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The ICCHIBAN intercomparison experiments for space radiation instruments using ion beams from accelerators have been performed at HIMAC, Chiba, Japan and Loma Linda Univ. Medical Center (LLUMC), California, USA. Investigators from 17 laboratories in 10 nations participated in these experiments. To date, five intercomparison experiments have performed at HIMAC using heavy ion beams, including He, C, Ne, Si, Ar and Fe, that are of importance in the galactic cosmic-ray spectrum. At LLUMC, an experiment was performed using a proton beam to simulate a solar particle event. Additional experiments, including an intercomparison using relativistic Fe, Si and proton beams at NSRL, are currently being planned. The objectives of the ICCHIBAN intercomparison experiments are to 1) determine the response of space radiation instruments to heavy ions and protons; 2) intercompare the response and sensitivity of these instruments; 3) establish and characterize an accelerator-based "reference standard" against which these instruments can be calibrated.The participants of ICCHIBAN-1 and ICCHIBAN-2 experiments have analyzed their results and submitted reports to the ICCHIBAN working group (ICWG). ICWG has summarized the results and published as HIMAC Technical Report. For active instruments, the LET distributions from instruments using Si detectors and from TEPC were good agreement for 12C exposures, although the width of the main peak was broader for the TEPC exposures due to differences in the operating principles of the instruments. Several active instruments were found to lack sensitivity to high LET particles including the Fe beam used in the intercomparison. For passive dosimeters, ICWG exposed participants\u27 dosimeters to both \u27known\u27 and \u27blind\u27 conditions. The participants analyzed their dosimeters from the \u27known\u27 exposures to measure dose linearity and obtain high-LET dose efficiency response. In the blind exposure simulating an actual exposure in space (97% low LET particles and 3% high LET particles) most of dosimeters showed good agreement with the reference ion chamber measurements. But, in other blind exposures where high LET radiation was dominant, there was larger disagreement. This was largely due to the lack of efficiency of TLD and OSL dosimeters in registering dose from high-LET particles. Some of participants applied correction methods to the TLD or OSL data that greatly improved their response to high-LET particles. Only those passive detector laboratories that used a combination of CR-39 PNTD and TLD were able to measure both dose and dose equivalent.3rd International Workshop on Space Radiation Researc

Development of the analog ASIC for multi-channel readout X-ray CCD camera

We report on the performance of an analog application-specific integrated circuit (ASIC) developed aiming for the front-end electronics of the X-ray CCDcamera system onboard the next X-ray astronomical satellite, ASTRO-H. It has four identical channels that simultaneously process the CCD signals. Distinctive capability of analog-to-digital conversion enables us to construct a CCD camera body that outputs only digital signals. As the result of the front-end electronics test, it works properly with low input noise of =<30 uV at the pixel rate below 100 kHz. The power consumption is sufficiently low of about 150 mW/chip. The input signal range of 720 mV covers the effective energy range of the typical X-ray photon counting CCD (up to 20 keV). The integrated non-linearity is 0.2% that is similar as those of the conventional CCDs in orbit. We also performed a radiation tolerance test against the total ionizing dose (TID) effect and the single event effect. The irradiation test using 60Co and proton beam showed that the ASIC has the sufficient tolerance against TID up to 200 krad, which absolutely exceeds the expected amount of dose during the period of operating in a low-inclination low-earth orbit. The irradiation of Fe ions with the fluence of 5.2x10^8 Ion/cm2 resulted in no single event latchup (SEL), although there were some possible single event upsets. The threshold against SEL is higher than 1.68 MeV cm^2/mg, which is sufficiently high enough that the SEL event should not be one of major causes of instrument downtime in orbit.Comment: 16 pages, 6 figure

Structural studies of toxins and toxin-like proteins

Toxins are an ancient mechanism of interaction between cohabiting organisms: basal concentrations serve as an informal cue, enough as a warning signal; too much and the dialog is over. As such, the evolutionary race to arms led to the development of a vast trove of molecular unique biochemical mechanisms, from small molecules to protein toxins. The study of these mechanisms is not only essential for the treatment of toxin-related pathologies, but also as the potential source for novel therapeutic drugs. In this thesis, a series of studies of different toxins and toxin-like proteins are compiled. To further understand the biological function and relevance of each toxin, their detailed study and characterization were pursued. Here are described the advances made using a combination of different complementary biophysical and structural methods, chosen in each case to specifically target each molecule characteristics. In the first chapter, the general biological theme of this thesis is introduced: toxins, particularly protein toxins, their description, and classification, as well as the role of structural biology in the study of proteins in general. To set the theoretical background of the following chapters, are also described the general principles of two of the most prominent methods for the study of proteins in structural biology: nuclear magnetic resonance (NMR) spectroscopy, and X-ray diffraction. In the second chapter, the interaction between human FKBP12 chaperone protein and two similar bacterial small molecule toxins is detailed: rapamycin initially used as an anti-fungal before the discovery of its potent immunosuppressive properties as a mTOR inhibitor; and mycolactone, a bacterial toxin responsible for the disease Buruli ulcers in humans. In the third chapter, the cell-free protein expression system is introduced as a technique best suited for the expression of cytotoxic proteins and otherwise difficult targets, as explored further in the following chapters. In the fourth chapter, advancements towards the structural and conformational characterization of the membrane-inserted state of two similar pore-forming toxins are detailed: the bacterial Colicin Ia protein; and the human Bax protein, an apoptosis effector; using X-ray crystallography, solution NMR and solid-state NMR. Finally, in the fifth chapter, two FIC-domain bacterial toxins are investigated: the bacterial VbhTA toxin-antitoxin protein complex, and the structural determination with its cognate target, DNA GyraseB enzyme; and the auto-activation of the bacterial NmFIC protein; in both cases using a combination of X-ray crystallography and NMR spectroscopy, as well as other biophysical techniques

Induction of Non-Targeted Stress Responses in Mammary Tissues by Heavy Ions

Purpose Side effects related to radiation exposures are based primarily on the assumption that the detrimental effects of radiation occur in directly irradiated cells. However, several studies have reported over the years of radiation-induced non-targeted/ abscopal effects in vivo that challenge this paradigm. There is evidence that Cyclooxygenase-2 (COX2) plays an important role in modulating non-targeted effects, including DNA damages in vitro and mutagenesis in vivo. While most reports on radiation-induced non-targeted response utilize x-rays, there is little information available for heavy ions. Methods and Materials Adult female transgenic gpt delta mice were exposed to an equitoxic dose of either carbon or argon particles using the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences (NIRS) in Japan. The mice were stratified into 4 groups of 5 animals each: Control; animals irradiated under full shielding (Sham-irradiated); animals receiving whole body irradiation (WBIR); and animals receiving partial body irradiation (PBIR) to the lower abdomen with a 1 x 1 cm2 field. The doses used in the carbon ion group (4.5 Gy) and in argon particle group (1.5 Gy) have a relative biological effectiveness equivalent to a 5 Gy dose of x-rays. 24 hours after irradiation, breast tissues in and out of the irradiated field were harvested for analysis. Induction of COX2, 8-hydroxydeoxyguanosine (8-OHdG), phosphorylated histone H2AX (γ-H2AX), and apoptosis-related cysteine protease-3 (Caspase-3) antibodies were examined in the four categories of breast tissues using immunohistochemical techniques. Analysis was performed by measuring the intensity of more than 20 individual microscopic fields and comparing the relative fold difference. Results In the carbon ion group, the relative fold increase in COX2 expression was 1.01 in sham-irradiated group (p > 0.05), 3.07 in PBIR (p 0.05), 11.31 in PBIR (p 0.05), 8.41 in PBIR (p < 0.05) and 10.59 in WBIR (p < 0.05). Results for the argon particle therapy group showed a similar magnitude of changes in the various biological endpoints examined. There was no statistical significance observed in Caspase-3 expression among the 4 groups. Conclusions Our data show that both carbon and argon ions induced non-targeted, out of field induction of COX2 and DNA damages in breast tissues. These effects may pose new challenges to evaluate the risks associated with radiation exposure and understanding radiation-induced side effects

REFLECT – Research flight of EURADOS and CRREAT: Intercomparison of various radiation dosimeters onboard aircraft

Aircraft crew are one of the groups of radiation workers which receive the highest annual exposure to ionizing radiation. Validation of computer codes used routinely for calculation of the exposure due to cosmic radiation and the observation of nonpredictable changes in the level of the exposure due to solar energetic particles, requires continuous measurements onboard aircraft. Appropriate calibration of suitable instruments is crucial, however, for the very complex atmospheric radiation field there is no single reference field covering all particles and energies involved. Further intercomparisons of measurements of different instruments under real flight conditions are therefore indispensable. In November 2017, the REFLECT (REsearch FLight of EURADOS and CRREAT) was carried out. With a payload comprising more than 20 different instruments, REFLECT represents the largest campaign of this type ever performed. The instruments flown included those already proven for routine dosimetry onboard aircraft such as the Liulin Si-diode spectrometer and tissue equivalent proportional counters, as well as newly developed detectors and instruments with the potential to be used for onboard aircraft measurements in the future. This flight enabled acquisition of dosimetric data under well-defined conditions onboard aircraft and comparison of new instruments with those routinely used. As expected, dosimeters routinely used for onboard aircraft dosimetry and for verification of calculated doses such as a tissue equivalent proportional counter or a silicon detector device like Liulin agreed reasonable with each other as well as with model calculations. Conventional neutron rem counters underestimated neutron ambient dose equivalent, while extended-range neutron rem counters provided results comparable to routinely used instruments. Although the responses of some instruments, not primarily intended for the use in a very complex mixed radiation field such as onboard aircraft, were as somehow expected to be different, the verification of their suitability was one of the objectives of the REFLECT. This campaign comprised a single short flight. For further testing of instruments, additional flights as well as comparison at appropriate reference fields are envisaged. The REFLECT provided valuable experience and feedback for validation of calculated aviation doses