Neoplastic cell transformation by high-LET radiation: molecular mechanisms.

Experimental data on molecular mechanisms are essential for understanding the bioeffects of radiation and for developing biophysical models, which can help in determining the shape of dose-response curves at very low doses, e.g., doses less than 1 cGy. Although it has been shown that ionizing radiation can cause neoplastic cell transformation directly, that high-LET heavy ions in general can be more effective than photons in transforming cells, and that the radiogenic cell transformation is a multi-step process [correction of processes], we know very little about the molecular nature of lesions important for cell transformation, the relationship between lethal and transformational damages, and the evolution of initial damages into final chromosomal aberrations which alter the growth control of cells. Using cultured mouse embryo cells (C3H10T1/2) as a model system, we have collected quantitative data on dose-response curves for heavy ions with various charges and energies. An analysis of these quantitative data suggested that two DNA breaks formed within 80 angstroms may cause cell transformation and that two DNA breaks formed within 20 angstroms may be lethal. Through studies with restriction enzymes which produce DNA damages at specific sites, we have found that DNA double strand breaks, including both blunt- and cohesive-ended breaks, can cause cell transformation in vitro. These results indicate that DNA double strand breaks can be important primary lesions for radiogenic cell transformation and that blunt-ended double strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship is similar for HGPRT gene mutation, chromosomal deletion, and cell transformation, suggesting common lesions may be involved in these radiation effects. The high RBE of high-LET radiation for cell killing and neoplastic cell transformation is most likely related to its effectiveness in producing DNA double strand breaks in mammalian cells. At present the role of oncogenes in radiation cell transformation is unclear.     

Potential sites for the perception of gravity in the acellular slime mold Physarum polycephalum.

Recently a gravisensitivity of the acellular slime mold Physarum polycephalum, which possesses no specialized gravireceptor, could be established by conducting experiments under simulated and under real near weightlessness. In these experiments macroplasmodia showed a modulation of their contraction rhythm followed by regulation phenomena. Until now the perception mechanism for the gravistimulus is unknown, but several findings indicate the involvement of mitochondria: A) During the impediment of respiration the 0g-reaction is inhibited and the regulation is reduced. B) The response to a light stimulus and the following regulation phenomena strongly resemble the behavior during exposure to 0g, the only difference is that the two reactions are directed into opposite directions. In the blue-light reaction a flavin of the mitochondrial matrix seems to be involved in the light perception. C) The contraction rhythm as well as its modulations are coupled to rhythmic changes in the levels of ATP and calcium ions, involving the mitochondria as sites of energy production and of Ca(++)-storage. So the mitochondria could be the site of the regulation and they possibly are the receptor sites for the light and gravity stimuli. Also the observation of a morphologic polarity of the slime mold's plasmodial strands has to be considered: Cross-sections reveal that the ectoplasmic wall surrounding the streaming endoplasm is much thinner on the physically lower side than on the upper side of the strand--this applies to strands lying on or hanging on a horizontal surface. So, in addition to the mitochondria, also the morphologic polarity may be involved in the perception mechanism of the observed gravisensitivity and of the recently established geotaxis. The potential role of the nuclei and of the contractile elements in the perception of gravity is also discussed.     

Broadband light source for fiber-optic measurement system in spaceborne applications

Measuring temperatures, mechanical loads and derived quantities precisely and reliably play an important role in spaceflight. With spacecraft becoming increasingly complex, upscaling of present telemetry techniques can become cumbersome. Additionally, there are entirely new sensory requirements, resulting from emerging technologies such as smart structures, active vibration damping and composite material health monitoring. It has been demonstrated in preceding studies that these measurements can be advantageously and efficiently carried out by means of fiber-optic systems. The most prominent fiber-optic strain and temperature sensor is the fiber Bragg grating. Typically, multiple fiber Bragg gratings are used to translate entire temperature and strain fields into an optical wavelength information. For the interrogation of these sensors, a broadband or scanning light source is required. Additional requirements with respect to the light source are high intensity and unpolarized illumination of the gratings. These constraints can be met by a light source that is based on amplified spontaneous emission in a rare-earth-doped fiber. In the presented work, a compact light source, adapted for measurement applications and targeted towards space applications, has been developed. The design of this light source is presented, as well as its implementation. The light source has been designed and tested for selected core aspects of space robustness and the results of these tests are summarized.     

Critique of some neural network architectures and claims forcontrol and estimation

While there is great potential for successful use of neural network (NN) algorithms in automatic target recognition (ATR) and other pattern identification/classification applications, significant barriers have been encountered that, to date, defy rigorous use of NNs within feedback control designs. The status of several problems and contradictions involving NNs relating to control and estimation theory applications (and to practical failure detection within INS/GPS navigation systems) are summarized here. To give a positive spin and for a balanced perspective, we also mention many novel laudable NN results obtained by invoking the techniques and results of control and estimation theory     

Neoplastic transformation of hamster embryo cells by heavy ions

We have studied the induction of morphological transformation of Syrian hamster embryo cells by low doses of heavy ions with different linear energy transfer (LET), ranging from 13 to 400 keV/μm. Exponentially growing cells were irradiated with ¹²C or ²⁸Si ion beams generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC), inoculated to culture dishes, and transformed colonies were identified when the cells were densely stacked and showed a crisscross pattern. Over the LET range examined, the frequency of transformation induced by the heavy ions increased sharply at very low doses no greater than 5 cGy. The relative biological effectiveness (RBE) of the heavy ions relative to 250 kVp X-rays showed an initial increase with LET, reaching a maximum value of about 7 at 100 keV/μm, and then decreased with the further increase in LET. Thus, we confirmed that high LET heavy ions are significantly more effective than X-rays for the induction of in vitro cell transformation.     

Repair of DNA double-strand breaks and cell killing by charged particles.

It has been suggested that it is not simple double-strand breaks (dsb) but the non-reparable breaks which correlate well with the high biological effectiveness of high LET radiations for cell killing (Kelland et al., 1988; Radford, 1986). We have compared the effects of charged particles on cell death in 3 pairs of cell lines which are normal or defective in the repair of DNA dsbs. For the cell lines SL3-147, M10, and SX10 which are deficient in DNA dsb repair, RBE values were close to unity for cell killing induced by charged particles with linear energy transfer (LET) up to 200 keV/micrometer and were even smaller than unity for the LET region greater than 300 keV/micrometer. The inactivation cross section (ICS) increased with LET for all 3 pairs. The ICS of dsb repair deficient mutants was always larger than that of their parents for all the LET ranges, but with increasing LET the difference in ICS between the mutant and its parent became smaller. Since a small difference in ICS remained at LET of about 300 keV/micrometer, dsb repair may still take place at this high LET, even if its role is apparently small. These results suggest that the DNA repair system does not play a major role in protection against the attack of high LET radiations and that a main muse of cell death is non-reparable dsb which are produced at a higher yield compared with low LET radiations. No correlation was observed between DNA content or nuclear area and ICS.     

PowerCore combining structure and batteries for increased energy toweight ratio

Much of the mass of a battery is comprised of nonreactive materials. In an NiH₂ battery, this includes the pressure vessel and 50% of the positive electrode. PowerCore reconfigures the battery materials to serve as a structural sandwich panel. The effective specific energy of the new device can exceed 100 Wh/kg. PowerCore is intended to handle power demands of low Earth orbiting communications satellites such as IRIDIUM. This paper describes the concept and development progress     

Effect of track structure and radioprotectors on the induction of oncogenic transformation in murine fibroblasts by heavy ions

The oncogenic potential of high-energy ⁵⁶Fe particles (1 GeV/nucleon) accelerated with the Alternating Gradient Synchrotron at the Brookhaven National Laboratory was examined utilizing the mouse C3H 10T1/2 cell model. The dose-averaged LET for high-energy ⁵⁶Fe is estimated to be 143 keV/μm with the exposure conditions used in this study. For ⁵⁶Fe ions, the maximum relative biological effectiveness (RBE_max) values for cell survival and oncogenic transformation were 7.71 and 16.5 respectively. Compared to 150 keV/μm ⁴He nuclei, high-energy ⁵⁶Fe nuclei were significantly less effective in cell killing and oncogenic induction. The prostaglandin E₁ analog misoprostol, an effective oncoprotector of C3H 10T1/2 cells exposed to X rays, was evaluated for its potential as a radioprotector of oncogenic transformation with high-energy ⁵⁶Fe. Exposure of cells to misoprostol did not alter ⁵⁶Fe cytotoxicity or the rate of ⁵⁶Fe-induced oncogenic transformation.     

Clinorotation reduces number, but not size, of cartilaginous nodules formed in micromass cultures of mouse limbbud cells.

In previous studies we used a ground based model to investigate the cellular responses to microgravity by exposing micromass cultures of embryonic limb cells to simulated weightlessness on a clinostat. Cultures set up in T-flasks and rotated at 30 rpm showed that clinostatted cultures had less chondrocyte differentiation than stationary or rotation controls, as assessed by number of nodules/culture stained with cartilage specific Alcian blue. In the current study, nodule size and shape of these nodules was assessed by interactive measurement of area, perimeter, circularity, and equivalent diameters, using the Optimas imaging software. Results show no significant difference in any of the measurements, indicating that clinorotation has no effect on expansion of the nodules either by differentiation of cells within the nodule, or by recruitment of cells into the nodule. The reduction in number of nodules without an alteration in size and shape indicates that the effect of simulated microgravity is to reduce the cell interactions required for the initial condensation of cells into a nodule, probably by interference with cell adhesion molecules.     

Ground assisted rendezvous with geosynchronous satellites for the disposal of space debris by means of Earth-oriented tethers

Previous studies have shown that extended length Earth-oriented tethers in the geosynchronous (GEO) region can be used to re-orbit satellites to disposal orbits. One such approach involves the extension of a GEO based tether, collection of a debris object, and retraction of the tether, which transfers the retracted configuration to a higher energy orbit for debris disposal. The re-extension of the tether after debris disposal returns the configuration to the near-GEO altitude. The practical feasibility of such a system depends on the ability to collect GEO debris objects, attach them to a deployed tether system, and retract the tethers for transfer to the disposal orbits.This study addresses the collection and delivery of debris objects to the deployed tether system in GEO. The investigation considers the number, type and the characteristics of the debris objects as well as the collection tug that can be ground controlled to detect, rendezvous and dock with the debris objects for their delivery to the tethers system.A total of more than 400 objects are in drift orbits crossing all longitudes either below or above the geostationary radius. More than 130 objects are also known to librate around the stable points in GEO with periods of libration up to five or more years. A characterization of the position and velocity of the debris objects relative to the collection tug is investigated. Typical rendezvous performance requirements for uncooperative GEO satellites are examined, and the similarities with other approaches such as the ESA's CX-OLEV commercial mission proposal to extend the life of geostationary telecommunication satellites are noted.