attempted to establish mutagenesis in U. pinnatifida using Ar and C ion beams as mutagens to meet future demands. To screen irradiated generations for mutants, U. pinnatifida zoospores irradiated with Ar and C ion beams were cultivated in plastic Petri dishes. Some gametophytes derived from the irradiated zoospores showed growth arrest or cell death at the initial developmental stage. Although the growth inhibition and lethal effects were observed at high doses of each ion irradiation, the Ar ion irradiation had high biological effects on cell division and growth. The gametophytes that showed a reduction in cell elongation were designated as an inhibited cell elongation mutant. A comparison of the mutant induction frequencies revealed that the C ion beam showed a higher frequency than the Ar ion beam. The highest frequency was 0.83% at 12.5 Gy of the C ion beam. We determined the total number of sporophytes and embryos per female gametophyte after sporophyte induction. High‐dose irradiation with the Ar ion beam decreased the embryo and sporophyte formation, suggesting that the Ar ion beam also has exhibited high biological effects on the fertilization or embryogenesis processes or both. The developed heavy ion mutagenesis and mutant screening methods would be useful for mutation breeding and constructing specific mutant libraries in brown algae, and not only in U. pinnatifida. [ABSTRACT FROM AUTHOR]

Time courses of the redox status in the brains of mice after X-ray or carbon-ion beam irradiation were observed by magnetic resonance redox imaging (MRRI). The relationship between radiation-induced oxidative stress on the cerebral nervous system and the redox status in the brain was discussed. The mice were irradiated by 8-Gy X-ray or carbon-ion beam (C-beam) on their head under anesthesia. C-beam irradiation was performed at HIMAC (Heavy-Ion Medical Accelerator in Chiba, NIRS/QST, Chiba, Japan). MRRI measurements using a blood-brain-barrier-permeable nitroxyl contrast agent, MCP or TEMPOL, were performed using 7-T scanner at several different times, i.e., 5–10 h, 1, 2, 4, and 8 day(s) after irradiation. Decay rates of the nitroxyl-enhanced T 1 -weighted MR signals in the brains were estimated from MRRI data sets, and variation in the decay rates after irradiation was assessed. The variation in decay rates of MCP and TEMPOL after X-ray or C-beam irradiation was similar, but different variation patterns were observed between X-ray and C-beam. The apparent decay rate of both MCP and TEMPOL decreased due to the temporal reduction of blood flow in the brain several hours after X-ray and/or C-beam irradiation. After decreasing, the apparent decay rates of nitroxyl radicals in the brain gradually increased during the following days after X-ray irradiation or rapidly increased 1 day after C-beam irradiation. The sequential increase in nitroxyl decay rates may have been due to the oxidative atmosphere in the tissue due to ROS generation. X-ray and C-beam irradiation resulted in different redox responses, which may have been due to time-varying oxidative stress/injury, in the mouse brain. The C-beam irradiation effects were more acute and larger than those of X-ray irradiation. Image 1 • Amphiphilic nitroxyl radicals could be BBB-permeable functional MR contrast agents. • Redox status in a mouse brain was estimated by magnetic resonance redox imaging. • Temporal reduction of blood flow in the brain hours after irradiation was expected. • Delayed ROS generation days after irradiation were expected in the brain. • X-ray and C-beam irradiation resulted in different redox responses in the brain. [ABSTRACT FROM AUTHOR]

Particle, essentially, proton radiotherapy (RT) could provide some benefits over photon RT, especially in reducing the side effects of RT. We performed a systematic review to identify the performed randomised clinical trials (RCTs) and ongoing RCTs comparing particle RT with photon therapy. So far, there are no results available from phase 3 RCTs comparing particle RT with photon therapy. Furthermore, the results on side effects comparing proton and carbon ion beam RT with photon RT do vary. The introduction of new techniques in photon RT, such as image-guided RT (IGRT), intensity-modulated RT (IMRT), volumetric arc therapy (VMAT) and stereotactic body RT (SBRT) was already effective in reducing side effects. At present, the lack of evidence limits the indications for proton and carbon ion beam RTs and makes the particle RT still experimental. [ABSTRACT FROM AUTHOR]

Understanding the characteristics of carbon ion beam irradiation-induced mutation is essential to its potential application in plant breeding. A carbon ion beam-mutagenized soybean population was generated from the newly released soybean variety Dongsheng 28, with irradiation dosages of 100 Gy, 120 Gy and 140 Gy. Many phenotypic variations and novel mutants with heritable tendencies including plant height mutants, sterile mutants, early mature mutants, rolled leaves and short petioles mutants, yield-related mutants and lodging-resistant mutants were identified. Diverse variations in seed size, seed protein and oil concentration were found. Increasing irradiation dosage from 100 Gy to 140 Gy increased leaf chlorophyll concentration in M1 generation, but this effect was significantly reduced in M2 generation. The activities of superoxide dismutase (SOD), peroxidase (POD) and malondialdehyde (MDA) concentration all showed wider variation in M1 and M2 generation, the only exception being that the MDA concentration was similar to the control in the M2 generation. Overall, we suggest that treating soybean seeds with carbon ion beam irradiation at a dosage of 120 Gy (80 Mev/u) could be effective in soybean mutation breeding.

Mutations caused by ion beams have been well-studied in plants, including ornamental flowers, rice, and algae. It has been shown that ion beams have several significantly interesting features, such as a high biological effect and unique mutation spectrum, which is in contrast to low linear energy transfer (LET) radiation such as gamma rays. In this study, the effects of double strand breaks and 8-oxo-2′-deoxyguanosine (8-oxodG) caused by ion-beam irradiation were examined. We irradiated repair-gene-inactive strains rad52, ogg1, and msh2 using carbon ion beams, analyzed the lethality and mutagenicity, and characterized the mutations. High-LET carbon ion-beam radiation was found to cause oxidative base damage, such as 8-oxodG, which can lead to mutations. The present observations suggested that nucleotide incorporation of oxidative damage gave only a limited effect on cell viability and genome fidelity. The ion-beam mutations occurred predominantly in 5′-ACA-3′ sequences, and we detected a hotspot at around +79 to +98 in URA3 in wild-type and mutant lines, suggesting the presence of a mutation-susceptible region.

Carbon ion beam irradiation is a powerful method for creating mutants and has been used in crop breeding more and more. To investigate the effects of carbon ion beams on Lotus japonicus , dry seeds were irradiated by 80 MeV/u carbon ion beam at dosages of 0, 100, 200, 300, 400, 500 and 600 Gy. The germination rate, survival rate and root length of M 1 populations were explored and the dose of 400 Gy was selected as the median lethal dose (LD 50 ) for a large-scale mutant screening. Among 2472 M 2 plants, 127 morphological mutants including leaf, stem, flower and fruit phenotypic variation were found, and the mutation frequency was approximately 5.14%. Inter simple sequence repeat (ISSR) assays were utilized to investigate the DNA polymorphism between seven mutants and eight plants without phenotypic variation from M 2 populations. No remarkable differences were detected between these two groups, and the total polymorphic rate was 0.567%. [ABSTRACT FROM AUTHOR]

We compare the thermoluminescence (TL) behavior of Ce3+ ion-activated LiCaAlF6 exposed to γ-rays and a carbon ion beam. The reported phosphor is synthesized using an in-house precipitation method with varying concentrations of activator ion and is characterized by X-ray diffraction (XRD) and TL. Rietveld refinement is performed to study the structural statistics. The TL glow curve consists of a prominent glow peak at 232°C with three shoulders at 115, 159 and 333°C when exposed to γ-rays from a 60Co source. When exposed to a C5+ ion beam, the TL glow curve consists of five peaks with peak temperatures near 156, 221, 250, 287 and 330°C, and is found to vary slightly with changing fluence. Glow curve convolution deconvolution (GCCD) functions are applied to the TL curves for complete analysis of the glow curve structure and TL traps. The order of kinetics ( b), activation energy ( E) and frequency factor are determined using Chen's peak shape method and theoretical curves are drawn using GCCD functions. A track interaction model (TIM) is used to explain the sublinearity/saturation at higher fluences. Ion beam parameters are analyzed using Monte-Carlo simulation-based SRIM-2013 code. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The industrial production of monascus yellow pigments (MYPs) has not yet been done due to the lack of high-quality industrial Monascus strains. In this work, we employed carbon ion beam (12C6+) irradiation to screen Monascus strains that produce high-quality extracellular MYPs (extr-MYPs). One genetically stable M. purpureus mutant of BWY-5 with extr-MYPs accumulation was obtained under 12C6+ irradiation (80 MeV/u, 200 Gy). M. purpureus BWY-5 could use various nitrogen sources to produce single pH stable extr-MYPs (around 80 AU at 370 nm). Moreover, citrinin was not detected by HPLC method. Transcriptomics of the MYP production strain suggested that Carbon ion beam irradiation led to deletion (MpigF , MpigG and MpigH), downregulation (CtnE , CtnH and CtnI) and upregulation (MpigM) of genes related with biosynthesis of MOPs and MRPs, citrinin, and extr-MYPs, respectively. The results showed that M. purpureus BWY-5 has the potential to be used as an industrial Monascus strain and platform for extr-MYPs production and monascus polyketide synthetic pathway studies, respectively. [Display omitted] • Mutant of Monascus with high-yielding MYPs and citrinin-free production obtained by carbon ion beam irradiation. • Excellent pH stability of extr-MYPs that can be produced by Monascus mutant using various nitrogen sources. • The increase of extr-MYPs may be attributed to the up-regulation expression of gene MpigM (coding for P450 monooxygenase). [ABSTRACT FROM AUTHOR]

Noninvasive AF Ablation With Carbon Ions Introduction Catheter ablation with isolation of the pulmonary veins is a common treatment option for atrial fibrillation but still has insufficient success rates and carries several interventional risks. These treatment planning studies assessed if high-dose single fraction treatment with scanned carbon ions (12C) can be reliably delivered for AF ablation, while sparing risk structures and considering respiratory and contractile target motion. Methods and Results Time resolved CT scans of complete respiratory and cardiac cycles of 9 and 5 patients, respectively, were obtained. Ablation lesions and organs at risk for beam delivery were contoured. Single fraction intensity-modulated particle therapy with target doses of 25 and 40 Gy were studied and motion influences on these deliveries mitigated. Respiration had a large influence on lesion displacement (≤ 2 cm). End expiration could be exploited as a stable gating window. Smaller, but less predictable, heartbeat displacements (< 6 mm) remained to be mitigated because cardiac contraction resulted in insufficient dose coverage (V95 < 90 %) if uncompensated. Repeated irradiation (12C beam rescanning) during breath hold was used to accommodate contractile motion, resulting in good dose coverage. Dose depositions to all organs at risk were carefully examined and did not exceed values for X-ray cancer treatment. Conclusion Treatment planning of 12C with delivery of physical ionizing radiation doses that have been described to induce complete block is feasible for AF ablation, considering human anatomy, dose constraints, and encasing underlying motion patterns from respiration and cardiac contraction at the LA-PV junction into treatment planning. [ABSTRACT FROM AUTHOR]

High linear energy transfer (LET) carbon ion beam (CIB) is becoming very promising tool for various cancer treatments and is more efficient than conventional low LET gamma or X-rays to kill malignant or radio-resistant cells, although detailed mechanism of cell death is still unknown. Poly (ADP-ribose) polymerase-1 (PARP-1) is a key player in DNA repair and its inhibitors are well-known as radio-sensitizer for low LET radiation. The objective of our study was to find mechanism(s) of induction of apoptosis by CIB and role of PARP-1 in CIB-induced apoptosis. We observed overall higher apoptosis in PARP-1 knocked down HeLa cells (HsiI) compared with negative control H-vector cells after irradiation with CIB (0-4 Gy). CIB activated both intrinsic and extrinsic pathways of apoptosis via caspase-9 and caspase-8 activation respectively, followed by caspase-3 activation, apoptotic body, nucleosomal ladder formation and sub-G accumulation. Apoptosis inducing factor translocation into nucleus in H-vector but not in HsiI cells after CIB irradiation contributed caspase-independent apoptosis. Higher p53 expression was observed in HsiI cells compared with H-vector after exposure with CIB. Notably, we observed about 37 % fall of mitochondrial membrane potential, activation of caspase-9 and caspase-3 and mild activation of caspase-8 without any detectable apoptotic body formation in un-irradiated HsiI cells. We conclude that reduction of PARP-1 expression activates apoptotic signals via intrinsic and extrinsic pathways in un-irradiated cells. CIB irradiation further intensified both intrinsic and extrinsic pathways of apoptosis synergistically along with up-regulation of p53 in HsiI cells resulting overall higher apoptosis in HsiI than H-vector. [ABSTRACT FROM AUTHOR]