DNA damage and repair in oncogenic transformation by heavy ion radiation.

Energetic heavy ions are present in galactic cosmic rays and solar particle events. One of the most important late effects in risk assessment is carcinogenesis. We have studied the carcinogenic effects of heavy ions at the cellular and molecular levels and have obtained quantitative data on dose-response curves and on the repair of oncogenic lesions for heavy particles with various charges and energies. Studies with repair inhibitors and restriction endonucleases indicated that for oncogenic transformation DNA is the primary target. Results from heavy ion experiments showed that the cross section increased with LET and reached a maximum value of about 0.02 micrometer2 at about 500 keV/micrometer. This limited size of cross section suggests that only a fraction of cellular genomic DNA is important in radiogenic transformation. Free radical scavengers, such as DMSO, do not give any effect on induction of oncogenic transformation by 600 MeV/u iron particles, suggesting most oncogenic damage induced by high-LET heavy ions is through direct action. Repair studies with stationary phase cells showed that the amount of reparable oncogenic lesions decreased with an increase of LET and that heavy ions with LET greater than 200 keV/micrometer produced only irreparable oncogenic damage. An enhancement effect for oncogenic transformation was observed in cells irradiated by low-dose-rate argon ions (400 MeV/u; 120 keV/micrometer). Chromosomal aberrations, such as translocation and deletion, but not sister chromatid exchange, are essential for heavy-ion-induced oncogenic transformation. The basic mechanism(s) of misrepair of DNA damage, which form oncogenic lesions, is unknown.     

The role of DNA repair on cell killing by charged particles.

It can be noted that it is not simple double strand breaks (dsb) but the non-reparable breaks that are associated with high biological effectiveness in the cell killing effect for high LET radiation. Here, we have examined the effectiveness of fast neutrons and low (initial energy = 12 MeV/u) or high (135 MeV/u) energy charged particles on cell death in 19 mammalian cell lines including radiosensitive mutants. Some of the radiosensitive lines were deficient in DNA dsb repair such as LX830, M10, V3, and L5178Y-S cells and showed lower values of relative biological effectiveness (RBE) for fast neutrons if compared with their parent cell lines. The other lines of human ataxia-telangiectasia fibroblasts, irs 1, irs 2, irs 3 and irs1SF cells, which were also radiosensitive but known as proficient in dsb repair, showed moderated RBEs. Dsb repair deficient mutants showed low RBE values for heavy ions. These experimental findings suggest that the DNA repair system does not play a major role against the attack of high linear energy transfer (LET) radiations. Therefore, we hypothesize that a main cause of cell death induced by high LET radiations is due to non-reparable dsb, which are produced at a higher rate compared to low LET radiations.     

Austrian dose measurements onboard space station MIR and the International Space Station--overview and comparison.

The Atominstitute of the Austrian Universities has conducted various space research missions in the last 12 years in cooperation with the Institute for Biomedical Problems in Moscow. They dealt with the exact determination of the radiation hazards for cosmonauts and the development of precise measurement devices. Special emphasis will be laid on the last experiment on space station MIR the goal of which was the determination of the depth distribution of absorbed dose and dose equivalent in a water filled Phantom. The first results from dose measurements onboard the International Space Station (ISS) will also be discussed. The spherical Phantom with a diameter of 35 cm was developed at the Institute for Biomedical Problems and had 4 channels where dosimeters can be exposed in different depths. The exposure period covered the timeframe from May 1997 to February 1999. Thermoluminescent dosimeters (TLDs) were exposed inside the Phantom, either parallel or perpendicular to the hull of the spacecraft. For the evaluation of the linear energy transfer (LET), the high temperature ratio (HTR) method was applied. Based on this method a mean quality factor and, subsequently, the dose equivalent is calculated according to the Q(LET infinity) relationship proposed in ICRP 26. An increased contribution of neutrons could be detected inside the Phantom. However the total dose equivalent did not increase over the depth of the Phantom. As the first Austrian measurements on the ISS dosimeter packages were exposed for 248 days, starting in February 2001 at six different locations onboard the ISS. The Austrian dosimeter sets for this first exposure on the ISS contained five different kinds of passive thermoluminescent dosimeters. First results showed a position dependent absorbed dose rate at the ISS.     

Simulation experiments of the effect of space environment on bacteriophage and DNA thin films.

The main goal of PUR experiment (phage and uracil response) is to examine and quantify the effect of specific space conditions on nucleic acid models. To achieve this an improved method was elaborated for the preparation of DNA and bacteriophage thin films. The homogeneity of the films was controlled by UV spectroscopy and microscopy. To provide experimental evidence for the hypothesis that interplanetary transfer of the genetic material is possible, phage T7 and isolated T7 DNA thin films have been exposed to selected space conditions: intense UVC radiation (lambda=254 nm) and high vacuum (10(-4) Pa). The effects of DNA hydration, conformation and packing on UV radiation damage were examined. Characteristic changes in the absorption spectrum, in the electrophoretic pattern of DNA and the decrease of the amount of PCR products have been detected indicating the photodamage of isolated and intraphage DNA.     

Properties and performance of extended target motion analysis

The problem of target motion analysis (TMA) has been the subject of an important literature. However, present methods use data estimated by a short time analysis (azimuths, Dopplers, etc.). For far sources, the nonstationarities of the array processing outputs, induced by the sources motion, may be simply modeled. This model leads one to consider directly a spatio-temporal TMA. Then new (spatio-temporal) data can be estimated. These estimates correspond to a long time analysis. Further, note that they are estimated independently of the (classical) bearings. In this general framework, the concept of source trajectory replaces the classical instantaneous bearings. Corresponding TMA algorithms are then studied. Then the study of statistical performance is carefully studied     

Influence of long-term altered gravity on the swimming performance of developing cichlid fish: including results from the 2nd German Spacelab Mission D-2.

This study presents qualitative and quantitative data concerning gravity-dependent changes in the swimming behaviour of developing cichlid fish larvae (Oreochromis mossambicus) after a 9 resp. 10 days exposure to increased acceleration (centrifuge experiments), to reduced gravity (fast-rotating clinostat), changed accelerations (parabolic aircraft flights) and to near weightlessness (2nd German Spacelab Mission D-2). Changes of gravity initially cause disturbances of the swimming performance of the fish larvae. With prolonged stay in orbit a step by step normalisation of the swimming behaviour took place in the fish. After return to 1g earth conditions no somersaulting or looping could be detected concerning the fish, but still slow and disorientated movements as compared to controls occurred. The fish larvae adapted to earth gravity within 3-5 days. Fish seem to be in a distinct early developmental stages extreme sensitive and adaptable to altered gravity; However, elder fish either do not react or show compensatory behaviour e.g. escape reactions.     

AFIT neural network research

A brief summary of research done at the Air Force Institute of Technology (AFIT) in the area of neural networks is provided. It has been shown that backpropagation, used for feedforward artificial neural networks, is just a degenerate version of an extended Kalman filter, and that networks can do about as well as the optimum statistical classification technique. A method of finding the importance of features for use by a neural network classifier has been determined. Techniques for using neural networks for image segmentation have been developed. In optical pattern recognition, techniques that allow the processing of real FLIR (forward-looking infrared) images with existing binary spatial light modulators have been devised. An optical direction of arrival detector applicable to laser illumination direction determination has been designed and tested; the design is similar to a fly's eye. Coated mirrors for the optical confocal Fabry-Perot interferometer have been designed, specified, fabricated, and installed. Significant progress has been made in the use of neural networks for processing multiple-feature sets for speech recognition     

A wavelet multiresolution analysis for spatio-temporal signals

The wavelet filters of the conventional 3D multiresolution analysis possess homogeneous spatial and temporal frequency characteristics which limits one's ability to match filter frequency characteristics to signal frequency behavior. Also, the conventional 3D multiresolution analysis employs an oct-tree decomposition structure which restricts the analysis of signal details to identical resolutions in space and time. This paper presents a 3D wavelet multiresolution analysis constructed from nonhomogeneous spatial and temporal filters, and an orthogonal sub-band coding scheme that decouples the spatial and temporal decomposition processes     

Simulation of fast ablation

A brief review of studies on simulation and control of a porous cooling process taking into account material transpiration is given. An approximated solution for an equation of the one-dimensional problem of fast ablation is also presented.     

Design and implementation of near-field, wideband synthetic aperture beamformers

A coarray-based near-field, wideband synthetic aperture beamformer using stepped-frequency signal synthesis and post-data acquisition processing is presented. While coarray techniques offer significant reduction in the number of array elements for a given angular resolution, the hybrid subarray-stepped frequency realization of wideband systems simplifies implementations and offers flexibility in beamforming. Proof of concept is provided using real data collected in an anechoic chamber for several pulse shapes and array weightings.