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At least 271 records · Page 15
All sourcesNASA NTRSDOE OSTI
NASA NTRS2000

Bioavailability and Pharmacodynamics of Promethazine in Human Subjects

Space Motion Sickness (SMS) is often treated in space with promethazine (PMZ). Anecdotal reports indicate that the common side effects of drowsiness and decrements in cognitive performance that are associated with PMZ administration (50 mg IM on the ground, are absent or less pronounced in space suggesting I that-the bioavailability and/or pharmacodynamic behavior of PMZ may be altered during space flight. There are limited flight opportunities available for clinical research in space, the NRA-99, therefore, solicits research required to improve, or answer specific questions about in-flight diagnosis, therapy, and post-flight rehabilitation. We propose here, to establish a noninvasive method for pharmacodynamic and therapeutic assessment of PMZ. The specific objectives of the proposed research are to, 1. Establish a saliva to plasma ratio of PMZ after administration, 2. Estimate the relative bioavailability of the three flight-specific dosage forms of PMZ, and 3. Establish the dose-response relationship of PMZ. We will estimate the bioavailability of intramuscular injection (IM), oral tablets and rectal suppositories in normal subjects during ambulatory and antiorthostatic; bed rest (ABR) conditions using novel stable isotope techniques. Drowsiness, cognitive performance and salivary flow rate will be measured as a function of circulating drug concentrations after administration of three IM doses of PMZ. We will compare and contrast the bioavailability of PMZ during normal and ABR conditions to examine whether or not ABR can simulate changes in drug, absorption and availability similar to those anticipated in a microgravity environment. Results of this study will validate methods for an approved study with this medication awaiting a flight opportunity for manifestation. These data will also provide the much needed information on the dynamics and therapeutic index. of this medication and their implications on crew fatigue and performance in space. Key words: Promethazine, stable isotopes, bioavailability, pharmacodynamics, cognitive performance, antiorthostatic bed rest.

Putcha, Lakshmi↗
NASA NTRS2000

Neutrons in Space: Shield Models and Design Issues

The normal working and living areas of the astronaut are designed to provide an acceptable level of protection against the hazards of ionizing space radiation. Attempts to reduce the exposures require intervening shield materials to reduce the transmitted radiation. An unwelcome side effect of the shielding is the production of neutrons, which are themselves dangerous particles that can be (but are not always) more hazardous than the particles that produced them. This is especially true depending on the choice of shield materials. Although neutrons are not a normal part of the space environment, this paper focuses on them as principle component of astronaut exposure in the massive spacecraft's required for human space travel and habitation near planetary surfaces or other large bodies of material in space.

Wilson, J. W.↗
NASA NTRS2001

Improving Simulated Annealing by Recasting it as a Non-Cooperative Game

The game-theoretic field of COllective INtelligence (COIN) concerns the design of computer-based players engaged in a non-cooperative game so that as those players pursue their self-interests, a pre-specified global goal for the collective computational system is achieved "as a side-effect". Previous implementations of COIN algorithms have outperformed conventional techniques by up to several orders of magnitude, on domains ranging from telecommunications control to optimization in congestion problems. Recent mathematical developments have revealed that these previously developed game-theory-motivated algorithms were based on only two of the three factors determining performance. Consideration of only the third factor would instead lead to conventional optimization techniques like simulated annealing that have little to do with non-cooperative games. In this paper we present an algorithm based on all three terms at once. This algorithm can be viewed as a way to modify simulated annealing by recasting it as a non-cooperative game, with each variable replaced by a player. This recasting allows us to leverage the intelligent behavior of the individual players to substantially improve the exploration step of the simulated annealing. Experiments are presented demonstrating that this recasting improves simulated annealing by several orders of magnitude for spin glass relaxation and bin-packing.

Wolpert, David↗
NASA NTRS2001

Improving Simulated Annealing by Replacing Its Variables with Game-Theoretic Utility Maximizers

The game-theory field of Collective INtelligence (COIN) concerns the design of computer-based players engaged in a non-cooperative game so that as those players pursue their self-interests, a pre-specified global goal for the collective computational system is achieved as a side-effect. Previous implementations of COIN algorithms have outperformed conventional techniques by up to several orders of magnitude, on domains ranging from telecommunications control to optimization in congestion problems. Recent mathematical developments have revealed that these previously developed algorithms were based on only two of the three factors determining performance. Consideration of only the third factor would instead lead to conventional optimization techniques like simulated annealing that have little to do with non-cooperative games. In this paper we present an algorithm based on all three terms at once. This algorithm can be viewed as a way to modify simulated annealing by recasting it as a non-cooperative game, with each variable replaced by a player. This recasting allows us to leverage the intelligent behavior of the individual players to substantially improve the exploration step of the simulated annealing. Experiments are presented demonstrating that this recasting significantly improves simulated annealing for a model of an economic process run over an underlying small-worlds topology. Furthermore, these experiments reveal novel small-worlds phenomena, and highlight the shortcomings of conventional mechanism design in bounded rationality domains.

Wolpert, David H.↗
NASA NTRS2002

Magnetic Microspheres for Therapeutical Applications

Hyperthermia is a well known cancer therapy and consists of heating a tumor region to the elevated temperatures in the range of 40-45 C for an extended period of time (2-8 hours). This leads to thermal inactivation of cell regulatory and growth processes with resulting widespread necrosis, carbonization and coagulation. Moreover, heat boosts the tumor response to other treatments such as radiation, chemotherapy or immunotherapy. Of particular importance is careful control of generated heat in the treated region and keeping it localized. Higher heating, to about 56 C can lead to tissue thermo-ablation. With accurate temperature control, hyperthermia has the advantage of having minimal side effects. Several heating techniques are utilized for this purpose, such as whole body hyperthermia, radio-frequency (RF) hyperthermia, ultrasound technique, inductive microwave antenna hyperthermia, inductive needles (thermoseeds), and magnetic fluid hyperthermia (MFH).MFH offers many advantages as targeting capability by applying magnets. However, this technology still suffers significant inefficiencies due to lack of thermal control. This paper will provide a review of the topic and outline the ongoing work in this area. The main emphasis is in devising ways to overcome the technical difficulty in hyperthermia therapy of achieving a uniform therapeutic temperature over the required region of the body and holding it steady. The basic obstacle of the present heating methods are non-uniform thermal properties of the tissue. Our approach is to develop a novel class of magnetic fluids which have inherent thermoregulating properties. We have identified a few magnetic alloys which can serve as a suitable nano-particle material. The objective is to synthesize, characterize and evaluate the efficacy of TRMF for hyperthermia therapy.

Mazuruk, K.↗
NASA NTRS2002

Spin-Up Instability of a Levitated Molten Drop in MHD-Flow Transition to Turbulence

When an alternating magnetic field interacts with induced eddy currents in a conducting body, there will be a repulsive force between the body and the driving coil system generating the field. This repulsive force is the basis of electromagnetic levitation, which allows containerless processing of different materials. The eddy currents in the conducting body also generate Joule heating. Axial rotation of electromagnetically levitated objects is a common observation in levitation systems and often an undesirable side effect of such experiments on 1-g and -g. There have been recent efforts to use magnetic damping and suppress this tendency of body rotation. The first report of rotation in EML drops was attributed to a slight asymmetry of the shape and location of the levitation coils could change the axis and speed of rotation. Other theories of sample rotation include a frequency difference in the traveling electromagnetic waves and a phase difference in two different applied fields of the same frequency. All of these different mechanisms share the following characteristics: the torque is small, constant for constant field strength, and very weakly dependent on the sample's temperature and phase (solid or liquid). During experiments on the MSL-1 (First Microgravity Science Laboratory) mission of the Space Shuttle (STS-83 and STS-94, April and July 1997), a droplet of palladium-silicon alloy was electromagnetically levitated for viscosity measurements. For the non-deforming droplet, the resultant MHD flow inside the drop is inferred from motion of impurities on the surface. These observations indicate formation of a pair of co-rotating toroidal flow structures inside the spheroidal levitated drop that undergo secondary flow instabilities. As rise in the fluid temperature rises, the viscosity falls and the internal flow accelerates and becomes oscillatory; and beyond a point in the experiments, the surface impurities exhibit non-coherent chaotic motion signifying emergence of turbulence inside the drop. In this work, a background of these set of observations will be given followed by a presentation of our results on the digital particle tracking analysis that has been performed on a number of available videos. The analysis indicates that the levitated drop attains a constant rotational speed during the melting phase and formation of the co-rotating axi-symmetric laminar toroidal structures. However, the rate of axial rotation increases dramatically during the deformation of the toroidal structures anti their breakup into chaotic entities. This new data suggests an interaction between the flow inside the levitated molten drop and the driving coils in the experiments. Possible mechanisms for this interaction will be reviewed. The data will also be used to make an assessment of existing theories on droplet rotation.

Abedian, B.↗
NASA NTRS1987

Error Prevention Aid

In a complex computer environment there is ample opportunity for error, a mistake by a programmer, or a software-induced undesirable side effect. In insurance, errors can cost a company heavily, so protection against inadvertent change is a must for the efficient firm. The data processing center at Transport Life Insurance Company has taken a step to guard against accidental changes by adopting a software package called EQNINT (Equations Interpreter Program). EQNINT cross checks the basic formulas in a program against the formulas that make up the major production system. EQNINT assures that formulas are coded correctly and helps catch errors before they affect the customer service or its profitability.

Source record↗
NASA NTRS2000

Under the Weather: Space Weather. The Magnetic Field of the Heliosphere

Normally, only people in the far north can enjoy the dancing beauty of the aurora borealis; however, an intense collision of charged solar particles with the Earth's magnetic field can magnify the Northern Lights so much that they are visible in the southern United States. Behind the light show lies enough flux of energetic particles carried by solar wind to render our planet uninhabitable. The Earth's magnetic field, also known as the magnetosphere, is the only thing that shields us from the Sun. Even the magnetosphere cannot fully guard us from the wrath of the Sun. In March 1989, a powerful solar flare hit Earth with such energy that it burned out transformers in Quebec's electrical grid, plunging Quebec and the eastern United States into darkness for more than 9 hours. Northern lights and energy grid overloads are not the only ways that a solar wind can affect us. A solar storm in July 1999 interrupted radio broadcasts. Solar activity can disorient radars and satellite sensors, break up cell phone connections, and threaten the safety of astronauts. A large bombardment of solar particles can even reduce the amount of ozone in the upper atmosphere. Magnetohydrodynamics (MHD), the study of magnetic fields in magnetized plasmas, can help scientists predict, and therefore prepare for, the harmful side effects of solar weather in the magnetosphere.

Roberts, Aaron↗
NASA NTRS2003

Design for Verification: Using Design Patterns to Build Reliable Systems

Components so far have been mainly used in commercial software development to reduce time to market. While some effort has been spent on formal aspects of components, most of this was done in the context of programming language or operating system framework integration. As a consequence, increased reliability of composed systems is mainly regarded as a side effect of a more rigid testing of pre-fabricated components. In contrast to this, Design for Verification (D4V) puts the focus on component specific property guarantees, which are used to design systems with high reliability requirements. D4V components are domain specific design pattern instances with well-defined property guarantees and usage rules, which are suitable for automatic verification. The guaranteed properties are explicitly used to select components according to key system requirements. The D4V hypothesis is that the same general architecture and design principles leading to good modularity, extensibility and complexity/functionality ratio can be adapted to overcome some of the limitations of conventional reliability assurance measures, such as too large a state space or too many execution paths.

Mehlitz, Peter C.↗
NASA NTRS2003

Propel: Tools and Methods for Practical Source Code Model Checking

The work reported here is an overview and snapshot of a project to develop practical model checking tools for in-the-loop verification of NASA s mission-critical, multithreaded programs in Java and C++. Our strategy is to develop and evaluate both a design concept that enables the application of model checking technology to C++ and Java, and a model checking toolset for C++ and Java. The design concept and the associated model checking toolset is called Propel. It builds upon the Java PathFinder (JPF) tool, an explicit state model checker for Java applications developed by the Automated Software Engineering group at NASA Ames Research Center. The design concept that we are developing is Design for Verification (D4V). This is an adaption of existing best design practices that has the desired side-effect of enhancing verifiability by improving modularity and decreasing accidental complexity. D4V, we believe, enhances the applicability of a variety of V&V approaches; we are developing the concept in the context of model checking. The model checking toolset, Propel, is based on extending JPF to handle C++. Our principal tasks in developing the toolset are to build a translator from C++ to Java, productize JPF, and evaluate the toolset in the context of D4V. Through all these tasks we are testing Propel capabilities on customer applications.

Mansouri-Samani, Massoud↗
NASA NTRS2003

Improving Resource Selection and Scheduling Using Predictions

The introduction of computational grids has resulted in several new problems in the area of scheduling that can be addressed using predictions. The first problem is selecting where to run an application on the many resources available in a grid. Our approach to help address this problem is to provide predictions of when an application would start to execute if submitted to specific scheduled computer systems. The second problem is gaining simultaneous access to multiple computer systems so that distributed applications can be executed. We help address this problem by investigating how to support advance reservations in local scheduling systems. Our approaches to both of these problems are based on predictions for the execution time of applications on space- shared parallel computers. As a side effect of this work, we also discuss how predictions of application run times can be used to improve scheduling performance.

Smith, Warren↗
NASA NTRS2003

Magnetic Microspheres and Tissue Model Studies for Therapeutical Applications

Hyperthermia is a well known cancer therapy and consists of heating a tumor region to the elevated temperatures in the range of 40-45 C for an extended period of time (2-8 hours). This leads to thermal inactivation of cell regulatory and growth processes with resulting widespread necrosis, carbonization and coagulation. Moreover, heat boosts the tumor response to other treatments such as radiation, chemotherapy or immunotherapy. Of particular importance is careful control of generated heat in the treated region and keeping it localized. Higher heating, to about 56 C can lead to tissue thermo-ablation. With accurate temperature control, hyperthermia has the advantage of having minimal side effects. Several heating techniques are utilized for this purpose, such as whole body hyperthermia, radio-frequency (RF) hyperthermia, ultrasound technique, inductive microwave antenna hyperthermia, inductive needles (thermoseeds), and magnetic fluid hyperthermia (MFH).MFH offers many advantages as targeting capability by applying magnets. However, this technology still suffers significant inefficiencies due to lack of thermal control. This paper will provide a review of the topic and outline the ongoing work in this area. The main emphasis is in devising ways to overcome the technical difficulty in hyperthermia breast therapy of achieving a uniform therapeutic temperature over the required region of the body and holding it steady for an extended period (2-3 hours). The basic shortcomings of the presently utilized heating methods stem from the non-uniform thermal properties of the tissue and the point heating characteristics of the techniques without any thermal control. Our approach is to develop a novel class of magnetic fluids, which have inherent thermoregulating properties. We have identified a few magnetic alloys which can serve as suitable nano to micron-size particle material. The objective is to synthesize, characterize and evaluate the efficacy of Thermo Regulating Magnetic Fluids (TRMF) for hyperthermia therapy. The development of a tissue model and testing the fluid dynamics of particle motion, settling, distribution in the tissue matrix and heat generation will be discussed.

Ramachandran, N.↗
NASA NTRS2004

Biophotonics and Bone Biology

One of the more serious side effects of extended space flight is an accelerated bone loss. 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 is well known that bone remodeling responds to mechanical forces. We are developing two-photon microscopy techniques to study bone tissue and bone cell cultures to better understand the fundamental response mechanism in bone remodeling. Osteoblast and osteoclast cell cultures are being studied, and the goal is to use molecular biology techniques in conjunction with Fluorescence Lifetime Imaging Microscopy (FLIM) to study the physiology of in-vitro cell cultures in response to various stimuli, such as fluid flow induced shear stress and mechanical stress. We have constructed a two-photon fluorescence microscope for these studies, and are currently incorporating FLIM detection. Current progress will be reviewed. This work is supported by the NASA John Glenn Biomedical Engineering Consortium.

Zimmerli, Gregory↗
NASA NTRS2002

Oxygen control of ethylene biosynthesis during seed development in Arabidopsis thaliana (L.) Heynh

An unforeseen side-effect on plant growth in reduced oxygen is the loss of seed production at concentrations around 25% atmospheric (50 mmol mol-1 O2). In this study, the model plant Arabidopsis thaliana (L.) Heynh. cv. 'Columbia' was used to investigate the effect of low oxygen on ethylene biosynthesis during seed development. Plants were grown in a range of oxygen concentrations (210 [equal to ambient], 160, 100, 50 and 25 mmol mol-1) with 0.35 mmol mol-1 CO2 in N2. Ethylene in full-sized siliques was sampled using gas chromatography, and viable seed production was determined at maturity. Molecular analysis of ethylene biosynthesis was accomplished using cDNAs encoding 1-aminocyclopropane-1-carboxylic acid (ACC) synthase and ACC oxidase in ribonuclease protection assays and in situ hybridizations. No ethylene was detected in siliques from plants grown at 50 and 25 mmol mol-1 O2. At the same time, silique ACC oxidase mRNA increased three-fold comparing plants grown under the lowest oxygen with ambient controls, whereas ACC synthase mRNA was unaffected. As O2 decreased, tissue-specific patterning of ACC oxidase and ACC synthase gene expression shifted from the embryo to the silique wall. These data demonstrate how low O2 modulates the activity and expression of the ethylene biosynthetic pathway during seed development in Arabidopsis.

NASA Discipline Plant Biology↗
NASA NTRS1993

Stabilization of pH in solid-matrix hydroponic systems

2-[N-morpholino]ethanesulfonic acid (MES) buffer or Amberlite DP-1 (cation-exchange resin beads) were used to stabilize substrate pH of passive-wicking, solid-matrix hydroponic systems in which small canopies of Brassica napus L. (CrGC 5-2, genome : ACaacc) were grown to maturity. Two concentrations of MES (5 or 10 mM) were included in Hoagland 1 nutrient solution. Alternatively, resin beads were incorporated into the 2 vermiculite : 1 perlite (v/v) growth medium at 6% or 12% of total substrate volume. Both strategies stabilized pH without toxic side effects on plants. Average seed yield rates for all four pH stabilization treatments (13.3 to 16.9 g m-2 day-1) were about double that of the control (8.2 g m-2 day-1), for which there was no attempt to buffer substrate pH. Both the highest canopy seed yield rate (16.9 g m-2 day-1) and the highest shoot harvest index (19.5%) occurred with the 6% resin bead treatment, even though the 10 mM MES and 12% bead treatments maintained pH within the narrowest limits. The pH stabilization methods tested did not significantly affect seed oil and protein contents.

NASA Discipline Number 93-10↗
NASA NTRS2004

Potential Application of Anaerobic Extremophiles for Hydrogen Production

During substrate fermentation many anaerobes produce the hydrogen as a waste product, which often regulates the growth of the cultures as an inhibitor. In nature the hydrogen is usually removed from the ecosystem due to its physical properties or by consumption of hydrogen by secondary anaerobes, which sometimes behave as competitors for electron donors as is seen in the classical example in anaerobic microbial communities via the interaction between methanogens and sulfate- or sulfur- reducers. It was demonstrated previously on mixed cultures of anaerobes at neutral pH that bacterial hydrogen production could provide an alternative energy source. But at neutral pH the original cultures can easily be contaminated by methanogens, a most unpleasant side effect of these conditions is the development of pathogenic bacteria. In both cases the rate of hydrogen production was dramatically decreased since some part of the hydrogen was transformed to methane, and the cultivation of human pathogens on a global scale is very dangerous. In our laboratory, experiments with obligately alkaliphilic bacteria that excrete hydrogen as the end metabolic product were performed at different temperature regimes. Mesophilic and moderately thermophilic bacterial cultures have been studied and compared for the most effective hydrogen production. For high-mineralized media with pH 9.5-10.0 not many methanogens are known to exist. Furthermore, the development of pathogenic contaminant microorganisms is virtually impossible: carbonate-saturated solutions are used as antiseptics in medicine. Therefore the cultivation of alkaliphilic hydrogen producing bacteria could be considered as most safe process for global Scale industry in future. Here we present experimental data on the rates of hydrogen productivity for mesophilic, alkaliphilic, obligately anaerobic bacterium Spirocheta americana ASpG1 and moderately thermophilic, alkaliphilic, facultative anaerobe Anoxybacillus pushchinoensis K1 and discuss the potential implications for alternative energy sources.

Pikuta, Elena V.↗
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↗