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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
NASA NTRS1994

Charged-particle mutagenesis 2. Mutagenic effects of high energy charged particles in normal human fibroblasts

The biological effects of high Linear Energy Transfer (LET) charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 sq micrometer and 0.09 to 5.56 x 10(exp -3) sq micrometer respectively. The maximum values were obtained by Fe-56 with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(exp -5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.

Chen, D. J.↗
NASA NTRS1994

Kinetics model for initiation and promotion for describing tumor prevalence from HZE radiation

A kinetics model for cellular repair and misrepair for multiple radiation-induced lesions (mutation-inactivation) is coupled to a two-mutation model of initiation and promotion in tissue to provide a parametric description of tumor prevalence in the Harderian gland in a mouse. Dose-response curves are described for gamma-rays and relativistic ions. The effects of nuclear fragmentation are also considered for high-energy proton and alpha particle exposures The model described provides a parametric description of age-dependent cancer induction for a wide range of radiation fields. We also consider the two hypotheses that radiation acts either solely as an initiator or as both initiator and promoter and make model calculations for fractionation exposures from gamma-rays and relativistic Fe ions. For fractionated Fe exposures, an inverse dose-rate effect is provided by a promotion hypothesis using a mutation rate for promotion typical of single-gene mutations.

Cucinotta, Francis A.↗
NASA NTRS1994

DNA-DSB in CHO-K1 cells induced by heavy-ions: Break rejoining and residual damage (GSI)

DNA double strand breaks (DSB's) are the critical lesions involved in cellular effects of ionizing radiation. Therefore, the evaluation of DSB induction in mammalian cells after heavy ion irradiation is an essential task for the assessment of high-LET radiation risk in space. Of particular interest has been the question of how the biological efficiency for the cellular inactivation endpoint relates to the initial lesions (DSBs) at varying LETs. For cell killing, an increased Relative Biological Efficiency (RBE) has been determined for highLET radiation around 100-200 keV/mu m. At higher LET, the RBE's decrease again to values below one for the very heavy particles. At GSI, DSB-induction was measured in CHO-K1 cells following irradiation with accelerated particles covering a wide LET range. The electrophoretic elution of fragmented DNA out of agarose plugs in a constant electrical field was applied for the detection of DSB's. The fraction of DNA retained was determined considering the relative intensities of ethidium bromide fluorescence in the well and in the gel lane. Dose-effect curves were established, from which the RBE for DSB induction was calculated at a fraction of 0.7 of DNA retained In summary, these rejoining studies are in line with an enhanced severity of the DNA DSB's at higher LET's, resulting in a decreased repairability of the induced lesions. However, no information concerning the fidelity of strand breaks rejoining is provided in these studies. To assess correct rejoining of DNA fragments an experimental system involving individual DNA hybridization bands has been set up. In preliminary experiments Sal I generated DNA fragments of 0.9 Mbp were irradiated with xrays and incubated for repair However, restitution of the original signals was not observed, probably due to the high radiation dose necessary for breakage of a fragment of this size. A banding pattern with NotI hybridization signals in a higher MW range (3Mbp) has been obtained by varying the electrophoretic conditions and correct rejoining studies will be further developed in this system.

Taucher-Scholz, G.↗
NASA NTRS2000

Fate of Earth Microbes on Mars -- UV Radiation Effects

A radiative transfer model is used to quantitatively investigate aspects of the martian ultraviolet radiation environment. Biological action spectra for DNA inactivation are used to estimate biologically effective irradiances for the martian surface under cloudless skies. Although the present-day martian UV flux is similar to early earth and thus may not be a limitation to life in the evolutionary context, it is a constraint to an unadapted biota and will rapidly kill spacecraft-borne microbes not covered by a martian dust layer. Here calculations for loss of microbial viability on the Pathfinder and Polar lander spacecraft are presented and the effects of martian dust on loss of viability are discussed. Details of the radiative transfer model are presented.

Cockell, Charles↗
NASA NTRS2000

Fate of Earth Microbes on Mars: UV Radiation Effects

A radiative transfer model is used to quantitatively investigate aspects of the martian ultraviolet radiation environment. Biological action spectra for DNA inactivation are used to estimate biologically effective irradiances for the martian surface under cloudless skies. Although the present-day martian UV flux is similar to early earth and thus may not be a limitation to life in the evolutionary context, it is a constraint to an unadapted biota and will rapidly kill spacecraft-borne microbes not covered by a martian dust layer. Here calculations for loss of microbial viability on the Pathfinder and Polar lander spacecraft are presented and the effects of martian dust on loss of viability are discussed. Details of the radiative transfer model are presented.

Cockell, Charles↗
NASA NTRS1999

Biological Sterilization of Returned Mars Samples

Martian rock and soil, collected by robotic spacecraft, will be returned to terrestrial laboratories early in the next century. Current plans call for the samples to be immediately placed into biological containment and tested for signs of present or past life and biological hazards. It is recommended that "Controlled distribution of unsterilized materials from Mars should occur only if rigorous analyses determine that the materials do not constitute a biological hazard. If any portion of the sample is removed from containment prior to completion of these analyses it should first be sterilized." While sterilization of Mars samples may not be required, an acceptable method must be available before the samples are returned to Earth. The sterilization method should be capable of destroying a wide range of organisms with minimal effects on the geologic samples. A variety of biological sterilization techniques and materials are currently in use, including dry heat, high pressure steam, gases, plasmas and ionizing radiation. Gamma radiation is routinely used to inactivate viruses and destroy bacteria in medical research. Many commercial sterilizers use Co-60 , which emits gamma photons of 1.17 and 1.33 MeV. Absorbed doses of approximately 1 Mrad (10(exp 8) ergs/g) destroy most bacteria. This study investigates the effects of lethal doses of Co-60 gamma radiation on materials similar to those anticipated to be returned from Mars. The goals are to determine the gamma dose required to kill microorganisms in rock and soil samples and to determine the effects of gamma sterilization on the samples' isotopic, chemical and physical properties. Additional information is contained in the original extended abstract.

Allen, C. C.↗
NASA NTRS2000

On a Self-Tuning Impact Vibration Damper for Rotating Turbomachinery

A self-tuning impact damper is investigated analytically and experimentally as a device to inhibit vibration and increase the fatigue life of rotating components in turbomachinery. High centrifugal loads in rotors can inactivate traditional impact dampers because of friction or misalignment of the damper in the g-field. Giving an impact damper characteristics of an acceleration tuned-mass damper enables the resulting device to maintain damper mass motion and effectiveness during high-g loading. Experimental results presented here verify that this self-tuning impact damper can be designed to follow an engine order line. damping rotor component resonance crossings.

Duffy, Kirsten P.↗
NASA NTRS2001

Viscosity Relaxation in Molten HgZnTe

Rotating cup measurements of the viscosity of the pseudo-binary melt, HgZnTe have shown that the isothermal liquid with zinc mole fraction 0.16 requires tens of hours of equilibration time before a steady viscous state can be achieved. Over this relaxation period, the viscosity at 790 C increases by a factor of two, while the viscosity at 810 C increases by 40%. Noting that the Group VI elements tend to polymerize when molten, we suggest that the viscosity of the melt is enhanced by the slow formation of Te atom chains. To explain the build-up of linear Te n-mers, we propose a scheme, which contains formation reactions with second order kinetics that increase the molecular weight, and decomposition reactions with first order kinetics that inactivate the chains. The resulting rate equations can be solved for the time dependence of each molecular weight fraction. Using these molecular weight fractions, we calculate the time dependence of the average molecular weight. Using the standard semi-empirical relation between polymer average molecular weight and viscosity, we then calculate the viscosity relaxation curve. By curve fitting, we find that the data imply that the rate constant for n-mer formation is much smaller than the rate constant for n-mer deactivation, suggesting that Te atoms only weakly polymerize in molten HgZnTe. The steady state toward which the melt relaxes occurs as the rate of formation of an n-mer becomes exactly balanced by the sum of the rate for its deactivation and the rate for its polymerization to form an (n+1)-mer.

Su, Ching-Hua↗
NASA NTRS1995

Inhibition of the ATPase from Halobacterium Saccharovorum by Thiol Inhibitors: Evidence for the Presence of More Than One Essential Cysteinyl Residue

The vacuolar-like ATPase from Halobacterium saccha vorum is inhibited by N-ethylmaleimide and p-chloromercudphenylsulfonate. The failure of adenine nucleotides to protect against p-chloromercuriphenyisulfonate inhibition, of p-chloromercuriphenylsulfonate to protect against N-ethylmaleimide inhibition, and the difference in the temperature dependence of inactivation infers that the enzyme contains at least two thiols that are essential for enzyme activity. CNBr cleavage of C-14-N-ethylmaleimide labeled subunit results in two radioactive peptides that locates the N-ethylmaleimide-reactive cysteinyl residue as cysteine-262 in the H. salinarium sequence.

Hochstein, Lawrence I.↗
NASA NTRS2002

Functional Characterization of G12, a Gene Required for Mitotic Progression during Gastrulation in Zebrafish

In a differential RNA display screen we have isolated a zebrafish gene, G12, for which homologs can only be found in DNA databases for vertebrates, but not invertebrates. This suggests that this is a gene required specifically in vertebrates. G12 expression is upregulated at mid-blastula transition (MBT). Morpholino inactivation of this gene by injection into 1-cell embryos results in mitotic defects and apoptosis shortly after MBT. Nuclei in morpholino treated embryos also display segregation defects. We have characterized the localization of this gene as a GFP fusion in live and fixed embryos. Overexpression of G12-GFP is non-toxic. Animals retain GFP expression for at least 7 days with no developmental defects, Interestingly in these animals G12-GFP is never detectable in blood cells though blood is present. In the deep cells of early embryos, G 12GFP is localized to nuclei and cytoskeletal elements in interphase and to the centrosome and spindle apparatus during mitosis. In the EVL, G12-GFP shows additional localization to the cell periphery, especially in mitosis. In the yolk syncytium, G12-GFP again localizes to nuclei and strongly to cytoplasmic microtubules of migrating nuclei at the YSL margin. Morpholinc, injection specifically into the YSL after cellularization blocks epiboly and nuclei of the YSL show mitotic defects while deep cells show no mitotic defects and continue to divide. Rescue experiments in which morpholino and G12-GFP RNA are co-injected indicate partial rescue by the G12-GFP. The rescue is cell autonomous; that is, regions of the embryo with higher G12-GFP expression show fewer mitotic defects. Spot 14, the human bomolog of G12, has been shown to be amplified in aggressive breast tumors. This finding, along with our functional and morphological data suggest that G12 and spot 14 are vertebrate-specific and may function either as mitotic checkpoints or as structural components of the spindle apparatus.

Reinsch, Sigrid↗
NASA NTRS2002

Magnetic Microspheres for Therapeutical Applications

Hyperthermia is a well known cancer therapy and consists of heating a tumor region to the elevated temperatures in the range of 40-45 C for an extended period of time (2-8 hours). This leads to thermal inactivation of cell regulatory and growth processes with resulting widespread necrosis, carbonization and coagulation. Moreover, heat boosts the tumor response to other treatments such as radiation, chemotherapy or immunotherapy. Of particular importance is careful control of generated heat in the treated region and keeping it localized. Higher heating, to about 56 C can lead to tissue thermo-ablation. With accurate temperature control, hyperthermia has the advantage of having minimal side effects. Several heating techniques are utilized for this purpose, such as whole body hyperthermia, radio-frequency (RF) hyperthermia, ultrasound technique, inductive microwave antenna hyperthermia, inductive needles (thermoseeds), and magnetic fluid hyperthermia (MFH).MFH offers many advantages as targeting capability by applying magnets. However, this technology still suffers significant inefficiencies due to lack of thermal control. This paper will provide a review of the topic and outline the ongoing work in this area. The main emphasis is in devising ways to overcome the technical difficulty in hyperthermia therapy of achieving a uniform therapeutic temperature over the required region of the body and holding it steady. The basic obstacle of the present heating methods are non-uniform thermal properties of the tissue. Our approach is to develop a novel class of magnetic fluids which have inherent thermoregulating properties. We have identified a few magnetic alloys which can serve as a suitable nano-particle material. The objective is to synthesize, characterize and evaluate the efficacy of TRMF for hyperthermia therapy.

Mazuruk, K.↗
NASA NTRS2003

Magnetic Microspheres and Tissue Model Studies for Therapeutical Applications

Hyperthermia is a well known cancer therapy and consists of heating a tumor region to the elevated temperatures in the range of 40-45 C for an extended period of time (2-8 hours). This leads to thermal inactivation of cell regulatory and growth processes with resulting widespread necrosis, carbonization and coagulation. Moreover, heat boosts the tumor response to other treatments such as radiation, chemotherapy or immunotherapy. Of particular importance is careful control of generated heat in the treated region and keeping it localized. Higher heating, to about 56 C can lead to tissue thermo-ablation. With accurate temperature control, hyperthermia has the advantage of having minimal side effects. Several heating techniques are utilized for this purpose, such as whole body hyperthermia, radio-frequency (RF) hyperthermia, ultrasound technique, inductive microwave antenna hyperthermia, inductive needles (thermoseeds), and magnetic fluid hyperthermia (MFH).MFH offers many advantages as targeting capability by applying magnets. However, this technology still suffers significant inefficiencies due to lack of thermal control. This paper will provide a review of the topic and outline the ongoing work in this area. The main emphasis is in devising ways to overcome the technical difficulty in hyperthermia breast therapy of achieving a uniform therapeutic temperature over the required region of the body and holding it steady for an extended period (2-3 hours). The basic shortcomings of the presently utilized heating methods stem from the non-uniform thermal properties of the tissue and the point heating characteristics of the techniques without any thermal control. Our approach is to develop a novel class of magnetic fluids, which have inherent thermoregulating properties. We have identified a few magnetic alloys which can serve as suitable nano to micron-size particle material. The objective is to synthesize, characterize and evaluate the efficacy of Thermo Regulating Magnetic Fluids (TRMF) for hyperthermia therapy. The development of a tissue model and testing the fluid dynamics of particle motion, settling, distribution in the tissue matrix and heat generation will be discussed.

Ramachandran, N.↗
NASA NTRS2004

Enzymatic Properties of an Alkaline and Chelator Resistant alpha-amylase from the Alkaliphilic Bacillus sp. Isolate L1711

An alkaliphilic amylase producing bacterium, Bacillus sp. strain L 711, was selected among 13 soda lakes isolates. When grown at pH 10.5 and 37 C, strain L711 produced multiple forms of amylases in the culture broth. One of these, BAA, was purified from the culture supernatant by QAE column chromatography and preparative native gel electrophoresis. The molecular weight of BAA was determined to be 51 kDa by denaturing gel electrophoresis. The pH optima for activity below and above 40 C were 9.5 - 10.0 and 7.0 - 7.5 respectively. BAA was stable in the pH range 6-11 and was completely inactivated at 55 C. The thermostability was not increased in the presence of Ca(2+). The enzyme was strongly inhibited by Ca(2+), Zn(2+), Mg(2+), Mn(2+), Ba(2+) and Cu(2+), whereas the presence of Na(+), Co(2+) and EDTA (10 mM) enhanced enzymatic activity. The K(sub m), and specific activity of BAA on soluble starch were 1.9 mg/ml and 18.5 U/mg respectively. The main end products of hydrolysis were maltotetraose, maltose and glucose.

Bernhardsdotter, Eva C. M. J.↗
NASA NTRS2004

Lunar and Planetary Science XXXV: Astrobiology Stew: Pinch of Microbes, Smidgen of UV, Touch of Organics, and Dash of Meteorites

The session Astrobiology Stew: Pinch of Microbes, Smidgen of UV, Touch of Organics, and Dash of Meteorites includes the following topics: 1) Investigating the Impact of UV Radiation on High-Altitude Shallow Lake Habitats, Life Diversity, and Life Survival Strategies: Clues for Mars' Past Habitability Potential? 2) An Analysis of Potential Photosynthetic Life on Mars; 3) Radiation Inactivation of Bacterial spores on Mars; 4) Hydrophobic Surfaces of Spacecraft Components Enhance the Aggregation of Microorganisms and May Lead to Higher Survival Rates of Bacteria on Mars Landers; 5) Optical Detection of Organic Chemical Biosignatures at Hydrothermal Vents; 6) Signs of Life in Meridiani Planum-What Might Opportunity See (or Miss)? 7) Isolation of PUrines and Pyrimidines from the Murchison Meteorite Using Sublimation; and 8) Relative Amino Acid Composition of CM1 Carbonaceous Chondrites.

Source record↗
NASA NTRS2004

Enzymatic Properties of an Alkaline and Chelator Resistant Proportional to alpha-Amylase from the Alkaliphilic Bacillus sp. Isolate L1711

An alkaliphilic amylase producing bacterium, Bacillus sp. strain L1711, was selected among 13 soda lakes isolates. When grown at pH 10.5 and 370 C, strain L1711 produced multiple forms of amylases in the culture broth. One of these, BAA, was purified from the culture supernatant by QAE column chromatography and preparative native gel electrophoresis. The molecular weight of BAA was determined to be 51 kDa by denaturing gel electrophoresis. The pH optima for activity below and above 40 C were 9.5-10.0 and 7.0-7.5 respectively. BAA was stable in the pH range 6-11 and was completely inactivated at 55?C. The thermostability was not increased in the presence of Ca(2+). The enzyme was strongly inhibited by Ca(2+), Zn(2+), Mg(2+), Mn(2+), Ba(2+) and Cu(2+), whereas the presence of Na(+), Co2+ and EDTA (10 mM) enhanced enzymatic activity. The K(sub m) and specific activity of BAA on soluble starch were 1.9 mg/ml and 18.5 U/mg respectively. The main end products of hydrolysis were maltotetraose, maltose and glucose .

Bernhardsdotter, Eva C. M. J.↗
NASA NTRS2003

Survival of endospores of Bacillus subtilis on spacecraft surfaces under simulated martian environments: implications for the forward contamination of Mars

Experiments were conducted in a Mars simulation chamber (MSC) to characterize the survival of endospores of Bacillus subtilis under high UV irradiation and simulated martian conditions. The MSC was used to create Mars surface environments in which pressure (8.5 mb), temperature (-80, -40, -10, or +23 degrees C), gas composition (Earth-normal N2/O2 mix, pure N2, pure CO2, or a Mars gas mix), and UV-VIS-NIR fluence rates (200-1200 nm) were maintained within tight limits. The Mars gas mix was composed of CO2 (95.3%), N2 (2.7%), Ar (1.7%), O2 (0.2%), and water vapor (0.03%). Experiments were conducted to measure the effects of pressure, gas composition, and temperature alone or in combination with Mars-normal UV-VIS-NIR light environments. Endospores of B. subtilis, were deposited on aluminum coupons as monolayers in which the average density applied to coupons was 2.47 x 10(6) bacteria per sample. Populations of B. subtilis placed on aluminum coupons and subjected to an Earth-normal temperature (23 degrees C), pressure (1013 mb), and gas mix (normal N2/O2 ratio) but illuminated with a Mars-normal UV-VIS-NIR spectrum were reduced by over 99.9% after 30 sec exposure to Mars-normal UV fluence rates. However, it required at least 15 min of Mars-normal UV exposure to reduce bacterial populations on aluminum coupons to non-recoverable levels. These results were duplicated when bacteria were exposed to Mars-normal environments of temperature (-10 degrees C), pressure (8.5 mb), gas composition (pure CO2), and UV fluence rates. In other experiments, results indicated that the gas composition of the atmosphere and the temperature of the bacterial monolayers at the time of Mars UV exposure had no effects on the survival of bacterial endospores. But Mars-normal pressures (8.5 mb) were found to reduce survival by approximately 20-35% compared to Earth-normal pressures (1013 mb). The primary implications of these results are (a) that greater than 99.9% of bacterial populations on sun-exposed surfaces of spacecraft are likely to be inactivated within a few tens of seconds to a few minutes on the surface of Mars, and (b) that within a single Mars day under clear-sky conditions bacterial populations on sun-exposed surfaces of spacecraft will be sterilized. Furthermore, these results suggest that the high UV fluence rates on the martian surface can be an important resource in minimizing the forward contamination of Mars. c2003 Elsevier Inc. All rights reserved.

Bacillus subtilis/growth & development/physiology/↗
NASA NTRS2003

Control of T lymphocyte morphology by the GTPase Rho

BACKGROUND: Rho family GTPase regulation of the actin cytoskeleton governs a variety of cell responses. In this report, we have analyzed the role of the GTPase Rho in maintenance of the T lymphocyte actin cytoskeleton. RESULTS: Inactivation of the GTPase Rho in the human T lymphocytic cell line HPB-ALL does not inhibit constitutively high adhesion to the integrin beta1 substrate fibronectin. It did however result in the aberrant extension of finger-like dendritic processes on the substrates VCAM-1, Fn, and mAb specific to beta1 integrins. Time-lapse video microscopy demonstrated that C3 induced extensions were primarily the result of an altered pseudopod elongation rather than retraction. Once the stellate pseudopodia extended, none retracted, and cells became completely immobile. Filipodial structures were absent and the dendritic-like processes in C3 treated cells were rich in filamentous actin. Immunolocalization of RhoA in untreated HPB-ALL cells spreading on fibronectin demonstrated a diffuse staining pattern within the pseudopodia. In C3 treated cells, clusters of RhoA were pronounced and localized within the altered extensions. CONCLUSIONS: GTPase Rho is actively involved in the regulation of T lymphocyte morphology and motility.

Non-NASA Center↗
NASA NTRS2000

The ultraviolet environment of Mars: biological implications past, present, and future

A radiative transfer model is used to quantitatively investigate aspects of the martian ultraviolet radiation environment, past and present. Biological action spectra for DNA inactivation and chloroplast (photosystem) inhibition are used to estimate biologically effective irradiances for the martian surface under cloudless skies. Over time Mars has probably experienced an increasingly inhospitable photobiological environment, with present instantaneous DNA weighted irradiances 3.5-fold higher than they may have been on early Mars. This is in contrast to the surface of Earth, which experienced an ozone amelioration of the photobiological environment during the Proterozoic and now has DNA weighted irradiances almost three orders of magnitude lower than early Earth. Although the present-day martian UV flux is similar to that of early Earth and thus may not be a critical limitation to life in the evolutionary context, it is a constraint to an unadapted biota and will rapidly kill spacecraft-borne microbes not covered by a martian dust layer. Microbial strategies for protection against UV radiation are considered in the light of martian photobiological calculations, past and present. Data are also presented for the effects of hypothetical planetary atmospheric manipulations on the martian UV radiation environment with estimates of the biological consequences of such manipulations.

NASA Center ARC↗