Sivelestat's effect on Candida albicans water-soluble fraction-induced vasculitis.

BACKGROUND: We investigated the efficacy of sivelestat sodium hydrate (SSH) as a treatment for Kawasaki disease, and its pharmacological action sites, in mice with Candida albicans water-soluble fraction-induced vasculitis. METHODS: Sivelestat sodium hydrate was administered intraperitoneally to Candida albicans water-soluble fraction-induced vasculitis model mice to assess its efficacy in preventing the development of coronary artery lesions based on the degree of inflammatory cell infiltration in the aortic root and coronary arteries (vasculitis score). The pharmacological sites of action were investigated based on changes in neutrophil elastase (NE) and intercellular adhesion molecule 1 (ICAM-1) positive areas, ICAM-1 and tumor necrosis factor-α mRNA expression levels in the upper heart, and the proportion of monocytes in the peripheral blood. RESULTS: The vasculitis score decreased below the lower limit of the 95% confidence interval of untreated mice in 69% of the SSH-treated mice. The NE- and ICAM-1-positive regions, and the mRNA expression of ICAM-1 and tumor necrosis factor-α were lower in the SSH-treated mice than in the untreated mice. The proportion of monocytes in the peripheral blood was higher in the SSH-treated mice than in the untreated mice, whereas monocyte migration to inflammation areas was suppressed in the SSH-treated mice. CONCLUSIONS: Our results showed that SSH might prevent the development of coronary artery lesions and ameliorate disease activity. In addition to its NE-inhibitory effect, SSH sites of action may also include monocytes.

SIMULATION OF NEUTRON RESPONSE FUNCTIONS OF SILICON SENSOR APPLIED TO REAL-TIME PERSONAL ALBEDO NEUTRON DOSEMETER IN THE ENERGY RANGE BETWEEN 0.01 EV AND 10 KEV.

Neutron response functions of a silicon sensor, which is applied to a new real-time personal albedo neutron dosemeter, have been simulated for low energy neutrons from 0.01 eV to 10 keV using the Monte Carlo technique. The angular neutron response functions were obtained by multiplying simulated neutron energy spectra crossing the neutron sensor and the cross-section of the 6Li(n,t)4He reaction. The neutron response functions have been closed to the dose conversion coefficient of personal doses, Hp(10) recommended by the International Commission on Radiological Protection by selecting neutrons incident from angles of 105° to 180° with respect to an axis perpendicular to an acrylic phantom surface. From these simulation results, the neutron energy response function has been improved by shielding the sensor with cadmium box without a face toward the phantom. The neutron sensor provides a good conformance to the Hp(10) conversion coefficients within 15% for low energy neutrons.

Development of a real-time neutron beam detector for boron neutron capture therapy using a thin silicon sensor.

We have developed a new real-time neutron detector, which is able to measure a direct neutron beam of boron neutron capture therapy. The detector consists of both a 40-µm-thick pn diode and around 0.09-µm-thick LiF neutron converter. Experimental results indicate that this neutron detector can measure neutron flux up to 1 × 109 (cm-2 s-1), separately from gamma rays around 500 mGy/h. The measured depth distribution of neutron flux in an acrylic block is in agreement with the activation results of gold.

SIMULATED 8 MeV NEUTRON RESPONSE FUNCTIONS OF A THIN SILICON NEUTRON SENSOR.

Neutron response functions of a thin silicon neutron sensor are simulated using PHITS2 and MCNP6 codes for an 8 MeV neutron beam at angles of incidence of 0°, 30° and 60°. The contributions of alpha particles created from the 28Si(n,α)25Mg reaction and the silicon nuclei scattered elastically by neutrons in the silicon sensor have not been well reproduced using the MCNP6 code. The 8 MeV neutron response functions simulated using the PHITS2 code with an accurate event generator mode are in good agreement with experimental results and include the contributions of the alpha particles and silicon nuclei.

Measurement of the gamma-ray energy spectrum of the educational Kinki University Reactor (UTR-KINKI).

The gamma-ray energy spectrum of the Kinki University Reactor (UTR-KINKI) was estimated from Ge detector measurements combined with Monte Carlo N-particle transport criticality calculations. The gamma rays mainly originated from prompt fission components, although small amounts of gamma rays from (n,γ) reactions, fission product gamma rays, and activation gamma rays were detected. The averaged gamma-ray tissue kerma rate in the irradiation port during UTR-KINKI operation at 1W was calculated as 10.5cGy/h based on the estimated gamma-ray energy spectrum. This value is consistent with a previous measurement with paired ionization chambers and a tissue equivalent gas proportional counter. This result demonstrates the reliability of the estimated gamma-ray energy spectrum.

Estimating Annual Individual Doses for Evacuees Returning Home to Areas Affected by the Fukushima Nuclear Accident.

To contribute to the reconstruction and revitalization of Fukushima Prefecture following the 2011 nuclear power disaster, annual individual doses were estimated for evacuees who will return home to Tamura City, Kawauchi Village, and Iitate Village in Fukushima. Ambient external dose rates and individual doses obtained with personal dosimeters were measured at many residential and occupational sites throughout the study areas to obtain fundamental data needed for the estimation. The measurement results indicated that the ratio of individual dose based on a personal dosimeter to the ambient external dose measurement was 0.7 with 10% uncertainty. Multiplying the ambient external dose by 0.7 may be an appropriate measure of the effective dose to an individual in the investigated area. Annual individual doses were estimated for representative lifestyles and occupations based on the ambient external dose rates at the measurement sites, taking into account the relationship between the ambient external dose and individual dose. The results were as follows: 0.6-2.3 mSv y in Tamura, 1.1-5.5 mSv y in Kawauchi, and 3.8-17 mSv y in Iitate. For all areas investigated, the estimated dose to outdoor workers was higher than that to indoor workers. Identifying ways to reduce the amount of time that an outdoor worker spends outdoors would provide an effective measure to reduce dose.

Radial dependence of lineal energy distribution of 290-MeV/u carbon and 500-MeV/u iron ion beams using a wall-less tissue-equivalent proportional counter.

Using a wall-less tissue-equivalent proportional counter for a 0.72-µm site in tissue, we measured the radial dependence of the lineal energy distribution, yf(y), of 290-MeV/u carbon ions and 500-MeV/u iron ion beams. The measured yf(y) distributions and the dose-mean of y, [Formula: see text], were compared with calculations performed with the track structure simulation code TRACION and the microdosimetric function of the Particle and Heavy Ion Transport code System (PHITS). The values of the measured [Formula: see text] were consistent with calculated results within an error of 2%, but differences in the shape of yf(y) were observed for iron ion irradiation. This result indicates that further improvement of the calculation model for yf(y) distribution in PHITS is needed for the analytical function that describes energy deposition by delta rays, particularly for primary ions having linear energy transfer in excess of a few hundred keV µm(-1).

Development of target system for intense neutron source of p-Li reaction.

A target cooling system was developed for an intense neutron source of p-Li reaction. The system consists of target cooling devices and protection devices for lithium evaporation. A pin-structure cooling device was developed to enhance cooling power. Functional graded material was utilized for the evaporation of lithium. Test experiments were performed by using the neutron exposure accelerator system for biological effect experiments (NASBEE) at the National Institute of Radiological Sciences (NIRS) in Japan. The target system was confirmed to be applicable for accelerator-based boron neutron capture therapy.

Simulation of response functions of fast neutron sensors and development of thin neutron silicon sensor.

On radiation detection using silicon sensor, signals are produced from collected charges in a depletion layer; however, for high-energy particles, this depletion layer is extended due to funnelling phenomenon. The lengths of charge collection were experimentally obtained from proton peak energies in measured pulse-heights. The length is extended with increasing proton energy of up to 6 MeV, and then, is constant over 6 MeV. The response functions of fast neutron sensors were simulated for 5- and 15-MeV monoenergetic and (252)Cf neutron sources using the Monte Carlo N-Particle eXtended code. The simulation results agree well with the experimental ones, including the effect of funnelling phenomenon. In addition, a thin silicon sensor was developed for a new real-time personal neutron dosemeter. Photon sensitivity is vanishingly smaller than neutron one by a factor of 5×10(-4).

Angular distributions of absorbed dose of Bremsstrahlung and secondary electrons induced by 18-, 28- and 38-MeV electron beams in thick targets.

Angular distributions of absorbed dose of Bremsstrahlung photons and secondary electrons at a wide range of emission angles from 0 to 135°, were experimentally obtained using an ion chamber with a 0.6 cm(3) air volume covered with or without a build-up cap. The Bremsstrahlung photons and electrons were produced by 18-, 28- and 38-MeV electron beams bombarding tungsten, copper, aluminium and carbon targets. The absorbed doses were also calculated from simulated photon and electron energy spectra by multiplying simulated response functions of the ion chambers, simulated with the MCNPX code. Calculated-to-experimental (C/E) dose ratios obtained are from 0.70 to 1.57 for high-Z targets of W and Cu, from 15 to 135° and the C/E range from 0.6 to 1.4 at 0°; however, the values of C/E for low-Z targets of Al and C are from 0.5 to 1.8 from 0 to 135°. Angular distributions at the forward angles decrease with increasing angles; on the other hand, the angular distributions at the backward angles depend on the target species. The dependences of absorbed doses on electron energy and target thickness were compared between the measured and simulated results. The attenuation profiles of absorbed doses of Bremsstrahlung beams at 0, 30 and 135° were also measured.

Early in situ measurement of radioactive fallout in Fukushima city due to Fukushima Daiichi nuclear accident.

Using a high-purity germanium detector, both indoor and outdoor radionuclides that had deposited 1.5 d after the radioactive fallout events in the city of Fukushima were experimentally measured. Eleven artificial ((131)I, (132)I, (134)Cs, (136)Cs, (137)Cs, (129)Te, (129m)Te, (131m)Te, (132)Te, (140)La and (99m)Tc) and 5 natural radionuclides were identified. Total air kerma rates were mainly due to (132)I, (134)Cs and (136)Cs from 4 to 6 µGy/h at a 7.5-cm height from the ground. Radioactive contamination on the ground was contributed by (132)I and (132)Te, from 330 to 420 Bq/cm(2). In a worst-case scenario, the maximum skin dose rates were estimated to be from 520 to 670 µGy/h. Effective dose rates were evaluated to be 10 to 15 µSv/h and reached 17.9 µSv/h at 4 a.m. on 16 March. In the effective dose rates, (132)I, (134)Cs and (132)Te were the main contributors. Our measurements are useful for estimating dose levels in the public in the city of Fukushima during the days after radioactive fallout contamination.

Systematic measurement of lineal energy distributions for proton, He and Si ion beams over a wide energy range using a wall-less tissue equivalent proportional counter.

The frequency distributions of the lineal energy, y, of 160 MeV proton, 150 MeV/u helium, and 490 MeV/u silicon ion beams were measured using a wall-less tissue equivalent proportional counter (TEPC) with a site size of 0.72 µm. The measured frequency distributions of y as well as the dose-mean values, y(D), agree with the corresponding data calculated using the microdosimetric function of the particle and heavy ion transport code system PHITS. The values of y(D) increase in the range of LET below ~10 keV µm(-1) because of discrete energy deposition by delta rays, while the relation is reversed above ~10 keV µm(-1) as the amount of energy escaping via delta rays increases. These results indicate that care should be taken with the difference between y(D) and LET when estimating the ionization density that usually relates to relative biological effectiveness (RBE) of energetic heavy ions.

Measuring cosmic-ray exposure in aircraft using real-time personal dosemeters.

Aircrew exposure to radiation was measured on several long-haul flights using two small commercial electronic personal dosemeters: one was a photon dosemeter, the NRF20; the other was a neutron dosemeter, the NRY21-both manufactured by Fuji Electric Systems Co. Ltd. for radiation protection at nuclear facilities. Non-neutron doses were measured using the photon dosemeter, and neutron doses were measured using the neutron dosemeter. The measured non-neutron doses at commercial aviation altitudes agree with the EPCARD (European Program Package for the Calculation of Aviation Route Doses) dose calculation within a difference of 8 %. However, the recorded neutron doses were 5-15 times larger than the EPCARD calculation. These over-measurements are dependent on cut-off rigidities.

Measurement of microdosimetric spectra with a wall-less tissue-equivalent proportional counter for a 290 MeV/u 12C beam.

The frequency distribution of the lineal energy, y, of a 290 MeV/u carbon beam was measured to obtain the dose-weighted mean of y and compare it with the linear energy transfer (LET). In the experiment, a wall-less tissue-equivalent proportional counter (TEPC) in a cylindrical volume with a simulated diameter of 0.72 microm was used. The measured frequency distribution of y as well as its dose-mean value agrees within 10% uncertainty with the corresponding data from microdosimetric calculations using the PHITS code. The ratio of the measured dose-mean lineal energy to the LET of the 290 MeV/u carbon beam is 0.73, which is much smaller than the corresponding data obtained by a wall TEPC. This result demonstrates that a wall-less TEPC is necessary to precisely measure the dose-mean of y for energetic heavy ion beams.

Measurement of microdosimetric spectra produced from a 290 MeV/n Spread Out Bragg Peak carbon beam.

This study describes measurements on secondary particles produced by a 290 MeV/n Spread Out Bragg Peak (SOBP) carbon beam. Microdosimetric distributions of secondary fragments from the SOBP carbon beam have been measured by using a new tissue equivalent proportional counter (TEPC) system at the Heavy Ion Medical Accelerator in Chiba of the National Institute of Radiological Sciences. The new TEPC system consists of a TEPC, two solid-state detectors (SSD) and a scintillation counter (FSC: forward scintillation counter). The SSDs and FSC can separately identify charged fragments and secondary neutrons produced by the incident carbon ions. Microdosimetric distributions were measured for secondary particles including neutrons produced by a body-simulated phantom consisting of various PMMA plates (thickness: 0, 34.81, 55.2, 60.95, 64.83, 95.03, 114.79, 124.69, 135.2 and 144.98 mm, respectively) to cover the SOBP (at 60-125 mm depth). The new system can separately determine produced fragments from the incident SOBP carbon beam in a body-simulated phantom.

Responses of selected neutron monitors to cosmic radiation at aviation altitudes.

Cosmic radiation exposure of aircraft crew, which is generally evaluated by numerical simulations, should be verified by measurements. From the perspective of radiological protection, the most contributing radiation component at aviation altitude is neutrons. Measurements of cosmic neutrons, however, are difficult in a civilian aircraft because of the limitations of space and electricity; a small, battery-operated dosimeter is required whereas larger-size instruments are generally used to detect neutrons with a broad range of energy. We thus examined the applicability of relatively new transportable neutron monitors for use in an aircraft. They are (1) a conventional rem meter with a polyethylene moderator (NCN1), (2) an extended energy-range rem meter with a tungsten-powder mixed moderator (WENDI-II), and (3) a recoil-proton scintillation rem meter (PRESCILA). These monitors were installed onto the racks of a business jet aircraft that flew two times near Japan. Observed data were compared to model calculations using a PHITS-based Analytical Radiation Model in the Atmosphere (PARMA). Excellent agreement between measured and calculated values was found for the WENDI-II. The NCN1 showed approximately half of predicted values, which were lower than those expected from its response function. The observations made with PRESCILA showed much higher than expected values; which is attributable to the presence of cosmic-ray protons and muons. These results indicate that careful attention must be paid to the dosimetric properties of a detector employed for verification of cosmic neutron dose.

Microdosimetric study for secondary neutrons in phantom produced by a 290 MeV/nucleon carbon beam.

Absorbed doses from main charged-particle beams and charged-particle fragments have been measured with high accuracy for particle therapy, but there are few reports for doses from neutron components produced as fragments. This study describes the measurements on neutron doses produced by carbon beams; microdosimetric distributions of secondary neutrons produced by 290 MeV/nucleon carbon beams have been measured by using a tissue equivalent proportional counter at the Heavy Ion Medical Accelerator in Chiba, Japan at the National Institute of Radiological Sciences. The microdosimetric distributions of the secondary neutron were measured on the distal and lateral faces of a body-simulated acrylic phantom (300 mm height x 300 mm width x 253 mm thickness). To confirm the dose measurements, the neutron energy spectra produced by incident carbon beams in the acrylic phantom were simulated by the particle and heavy ion transport code system. The absorbed doses obtained by multiplying the simulated neutron energy spectra with the kerma factor calculated by MCNPX agree with the corresponding experimental data fairly well. Downstream of the Bragg peak, the ratio of the neutron dose to the carbon dose at the Bragg peak was found to be a maximum of 1.4 x 10(-4) and the ratio of neutron dose was a maximum of 3.0 x 10(-7) at a lateral face of the acrylic phantom. The ratios of neutrons to charged particle fragments were 11% to 89% in the absorbed doses at the lateral and the distal faces of the acrylic phantom. We can conclude that the treatment dose will not induce serious secondary neutron effects at distances greater than 90 mm from the Bragg peak in carbon particle therapy.

Microdosimetric evaluation of secondary particles in a phantom produced by carbon 290 MeV/nucleon ions at HIMAC.

Microdosimetric single event spectra as a function of depth in a phantom for the 290 MeV/nucleon therapeutic carbon beam at HIMAC were measured by using a tissue equivalent proportional counter (TEPC). Two types of geometries were used: one is a fragment particle identification measurement (PID-mode) with time of flight (TOF) method without a backward phantom, and the other is an in-phantom measurement (IPM-mode) with a backward phantom. On the PID-mode geometry, fragments produced by carbon beam in a phantom are identified by the DeltaE-TOF distribution between two scintillation counters positioned up- and down-stream relative to the tissue equivalent proportional counter (TEPC). Lineal energy distributions for carbon and five ion fragments (proton, helium, lithium, beryllium and boron) were obtained in the lineal-energy range of 0.1-1000 keV/microm at eight depths (7.9-147.9 mm) in an acrylic phantom. In the IPM-mode geometry, the total lineal energy distributions measured at eight depths (61.9-322.9 mm) were compared with the distributions in the PID-mode. Both spectra are consistent with each other. This shows that the PID-mode measurement can be discussed as the equivalent of the phantom measurement. The dose distribution of the carbon beam and fragments were obtained separately. In the depth dose curve, the Bragg peak was observed. Relative biological effectiveness (RBE) for the carbon beam in the acrylic phantom was obtained based on a biological response function as a lineal-energy. The RBE of carbon beam had a maximum of 4.5 at the Bragg peak. Downstream of the Bragg peak, the RBE rapidly decreases. The RBE of fragments is dominated by Boron particles around the Bragg peak region.

Estimation of yields of OH radicals in water irradiated by ionizing radiation.

The yield of OH radical induced by ionizing radiation was estimated by an empirical model; a prescribed diffusion model for a spur of single size applying to neutral water. Two representative spur distances were introduced, one for an incident primary charged particle and one for a representative secondary electron, to calculate chemical yields among active species in a spur. The total yield from the track was a combination of these primary and secondary yields. Two coefficients of this combination were the parameters of the present model. Based on an optimization of these parameters by existing experimental Fricke G-values, the present model estimates the yields of OH at the microsecond timescale after an irradiation, in a unified manner from electrons to heavy ions. The predicted yields of OH around the nanosecond timescale after an irradiation may be a relevant basis for a study on the mechanisms of radiation effects. This prediction by the present model was exemplified for electrons, photons and heavy ions (proton, helium, carbon, neon, argon and iron).

Microdosimetric evaluation of the 400 MeV/nucleon carbon beam at HIMAC.

Microdosimetric single event spectra were determined as a function of depth in an acrylic phantom for the carbon beam at HIMAC using a tissue equivalent proportional counter (TEPC) coupled to a scintillation counter system. The fragments produced by the carbon beam were identified by the deltaE-time of flight distribution obtained from two scintillation counters which were positioned at the up- and down-stream of the TEPC. Lineal energy distribution for the carbon beam and its five fragments, namely, proton, helium, lithium, beryllium, and boron ions, were measured in the lineal-energy range of 5-1000 keV/microm at five phantom depths between 0 and 230 mm. The dose distribution for the carbon beam and its fragments were obtained separately. The relative biological effectiveness (RBE) of the carbon beam in the phantom was calculated using a response function. The maximum RBE for the carbon beam was found to be about 5 near the Bragg peak. It was observed to rapidly decrease for Bragg peaks occurring at deeper positions in the phantom. The dose from the beam fragments accounted for about 30% to the total dose, however, its contribution to the RBE was less than 17%.