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This study investigates, both experimentally and numerically, the radiation shielding properties of two types of heavyweight concretes, one containing barite and one made with Electric Arc Furnace (EAF) slag as coarse aggregates. Fresh and hardened concrete properties are preliminary analyzed and compared to a conventional mix containing natural aggregates, namely: fresh and hard bulk density, consistency, compressive and tensile strength, elastic modulus. Three specimens per each mix are subsequently irradiated with both a high-activity (8.97 TBq) and a low-activity (280 kBq) 60Co gamma-ray source to measure their linear attenuation coefficients. Gamma-ray shielding characteristics are also numerically analyzed via a Monte Carlo code assessing radiation transport calculations. Experimental and numerical results indicate that EAF concrete has comparable shielding properties to baritic one, and it allows a certain decrease in thickness of the radiation shield, if compared to an ordinary concrete, however it has superior mechanical properties than the other studied mixtures.

ks. ROBERTO CHERUBINI – patrolog, wykladowca Papieskiego Uniwersytetu Urbaniana w Rzymie, administrator parafii św. Krzyza w Terni (Italia). Kaplan diecezjalny, czlonek Bractwa Misyjnego Wspolnoty św. Egidio. Autor kilku ksiązek, m.in. Conoscere Dio: lettere e altri scritti di Ammonas, Citta del Vaticano: Urbaniana University Press, 2011; La strada si fa maestra: imparare dai poveri la lingua della misericordia, Milano: Ancora, 2016.

Experimental nanodosimetry aims to develop a new concept of radiation quality, based on the correlation between initial features of particle tracks and late biological outcome. A direct proportionality has been observed between the cumulative probability of measuring at least k ionisations within a nanometric volume and inactivation cross sections at specific survival levels. Based on this proportionality, physical quantities which are measurable at the nanometre level can be used to estimate the alpha and beta parameters of the linear-quadratic dose-response model, provided that two proportionality factors are determined in a reference radiation field. This work describes the procedure and first results applied to published data for V79 cell survival after irradiation with protons and carbon ions.

For precision cancer radiotherapy, high linear energy transfer (LET) particle irradiation offers a substantial advantage over photon-based irradiation. In contrast to the sparse deposition of low-density energy by &chi, or &gamma, rays, particle irradiation causes focal DNA damage through high-density energy deposition along the particle tracks. This is characterized by the formation of multiple damage sites, comprising localized clustered patterns of DNA single- and double-strand breaks as well as base damage. These clustered DNA lesions are key determinants of the enhanced relative biological effectiveness (RBE) of energetic nuclei. However, the search for a fingerprint of particle exposure remains open, while the mechanisms underlying the induction of chromothripsis-like chromosomal rearrangements by high-LET radiation (resembling chromothripsis in tumors) await to be elucidated. In this work, we investigate the transformation of clustered DNA lesions into chromosome fragmentation, as indicated by the induction and post-irradiation repair of chromosomal damage under the dynamics of premature chromosome condensation in G0 human lymphocytes. Specifically, this study provides, for the first time, experimental evidence that particle irradiation induces localized shattering of targeted chromosome domains. Yields of chromosome fragments and shattered domains are compared with those generated by &gamma, rays, and the RBE values obtained are up to 28.6 for &alpha, particles (92 keV/&mu, m), 10.5 for C-ions (295 keV/&mu, m), and 4.9 for protons (28.5 keV/&mu, m). Furthermore, we test the hypothesis that particle radiation-induced persistent clustered DNA lesions and chromatin decompaction at damage sites evolve into localized chromosome shattering by subsequent chromatin condensation in a single catastrophic event&mdash, posing a critical risk for random rejoining, chromothripsis, and carcinogenesis. Consistent with this hypothesis, our results highlight the potential use of shattered chromosome domains as a fingerprint of high-LET exposure, while conforming to the new model we propose for the mechanistic origin of chromothripsis-like rearrangements.

International audience; The cyclotron ARRONAX can deliver different types of particles (protons, deuterons, alpha-particles) in an energy range up to 68 MeV. One of its six experimental halls is dedicated to studying the interactions of radiation with matter including living matter. A horizontal beamline for cell irradiation has been setup and characterized. The radiobiological characterization was done in terms of V79 cells survival after irradiation with 68 MeV protons. The results demonstrate that radiobiological studies can be successfully performed confirming the high potential of the facility.

Purpose: To study EBT3 GafChromic film in low-energy protons, and for comparison purposes, in a reference 60Co beam in order to use it as a calibrated dosimetry system in the proton irradiation facility under construction within the framework of the Oncological Therapy with Protons (TOP)-Intensity Modulated Proton Linear Accelerator for RadioTherapy (IMPLART) Project at ENEA-Frascati, Italy. Methods: EBT3 film samples were irradiated at the Istituto Nazionale di Fisica Nucleare—Laboratori Nazionali di Legnaro, Italy, with a 5 MeV proton beam generated by a 7 MV Van de Graaff CN accelerator. The nominal dose rates used were 2.1 Gy/min and 40 Gy/min. The delivered dose was determined by measuring the particle fluence and the energy spectrum in air with silicon surface barrier detector monitors. A preliminary study of the EBT3 film beam quality dependence in low-energy protons was conducted by passively degrading the beam energy. EBT3 films were also irradiated at ENEA-National Institute of Ionizing Radiation Metrology with gamma radiation produced by a 60Co source characterized by an absorbed dose to water rate of 0.26 Gy/min as measured by a calibrated Farmer type ionization chamber. EBT3 film calibration curves were determined by means of a set of 40 film pieces irradiated to various doses ranging from 0.5 Gy to 30 Gy absorbed dose to water. An EPSON Expression 11000XL color scanner in transmission mode was used for film analysis. Scanner response stability, intrafilm uniformity, and interfilm reproducibility were verified. Optical absorption spectra measurements were performed on unirradiated and irradiated EBT3 films to choose the most sensitive color channel to the dose range used. Results: EBT3 GafChromic films show an under response up to about 33% for low-energy protons with respect to 60Co gamma radiation, which is consistent with the linear energy transfer dependence already observed with higher energy protons, and a negligible dose-rate dependence in the 2–40 Gy/min range. Short- and long-term scanner stabilities were 0.5% and 1.5%, respectively; film uniformity and reproducibility were better than 0.5%. Conclusions: The main purpose of this study was to implement EBT3 dosimetry in the proton low-energy radiobiology line of the TOP-IMPLART accelerator, having a maximum energy of 7 MeV. Low-energy proton and 60Co calibrated sources were used to investigate the behavior of film response vs to be written in italicum dose. The calibration in 5 MeV protons is currently used for dose assessment in the radiobiological experiments at the TOP-IMPLART accelerator carried out at that energy value.

In the past two decades, a body of experimental evidences in vitro has shown the presence of a plethora of phenomena occurring after low-dose irradiation [including hypersensitivity and induced radioresistance (IRR), adaptive response, bystander effect (BE) and genomic instability], which might imply a non-linear behaviour of cancer risk curves in the low-dose region and question the validity of the linear no-threshold model for cancer risk assessment in such a dose region. In this framework, a systematic investigation have been undertaken on non-linear effects at low doses as a function of different radiation quality and cellular radiosensitivity and in terms of different biological end points. The present article reports the recent results on hyper-radiosensitivity and IRR and BE phenomena, in terms of clonogenic survival in V79 Chinese hamster cells and T98G human glioblastoma cells irradiated with protons and carbon ions with different energy, as a function of dose (and fluence).

The present investigation aimed to characterise the shape of dose-response curve and determining the frequency distribution of various aberration types as a function of dose and radiation quality in AG01522 primary human fibroblasts in the 0.1- to 1-Gy dose range. For this purpose, the cells were irradiated with 7.7 and 28.5 keV µm(-1) low-energy protons, 62 keV µm(-1 4)He(2+) ions (LNL Radiobiology facility) or X rays and samples collected for 24-colour mFISH analysis. X rays and 7.7 keV µm(-1) protons displayed a quadratic dose-response curve solely for total and simple exchanges, whereas for high-linear energy transfer radiations, a linear dose-response curve was observed for all the aberration categories, with the exception of complex exchanges.

Telomere integrity is important for chromosome stability. The main objective of our study was to investigate the relationship between telomere length modulation and mitotic chromosome segregation induced by ionizing radiation in human primary fibroblasts. We used X-rays and low-energy protons because of their ability to induce different telomeric responses. Samples irradiated with 4 Gy were fixed at different times up to 6 days from exposure and telomere length, anaphase abnormalities, and chromosome aberrations were analyzed. We observed that X-rays induced telomere shortening in cells harvested at 96 hrs, whereas protons induced a significant increase in telomere length at short as well as at long harvesting times (24 and 96 hrs). Consistent with this, the analysis of anaphase bridges at 96 hrs showed a fourfold increase in X-ray- compared with proton-irradiated samples, suggesting a correlation between telomere length/dysfunction and chromosome missegregation. In line with these findings, the frequency of dicentrics and rings decreased with time for protons whereas it remained stable after X-rays irradiation. Telomeric FISH staining on anaphases revealed a higher percentage of bridges with telomere signals in X-ray-treated samples than that observed after proton irradiation, thus suggesting that the aberrations observed after X-ray irradiation originated from telomere attrition and consequent chromosome end-to-end fusion. This study shows that, beside an expected "early" chromosome instability induced shortly after irradiation, a delayed one occurs as a result of alterations in telomere metabolism and that this mechanism may play an important role in genomic stability.

The radiation induced free radical damage in Chinese hamster lung fibroblast V-79 cells stored in DMEM culture medium containing 10% DMSO has been investigated by matrix EPR spectroscopy in connection with the H2O/DMSO binary phase diagram. A major part of the indirect effect is due to radicals from the DMSO·3H2O phase in the freezing medium, which are released on warming in the temperature range between 130 K and 160 K, that is, far below the eutectic melting temperature (210 K). The radicals trapped in the DMSO·3H2O phase react with oxygen above 160 K giving reactive oxygen species (ROS) of the type of peroxyl radicals. A lower limit yield of 10–15% was calculated for this conversion. Scavenging experiments with a stable nitroxyl radical (tempol) have demonstrated that part of the DMSO·3H2O radicals escape by mutual recombination on melting and are therefore available for inducing indirect cell damage. The same experiments performed with pure frozen water have shown that OH radicals are not available for inducing cell damage. The EPR measurements performed on H2O/DMSO frozen mixtures suggest that the radiation induced radical forming process does not change when passing to the low dose range below 1 Gy, in agreement with the linear model.

High-resolution multicolour banding FISH (mBAND) and multiplex FISH (mFISH) were used to analyse the aberrations of chromosome 1 in irradiated-AG01522 human primary fibroblasts. The cells were exposed to 1Gy of a panel of radiation of different qualities, such as X-rays, low-energy protons (28keV/μm), helium-ions (62keV/μm) and carbon-ions (96 and 252keV/μm). mBAND and mFISH analysis in calyculin-A G2-condensed chromosome spreads allowed us to detect intra- and interchromosome aberrations involving chromosome 1, including simple and complex-type exchanges, inversions (both para- and pericentric ones), deletions and rings. The data indicate that the induction of chromosomal exchanges was influenced by both Linear energy transfer (LET) and particle types. Moreover, the complex-to-simple exchanges ratio (C-ratio) and interchromosome to intrachromosome exchanges ratio (F-ratio) were evaluated by mFISH and mBAND techniques, respectively. Our results indicate that the C-ratio is a more reliable marker of radiation quality, with values that increased linearly in an LET-dependent manner. In addition, by means of mBAND analysis, the distribution of radiation-induced breakpoints along chromosome 1 was analyzed and compared with the expected distributions of the breaks. The expected values were calculated assuming a random distribution of the breakpoints. The data indicate that, irrespective of the radiation that was used, the breakpoints were non-randomly distributed along chromosome 1. In particular, breaks in the pericentromeric region were encountered at a higher frequency than expected. A deeper analysis revealed that breaks were not located in the constitutive heterochromatin (G-bands 1p11/1q11 and 1q12), but rather in a region comprised between 1p11.2 and 1p22.1, which includes G-light and G-dark bands.

Practical assessment of human radiation exposure risk deserves particular attention especially for low doses (and low dose rates), which concern environmental and occupational exposure. At these dose levels ionizing radiation exposures involve mainly isolated charged particle tracks, which strike individual cells at time intervals averaging from weeks to several years apart. Accelerator-based microbeam irradiation technique offers a unique tool to mimic such an exposure, allowing irradiating single cells individually with micrometer precision and with a preset number of charged particles down to one particle per cell. A horizontal single-ion microbeam facility for single-cell irradiations has been designed and set up at the INFN-LNL 7MV CN Van de Graaff accelerator. The light ion beam is collimated in air down to a section of 2-3µm in diameter by means of appropriate pinholes. Semi-automatic cell visualization and automatic cell positioning and revisiting system, based on an inverted phase contrast optical microscope and on X-Y translation stages with 0.1µm positioning precision, has been developed. An in-house-written software allows to control remotely the irradiation protocol. As a distinctive feature of the facility, cell recognition is performed without using fluorescent staining and UV light. Particle detection in air, behind the biological sample, is based on a silicon detector while in-air beam profile and precise hit position measurements are accomplished by a custom-made cooled-CCD camera and Solid State Nuclear Track detectors, respectively. A particle counting rate of less than 1 ion/sec can be reached.

Charged-particle microbeams are unique tools to mimic low-dose exposure in vitro by delivering a defined number of particles to single mammalian cells down to only one particle per cell or group of cells. A horizontal single-ion microbeam facility has been built at the INFN-Laboratori Nazionali di Legnaro 7 MV Van de Graaff accelerator. Different light ions (1H+, 2H+, 3He2+, 4He2+) are available covering a wide range of LET from 7 to 150 keV/microm. Collimators of different geometries and materials have been tested, and beam spots 2-3 microm in diameter have been obtained using a tantalum disc. Cell visualization and recognition are performed with a phase-contrast optical microscope coupled with dedicated software. One unique characteristic of such a system is that neither cell staining nor UV light is used. Cells are automatically positioned on the beam spot through remotely controlled precision XY translation stages. A particle detector is positioned downstream of a specially designed petri dish to perform energy measurements and count particles crossing the cell. A particle counting rate of less than 1 ion/s can be reached. This feature, combined with a fast beam deflection system, ensures high reproducibility in administering a preset number of particles per cell.

To quantify the role played by radiation track structure and background fragments in modulating DNA fragmentation in human cells exposed to gamma-rays and light ions.Human fibroblasts were exposed in vitro to different doses (in the range from 40 - 200 Gy) of (60)Co gamma-rays and 0.84 MeV protons (Linear Energy Transfer, LET, in tissue 28.5 keV/microm). The resulting DNA fragments were scored under two electrophoretic conditions, in order to optimize separation in the size ranges 0.023 - 1.0 Mbp and 1.0 - 5.7 Mbp. In parallel, DNA fragmentation was simulated both with a phenomenological approach based on the "generalized broken-stick" model, and with a mechanistic approach based on the PARTRAC (acronym of PARticle TRACk) Monte Carlo code (1.32 MeV photons were used for the simulation of (60)Co gamma-rays).For both gamma-rays and protons, the experimental dose response in the range 0.023 - 5.7 Mbp could be approximated as a straight line, the slope of which provided a yield of (5.3 +/- 0.4) x 10(-9) Gy(-1) bp(-1) for gamma-rays and (7.1 +/- 0.6) x 10(-9) Gy(-1) bp(-1) for protons, leading to a Relative Biological Effectiveness (RBE) of 1.3 +/- 0.2. From both theoretical analyses it appeared that, while gamma-ray data were consistent with double-strand breaks (DSB) random induction, protons at low doses showed significant deviation from randomness, implying enhanced production of small fragments in the low molecular weight part of the experimental range. The theoretical analysis of fragment production was then extended to ranges where data were not available, i.e. to fragments larger than 5.7 Mbp and smaller than 23 kbp. The main outcome was that small fragments (23 kbp) are produced almost exclusively via non-random processes, since their number is considerably higher than that produced by a random insertion of DSB. Furthermore, for protons the number of these small fragments is a significant fraction (about 20%) of the total number of fragments; these fragments remain undetected in these experiments. Calculations for 3.3 MeV alpha particle irradiation (for which no experimental data were available) were performed to further investigate the role of fragments smaller than 23 kbp; in this case, besides the non-random character of their production, their number resulted to be at least as much as half of the total number of fragments.Comparison between experimental data and two different theoretical approaches provided further support to the hypothesis of an important role of track structure in modulating DNA damage. According to the theoretical approaches, non-randomness of fragment production was found for proton irradiation for the smaller fragments in the experimental size range and, in a significantly larger extent, for fragments of size less than 23 kbp, both for protons and alpha particles.

To evaluate and compare cytotoxic and mutational effects of graded doses of gamma-rays and 4He++ ions at different LET values (nominally 80 and 123 keV/microm) in V79 cells.4He++ ion beams at 80 and 123 keV/microm were supplied by the 7 MV Van de Graaff CN accelerator of the INFN-LNL in the dose range 0.3 2.4 Gy at a dose rate of 1 Gy/min. Gamma-irradiation was performed by the 60Co 'gamma beam' of CNR-FRAE (at the INFN-LNL) in the dose range 0.5 6.0 Gy at a dose rate of 1 Gy/min. After irradiation, the cells were seeded to measure surviving fraction (SF) and mutant frequency (MF) at the Hprt locus on the basis of 6-thioguanine resistance. Alterations at minisatellite sequences (MS) of clones derived from irradiated and unirradiated cells were detected by Southern blot analysis using a multi-locus probe (DNA fingerprinting).Survival data from 4He++ irradiation at two LET values (80 and 123 keV/microm) yielded similar results: alpha = (1.08 +/- 0.04)/Gy and (0.90 +/- 0.03)/Gy, respectively. The best fit for mutant induction at the Hprt locus after 80keV/microm 4He++ was a linear function of the dose in the dose-interval 0-1.5 Gy: alpha= (47.77 +/- 16.01) x 10(-6)/Gy. The best fit for mutant induction after 123 keV/microm 4He++ in the dose-interval 0-1.2 Gv was a linear-quadratic function: alpha=(86.01 +/- 13.80) x 10(-6)/Gy; beta = (42.87 +/- 11.03) x 10(-6)/Gy2. For gamma-irradiation, the best fit of Hprt mutation data gave: alpha = (4.14+2.67)x 10(-6)/Gy: beta = (0.63 +/- 0.86) x 10(-6)/Gy2. The best fitting of MS alteration data with linear-quadratic or linear relationships gave: for gamma-rays, alpha = 0.56 mutants/Gy and beta = 0.52 mutants/Gy2; for 80 keV/microm 4He++, alpha = 3.70 mutants/Gy and beta = 9.00 mutants/Gy2; for 123keV/microm 4He++, alpha = 4.36 mutants/Gy.The results reported here confirmed the higher cytotoxic and mutagenic effects of helium ions in comparison with gamma-irradiation and the ability of DNA fingerprint analysis to investigate DNA damage induced by different ionizing radiations. The results of the mutagenic effects measured by the two tests are in agreement.

Blind holes (columnar defects created only across a part of the samples) and crossing columnar defects are compared as tools to enhance the superconducting properties of Bi-2212 single crystals. These two different kinds of defects are created, into two twin samples by means of Au ion irradiation, respectively. Extrinsic defects are competing with particular intrinsic defects (shaped as “lamellae”) which control the flux entering in such crystals. Complementary measurements are performed by means of susceptometric and magneto-optical analysis. It is shown that blind holes are at least as effective as crossing columnar defects in competing with these intrinsic defects in different vortex phases.

Elucidation of how effects of densely ionizing radiation at cellular level are linked to DNA damage is fundamental for a better understanding of the mechanisms leading to genomic damage (especially chromosome aberrations) and developing biophysical models to predict space radiation effects. We have investigated the DNA fragmentation patterns induced in Chinese hamster V79 cells by 31 keV/micrometer protons, 123 keV/micrometer helium-4 ions and gamma rays in the size range 0.023-5.7 Mbp, using calibrated Pulsed Field Gel Electrophoresis (PFGE). The frequency distributions of fragments induced by the charged particles were shifted towards smaller sizes with respect to that induced by comparable doses of gamma rays. The DSB yields, evaluated from the fragments induced in the size range studied, were higher for protons and helium ions than for gamma rays by a factor of about 1.9 and 1.2, respectively. However, these ratios do not adequately reflect the RBE observed on the same cells for inactivation and mutation induced by these beams. This is a further indication for the lack of correlation between the effects exerted at cellular level and the initial yield of DSB. The dependence on radiation quality of the fragmentation pattern suggests that it may have a role in damage repairability. We have analyzed these patterns with a "random breakage" model generalized in order to consider the initial non-random distribution of the DNA molecules. Our results suggest that a random breakage mechanism can describe with a reasonable approximation the DNA fragmentation induced by gamma rays, while the approximation is not so good for light ions, likely due to the interplay between ion tracks and chromatin organization at the loop level.

To study the induction and the time-course of rejoining of DNA double strand breaks (DSB) in V79 cells irradiated with light ions with different linear energy transfer (LET).V79 cells were irradiated in monolayer with monoenergetic proton, deuteron, helium-3 or helium-4 ion beams, each at two different energy values. Gamma rays were used as reference radiation. DSB have been measured by constant field gel electrophoresis (CFGE).The initial yield depended little on the particle type and LET. The amount of DSB left unrejoined for up to 2 h incubation time could be roughly described by a decreasing exponential function with a final plateau, although more complex functions cannot be excluded. Radiation quality had little effect on the rejoining rate but affected the plateau. The amount of residual DSB after 2 h was higher for densely than for sparsely ionizing radiation, and for the same particle was dependent on LET. The corresponding RBE ranged from 1.8 to 6.0.The results support the hypothesis that complex, less reparable DSB are induced in higher proportion by light ions with respect to gamma-rays and that, for the same ion, increasing LET leads to an increase in this proportion.

The possibility to enhance in a predictable way the superconducting properties behavior of a bulk material by introducing linearly correlated defects within a surface layer has been demonstrated. Ag/BSCCO-2223 tapes were irradiated by means of 0.25 GeV Au ions at different fluences, with a dose equivalent field B ϕ ranging from 1 T to 5 T. The implantation depth was about 15 μm corresponding to about 15% of the total sample thickness. Sample independent enhancements of different a.c and d.c properties show up, due to vortex confinement in the whole sample. The sample independence exhibited by all the experimental findings as well as, on the other side, the dose dependence of the enhancements, allow to design in advance the performances of a monofilamentary tape where defect trenches of nanometric size are scratched.

Purpose RBE-LET relationships for cell inactivation and hprt mutation in V79 cells have been studied with mono-energetic low-energy proton beams at the radiobiological facility of the INFN-Laboratori Nazionali di Legnaro (LNL), Padova, Italy. Materials and methods V79 cells were irradiated in mono-layer on mylar coated stainless steel petri dishes, in air. Inactivation data were obtained at 7.7, 34.6 and 37.8 keV/microm and hprt mutation was studied at 7 7 and 37.8 keV/microm. Additional data were also collected for both the end points with the proton LET already considered in our previous publications, namely 11.0, 20.0 and 30.5 keV/microm. Results A maximum in the RBE-LET relationship for cell inactivation was found at around 31 keV/microm, while the RBE for mutation induction increased continuously with LET. Conclusions The proton RBE-LET relationship for cell inactivation is shifted to lower LET values compared with that for heavier ions. For mutation induction, protons of LET equal to 7.7keV/microm gave an RBE value comparable with that obtained by helium ions of about 20 keV/microm. Mutagenicity and lethality caused by protons at low doses in the LET range 7.7-31 keV/microm were proportional, while the data at 37.8 keV/microm suggest that this may not hold at higher LET values.

The possibility of predictably enhancing the critical current density of a bulk material with a strong uncorrelated disorder by introducing linearly correlated defects into just the top and bottom surface layers has been investigated. The task was fully demonstrated for melt-textured YBa2Cu3O7−δ having irradiation modified percent thickness ranging from 13% to 5%. The characteristic signatures of vortex localization were observed in the higher range of temperature and magnetic field.

We compare temperature and magnetic field dependence of the critical current density of melt textured YBCO, irradiated with monoenergetic 3.5 and 6.5 MeV protons, and with 235 MeV Au ions, respectively. The Au irradiation affected only a surface layer on the top and on the bottom of our bulk samples,i.e. a volume fraction ranging, in different specimens, from 5% to 13% of the total volume. The point-like defects producedJc enhancements decreasing with the temperature up to a (B, T) point where a crossover to damage occurs. On the contrary, surface columnar defects allow to control the vortex dynamics in the full sample, so that the critical current density enhancement increases as the temperature and the magnetic-field increase. While the addition of point-like defects does not significantly modify the irreversibility line (IL), the ILs of the Au irradiated samples present a shift towards higher temperature as well as smooth matching effects near the dose equivalent field. Magnetic relaxation rates andJc measurements give results in accordance with recent theoretical findings.

Mitochondria are the main cellular source of Reactive Oxygen Species (ROS). Alterations of mitochondrial metabolism and consequent loss of mitochondrial membrane potential may lead to redox imbalance and in turn to DNA damage, chromosomal instability and apoptosis. On the other hand, impaired mitochondrial functions may either exacerbate the detrimental effects of geno- and cytotoxic agents or may bring beneficial cellular responses. To study the role of mitochondria within this framework, AG01522 human primary fibroblasts were incubated with the mitochondrial polymerase γ inhibitor 2',3'-dideoxycytidine (ddC), leading to mitochondrial DNA (mtDNA) depletion and to mitochondrial dysfunctions. The successful treatment toward mtDNA depletion was confirmed by Complex-IV subunit I (COX-I) immunofluorescence and western blot assays. mtDNA-depleted cells and their counterparts were ultrastructurally characterized by transmission electron microscopy. mtDNA-depleted cells showed dramatic mitochondrial alterations such as fragmentation and cristae disruption along with a reduction of the mitochondrial membrane potential and elevated levels of ROS. Despite increased ROS levels, we did not find any difference in telomere length between ddC-treated and untreated cells. The spontaneous rate of DNA double-strand breaks (DSBs) and chromosome aberrations was significantly enhanced in mtDNA-depleted cells whereas the induction of DSBs by low-Linear Energy Transfer (LET) (X-rays; 7.7keV/μm protons) and high-LET radiations (28.5keV/μm protons) did not differ when compared with normal cells. However, in irradiated cells impaired mitochondrial functions seemed to bring beneficial cellular responses to the detrimental effect of radiations. In fact, after X-irradiation mtDNA-depleted cells show less remaining unrejoined DSBs than normal cells and furthermore a lower induction of cytogenetic damage. Overall, these data show that active mitochondrial functions are required for the proper maintenance of cellular genome stability in primary fibroblasts.

The paper deals with nanostructuring of superconducting materials by means of swift heavy ion beams. The aim is to modify their structural, optical and electromagnetic properties in a controlled way, to provide possibility of making them functional for specific applications. Results are presented concerning flux pinning effects (implantation of columnar defects with nanosize cross section to enhance critical currents and irreversibility fields), confined flux-flow and vortex guidance, design of devices by locally tailoring the superconducting material properties, analysis of disorder-induced effects in multi-band superconductors. These studies were carried out on different kinds of superconducting samples, from single crystals to thin films, from superconducting oxides to magnesium diboride, to recently discovered iron-based superconductors.

""Purpose: Biological effects produced by low doses of ionizing radiations, though relevant for the risk assessment, have not been fully elucidated. The aim of the present work was to evaluate cytogenetic endpoints, as telomere dysfunctions and chromosome instability in the low-dose range as a function of radiation quality. In particular, we analyzed whether the telomere length was modulated, as well as the involvement of telomeres in chromosomal alterations at anaphase, and the yield of stable simple and complex chromosome aberrations. Materials and methods: AG01522 human primary fibroblasts were irradiated with 0.1-1 Gy of X-rays, protons (28.5 keV\\\/μm), and 4He2+ ions (62 keV\\\/μm). Frequency of chromosome bridges carrying or not telomeric signals and telomere length were measured in irradiated samples up to 72 h. Moreover, chromosome instability was measured using multicolor fluorescence in situ hybridization (mFISH). Results: The results evidenced a linear energy transfer (LET)- and dose-dependent response in the frequency of anaphase bridges induction and in their persistence as a function of time. However, neither variation in telomere length and telomere loss, nor in the proportion of bridges bearing telomeric signals, was detected, thus indicating a minor role of telomeres in the generation of the radiation-induced chromosome bridges. Chromosome instability followed a linear-dependence with dose and LET, showing a far higher extent of complex translocations in helium-ion-irradiated cells than in proton- or X-ray-irradiated samples. Conclusions: Altogether, the results indicated the lack of telomere involvement in cytogenetic effects induced by low-dose ionizing radiation. On the contrary, chromosome aberration yield and spectrum were LET- and dose-dependent.. . ""

PIGE and PIXE techniques were employed for the determination of the major, minor and trace elemental concentrations in chewing sticks of pharmacological importance namely: Butyrospermum paradoxum, Garcinia kola, Distemonanthus benthamianus, Bridelia ferruginea, Anogeissus leiocarpus, Terminalia glaucescens and Fagara rubescens, respectively. The concentration of fluorine which is very important for human dental enamel was specially determined using the 19F(p, p′γ)19F reaction. For decades these chewing sticks when used alone without toothpastes have proven to be very efficient, effective and reliable in cleaning the teeth of many people particularly in Nigeria and some other countries in Africa. The teeth of users are usually very strong, clean, fresh and devoid of germs and caries. Even with the advent of modern toothpastes with special additions of fluorine, the use of these popular and efficient chewing sticks is still unabated. Many people including the elite use them solely, a few others combine their use with modern toothpastes and brush. Proton beams produced by the 7 MV CN and 2.5 MV AN 2000 Van de Graaff accelerators at INFN, Laboratori Nazionali di Legnaro (LNL), Padova, Italy were used for the PIGE and PIXE analysis, respectively. Results of this novel study are presented and discussed.

The complementary nuclear techniques of PIXE, PIGE, SEM and EDAX were employed to the study of geological samples from Wuyo, North East of Nigeria. The geological samples studied include (i) sandstones (fresh, mylonised and silicified), (ii) granites (fresh and brecciated) and (iii) brecciated and uraniferous samples. The microstructure of the samples was studied using SEM, while PIXE, PIGE and EDAX gave the qualitative and quantitative geochemical data of the major, minor and trace elements in them. PIXE and PIGE measurements were carried out using proton beams produced by the 2.5 MV AN-2000 and 7 MV CN Van de Graaff accelerators at INFN-Laboratori Nazionali di Legnaro (LNL), Padova, Italy, respectively. The facilities at the same institute were used for the SEM and EDAX measurements. Results of this novel study are presented and discussed.

PIGE-PIXE nuclear techniques were employed for the determination of the elemental composition of human breast milk which is the main source of nutrients to babies in Nigeria. Samples were collected from 32 healthy lactating mothers from Obafemi Awolowo Teaching University Hospital, Ile-Ife, Nigeria. The samples were homogenized and immediately frozen, and then freeze-dried. Pellets were made using a Perkin Elmer instrument and its accessory the 13 mm die. PIGE measurements of light elements were performed using 3.5 MeV collimated protons from the 7 MV CN Van de Graaff accelerator of INFN, LNL, Legnaro (Padova) Italy while PIXE analysis was carried out using 1.8 MeV collimated proton beam from the 2.5 MV AN 2000 Van de Graaff accelerator of the same Institute. The results show the presence of important elements that are essential for growth and development of babies. We searched for certain toxic elements which include As, Cd, Hg, Pb, etc. because of their negative roles in enhancing infant mortality rates, but none of them was detected except Pb.

This paper deals with proton irradiation effects on the intragrain and intergrain magnetic and transport properties of sintered YBCO. We have irradiated slab-shaped samples with beams at different fluences and energies, aiming at checking the possibility to modify in a planned way critical currents by means of proton implantation. Magnetic characterizations show enhanced intragrain pinning. Emphasis is given to the possibility to modulate intergrain magnetic properties by irradiation, determining critical current enhancement in optimal field and temperature ranges. Resistive measurements were performed in order to investigate the complex transport phenomena in polycrystalline materials, where superconducting and normal conduction mechanisms coexist. Irradiation-induced effects on both superconducting and normal state resistivity are studied. The addition of extrinsic defects leads to enhanced transport properties, emerging especially when a magnetic field is applied.

Within the framework of radiation biophysics research in the hadrontherapy field, split-dose studies have been performed on four human cell lines with different radiation sensitivity (SCC25, HF19, H184B5 F5-1 M10, and SQ20B). Low energy protons of about 8 and 20 keV/micron LET and gamma-rays were used to study the relationship between the recovery ratio and the radiation quality. Each cell line was irradiated with two dose values corresponding to survival levels of about 5% and 1%. The same total dose was also delivered in two equal fractions separated by 1.5, 3, and 4.5 hours. A higher maximum recovery ratio was observed for radiosensitive cell lines as compared to radioresistant cells. The recovery potential after split doses was small for slow protons, compared to low-LET radiation. These data show that radiosensitivity may not be related to a deficient recovery, and suggest a possible involvement of inducible repair mechanisms.

This study investigated the efficiency of Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR) repair systems in rejoining DNA double-strand breaks (DSB) induced in CCD-34Lu cells by different γ-ray doses. The kinetics of DNA repair was assessed by analyzing the fluorescence decrease of γ-H2AX foci measured by SOID (Sum Of Integrated Density) parameter and counting foci number in the time-interval 0.5–24 hours after irradiation. Comparison of the two methods showed that the SOID parameter was useful in determining the amount and the persistence of DNA damage signal after exposure to high or low doses of ionizing radiation. The efficiency of DSB rejoining during the cell cycle was assessed by distinguishing G1, S, and G2 phase cells on the basis of nuclear fluorescence of the CENP-F protein. Six hours after irradiation, γ-H2AX foci resolution was higher in G2 compared to G1 cells in which both NHEJ and HR can cooperate. The rejoining of γ-H2AX foci in G2 phase cells was, moreover, decreased by RI-1, the chemical inhibitor of HR, demonstrating that homologous recombination is at work early after irradiation. The relevance of HR in DSB repair was assessed in DNA-PK-deficient M059J cells and in CCD-34Lu treated with the DNA-PKcs inhibitor, NU7026. In both conditions, the kinetics of γ-H2AX demonstrated that DSBs repair was markedly affected when NHEJ was absent or impaired, even in G2 phase cells in which HR should be at work. The recruitment of RAD51 at DSB sites was, moreover, delayed in M059J and in NU7026 treated-CCD-34Lu, with respect to DNA-PKcs proficient cells and continued for 24 hours despite the decrease in DNA repair. The impairment of NHEJ affected the efficiency of the HR system and significantly decreased cell survival after ionizing radiation, confirming that DSB rejoining is strictly dependent on the integrity of the NHEJ repair system.

Telomere integrity is important for chromosome stability. The main objective of our study was to investigate the relationship between telomere length modulation and mitotic chromosome segregation induced by ionizing radiation in human primary fibroblasts. We used X-rays and low-energy protons because of their ability to induce different telomeric responses. Samples irradiated with 4 Gy were fixed at different times up to 6 days from exposure and telomere length, anaphase abnormalities, and chromosome aberrations were analyzed. We observed that X-rays induced telomere shortening in cells harvested at 96 hrs, whereas protons induced a significant increase in telomere length at short as well as at long harvesting times (24 and 96 hrs). Consistent with this, the analysis of anaphase bridges at 96 hrs showed a fourfold increase in X-ray- compared with proton-irradiated samples, suggesting a correlation between telomere length/dysfunction and chromosome missegregation. In line with these findings, the frequency of dicentrics and rings decreased with time for protons whereas it remained stable after X-rays irradiation. Telomeric FISH staining on anaphases revealed a higher percentage of bridges with telomere signals in X-ray-treated samples than that observed after proton irradiation, thus suggesting that the aberrations observed after X-ray irradiation originated from telomere attrition and consequent chromosome end-to-end fusion. This study shows that, beside an expected "early" chromosome instability induced shortly after irradiation, a delayed one occurs as a result of alterations in telomere metabolism and that this mechanism may play an important role in genomic stability.

Bulk slabs of sintered YBCO were irradiated with monoenergetic protons at different energies (3.5 and 6.5 MeV) and different fluences, ranging from 1.8·1016 to 8.6·1016 p/cm2. The effects on intergrain critical currents of protons crossing the sample and the effects of protons implanting in the specimen, has been studied by means of a.c. susceptibility characterizations. D.c. hysteresis cycles were measured in low fields in order to investigate the modifications in the intergrain critical current density due to proton implantation. The main result is the evidence that the intergrain J c response to the applied field can be modulated by means of the proton irradiation. Resistive measurements were also performed in order to investigate the complex transport phenomena in polycrystalline materials. Irradiation-induced effects on both superconducting- and normal-state resistivity are studied. The addition of extrinsic defects can lead to enhanced transport properties, emerging especially when a magnetic field is applied.

The results for inactivation of V79 cells irradiated by monoenergetic deuterons with LET of 18, 26 and 31 keV.µm-1 and their direct comparison with protons of comparable LET are presented. The experimental results show that at 31 keV.µm-1 cell inactivation is similar for protons and deuterons while, at lower LET, deuterons appear to be less lethal than protons. The use of parameters other than L(, such as L100 or Z2 eff/ß2, does not completely reconcile the differences in biological effectiveness among the particles pointing out their inadequacy for describing the radiation quality of light ions. The experimental results have been compared with the Monte Carlo track structure simulations, using the code MOCA 14, carried out for monoenergetic track segments of protons, deuterons and alpha particles of selected LET in the range 20-40 keV.µm-1. Existing track structure codes, and indeed essentially all other physical descriptions of radiations used to date, are unable to explain the observed differences in biological effectiveness between deuterons and protons.

Previous and recent results on transport properties of sintered YBCO before and after 6.5 MeV proton implantation are reported. The samples under study come from two different batches, processed by nominally identical preparation methods. For the first batch, irradiation produces enhancement of the critical current density, while for the second one an average damage is observed. An SEM analysis of two different samples shows dissimilar preirradiation grain boundary structures. We infer that these different structures are responsible for the dissimilar response to the irradiation.

Telomeres are the end of linear chromosomes, responsible for chromosome stability and cell viability. It is well known that radiations are able to induce chromosome instability but it has not yet been investigated whether telomere structure is affected by the radiation exposure and if radiations with different quality act in a different way on telomeres. The effect of radiations with different quality on telomere structure and chromosome instability was analysed in human primary fibroblasts exposed to X rays or low-energy protons (28.5 keV μm(-1)). Telomere length was evaluated at different harvesting times from 24 h up to 360 h (15 days), whereas chromosome instability was evaluated in terms of sister chromatid exchanges (SCEs) (48 h from irradiation) and chromosome painting (360 h from irradiation). Results indicated a delayed telomere lengthening 360 h after X-ray treatment, whereas protons were able to induce such a lengthening shortly from irradiation as well as at longer harvesting times. Data obtained from chromosome instability analysis indicated an increase of SCE frequency only after proton irradiation, but, on the contrary, at the longer harvesting time chromosome painting analysis displayed a higher frequency of aberrations after X-ray treatment, suggesting a role of selective process against highly damaged cells.

A huge body of evidence about the hyper-radiosensitivity and induced radioresistance (HRS/IRR) phenomena and the bystander effect (BE) is reported in the literature, in many cell types and in terms of various biological endpoints, after high- and low-linear energy transfer irradiation. However, the mechanisms underlying these effects together with their inter-relationship, and the correlation of HRS/IRR and BE phenomena with radiation quality are not yet well established and elucidated. To study these phenomena, the radiation response of V79 cells has been evaluated in terms of cell survival after irradiation with broad beams of 7.7- and 28.5-keV μm(-1) protons. HRS/IRR has been investigated also in terms of micronuclei and chromosomal aberration induction. The presence of BE has been investigated with a 'partial shielding irradiation' system, which prevents the irradiation of 35 % (on average) of the cell population. No clear evidence of HRS/IRR, nor of a significant BE response, can be identified in the low-dose region of V79 dose-response curves after proton irradiation of different energies.

It is well established that high-LET radiations efficiently induce chromosome aberrations. However, data on the effect of protons on telomere maintenance, as involved in genomic stability, are scarce and contradictory. Here we demonstrate that high-LET protons induce telomere lengthening in human primary fibroblasts and that this elongation does not involve the telomerase enzyme, supporting the hypothesis that high-LET radiations are able to activate a telomerase-independent mechanism. In tumor cells that lack telomerase, one or more non-telomerase mechanisms for telomere maintenance are present, which are termed alternative lengthening of telomeres (ALT). Since ALT cells are characterized by recombinational events at telomeres, known as telomeric-sister chromatid exchanges (T-SCE), and colocalization of telomeres and premyelocytic leukemia protein (PML), we analyzed both T-SCE and PML. Our results show that high-LET protons induce a 2.5-fold increase of T-SCE and a colocalization of PML protein and telomeric DNA. Furthermore, our data show that the ALT pathway can be activated in human primary cells after induction of severe DNA damage. Thus, since telomeres are known to be involved in chromosome maintenance, the present work may contribute in the elucidation of the mechanism by which ionizing radiation induces genomic instability.

Large numbers of trace elements occur in coals used in coal burning power plants. In order to assess the environmental impact of the coal fuel cycle, coal and coal ash samples need to be analyzed for a number of toxic and radioactive elements. In this work we demonstrate the analytical use of X-ray and γ-ray spectroscopies. Concentration levels for a number of trace elements were determined by using X-ray fluorescence (XRF), proton-induced X-ray emission (PIXE), proton induced γ-ray emission (PIGE) and γ-radioactivity spectrometry. Special attention was paid to sample preparation procedures and quality control by analysis of standard reference materials.

Transport properties in pellets of YBCO and BISCO are studied before and after 6.5-MeV proton implantation. The average critical current was strongly enhanced but in one case also weakened, probably due to the unfavorable interaction with the pre-irradiation defect structure. Characteristic parameters are compared and discussed.

The effect of graded doses of high-linear energy transfer (LET) low-energy protons to induce cycle perturbations and genotoxic damage was investigated in normal human fibroblasts. Furthermore, such effects were compared with those produced by low-LET radiations. HFFF2, human primary fibroblasts were exposed to either protons (LET = 28.5 keV/microm) or X/gamma-rays, and endpoints related to cell cycle kinetics and DNA damage analysed. Following both type of irradiations, unsynchronized cells suffered an inhibition to entry into S-phase for doses of 1-4 Gy and remained arrested in the G(1)-phase for several days. The levels of induction of regulator proteins, such as TP53 and CDKN1A showed a clear LET-dependence. DSB induction and repair as measured by scoring for gamma-H2AX foci indicated that protons, with respect to X-rays, yielded a lower number of DSBs per Gy, which showed a slower kinetics of disappearance. Such result was in agreement with the extent of MN induction in binucleated cells after X-irradiation. No significant differences between the two types of radiations were observed with the clonogenic assay, resulting anyway the slope of gamma-ray curve higher than that the proton one. In conclusion, in normal human primary fibroblasts cell cycle arrest at the G(1)/S transition can be triggered shortly after irradiation and maintained for several hours post-irradiation of both protons and X-rays. DNA damage produced by protons appears less amenable to be repaired and could be transformed in cytogenetic damage in the form of MN.

Recent studies have shown that Esie stone sculptures, the largest collection in Africa, were carved using talc-tremolite, talc-chlorite, talc-tremolite-anthophyllite, and talc-amphibolite schists. However, the light elements were not covered because PIXE is not adequate for elements lighter than silicon. For the first time, PIGE analysis of the sculptures and the outcrops were carried out using protons produced by a 7 MV CN Van de Graaff accelerator at INFN Laboratori Nazionali di Legnaro, Padova, Italy, and a Ge(Li) detector. Talc-schists, the material from which the sculptures were carved, are quite important economically, finding use in the manufacture of paint, ceramics, abrasives, tiles, asbestos, cement and a few other metallurgical applications. Results of these novel measurements are presented.

The mutation induction at the HGPRT locus has been studied in V79-753B Chinese hamster cells irradiated with proton beams with energies of 3.36, 1.70 and 1.16 MeV, corresponding to average LET values of 10.6, 17.8 and 23.9 keV/microns, respectively. The mutation curve obtained with 200 kV X-rays was used for comparison. The mutation frequency induced by all the proton beams is considerably higher than that induced at the same dose by X-rays and it is linearly related to the dose. Moreover, the proton effectiveness increases with the LET. The RBEs (evaluated as the initial slope ratios) are 5.0 +/- 0.8, 5.4 +/- 0.8 and 7.7 +/- 1.2 for protons with average LETs of 10.6, 17.8 and 23.9 keV/microns, respectively. These values are higher than those reported in the literature for other ions of comparable LET. This finding parallels what we have already found for cell inactivation (for which RBEs of 3.0, 4.6 and 7.3 were obtained at the same LETs), and indicates that for mutation induction, also, the RBE-LET relationship may depend on the type of radiation.

Human cell line/Carbon-ion beams/Cell inactivation/Relative Biological Effectiveness (RBE)/Linear Energy Transfer (LET). This work aimed at measuring cell-killing effectiveness of monoenergetic and Spread-Out Bragg Peak ( SOBP) carbon-ion beams in normal and tumour cells with different radiation sensitivity. Clonogenic survival was assayed in normal and tumour human cell lines exhibiting different radiosensitivity to X- or γ-rays following exposure to monoenergetic carbon-ion beams (incident LET 13–303 keV/μm) and at various positions along the ionization curve of a therapeutic carbon-ion beam, corresponding to three doseaveraged LET (LETd) values (40, 50 and 75 keV/μm). Chinese hamster V79 cells were also used. Carbon-ion effectiveness for cell inactivation generally increased with LET for monoenergetic beams, with the largest gain in cell-killing obtained in the cells most radioresistant to X- or γ-rays. Such an increased effectiveness in cells less responsive to low LET radiation was found also for SOBP irradiation, but the latter was less effective compared with monoenergetic ion beams of the same LET. Our data show the superior effectiveness for cell-killing exhibited by carbon-ion beams compared to lower LET radiation, particularly in tum our cells radioresistant to X- or γ-rays, hence the advantage of using such beams in radiotherapy. The observed lower effectiveness of SOBP irradiation compared to monoenergetic carbon beam irradiation argues against the radiobiological equivalence between dose-averaged LET in a point in the SOBP and the corresponding monoenergetic beams.

We studied high temperature superconducting devices created by means of local nanostructuring with high-energy heavy-ion lithography. Linear arrays of alternate nanostructured and as-grown YBa2Cu3O7−x film regions are patterned on the microscale. The density of the induced nanostructures is tuned in such a way to locally depress the superconducting properties until a functional electromagnetic decoupling between nanostructured and as-grown microzones is achieved in suitable regions of the (B,T) phase diagram. Pilot prototypes engineered for operating as magnetic field detectors in harsh cryogenic environment are characterized by electric transport and surface morphology analysis at microscale and nanoscale. Sensitivity, linearity range, and bandwidth limits of the pilot prototype are established from electrical transport characterization. The morphological analysis reveals the salient aspects of the surface modifications occurring with high-fluence heavy-ion lithography. Radiation annealing experiments wi...

High-energy heavy-ion beams collimated by means of laser cut stainless-steel masks create microsize mesas surrounded by virgin regions into strip-shaped YBCO films. The ions induce columnar nanostructures whose density is tailored to generate locally weaker superconductivity. FESEM and AFM analyses show evidence of interface boundary regions with upward steps of about 20 nm. The mesas exhibit magneto-resistive performances, functional to localize and confine external electromagnetic excitations. This leads to envisage a road map aimed at using just superconducting electrodynamics for electromagnetic detection.