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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
NASA NTRS2000

Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease

The RNA and DNA tumor viruses have made fundamental contributions to two major areas of cancer research. Viruses were vital, first, to the discovery and analysis of cellular growth control pathways and the synthesis of current concepts of cancer biology and, second, to the recognition of the etiology of some human cancers. Transforming retroviruses carry oncogenes derived from cellular genes that are involved in mitogenic signalling and growth control. DNA tumor viruses encode oncogenes of viral origin that are essential for viral replication and cell transformation; viral oncoproteins complex with cellular proteins to stimulate cell cycle progression and led to the discovery of tumor suppressors. Viral systems support the concept that cancer development occurs by the accumulation of multiple cooperating events. Viruses are now accepted as bona fide etiologic factors of human cancer; these include hepatitis B virus, Epstein-Barr virus, human papillomaviruses, human T-cell leukemia virus type I and hepatitis C virus, plus several candidate human cancer viruses. It is estimated that 15% of all human tumors worldwide are caused by viruses. The infectious nature of viruses distinguishes them from all other cancer-causing factors; tumor viruses establish long-term persistent infections in humans, with cancer an accidental side effect of viral replication strategies. Viruses are usually not complete carcinogens, and the known human cancer viruses display different roles in transformation. Many years may pass between initial infection and tumor appearance and most infected individuals do not develop cancer, although immunocompromised individuals are at elevated risk of viral-associated cancers. Variable factors that influence viral carcinogenesis are reviewed, including possible synergy between viruses and environmental cofactors. The difficulties in establishing an etiologic role for a virus in human cancer are discussed, as well as the different approaches that proved viral links to cancer. Future directions for tumor virus studies are considered.

NASA Program Biomedical Research and Countermeasur↗
NASA NTRS2004

Biophotonics and Bone Biology

One of the more-serious side effects of extended space flight is an accelerated bone loss [Bioastronautics Critical Path Roadmap, http://research.hq.nasa.gov/code_u/bcpr/index.cfm]. Rates of bone loss are highest in the weight-bearing bones of the hip and spine regions, and the average rate of bone loss as measured by bone mineral density measurements is around 1.2% per month for persons in a microgravity environment. It shows that an extrapolation of the microgravity induced bone loss rates to longer time scales, such as a 2.5 year round-trip to Mars (6 months out at 0 g, 1.5 year stay on Mars at 0.38 g, 6 months back at 0 g), could severely compromise the skeletal system of such a person.

Zimmerli, Gregory↗
NASA NTRS1997

The role of reafference in recalibration of limb movement control and locomotion

The reafference model has frequently been used to explain spatial constancy during eye and head movements. We have found that its basic concepts also form part of the information processing necessary for the control and recalibration of reaching movements. Reaching was studied in a novel force environment--a rotating room that creates centripetal forces of the type that could someday substitute for gravity in space flight, and Coriolis forces which are side effects of rotation. We found that inertial, noncontacting Coriolis forces deviate the path and endpoint of reaching movements, a finding that shows the inadequacy of equilibrium position models of movement control. Repeated movements in the rotating room quickly lead to normal movement patterns and to a failure to perceive the perturbing forces. The first movements made after rotation stops, without Coriolis forces present, show mirror-image deviations and evoke perception of a perturbing force even though none is present. These patterns of sensorimotor control and adaptation can largely be explained on the basis of comparisons of efference copy, reafferent muscle spindle, and cutaneous mechanoreceptor signals. We also describe experiments on human locomotion using an apparatus similar to that which Mittelstaedt used to study the optomotor response of the Eristalis fly. These results show that the reafference principle relates as well to the perception of the forces acting on and exerted by the body during voluntary locomotion.

NASA Discipline Neuroscience↗
NASA NTRS1989

Motor and cognitive testing of bone marrow transplant patients after chemoradiotherapy

Assessment of cognitive and motor performance of bone marrow transplant patients prior to, during, and following intensive toxic chemoradiotherapy may provide an important adjunct to measures of physiological and medical status. The present study is an attempt to assess whether, as side-effects, these aggressive treatments result in cognitive performance deficits, and if so, whether such changes recover posttreatment. Measurement of cognitive ability in this situation presents special problems not encountered with one-time tests intended for healthy adults. Such tests must be sensitive to changes within a single individual, which emphasizes the crucial importance of high reliability, stability across repeated-measures, and resistance to confounding factors such as motivation and fatigue. The present research makes use of a microbased portable test battery developed to have reliable and sensitive tests which were adapted to study the special requirements of transplant patients who may suffer cognitive deficits as a result of treatment. The results showed slight but significant changes in neuropsychological capacity when compared to baseline levels and controls, particularly near the beginning of treatment. The sensitivity of the battery in detecting such subtle temporary changes is discussed in terms of past research showing effects of other stressors, such as stimulated high altitude and ingestion of alcohol, on these measures.

Non-NASA Center↗
NASA NTRS2003

Determination and Applications of Environmental Costs at Different Sized Airports: Aircraft Noise and Engine Emissions

With the increasing trend of charging for externalities and the aim of encouraging the sustainable development of the air transport industry, there is a need to evaluate the social costs of these undesirable side effects, mainly aircraft noise and engine emissions, for different airports. The aircraft noise and engine emissions social costs are calculated in monetary terms for five different airports, ranging from hub airports to small regional airports. The number of residences within different levels of airport noise contours and the aircraft noise classifications are the main determinants for accessing aircraft noise social costs. Whist, based on the damages of different engine pollutants on the human health, vegetation, materials, aquatic ecosystem and climate, the aircraft engine emissions social costs vary from engine types to aircraft categories. The results indicate that the relationship appears to be curvilinear between environmental costs and the traffic volume of an airport. The results and methodology of environmental cost calculation could input for to the proposed European wide harmonized noise charges as well as the social cost benefit analysis of airports.

Lu, Cherie↗
NASA NTRS2005

Enabling the On-line Intrinsic Evolution of Analog Controllers

The intrinsic evolution of analog controllers to provide closed-loop control of the speed of a DC motor has been previously demonstrated at NASA Marshall Space Flight Center. A side effect of the evolutionary process is that during evolution there are necessarily poor configurations to be evaluated that could cause damage to the plant, This paper concerns the development and implementation of a safe Evolvable Analog Controller (EAC) architecture able to evolve controllers on-line even in the presence of these poor configurations, The EAC concept is discussed and experimental results are presented that show the feasibility of the approach This EAC architecture represents the first in a series of steps required to make deployment of an evolvable controller a reality.

Gwaltney, David A.↗
NASA NTRS2005

Consequences of cardiovascular adaptation to spaceflight: implications for the use of pharmacological countermeasures

There is little evidence obtained from space flight to support the notion that occurrence of cardiac dysrhythmias, impaired cardiac and vascular function, and manifestation of asymptomatic cardiovascular disease represent serious risks during space flight. Therefore, the development of orthostatic hypotension and instability immediately after return from spaceflight probably reflect the most significant operational risks associated with the cardiovascular system of astronauts. Significant reductions in stroke volume and lower reserve for increasing peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with less circulating blood volume while inadequate peripheral vasoconstriction may be caused partly by hyporeactivity of receptors that control arterial smooth muscle function. A focus for development of future countermeasures for hemodynamic responses to central hypovolemia includes the potential application of pharmacological agents that specifically target and restore blood volume (e.g., fludrocortisone, electrolyte-containing beverages) and reserve for vasoconstriction (e.g., midodrine, vasopressin). Based on systematic evaluations, acute physical exercise designed to elicit maximal effort or inspiratory resistance have shown promise as successful countermeasures that provide protection against development of orthostatic hypotension and intolerance without potential risks and side effects associated with specific pharmacological interventions.

Non-NASA Center↗
NASA NTRS2005

A Voice Enabled Procedure Browser for the International Space Station

Clarissa, an experimental voice enabled procedure browser that has recently been deployed on the International Space Station (ISS), is to the best of our knowledge the first spoken dialog system in space. This paper gives background on the system and the ISS procedures, then discusses the research developed to address three key problems: grammar-based speech recognition using the Regulus toolkit; SVM based methods for open microphone speech recognition; and robust side-effect free dialogue management for handling undos, corrections and confirmations.

Rayner, Manny↗
NASA NTRS2004

Bioavailability and Pharmacodynamics of Promethazine on Long Duration Missions to the International Space Station

Space motion sickness (SMS) is often treated in space with promethazine (PMZ). Common side effects of PMZ administration (50 mg intramuscular) on the ground are drowsiness and impaired cognitive performance. Anecdotal reports indicate that these effects are absent or less pronounced in space. This suggests that the availability of PMZ to the body (bioavailability) and/or the response of the body to PMZ (pharmacodynamics) may change during space flight. Opportunities for clinical research in space are limited. The study described here is our response to a NASA Research Announcement for proposals for flight-based research needed to improve, or answer specific questions about, diagnosis and therapy during space flight, and post-flight rehabilitation. We propose here to evaluate noninvasive methods for determining the bioavailability and pharmacodynamics of PMZ. The specific objectives of the proposed research are to 1) compare pharmacokinetic and pharmacodynamic parameters of PMZ, estimated from saliva and plasma levels after administration of PMZ, 2) estimate the relative bioavailability of the three dosage forms of PMZ that are often administered to control motion sickness symptoms in space, and 3) establish the dose-response relationship of PMZ. We will estimate the bioavailability of an intramuscular injection (IM), oral tablet, and rectal suppository of PMZ in noma1 subjects during ambulatory and antiorthostatic bed rest (ABR) conditions using novel stable isotope techniques. We will compare and contrast the bioavailability of PMZ during normal and microgravity conditions to examine changes in drug absorption and bioavailability during microgravit. Results of this study will validate methods for an approved in-flight investigation with this medication awaiting an opportunity for manifestation..

Putcha, Lakshmi↗
NASA NTRS2006

Physiological Targets of Artificial Gravity: The Sensory-Motor System

This chapter describes the pros and cons of artificial gravity applications in relation to human sensory-motor functioning in space. Spaceflight creates a challenge for sensory-motor functions that depend on gravity, which include postural balance, locomotion, eye-hand coordination, and spatial orientation. The sensory systems, and in particular the vestibular system, must adapt to weightlessness on entering orbit, and again to normal gravity upon return to Earth. During this period of adaptation, which persists beyond the actual gravity-level transition itself the sensory-motor systems are disturbed. Although artificial gravity may prove to be beneficial for the musculoskeletal and cardiovascular systems, it may well have negative side effects for the neurovestibular system, such as spatial disorientation, malcoordination, and nausea.

Paloski, William↗
NASA NTRS2007

Determination of Scopolamine in Human Saliva Using Solid Phase Extraction and LC/MS/MS

Purpose: Scopolamine is the preferred treatment for motion sickness during space flight because of its quick onset of action, short half-life and favorable side-effect profile. The dose administered depends on the mode of administration and usually ranges between 0.1 and 0.8 mg. Such small doses make it difficult to detect concentrations of scopolamine in biological fluids by using conventional HPLC methods. To measure scopolamine in saliva and thereby to evaluate the pharmacokinetics of scopolamine, we developed an LC/MS/MS method using off-line solid phase extraction. Method: Samples (0.5mL) were loaded onto Waters Oasis HLB co-polymer cartridges (10 mg, 1 mL) and eluted with 0.5 mL methanol without evaporation and reconstitution. HPLC separation of the eluted sample was performed using an Agilent Zorbax SB-CN column (50 x 2.1 mm) at a flow rate of 0.2 mL/min for 4 minutes. The mobile phase for separation was 90:10 (v/v) methanol: ammonium acetate (2 mM) in water, pH 5.0 +/- 0.1. Concentrations of scopolamine were determined using a Micromass Quattro Micro(TM) mass spectrometer with electrospray ionization (ESI). ESI mass spectra were acquired in positive ion mode with multiple reaction monitoring for the determination of scopolamine m/z = 304.2 yields 138.1 and internal standard (IS) hyoscyamine m/z = 290.2 yields 124.1. Results: The method is rapid, reproducible, specific and has the following parameters: scopolamine and the IS are eluted at 1.7 and 3.2 min respectively. The linear range is 50-5000 pg/mL for scopolamine in saliva with correlation coefficients > 0.99 with a CV < 0.5 %. The intra-day and inter-day CVs are < 15 % for quality control samples with concentrations of 75, 300, 750 and 3000 pg/mL of scopolamine in human saliva. Conclusion: Solid phase extraction allows more rapid sample preparation and greater precision than liquid extraction. Furthermore, we increased the sensitivity and specificity by adjusting the LC mobile phase and using an MS/MS detector.

Wang, Zuwei↗
NASA NTRS2005

Aligned Single Wall Carbon Nanotube Polymer Composites Using an Electric Field

While high shear alignment has been shown to improve the mechanical properties of single wall carbon nanotubes (SWNT)-polymer composites, it is difficult to control and often results in degradation of the electrical and dielectric properties of the composite. Here, we report a novel method to actively align SWNTs in a polymer matrix, which allows for control over the degree of alignment of SWNTs without the side effects of shear alignment. In this process, SWNTs are aligned via field-induced dipolar interactions among the nanotubes under an AC electric field in a liquid matrix followed by immobilization by photopolymerization while maintaining the electric field. Alignment of SWNTs was controlled as a function of magnitude, frequency, and application time of the applied electric field. The degree of SWNT alignment was assessed using optical microscopy and polarized Raman spectroscopy and the morphology of the aligned nanocomposites was investigated by high resolution scanning electron microscopy. The structure of the field induced aligned SWNTs is intrinsically different from that of shear aligned SWNTs. In the present work, SWNTs are not only aligned along the field, but also migrate laterally to form thick, aligned SWNT percolative columns between the electrodes. The actively aligned SWNTs amplify the electrical and dielectric properties in addition to improving the mechanical properties of the composite. All of these properties of the aligned nanocomposites exhibited anisotropic characteristics, which were controllable by tuning the applied field conditions.

Park, Cheol↗
NASA NTRS2009

Drug Information in Space Medicine

Published drug information is widely available for terrestrial conditions. However, information on dosing, administration, drug interactions, stability, and side effects is scant as it relates to use in Space Medicine. Multinational crews on board the International Space Station present additional challenges for drug information because medication nomenclature, information available for the drug as well as the intended use for the drug is not standard across countries. This presentation will look at unique needs for drug information and how the information is managed in Space Medicine. A review was conducted of the drug information requests submitted to the Johnson Space Center Pharmacy by Space Medicine practitioners, astronaut crewmembers and researchers. The information requested was defined and cataloged. A list of references used was maintained. The wide range of information was identified. Due to the information needs for the medications in the on-board medical kits, the Drug Monograph Project was created. A standard method for answering specific drug information questions was generated and maintained by the Johnson Space Center Pharmacy. The Drug Monograph Project will be presented. Topic-centered requests, including multinational drug information, drug-induced adverse reactions, and medication events due to the environment will be highlighted. Information management of the drug information will be explained. Future considerations for drug information needs will be outlined.

Bayuse, Tina M.↗
NASA NTRS2005

Pharmacodynamics of Promethazine in Human Subjects

Promethazine (PMZ) is the drug of choice for the treatment of symptoms associated with space motion sickness in astronauts. Side effects of PMZ include sedation, dizziness and cognitive performance impairment. In this study, we examined pharmacodynamics (PD) in human subjects and validated methods for evaluating cognitive performance effects of medications in space. METHODS: PMZ (12.5,25, and 50 mg) or placebo was administered by IM injection to human subjects in a randomized double-blind treatment design. Samples and data were collected for 72 h post dose. PD evaluation was performed using a battery of performance tests administered using WinSCAT (Windows based Space Cognitive Assessment Test) on a laptop computer, and ARES (ANAM Readiness Evaluation System) on a PDA, plasma concentrations of PMZ were measured using a LC-MS method. RESULTS: Results indicate a linear correlation between PMZ concentration and cognitive performance parameters (p<0.01). Test accuracy decreased and test completion time and response time increased significantly with increasing plasma PMZ concentration. CONCLUSIONS: These results suggest a concentration dependent decrement in cognitive performance associated with PMZ. WinSCAT and ARES are sensitive tools for the assessment PMZ PD and may be applicable for such evaluations with other neurocognitive drugs.

Gatlin, K. T.↗
NASA NTRS2008

Intelligent Memory Module Overcomes Harsh Environments

Solar cells, integrated circuits, and sensors are essential to manned and unmanned space flight and exploration, but such systems are highly susceptible to damage from radiation. Especially problematic, the Van Allen radiation belts encircle Earth in concentric radioactive tori at distances from about 6,300 to 38,000 km, though the inner radiation belt can dip as low as 700 km, posing a severe hazard to craft and humans leaving Earth s atmosphere. To avoid this radiation, the International Space Station and space shuttles orbit at altitudes between 275 and 460 km, below the belts range, and Apollo astronauts skirted the edge of the belts to minimize exposure, passing swiftly through thinner sections of the belts and thereby avoiding significant side effects. This radiation can, however, prove detrimental to improperly protected electronics on satellites that spend the majority of their service life in the harsh environment of the belts. Compact, high-performance electronics that can withstand extreme environmental and radiation stress are thus critical to future space missions. Increasing miniaturization of electronics addresses the need for lighter weight in launch payloads, as launch costs put weight at a premium. Likewise, improved memory technologies have reduced size, cost, mass, power demand, and system complexity, and improved high-bandwidth communication to meet the data volume needs of the next-generation high-resolution sensors. This very miniaturization, however, has exacerbated system susceptibility to radiation, as the charge of ions may meet or exceed that of circuitry, overwhelming the circuit and disrupting operation of a satellite. The Hubble Space Telescope, for example, must turn off its sensors when passing through intense radiation to maintain reliable operation. To address the need for improved data quality, additional capacity for raw and processed data, ever-increasing resolution, and radiation tolerance, NASA spurred the development of the Radiation Tolerant Intelligent Memory Stack (RTIMS).

Source record↗
NASA NTRS2008

Countermeasure for Radiation Protection and Repair

Exposure to ionizing radiation during long-duration space missions is expected to cause short-term illness and increase long-term risk of cancer for astronauts. Radiation-induced free radicals overload the antioxidant defense mechanisms and lead to cellular damage at the membrane, enzyme, and chromosome levels. A large number of radioprotective agents were screened, but most had significant side effects. But there is increasing evidence that significant radioprotective benefit is achieved by increasing the dietary intake of foods with high antioxidant potential. Early plant-growing systems for space missions will be limited in both size and volume to minimize power and mass requirements. These systems will be well suited to producing plants containing high concentrations of bioprotective antioxidants. This project explored whether the production of bioprotective compounds could be increased by altering the lighting system, without increasing the space or power requirements for production, and evaluated the effects of environmental conditions (light quantity, light quality, and carbon dioxide [CO2] concentration) on the production of bioprotective compounds in lettuce, which provide a biological countermeasure for radiation exposure. The specific deliverables were to develop a database of bioprotectant compounds in plants that are suitable for use on longduration space missions, develop protocols for maintaining and increasing bioprotectant production under light emitting diodes (LEDs), recommend lighting requirements to produce dietary countermeasures of radiation, and publish results in the Journal of the American Society for Horticultural Science.

Source record↗
NASA NTRS2010

A New Approach for Constructing Highly Stable High Order CESE Schemes

A new approach is devised to construct high order CESE schemes which would avoid the common shortcomings of traditional high order schemes including: (a) susceptibility to computational instabilities; (b) computational inefficiency due to their local implicit nature (i.e., at each mesh points, need to solve a system of linear/nonlinear equations involving all the mesh variables associated with this mesh point); (c) use of large and elaborate stencils which complicates boundary treatments and also makes efficient parallel computing much harder; (d) difficulties in applications involving complex geometries; and (e) use of problem-specific techniques which are needed to overcome stability problems but often cause undesirable side effects. In fact it will be shown that, with the aid of a conceptual leap, one can build from a given 2nd-order CESE scheme its 4th-, 6th-, 8th-,... order versions which have the same stencil and same stability conditions of the 2nd-order scheme, and also retain all other advantages of the latter scheme. A sketch of multidimensional extensions will also be provided.

Chang, Sin-Chung↗
NASA NTRS2010

Atrial Fibrillation During an Exploration Class Mission

Background: A long-duration exploration class mission is fraught with numerous medical contingency plans. Herein, we explore the challenges of symptomatic atrial fibrillation (AF) occurring during an exploration class mission. The actions and resources required to ameliorate the situation, including the availability of appropriate pharmaceuticals, monitoring devices, treatment modalities, and communication protocols will be investigated. Challenges of Atrial Fibrillation during an Exploration Mission: Numerous etiologies are responsible for the initiation of AF. On Earth, we have the time and medical resources to evaluate and determine the causative situation for most cases of AF and initiate therapy accordingly. During a long-duration exploration class mission resources will be severely restricted. How is one to determine if new onset AF is due to recent myocardial infarction, pulmonary embolism, fluid overload, thyrotoxicosis, cardiac structural abnormalities, or CO poisoning? Which pharmaceutical therapy should be initiated and what potential side effects can be expected? Should anti-coagulation therapy be initiated? How would one monitor the therapeutic treatment of AF in microgravity? What training would medical officers require, and which communication strategies should be developed to enable the best, safest therapeutic options for treatment of AF during a long-duration exploration class mission? Summary: These questions will be investigated with expert opinion on disease elucidation, efficient pharmacology, therapeutic monitoring, telecommunication strategies, and mission cost parameters with emphasis on atrial fibrillation being just one illustration of the tremendous challenges that face a long-duration exploration mission. The limited crew training time, medical hardware, and drugs manifested to deal with such an event predicate that aggressive primary and secondary prevention strategies be developed to protect a multibillion-dollar asset like the International Space Station or a mission to the Moon or Mars. Learning Objectives: The audience will become familiar with the risks and challenges inherent to developing a therapeutic strategy for the treatment of atrial fibrillation during a long-term exploration class mission.

Lipset, Mark A.↗