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At least 595 records · Page 33

Radiation breakage of DNA: a model based on random-walk chromatin structure

Monte Carlo computer software, called DNAbreak, has recently been developed to analyze observed non-random clustering of DNA double strand breaks in chromatin after exposure to densely ionizing radiation. The software models coarse-grained configurations of chromatin and radiation tracks, small-scale details being suppressed in order to obtain statistical results for larger scales, up to the size of a whole chromosome. We here give an analytic counterpart of the numerical model, useful for benchmarks, for elucidating the numerical results, for analyzing the assumptions of a more general but less mechanistic "randomly-located-clusters" formalism, and, potentially, for speeding up the calculations. The equations characterize multi-track DNA fragment-size distributions in terms of one-track action; an important step in extrapolating high-dose laboratory results to the much lower doses of main interest in environmental or occupational risk estimation. The approach can utilize the experimental information on DNA fragment-size distributions to draw inferences about large-scale chromatin geometry during cell-cycle interphase.

Chromatin/radiation effects↗

Neuroimmunologic aspects of sleep and sleep loss

The complex and intimate interactions between the sleep and immune systems have been the focus of study for several years. Immune factors, particularly the interleukins, regulate sleep and in turn are altered by sleep and sleep deprivation. The sleep-wake cycle likewise regulates normal functioning of the immune system. Although a large number of studies have focused on the relationship between the immune system and sleep, relatively few studies have examined the effects of sleep deprivation on immune parameters. Studies of sleep deprivation's effects are important for several reasons. First, in the 21st century, various societal pressures require humans to work longer and sleep less. Sleep deprivation is becoming an occupational hazard in many industries. Second, to garner a greater understanding of the regulatory effects of sleep on the immune system, one must understand the consequences of sleep deprivation on the immune system. Significant detrimental effects on immune functioning can be seen after a few days of total sleep deprivation or even several days of partial sleep deprivation. Interestingly, not all of the changes in immune physiology that occur as a result of sleep deprivation appear to be negative. Numerous medical disorders involving the immune system are associated with changes in the sleep-wake physiology--either being caused by sleep dysfunction or being exacerbated by sleep disruption. These disorders include infectious diseases, fibromyalgia, cancers, and major depressive disorder. In this article, we will describe the relationships between sleep physiology and the immune system, in states of health and disease. Interspersed will be proposals for future research that may illuminate the clinical relevance of the relationships between sleeping, sleep loss and immune function in humans. Copyright 2001 by W.B. Saunders Company.

NASA Discipline Space Human Factors↗

Faster rates with less catalyst in template-directed reactions

We have recently shown that the polycytidylic acid-directed polymerization of guanosine 5'-monophosphate 2-methylimidazolide (2-MeImpG) is amenable to kinetic study and that rate determinations as a function of 2-MeImpG concentration can reveal much mechanistic detail (Kanavarioti et al. 1993). Here we report kinetic data which show that, once the reaction has been initiated by the formation of dimers, the elongation of dimers to form longer oligomers is accelerated by decreasing polycytidylate (poly(C)) concentration from 0.05 to 0.002 M. This result is consistent with the previously proposed mechanism. The increase in the observed pseudo-first order rate constant for formation of the trimer, k3', and the corresponding constant for formation of oligomers longer than the trimer, ki' (ki' is independent of oligomer length for i > or = 4), with decreasing template concentration for a given monomer concentration is attributed to an increase in template occupancy as template concentration is reduced.

NASA Discipline Exobiology↗

Affinity of guanosine derivatives for polycytidylate revisited

Evidence is presented for complexation of guanosine 5'-monophosphate 2-methylimidazolide (2-MeImpG) with polycytidylate (poly(C)) at pH 8.0 and 23 degrees C in the presence of 1.0 M NaCl2 and 0.2 M MgCl2 in water. The association of 2-MeImpG with poly(C) was investigated using UV-vis spectroscopy as well as by monitoring the kinetics of the nucleophilic substitution reaction of the imidazole moiety by amines. The results of both methods are consistent with moderately strong poly(C) 2-MeImpG complexation and the spectrophotometric measurements allowed the construction of a binding isotherm with a concentration of 2-MeImpG equal to 5.55 +/- 0.15 mM at half occupancy. UV spectroscopy was employed to establish the binding of other guanosine derivatives on poly(C). These derivatives are guanosine 5'-monophosphate (5'GMP), guanosine 5'-monophosphate imidazolide (ImpG), and guanosine 5'-monophosphate morpholidate (morpG). Within experimental error these guanosine derivatives exhibit the same affinity for poly(C) as 2-MeImpG.

Non-NASA Center↗

High Altitude Radiations Relevant to the High Speed Civil Transport (HSCT)

The Langley Research Center (LaRC) performed atmospheric radiation studies under the SST development program in which important ionizing radiation components were measured and extended by calculations to develop the existing atmospheric ionizing radiation (AIR) model. In that program the measured neutron spectrum was limited to less than 10 MeV by the available 1960-1970 instrumentation. Extension of the neutron spectrum to high energies was made using the LaRC PROPER-3C monte carlo code. It was found that the atmospheric neutrons contributed about half of the dose equivalent and approximately half of the neutron contribution was from high energy neutrons above 10 MeV. Furthermore, monte carlo calculations of solar particle events showed that potential exposures as large as 10-100 mSv/hr may occur on important high latitude routes but acceptable levels of exposure could be obtained if timely descent to subsonic altitudes could be made. The principal concern was for pregnant occupants onboard the aircraft. As a result of these studies the FAA Advisory Committee on the Radiobiological Aspects of the SST recommended: 1. Crew members will have to be informed of their exposure levels 2. Maximum exposures on any flight to be limited to 5 mSv 3. Airborne radiation detection devices for total exposure and exposure rates 4. Satellite monitoring system to provide SST aircraft real-time information on atmospheric radiation levels for exposure mitigation 5. A solar forecasting system to warn flight operations of an impending solar event for flight scheduling and alert status. These recommendations are a reasonable starting point to requirements for the HSCT with some modification reflecting new standards of protection as a result of changing risk coefficients.

Wilson, J. W.↗

Determining the amount of physical activity needed for long-term weight control

OBJECTIVE: To evaluate prospectively the influence of habitual physical activity on body weight of men and women and to develop a model that defines the role of physical activity on longitudinal weight change. DESIGN AND SETTING: Occupational cohort study conducted for a mean of 5.5 y. SUBJECTS: A total of 496 (341 male and 155 female) NASA/Johnson Space Center employees who completed the 3 month education component of the employee health-related fitness program and remained involved for a minimum of 2 y. MEASUREMENTS: Body weights were measured at baseline (T1) and follow-up (T2), and habitual physical activity was obtained from the mean of multiple ratings of the 11-point (0-10) NASA Activity Scale (NAS) recorded quarterly between T1 and T2. Other measures included age, gender, VO(2 max) obtained from maximal treadmill testing, body mass index (BMI), and body fat percentage. RESULTS: Multiple regression demonstrated that mean NAS, T1 weight, aging and gender all influence long-term T2 weight. T1 age was significant for the men only. Independently, each increase in mean NAS significantly (P<0.01) reduced T2 weight in men (b=-0.91 kg; 95% CI:-1.4 to-0.42 kg) and women (b=-2.14 kg; 95% CI:-2.93 to-1.35 kg). Mean NAS had a greater effect on T2 weight as T1 weight increased, and the relationship was dose-dependent. CONCLUSIONS: Habitual physical activity is a significant source of long-term weight change. The use of self-reported activity level is helpful in predicting long-term weight changes and may be used by health care professionals when counseling patients about the value of physical activity for weight control.

Exercise↗

Dibenzo-p-dioxins in the environment from ceramics and pottery produced from ball clay mined in the United States

Processed ball clay samples used in the production of ceramics and samples of the ceramic products were collected and analyzed for the presence and concentration of the 2,3,7,8-Cl substituted polychlorinated dibenzo-p-dioxins and -furans (PCDDs/PCDFs). The processed ball clay had average PCDD concentrations of 3.2 ng/g toxic equivalents, a congener profile, and isomer distribution consistent with those found previously in raw ball clay. The PCDF concentrations were below the average limit of detection (LOD) of 0.5 pg/g. The final fired ceramic products were found to be free of PCDDs/PCDFs at the LODs. A consideration of the conditions involved in the firing process suggests that the PCDDs, if not destroyed, may be released to the atmosphere and could represent an as yet unidentified source of dioxins to the environment. In addition, the PCDDs in clay dust generated during manufacturing operations may represent a potential occupational exposure.

Aluminum Silicates/chemistry↗

Mechanical control of cyclic AMP signalling and gene transcription through integrins

This study was carried out to discriminate between two alternative hypotheses as to how cells sense mechanical forces and transduce them into changes in gene transcription. Do cells sense mechanical signals through generalized membrane distortion or through specific transmembrane receptors, such as integrins? Here we show that mechanical stresses applied to the cell surface alter the cyclic AMP signalling cascade and downstream gene transcription by modulating local release of signals generated by activated integrin receptors in a G-protein-dependent manner, whereas distortion of integrins in the absence of receptor occupancy has no effect.

NASA Discipline Cell Biology↗

Biomarkers of exposure, sensitivity and disease

PURPOSE: This review is to evaluate the use of biomarkers as an indication of past exposure to radiation or other environmental insults, individual sensitivity and risk for the development of late occurring disease. OVERVIEW: Biomarkers can be subdivided depending on their applications. Markers of exposure and dose can be used to reconstruct and predict past accidental or occupational exposures when limited or no physical measurements were available. Markers of risk or susceptibility can help identify sensitivity individuals that are at increased risk for development of spontaneous disease and may help predict the increased risk in sensitive individuals associated with environmental or therapeutic radiation exposures. Markers of disease represent the initial cellular or molecular changes that occur during disease development. Each of these types of biomarkers serves a unique purpose. OUTLINE: This paper concentrates on biomarkers of dose and exposure and provides a brief review of biomarkers of sensitivity and disease. The review of biomarkers of dose and exposure will demonstrate the usefulness of biomarkers in evaluation of physical factors associated with radiation exposure, such as LET, doserate and dose distribution. It will also evaluate the use of biomarkers to establish relationships that exist between exposure parameters such as energy deposition, environmental concentration of radioactive materials, alpha traversals and dose. In addition, the importance of biological factors on the magnitude of the biomarker response will be reviewed. Some of the factors evaluated will be the influence of species, tissue, cell types and genetic background. The review will demonstrate that markers of sensitivity and disease often have little usefulness in dose-reconstruction and, by the same token, many markers of dose or exposure may not be applicable for prediction of sensitivity or risk.

Non-NASA Center↗

Dynamics of airborne fungal populations in a large office building

The increasing concern with bioaerosols in large office buildings prompted this prospective study of airborne fungal concentrations in a newly constructed building on the Gulf coast. We collected volumetric culture plate air samples on 14 occasions over the 18-month period immediately following building occupancy. On each sampling occasion, we collected duplicate samples from three sites on three floors of this six-story building, and an outdoor sample. Fungal concentrations indoors were consistently below those outdoors, and no sample clearly indicated fungal contamination in the building, although visible growth appeared in the ventilation system during the course of the study. We conclude that modern mechanically ventilated buildings prevent the intrusion of most of the outdoor fungal aerosol, and that even relatively extensive air sampling protocols may not sufficiently document the microbial status of buildings.

NASA Program Biomedical Research and Countermeasur↗

Time course of sleep inertia dissipation in human performance and alertness

Alertness and performance on a wide variety of tasks are impaired immediately upon waking from sleep due to sleep inertia, which has been found to dissipate in an asymptotic manner following waketime. It has been suggested that behavioural or environmental factors, as well as sleep stage at awakening, may affect the severity of sleep inertia. In order to determine the time course of sleep inertia dissipation under normal entrained conditions, subjective alertness and cognitive throughput were measured during the first 4 h after habitual waketime from a full 8-h sleep episode on 3 consecutive days. We investigated whether this time course was affected by either sleep stage at awakening or behavioural/environmental factors. Sleep inertia dissipated in an asymptotic manner and took 2-4 h to near the asymptote. Saturating exponential functions fitted the sleep inertia data well, with time constants of 0.67 h for subjective alertness and 1.17 h for cognitive performance. Most awakenings occurred out of stage rapid eye movement (REM), 2 or 1 sleep, and no effect of sleep stage at awakening on either the severity of sleep inertia or the time course of its dissipation could be detected. Subjective alertness and cognitive throughput were significantly impaired upon awakening regardless of whether subjects got out of bed, ate breakfast, showered and were exposed to ordinary indoor room light (approximately 150 lux) or whether subjects participated in a constant routine (CR) protocol in which they remained in bed, ate small hourly snacks and were exposed to very dim light (10-15 lux). These findings allow for the refinement of models of alertness and performance, and have important implications for the scheduling of work immediately upon awakening in many occupational settings.

Non-NASA Center↗

A Bootstrap Approach to Martian Manufacturing

In-Situ Resource Utilization (ISRU) is an essential element of any affordable strategy for a sustained human presence on Mars. Ideally, Martian habitats would be extremely massive to allow plenty of room to comfortably live and work, as well as to protect the occupants from the environment. Moreover, transportation and power generation systems would also require significant mass if affordable. For our approach to ISRU, we use the industrialization of the U.S. as a metaphor. The 19th century started with small blacksmith shops and ended with massive steel mills primarily accomplished by blacksmiths increasing their production capacity and product size to create larger shops, which produced small mills, which produced the large steel mills that industrialized the country. Most of the mass of a steel mill is comprised of steel in simple shapes, which are produced and repaired with few pieces of equipment also mostly made of steel in basic shapes. Due to this simplicity, we expect that the 19th century manufacturing growth can be repeated on Mars in the 21st century using robots as the primary labor force. We suggest a "bootstrap" approach to manufacturing on Mars that uses a "seed" manufacturing system that uses regolith to create major structural components and spare parts. The regolith would be melted, foamed, and sintered as needed to fabricate parts using casting and solid freeform fabrication techniques. Complex components, such as electronics, would be brought from Earth and integrated as needed. These parts would be assembled to create additional manufacturing systems, which can be both more capable and higher capacity. These subsequent manufacturing systems could refine vast amounts of raw materials to create large components, as well as assemble equipment, habitats, pressure vessels, cranes, pipelines, railways, trains, power generation stations, and other facilities needed to economically maintain a sustained human presence on Mars.

Dorais, Gregory A.↗

Forearm muscle oxygenation decreases with low levels of voluntary contraction

The purpose of our investigation was to determine if the near infrared spectroscopy technique was sensitive to changes in tissue oxygenation at low levels of isometric contraction in the extensor carpi radialis brevis muscle. Nine subjects were seated with the right arm abducted to 45 degrees, elbow flexed to 85 degrees, forearm pronated 45 degrees, and wrist and forearm supported on an armrest throughout the protocol. Altered tissue oxygenation was measured noninvasively with near infrared spectroscopy. The near infrared spectroscopy probe was placed over the extensor carpi radialis brevis of the subject's right forearm and secured with an elastic wrap. After 1 minute of baseline measurements taken with the muscle relaxed, four different loads were applied just proximal to the metacarpophalangeal joint such that the subjects isometrically contracted the extensor carpi radialis brevis at 5, 10, 15, and 50% of the maximum voluntary contraction for 1 minute each. A 3-minute recovery period followed each level of contraction. At the end of the protocol, with the probe still in place, a value for ischemic tissue oxygenation was obtained for each subject. This value was considered the physiological zero and hence 0% tissue oxygenation. Mean tissue oxygenation (+/-SE) decreased from resting baseline (100% tissue oxygenation) to 89 +/- 4, 81 +/- 8, 78 +/- 8, and 47 +/- 8% at 5, 10, 15, and 50% of the maximum voluntary contraction, respectively. Tissue oxygenation levels at 10, 15, and 50% of the maximum voluntary contraction were significantly lower (p < 0.05) than the baseline value. Our results indicate that tissue oxygenation significantly decreases during brief, low levels of static muscle contraction and that near infrared spectroscopy is a sensitive technique for detecting deoxygenation noninvasively at low levels of forearm muscle contraction. Our findings have important implications in occupational medicine because oxygen depletion induced by low levels of muscle contraction may be directly linked to muscle fatigue.

NASA Center ARC↗

Estimation of the Spin and Recovery Characteristics of the North American XSN2J-1 Airplane

The probable spin and recovery characteristics of the XSN2J-1 air-plane have been estimated on the basis of the results of brief test a performed on a model of an airplane of somewhat similar design. The spin-recovery tail-parachute requirements for the airplane were also determined end, in addition, an analysis was made to determine the best method of emergency pilot escape during a spin. The results of the investigation indicate that the recovery characteristics of the airplane will be satisfactory for all probable loading conditions of the airplane. A 6-foot-diameter tall parachute attached to a 30-foot tow-line will be satisfactory as a spin-recovery device for emergency recovery from demonstration spins. If the occupants of the airplane decide to abandon the airplane in a spin, they should leave the airplane from the outboard side of the cockpit and as far rearward as possible.

Snyder, Thomas L.↗

Health Monitoring System for Car Seat

A health monitoring system for use with a child car seat has sensors mounted in the seat to monitor one or more health conditions of the seat's occupant. A processor monitors the sensor's signals and generates status signals related to the monitored conditions. A transmitter wireless transmits the status signals to a remotely located receiver. A signaling device coupled to the receiver produces at least one sensory (e.g., visual, audible, tactile) output based on the status signals.

Susan Vinz Elrod↗

Atomistic Modeling of Pd Site Preference in NiTi

An analysis of the site subsitution behavior of Pd in NiTi was performed using the BFS method for alloys. Through a combination of Monte Carlo simulations and detailed atom-by-atom energetic analyses of various computational cells, representing compositions of NiTi with up to 10 at% Pd, a detailed understanding of site occupancy of Pd in NiTi was revealed. Pd subsituted at the expense of Ni in a NiTi alloy will prefer the Ni-sites. Pd subsituted at the expense of Ti shows a very weak preference for Ti-sites that diminishes as the amount of Pd in the alloy increases and as the temperature increases.

Bozzolo, Guillermo↗

Towards Measurement of the Time-resolved Heat Release of Protein Conformation Dynamics

We present a way to observe time-resolved heat release using a laminar flow diffusional mixer coupled with a highly sensitive infrared camera which measures the temperature change of the solvent. There are significant benefits to the use of laminar flow mixers for time-resolved calorimetry: (1) The thermal signal can be made position and time- stationary to allow for signal integration; (2) Extremely small volumes (nl/s) of sample are required for a measurement; (3) The same mixing environment can be observed spectroscopically to obtain state occupation information; (4) The mixer allows one to do out of equilibrium dynamic studies. The hope is that these measurements will allow us probe the non-equilibrium thermodynamics as a protein moves along a free energy trajectory from one state to another.

Puchalla, Jason↗

Space Resource Utilization and Extending Human Presence Across the Solar System

The Presidents Vision for Exploration is not a single mission, but an open ended journey that seeks to answer "How can we live on other worlds?" Using space resources is the only known approach for affordable, sustained, flexible, and self sufficient, human occupation beyond Earth orbit. Earth is a large planet. A simple analysis using the rocket equation shows that if Earth were a bit larger, chemical propulsion as a mechanism to access space would become impractical. Thus, even with the most efficient chemical rocket launch capability, the cost of lifting massive payloads into space will remain very steep (currently about $l00k/lb to the Moon and greater than $500k/lb to Mars). Space resource utilization should begin with an aggressive broad based demonstration program as afforded by the precursor missions implementation of the President's Vision of Exploration. Ion engine upper stages, for example, were studied for over 30 years, but only implemented in design after the Deep Space 1 in space demonstration. These demonstrations should include: extraction of elements from lunar regolith, and Martian soil and atmosphere, demonstration of power break even and growth from lunar or Mars moons derived photovoltaics, oxygen extraction for life support and propellant, and metals and alloys for in space repair and the production of habits and radiation shielding. Space resource utilization yields operational dividends through the subsequent programs including: propellant from lunar oxygen which could cut transportation costs from Earth in half, mega watts per year of power grown from lunar photovoltaics at decreasing cost per kW, decreased cost for human Mars missions by a factor of 10 by using propellant derived from Mars atmosphere for return, and in space manufacturing and food production with space resources yielding safe sustained and eventually self sufficient human presence in space. After the demonstration and implementation, the space resource utilization investment enables commercial and private viability beyond Earth orbit. For example, analysis has shown the lunar oxygen production for propellant becomes commercially viable after the exploration program completes the R&D, and power from lunar derived photovoltaics could, according to past NASA sponsored studies, pay for themselves while supplying most of Earth's electrical energy after about 17 years. Besides the Moon and Mars the resources of the near Earth asteroids enable the building of large space structures and science payloads. Analysis has shown that one of the thousands of these objects (some as easily accessible in space as the Moon and Mars), 2 km dia, the size of a typical open pit mine, would cost the total global financial product of Earth for 30,000 years if we were to launch it from Earth. Beyond Mars, the belt asteroids have been calculated to contain enough materials for habitat and life to support 10 quadrillion people. Thus, the development and use of space resources enables the extension of human life through the solar system allowing humanity to move from a planetary to a solar system society.

Curreri, Peter A.↗