Molecular alterations in tumorigenic human bronchial and breast epithelial cells induced by high LET radiation.

Carcinogenesis is a multi-stage process with sequence of genetic events governing the phenotypic expression of a series of transformation steps leading to the development of metastatic cancer. In the present study, immortalized human bronchial (BEP2D) and breast (MCF-10F) cells were irradiated with graded doses of either 150 keV/micrometer alpha particles or 1 GeV/nucleon 56Fe ions. Transformed cells developed through a series of successive steps before becoming tumorigenic in nude mice. Cell fusion studies indicated that radiation-induced tumorigenic phenotype in BEP2D cells could be completely suppressed by fusion with non-tumorigenic BEP2D cells. The differential expressions of known genes between tumorigenic bronchial and breast cells induced by alpha particles and their respective control cultures were compared using cDNA expression array. Among the 11 genes identified to be differentially expressed in BEP2D cells, three (DCC, DNA-PK and p21(CIP1)) were shown to be consistently down-regulated by 2 to 4 fold in all the 5 tumor cell lines examined. In contrast, their expressions in the fusion cell lines were comparable to control BEP2D cells. Similarly, expression levels of a series of genes were found to be altered in a step-wise manner among tumorigenic MCF-10F cells. The results are highly suggestive that functional alterations of these genes may be causally related to the carcinogenic process.     

Distributed flight control system using fiber distributed datainterface (FDDI)

The design of fault-tolerant distributed control systems is discussed. The application described is a generic flight control system (FCS) for a fighter aircraft. The system is designed for high redundancy and expandability to meet various requirements. The communication network is based on the fiber distributed data interface (FDDI), which provides a high level of electromagnetic interference resistance and reliability. The choice of fiber optic media also provides an extremely high bandwidth and tremendous growth capability for future communications needs. This study is not specific to FDDI or flight control systems. The methods and configurations presented should be applicable to many real-time control implementations     

Prototype design and testing of a Venus long duration,high altitude balloon

This paper describes the design, fabrication and testing of a full scale prototype balloon intended for long duration flight in the upper atmosphere of Venus. The balloon is 5.5 m in diameter and is designed to carry a 45 kg payload at an altitude of 55 km. The balloon material is a 180 g/m² multi-component laminate comprised of the following layers bonded together from outside to inside: aluminized Teflon film, aluminized Mylar film, Vectran fabric and a polyurethane coating. This construction provides the required balloon functional characteristics of low gas permeability, sulfuric acid resistance and high strength for superpressure operation. The design burst superpressure is 39,200 Pa which is predicted to be 3.3 times the worst case value expected during flight at the highest solar irradiance in the mission profile. The prototype is constructed from 16 gores with bi-taped seams employing a sulfuric acid resistant adhesive on the outside. Material coupon tests were performed to evaluate the optical and mechanical characteristics of the laminate. These were followed by full prototype tests for inflation, leakage and sulfuric acid tolerance. The results confirmed the suitability of this balloon design for use at Venus in a long duration mission. The various data are presented and the implications for mission design and operation are discussed.     

Genomic instability and tumorigenic induction in immortalized human bronchial epithelial cells by heavy ions

Carcinogenesis is postulated to be a progressive multistage process characterized by an increase in genomic instability and clonal selection with each mutational event endowing a selective growth advantage. Genomic instability as manifested by the amplification of specific gene fragments is common among tumor and transformed cells. In the present study, immortalized human bronchial (BEP2D) cells were irradiated with graded doses of either 1GeV/nucleon ⁵⁶Fe ions or 150 keV/μm alpha particles. Transformed cells developed through a series of successive steps before becoming tumorigenic in nude mice. Tumorigenic cells showed neither ras mutations nor deletion in the p16 tumor suppressor gene. In contrast, they harbored mutations in the p53 gene and over-expressed cyclin D1. Genomic instability among transformed cells at various stage of the carcinogenic process was examined based on frequencies of PALA resistance. Incidence of genomic instability was highest among established tumor cell lines relative to transformed, non-tumorigenic and control cell lines. Treatment of BEP2D cells with a 4 mM dose of the aminothiol WR-1065 significantly reduced their neoplastic transforming response to ⁵⁶Fe particles. This model provides an opportunity to study the cellular and molecular mechanisms involved in malignant transformation of human epithelial cells by heavy ions.     

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.     

On the Optimum Design of PCM Signals with System Constraints

This paper considers the design of PCM signals with system constraints using Pontryagin's maximum principle. The transmitter signal as well as the correlation signal are determined while maximizing the output signal-to-noise ratio. Both the single and three-pole transmitter filters are considered. An upper bound has been obtained on the performance of PCM signals with constraints.     

Antibody engineering--a valuable asset in preventing closed environment epidemics

Investigations of Mir, Space Shuttle, Skylab and Apollo missions report extensive colonisation of the spacecraft by bacteria and fungi, which can lead to degradative effects on spacecraft equipment and devastating effects on space-grown crops. More than 80% of terrestrial greenhouse epidemics are due to the fungal genera Phytophthora, Pythium and Fusarium, which have been found in life support system test-beds. The advent of recombinant antibody technologies, including ribosome display and phage display, has made it possible to develop antibodies against virtually any toxin or organism and allows for maturation of antibodies by in vitro molecular evolution. These antibodies may play an important role in an integrated pest management regime for life support systems. Efficacy of existing fungal countermeasures could be increased by chemical linkage to antibodies, which target the site of action of the biocide or trap the pathogen in a biofilter. Novel recombinant antibody-biocide fusions can be expressed in situ by plants or symbiotic microbes to create direct disease resistance.     

Effect of KOH concentration on LEO cycle life of IPVnickel-hydrogen flight cell-update II

For update I see Energy and Environment: A Continuing Partnership, vol.3, American Nuclear Society (1991). An update of validation test results confirming the breakthrough in the low-Earth-orbit (LEO) cycle life of nickel-hydrogen cells containing 26% KOH electrolyte is presented. The results are part of an investigation of the effect of KOH concentration on life cycle. The cycle life of boiler plate cells was about 40000 LEO cycles compared to 3500 cycles for cells containing 31% KOH. The cycle regime was a stressful accelerated LEO, which consisted of a 27.5 min charge followed by a 17.5 min discharge (2×normal rate). The depth-of-discharge (DOD) was 80%. The cell temperature was maintained at 23°C. Results for six 48-Ah recirculation design IPV nickel-hydrogen flight battery cells currently being evaluated to validate the above findings are reported. Three of the cells contain 26% KOH (test cells), and three contain 31% KOH (control cells). They are undergoing real-time LEO cycle life testing. The 31% KOH cells failed at cycles 3729, 4165, and 11355. One of the 26% KOH cells failed at cycle 15314. The other two 26% KOH cells have been cycled for over 16600 cycles without failure     

Antenna Beam-Shape Factor in Scanning Radars

The method by which the antenna beam-shape factor is taken into account in scanning radars has been reexamined. The ``conventional' method is shown to give results within ±0.25 dB of the ``correct' results, which provides ample justification of its use over the past years. However, by basing the procedure on the assumption of a properly matched postdetection integrator, and leaving the question of nonoptimum postdetection integration to be treated as a separate problem, somewhat more accurate results can be obtained. This study has also called attention to the fact that a mismatched postdetection integrator results in only half the degradation in performance that a corresponding predetection mismatch would cause.     

Remote Sensing of H from Ulysses and Galileo

We model interplanetary H Lyman-α (Lα) observations from Galileo UVS (Ultraviolet Spectrometer) and EUVS (Extreme Ultraviolet Spectrometer) (Hord et al., 1992) and the Ulysses interstellar neutral gas (GAS) instrument (Witte et al., 1992). EUVS measurements near solar maximum (max) in 1990–1992 have a peaked brightness maximum upwind due to a rather isotropic solar wind charge-exchange ionization pattern (A=0–0.25). GAS measurements from solar minimum (min) in 1997 have a plateau in the upwind direction that we model using Ulysses SWOOPS (solar wind plasma experiment) solar min data on solar wind density and velocity at different heliographic latitudes. The isotropic ionization pattern deduced from EUVS at solar max may be consistent with recent SWOOPS results (McComas et al., 2000b, c) that high speed solar wind is absent at high latitudes during solar max. Galileo and Ulysses Lα data favor higher H temperatures (15 000–18 000 K) than previous models. This revised version was published online in August 2006 with corrections to the Cover Date.