Neutron Irradiation Experiments Research Articles

Nonclinical pharmacodynamics of boron neutron capture therapy using direct intratumoral administration of a folate receptor targeting novel boron carrier

Abstract Background Boron Neutron Capture Therapy (BNCT) is a precise particle radiation therapy known for its unique cellular targeting ability. The development of innovative boron carriers is crucial for the advancement of BNCT technologies. Our previous study demonstrated the potential of PBC-IP administered via Convection-Enhanced Delivery (CED) in an F98 rat glioma model. This approach significantly extended rat survival in neutron irradiation experiments, with half achieving long-term survival, akin to a cure, in a rat brain tumor model. Our commitment to clinical applicability has spurred additional non-clinical pharmacodynamic research, including an investigation into the effects of cannula position and the time elapsed post-CED administration. Methods In comprehensive in vivo experiments conducted on an F98 rat brain tumor model, we meticulously examined the boron distribution and neutron irradiation experiments at various sites and multiple time intervals following CED administration. Results The PBC-IP showed substantial efficacy for BNCT, revealing minimal differences in tumor boron concentration between central and peripheral CED administration, although a gradual decline in intratumoral boron concentration post-administration was observed. Therapeutic efficacy remained robust, particularly when employing cannula insertion at the tumor margin, compared to central injections. Even delayed neutron irradiation showed notable effectiveness, albeit with a slightly reduced survival period. These findings underscore the robust clinical potential of CED-administered PBC-IP in the treatment of malignant gliomas, offering adaptability across an array of treatment protocols. Conclusions This study represents a significant leap forward in the quest to enhance BNCT for the management of malignant gliomas, opening promising avenues for clinical translation.

Neutron irradiation and polarization effect of 4H–SiC Schottky detector

Neutron irradiation experiments were carried out on a 4H–SiC Schottky detector. The effects of neutron and accompanying γ-rays irradiation on the electrical properties, charge collection efficiency (CCE), energy resolution and crystal defects of 4H–SiC detectors were investigated. The total irradiation fluence was 1.24 × 1014 n/cm2, with an equivalent 1 MeV neutron fluence of 1.33 × 1015 n/cm2. Following neutron irradiation, the turn-on voltage increased significantly, and the capacitance of the Schottky junction no longer varied with the reverse bias voltage. The CCE of the detector decreased from 100% to 90.8%, while the energy resolution increased from 0.79% to 1.49%. The irradiated detector required a higher bias voltage for optimal performance. Additionally, we observed two defect levels, Ec-0.5 eV and Ec-0.35 eV, in the 4H–SiC crystals after irradiation. Their generation is also related to gamma ray irradiation. The detector exhibited a polarization effect, where the energy spectrum split into two distinct components during prolonged measurement of monoenergetic α particles. The peak position gradually shifted towards the lower energy side with increasing testing time. These effects can be mitigated by increasing the bias voltage to enhance the electric field strength in the drift region.

Combining BNCT with carbonic anhydrase inhibition for mesothelioma treatment: Synthesis, in vitro, in vivo studies of ureidosulfamido carboranes

Mesothelioma is a malignant neoplasm of mesothelial cells caused by exposure to asbestos. The average survival time after diagnosis is usually nine/twelve months. A multi-therapeutic approach is therefore required to treat and prevent recurrence. Boronated derivatives containing a carborane cage, a sulfamido group and an ureido functionality (CA-USF) have been designed, synthesised and tested, in order to couple Boron Neutron Capture Therapy (BNCT) and the inhibition of Carbonic Anhydrases (CAs), which are overexpressed in many tumours. In vitro studies showed greater inhibition than the reference drug acetazolamide (AZ). To increase solubility in aqueous media, CA-USFs were used as inclusion complexes of hydroxypropyl β-cyclodextrin (HP-β-CD) in all the inhibition and cell experiments. BNCT experiments carried out on AB22 (murine mesothelioma) cell lines showed a marked inhibition of cell proliferation by CA-USFs, and in one case a complete inhibition of proliferation twenty days after neutron irradiation. Finally, in vivo neutron irradiation experiments on a mouse model of mesothelioma demonstrated the efficiency of combining CA IX inhibition and BNCT treatment. Indeed, a greater reduction in tumour mass was observed in treated mice compared to untreated mice, with a significant higher effect when combined with BNCT. For in vivo experiments CA-USFs were administered as inclusion complexes of higher molecular weight β-CD polymers thus increasing the selective extravasation into tumour tissue and reducing clearance. In this way, boron uptake was maximised and CA-USFs demonstrated to be in vivo well tolerated at a therapeutic dose. The therapeutic strategy herein described could be expanded to other cancers with increased CA IX activity, such as melanoma, glioma, and breast cancer.

Helium bubble evolution under cascade in bcc iron relevant to fusion conditions investigated by a novel coupling MD-OKMC method

The direct interaction between cascade and helium bubbles during the thermal spike phase plays an important role in the helium bubbles evolution in metals, which was not fully considered by the present long-time simulation methods. To address this issue, in this work we developed a coupling MD-OKMC method to investigate the helium bubble evolution under irradiation cascade in bcc iron. The short-time collision cascade was simulated by the molecular dynamics (MD), and the long-time helium bubble evolution was modeled by the object kinetic Monte Carlo (OKMC). The MD and OKMC simulations were alternated to imitate the gradual increase of both irradiation dose and helium concentration under experiment conditions. The impact of temperature on the helium bubble evolution under irradiation cascade in bcc iron was investigated and the results were compared with the data from neutron irradiation experiment. It's found that the results of the coupling MD-OKMC were consistent with the experiment results, and were better in agreement with the experiment than the traditional OKMC.

Molecular engineering of AIE-active boron clustoluminogens for enhanced boron neutron capture therapy.

The development of boron delivery agents bearing an imaging capability is crucial for boron neutron capture therapy (BNCT), yet it has been rarely explored. Here we present a new type of boron delivery agent that integrates aggregation-induced emission (AIE)-active imaging and a carborane cluster for the first time. In doing so, the new boron delivery agents have been rationally designed by incorporating a high boron content unit of a carborane cluster, an erlotinib targeting unit towards lung cancer cells, and a donor-acceptor type AIE unit bearing naphthalimide. The new boron delivery agents demonstrate both excellent AIE properties for imaging purposes and highly selective accumulation in tumors. For example, at a boron delivery agent dose of 15 mg kg-1, the boron amount reaches over 20 μg g-1, and both tumor/blood (T/B) and tumor/normal cell (T/N) ratios reach 20-30 times higher than those required by BNCT. The neutron irradiation experiments demonstrate highly efficient tumor growth suppression without any observable physical tissue damage and abnormal behavior in vivo. This study not only expands the application scopes of both AIE-active molecules and boron clusters, but also provides a new molecular engineering strategy for a deep-penetrating cancer therapeutic protocol based on BNCT.

Materials qualification through the Nuclear Science User Facilities (NSUF): a case study on irradiated PM-HIP structural alloys

This article presents neutron irradiation and post-irradiation examination (PIE) capabilities available to the nuclear materials research community through the US Department of Energy’s Nuclear Science User Facilities (NSUF). The pressing need to deploy advanced nuclear reactors to combat climate change requires qualification of new fuels and materials. Among advanced manufacturing processes, powder metallurgy with hot isostatic pressing (PM-HIP) is nearest to becoming qualified for nuclear applications. This article provides examples from a recent irradiation and PIE program on a series of structural alloys fabricated by PM-HIP to illustrate how NSUF capabilities can be used to generate qualification data. The neutron irradiation experiments are described, and a sampling of results from tensile testing, nanoindentation, transmission electron microscopy, and atom probe tomography are presented, showing the favorable performance of PM-HIP alloys compared to their cast or forged counterparts under irradiation. This article provides a perspective on leveraging NSUF for future nuclear fuels and materials testing and qualification.

Material and component developments for the DEMO divertor using fibre reinforcement and additive manufacturing

Within the research along the European Fusion Roadmap, water-cooled divertor PFCs are foreseen in the design of a first fusion demonstration power plant (DEMO) in order to provide reliable heat removal capability. In the frame of this concerted attempt, the Max Planck Institute for Plasma Physics is concentrating on the development and testing of composite materials based on tungsten (W, preferred armour material) and copper (Cu, preferred heat sink material). W fibres (Wf) as monofilaments and yarns as reinforcement play a central role in these investigations due to their extraordinary properties concerning ductility already at room temperature and high tensile strength. Recent investigations on the impact of radiation damage suggest that the fibres retain their ductility upon irradiation. W reinforced with W fibres (Wf/W) allows to overcome the intrinsic brittleness of W. Quantitative mechanical fracture tests of Wf /W confirm the basic mechanisms of fibre reinforcement and the increased resistance to mechanical fatigue. The good wettability of W with liquid Cu and the absence of any metallurgical solubility make up an ideal material pairing for composite production. W fibre-reinforced Cu (Wf/Cu) cooling tubes provide a rather high thermal conductivity (> 250 W mK−1) and at least twice the strength of CuCrZr in hoop direction in the temperature range up to at least 500 °C. Very recent neutron irradiation experiments confirm the sustainment of ductility of the Wf/Cu composite. Numerical simulations suggest that thermal stresses in W-Cu PFCs could be strongly reduced by tailoring the local W and Cu volume fraction. This ‘freely’ distributed material composition can be achieved by means of additively manufactured W skeletons consecutively infiltrated by Cu. Investigations with W preforms produced by Laser Beam Powder Bed Fusion and infiltrated by Cu demonstrate the feasibility of this approach while testing of specifically prepared specimen is ongoing.

The efficacy of boron neutron capture therapy with folate receptor targeted novel boron carrier in F98 rat brain tumor models.

21 Background: Boron neutron capture therapy (BNCT) is a particle therapy that can be targeted at the cellular level. The most commonly used boron carrier in clinical BNCT is boronophenylalanine (BPA), which is taken up into the tumor cell via L type amino acid transporter (LAT-1). The development of new boron carrier is an important issue, because BNCT using BPA is sometimes ineffective. Focusing on folate receptors that are highly expressed in malignant gliomas, PBC-IP which contained the pteroyl group was developed. The efficacy of BNCT with this drug was evaluated. The efficacy of BNCT using PBC-IP in the F98 rat brain tumor model has been evaluated. Methods: F98 rat glioma cells were used in the in vitro cellular uptake experiment.F98 rat glioma cells were exposed to BPA, sodium borocaptate (BSH), and PBC-IP. F98 rat brain tumor models were used in biodistribution experiment and neutron irradiation experiment. PBC-IP was administered by Convection enhanced delivery (CED). Results: In vitro cellular uptake experiment showed the boron concentration of PBC-IP was much higher than that of BPA and BSH. In vivo biodistribution experiment showed that boron concentration in the tumor using PBC-IP CED was the highest at 3 hours after the termination of 24 h administration. In the in vivo neutron irradiation experiment, significantly difference was observed between BNCT BPA group and combination BNCT (BPA + PBC-IP) group. In addition, long time survivors were observed in BNCT using PBC-IP groups, which were not observed in BNCT BPA groups. Conclusions: This study showed that PBC-IP in combination with BPA may provide the multi-targeted neutron capture therapy, this is because the mechanism of tumor accumulation of PBC-IP is different from that of BPA. In addition, therapeutic strategies targeting folate receptors may be useful, and further research is warranted.

Effects of neutron radiation generated in deep space-like environments on food resources

The impact of deep space cosmic rays on food resources is as important as the risks of cosmic rays to the human body. This study demonstrates the potential for neutrons as secondary radiation in deep space spacecraft to cause meat activation and oxidative modification of proteins and lipids. We conducted a series of experiments such as the neutron irradiation experiment, the radioactivation analysis and the biochemical analysis. Neutrons with energies from 1 to 5 MeV with doses from 0.01 Gy to 4 Gy were irradiated by the RIKEN accelerated-driven neutron source (RANS). Radioactive nuclei, 24Na, 42K, and 38Cl, were detected in the neutron-irradiated meat. The modification products of the proteins by oxidative nitration, 6-nitrotryptophan (6NO2Trp), and by a lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE), were detected in several proteins with neutron dose dependent. The proteome analysis showed that many oxidative modifications were detected in actin and myosin which are major proteins of myofibrils. This study is of crucial importance not only as risk factors for human space exploration, but also as fundamental effects of radiation on the components of the human body.

Experimental Analyses of Capture Reaction Rates for Epithermal and Resonance Neutrons in Source-Driven Subcritical Cores

Neutron irradiation experiments are carried out in source-driven subcritical cores with high-energy neutrons generated by spallation reactions between a 100-MeV proton beam and a lead-bismuth target at the Kyoto University Critical Assembly. The main objective of the experiments is to investigate the effect of epithermal and resonance neutrons on the accuracy of capture reaction rates with respect to a subcriticality variation. Activation foils of copper, indium, tantalum, and tungsten are employed to obtain capture reaction rates for epithermal and resonance neutrons by applying the cadmium difference method. Also, the applicability of the foils for the measurement of the reaction rates for epithermal and resonance neutrons is substantiated in the critical irradiation experiments performed prior to the subcritical experiments. The subcritical experiments are conducted with three different subcriticalities by changing the control rod insertion pattern. The measured reaction rates are compared with the calculated values obtained by the Monte Carlo code MVP with JENDL-4.0, and the ratio of the calculation and experiment values of the reaction rates shows equivalent values within the 1σ errors regardless of a difference in the subcriticality. The compared results indicate that the numerical analyses have a consistent accuracy of reaction rates in epithermal and resonance energy regions for a subcriticality variation in source-driven subcritical cores.

Study on the failure rate of high-power thyristors irradiated by artificial neutron irradiation under different DC bias voltages

High-voltage semiconductor devices such as thyristors, due to the high voltage applied, when encountering atmospheric neutrons in the operating state, may appear single event burnout due to charge multiplication in high-altitude areas. The atmospheric neutron radiation in high-altitude areas can cause damage and interference to semiconductor devices, which seriously threatens their safe operation. However, there is little research on the influence of atmospheric neutron irradiation on the operating life of high-voltage DC transmission system thyristors in high-altitude areas. Therefore, in this paper, the neutron beam of the Atmospheric Neutron Irradiation Spectrometer (ANIS) of China Spallation Neutron Source (CSNS) was used to irradiate the high-power thyristors. The failure rates of different applied voltages under 6.74 × 106 n/cm2/s neutron flux irradiation and the leakage current changes during irradiation were obtained. The failure rate applied voltage relationship curve obtained from the artificial neutron irradiation experiment was converted to the corresponding value in Yangbajing area, China. Through the results of the artificial neutron accelerated irradiation experiment, the thyristor failure rate-voltage formula in different areas can be more accurately estimated. In this way, the reasonable working voltage can be determined according to the operating life demand of the thyristor, and determine the thyristor configuration scheme of the design of the converter station. In addition, it is found that the leakage current of thyristor increases with the increase of neutron irradiation time, which may eventually lead to the degradation of thyristor performance and affect its reliability in the DC transmission system.

Neutron calorimeter development at fission and fusion pulsed neutron sources

A neutron calorimeter fielded in pulsed neutron irradiation experiments at the National Ignition Facility (NIF) and White Sands Missile Range Fast Burst Reactor (WSMR FBR) is described, and results are provided and discussed. The calorimeter is modular in design to allow fielding of various neutron absorber materials and thicknesses, as well as use at both fission and fusion sources, all of which has been done. Neutron calorimeters designed for fission sources have been fielded at fusion sources as well, but these instances are not documented in available literature—making this work novel. The functional calorimeter consists of a neutron absorber and two sheathed, grounded thermocouples secured within a subassembly made of thermally insulating materials. This subassembly is placed into a sealed vessel for material and facility safety considerations. The device was fielded at NIF in four polar-direct-drive exploding pusher shots and eleven WSMR FBR pulses. Calorimeter data from NIF experiments show a discernable thermal response accredited to neutron heating within the first 10 s, but the data are dominated by noise from ambient X-ray heating after time = 10 s post-pulse. This response is highly consistent between shots and linearly related to incident neutron fluence and neutron absorber thickness. A temperature rise of 1.1E−2 K/(1013 neutrons/cm2) per millimeter of absorber thickness was determined for both 0.4 mm and 1 mm thick depleted uranium absorbers with linear best fit R2 of 0.97 and 0.98 for each thickness and y-axis offsets of 8.8E−3 and 1.3E−2, respectively. WSMR FBR experiment data show a temperature rise of 6.2E−2 K/(1013 neutrons/cm2) with linear best fit R2 of 0.14 and y-axis offset of 7.6E−3 for a calorimeter with a 1 mm thick enriched boron carbide (10B4C) absorber, though it must be noted that device-to-device variability is significant at both facilities. These data are also affected by noise on a similar timescale as at NIF, though the noise is significantly lesser in magnitude but oscillatory.

Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model

Integrin αvβ3 is more highly expressed in high-grade glioma cells than in normal tissues. In this study, a novel boron-10 carrier containing maleimide-functionalized closo-dodecaborate (MID), serum albumin as a drug delivery system, and cyclic arginine-glycine-aspartate (cRGD) that can target integrin αvβ3 was developed. The efficacy of boron neutron capture therapy (BNCT) targeting integrin αvβ3 in glioma cells in the brain of rats using a cRGD-functionalized MID-albumin conjugate (cRGD-MID-AC) was evaluated. F98 glioma cells exposed to boronophenylalanine (BPA), cRGD-MID-AC, and cRGD + MID were used for cellular uptake and neutron-irradiation experiments. An F98 glioma-bearing rat brain tumor model was used for biodistribution and neutron-irradiation experiments after BPA or cRGD-MID-AC administration. BNCT using cRGD-MID-AC had a sufficient cell-killing effect in vitro, similar to that with BNCT using BPA. In biodistribution experiments, cRGD-MID-AC accumulated in the brain tumor, with the highest boron concentration observed 8 h after administration. Significant differences were observed between the untreated group and BNCT using cRGD-MID-AC groups in the in vivo neutron-irradiation experiments through the log-rank test. Long-term survivors were observed only in BNCT using cRGD-MID-AC groups 8 h after intravenous administration. These findings suggest that BNCT with cRGD-MID-AC is highly selective against gliomas through a mechanism that is different from that of BNCT with BPA.

Multi-Targeted Neutron Capture Therapy Combined with an 18 kDa Translocator Protein-Targeted Boron Compound Is an Effective Strategy in a Rat Brain Tumor Model

Boron neutron capture therapy (BNCT) has been adapted to high-grade gliomas (HG); however, some gliomas are refractory to BNCT using boronophenylalanine (BPA). In this study, the feasibility of BNCT targeting the 18 kDa translocator protein (TSPO) expressed in glioblastoma and surrounding environmental cells was investigated. Three rat glioma cell lines, an F98 rat glioma bearing brain tumor model, DPA-BSTPG which is a boron-10 compound targeting TSPO, BPA, and sodium borocaptate (BSH) were used. TSPO expression was evaluated in the F98 rat glioma model. Boron uptake was assessed in three rat glioma cell lines and in the F98 rat glioma model. In vitro and in vivo neutron irradiation experiments were performed. DPA-BSTPG was efficiently taken up in vitro. The brain tumor has 16-fold higher TSPO expressions than its brain tissue. The compound biological effectiveness value of DPA-BSTPG was 8.43 to F98 rat glioma cells. The boron concentration in the tumor using DPA-BSTPG convection-enhanced delivery (CED) administration was approximately twice as high as using BPA intravenous administration. BNCT using DPA-BSTPG has significant efficacy over the untreated group. BNCT using a combination of BPA and DPA-BSTPG gained significantly longer survival times than using BPA alone. DPA-BSTPG in combination with BPA may provide the multi-targeted neutron capture therapy against HG.

Simulation of neutron irradiation-induced recrystallization of tungsten

<sec>Tungsten is the candidate for divertor target material in future fusion reactors. The tungsten divertor target is expected to long serve in a harsh environment of high temperature and high-energy neutron irradiation. This can lead to neutron irradiation-induced recrystallization of tungsten, thereby increasing the possibility of intergranular brittle failure and compromising the safe operation of the divertor. Thus, clarifying the mechanism of neutron irradiation-induced tungsten recrystallization is important. However, the current model, which only considers the irradiation-enhanced effect on recrystallization driving force, underestimates the irradiation effect on recrystallization compared with the results observed in recent high-temperature neutron irradiation experiments in the HFIR reactor. It indicates that other irradiation effects can also influence the recrystallization process.</sec><sec>In this study, we introduce the irradiation-enhanced grain boundary migration factor (<i>R</i>) into the established irradiation-induced recrystallization kinetic model, on the assumption that the grain boundary migration velocity is proportional to the self-diffusion coefficient. The simulation results show that after considering both irradiation-enhanced recrystallization driving force and grain boundary migration effect, the calculated half-recrystallization time (<inline-formula><tex-math id="M4">\begin{document}${t}_{{X}\text{}=\text{}0.5}$\end{document}</tex-math><alternatives><graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="16-20230531_M4.jpg"/><graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="16-20230531_M4.png"/></alternatives></inline-formula>) at 850 ℃ from the model matches the one obtained in the neutron irradiation experiment in the HFIR reactor. This result indicates that the irradiation-enhanced grain boundary migration effect is one of the important factors affecting irradiation-induced recrystallization. In addition, the difference between irradiated and unirradiated <i>t</i><sub><i>X</i>=0.5</sub> decreases with temperature increasing. This phenomenon is due to the fact that as the temperature increases, the contribution of irradiation defects to the driving force for recrystallization decreases owing to the irradiation defect recombination. Moreover, the increase of thermal activation diffusion coefficient is more significant than the increase of the irradiation-enhanced diffusion coefficient. These findings suggest that the thermal activation effect eventually dominates the recrystallization process over the irradiation effect as temperature increases.</sec>

Estimating the dimensional change behavior of nuclear graphite with heavy-ion irradiation-induced bending

Two promising reactor Generation IV designs employ nuclear graphite as their moderator and reflector. To this end, new graphite grades are being developed, which will require their suitability for reactor design to be established. Understanding graphite irradiation behavior, especially dimensional change, is critical when selecting a particular nuclear graphite grade. This is usually established by fast neutron irradiation experiments in a material test reactor (MTR). However, due to the limited accessibility to the MTR irradiation facility, cost, and the time required for such experiments to be carried out, the development of new nuclear graphite grades is restrictive. Here, a novel approach is proposed to enable suitable grades to be selected from a number of candidates before an MTR program is implemented by estimating the irradiation-induced dimensional change behaviors of several nuclear graphite grades based on the bending of graphite foils under ion irradiation. The method is capable of efficiently distinguishing the most dimensionally stable graphite grades in the laboratory without the need to irradiate many samples in an MTR program.

Experiment design for the neutron irradiation of PM-HIP alloys for nuclear reactors

This article describes the design of an Advanced Test Reactor (ATR) drop-in neutron irradiation experiment aiming to directly compare the performance of nuclear structural alloys fabricated by powder metallurgy with hot isostatic pressing (PM-HIP) against conventional casting or forging. There is growing interest in PM-HIP alloys for nuclear applications because of their microstructural uniformity, superior mechanical properties, and reduced dependence on welding and machining, compared to cast/forged alloys. Nuclear code-qualification of PM-HIP alloys requires neutron irradiation testing to demonstrate performance under relevant conditions. In this experiment, six nuclear structural alloys were irradiated: Ni-based alloys 625 and 690, Grade 91 ferritic steel, SA508 pressure vessel steel, and 304L and 316L austenitic stainless steels. The experiment is assembled into seven capsules in four test trains and irradiated in three ATR inboard A positions. Both the PM-HIP and cast/forged versions of each alloy were irradiated under nearly identical conditions for comparative purposes, to target doses of 1 ± 0.2 and 3 ± 0.2 dpa at temperatures of 300 ± 50 °C and 400 ± 50 °C. A thorough description of the experiment design and thermal, structural and neutronic analyses performed to ensure the targeted irradiation conditions are met is provided. Specimens were configured as small disks, compact tension specimens and tensile bars to facilitate post-irradiation examination (PIE) that will include mechanical testing, microstructure characterization, and fracture toughness testing. Given the considerations for ASTM standardized mechanical testing, comparative fluence and temperature across specimen pairs, and comprehensive PIE planning herein, this work serves as a template for future nuclear materials qualification experiment designs.

ET-4 BASIC RESEARCH OF BORON NEUTRON CAPTURE THERAPY USING A NOVEL BORON COMPOUND TARGETED TO INTEGRIN

Abstract Background Boron neutron capture therapy (BNCT) is a particle radiation modality capable of selectively destroying tumor cells. The most commonly used boron compound for BNCT is boronphenylalanine (BPA). BPA is taken up into the tumor cell via the L-type aminoacid transporter (LAT-1). However, there are some BPA-refractory situations. Therefore, a novel boron compound is expected to improve the therapeutic performance of BNCT. We focused on integrinαvβ3, which is overexpressed in malignant gliomas as in many cancer cells, and have developed cRGD-MID-AC, a conjugate of cyclic RGD (cRGD), which selectively inhibited integrinαvβ3, and MID-AC, which we have already reported as effective on BNCT as BPA as a boron compound in F98 rat glioma models. We evaluated the efficacy of BNCT using this novel compound.Methods: F98 glioma cells were exposed to BPA, cRGD-MID-AC, and cRGD-MID for cellular uptake and neutron irradiation experiment. Intracellular boron concentrations and compound biological effectiveness (CBE) for each boron compound was calculated. After intravenous administration (i.v.) of cRGD-MID-AC or BPA, the biodistribution of boron compounds was measured and neutron irradiation experiment were performed in F98 rat glioma models. Results Intracellular boron concentrations of BPA and cRGD-MID-AC were increased gradually at all exposed time, and CBE for cRGD-MID-AC was comparable to that for BPA. In cRGD-MID-AC, the boron concentration in the tumor was the highest at 8 h after i.v. and tended to be retained longer at 24h. In vivo neutron irradiation experiment, long-term survival was observed only in the group irradiated 8 h after cRGD-MID-AC i.v.. These experiments suggest that cRGD-MID-AC has sufficient cell-killing effect and may be more effective in vivo. Conclusion cRGD-MID-AC has a tumor accumulation mechanism different from that of BPA, and could be an effective boron carrier in BNCT for malignant gliomas.

Probabilistic failure assessment of an irradiated DEMO breeding blanket component under ferromagnetic loads: Impacts of material data scattering and uncertainty in local stress intensities

The most significant technical challenge in developing structural materials for in-vessel components in the Demonstration Power Plant (DEMO) fusion reactor is to qualify the lifetime of material to guarantee the lifetime of components. The qualification needs to be conducted theoretically rather than empirically because it is conducted based on the knowledge and data acquired in fission neutron irradiation experiments and various simulation irradiation experiments rather than in experiments performed in the actual fusion environment. Such experiments will not be achievable until the DEMO fusion reactor becomes operational. Consequently, various uncertainties are expected in irradiation data and loading conditions.The probabilistic approach, where the probability of failure is calculated based on the probability density function of postulated load distribution and material property distribution, is one path to mitigate such uncertainties. In this approach, those probabilities constitute the subjective probability based on the theoretical understanding of fusion neutron irradiation effects on materials to maximize the confidence in the estimated value.A case study of the Japanese DEMO breeding blanket is the basis for the discussion of the technical issues involved in the probabilistic approach. The breeding blanket design was simplified, the failure probability was estimated, and the impact of electromagnetic force on ferromagnetic material caused by a strong magnetic field induced by toroidal field coils was considered. The discussion of the impact of the irradiation damage is based on the irradiation data for F82H reduced-activation ferritic/martensitic steel. A direction for the development of fusion structural materials is suggested in terms of design technology and the statistical quality of the irradiation database.

Investigating the reliability impacts of neutron-induced soft errors in aerial image classification CNNs implemented in a softcore SRAM-based FPGA GPU

This work investigates the impacts of neutron-induced soft errors on the reliability of aerial image classification neural networks running on a softcore GPU implemented in an SRAM-based FPGA. We designed and trained fixed-point and floating-point all-convolutional neural networks to classify four-channel aerial images from the SAT-6 dataset, extracted from the U.S. National Agriculture Imagery Program, and implemented on FGPU, a configurable open-source GPU-like processor with floating-point arithmetic hardware. Results from fast neutron and thermal neutron irradiation experiments coupled with configuration bitstream fault injection campaigns show that the impact of soft errors in the aerial image classification must be taken care of with hardening techniques.