Overview of the Liulin type instruments for space radiation measurement and their scientific results.

Ionizing radiation is recognized to be one of the main health concerns for humans in the space radiation environment. Estimation of space radiation effects on health requires the accurate knowledge of the accumulated absorbed dose, which depends on the global space radiation distribution, solar cycle and local shielding generated by the 3D mass distribution of the space vehicle. This paper presents an overview of the spectrometer-dosimeters of the Liulin type, which were developed in the late 1980s and have been in use since then. Two major measurement systems have been developed by our team. The first one is based on one silicon detector and is known as a Liulin-type deposited energy spectrometer (DES) (Dachev et al., 2002, 2003), while the second one is a dosimetric telescope (DT) with two or three silicon detectors. The Liulin-type instruments were calibrated using a number of radioactive sources and particle accelerators. The main results of the calibrations are presented in the paper. In the last section of the paper some of the most significant scientific results obtained in space and on aircraft, balloon and rocket flights since 1989 are presented.

Calibration of modified Liulin detector for cosmic radiation measurements on-board aircraft.

The annual effective doses of aircrew members often exceed the limit of 1 mSv for the public due to the increased level of cosmic radiation at the flight altitudes, and thus, it is recommended to monitor them. Aircrew dosimetry is usually performed using special computer programs mostly based on results of Monte Carlo simulations. Contemporary, detectors are used mostly for validation of these computer codes, verification of effective dose calculations and for research purposes. One of such detectors is active silicon semiconductor deposited energy spectrometer Liulin. Output quantities of measurement with the Liulin detector are the absorbed dose in silicon D and the ambient dose equivalent H*(10); to determine it, two calibrations are necessary. The purpose of this work was to develop a calibration methodology that can be used to convert signal from the detector to D independently on calibration performed at Heavy Ion Medical Accelerator facility in Chiba, Japan.

Measurement of dose equivalent distribution on-board commercial jet aircraft.

The annual effective doses of aircrew members often exceed the limit of 1 mSv for the public due to the increased level of cosmic radiation at the flight altitudes, and thus, it is recommended to monitor them [International Commission on Radiation Protection. 1990 Recommendations of the International Commission on Radiological Protection. ICRP Publication 60. Ann. ICRP 21: (1-3), (1991)]. According to the Monte Carlo simulations [Battistoni, G., Ferrari, A., Pelliccioni, M. and Villari, R. Evaluation of the doses to aircrew members taking into consideration the aircraft structures. Adv. Space Res. 36: , 1645-1652 (2005) and Ferrari, A., Pelliccioni, M. and Villari, R. Evaluation of the influence of aircraft shielding on the aircrew exposure through an aircraft mathematical model. Radiat. Prot. Dosim. 108: (2), 91-105 (2004)], the ambient dose equivalent rate H*(10) depends on the location in the aircraft. The aim of this article is to experimentally evaluate H*(10) on-board selected types of aircraft. The authors found that H*(10) values are higher in the front and the back of the cabin and lesser in the middle of the cabin. Moreover, total dosimetry characteristics obtained in this way are in a reasonable agreement with other data, in particular with the above-mentioned simulations.

Single extreme low dose/low dose rate irradiation causes alteration in lifespan and genome instability in primary human cells.

To investigate the long-term biological effect of extreme low dose ionising radiation, we irradiated normal human fibroblasts (HFLIII) with carbon ions (290 MeV u(-1), 70 keV microm(-1)) and gamma-rays at 1 mGy (total dose) once at a low dose rate (1 mGy 6-8 h(-1)), and observed the cell growth kinetics up to 5 months by continuous culturing. The growth of carbon-irradiated cells started to slow down considerably sooner than that of non-irradiated cells before reaching senescence. In contrast, cells irradiated with gamma-rays under similar conditions did not show significant deviation from the non-irradiated cells. A DNA double strand break (DSB) marker, gamma-H2AX foci, and a DSB repair marker, phosphorylated DNA-PKcs foci, increased in number when non-irradiated cells reached several passages before senescence. A single low dose/low dose rate carbon ion exposure further raised the numbers of these markers. Furthermore, the numbers of foci for these two markers were significantly reduced after the cells became fully senescent. Our results indicate that high linear energy transfer (LET) radiation (carbon ions) causes different effects than low LET radiation (gamma-rays) even at very low doses and that a single low dose of heavy ion irradiation can affect the stability of the genome many generations after irradiation.

The intercomparison of cosmic rays with heavy ion beams at NIRS (ICCHIBAN) project.

The ICCHIBAN-2 experiment, the first dedicated to the ground-based intercomparison of passive space dosemeters, was carried out between 23 May and 28 May 2002 at the National Institute of Radiological Sciences in Chiba, Japan. The primary objective of the ICCHIBAN-2 experiment was to intercompare the response of passive dosemeters used in space crew dosimetry to monoenergetic heavy ions of charge and energy spanning a significant portion of the galactic cosmic ray (GCR) spectrum. During the ICCHIBAN-2 experiment, dosemeters from 12 different laboratories in 9 countries were irradiated under identical conditions to heavy ion beams of 150 MeV n(-1) (4)He, 400 MeV n(-1) (12)C, 490 MeV n(-1) (28)Si and 500 MeV n(-1) (56)Fe at the NIRS Heavy Ion Medical Accelerator.

Reduction in life span of normal human fibroblasts exposed to very low-dose-rate charged particles.

We studied the effect of chronic low-dose irradiation with heavy ions on the life span of normal human fibroblasts in vitro. Cells were cultured in a CO2 incubator that was placed in the irradiation room for biological studies of heavy ions in the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences (NIRS) and were exposed to scattered radiations produced by heavy-ion beams for the life span of the cell population. The absorbed dose, which was measured using a thermoluminescence dosimeter (TLD) and a silicon semiconductor detector, was 1.4 mGy per day when the HIMAC was operated for biological experiments. The total number of population doublings of the exposed cells as reduced to 79-93% of that of nonexposed control cells. However, the life span of cells exposed to low-dose 137Cs gamma rays (approximately 1 mGy/day) in the CO2 incubator in the gamma-irradiation room in NIRS was prolonged to 104-106% of that of nonexposed control cells. Thus there is evidence that exposure to chronic low-dose heavy-ion radiation reduces the life span of cells.

Radiation measurements aboard NASA ER-2 high altitude aircraft with the Liulin-4J portable spectrometer.

The risks to aircrew health posed by prolonged exposure to low levels of ionizing radiation at aircraft altitudes have recently received renewed attention. Civil and military aircraft currently on the drawing board are expected to operate at higher altitudes (>12 km) and fly longer ranges than do existing aircraft, thereby exposing their crews to higher levels of ionizing radiation, for longer periods of time. We are currently carrying out dosimetric measurements of the ionizing radiation environment at approximately 20 km altitude using portable Si detectors aboard NASA's two ER-2 high altitude research aircraft. The instruments, Liulin-4J, have been extensively calibrated at several particle accelerators. With these instruments, we can measure not only absorbed dose, but also variation of the absorbed dose as a function of time. We report radiation dose measurements as function of time, altitude, and latitude for several ER-2 missions.

Microdosimetric distribution of protons, Ep = 19-65 MeV, measured with a low pressure proportional counter.

Microdosimetric measurements of 19, 32, 43, 55, and 65 MeV protons were carried out with the A-150-walled low pressure proportional counter (LPPC). The spectra are deconvoluted into three components, which are energy loss by directly incident protons, secondary electrons, and scattered protons and heavy charged particle (including protons) produced by proton nuclear reactions with the TE wall. Dose-mean lineal energies of protons are large as usual, because larger lineal energies by proton reaction events are affected.

Calibration results obtained with Liulin-4 type dosimeters.

The Mobile Radiation Exposure Control System's (Liulin-4 type) main purpose is to monitor simultaneously the doses and fluxes at 4 independent places. It can also be used for personnel dosimetry. The system consists of 4 battery-operated 256-channel dosimeters-spectrometers. We describe results obtained during the calibrations of the spectrometers at the Cyclotron facilities of the University of Louvain, Belgium and of the National Institute of Radiological Sciences-STA, Chiba, Japan with protons of energies up to 70 MeV. The angular sensitivities of the devices are studied and compared with Monte-Carlo predictions. We also present the results obtained at the HIMAC accelerator with 500 MeV/u Fe ions and at the CERN high energy radiation reference fields. Records made during airplane flights are shown and compared with the predictions of the CARI-6 model.

Vitreous levels of insulin-like growth factor-I in patients with proliferative diabetic retinopathy.

The levels of IGF-I in the vitreous body and the intraocular fluid of patients with proliferative diabetic retinopathy (PDR) were determined using radioimmunoassay (RIA). Eleven vitreous specimens were obtained from the intraocular fluid of eyes of patients with PDR who underwent surgery during the operation. Eleven intraocular fluids from the same patients during reoperations were compared with controls. The expression of IGF-I mRNA in cultured human Muller glial cells was evaluated using reverse transcription-polymerase chain reaction (RT-PCR). The mean IGF-I level in the vitreous samples during initial PDR surgery and reoperation was significantly higher than that found in the vitreous of the control (p < 0.05). The level of IGF-I increased in 6 of the 11 cases. Cultured human Muller cells expressed IGF-I mRNA. The results indicate increased levels of IGF-I both in the initial vitreous and ocular fluid at post-operative re-proliferation. Muller cell is suggested as an origin of local IGF-I production.

Differential dosimetry in a neutron-proton mixed field with low-pressure proportional counters.

For a mixed radiation field of neutrons and protons, radiation events were discriminated between photons, neutrons, and protons using a thin plastic scintillator. Distributions of lineal energy were measured with low-pressure proportional counters (LPPCs). To estimate the distribution of lineal energy for ICRU muscle, measurements were carried out using A-150-walled, graphite-walled, ZrO2-walled, and Zr-walled counters. Data were corrected for different atomic compositions between the A-150 plastic and ICRU muscle.

A case of an intraocular foreign body due to graphite pencil lead complicated by endophthalmitis.

We report a case of an 8-year-old boy who presented with an intraocular foreign body composed of graphite pencil lead. The patient had been accidentally poked in the right eye with a graphite pencil. Primary care consisted of corneal suturing and lens extraction. Two pieces of the pencil lead remained in the vitreous cavity following surgery, and 2 days later the patient developed endophthalmitis. Pars plana vitrectomy was performed immediately and the intraocular foreign bodies were removed through the scleral wound. Cultures of the vitreous fluid revealed no bacterial organisms. X-ray fluoroscopic analysis of the vitreous detected 1 ppm of aluminum (a constituent of the pencil lead). Although the clinical presentation indicated probable bacterial endophthalmitis, the detection of elemental aluminum within the vitreous cavity also suggested the possibility of further retinal toxicity due to some dissolving of the pencil lead.

Clinical characteristics of acyclovir-resistant herpetic keratitis and experimental studies of isolates.

BACKGROUND: We treated two patients with dendritic keratitis that did not respond to acyclovir (ACV) ointment therapy. Their systemic immune status was normal: however, one patient had a long history of atopic disease and the other had previously undergone topical corticosteroid treatment. HSV-1 was isolated from the patients and inoculated into animals to investigate its viral pathogenicity and latent infection. METHODS: HSV-1 isolates from the patients were tested for drug sensitivity to acyclovir, ganciclovir, idoxuridine, trifluridine, foscarnet and interferon-beta in vitro. In in vivo studies, bilateral corneas of two New Zealand white rabbits and 10 BALB/c mice in each of four groups were infected by the respective viral isolates. The extent of corneal epithelial and/or stromal lesions produced by the viruses was evaluated. The trigeminal ganglial tissues of the mice were examined for viral latent infection by co-culture with Vero cells. RESULTS: Herpetic keratitis in both patients was characterized by prolonged clinical course, succeeded by various types of corneal lesions and ocular complications. In in vitro studies, the two HSV-1 isolates demonstrated cross-resistance to ACV, ganciclovir and/or idoxuridine. Both strains demonstrated weakly virulent corneal epithelial and/or stromal lesions in rabbits and mice. One isolate displayed delayed advent but prolonged course of epithelial lesions in rabbits. The latent infection incidences of the isolates in mice trigeminal ganglia were 6.25% (1/16) and 0% (0/18) respectively. CONCLUSION: Topical immune depression may induce ACV-resistant HSV-1 infection in the cornea, with a prolonged course in association with ocular complications. The prolonged infectious course of the viral isolates in the animal study partially supported the clinical demonstrations in the patient. The existence of latent infection by one ACV-resistant HSV-1 in its animals may indicate the possibility of its recurrence. Trifluridine may be an alternative choice for treating corneal epithelial lesions caused by ACV-resistant HSV-1.

Glutamate as a neuron-to-glial signal for mitogenesis: role of glial N-methyl-D-aspartate receptors.

The presence on glial cells of receptors for neurotransmitters suggests the capability of neuron-to-glial signalling. Here, we asked whether the retinal transmitter, glutamate, may serve as a mitogenic signal for human retinal glial cells. Using cultured glial from the adult postmortem retina, we found that glutamate stimulated the proliferation of these glial cells. Pharmacological experiments indicated that this proliferative effect involved activation of N-methyl-D-aspartate (NMDA) receptor channels. Activation of NMDA receptors on retinal glial cells may mediate a proliferative response of these cells to pathophysiologic conditions causing a sustained elevation of glutamate.

Mitogenic and chemotactic effects of platelet-derived growth factor on human retinal glial cells.

Glial cell migration and proliferation appear to play a role in many of the proliferative retinopathies. Knowledge concerning the regulation of the migratory and proliferative responses of glial cells to pathophysiologic conditions in the human retina is limited. Here, we report that platelet-derived growth factor (PDGF) has both mitogenic and chemotactic effects on human retinal glial cells in culture. These effects of PDGF support the idea that this growth factor may be one of the molecules influencing glial cell activities in the proliferative retinopathies. Both the mitogenic and chemotactic responses of retinal glial cells to PDGF could be inhibited by the calcium-channel blocker, nifedipine. Although this finding suggests that nifedipine-sensitive calcium channels may help mediate these responses to PDGF, an electrophysiologic effect of PDGF on voltage-gated calcium channels was not detected. Also, the concentration of nifedipine required to inhibit proliferation was higher than the dose needed to block calcium channels. It seems likely that nifedipine inhibits the mitogenic and chemotactic responses of human retinal glial cells to PDGF by affecting cellular processes in addition to calcium channels.

Subretinal neovascularisation in eyes with localised inferior posterior staphylomas.

We report seven cases of subretinal neovascularisation with inferior posterior staphyloma. The upper border of the shallow staphyloma, detected by B-mode echography, invaded the macular area, and there was a neovascular net at the edge of the staphyloma. Three of the cases showed chorioretinal atrophy at the upper edge of the staphyloma in the same location as the neovascular net. Our cases were identical to those of subretinal neovascularisation in high myopic eyes in which the rupture of Bruch's membrane was related to the deformity of the scleral shell. As our cases included not-high-myopic eyes, the results suggest that the identical mechanism might be involved in the occurrence of neovascular maculopathy in the pathological high myopic eye and in the not-high-myopic eye with posterior staphyloma. Localised inferior posterior staphyloma may be an important cause of 'idiopathic' subretinal neovascularisation.

Measurement of retinal permeability to sodium fluorescein in vitro.

Fluorescein permeabilities of isolated dog retinal pigment epithelium (RPE)-choroid and sensory retina were measured individually. Retina to choroid (outward) permeability of sodium fluorescein was significantly larger than choroid to retina (inward) permeability at RPE-choroid under both open- and short-circuit conditions. Outward permeability was decreased by the addition of 10(-3) M KCN and of 10(-4) M probeneside but was not affected by 10(-6) M ouabain. These drugs decreased transepithelial potential and short-circuit current. No directional difference of fluorescein permeability for sensory retina was found. Active transport of fluorescein across RPE from retina to choroid is suggested. Fluorescein permeability of sensory retina was larger than inward but less than outward permeability of RPE-choroid. The result indicates that the sensory retina acts as a diffusion barrier for sodium fluorescein.