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NASA NTRS2002

Enhanced animal growth via ligand-regulated GHRH myogenic-injectable vectors

Regulated animal growth occurred following a single electroporated injection of a mixture of two plasmids (10 microg of DNA), one expressing the GeneSwitch regulator protein, the other an inducible growth hormone releasing hormone (GHRH) gene, into the tibialis anterior muscles of adult SCID mice. Administration of the ligand mifepristone (MFP) up-regulated GHRH expression, as shown by elevations of IGF-I levels, and when MFP dosing was withdrawn, IGF-I returned to baseline levels. Five cycles of IGF-I induction were observed during a five-month period. Chronic MFP dosing for 25 days increased lean body mass, weight gain, and bone mineral density significantly compared with non-MFP treated controls. In summary, long-term drug-regulated GHRH expression was achieved following plasmid-based gene therapy, and chronic induction of GHRH expression in adult animals led to improvements in weight gain and body composition.

NASA Discipline Musculoskeletal↗

NASA NTRS2018

The Fusion Driven Rocket: Nuclear Propulsion through Direct Conversion of Fusion Energy

The future of manned space exploration and development of space depends critically on the creation of a dramatically more efficient propulsion architecture for in-space transportation. A very persuasive reason for investigating the applicability of nuclear power in rockets is the vast energy density gain of nuclear fuel when compared to chemical combustion energy. The Fusion Driven rocket (FDR) represents a revolutionary approach to fusion propulsion where the power source releases its energy directly into the propellant, not requiring conversion to electricity. It employs a solid lithium propellant that requires no significant tankage mass. The propellant is rapidly heated and accelerated to high exhaust velocity (> 30 km/s), while having no substantial physical interaction with the spacecraft thereby avoiding damage to the rocket and limiting both the thermal heat load and radiator mass. The key to achieving this stems from research at MSNW and the UW on the magnetically driven implosion of metal foils onto a magnetized plasma target to obtain fusion conditions. A logical extension of this work leads to a method that utilizes these metal shells (or liners) to not only achieve fusion conditions, but to serve as the propellant as well. Several low-mass, magnetically driven metal liners are inductively driven to converge radially and axially and form a thick blanket surrounding the target plasmoid and compress the plasmoid to fusion conditions. Virtually all of the radiant, neutron and particle energy from the plasma is absorbed by the encapsulating, thick metal blanket thereby isolating the spacecraft from the fusion. This energy, in addition to the intense Ohmic heating at peak magnetic field compression, is adequate to vaporize and ionize the metal blanket. The expansion of this hot, ionized metal propellant through a magnetically insulated nozzle produces high thrust at the optimal Isp. The energy from the fusion process, along with the waste heat, is thus utilized at very high efficiency. The basic scheme for FDR is illustrated and described in the report (see Fig. 2) The two most critical issues in meeting challenges introduced employing magneto-inertial fusion as the power source is driver efficiency and “stand-off” – the ability to isolate and protect fusion and thruster from the resultant fusion energy. By employing metal shells for compression, it is possible to produce the desired convergent motion inductively by inserting the metal sheets along the inner surface of cylindrical or conically tapered coils. Both stand-off and energy efficiency issues are solved by this arrangement. 3 This two year effort focused on achieving three key criteria for the Fusion Driven Rocket to move forward for technological development: (1) the physics of the FDR must be fully understood and validated, (2) the design and technology development for the FDR required for its implementation in space must be fully characterized, and (3) an in-depth analysis of the rocket design and spacecraft integration as well as mission architectures enabled by the FDR need to be performed. A subscale, laboratory liner compression test facility was assembled at the University of Washington Plasma Dynamics Laboratory with sufficient liner kinetic energy (~ 0.5 MJ) to reach conditions required for fusion breakeven conditions. Detailed experimental studies of the dynamic behavior of the driven liners as well as liner convergence and magnetic compression were performed. The development of both the 1D liner dynamics code and the full 3D ANSYS® liner calculations was achieved. The characterization of both the FDR and spacecraft as well as a design architecture analysis was conducted that included an examination of a wide range of mission architectures and destinations for which this fusion propulsion system would be enabling or critical. In particular a rapid, single launch manned Mars mission was developed.

Energy↗

NASA NTRS2000

An early ethylene up-regulated gene encoding a calmodulin-binding protein involved in plant senescence and death

35S-Labeled calmodulin (CaM) was used to screen a tobacco anther cDNA library. A positive clone (NtER1) with high homology to an early ethylene-up-regulated gene (ER66) in tomato, and an Arabidopsis homolog was isolated and characterized. Based on the helical wheel projection, a 25-mer peptide corresponding to the predicted CaM-binding region of NtER1 (amino acids 796-820) was synthesized. The gel-mobility shift assay showed that the peptide formed a stable complex with CaM only in the presence of Ca(2+). CaM binds to NtER1 with high affinity (K(d) approximately 12 nm) in a calcium-dependent manner. Tobacco flowers at different stages of development were treated with ethylene or with 1-methylcyclopropene for 2 h before treating with ethylene. Northern analysis showed that the NtER1 was rapidly induced after 15 min of exposure to ethylene. However, the 2-h 1-methylcyclopropene treatment totally blocked NtER1 expression in flowers at all stages of development, suggesting that NtER1 is an early ethylene-up-regulated gene. The senescing leaves and petals had significantly increased NtER1 induction as compared with young leaves and petals, implying that NtER1 is developmentally regulated and acts as a trigger for senescence and death. This is the first documented evidence for the involvement of Ca(2+)/CaM-mediated signaling in ethylene action.

Non-NASA Center↗

NASA NTRS2000

Comparison of repair of DNA double-strand breaks in identical sequences in primary human fibroblast and immortal hamster-human hybrid cells harboring a single copy of human chromosome 11

We have optimized a pulsed-field gel electrophoresis assay that measures induction and repair of double-strand breaks (DSBs) in specific regions of the genome (Lobrich et al., Proc. Natl. Acad. Sci. USA 92, 12050-12054, 1995). The increased sensitivity resulting from these improvements makes it possible to analyze the size distribution of broken DNA molecules immediately after the introduction of DSBs and after repair incubation. This analysis shows that the distribution of broken DNA pieces after exposure to sparsely ionizing radiation is consistent with the distribution expected from randomly induced DSBs. It is apparent from the distribution of rejoined DNA pieces after repair incubation that DNA ends continue to rejoin between 3 and 24 h postirradiation and that some of these rejoining events are in fact misrejoining events, since novel restriction fragments both larger and smaller than the original fragment are generated after repair. This improved assay was also used to study the kinetics of DSB rejoining and the extent of misrejoining in identical DNA sequences in human GM38 cells and human-hamster hybrid A(L) cells containing a single human chromosome 11. Despite the numerous differences between these cells, which include species and tissue of origin, levels of TP53, expression of telomerase, and the presence or absence of a homologous chromosome for the restriction fragments examined, the kinetics of rejoining of radiation-induced DSBs and the extent of misrejoining were similar in the two cell lines when studied in the G(1) phase of the cell cycle. Furthermore, DSBs were removed from the single-copy human chromosome in the hamster A(L) cells with similar kinetics and misrejoining frequency as at a locus on this hybrid's CHO chromosomes.

NASA Program Biomedical Research and Countermeasur↗

NASA NTRS2005

Early immune response and regulation of IL-2 receptor subunits

Affymetrix oligonucleotide arrays were used to monitor expression of 8796 genes and probe sets in activated T-cells; analysis revealed that 217 genes were significantly upregulated within 4 h. Induced genes included transcription factors, cytokines and their receptor genes. Analysis by semi-quantitative RT-PCR confirmed the significant induction of IL-2, IL-2R(gamma) and IL-2R(alpha). Forty-eight of the 217 induced genes are known to or predicted to be regulated by a CRE promoter/enhancer. We found that T-cell activation caused a significant increase in CREB phosphorylation furthermore, inhibition of the PKC pathway by GF109203 reduced CREB activation by 50% and inhibition of the PKA pathway caused a total block of CREB phosphorylation and significantly reduced IFN(gamma), IL-2 and IL-2R(alpha) gene expression by approximately 40% (p<0.001). PKC(theta) plays a major role in T-cell activation: inhibition of PKC significantly reduced the expression of IFN(gamma), IL-2 and IL-2R(alpha). Since PKC blocked activation of CREB, we studied potential cross-talk between the PKC and the PKA/MAPK pathways, PMA-stimulated Jurkat cells were studied with specific signal pathway inhibitors. Extracellular signal-regulated kinase-2 (ERK2) pathway was found to be significantly activated greater than seven-fold within 30 min; however, there was little activation of ERK-1 and no activation of JNK or p38 MAPK. Inhibition of the PKA pathway, but not the PKC pathway, resulted in inhibition of ERK1/2 activation at all time points, inhibition of MEK1 and 2 significantly blocked expression of IL-2 and IL-2R(alpha). Gene expression of IL-2R(alpha) and IFN(gamma) was dependent on PKA in S49 wt cells but not in kin- mutants. Using gel shift analysis, we found that forskolin activation of T-cells resulted in activation of AP1 sites; this increase in nuclear extract AP1 was significantly blocked by MEK1 inhibitor U0126. Taken together, these results suggest that the PKA in addition to PKC and MAPK pathways plays a role in early T-cell activation and induction of IL-2, IL-2R(alpha) and IFN(gamma) gene expression.

Non-NASA Center↗

NASA NTRS1995

Effects of alpha-particles on survival and chromosomal aberrations in human mammary epithelial cells

We have studied the radiation responses of a human mammary epithelial cell line, H184B5 F5-1 M/10. This cell line was derived from primary mammary cells after treatment with chemicals and heavy ions. The F5-1 M/10 cells are immortal, density-inhibited in growth, and non-tumorigenic in athymic nude mice and represent an in vitro model of the human epithelium for radiation studies. Because epithelial cells are the target of alpha-particles emitted from radon daughters, we concentrated our studies on the efficiency of alpha-particles. Confluent cultures of M/10 cells were exposed to accelerated alpha-particles [beam energy incident at the cell monolayer = 3.85 MeV, incident linear energy transfer (LET) in cell = 109 keV/microns] and, for comparison, to 80 kVp x-rays. The following endpoints were studied: (1) survival, (2) chromosome aberrations at the first postirradiation mitosis, and (3) chromosome alterations at later passages following irradiation. The survival curve was exponential for alpha-particles (D0 = 0.73 +/- 0.04 Gy), while a shoulder was observed for x-rays (alpha/beta = 2.9 Gy; D0 = 2.5 Gy, extrapolation number 1.6). The relative biological effectiveness (RBE) of high-LET alpha-particles for human epithelial cell killing was 3.3 at 37% survival. Dose-response curves for the induction of chromosome aberrations were linear for alpha-particles and linearquadratic for x-rays. The RBE for the induction of chromosome aberrations varied with the type of aberration scored and was high (about 5) for chromosome breaks and low (about 2) for chromosome exchanges.(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Center JSC↗

NASA NTRS2016

Single-Event Latchup Testing of the Micrel MIC4424 Dual Power MOSFET Driver

We conducted 47 exposures of four different MIC4424 devices and did not observe any SEL or high-current events. This included worst-case conditions with a LET of 81 MeV-sq cm/mg, applied voltage of 18.5 V, a case temperature greater than 120 C, and a final fluence of 1x10(exp 7)/sq cm. We also monitored both the outputs for the presence of SETs. While the period of the 1 MHz square wave was slightly altered in some cases, no pulses were added or deleted. 1. Purpose: The purpose of this testing is to characterize the BiCMOS/DMOS Micrel MIC4424 dual, non-inverting MOSFET driver for single-event latchup (SEL) susceptibility. These data will be used for flight lot evaluation purposes. 2. Devices Tested: The MIC4423/4424/4425 family are highly reliable BiCMOS/DMOS buffer/driver MOSFET drivers. They are higher output current versions of the MIC4426/4427/4428. They can survive up to 5V of noise spiking, of either polarity, on the ground pin. They can accept, without either damage or logic upset, up to half an amp of reverse current (either polarity) forced back into their outputs. Primarily intended for driving power MOSFETs, the MIC4423/4424/4425 drivers are suitable for driving other loads (capacitive, resistive, or inductive) which require low-impedance, high peak currents, and fast switching times. Heavily loaded clock lines, coaxial cables, or piezoelectric transducers are some examples. The only known limitation on loading is that total power dissipated in the driver must be kept within the maximum power dissipation limits of the package. Five (5) parts were provided for SEL testing. We prepared four parts for irradiation and reserved one piece as an un-irradiated control. More information about the devices can be found in Table 1. The parts were prepared for testing by removing the lid from the CDIP package to expose the target die. The parts were then soldered to small copper circuit adapter boards for easy handling. These parts are fabricated in a bulk BiCMOS/DMOS technology. Since we do not know the number of overlayers used in the fabrication processes, linear energy transfer calculations are determined based on the top-surface incident ion species and kinetic energy.

Power MOSFET↗

NASA NTRS2002

Spatial separation of light perception and growth response in maize root phototropism

Although the effects of gravity on root growth are well known and interactions between light and gravity have been reported, details of root phototropic responses are less documented. We used high-resolution image analysis to study phototropism in primary roots of Zea mays L. Similar to the location of perception in gravitropism, the perception of light was localized in the root cap. Phototropic curvature away from the light, on the other hand, developed in the central elongation zone, more basal than the site of initiation of gravitropic curvature. The phototropic curvature saturated at approximately 10 micromoles m-2 s-1 blue light with a peak curvature of 29 +/- 4 degrees, in part due to induction of positive gravitropism following displacement of the root tip from vertical during negative phototropism. However, at higher fluence rates, development of phototropic curvature is arrested even if gravitropism is avoided by maintaining the root cap vertically using a rotating feedback system. Thus continuous illumination can cause adaptation in the signalling pathway of the phototropic response in roots.

NASA Discipline Plant Biology↗

NASA NTRS2014

Properties of Desert Sand and CMAS Glass

As-received desert sand from a Middle East country has been characterized for its phase composition and thermal stability. X-ray diffraction analysis showed the presence of quartz (SiO2), calcite (CaCO3), gypsum (CaSO4.2H2O), and NaAlSi3O8 phases in as-received desert sand and showed weight loss of approx. 35 percent due to decomposition of CaCO3 and CaSO4.2H2O when heated to 1400 C. A batch of as-received desert sand was melted into calcium magnesium aluminosilicate (CMAS) glass at approx. 1500 C. From inductively coupled plasma-atomic emission spectrometry, chemical composition of the CMAS glass was analyzed to be 27.8CaO-4MgO-5Al2O3-61.6SiO2-0.6Fe2O3-1K2O (mole percent). Various physical, thermal and mechanical properties of the glass have been evaluated. Bulk density of CMAS glass was 2.69 g/cc, Young's modulus 92 GPa, Shear modulus 36 GPa, Poisson's ratio 0.28, dilatometric glass transition temperature (T (sub g)) 706 C, softening point (T (sub d)) 764 C, Vickers microhardness 6.3 +/- 0.4 GPa, indentation fracture toughness 0.75 +/- 0.15 MPa.m (sup 1/2), and coefficient of thermal expansion (CTE) 9.8 x 10 (exp -6)/degC in the temperature range 25 to 700 C. Temperature dependence of viscosity has also been estimated from various reference points of the CMAS glass using the Vogel-Fulcher-Tamman (VFT) equation. The glass remained amorphous after heat treating at 850 C for 10 hr but crystallized into CaSiO3 and Ca-Mg-Al silicate phases at 900 C or higher temperatures. Crystallization kinetics of the CMAS glass has also been investigated by differential thermal analysis (DTA). Activation energies for the crystallization of two different phases in the glass were calculated to be 403 and 483 kJ/mol, respectively.

Desert sand↗

NASA NTRS1996

Rejoining and misrejoining of radiation-induced chromatin breaks. I. experiments with human lymphocytes

Fluorescence in situ hybridization with a composite probe for human chromosome 4 and a probe that stained all centromeres was used to study gamma-ray induced breakage, rejoining and misrejoining in prematurely condensed chromosomes in human lymphocytes. Dose-response curves for the induction of all types of aberrations in prematurely condensed human chromosomes 4 were determined immediately after irradiation and after 8 h postirradiation incubation. In addition, aberrations were measured after various incubation times from 0 to 18 h after a dose of 7 Gy. Unrejoined chromosome breaks were the most frequent type of aberration observed immediately after irradiation. Approximately 15% of total aberrations observed were chromosome exchanges. After 8 h postirradiation incubation, the frequency of breaks in prematurely condensed chromosomes declined to about 20% of the initial value, and chromosomal exchanges became the most frequent aberration. Results of metaphase analysis were similar to those for prematurely condensed chromosomes after 8 h incubation with the exception that a significantly lower frequency of fragments was observed. Symmetrical and asymmetrical interchanges were found at similar frequencies at all doses. No complex exchanges were observed in lymphocyte chromosomes immediately after exposure. They accounted for about 1% of total exchanges in metaphase chromosomes at doses <3 Gy and about 14% at 7 Gy. Incomplete exchanges amounted to approximately 15% of total exchanges at all doses. The kinetics of break rejoining was exponential, and the frequency of exchanges increased with kinetics similar to that observed for the rejoining of the breaks. This increase in the total exchanges as a function of the time between irradiation and fusion was due to a rapid increase in reciprocal interchanges, and a slower increase in complex exchanges; the frequency of incomplete exchanges increased initially, then decreased with prolonged incubation to the level observed in metaphase. It is concluded that the formation of each kind of chromosome aberrations follows different kinetics.

NASA Discipline Radiation Health↗

NASA NTRS1996

Biological dosimetry by interphase chromosome painting

Both fluorescence in situ hybridization of metaphase spreads with whole-chromosome probes and premature chromosome condensation in interphase nuclei have been used in the past to estimate the radiation dose to lymphocytes. We combined these techniques to evaluate the feasibility of using painted interphase chromosomes for biodosimetry. Human peripheral lymphocytes were exposed to gamma rays and fused to mitotic Chinese hamster cells either immediately after irradiation or after 8 h incubation at 37 degrees C. Interphase or metaphase human chromosomes were hybridized with a composite probe specific for human chromosomes 3 and 4. The dose-response curve for fragment induction immediately after irradiation was linear; these results reflected breakage frequency in the total genome in terms of DNA content per chromosome. At 8 h after irradiation, the dose-response curve for chromosome interchanges, the prevalent aberration in interphase chromosomes, was linear-quadratic and similar to that observed for metaphase chromosomes. These results suggest that painting prematurely condensed chromosomes can be useful for biological dosimetry when blood samples are available shortly after the exposure, or when interphase cells are to be scored instead of mitotic cells.

NASA Discipline Radiation Health↗

NASA NTRS2012

Computational Transport Modeling of High-Energy Neutrons Found in the Space Environment

The high charge and high energy (HZE) particle radiation environment in space interacts with spacecraft materials and the human body to create a population of neutrons encompassing a broad kinetic energy spectrum. As an HZE ion penetrates matter, there is an increasing chance of fragmentation as penetration depth increases. When an ion fragments, secondary neutrons are released with velocities up to that of the primary ion, giving some neutrons very long penetration ranges. These secondary neutrons have a high relative biological effectiveness, are difficult to effectively shield, and can cause more biological damage than the primary ions in some scenarios. Ground-based irradiation experiments that simulate the space radiation environment must account for this spectrum of neutrons. Using the Particle and Heavy Ion Transport Code System (PHITS), it is possible to simulate a neutron environment that is characteristic of that found in spaceflight. Considering neutron dosimetry, the focus lies on the broad spectrum of recoil protons that are produced in biological targets. In a biological target, dose at a certain penetration depth is primarily dependent upon recoil proton tracks. The PHITS code can be used to simulate a broad-energy neutron spectrum traversing biological targets, and it account for the recoil particle population. This project focuses on modeling a neutron beamline irradiation scenario for determining dose at increasing depth in water targets. Energy-deposition events and particle fluence can be simulated by establishing cross-sectional scoring routines at different depths in a target. This type of model is useful for correlating theoretical data with actual beamline radiobiology experiments. Other work exposed human fibroblast cells to a high-energy neutron source to study micronuclei induction in cells at increasing depth behind water shielding. Those findings provide supporting data describing dose vs. depth across a water-equivalent medium. This poster presents PHITS data suggesting an increase in dose, up to roughly 10 cm depth, followed by a continual decrease as neutrons come to a stop in the target.

Cox, Brad↗

NASA NTRS2002

Activation of c-Jun N-terminal kinase and apoptosis in endothelial cells mediated by endogenous generation of hydrogen peroxide

Reactive oxygen species have been implicated in the activation of signal transduction pathways. However, extracellular addition of oxidants such as hydrogen peroxide (H2O2) often requires concentrations that cannot be readily achieved under physiological conditions to activate biological responses such as apoptosis. Explanations for this discrepancy have included increased metabolism of H2O2 in the extracellular environment and compartmentalization within the cell. We have addressed this issue experimentally by examining the induction of apoptosis of endothelial cells induced by exogenous addition of H2O2 and by a redox cycling agent, 2,3-dimethoxy-1,4-naphthoquinone, that generates H2O2 in cells. Here we show that low nanomolar steady-state concentrations (0.1-0.5 nmol x min(-1) x 10(6) cells) of H2O2 generated intracellularly activate c-Jun N terminal kinase and initiate apoptosis in endothelial cells. A comparison with bolus hydrogen peroxide suggests that the low rate of intracellular formation of this reactive oxygen species results in a similar profile of activation for both c-Jun N terminal kinase and the initiation of apoptosis. However, a detailed analysis reveals important differences in both the duration and profile for activation of these signaling pathways.

Non-NASA Center↗

NASA NTRS1996

Intracellular magnetophoresis of amyloplasts and induction of root curvature

High-gradient magnetic fields (HGMFs) were used to induce intracellular magnetophoresis of amyloplasts. The HGMFs were generated by placing a small ferromagnetic wedge into a uniform magnetic field or at the gap edge between two permanent magnets. In the vicinity of the tip of the wedge the dynamic factor of the magnetic field, delta(H2/2), was about 10(9) Oe2.cm-1, which subjected the amyloplasts to a force comparable to that of gravity. When roots of 2-d-old seedlings of flax (Linum usitatissimum L.) were positioned vertically and exposed to an HGMF, curvature away from the wedge was transient and lasted approximately 1 h. Average curvature obtained after placing magnets, wedge and seedlings on a 1-rpm clinostat for 2 h was 33 +/- 5 degrees. Roots of horizontally placed control seedlings without rotation curved about 47 +/- 4 degrees. The time course of curvature and changes in growth rate were similar for gravicurvature and for root curvature induced by HGMFs. Microscopy showed displacement of amyloplasts in vitro and in vivo. Studies with Arabidopsis thaliana (L.) Heynh. showed that the wild type responded to HGMFs but the starchless mutant TC7 did not. The data indicate that a magnetic force can be used to study the gravisensing and response system of roots.

Non-NASA Center↗

NASA NTRS2011

Differential Processing of Low and High LET Radiation Induced DNA Damage: Investigation of Switch from ATM to ATR Signaling

The members of the phosphatidylinositol kinase-like kinase family of proteins namely ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) are directly responsible for the maintenance of genomic integrity by mounting DDR through signaling and facilitating the recruitment of repair factors at the sites of DNA damage along with coordinating the deployment of cell cycle checkpoints to permit repair by phosphorylating Checkpoint kinase Chk1, Chk2 and p53. High LET radiation from GCR (Galactic Cosmic Rays) consisting mainly of protons and high energy and charged (HZE) particles from SPE (Solar Particle Event) pose a major health risk for astronauts on their space flight missions. The determination of these risks and the design of potential safeguards require sound knowledge of the biological consequences of lesion induction and the capability of the cells to counter them. We here strive to determine the coordination of ATM and ATR kinases at the break sites directly affecting checkpoint signaling and DNA repair and whether differential processing of breaks induced by low and high LET radiation leads to possible augmentation of swap of these damage sensors at the sites of DNA damage. Exposure of cells to IR triggers rapid autophosphorylation of serine-1981 that causes dimer dissociation and initiates monomer formation of ATM. ATM kinase activity depends on the disruption of the dimer, which allows access and phosphorylation of downstream ATM substrates like Chk2. Evidence suggests that ATM is activated by the alterations in higher-order chromatin structure although direct binding of ATM to DSB ends may be a crucial step in its activation. On the other hand, in case of ATR, RPA (replication protein A)-coated ssDNA (single-stranded DNA) generated as a result of stalled DNA replication or during processing of chromosomal lesions is crucial for the localization of ATR to sites of DNA damage in association with ATR-interacting protein (ATRIP). Although the majority of RPA-coated ssDNA is generally present only during DNA replication, ATR activation in G1 and G2-phase might still require formation of RPA-coated ssDNA, probably initiated by the MRN-CtIP complex and then extended by the Exo1- or BLM-dependent mechanisms at the sites of DSBs. Evidence accumulates that activation of ATM and ATR are oppositely regulated by the length of single stranded overhangs generated at the break sites by processes mentioned above and these stretches of single stranded overhangs hold the clue for ATM to ATR switch at broken DNA ends. We irradiated 82-6hTERT human fibroblast cells with low LET gamma-rays and high LET Fe and Si particles. Preliminary results with cells exposed to 1Gy gamma-rays show that the kinetics of pChk2-pT68 foci formation is comparable to that of gamma-H2AX although they appear to recede quicker. The number and intensity of observed foci reaches a maximum at 30 min and 60 min post IR for Chk2-pT68 and gamma-H2AX foci respectively and all Chk2-pT68 foci colocalize with gamma-H2AX foci. The kinetics of Chk1-pS345 and ATRIP are being determined. Results of Chk2-pT68 foci kinetics was also corroborated by western blot experiments, although phosphorylation was detected as early as 10 min and started receding 30 min post IR with 2Gy of gamma-rays. On the other hand, level of ATR-pS428 reached its maximum between 60 and 120 min and was maintained until the last measured time point of 4 hours post IR as determined by western blotting. Experiments performed with high LET Fe and Si particles will be reported.

Saha, Janapriya↗

NASA NTRSDate not supplied

Hall Magnetohydrodynamic Power Generation and Drag Augmentation Using A Coaxial-Electrode Configuration During Hypersonic Entry

For interplanetary missions, a spacecraft must reduce its relative velocity from orbital speeds of multiple kilometers per second to zero in order to safely land on the surface of a planetary body. During this phase known as planetary reentry, the spacecraft undergoes high speed above Mach 5 up to Mach 30. This hyper-sonic flight regime imposes a strong bow shock in front of the vehicle that imparts extreme aerodynamic and thermal effects. In addition, during portions of this regime, a plasma is formed in the post-shock flow-field around the vehicle due to these high temperatures. Interaction between an applied magnetic field with this electrically conductive fluid, or magnetohydrodynamic (MHD) interaction, can be utilized to convert kinetic energy from the flow into storable electrical energy. Onboard MHD energy generation can benefit the spacecraft by increasing the power of active thermal control components and vehicle control systems during reentry. MHD interaction also exerts a Lorentz body force on the plasma flow that can be manipulated to act as an additional drag force through the vehicle body. MHD drag augmentation can benefit the spacecraft with an additional control mechanism that operates without moving parts. This can be utilized at higher altitudes and subsequently reduce convective heat transfer to the vehicle. MHD interaction with plasma flow suggests that both power generation and drag augmentation can be integrated together in one design. Modern numerical studies have only demonstrated the viability and potential of MHD energy generation and drag modulation separately for implementation into future spacecraft designs [1] [2] [3]. Steeves et. al. presented one possible generator design specifically for reentry vehicles that utilized a modular panel with two embedded electromagnets and two extruding electrodes for air plasma to flow between. Fujino et. al. presented results that indicated increased total drag with a permanent magnet embedded in the blunt body of the Orbital Reentry Experiment (OREX) trajectory. Furthermore, experimental investigations of these two MHD applications have been limited and separate due to the difficult technical nature of experimental de-sign and analysis. For MHD energy generation, there have been two designs which used a cylindrical fore-body with two embedded permanent magnets and two outward facing curved electrodes for tangency to an artificially ionized plasma that flowed along the body length [4] [5]. The first design was studied using an air microwave (MW) ionized supersonic plasma wind tunnel and the second design used radio frequency (RF) ionization of Argon, but both physically demonstrated the feasibility of MHD energy generation in reentry plasma conditions. For MHD drag modulation, one study involved a small-scale cylindrical blunt body embedded with permanent magnets immersed in plasma flow in an arcjet tunnel [6], and another utilized a spherical permanent magnet enclosed with a spherical forebody that was evaluated in a shock expansion tunnel [7]. Both experimental studies provided physical evidence of drag augmentation due to MHD interactions. Therefore, because of the multi-faceted effects of MHD along with both applications having been deemed feasible and beneficial during reentry, this indicates that a coupled power generation and drag modulation design could be achievable. The axi-symmetric nature of blunt bodies for reentry suggests that a spherical set of two ring electrodes near the nose along the body axis. Based on first principles, flow along the walls of the spherical body can then produce MHD interactions between the electrodes. As a result, two currents are generated: a Hall current that produces power and a primary inductive current that augments the drag force. The goal of this work is to provide a simulated design of a coaxial-electrode con-figuration for power generation and drag modulation for experimental testing.

E. Leong↗