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At least 235 records · Page 13

Cytogenetic Response to Ionizing Radiation Exposure in Human Fibroblasts with Suppressed Expression of Non-DSB Repair Genes

Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in double-strand break (DSB) repair, and its impact on cytogenetic responses has not been well studied. The purpose of this study is to identify new roles of IR inducible genes in radiation-induced chromosome aberrations and micronuclei formation. In the study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by small interfering RNA in human fibroblast cells. Frequencies of micronuclei (MN) formation and chromosome aberrations were measured to determine the efficiency of cytogenetic repair, and the fraction of bi-nucleated cells in the MN analysis was used as a marker for cell cycle progression. In response to gamma radiation, the formation of MN was significantly increased by suppressed expression of five genes: Ku70 (DSB repair pathway), XPA (nucleotide excision repair pathway), RPA1 (mismatch repair pathway), RAD17 and RBBP8 (cell cycle control). Knocked-down expression of four genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Moreover, decreased XPA, p21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Nine of these eleven genes, whose knock-down expression affected cytogenetic repair, were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate IR-induced biological consequences. Furthermore, eight non-DBS repair genes showed involvement in regulating DSB repair, indicating that successful DSB repair requires both DSB repair mechanisms and non-DSB repair systems.

Zhang, Ye↗

Theory and observations of electromagnetic ion cyclotron waves in Saturn's inner magnetosphere

High-resolution Voyager 1 magnetic field observations of Saturn's inner magnetosphere are examined for the presence of ULF waves. Quasi-circular left-hand polarized transverse oscillations are found in the near-equatorial region of 5-7 Rs with a wave period about 10 s and peak amplitude of about 2 nT. The wave is identified as the electromagnetic oxygen cyclotron mode occurring at a frequency just below the O(+) ion cyclotron frequency. A theoretical model of wave excitation based on gyroresonant coupling through a temperature anisotropy of O(+) pickup ions is developed which accounts for the principal features of the wave spectrum. It is hypothesized that wave-particle interactions provide a level of scattering commensurate with the weak pitch angle diffusion regime but nonetheless one that regulates and maintains a constant thermal anisotropy of ions along the magnetic field. Arguments are also presented that O(+) was the dominant thermal ion of the Dione-Tethys plasma torus at the time of the Pioneer 11 encounter the year previous to the Voyager 1 measurements.

Barbosa, D. D.↗

p53 deficiency alters the yield and spectrum of radiation-induced lacZ mutants in the brain of transgenic mice

Exposure to heavy particle radiation in the galacto-cosmic environment poses a significant risk in space exploration and the evaluation of radiation-induced genetic damage in tissues, especially in the central nervous system, is an important consideration in long-term manned space missions. We used a plasmid-based transgenic mouse model system, with the pUR288 lacZ transgene integrated in the genome of every cell of C57Bl/6(lacZ) mice, to evaluate the genetic damage induced by iron particle radiation. In order to examine the importance of genetic background on the radiation sensitivity of individuals, we cross-bred p53 wild-type lacZ transgenic mice with p53 nullizygous mice, producing lacZ transgenic mice that were either hemizygous or nullizygous for the p53 tumor suppressor gene. Animals were exposed to an acute dose of 1 Gy of iron particles and the lacZ mutation frequency (MF) in the brain was measured at time intervals from 1 to 16 weeks post-irradiation. Our results suggest that iron particles induced an increase in lacZ MF (2.4-fold increase in p53+/+ mice, 1.3-fold increase in p53+/- mice and 2.1-fold increase in p53-/- mice) and that this induction is both temporally regulated and p53 genotype dependent. Characterization of mutants based on their restriction patterns showed that the majority of the mutants arising spontaneously are derived from point mutations or small deletions in all three genotypes. Radiation induced alterations in the spectrum of deletion mutants and reorganization of the genome, as evidenced by the selection of mutants containing mouse genomic DNA. These observations are unique in that mutations in brain tissue after particle radiation exposure have never before been reported owing to technical limitations in most other mutation assays.

Non-NASA Center↗

Osteogenic Transcription Regulated by Exaggerated Stretch Loading via Convergent Wnt Signaling

Cell and animal studies conducted onboard the International Space Station and formerly the Shuttle flights have provided data illuminating the deleterious biological response of bone to mechanical unloading. Down regulation of proliferative mechanisms within stem cell populations of the osteogenic niche is a suggested mechanism for loss of bone mass. However the intercellular communicative cues from osteoblasts and osteocytes in managing stem cell proliferation and osteogenic differentiation are largely unknown. In this investigation, MLO-Y4 osteocyte-like and MC3T3-E1 osteoblast-like cells, are co-culture under dynamic tensile conditions and evaluated for phenotypic expression of biochemical signaling proteins influential in driving stem cell differentiation. MLO-Y4 and MC3T3-E1 were co-cultured on polyethersulfone membrane with a 0.45m porosity to permit soluble factor transfer and direct cell-cell gap junction signaling. Cyclic tensile stimulation was applied for 48 h at a frequency of 0.1Hz and strain of 0.1. Total Live cell counts indicate mechanical activation of MC3T3-E1s inhibits proliferation while MLO-Y4s increase in number. However, the percent of live MLO-Y4s within the population is low (46.3 total count, *p0.05, n4) suggesting a potential apoptotic signaling cascade. Immunofluorescence demonstrated that stimulation of co-cultures elicits increased gap junction communication. Previously reported PCR evaluation of osteogenic markers further corroborate that the co-cultured populations communicative networks play a role in translating mechanical signals to molecular messaging. These findings suggest that an osteocyte-osteoblast signaling feedback mechanism may regulate mechanotransduction of an apoptotic cascade within osteocytes and transcription of cytokine signaling proteins responsible for stem cell niche recruitment much more directly than previously believed.

mechanical stimulation↗

Low-to-Medium Power Single Chip Digital Controlled DC-DC Regulator for Point-of-Load Applications

A DC-DC converter for generating a DC output voltage includes: a digitally controlled pulse width modulator (DPWM) for controlling a switching power stage to supply a varying voltage to an inductor; and a digital voltage feedback circuit for controlling the DPWM in accordance with a feedback voltage corresponding to the DC output voltage, the digital voltage feedback circuit including: a first voltage controlled oscillator for converting the feedback voltage into a first frequency signal and to supply the first frequency signal to a first frequency discriminator; a second voltage controlled oscillator for converting a reference voltage into a second frequency signal and to supply the second frequency signal to a second frequency discriminator; a digital comparator for comparing digital outputs of the first and second frequency discriminators and for outputting a digital feedback signal; and a controller for controlling the DPWM in accordance with the digital feedback signal.

Adell, Philippe C.↗

En route noise: NASA propfan test aircraft (corrected data - simplified procedure)

Surface noise measurements were made during a joint National Aeronautics and Space Administration (NASA) and Federal Aviation Administration (FAA) program to study the high-altitude, low-frequency acoustic noise propagation characteristics of the Advanced Turboprop (propfan) Aircraft. The measurements were made on October 26-31, 1987 in Huntsville, Alabama and on April 3-13, 1989 at the White Sands Missile Range (WSMR), New Mexico. To effectively compare flight-to-flight data as received on the ground, the procedures and practices of Federal Air Regulation (FAR) Part 36 were used as a guide in adjusting the measured ground data at the time of LA(sub MAX) to a set of reference conditions. After the data for each event were processed using slow detector characteristics, the data record at LA(sub MAX) was then identified and the coordinates of the aircraft at the time of emission were calculated, taking into account atmospheric refraction effects. The effects of atmospheric absorption through the test day and reference day atmosphere were also taken into account and the 1/3-octave data were adjusted accordingly.

Rickley, E. J.↗

Properties of nearly perfect crystals at very low temperatures

Data shows that the frequency stability of 5 MHz AT-cut quartz crystal oscillators is improved by lowering the temperature to 4.3 K. The resultant level of stability is apparently not, at this point, sufficient for a clock accurate to 1 part in 10(exp 17). However, many improvements are possible in the scheme presented here. These would involve better temperature regulation, better crystal mounting and vibration isolation, and lower temperatures. Below the lambda-transition at 2.17 K the residual bubbling of the bath would be eliminated. Thus, the prospect of a successful clock built on this scheme is not ruled out.

Weber, J.↗

Altered Gene Expressions and Cytogenetic Repair Efficiency in Cells with Suppressed Expression of XPA after Proton Exposure

Cellular responses to damages from ionizing radiation (IR) exposure are influenced not only by the genes involved in DNA double strand break (DSB) repair, but also by non- DSB repair genes. We demonstrated previously that suppressed expression of several non-DSB repair genes, such as XPA, elevated IR-induced cytogenetic damages. In the present study, we exposed human fibroblasts that were treated with control or XPA targeting siRNA to 250 MeV protons (0 to 4 Gy), and analyzed chromosome aberrations and expressions of genes involved in DNA repair. As expected, after proton irradiation, cells with suppressed expression of XPA showed a significantly elevated frequency of chromosome aberrations compared with control siRNA treated (CS) cells. Protons caused more severe DNA damages in XPA knock-down cells, as 36% cells contained multiple aberrations compared to 25% in CS cells after 4Gy proton irradiation. Comparison of gene expressions using the real-time PCR array technique revealed that expressions of p53 and its regulated genes in irradiated XPA suppressed cells were altered similarly as in CS cells, suggesting that the impairment of IR induced DNA repair in XPA suppressed cells is p53-independent. Except for XPA, which was more than 2 fold down regulated in XPA suppressed cells, several other DNA damage sensing and repair genes (GTSE1, RBBP8, RAD51, UNG and XRCC2) were shown a more than 1.5 fold difference between XPA knock-down cells and CS cells after proton exposure. The possible involvement of these genes in the impairment of DNA repair in XPA suppressed cells will be further investigated.

Zhang, Ye↗

Nonlinear feedback control of highly manoeuvrable aircraft

This paper describes the application of nonlinear quadratic regulator (NLQR) theory to the design of control laws for a typical high-performance aircraft. The NLQR controller design is performed using truncated solutions of the Hamilton-Jacobi-Bellman equation of optimal control theory. The performance of the NLQR controller is compared with the performance of a conventional P + I gain scheduled controller designed by applying standard frequency response techniques to the equations of motion of the aircraft linearized at various angles of attack. Both techniques result in control laws which are very similar in structure to one another and which yield similar performance. The results of applying both control laws to a high-g vertical turn are illustrated by nonlinear simulation.

Garrard, William L.↗

Electrical signal transmission in a bone cell network: the influence of a discrete gap junction

A refined electrical cable model is formulated to investigate the role of a discrete gap junction in the intracellular transmission of electrical signals in an electrically coupled system of osteocytes and osteoblasts in an osteon. The model also examines the influence of the ratio q between the membrane's electrical time constant and the characteristic time of pore fluid pressure, the circular, cylindrical geometry of the osteon, and key simplifying assumptions in our earlier continuous cable model (see Zhang, D., S. C. Cowin, and S. Weinbaum. Electrical signal transmission and gap junction regulation in a bone cell network: A cable model for an osteon. Ann. Biomed. Eng. 25:379-396, 1997). Using this refined model, it is shown that (1) the intracellular potential amplitude at the osteoblastic end of the osteonal cable retains the character of a combination of a low-pass and a high-pass filter as the corner frequency varies in the physiological range; (2) the presence of a discrete gap junction near a resting osteoblast can lead to significant modulation of the intracellular potential and current in the osteoblast for measured values of the gap junction coupling strength; and (3) the circular, cylindrical geometry of the osteon is well simulated by the beam analogy used in Zhang et al.

Non-NASA Center↗

Status of the Signals of Opportunity Airborne Demonstrator (SoOp-AD)

Root zone soil moisture (RZSM) is not directly measured by any current satellite instrument, despite its importance as a key link between surface hydrology and deeper processes. Presently, model assimilation of surface measurements or indirect estimates using other methods must be used to estimate this value. Signals of Opportunity (SoOp) methods, exploiting reflected P- and S-band communication satellite signals, have many of the benefits of both active and passive microwave remote sensing. Reutilization of active transmitters, with forward-scattering geometry, presents a strong reflected signal even at orbital altitudes. Microwave radiometry is advantageous as it measures emissivity, which is directly related to dielectric constant and sensitive to water content of soil. Synthetic aperture radar (SAR) is used in P-band (400 MHz) for soil moisture and biomass, but faces issues in obtaining permission to transmit due to spectrum regulations, particularly over North America and Europe. A primary advantage of SAR is excellent spatial resolution. Signals-of-opportunity (SoOp) reflectometry provides a good compromise between radiometry and SAR by providing decent sensitivity and special resolution for RZSM measurements without issues of spectrum access. Further, a SoOp instrument would not be limited to operating in only a few protected frequencies and is also expected to have less susceptibility to radio-frequency interference (RFI). Although advantageous if available, SoOp techniques do not require the ability to demodulate or decode the communication signals. The SoOp instrument is receive only and therefore requires much less electrical power than a SAR and is more similar to a radiometer in receiver architecture. These unique features of SoOp circumvent past obstacles to a spaceborne P-band remote sensing mission and have the potential to enable new RZSM measurements that are not possible with present technology. We will present the latest development status of a SoOp reflectometer airborne demonstrator (SoOp-AD) operating at 250 MHz to take advantage of existing communication satellite. The instrument is currently in laboratory integration and test.

Reflectometers↗

[Individual peculiarities of adaptation to long-term space flights: 24-hour heart rhythm monitoring]

Presented are results of studying 24-hr variability of the cardiac rhythm which characterizes individual difference in reactions of two crew members to the same set of stresses during a 115-day MIR mission. Spacelab (USA) cardiorecorders were used. Data of monitoring revealed significantly different baseline health statuses of the cosmonauts. These functional differences were also observed in the mission. In one of the cosmonauts, the cardiac regulation changed over to a more economic functioning with the autonomous balance shifted towards enhanced sympathetic activity. After 2-3 months on mission he had almost recovered pre-launch level of regulation. In the other, the regulatory system was appreciably strained at the beginning of the mission as compared with preflight baseline. Later on, on flight months 2-3, this strain kept growing till a drastic depletion of the functional reserve. On return to Earth, this was manifested by a strong stress reaction with a sharp decline in power of high-frequency and grow in power of very low frequency components of the heart rhythm. The data suggest that adaptation to space flight and reactions in the readaptation period are dependent on initial health status of crew members, and functional reserve.

long duration↗

Static DC to DC Power Conditioning-Active Ripple Filter, 1 MHZ DC to DC Conversion, and Nonlinear Analysis

Dc to dc static power conditioning systems on unmanned spacecraft have as their inputs highly fluctuating dc voltages which they condition to regulated dc voltages. These input voltages may be less than or greater than the desired regulated voltages. The design of two circuits which address specific problems in the design of these power conditioning systems and a nonlinear analysis of one of the circuits are discussed. The first circuit design is for a nondissipative active ripple filter which uses an operational amplifier to amplify and cancel the sensed ripple voltage. A dc to dc converter operating at a switching frequency of 1 MHz is the second circuit discussed. A nonlinear analysis of the type of dc to dc converter utilized in designing the 1 MHz converter is included.

Sander, W. A., III↗

Use of optical edge and optical flow rate: Information in the perception and control of ground velocity

Previous research (Denton, 1980; Larish & Flach, 1990; Owen, Wolpert, & Warren, 1984; Awe & Johnson, 1989) suggests that people will use one or both of two optical variables as information for the perception and/or regulation of ground velocity. The first variable, global optical flow rate (FR), reflects the angular optical speed, and is proportional to the observer's ground velocity scaled in altitude units, i.e. velocity divided by altitude. Therefore, flow rate is a reliable indicator of ground velocity only under the condition of constant altitude. The second variable, optical edge rate (ER), reflects ground velocity as the frequency at which the optically specified ground edges pass across some optical region. Therefore, edge rate is an accurate indicator of ground velocity when altitude varies, but not when texture density varies. Since both flow rate and edge rate can vary independently of forward ground velocity, accurate ground-velocity control may depend upon using the best optical variable.

Johnson, Walter W.↗

The effect of a microgravity (space) environment on the expression of expansins from the peg and root tissues of Cucumis sativus

In young cucumber seedlings, the peg is a polar outgrowth of tissue that functions by snagging the seed coat, thereby freeing the cotyledons. The development of the peg is thought to be gravity-dependent and has become a model system for plant-gravity response. Peg development requires rapid cell expansion, a process thought to be catalyzed by alpha-expansins, and thus was a good system to identify expansins that were regulated by gravity. This study identified 7 new alpha-expansin cDNAs from cucumber seedlings (Cucumis sativus L. cv Burpee Hybrid II) and examined their expression patterns. Two alpha-expansins (CsExp3 and CsExp4) were more highly expressed in the peg and the root. Earlier reports stated that pegs tend not to form in the absence of gravity, so the expression levels were compared in the pegs of seedlings grown in space (STS-95), on a clinostat, and on earth (1 g). Pegs were observed to form at high frequency on clinostat and space-grown seedlings, yet on clinostats there was more than a 4-fold reduction in the expression of CsExp3 in the pegs of seedlings grown on clinostats vs. those grown at 1 g, while the CsExp4 gene appeared to be turned off (below detection limits). There were no detectable differences in expansin gene expression levels for the pegs of seedlings grown in space or in the orbiter environmental simulator (OES) (1 g) at NASA. The microgravity environment did not affect the expression of CsExp3 or CsExp4, and the clinostat did not simulate the microgravity environment well.

manned↗

Adaptive Identification and Control of Flow-Induced Cavity Oscillations

Progress towards an adaptive self-tuning regulator (STR) for the cavity tone problem is discussed in this paper. Adaptive system identification algorithms were applied to an experimental cavity-flow tested as a prerequisite to control. In addition, a simple digital controller and a piezoelectric bimorph actuator were used to demonstrate multiple tone suppression. The control tests at Mach numbers of 0.275, 0.40, and 0.60 indicated approx. = 7dB tone reductions at multiple frequencies. Several different adaptive system identification algorithms were applied at a single freestream Mach number of 0.275. Adaptive finite-impulse response (FIR) filters of orders up to N = 100 were found to be unsuitable for modeling the cavity flow dynamics. Adaptive infinite-impulse response (IIR) filters of comparable order better captured the system dynamics. Two recursive algorithms, the least-mean square (LMS) and the recursive-least square (RLS), were utilized to update the adaptive filter coefficients. Given the sample-time requirements imposed by the cavity flow dynamics, the computational simplicity of the least mean squares (LMS) algorithm is advantageous for real-time control.

Kegerise, M. A.↗

Carotid baroreflex regulation of sympathetic nerve activity during dynamic exercise in humans

We sought to determine whether carotid baroreflex (CBR) control of muscle sympathetic nerve activity (MSNA) was altered during dynamic exercise. In five men and three women, 23.8 +/- 0.7 (SE) yr of age, CBR function was evaluated at rest and during 20 min of arm cycling at 50% peak O(2) uptake using 5-s periods of neck pressure and neck suction. From rest to steady-state arm cycling, mean arterial pressure (MAP) was significantly increased from 90.0 +/- 2.7 to 118.7 +/- 3.6 mmHg and MSNA burst frequency (microneurography at the peroneal nerve) was elevated by 51 +/- 14% (P < 0.01). However, despite the marked increases in MAP and MSNA during exercise, CBR-Delta%MSNA responses elicited by the application of various levels of neck pressure and neck suction ranging from +45 to -80 Torr were not significantly different from those at rest. Furthermore, estimated baroreflex sensitivity for the control of MSNA at rest was the same as during exercise (P = 0.74) across the range of neck chamber pressures. Thus CBR control of sympathetic nerve activity appears to be preserved during moderate-intensity dynamic exercise.

Non-NASA Center↗

Two time scale stabilization of systems with output feedback

The problem of constant gain output feedback regulator design for linear systems with ill-conditioned dynamics is considered in the context of singular perturbation theory. A design approach is developed in which gains can be separately calculated to stabilize reduced-order slow and fast subsystem models. By employing the notion of combined control and observation spillover suppression, conditions are derived assuring that these gains will stabilize the full-order system, assuming sufficient frequency separation between the slow and fast subsystems. An LQ design procedure is described in which the spillover suppression conditions are satisfied by adjoining penalty functions to the subsystem performance indices. The theory is demonstrated in a controller design for a flexible space structure.

Moerder, D. D.↗