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Redox-mediated activation of latent transforming growth factor-beta 1

Transforming growth factor beta 1 (TGF beta) is a multifunctional cytokine that orchestrates response to injury via ubiquitous cell surface receptors. The biological activity of TGF beta is restrained by its secretion as a latent complex (LTGF beta) such that activation determines the extent of TGF beta activity during physiological and pathological events. TGF beta action has been implicated in a variety of reactive oxygen-mediated tissue processes, particularly inflammation, and in pathologies such as reperfusion injury, rheumatoid arthritis, and atherosclerosis. It was recently shown to be rapidly activated after in vivo radiation exposure, which also generates reactive oxygen species (ROS). In the present studies, the potential for redox-mediated LTGF beta activation was investigated using a cell-free system in which ROS were generated in solution by ionizing radiation or metal ion-catalyzed ascorbate reaction. Irradiation (100 Gray) of recombinant human LTGF beta in solution induced 26% activation compared with that elicited by standard thermal activation. Metal-catalyzed ascorbate oxidation elicited extremely efficient recombinant LTGF beta activation that matched or exceeded thermal activation. The efficiency of ascorbate activation depended on ascorbate concentrations and the presence of transition metal ions. We postulate that oxidation of specific amino acids in the latency-conferring peptide leads to a conformation change in the latent complex that allows release of TGF beta. Oxidative activation offers a novel route for the involvement of TGF beta in tissue processes in which ROS are implicated and endows LTGF beta with the ability to act as a sensor of oxidative stress and, by releasing TGF beta, to function as a signal for orchestrating the response of multiple cell types. LTGF beta redox sensitivity is presumably directed toward recovery of homeostasis; however, oxidation may also be a mechanism of LTGF beta activation that can be deleterious during disease mechanisms involving chronic ROS production.

Non-NASA Center↗

Investigation of the Effects of Facility Background Pressure on the Performance and Voltage-Current Characteristics of the High Voltage Hall Accelerator

The National Aeronautics and Space Administration (NASA) Science Mission Directorate In-Space Propulsion Technology office is sponsoring NASA Glenn Research Center to develop a 4 kW-class Hall thruster propulsion system for implementation in NASA science missions. A study was conducted to assess the impact of varying the facility background pressure on the High Voltage Hall Accelerator (HiVHAc) thruster performance and voltage-current characteristics. This present study evaluated the HiVHAc thruster performance in the lowest attainable background pressure condition at NASA GRC Vacuum Facility 5 to best simulate space-like conditions. Additional tests were performed at selected thruster operating conditions to investigate and elucidate the underlying physics that change during thruster operation at elevated facility background pressure. Tests were performed at background pressure conditions that are three and ten times higher than the lowest realized background pressure. Results indicated that the thruster discharge specific impulse and efficiency increased with elevated facility background pressure. The voltage-current profiles indicated a narrower stable operating region with increased background pressure. Experimental observations of the thruster operation indicated that increasing the facility background pressure shifted the ionization and acceleration zones upstream towards the thruster's anode. Future tests of the HiVHAc thruster are planned at background pressure conditions that are expected to be two to three times lower than what was achieved during this test campaign. These tests will not only assess the impact of reduced facility background pressure on thruster performance, voltage-current characteristics, and plume properties; but will also attempt to quantify the magnitude of the ionization and acceleration zones upstream shifting as a function of increased background pressure.

Electric Propulsion↗

Investigation of the Effects of Facility Background Pressure on the Performance and Voltage-Current Characteristics of the High Voltage Hall Accelerator

The National Aeronautics and Space Administration (NASA) Science Mission Directorate In-Space Propulsion Technology office is sponsoring NASA Glenn Research Center to develop a 4 kW-class Hall thruster propulsion system for implementation in NASA science missions. A study was conducted to assess the impact of varying the facility background pressure on the High Voltage Hall Accelerator (HiVHAc) thruster performance and voltage-current characteristics. This present study evaluated the HiVHAc thruster performance in the lowest attainable background pressure condition at NASA GRC Vacuum Facility 5 to best simulate space-like conditions. Additional tests were performed at selected thruster operating conditions to investigate and elucidate the underlying physics that change during thruster operation at elevated facility background pressure. Tests were performed at background pressure conditions that are three and ten times higher than the lowest realized background pressure. Results indicated that the thruster discharge specific impulse and efficiency increased with elevated facility background pressure. The voltage-current profiles indicated a narrower stable operating region with increased background pressure. Experimental observations of the thruster operation indicated that increasing the facility background pressure shifted the ionization and acceleration zones upstream towards the thrusters anode. Future tests of the HiVHAc thruster are planned at background pressure conditions that are expected to be two to three times lower than what was achieved during this test campaign. These tests will not only assess the impact of reduced facility background pressure on thruster performance, voltage-current characteristics, and plume properties; but will also attempt to quantify the magnitude of the ionization.

Pressure Effects↗

Isotopic, Chemical and Mineralogical Investigations of Extraterrestrial Materials

The principal aim of our work was to improve our understanding of the earliest evolutionary period of our solar system (i.e. the first tens of millions of years). We have studied its chronology by using short and long term chronometers (based on extinct and long lived radioactive nuclei), explored the bearing of short lived nuclei on planetary heating and differentiation, and the addition of 'exotic' nuclei to solar system matter to help constrain models of nucleosynthesis. Our basic tool is high precision Thermal Ionization Mass Spectrometry (TIMS). Over the years we have developed clean chemical separation procedures for many elements. The chemical elements most relevant to our investigations are Cr, Ni, Rb, Sr, Sm, Nd, Pb, and U, for which highly efficient measurement techniques by TIMS have been developed and have been in use in our laboratory for many years. We have explored the Mn-53 Cr-53 system (T (Mn-53) = 3.7 Ma) and have found it to be a powerful tool to obtain relative ages of meteorite formation and, more general, of early solar system processes with a time resolution of approx. 1 Ma. By measuring the Mn-Cr system in many meteorite types (chondrites, basaltic achondrites, angrites, pallasites, etc.) we have found that this condition is indeed met for most meteorite families.

Lugmair, Guenter W.↗

Elemental, Isotopic, and Organic Analysis on Mars with Laser TOF-MS

The in-depth landed exploration of Mars will require increasingly sophisticated robotic analytical tools for both in situ composition science [1] and reconnaissance for sample return [2]. Beyond dust, rock surfaces, and topsoil, samples must be accessed within rocks and ice, well below surface soil, and possibly in elevated deposit layers. A range of spatial scales will be studied, and for the most information-rich microscopic analyses, samples must be acquired, prepared, and positioned with high precision. In some cases samples must also be brought into a vacuum chamber. After expending such resources, it will be important to apply techniques that provide a wide range of information about the samples. Microscopy, mineralogy, and molecular/organic, elemental, and isotopic analyses are all needed, at a minimum, to begin to address the in situ goals at Mars. These techniques must work as an efficient suite to provide layers of data, each layer helping to determine if further analysis on a given sample is desired. In the spirit of broad-band and efficient data collection, we are developing miniature laser time-of-flight mass spectrometers (TOF-MS) for elemental, isotopic, and molecular/organic microanalysis of unprepared solid samples. Laser TOF-MS uses a pulsed laser to volatilize and ionize material from a small region on the sample. The laser energy and focus can be adjusted for atomic and molecular content, sampling area, and depth. Ions travel through the instrument and are detected at a sequence of times proportional to the square root of their mass-to- charge ratios. Thus, each laser pulse produces a complete mass spectrum (in less than 50 microseconds). These instruments can now be significantly miniaturized (potentially to the size of a soda can) without a loss in performance. This effort is reviewed here with an emphasis on applications to Mars exploration.

Brinckerhoff, W. B.↗

Status of Pulsed Inductive Thruster Research

The TRW Pulsed Inductive Thruster (PIT) is an electromagnetic propulsion system that can provide high thrust efficiency over a wide range of specific impulse values. In its basic form, the PIT consists of a flat spiral coil covered by a thin dielectric plate. A pulsed gas injection nozzle distributes a thin layer of gas propellant across the plate surface at the same time that a pulsed high current discharge is sent through the coil. The rising current creates a time varying magnetic field, which in turn induces a strong azimuthal electric field above the coil. The electric field ionizes the gas propellant and generates an azimuthal current flow in the resulting plasma. The current in the plasma and the current in the coil flow in opposite directions, providing a mutual repulsion that rapidly blows the ionized propellant away from the plate to provide thrust. The thrust and specific impulse can be tailored by adjusting the discharge power, pulse repetition rate, and propellant mass flow, and there is minimal if any erosion due to the electrodeless nature of the discharge. Prior single-shot experiment,; performed with a Diameter diameter version of the PIT at TRW demonstrated specific impulse values between 2,000 seconds and 8,000 seconds, with thruster efficiencies of about 52% for ammonia. This paper outlines current and planned activities to transition the single shot device into a multiple repetition rate thruster capable of supporting NASA strategic enterprise missions.

Hrbud, Ivana↗

Design of closed-cycle MHD generator with nonequilibrium ionization and system

A method is developed to include the nonequilibrium ionization process in the MHD generator duct design equations, and these equations are coupled to the thermodynamic conditions of the closed cycle system. This is used to relate MHD generator size, configuration and gas conditions to the overall thermodynamic efficiency of the system. The system studied consists of an MHD loop (Ar + Cs or He + Cs) topping a steam bottoming plant.

Voshall, R. E.↗

Asymmetric Memory Circuit Would Resist Soft Errors

Some nonlinear error-correcting codes more efficient in presence of asymmetry. Combination of circuit-design and coding concepts expected to make integrated-circuit random-access memories more resistant to "soft" errors (temporary bit errors, also called "single-event upsets" due to ionizing radiation). Integrated circuit of new type made deliberately more susceptible to one kind of bit error than to other, and associated error-correcting code adapted to exploit this asymmetry in error probabilities.

Buehler, Martin G.↗

Status of Pulsed Inductive Thruster Research

The TRW Pulsed Inductive Thruster (PIT) is an electromagnetic propulsion system that can provide high thrust efficiency over a wide range of specific impulse values. In its basic form, the PIT consists of a flat spiral coil covered by a thin dielectric plate. A pulsed gas injection nozzle distributes a thin layer of gas propellant across the plate surface at the same time that a pulsed high current discharge is sent through the coil. The rising current creates a time varying magnetic field, which in turn induces a strong azimuthal electric field above the coil. The electric field ionizes the gas propellant and generates an azimuthal current flow in the resulting plasma. The current in the plasma and the current in the coil flow in opposite directions, providing a mutual repulsion that rapidly blows the ionized propellant away from the plate to provide thrust. The thrust and specific impulse can be tailored by adjusting the discharge power, pulse repetition rate, and propellant mass flow, and there is minimal if any erosion due to the electrodeless nature of the discharge. Prior single-shot experiments performed with a 1-meter diameter version of the PIT at TRW demonstrated specific impulse values between 2,000 seconds and 8,000 seconds, with thruster efficiencies exceeding 55% for ammonia and hydrazine propellants. This paper outlines current and planned activities to transition the single shot device into a multiple repetition rate thruster capable of supporting future DOD and NASA strategic enterprise missions.

Hrbud, Ivana↗

Results on the energy dependence of cosmic-ray charge composition

Results of measurements by a balloon-borne ionization spectrometer of the energy dependence of high-energy cosmic-ray charge composition. The results presented are greatly improved over those obtained earlier by Ormes et al. (1971) by the use of a multidimensional charge analysis with more efficient background rejection, and a more accurate energy determination. Complex couplings between the charge, energy, and trajectory information were taken into account and are discussed. The spectra of individual elements up to oxygen and of groups of nuclei up through iron were measured up to almost 100 GeV per nucleon. The energy spectrum of the secondary nuclei, B + N, is found to be steeper than that of the primary nuclei, C + O, in agreement with Smith et al. (1973). The most dramatic finding is that the spectrum of the iron nuclei is flatter than that of the carbon and oxygen nuclei by 0.57 plus or minus 0.14 of a power.

Balasubrahmanyan, V. K.↗

Helium Pressure Shift of the Hyperfine Clock Transition in Hg-201(+)

There are two stable odd isotopes of mercury with singly ionized hyperfine structure suitable for a microwave atomic clock: Hg-199(+) and Hg-201(+). We are investigating the viability of a trapped ion clock based on Hg-201(+) in a configuration that uses a buffer gas to increase ion loading efficiency and counter ion heating from rf trapping fields. Traditionally, either helium or neon is used as the buffer gas at approx. 10(exp -5) torr to confine mercury ions near room temperature. In addition to the buffer gas, other residual background gasses such as H2O, N2, O2, CO, CO2, and CH2 may be present in trace quantities. Collisions between trapped ions and buffer gas or background gas atoms/molecules produce a momentary shift of the ion clock transition frequency and constitute one of the largest systematic effects in this type of clock. Here we report an initial measurement of the He pressure shift in Hg-201(+) and compare this to Hg-199(+).

Larigani, S. Taghavi↗

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.↗

Method to Remove Particulate Matter from Dusty Gases at Low Pressures

Future human exploration of Mars will rely on local Martian resources to reduce the mass, cost, and risk of space exploration launched from Earth. NASA's In Situ Resource Utilization (ISRU) Project seeks to produce mission consumables from local Martian resources, such as atmospheric gas. The Martian atmosphere, however, contains dust particles in the 2-to-10 -micrometer range. These dust particles must be removed before the Martian atmospheric gas can be processed. The low pressure of the Martian atmosphere, at 5 to 10 mbars, prevents the development of large voltages required for a standard electrostatic precipitator. If the voltage is increased too much, the corona transitions into a glow/streamer discharge unsuitable for the operation of a precipitator. If the voltage is not large enough, the dust particles are not sufficiently charged and the field is not strong enough to drive the particles to the collector. A method using electrostatic fields has been developed to collect dust from gaseous environments at low pressures, specifically carbon dioxide at pressures around 5 to 10 mbars. This method, commonly known as electrostatic precipitation, is a mature technology in air at one atmosphere. In this case, the high voltages required for the method to work can easily be achieved. However, in carbon dioxide at low pressures, such as those found on Mars, large voltages are not possible. The innovation reported here consists of two concentric cylindrical electrodes set at specific potential difference that generate an electric field that produces a corona capable of imparting an electrostatic charge to the incoming dust particles. The strength of the field is carefully balanced so as to produce a stable charging corona at 5 to 10 mbars, and is also capable of imparting a force to the particles that drives them to the collecting electrode. There are only two possible ways that dust can be removed from Martian atmospheric gas intakes: with this electrostatic precipitator design, and with the use of filters. However, filters require upstream compression of the gas to be treated because the atmospheric pressure on Mars is too close to vacuum to use a vacuum pump downstream to the filter to draw the gas through the filter. The electrostatic precipitator is the best and more efficient solution for this environment. No other precipitator designs have been developed for the environment of Mars due to the challenges of the low atmospheric pressure. Dust particles are charged using corona generation around the high-voltage discharge electrode, which ionizes gas molecules. Since the atmospheric gas intakes for the ISRU processing chambers will likely be cylindrical, cylindrical precipitator geometry was chosen. The electrostatic precipitator design presented here removes simulated Martian dust particles in the required range in a simulated Martian atmospheric environment. The current-voltage (I-V) characteristic curves taken for the nine precipitator configurations at 9 mbars of pressure showed that a cylindrical collecting electrode 7.0 cm in diameter with a concentric positive high voltage electrode 100 m thick provides the best range of voltage and charging corona current. This precipitator design is effective for the size of the dust particles expected in the Martian atmosphere. Mass determination, as well as microscopic images and particle size distributions of dust collected on a silicon wafer placed directly below the precipitator with the field on and off, showed excellent initial results.

Calle, Carlos↗

Evolution of interstellar pickup ions in the solar wind

A model is constructed for the evolution of an interstellar pickup ion distribution in the solar wind. The model assumes that the ions are immediately isotropized at ionization and follows the subsequent development of the distribution function as the particles are convected with the solar wind. The effects of energy diffusion in an ambient wave field with a power law spectrum, adiabatic deceleration in the expanding solar wind, and continual addition of newly ionized particles are all included in the model. An analytical expression describing the evolution of the distribution function in phase space velocity and heliocentric radius is obtained. The distribution quickly approaches an asymptotic shape in phase space which depends on the relative efficiency of the energy diffusion process compared to that of adiabatic deceleration. At large distances from the sun the density of pickup ions falls as 1/r in this model. An expression for the distribution function at large distances and for large particle speed is presented. The asymptotic shape should describe the distribution of pickup ions in the outer heliosphere and could be used as an input distribution for a model of the anomalous component of heliosphere and could be used as an input distribution for a model of the anomalous component of cosmic rays. Comparison of this work with the recent observation of He(+) at 1 AU implies that the energy diffusion process is very weak inside 1 AU.

Isenberg, Philip A.↗

Properties of a B0 I stellar wind and interstellar grains derived from Ginga observations of the binary X-ray pulsar 4U 1538-52

From measurements of the X-ray eclipse phenomena of the binary X-ray pulsar 4U 1538-52, we derive properties of the stellar wind of its B0 I companion, QV Nor, and a constraint on models of interstellar grains. Estimates of the wind density as a function of the distance from the center of QV Nor are obtained from an analysis of the variation of X-ray attenuation during an eclipse egress. A Monte Carlo computation of the absorption and scattering of X-rays in the X-ray-ionized wind accounts for approximately two-thirds of the spectrum of X-rays with energies above 4.5 keV observed during the eclipse. Our upper limit on R(sub XV) is 0.06/mag, which implies that the X-ray scattering efficiency of interstellar dust is less than expected for solid grains with a size distribution of the form n(sub g)(a) approximately a(exp -3.5) in the range from 0.005 to 0.25 microns and composed of silicate (R(sub XV) = 0.22/mag) or a silicate-graphite mixture (R(sub XV) = 0.11/mag) as derived from the calculations of Martin & Rouleau (1991). This lends support to the idea (Mathis & Whiffen 1989) that interstellar grains are 'fluffy' aggregates with an average bulk density less than that of their constitutent particles. Such aggregates would have a smaller ratio of X-ray scattering efficiency to optical extinction efficiency compared with solid grains of the same material.

Clark, George W.↗

A Green's Function Approach to Simulate DNA Damage by the Indirect Effect

The DNA damage is of fundamental importance in the understanding of the effects of ionizing radiation. DNA is damaged by the direct effect of radiation (e.g. direct ionization) and by indirect effect (e.g. damage by.OH radicals created by the radiolysis of water). Despite years of research, many questions on the DNA damage by ionizing radiation remains. In the recent years, the Green's functions of the diffusion equation (GFDE) have been used extensively in biochemistry [1], notably to simulate biochemical networks in time and space [2]. In our future work on DNA damage, we wish to use an approach based on the GFDE to refine existing models on the indirect effect of ionizing radiation on DNA. To do so, we will use the code RITRACKS [3] developed at the NASA Johnson Space Center to simulate the radiation track structure and calculate the position of radiolytic species after irradiation. We have also recently developed an efficient Monte‐Carlo sampling algorithm for the GFDE of reversible reactions with an intermediate state [4], which can be modified and adapted to simulate DNA damage by free radicals. To do so, we will use the known reaction rate constants between radicals (OH, eaq, H,...) and the DNA bases, sugars and phosphates and use the sampling algorithms to simulate the diffusion of free radicals and chemical reactions with DNA. These techniques should help the understanding of the contribution of the indirect effect in the formation of DNA damage and double‐strand breaks.

Plante, Ianik↗

Taking SiC Power Devices to the Final Frontier: Addressing Challenges of the Space Radiation Environment

Silicon carbide power device technology has the potential to enable a new generation of aerospace power systems that demand high efficiency, rapid switching, and reduced mass and volume in order to expand space-based capabilities. For this potential to be realized, SiC devices must be capable of withstanding the harsh space radiation environment. Commercial SiC components exhibit high tolerance to total ionizing dose but to date, have not performed well under exposure to heavy ion radiation representative of the on-orbit galactic cosmic rays. Insertion of SiC power device technology into space applications to achieve breakthrough performance gains will require intentional development of components hardened to the effects of these highly-energetic heavy ions. This work presents heavy-ion test data obtained by the authors over the past several years for discrete SiC power MOSFETs, JFETs, and diodes in order to increase the body of knowledge and understanding that will facilitate hardening of this technology to space radiation effects. Specifically, heavy-ion irradiation data taken under different bias, temperature, and ion beam conditions is presented for devices from different manufacturers, and the emerging patterns discussed.

Power semiconductor devices↗

5.8kV SiC PiN Diode for Switching of High-Efficiency Inductive Pulsed Plasma Thruster Circuits

Inductive Pulsed Plasma Thruster (IPPT) pulse circuits, such as those needed to operate the Pulsed Inductive Thruster (PIT), are required to quickly switch capacitor banks operating at a period of μs while conducting current at levels on the order of at least 10 kA. [1,2] For all iterations of the PIT to date, spark gaps have been used to discharge the capacitor bank through an inductive coil. Recent availability of fast, high‐power solid state switching devices makes it possible to consider the use of semiconductor switches in modern IPPTs. In addition, novel pre‐ionization schemes have led to a reduction in discharge energy per pulse for electric thrusters of this type, relaxing the switching requirements for these thrusters. [3,4] Solid state switches offer the advantage of greater controllability and reliability, as well as decreased drive circuit dimensions and mass relative to spark gap switches. The use of solid state devices such as Integrated Gate Bipolar Transistors (IGBTs), Gate Turn‐off Thyristors (GTOs) and Silicon‐Controlled Rectifiers (SCRs) often involves the use of power diodes. These semiconductor devices may be connected antiparallel to the switch for protection from reverse current, or used to reduce power loss in a circuit by clamping off current ringing. In each case, higher circuit efficiency may be achieved by using a diode that is able to transition, or 'switch,' from the forward conducting state ('on' state) to the reverse blocking state ('off' state) in the shortest amount of time, thereby minimizing current ringing and switching losses. Silicon Carbide (SiC) PiN diodes offer significant advantages to conventional fast‐switching Silicon (Si) diodes for high power and fast switching applications. A wider band gap results in a breakdown voltage 10 times that of Si, so that a SiC device may have a thinner drift region for a given blocking voltage. [5] This leads to smaller, lighter devices for high voltage applications, as well as reduced forward conduction losses, faster reverse recovery time (faster turn‐off), and lower‐magnitude reverse recovery current. In addition, SiC devices have lower leakage current as compared to their Si counterparts, and a high thermal conductivity, potentially allowing the former to operate at higher temperatures with a smaller, lighter heatsink (or no heatsink at all).

Toftul, Alexandra↗