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At least 379 records · Page 21

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↗

2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.

Non-NASA Center↗

Gamma-Ray Focusing Optics for Small Animal Imaging

There is a well-established need for high-resolution radionuclide imaging techniques that provide non-invasive measurement of physiological function in small animals. We, therefore, have begun developing a small animal radionuclide imaging system using grazing incidence mirrors to focus low-energy gamma-rays emitted by I-125, and other radionuclides. Our initial prototype optic, fabricated from thermally-formed glass, demonstrated a resolution of 1500 microns, consistent with the performance predicted by detailed simulations. More recently, we have begun constructing mirrors using a replication technique that reduces low spatial frequency errors in the mirror surface, greatly improving the resolution. Each technique offers particular advantages: e.g., multilayer coatings are easily deposited on glass, while superior resolution is possible with replicated optics. Scaling the results from our prototype optics, which only have a few nested shells, to system where the lens has a full complement of several tens of nested shells, a sensitivity of approx. 1 cps/micro Ci is possible, with the exact number dependent on system magnification and radionuclide species. (Higher levels of efficiency can be obtained with multi-optic imaging systems.) The gamma-ray lens will achieve a resolution as good as 100 microns, independent of the final sensitivity. The combination of high spatial resolution and modest sensitivity will enable in vivo single photon emission imaging studies in small animals.

Pivovaroff, M. J.↗

Optical Metrology for the Segmented Optics on the Constellation-X Spectroscopy X-Ray Telescope

We present the metrology requirements and metrology implementation necessary to prove out the reflector technology for the Constellation X(C-X) spectroscopy X-ray telescope (SXT). This segmented, 1.6m diameter highly nested Wolter-1 telescope presents many metrology and alignment challenges. In particular, these mirrors have a stringent imaging error budget as compared to their intrinsic stiffness; This is required for Constellation-X to have sufficient effective area with the weight requirement. This has implications for the metrology that can be used. A variety of contract and noncontact optical profiling and interferometric methods are combined to test the formed glass substrates before replication and the replicated reflector segments.The reflectors are tested both stand-alone and in-situ in an alignment tower.Some of these methods have not been used on prior X-ray telescopes and some are feasible only because of the segmented approach used on the SXT. Methods discussed include high precision coordinate measurement machines using very low force or optical probe axial interferometric profiling azimuthal circularity profiling and use of advanced null optics such as conical computer generated hologram (CGHs).

Content, David↗

[Development of Nanotechnology for X-Ray Astronomy Instrumentation]

This Research Grant provides support for development of nanotechnology for x-ray astronomy instrumentation. MIT has made significant progress in several development areas. In the last year we have made considerable progress in demonstrating the high-fidelity patterning and replication of x-ray reflection gratings. We developed a process for fabricating blazed gratings in silicon with extremely smooth and sharp sawtooth profiles, and developed a nanoimprint process for replication. We also developed sophisticated new fixturing for holding thin optics during metrology without causing distortion. We developed a new image processing algorithm for our Shack-Hartmann tool that uses Zernike polynomials. This has resulted in much more accurate and repeatable measurements on thin optics.

Schattenburg, Mark L.↗

Three stages in the evolution of the genetic code

A diversification of the genetic code based on the number of codons available for the proteinous amino acids is established. Three groups of amino acids during evolution of the code are distinguished. On the basis of their chemical complexity those amino acids emerging later in a translation process are derived. Codon number and chemical complexity indicate that His, Phe, Tyr, Cys and either Lys or Asn were introduced in the second stage, whereas the number of codons alone gives evidence that Trp and Met were introduced in the third stage. The amino acids of stage 1 use purine-rich codons, while all the amino acids introduced in the second stage, in contrast, use pyrimidines in the third position of their codons. A low abundance of pyrimidines during early translation is derived. This assumption is supported by experiments on non-enzymatic replication and interactions of hairpin loops with a complementary strand. A back extrapolation concludes a high purine content of the first nucleic acids, which gradually decreased during their evolution. Amino acids independently available from prebiotic synthesis were thus correlated to purine-rich codons. Implications on the prebiotic replication are discussed also in the light of recent codon usage data.

Review↗

What Information Theory Says about Bounded Rational Best Response

Probability Collectives (PC) provides the information-theoretic extension of conventional full-rationality game theory to bounded rational games. Here an explicit solution to the equations giving the bounded rationality equilibrium of a game is presented. Then PC is used to investigate games in which the players use bounded rational best-response strategies. Next it is shown that in the continuum-time limit, bounded rational best response games result in a variant of the replicator dynamics of evolutionary game theory. It is then shown that for team (shared-payoff) games, this variant of replicator dynamics is identical to Newton-Raphson iterative optimization of the shared utility function.

Wolpert, David H.↗

Initial Development of a Metric to Describe the Level of Safety Associated with Piloting an Aircraft with Synthetic Vision Systems (SVS) Displays

Synthetic Vision Systems (SVS) displays provide pilots with a continuous view of terrain combined with integrated guidance symbology in an effort to increase situation awareness (SA) and decrease workload during operations in Instrument Meteorological Conditions (IMC). It is hypothesized that SVS displays can replicate the safety and operational flexibility of flight in Visual Meteorological Conditions (VMC), regardless of actual out-the-window (OTW) visibility or time of day. Significant progress has been made towards evolving SVS displays as well as demonstrating their ability to increase SA compared to conventional avionics in a variety of conditions. While a substantial amount of data has been accumulated demonstrating the capabilities of SVS displays, the ability of SVS to replicate the safety and operational flexibility of VMC flight performance in all visibility conditions is unknown to any specific degree. In order to more fully quantify the relationship of flight operations in IMC with SVS displays to conventional operations conducted in VMC, a fundamental comparison to current day general aviation (GA) flight instruments was warranted. Such a comparison could begin to establish the extent to which SVS display concepts are capable of maintaining an "equivalent level of safety" with the round dials they could one day replace, for both current and future operations. A combination of subjective and objective data measures were used to quantify the relationship between selected components of safety that are associated with flying an approach. Four information display methods ranging from a "round dials" baseline through a fully integrated SVS package that includes terrain, pathway based guidance, and a strategic navigation display, were investigated in this high fidelity simulation experiment. In addition, a broad spectrum of pilots, representative of the GA population, were employed for testing in an attempt to enable greater application of the results and determine if "equivalent levels of safety" are achievable through the incorporation of SVS technology regardless of a pilot's flight experience.

Bartolone, Anthony P.↗

Integrated Solar Upper Stage Technical Support

NASA Lewis Research Center is participating in the Integrated Solar Upper Stage (ISUS) program. This program is a ground-based demonstration of an upper stage concept that will be used to generate both solar propulsion and solar power. Solar energy collected by a primary concentrator is directed into the aperture of a secondary concentrator and further concentrated into the aperture of a heat receiver. The energy stored in the receiver-absorber-converter is used to heat hydrogen gas to provide propulsion during the orbital transfer portion of the mission. During the balance of the mission, electric power is generated by thermionic diodes. Several materials issues were addressed as part of the technical support portion of the ISUS program, including: 1) Evaluation of primary concentrator coupons; 2) Evaluation of secondary concentrator coupons; 3) Evaluation of receiver-absorber-converter coupons; 4) Evaluation of in-test witness coupons. Two different types of primary concentrator coupons were evaluated from two different contractors-replicated coupons made from graphite-epoxy composite and coupons made from microsheet glass. Specular reflectivity measurements identified the replicated graphite-epoxy composite coupons as the primary concentrator material of choice. Several different secondary concentrator materials were evaluated, including a variety of silver and rhodium reflectors. The specular reflectivity of these materials was evaluated under vacuum at temperatures up to 800 C. The optical properties of several coupons of rhenium on graphite were evaluated to predict the thermal performance of the receiver-absorber-converter. Finally, during the ground test demonstration, witness coupons placed in strategic locations throughout the thermal vacuum facility were evaluated for contaminants. All testing for the ISUS program was completed successfully in 1997. Investigations related to materials issues have proven helpful in understanding the operation of the test article, leading to a potential ISUS flight test in 2002.

Jaworske, Donald A.↗

Engine-Scale Combustor Rig Designed, Fabricated, and Tested for Combustion Instability Control Research

Low-emission combustor designs are prone to combustor instabilities. Because active control of these instabilities may allow future combustors to meet both stringent emissions and performance requirements, an experimental combustor rig was developed for investigating methods of actively suppressing combustion instabilities. The experimental rig has features similar to a real engine combustor and exhibits instabilities representative of those in aircraft gas turbine engines. Experimental testing in the spring of 1999 demonstrated that the rig can be tuned to closely represent an instability observed in engine tests. Future plans are to develop and demonstrate combustion instability control using this experimental combustor rig. The NASA Glenn Research Center at Lewis Field is leading the Combustion Instability Control program to investigate methods for actively suppressing combustion instabilities. Under this program, a single-nozzle, liquid-fueled research combustor rig was designed, fabricated, and tested. The rig has many of the complexities of a real engine combustor, including an actual fuel nozzle and swirler, dilution cooling, and an effusion-cooled liner. Prior to designing the experimental rig, a survey of aircraft engine combustion instability experience identified an instability observed in a prototype engine as a suitable candidate for replication. The frequency of the instability was 525 Hz, with an amplitude of approximately 1.5-psi peak-to-peak at a burner pressure of 200 psia. The single-nozzle experimental combustor rig was designed to preserve subcomponent lengths, cross sectional area distribution, flow distribution, pressure-drop distribution, temperature distribution, and other factors previously found to be determinants of burner acoustic frequencies, mode shapes, gain, and damping. Analytical models were used to predict the acoustic resonances of both the engine combustor and proposed experiment. The analysis confirmed that the test rig configuration and engine configuration had similar longitudinal acoustic characteristics, increasing the likelihood that the engine instability would be replicated in the rig. Parametric analytical studies were performed to understand the influence of geometry and condition variations and to establish a combustion test plan. Cold-flow experiments verified that the design values of area and flow distributions were obtained. Combustion test results established the existence of a longitudinal combustion instability in the 500-Hz range with a measured amplitude approximating that observed in the engine. Modifications to the rig configuration during testing also showed the potential for injector independence. The research combustor rig was developed in partnership with Pratt & Whitney of West Palm Beach, Florida, and United Technologies Research Center of East Hartford, Connecticut. Experimental testing of the combustor rig took place at United Technologies Research Center.

DeLaat, John C.↗

Design and Optimization of the SPOT Primary Mirror Segment

The 3m Spherical Primary Optical Telescope (SPOT) will utilize a single ring of 0.86111 point-to-point hexagonal mirror segments. The f2.85 spherical mirror blanks will be fabricated by the same replication process used for mass-produced commercial telescope mirrors. Diffraction-limited phasing will require segment-to-segment radius of curvature (ROC) variation of approx.1 micron. Low-cost, replicated segment ROC variations are estimated to be almost 1 mm, necessitating a method for segment ROC adjustment & matching. A mechanical architecture has been designed that allows segment ROC to be adjusted up to 400 microns while introducing a minimum figure error, allowing segment-to-segment ROC matching. A key feature of the architecture is the unique back profile of the mirror segments. The back profile of the mirror was developed with shape optimization in MSC.Nastran(TradeMark) using optical performance response equations written with SigFit. A candidate back profile was generated which minimized ROC-adjustment-induced surface error while meeting the constraints imposed by the fabrication method. Keywords: optimization, radius of curvature, Pyrex spherical mirror, Sigfit

Budinoff, Jason G.↗

Space Qualification of Laser Diode Arrays

Laser instruments have great potential in enabling a new generation of remote-sensing scientific instruments. NASA s desire to employ laser instruments aboard satellites, imposes stringent reliability requirements under severe conditions. As a result of these requirements, NASA has a research program to understand, quantify and reduce the risk of failure to these instruments when deployed on satellites. Most of NASA s proposed laser missions have base-lined diode-pumped Nd:YAG lasers that generally use quasi-constant wave (QCW), 808 nm Laser Diode Arrays (LDAs). Our group has an on-going test program to measure the performance of these LDAs when operated in conditions replicating launch and orbit. In this paper, we report on the results of tests designed to measure the effect of vibration loads simulating launch into space and the radiation environment encountered on orbit. Our primary objective is to quantify the performance of the LDAs in conditions replicating those of a satellite instrument, determine their limitations and strengths which will enable better and more robust designs. To this end we have developed a systematic testing strategy to quantify the effect of environmental stresses on the optical and electrical properties of the LDA.

Troupaki, Elisavet↗

Gesture Based Control and EMG Decomposition

This paper presents two probabilistic developments for use with Electromyograms (EMG). First described is a new-electric interface for virtual device control based on gesture recognition. The second development is a Bayesian method for decomposing EMG into individual motor unit action potentials. This more complex technique will then allow for higher resolution in separating muscle groups for gesture recognition. All examples presented rely upon sampling EMG data from a subject's forearm. The gesture based recognition uses pattern recognition software that has been trained to identify gestures from among a given set of gestures. The pattern recognition software consists of hidden Markov models which are used to recognize the gestures as they are being performed in real-time from moving averages of EMG. Two experiments were conducted to examine the feasibility of this interface technology. The first replicated a virtual joystick interface, and the second replicated a keyboard. Moving averages of EMG do not provide easy distinction between fine muscle groups. To better distinguish between different fine motor skill muscle groups we present a Bayesian algorithm to separate surface EMG into representative motor unit action potentials. The algorithm is based upon differential Variable Component Analysis (dVCA) [l], [2] which was originally developed for Electroencephalograms. The algorithm uses a simple forward model representing a mixture of motor unit action potentials as seen across multiple channels. The parameters of this model are iteratively optimized for each component. Results are presented on both synthetic and experimental EMG data. The synthetic case has additive white noise and is compared with known components. The experimental EMG data was obtained using a custom linear electrode array designed for this study.

Wheeler, Kevin R.↗

Application of the Bootstrap Statistical Method in Deriving Vibroacoustic Specifications

This paper discusses the Bootstrap Method for specification of vibroacoustic test specifications. Vibroacoustic test specifications are necessary to properly accept or qualify a spacecraft and its components for the expected acoustic, random vibration and shock environments seen on an expendable launch vehicle. Traditionally, NASA and the U.S. Air Force have employed methods of Normal Tolerance Limits to derive these test levels based upon the amount of data available, and the probability and confidence levels desired. The Normal Tolerance Limit method contains inherent assumptions about the distribution of the data. The Bootstrap is a distribution-free statistical subsampling method which uses the measured data themselves to establish estimates of statistical measures of random sources. This is achieved through the computation of large numbers of Bootstrap replicates of a data measure of interest and the use of these replicates to derive test levels consistent with the probability and confidence desired. The comparison of the results of these two methods is illustrated via an example utilizing actual spacecraft vibroacoustic data.

Hughes, William O.↗

Multi-segment detector

A plurality of stretcher detector segments are connected in series whereby detector signals generated when a bubble passes thereby are added together. Each of the stretcher detector segments is disposed an identical propagation distance away from passive replicators wherein bubbles are replicated from a propagation path and applied, simultaneously, to the stretcher detector segments. The stretcher detector segments are arranged to include both dummy and active portions thereof which are arranged to permit the geometry of both the dummy and active portions of the segment to be substantially matched.

George, Peter K.↗

Technology Development for Nickel X-Ray Optics Enhancement

We are developing grazing-incidence x-ray optics for high-energy astrophysics using the electroform-nickel replication process. In this process, mirror shells are fabricated by replication off super-polished cylindrical mandrels. The mirrors fabricated using this process have a demonstrated optical performance at the level of 11-12 arc seconds resolution (HPD) for 30 keV x rays. Future missions demand ever higher angular resolutions and this places stringent requirements on the quality of the mandrels, the precision of the metrology, and the mounting and alignment of the mirror shells in their housings. A progress report on recent technology developments in all these areas will be presented along with a discussion on possible post fabrication, in-situ improvement of the x-ray mirrors quality.

Bubarev, Mikhail↗

General Purpose Heat Source Simulator

The General Purpose Heat Source (GPHS) simulator project is designed to replicate through the use of electrical heaters, the form, fit, and function of actual GPHS modules which generate heat through the radioactive decay of Pu238. The use of electrically heated modules rather than modules containing Pu238 facilitates the testing of spacecraft subsystems and systems without sacrificing the quantity and quality of the test data gathered. Previous GPHS activities are centered around developing robust heater designs with sizes and weights that closely matched those of actual Pu238 fueled GPHS blocks. These efforts were successful, although their maximum temperature capabilities were limited to around 850 C. New designs are being pursued which also replicate the sizes and weights of actual Pu238 fueled GPHS blocks but will allow operation up to 1100 C.

Emrich, Bill↗

Microgravity Analogues of Herpes Virus Pathogenicity: Human Cytomegalovirus (hCMV) and Varicella Zoster (VZV) Infectivity in Human Tissue Like Assemblies (TLAs)

The old adage we are our own worst enemies may perhaps be the most profound statement ever made when applied to man s desire for extraterrestrial exploration and habitation of Space. Consider the immune system protects the integrity of the entire human physiology and is comprised of two basic elements the adaptive or circulating and the innate immune system. Failure of the components of the adaptive system leads to venerability of the innate system from opportunistic microbes; viral, bacteria, and fungal, which surround us, are transported on our skin, and commonly inhabit the human physiology as normal and imunosuppressed parasites. The fine balance which is maintained for the preponderance of our normal lives, save immune disorders and disease, is deregulated in microgravity. Thus analogue systems to study these potential Risks are essential for our progress in conquering Space exploration and habitation. In this study we employed two known physiological target tissues in which the reactivation of hCMV and VZV occurs, human neural and lung systems created for the study and interaction of these herpes viruses independently and simultaneously on the innate immune system. Normal human neural and lung tissue analogues called tissue like assemblies (TLAs) were infected with low MOIs of approximately 2 x 10(exp -5) pfu hCMV or VZV and established active but prolonged low grade infections which spanned .7-1.5 months in length. These infections were characterized by the ability to continuously produce each of the viruses without expiration of the host cultures. Verification and quantification of viral replication was confirmed via RT_PCR, IHC, and confocal spectral analyses of the respective essential viral genomes. All host TLAs maintained the ability to actively proliferate throughout the entire duration of the experiments as is analogous to normal in vivo physiological conditions. These data represent a significant advance in the ability to study the triggering mechanisms which surround Herpes vial reactivation and proliferation. Additionally, prolonged replication of these viruses will allow the tracking of viral genomic shift.

Goodwin, T. J.↗