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Abstract Boron neutron capture therapy (BNCT) is a unique radiotherapy of selectively eradicating tumor cells using boron compounds (e.g., 4-borono-l-phenylalanine [BPA]) that are heterogeneously taken up at the cellular level. Such heterogenicity potentially reduces the curative efficiency. However, the effects of temporospatial heterogenicity on cell killing remain unclear. With the technical combination of radiation track detector and biophysical simulations, this study revealed the cell cycle-dependent heterogenicity of BPA uptake and subsequent biological effects of BNCT on HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators, as well as the modification effects of polyvinyl alcohol (PVA). The results showed that the BPA concentration in the S/G2/M phase was higher than that in the G1/S phase and that PVA enhances the biological effects both by improving the uptake and by canceling the heterogenicity. These findings might contribute to a maximization of therapeutic efficacy when BNCT is combined with PVA and/or cell cycle-specific anticancer agents.

Abstract The knowledge on responses of human lens epithelial cells (HLECs) to ionizing radiation exposure is important to understand mechanisms of radiation cataracts that are of concern in the field of radiation protection and radiation therapy. However, biological effects in HLECs following protracted exposure have not yet fully been explored. Here, we investigated the temporal kinetics of γ-H2AX foci as a marker for DNA double-strand breaks (DSBs) and cell survival in HLECs after exposure to photon beams at various dose rates (i.e., 150 kVp X-rays at 1.82, 0.1, and 0.033 Gy/min, and 137Cs γ-rays at 0.00461 Gy/min (27.7 cGy/h) and 0.00081 Gy/min (4.9 cGy/h)), compared to those in human lung fibroblasts (WI-38). In parallel, we quantified the recovery for DSBs and cell survival using a biophysical model. The study revealed that HLECs have a lower DSB repair rate than WI-38 cells. There is no significant impact of dose rate on cell survival in both cell lines in the dose-rate range of 0.033–1.82 Gy/min. In contrast, the experimental residual γ-H2AX foci showed inverse dose rate effects (IDREs) compared to the model prediction, highlighting the importance of the IDREs in evaluating radiation effects on the ocular lens.

The International Partner Agencies of the International Space Station (ISS) present a comparison of the ionizing radiation absorbed dose and risk quantities used to characterize example missions in lunar space. This effort builds on previous collaborative work that characterizes radiation environments in space to support radiation protection for human spaceflight on ISS in low-Earth orbit (LEO) and exploration missions beyond (BLEO). A “shielded” ubiquitous galactic cosmic radiation (GCR) environment combined with––and separate from––the transient challenge of a solar particle event (SPE) was modelled for a simulated 30-day mission period. Simple geometries of relatively thin and uniform shields were chosen to represent the space vehicle and other available shielding, and male or female phantoms were used to represent the body’s self-shielding. Absorbed dose in organs and tissues and the effective dose were calculated for males and females. Risk parameters for cancer and other outcomes are presented for selected organs. The results of this intracomparison between ISS Partner Agencies itself provide insights to the level of agreement with which space agencies can perform organ dosimetry and calculate effective dose. This work was performed in collaboration with the advisory and guidance efforts of the International Commission on Radiological Protection (ICRP) Task Group 115 and will be presented in an ICRP Report

The analytical microdosimetric function (AMF) implemented in the Monte Carlo code PHITS is a unique tool that bridges the gap between macro- and microscopic scales of radiation interactions, enabling accurate microdosimetric calculations over macroscopic bodies. The original AMF was published in 2006, based on the results of track structure calculations. Recently, a newer version of the AMF was proposed, incorporating an improved description of the energy loss at the microscopic scale. This study compares the older and the newer AMFs in computing microdosimetric probability distributions, mean values, and the relative biological effectiveness (RBE). To this end, 16000 microdosimetric lineal energy probability density distributions were simulated with PHITS for ions from 1H to 238U over a broad energy range (1–1000 MeV/n). The newer AMF was found to offer superior performance, particularly for very heavy ions, producing results that align more closely with published in vitro clonogenic survival experiments. These findings suggest that the updated AMF provides a more reliable tool for microdosimetric calculations and RBE modeling, essential for ion radiation therapy and space radiation protection.

Subfoveal perfluorocarbon liquid (PFL) is a vision-threatening complication that requires removal as safely as possible. We experienced a surgical case of proliferative vitreoretinopathy, in which a subfoveal PFL droplet was removed through the fovea, without puncturing the retina. In this case, although the retina was completely attached after primary vitrectomy and cataract removal, a subfoveal PFL droplet was found. At the second surgery, after peeling the internal limiting membrane, the droplet was passively aspirated by placing a 25-gauge blunt needle on the surface of the retina. This useful technique avoids puncturing the retina and does not require the patient to maintain a specific position postoperatively.

Abstract Background Postpartum hemorrhage (PPH) is a potentially fatal condition requiring urgent and appropriate intervention. Uterine artery embolization (UAE) has a high hemostatic capacity for PPH, but it may fail. Disseminated intravascular coagulation (DIC) has been reported as a risk factor associated with the failure of UAE. Case presentation A 37-year-old primigravida with dichorionic diamniotic twins and placenta previa underwent cesarean section. The blood loss during surgery was 4950 mL. Hemostasis was achieved using an intrauterine balloon tamponade device. However, she lost a further 2400 mL of blood 5 h after surgery. We embolized both uterine arteries using gelatin sponges and confirmed hemostasis. She was suffering from DIC and received ample blood transfusions. However, a further 1300 mL of blood was lost 18 h after surgery and we performed repeated UAE, with complete recanalization of the uterine arteries on both sides and re-embolization with gelatin sponges. Her DIC was treated successfully by blood transfusions at this time, and she showed no further bleeding after the repeated UAE. Conclusions DIC is a risk factor for the failure of UAE. Repeated UAE may be effective after sufficient improvement of the hematological status in patients with PPH and DIC.

Abstract Cosmic-ray exposure to flight crews and passengers, which is called aviation radiation exposure, is an important topic in radiological protection, particularly for solar energetic particles (SEP). We therefore assessed the risks associated with the countermeasure costs to reduce SEP doses and dose rates for eight flight routes during five ground level enhancements (GLE). A four-dimensional dose-rate database developed by the Warning System for Aviation Exposure to Solar Energetic Particles, WASAVIES, was employed in the SEP dose evaluation. As for the cost estimation, we considered two countermeasures; one is the cancellation of the flight, and the other is the reduction of flight altitudes. Then, we estimated the annual occurrence frequency of significant GLE events that would bring the maximum flight route dose and dose rate over 1.0 mSv and 80 μSv/h, respectively, based on past records of GLE as well as historically large events observed by the cosmogenic nuclide concentrations in tree rings and ice cores. Our calculations suggest that GLE events of a magnitude sufficient to exceed the above dose and dose rate thresholds, requiring a change in flight conditions, occur once every 47 and 17 years, respectively, and their conservatively-estimated annual risks associated with the countermeasure costs are up to around 1.5 thousand USD in the cases of daily-operated long-distance flights.

Abstract Although solar activity may significantly impact the global environment and socioeconomic systems, the mechanisms for solar eruptions and the subsequent processes have not yet been fully understood. Thus, modern society supported by advanced information systems is at risk from severe space weather disturbances. Project for solar–terrestrial environment prediction (PSTEP) was launched to improve this situation through synergy between basic science research and operational forecast. The PSTEP is a nationwide research collaboration in Japan and was conducted from April 2015 to March 2020, supported by a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan. By this project, we sought to answer the fundamental questions concerning the solar–terrestrial environment and aimed to build a next-generation space weather forecast system to prepare for severe space weather disasters. The PSTEP consists of four research groups and proposal-based research units. It has made a significant progress in space weather research and operational forecasts, publishing over 500 refereed journal papers and organizing four international symposiums, various workshops and seminars, and summer school for graduate students at Rikubetsu in 2017. This paper is a summary report of the PSTEP and describes the major research achievements it produced.

Abstract We surveyed the relationship between the scale of space weather events and their occurrence rate in Japan, and we discussed the social impact of these phenomena during the Project for Solar–Terrestrial Environment Prediction (PSTEP) in 2015–2019. The information was compiled for domestic users of space weather forecasts for appropriate preparedness against space weather disasters. This paper gives a comprehensive summary of the survey, focusing on the fields of electricity, satellite operations, communication and broadcasting, satellite positioning usage, aviation, human space activity, and daily life on the Earth’s surface, using the cutting-edge knowledge of space weather. Quantitative estimations of the economic impact of space weather events on electricity supply and aviation are also given. Some topics requiring future research, which were identified during the survey are also described. Graphic Abstract

Abstract A solar energetic particle (SEP) event generates a shower of secondary generated particles in the Earth’s atmosphere down to lower altitudes to cause an atmospheric radiation storm (ARS). The high-energy secondary particles cause additional radiation dose at altitudes where aircraft flies. The space weather information provided by the International Civil Aviation Organization (ICAO) designated space weather centers includes advisories on the solar radiation storm. The Warning System for AVIation Exposure to Solar energetic particle (WASAVIES), we can estimate the effective dose rate (EDR) along the flight path of the aircraft. However, it has not been well established how the operators of aircraft should react with the space weather advisories on the solar radiation storm. By using a flight trajectory generation algorithm and the global EDR distribution, the economic impacts of ARS associated with SEP events on aircraft operation, namely the flight path length, flight time, and fuel consumption, are estimated. The conditions of the peak of the ARS event on 20 January 2005 are used. The economic impacts for a flight route from New York, US to Tokyo, Japan, are estimated with constraints in flight routes to avoid the hazard of radiation and compared with those of the reference case without the ARS effects. The fuel consumption is shown to increase by 39–69 tons (33–58%) for a twin-engine, wide-body jet passenger aircraft, when a constraint is imposed on the flight altitude only. When the constraints are set on the aircraft altitude and the latitude, the flight time and the fuel consumption are both increased by 2.2–2.8 h (17–20%) and 32–48 tons (27–41%), respectively. If the ARS event duration is limited for 3 h, the increase in the fuel consumption is about 7.6–14 tons (6.4–12%). This economic impact may be reduced, if the space weather nowcast and forecast for the ARS and an optimal flight trajectory generation algorithm are used together. Setting more flexible constraints on the flight route and generating optimal flight trajectories with minimal economic impacts by fully utilizing the global EDR distribution is the next step.

Abstract Background An individual dosimetry system is essential for the evaluation of precise doses in nuclear medicine. The purpose of this study was to develop a system for calculating not only absorbed doses but also EQDX(α/β) from the PET-CT images of patients for targeted alpha therapy (TAT), considering the dose dependence of the relative biological effectiveness, the dose-rate effect, and the dose heterogeneity. Methods A general-purpose Monte Carlo particle transport code PHITS was employed as the dose calculation engine in the system, while the microdosimetric kinetic model was used for converting the absorbed dose to EQDX(α/β). PHITS input files for describing the geometry and source distribution of a patient are automatically created from PET-CT images, using newly developed modules of the radiotherapy package based on PHITS (RT-PHITS). We examined the performance of the system by calculating several organ doses using the PET-CT images of four healthy volunteers after injecting 18F-NKO-035. Results The deposition energy map obtained from our system seems to be a blurred image of the corresponding PET data because annihilation γ-rays deposit their energies rather far from the source location. The calculated organ doses agree with the corresponding data obtained from OLINDA 2.0 within 20%, indicating the reliability of our developed system. Test calculations by replacing the labeled radionuclide from 18F to 211At suggest that large dose heterogeneity in a target volume is expected in TAT, resulting in a significant decrease of EQDX(α/β) for higher-activity injection. Conclusions As an extension of RT-PHITS, an individual dosimetry system for nuclear medicine was developed based on PHITS coupled with the microdosimetric kinetic model. It enables us to predict the therapeutic and side effects of TAT based on the clinical data largely available from conventional external radiotherapy.

Abstract Background and Aim Considering the increasing prevalence of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis (NASH), the development of an effective screening and follow‐up system that enables the recognition of etiological changes by primary physicians in clinics and specialists in hospitals is required. Methods Chronic hepatitis B (HBV) and C (HCV), NASH, and alcoholic steatohepatitis (ASH) patients who were assayed for Mac‐2‐binding protein glycosylation isomer (M2BPGi) (n = 272) and underwent magnetic resonance elastography (MRE) (n = 119) were enrolled. Patients who underwent MRE were also tested by ultrasound elastography (USE) (n = 80) and for M2BPGi (n = 97), autotaxin (ATX) (n = 62), and platelet count (n = 119), and their fibrosis‐4 (FIB‐4) index was calculated (n = 119). Results FIB‐4 index >2, excluding HBV‐infected patients, M2BPGi >0.5, ATX >0.5, and platelet count F3 or F4; it could efficiently predict collateral circulation with high sensitivity, which can replace USE. We also identified etiological features and found that collateral circulation in NASH/ASH patients tended to exceed high‐risk levels; moreover, these patients exhibited more variation in HCC‐associated liver stiffness than the HBV and HCV patients. Conclusions Using appropriate markers and tools, we can establish a stepwise, practical, noninvasive, and etiology‐based screening and follow‐up system in primary and specialty care.

The displacement damage dose (DDD) is a common index used to predict the life of semiconductor devices employed in space-based environments where they will be exposed to radiation. The DDD is commonly estimated from the non-ionizing energy loss based on the Norgett-Robinson-Torrens (NRT) model, although a new definition for a so-called effective DDD considers the molecular dynamic (MD) simulation with the amorphization in semiconductors. The present work developed a new model for calculating the conventional and effective DDD values for silicon carbide (SiC), indium arsenide (InAs), gallium arsenide (GaAs) and gallium nitride (GaN) semiconductors. This model was obtained by extending the displacement per atom tally implemented in the particle and heavy ion transport code system (PHITS). This new approach suggests that the effective DDD is higher than the conventional DDD for arsenic-based compounds due to the amorphization resulting from direct impacts, while this relationship is reversed for SiC because of recombination defects. In the case of SiC and GaN exposed to protons, the effective DDD/conventional DDD ratio decreases with proton energy. In contrast, for InAs and GaAs, this ratio increases to greater than 1 at proton energies up to 100 MeV and plateaus because the defect production efficiency, which is the ratio of the number of stable displacements at the end of collision cascade simulated by MD simulations to the number of defects calculated by NRT model, does not increase at damage energy values above 20 keV. The practical application of this model was demonstrated by calculating the effective DDD values for semiconductors sandwiched between a thin glass cover and an aluminum plate in a low-Earth orbit. The results indicated that the effective DDD could be dramatically reduced by increasing the glass cover thickness to 200 μm, thus confirming the importance of shielding semiconductor devices used in space. This improved PHITS technique is expected to assist in the design of semiconductors by allowing the effective DDD values for various semiconductors having complex geometries to be predicted in cosmic ray environments.

Astatine (211At) is an alpha-emitter with a better treatment efficacy against differentiated thyroid cancer compared with iodine (131I), a conventional beta-emitter. However, its therapeutic comparison has not been fully evaluated. In this study, we compared the therapeutic effect between [211At]NaAt and [131I]NaI. In vitro analysis of a double-stranded DNA break (DSB) and colony formation assay were performed using K1-NIS cells. The therapeutic effect was compared using K1-NIS xenograft mice administered with [211At]NaAt (0.4 MBq (n = 7), 0.8 MBq (n = 9), and 1.2 MBq (n = 4)), and [131I]NaI (1 MBq (n = 4), 3 MBq (n = 4), and 8 MBq (n = 4)). The [211At]NaAt induced higher numbers of DSBs and had a more reduced colony formation than [131I]NaI. In K1-NIS mice, dose-dependent therapeutic effects were observed in both [211At]NaAt and [131I]NaI. In [211At]NaAt, a stronger tumour-growth suppression was observed, while tumour regrowth was not observed until 18, 25, and 46 days after injection of 0.4, 0.8, and 1.2 MBq of [211At]NaAt, respectively. While in [131I]NaI, this was observed within 12 days after injection (1, 3, and 8 MBq). The superior therapeutic effect of [211At]NaAt suggests the promising clinical applicability of targeted alpha therapy using [211At]NaAt in patients with differentiated thyroid cancer refractory to standard [131I]NaI treatment.

Purpose: To report a case with focal choroidal excavation (FCE) accompanied by type 2 choroidal neovascularization (CNV), in which the CNV was successfully treated with intravitreal aflibercept, after which the FCE was no longer detectable. Observations: A conforming type of FCE was detected in the left eye of a 34-year-old Japanese man who visited our hospital for a second opinion regarding treatment for his right eye. Three months later, type 2 CNV developed in the region corresponding to the FCE in the left eye. After treatment with intravitreal aflibercept, the CNV disappeared, and FCE was no longer detected. No recurrence has been observed in the 12 months following the treatment. Conclusions and Importance: Although the etiology of FCE has not been fully elucidated, we discussed the mechanisms underlying its occurrence, its association with CNV, and the disappearance of both conditions after treatment.

Abstract Insoluble radioactive microparticles emitted by the incident at the Fukushima nuclear power plant have drawn keen interests from the viewpoint of radiation protection. Cs-bearing particles have been assumed to adhere in the long term to trachea after aspirated into respiratory system, leading to heterogeneous dose distribution within healthy tissue around the particles. However, the biological effects posed by an insoluble radioactive particle remain unclear. Here, we show cumulative DNA damage in normal human lung cells proximal and distal to the particle (β-ray and γ-ray-dominant areas, respectively) under localized chronic exposure in comparison with uniform exposure. We put a Cs-bearing particle into a microcapillary tip and placed it onto a glass-base dish containing fibroblast or epithelial cells cultured in vitro. A Monte Carlo simulation with PHITS code provides the radial distribution of absorbed dose-rate around the particle, and subsequently we observed a significant change in nuclear γ-H2AX foci after 24 h or 48 h exposure to the particle. The nuclear foci in the cells distal to the particle increased even under low-dose-rate exposure compared with uniform exposure to 137Cs γ-rays, which was suppressed by a treatment with a scavenger of reactive oxygen species. In contrast, such focus formation was less manifested in the exposed cells proximal to the particle compared with uniform exposure. These data suggest that the localized exposure to a Cs-bearing particle leads to not only disadvantage to distal cells but also advantage to proximal cells. This study is the first to provide quantitative evaluation for the spatial distribution of DNA double strand breaks after the heterogeneous chronic exposure to a Cs-bearing particle in comparison with uniform Cs exposure.

Abstract Transient mesospheric echo in the VHF range was detected at an altitude of 65–70 km during the auroral breakup that occurred from 2220 to 2226 UT on June 30, 2017. During this event, the footprint of the Arase satellite was located within the field of view of the all-sky imagers at Syowa Station in the Antarctic. Auroral observations at Syowa Station revealed the dominant precipitation of relatively soft electrons during the auroral breakup. A corresponding spike in cosmic noise absorption was also observed at Syowa Station, while the Arase satellite observed a flux enhancement of > 100 keV electrons and a broadband noise without detecting chorus waves or electromagnetic ion cyclotron waves. A general-purpose Monte Carlo particle transport simulation code was used to quantitatively evaluate the ionization in the middle atmosphere. Results of this study indicate that the precipitation of energetic electrons of > 100 keV, rather than X-rays from the auroral electrons, played a dominant role in the transient and deep (65–70 km) mesospheric ionization during the observed auroral breakup.

Purpose. To assess the correlation between postoperative refractive astigmatism and preoperative parameters in cataract surgery. Methods. Left eyes of 100 consecutive patients scheduled for cataract surgery with a 2.4 mm clear corneal incision were examined prospectively. Refractive astigmatism was measured using an autokerato/refractometer. Corneal astigmatism of the total cornea was calculated using a Scheimpflug camera. The vertical/horizontal component (J0) and oblique component (J45) of refractive and total corneal astigmatism were determined using power vector analysis. Refractive astigmatism at 8 weeks postoperatively was estimated using multivariate linear regression analysis. Independent variables analyzed included age, sex, refractive astigmatism, total corneal astigmatism, sphere, intraocular pressure, corneal thickness, anterior chamber depth, lens thickness, axial length, and pupil diameter. Results. Multivariate regression analysis identified total corneal J0 and age as significant contributors to postoperative refractive J0 (P

Cataracts have long been known, but a biomathematical model is still unavailable for cataratogenesis. There has been a renewed interest in ionizing radiation cataracts because the recent international recommendation of the reduced lens dose limit stimulated the discussion toward its regulatory implementation in various countries. Nevertheless, a relationship between radiation (dose and dose rate) and response (e.g., incidence, onset and progression) remains incompletely understood, raising the need for a risk-predictive mathematical model. We here report for the first time an in silico model for cataractogenesis. First, a simplified cell proliferation model was developed for human lens growth based on stem and progenitor cell proliferation as well as epithelial-fiber cell differentiation. Then, a model for spontaneous cataractogenesis was developed to reproduce the human data on a relationship between age and cataract incidence. Finally, a model for radiation cataractogenesis was developed that can reproduce the human data on a relationship between dose and cataract onset at various ages, which was further applied to estimate cataract incidence following chronic lifetime exposure. The model can serve as the foundation for further development of the risk-predictive model for cataractogenesis along with additional considerations of various biological mechanisms and epidemiological datasets.

Complex DNA damage, defined as at least two vicinal lesions within 10−20 base pairs (bp), induced after exposure to ionizing radiation, is recognized as fatal damage to human tissue. Due to the difficulty of directly measuring the aggregation of DNA damage at the nano-meter scale, many cluster analyses of inelastic interactions based on Monte Carlo simulation for radiation track structure in liquid water have been conducted to evaluate DNA damage. Meanwhile, the experimental technique to detect complex DNA damage has evolved in recent decades, so both approaches with simulation and experiment get used for investigating complex DNA damage. During this study, we propose a simplified cluster analysis of ionization and electronic excitation events within 10 bp based on track structure for estimating complex DNA damage yields for electron and X-ray irradiations. We then compare the computational results with the experimental complex DNA damage coupled with base damage (BD) measured by enzymatic cleavage and atomic force microscopy (AFM). The computational results agree well with experimental fractions of complex damage yields, i.e., single and double strand breaks (SSBs, DSBs) and complex BD, when the yield ratio of BD/SSB is assumed to be 1.3. Considering the comparison of complex DSB yields, i.e., DSB + BD and DSB + 2BD, between simulation and experimental data, we find that the aggregation degree of the events along electron tracks reflects the complexity of induced DNA damage, showing 43.5% of DSB induced after 70 kVp X-ray irradiation can be classified as a complex form coupled with BD. The present simulation enables us to quantify the type of complex damage which cannot be measured through in vitro experiments and helps us to interpret the experimental detection efficiency for complex BD measured by AFM. This simple model for estimating complex DNA damage yields contributes to the precise understanding of the DNA damage complexity induced after X-ray and electron irradiations.

The scintillation light yield of plastic scintillator considering the quenching effect is reproduced by a calculation model based on a track-structure simulation code and the Förster effect. Energy deposition and its nm-scale spatial arrangement in the irradiation by electrons, protons, and heavy ions (4He to 81Br) in an NE-102A scintillator were simulated by a track-structure simulation code. The spatial arrangements of the excited molecules emitting scintillation light and those dissipating the excitation energy were then obtained to calculate the strength of the quenching effect. Light emission from the excited molecules was integrated to finally obtain the observable light yield. The calculated light yields are in good agreement with the earlier measurement data. Moreover, in the case of low-LET particle incidence, a statistical micro-dosimetric model can substitute the track-structure simulation code for reproducing the light yield.

We aimed to determine the anti-angiogenic effect of tenomodulin (TeM) on retinal neovascularization in an oxygen-induced retinopathy (OIR) mouse model. OIR was induced in C57BL/6 mice by exposing seven-day-old mice to 75% oxygen for five days followed by room air for five days. Control mice were exposed to room air from birth until postnatal day 17. Mice received intravitreal injections of 1 μg of TeM in one eye and PBS in the contralateral eye at P7 before being exposed to 75% oxygen. Eyes were collected at postnatal day 17. Retinal blood vessel patterns were visualized by fluorescein angiography. We quantified the number of neovascular nuclei that were present beyond the inner limiting membrane (ILM) using histological methods with a masked approach. Furthermore, double immunohistochemical staining of TeM was performed on retinas to identify nuclei protruding into the vitreous cavity. Western blot was used to detect exogenous TeM protein. The central nonperfusion area (NPA, mm2) of TeM-injected eyes was significantly different from that of OIR and PBS-injected eyes, and the number of nuclei in new blood vessels breaking through the ILM in each retinal cross-section significantly differed from that of OIR eyes and PBS-injected control eyes. Cellular nuclei of new blood vessels protruding into the vitreous cavity were also observed in TeM-injected retinas by immunohistochemistry. Western blotting revealed a 16-kDa immunoreactive protein, indicating incorporation of an exogenous TeM fragment into the retina. Our data shows that TeM can effectively inhibit pathological angiogenesis in mouse eyes; indicating its potential role in prevention and treatment of ocular neovascularization.

A new model called "PHITS-based Analytical Radiation Model in the Atmosphere (PARMA) version 4.0" was developed to facilitate instantaneous estimation of not only omnidirectional but also angular differential energy spectra of cosmic ray fluxes anywhere in Earth's atmosphere at nearly any given time. It consists of its previous version, PARMA3.0, for calculating the omnidirectional fluxes and several mathematical functions proposed in this study for expressing their zenith-angle dependences. The numerical values of the parameters used in these functions were fitted to reproduce the results of the extensive air shower simulation performed by Particle and Heavy Ion Transport code System (PHITS). The angular distributions of ground-level muons at large zenith angles were specially determined by introducing an optional function developed on the basis of experimental data. The accuracy of PARMA4.0 was closely verified using multiple sets of experimental data obtained under various global conditions. This extension enlarges the model's applicability to more areas of research, including design of cosmic-ray detectors, muon radiography, soil moisture monitoring, and cosmic-ray shielding calculation. PARMA4.0 is available freely and is easy to use, as implemented in the open-access EXcel-based Program for Calculating Atmospheric Cosmic-ray Spectrum (EXPACS).

By extending our previously established model, here we present a new model called "PHITS-based Analytical Radiation Model in the Atmosphere (PARMA) version 3.0," which can instantaneously estimate terrestrial cosmic ray fluxes of neutrons, protons, ions with charge up to 28 (Ni), muons, electrons, positrons, and photons nearly anytime and anywhere in the Earth's atmosphere. The model comprises numerous analytical functions with parameters whose numerical values were fitted to reproduce the results of the extensive air shower (EAS) simulation performed by Particle and Heavy Ion Transport code System (PHITS). The accuracy of the EAS simulation was well verified using various experimental data, while that of PARMA3.0 was confirmed by the high R2 values of the fit. The models to be used for estimating radiation doses due to cosmic ray exposure, cosmic ray induced ionization rates, and count rates of neutron monitors were validated by investigating their capability to reproduce those quantities measured under various conditions. PARMA3.0 is available freely and is easy to use, as implemented in an open-access software program EXcel-based Program for Calculating Atmospheric Cosmic ray Spectrum (EXPACS). Because of these features, the new version of PARMA/EXPACS can be an important tool in various research fields such as geosciences, cosmic ray physics, and radiation research.

We here propose a new model assembly for estimating the surviving fraction of cells irradiated with various types of ionizing radiation, considering both targeted and nontargeted effects in the same framework. The probability densities of specific energies in two scales, which are the cell nucleus and its substructure called a domain, were employed as the physical index for characterizing the radiation fields. In the model assembly, our previously established double stochastic microdosimetric kinetic (DSMK) model was used to express the targeted effect, whereas a newly developed model was used to express the nontargeted effect. The radioresistance caused by overexpression of anti-apoptotic protein Bcl-2 known to frequently occur in human cancer was also considered by introducing the concept of the adaptive response in the DSMK model. The accuracy of the model assembly was examined by comparing the computationally and experimentally determined surviving fraction of Bcl-2 cells (Bcl-2 overexpressing HeLa cells) and Neo cells (neomycin resistant gene-expressing HeLa cells) irradiated with microbeam or broadbeam of energetic heavy ions, as well as the WI-38 normal human fibroblasts irradiated with X-ray microbeam. The model assembly reproduced very well the experimentally determined surviving fraction over a wide range of dose and linear energy transfer (LET) values. Our newly established model assembly will be worth being incorporated into treatment planning systems for heavy-ion therapy, brachytherapy, and boron neutron capture therapy, given critical roles of the frequent Bcl-2 overexpression and the nontargeted effect in estimating therapeutic outcomes and harmful effects of such advanced therapeutic modalities.

The risk of internal exposure to 137Cs, 134Cs, and 131I is of great public concern after the accident at the Fukushima-Daiichi nuclear power plant. The relative biological effectiveness (RBE, defined herein as effectiveness of internal exposure relative to the external exposure to γ-rays) is occasionally believed to be much greater than unity due to insufficient discussions on the difference of their microdosimetric profiles. We therefore performed a Monte Carlo particle transport simulation in ideally aligned cell systems to calculate the probability densities of absorbed doses in subcellular and intranuclear scales for internal exposures to electrons emitted from 137Cs, 134Cs, and 131I, as well as the external exposure to 662 keV photons. The RBE due to the inhomogeneous radioactive isotope (RI) distribution in subcellular structures and the high ionization density around the particle trajectories was then derived from the calculated microdosimetric probability density. The RBE for the bystander effect was also estimated from the probability density, considering its non-linear dose response. The RBE due to the high ionization density and that for the bystander effect were very close to 1, because the microdosimetric probability densities were nearly identical between the internal exposures and the external exposure from the 662 keV photons. On the other hand, the RBE due to the RI inhomogeneity largely depended on the intranuclear RI concentration and cell size, but their maximum possible RBE was only 1.04 even under conservative assumptions. Thus, it can be concluded from the microdosimetric viewpoint that the risk from internal exposures to 137Cs, 134Cs, and 131I should be nearly equivalent to that of external exposure to γ-rays at the same absorbed dose level, as suggested in the current recommendations of the International Commission on Radiological Protection.