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Cucinotta, F.

Publications and source records attributed to Cucinotta, F..

At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2011

The Analysis of the Patterns of Radiation-Induced DNA Damage Foci by a Stochastic Monte Carlo Model of DNA Double Strand Breaks Induction by Heavy Ions and Image Segmentation Software

To create a generalized mechanistic model of DNA damage in human cells that will generate analytical and image data corresponding to experimentally observed DNA damage foci and will help to improve the experimental foci yields by simulating spatial foci patterns and resolving problems with quantitative image analysis. Material and Methods: The analysis of patterns of RIFs (radiation-induced foci) produced by low- and high-LET (linear energy transfer) radiation was conducted by using a Monte Carlo model that combines the heavy ion track structure with characteristics of the human genome on the level of chromosomes. The foci patterns were also simulated in the maximum projection plane for flat nuclei. Some data analysis was done with the help of image segmentation software that identifies individual classes of RIFs and colocolized RIFs, which is of importance to some experimental assays that assign DNA damage a dual phosphorescent signal. Results: The model predicts the spatial and genomic distributions of DNA DSBs (double strand breaks) and associated RIFs in a human cell nucleus for a particular dose of either low- or high-LET radiation. We used the model to do analyses for different irradiation scenarios. In the beam-parallel-to-the-disk-of-a-flattened-nucleus scenario we found that the foci appeared to be merged due to their high density, while, in the perpendicular-beam scenario, the foci appeared as one bright spot per hit. The statistics and spatial distribution of regions of densely arranged foci, termed DNA foci chains, were predicted numerically using this model. Another analysis was done to evaluate the number of ion hits per nucleus, which were visible from streaks of closely located foci. In another analysis, our image segmentaiton software determined foci yields directly from images with single-class or colocolized foci. Conclusions: We showed that DSB clustering needs to be taken into account to determine the true DNA damage foci yield, which helps to determine the DSB yield. Using the model analysis, a researcher can refine the DSB yield per nucleus per particle. We showed that purely geometric artifacts, present in the experimental images, can be analytically resolved with the model, and that the quantization of track hits and DSB yields can be provided to the experimentalists who use enumeration of radiation-induced foci in immunofluorescence experiments using proteins that detect DNA damage. An automated image segmentaiton software can prove useful in a faster and more precise object counting for colocolized foci images.

Ponomarev, Artem↗
NASA NTRS2011

Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT cells and misrejoined breaks increased in both cell lines. The present study suggests that AT cells begin to rejoin breaks when a certain number of breaks are accumulated and an increased number of exchanges were observed in G0 AT cells, which is similar situation after high-dose-rate irradiation.

Kawata, T.↗
NASA NTRS2006

Understanding Cataract Risk in Aerospace Flight Crew And Review of Mechanisms of Cataract Formation

Induction of cataracts by occupational exposure in flight crew has been an important topic of interest in aerospace medicine in the past five years, in association with numerous reports of flight-associated disease incidences. Due to numerous confounding variables, it has been difficult to determine if there is increased cataract risk directly caused by interaction with the flight environment, specifically associated with added radiation exposure during flight. Military aviator records from the United States Air Force (USAF) and Navy (USN) and US astronauts at the National Aeronautics and Space Administration (NASA)/Lyndon B. Johnson Space Center (JSC) were evaluated for the presence, location and age of diagnosis of cataracts. Military aviators were found to have a statistically significant younger average age of onset of their cataracts compared with astronauts, however the incidence density of cataracts was found to be statistically higher in astronauts than in military aviators. USAF and USN aviator s cataracts were most commonly located in the posterior subcapsular region of the lens while astronauts cataracts were most likely to originate generally in the cortical zone. A prospective clinical trial which controls for confounding variables in examination technique, cataract classification, diet, exposure, and pharmacological intervention is needed to determine what percentage of the risk for cataracts are due to radiation, and how to best develop countermeasures to protect flight crews from radiation bioeffects in the future.

Jones, Jeffrey A.↗
NASA NTRS2004

Requirements for Simulating Space Radiation With Particle Accelerators

Interplanetary space radiation consists of fully ionized nuclei of atomic elements with high energy for which only the few lowest energy ions can be stopped in shielding materials. The health risk from exposure to these ions and their secondary radiations generated in the materials of spacecraft and planetary surface enclosures is a major limiting factor in the management of space radiation risk. Accurate risk prediction depends on a knowledge of basic radiobiological mechanisms and how they are modified in the living tissues of a whole organism. To a large extent, this knowledge is not currently available. It is best developed at ground-based laboratories, using particle accelerator beams to simulate the components of space radiation. Different particles, in different energy regions, are required to study different biological effects, including beams of argon and iron nuclei in the energy range 600 to several thousand MeV/nucleon and carbon beams in the energy range of approximately 100 MeV/nucleon to approximately 1000 MeV/nucleon. Three facilities, one each in the United States, in Germany and in Japan, currently have the partial capability to satisfy these constraints. A facility has been proposed using the Brookhaven National Laboratory Booster Synchrotron in the United States; in conjunction with other on-site accelerators, it will be able to provide the full range of heavy ion beams and energies required. International cooperation in the use of these facilities is essential to the development of a safe international space program.

Schimmerling, W.↗
NASA NTRS2004

Heavy ion observations by MARIE in cruise phase and Mars orbit

The charged particle spectrum for nuclei from protons to neon, (charge Z=10) was observed during the cruise phase and orbit around Mars by the MARIE charged particle spectrometer on the Odyssey spacecraft. The cruise data were taken between April 23, 2001 and mid-August 2001. The Mars orbit data were taken March 5, 2002 through May 2002 and are scheduled to continue until August 2004. Charge peaks are clearly separated for charges up to Z=10. Especially prominent are the carbon and oxygen peaks, with boron and nitrogen also clearly visible. Although heavy ions are much less abundant than protons in the cosmic ray environment, it is important to determine their abundances because their ionization energy losses (proportional to Z2) are far more dangerous to humans and to instruments. Thus the higher charged nuclei make a significant contribution to dose and dose equivalent received in space. Results of the charged particle spectrum measurements will be reported. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

NASA Center JSC↗
NASA NTRS2004

Overview of the Martian radiation environment experiment

Space radiation presents a hazard to astronauts, particularly those journeying outside the protective influence of the geomagnetosphere. Crews on future missions to Mars will be exposed to the harsh radiation environment of deep space during the transit between Earth and Mars. Once on Mars, they will encounter radiation that is only slightly reduced, compared to free space, by the thin Martian atmosphere. NASA is obliged to minimize, where possible, the radiation exposures received by astronauts. Thus, as a precursor to eventual human exploration, it is necessary to measure the Martian radiation environment in detail. The MARIE experiment, aboard the 2001 Mars Odyssey spacecraft, is returning the first data that bear directly on this problem. Here we provide an overview of the experiment, including introductory material on space radiation and radiation dosimetry, a description of the detector, model predictions of the radiation environment at Mars, and preliminary dose-rate data obtained at Mars. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

NASA Program Biomedical Research and Countermeasur↗
NASA NTRS2004

Effects of heavy ions on visual function and electrophysiology of rodents: the ALTEA-MICE project

ALTEA-MICE will supplement the ALTEA project on astronauts and provide information on the functional visual impairment possibly induced by heavy ions during prolonged operations in microgravity. Goals of ALTEA-MICE are: (1) to investigate the effects of heavy ions on the visual system of normal and mutant mice with retinal defects; (2) to define reliable experimental conditions for space research; and (3) to develop animal models to study the physiological consequences of space travels on humans. Remotely controlled mouse setup, applied electrophysiological recording methods, remote particle monitoring, and experimental procedures were developed and tested. The project has proved feasible under laboratory-controlled conditions comparable in important aspects to those of astronauts' exposure to particle in space. Experiments are performed at the Brookhaven National Laboratories [BNL] (Upton, NY, USA) and the Gesellschaft fur Schwerionenforschung mbH [GSI]/Biophysik (Darmstadt, FRG) to identify possible electrophysiological changes and/or activation of protective mechanisms in response to pulsed radiation. Offline data analyses are in progress and observations are still anecdotal. Electrophysiological changes after pulsed radiation are within the limits of spontaneous variability under anesthesia, with only indirect evidence of possible retinal/cortical responses. Immunostaining showed changes (e.g. increased expression of FGF2 protein in the outer nuclear layer) suggesting a retinal stress reaction to high-energy particles of potential relevance in space. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

NASA Center JSC↗
NASA NTRS2004

Solar Particle Events at Mars Seen by MARIE, 2002-2003

The MARIE detector aboard the 200 1 Mars Odyssey operated continuously between March 13, 2002, and October 28, 2003. During these twenty months, approximately 12 periods of enhanced solar particle activity were observed. The last of these, on October 26-28, 2003, caused the instrument to lose communication with the spacecraft. In addition to that very large event, several other major Solar Particle Events (SPEs) were observed. Those prior to March 2003 have been discussed elsewhere [I] and will be reviewed here. Many of the solar events seen at Mars correspond well to observations by GOES and ACE satellites near Earth. Some SPEs were observed by MARIE when Mars was on, or near, the opposite side of the sun as seen from Earth; and while a few of them - most notably the large full-halo Coronal Mass Ejections of July 2002 - coincided with events seen by the near-Earth satellites, others were not seen at Earth. Conversely, in this same time period, some SPEs were seen at Earth but not at Mars. Subsequent to February 2003, three SPEs were observed by MARIE, on March 18- 20, May 28 - June 3, and Oct. 26-28. Observations of solar energetic particles at Mars can be combined with data from other points in the heliosphere from, e.g., the Solar Heliospheric Observatory, ACE/CRIS, and GOES satellites near Earth, and Ulysses. Having several different observation points is useful for testing models of CME initiation and propagation.

Cleghorn, T.↗
NASA NTRS2003

A Comparison of Model Calculation and Measurement of Absorbed Dose for Proton Irradiation

With the increase in the amount of time spent EVA that is necessary to complete the construction and subsequent maintenance of ISS, it will become increasingly important for ground support personnel to accurately characterize the radiation exposures incurred by EVA crewmembers. Since exposure measurements cannot be taken within the organs of interest, it is necessary to estimate these exposures by calculation. To validate the methods and tools used to develop these estimates, it is necessary to model experiments performed in a controlled environment. This work is such an effort. A human phantom was outfitted with detector equipment and then placed in American EMU and Orlan-M EVA space suits. The suited phantom was irradiated at the LLUPTF with proton beams of known energies. Absorbed dose measurements were made by the spaceflight operational dosimetrist from JSC at multiple sites in the skin, eye, brain, stomach, and small intestine locations in the phantom. These exposures are then modeled using the BRYNTRN radiation transport code developed at the NASA Langley Research Center, and the CAM (computerized anatomical male) human geometry model of Billings and Yucker. Comparisons of absorbed dose calculations with measurements show excellent agreement. This suggests that there is reason to be confident in the ability of both the transport code and the human body model to estimate proton exposure in ground-based laboratory experiments.

Zapp, N.↗
NASA NTRS2003

Visualization of Radiation Environment on Mars: Assessment with MARIE Measurements

For a given GCR (Galactic Cosmic Ray) environment at Mars, particle flux of protons, alpha particles, and heavy ions, are also needed on the surface of Mars for future human exploration missions. For the past twelve months, the MARJE (Martian Radiation Environment Experiment) instrument onboard the 200J Mars Odyssey has been providing the radiation measurements from the Martian orbit. These measurements are well correlated with the HZETRN (High Z and Energy Transport) and QMSFRG (Quantum Multiple-Scattering theory of nuclear Fragmentation) model calculations. These model calculations during these specific GCR environment conditions are now extended and transported through the CO2 atmosphere onto the Martian surface. These calculated pa11icle flux distributions are presented as a function of the Martian topography making use of the MOLA (Mars Orbiter Laser Altimeter) data from the MGS (Mars Global Surveyor). Also, particle flux calculations are presented with visualization in the human body from skin depth to the internal organs including the blood-forming organs.

Saganti, P.↗
NASA NTRS2003

Monte Carlo Simulations of the Response of the MARIE Instrument

The MARIE instrument aboard Mars Odyssey functions as a telescope for the detection of charged, energetic, nuclei. The directionality that leads to the telescope description is achieved by requiring coincident signals in two designated detectors in MARIE s silicon detector stack for the instrument to trigger. Because of this, MARIE is actually a bi directional telescope. Triggering particles can enter the detector stack by passing through the lightly shielded front of the instrument, but can also enter the back of the instrument by passing through the bulk of Odyssey. Because of this, understanding how to relate the signals recorded by MARIE to astrophysically important quantities such as particle fluxes or spectra exterior to the spacecraft clearly requires detailed modeling of the physical interactions that occur as the particles pass through the spacecraft and the instrument itself. In order to facilitate in the calibration of the MARIE data, we have begun a program to simulate the response of MARIE using the FLUKA [1] [2] Monte Carlo radiation transport code.

Andersen, V.↗
NASA NTRS2003

Heavy Ion Flux Comparison of MARIE and ACE/CRIS Instruments

The charged particle spectrum for nuclei from protons to neon, (charge Z=10) has been observed during the cruise phase and in orbit around Mars by the MARIE charge particle spectrometer aboard the Odyssey spacecraft. The cruise data was taken between April 23, 2001 and August 11, 2001. The Mars orbit data was taken from March 5, 2002 through December 2002. Both the cruise data set and the orbital data set are compared with the simultaneous observations made by the CRIS instrument aboard the ACE space-craft, located at L1. Any detectable differences between the two spacecraft data sets could lead to the understanding of the radial dependence of solar modulation.

Lee, K. T.↗
NASA NTRS2003

Results from the Martian Radiation Environment Experiment MARIE

One of the three science instruments aboard the 2001 Mars Odyssey spacecraft is the Martian Radiation Environment Experiment, MARIE. MARIE consists of a stack of silicon detectors, augmented by a Cerenkov detector. MARIE is designed to measure a portion of the particle spectrum of the Galactic Cosmic Rays (GCR), as well as the high fluxes of low-energy protons (energies less than about 100 MeV) that are intermittently produced by active regions on the sun in Solar Particle Events (SPE). MARIE is providing the first detailed information about the radiation environment near Mars.measurements. MARIE has been operating successfully for nearly a year. Solar particle events of considerable interest have been observed, and data have been obtained that will yield GCR spectra from a novel observation point in the solar system.

Zeitlin, C.↗
NASA NTRS2002

Exploration of the Mars Radiation Environment Using MARIE

One of three science instruments onboard Mars Odyssey is the Mars Radiation Environment Experiment (MARIE), which is described here. MARIE is an energetic particle spectrometer which will characterize the space radiation environment of Mars and determine its risk to human exploration. Additional information is contained in the original extended abstract.

Cucinotta, F.↗
NASA NTRS2002

Relative biological effectiveness of light ions in human tumoural cell lines: role of protein p53

Protons and alpha particles of high linear energy transfer (LET) have shown an increased relative biological effectiveness (RBE) with respect to X/gamma rays for several cellular and molecular endpoints in different in vitro cell systems. To contribute to understanding the biochemical mechanisms involved in the increased effectiveness of high LET radiation, an extensive study has been designed. The present work reports the preliminary result of this study on two human tumoural cell lines, DLD1 and HCT116, (with different p53 status), which indicate that for these cell lines, p53 does not appear to take a part in the response to radiation induced DNA damage, suggesting an alternative p53-independent pathway and a cell biochemical mechanism dependent on the cell type.

NASA Center JSC↗
NASA NTRS2001

Radiation Transmission Properties of In-Situ Materials

The development of a permanent human presence in space is a key element of NASA's strategic plan for the Human Exploration and Development of Space (HEDS). The habitation of the International Space Station (ISS) is one near-term HEDS objective; the exploration and settlement of the moon and Mars are long-term goals of that plan. Achieving these goals requires maintaining the health and safety of personnel involved in such space operations at a high level, while at the same time reducing the cost of those operations to a reasonable level. Among the limiting factors to prolonged human space operations are the health risks from exposure to the space ionizing radiation environment. In order to keep the risk of radiation induced cancer at acceptable levels, it is necessary to provide adequate shielding from the ionizing radiation environment. The research presented here is theoretical and ground-based experimental study of the neutron production from interactions of GCR-like particles in various shielding components. An emphasis is placed here on research that will aid in the development of in-situ resource utilization. The primary goal of the program is to develop an accurate neutron-production model that is relevant to the NASA HEDS program of designing technologies that will be used in the development of effective shielding countermeasures. A secondary goal of the program is the development of an experimental data base of neutron production cross sections and thick-target yields which will aid model development.

Heilbronn, L.↗
NASA NTRS1998

Evaluation of risk from space radiation with high-energy heavy ion beams

The most challenging radiation in space consists of fully ionized atomic elements with high energy for which only the few lowest energy ions can be stopped in shielding materials. The health risk from exposure to these ions and their secondary radiations generated in shield materials is poorly understood since there are few human data and a systematic study in relevant animal model systems has not been made. The accuracy of risk prediction is described as the major limiting factor in the management of space radiation risk. The expected impact of systematic studies is examined using the limited available biological data and models. Given the limitations of current predictions, models must be developed that are able to incorporate the required fundamental scientific data into accurate risk estimates. The important radiation components that can be provided for laboratory testing are identified. The use of ground-based accelerator beams to simulate space radiation is explained and quantitative scientific constraints on such facilities are derived. Three facilities, one each in the United States, in Germany and in Japan, currently have the partial capability to satisfy these constraints. A facility has been proposed using the Brookhaven National Laboratory Booster Synchrotron in the United States; in conjuction with other on-site accelerators, it will be able to provide the full range of heavy ion beams and energies required.

NASA Discipline Radiation Health↗