ALBERT

Description: Many colorectal cancers have high levels of cyclo-oxygenase 2 (COX-2), an enzyme that metabolizes the essential fatty acids into prostaglandins. Since the low-density lipoprotein receptor (LDLr) is involved in the uptake of essential fatty acids, we studied the effect of LDL on growth and gene regulation in colorectal cancer cells. DiFi cells grown in lipoprotein-deficient sera (LPDS) grew more slowly than cells with LDL. LDLr antibody caused significant inhibition of tumor cell growth but did not affect controls. In addition, LDL uptake did not change in the presence of excess LDL, suggesting that ldlr mRNA lacks normal feedback regulation in some colorectal cancers. Analysis of the ldlr mRNA showed that excess LDL in the medium did not cause down-regulation of the message even after 24 hr. The second portion of the study examined the mRNA expression of ldlr and its co-regulation with cox-2 in normal and tumor specimens from patients with colorectal adenocarcinomas. The ratio of tumor:paired normal mucosa of mRNA expression of ldlr and of cox-2 was measured in specimens taken during colonoscopy. ldlr and cox-2 transcripts were apparent in 11 of 11 carcinomas. There was significant coordinate up-regulation both of ldlr and of cox-2 in 6 of 11 (55%) tumors compared with normal colonic mucosa. There was no up-regulation of cox-2 without concomitant up-regulation of ldlr. These data suggest that the LDLr is abnormally regulated in some colorectal tumors and may play a role in the up-regulation of cox-2. Copyright 1999 Wiley-Liss, Inc.

Description: The well-defined osteoblast line, MC3T3-E1 was used to examine fibronectin (FN) mRNA levels, protein synthesis, and extracellular FN matrix accumulation after growth activation in spaceflight. These osteoblasts produce FN extracellular matrix (ECM) known to regulate adhesion, differentiation, and function in adherent cells. Changes in bone ECM and osteoblast cell shape occur in spaceflight. To determine whether altered FN matrix is a factor in causing these changes in spaceflight, quiescent osteoblasts were launched into microgravity and were then sera activated with and without a 1-gravity field. Synthesis of FN mRNA, protein, and matrix were measured after activation in microgravity. FN mRNA synthesis is significantly reduced in microgravity (0-G) when compared to ground (GR) osteoblasts flown in a centrifuge simulating earth's gravity (1-G) field 2.5 h after activation. However, 27.5 h after activation there were no significant differences in mRNA synthesis. A small but significant reduction of FN protein was found in the 0-G samples 2.5 h after activation. Total FN protein 27.5 h after activation showed no significant difference between any of the gravity conditions, however, there was a fourfold increase in absolute amount of protein synthesized during the incubation. Using immunofluorescence, we found no significant differences in the amount or in the orientation of the FN matrix after 27.5 h in microgravity. These results demonstrate that FN is made by sera-activated osteoblasts even during exposure to microgravity. These data also suggest that after a total period of 43 h of spaceflight FN transcription, translation, or altered matrix assembly is not responsible for the altered cell shape or altered matrix formation of osteoblasts.

Description: In serum-deprived MC3T3-E1 osteoblasts, mechanical stimulation caused by mild (287 x g) centrifugation induced a 10-fold increase in mRNA levels of the proto-oncogene, c-fos. Induction of c-fos was abolished by the cAMP-dependent protein kinase inhibitor H-89, suggesting that the transient c-fos mRNA increase is mediated by cAMP. Down-regulation of protein kinase C (PKC) activity by chronic TPA treatment failed to significantly reduce c-fos induction, suggesting that TPA-sensitive isoforms of PKC are not responsible for c-fos up-regulation. In addition, 287 x g centrifugation increased intracellular prostaglandin E2 (PGE2) levels 2.8-fold (P〈0. 005). Since we have previously shown that prostaglandin E2 (PGE2) can induce c-fos expression via a cAMP-mediated mechanism, we asked whether the increase in c-fos mRNA was due to centrifugation-induced PGE2 release. Pretreatment with the cyclooxygenase inhibitors indomethacin and flurbiprofen did not hinder the early induction of c-fos by mechanical stimulation. We conclude that c-fos expression induced by mild mechanical loading is dependent primarily on cAMP, not PKC, and initial induction of c-fos is not necessarily dependent on the action of newly synthesized PGE2.

Description: Maintaining contamination certification of multi-mission flight hardware is an innovative approach to controlling mission costs. Methods for assessing ground induced degradation between missions have been employed by the Hubble Space Telescope (HST) Project for the multi-mission (servicing) hardware. By maintaining the cleanliness of the hardware between missions, and by controlling the materials added to the hardware during modification and refurbishment both project funding for contamination recertification and schedule have been significantly reduced. These methods will be discussed and HST hardware data will be presented.

Description: With the advent of new, more stringent noise regulations in the next century, aircraft engine manufacturers are investigating new technologies to make the current generation of aircraft engines as well as the next generation of advanced engines quieter without sacrificing operating performance. A current NASA initiative called the Advanced Subsonic Technology (AST) Program has set as a goal a 6-EPNdB (effective perceived noise) reduction in aircraft engine noise relative to 1992 technology levels by the year 2000. As part of this noise program, and in cooperation with the Allison Engine Company, an advanced, low-noise, high-bypass-ratio fan stage design and several advanced technology stator vane designs were recently tested in NASA Lewis Research Center's 9- by 15-Foot Low-Speed Wind Tunnel (an anechoic facility). The project was called the NASA/Allison Low Noise Fan.

Description: Sleep disruption and associated waking sleepiness and fatigue are common during space flight. A survey of 58 crew members from nine space shuttle missions revealed that most suffered from sleep disruption, and reportedly slept an average of only 6.1 hours per day of flight as compared to an average of 7.9 hours per day on the ground. Nineteen percent of crewmembers on single shift missions and 50 percent of the crewmembers in dual shift operations reported sleeping pill usage (benzodiazepines) during their missions. Benzodiazepines are effective as hypnotics, however, not without adverse side effects including carryover sedation and performance impairment, anterograde amnesia, and alterations in sleep EEG. Our preliminary ground-based data suggest that pre-sleep administration of 0.3 mg of the pineal hormone melatonin may have the acute hypnotic properties needed for treating the sleep disruption of space flight without producing the adverse side effects associated with benzodiazepines. We hypothesize that pre-sleep administration of melatonin will result in decreased sleep latency, reduced nocturnal sleep disruption, improved sleep efficiency, and enhanced next-day alertness and cognitive performance both in ground-based simulations and during the space shuttle missions. Specifically, we have carried out experiments in which: (1) ambient light intensity aboard the space shuttle is assessed during flight; (2) the impact of space flight on sleep (assessed polysomnographically and actigraphically), respiration during sleep, circadian temperature and melatonin rhythms, waking neurobehavioral alertness and performance is assessed in crew members of the Neurolab and STS-95 missions; (3) the effectiveness of melatonin as a hypnotic is assessed independently of its effects on the phase of the endogenous circadian pacemaker in ground-based studies, using a powerful experimental model of the dyssomnia of space flight; (4) the effectiveness of melatonin as a hypnotic is assessed during the STS-90 (Neurolab) and STS-95 missions in a double-blind placebo-controlled trial. In both flight-based experiments, the effects of melatonin on sleep stages and spectral composition of the EEG during sleep will be determined as well as its effects on daytime alertness and performance; (5) the impact of space flight on sleep and waking neurobehavioral alertness and performance in 30-45-year-old astronauts is compared with its impact in a 77-year-old astronaut. This case study is the first to assess the effects of space flight on an older individual. Because the investigators are still blind to the treatment in this double-blind, placebo-controlled trial, preliminary results will be presented independent of the drug condition.

Description: Pyrotechnic shock, or pyroshock, is the transient response of a structure to loading induced by the ignition of pyrotechnic (explosive or propellant activated) devices. These devices are typically used to separate structural systems (e.g., separate a spacecraft from a launch vehicle) and deploy appendages (e.g., solar panels). Pyroshocks are characterized by high peak acceleration, high-frequency content, and short duration. Because of their high acceleration and high-frequency, pyroshocks can cause spaceflight hardware to fail. Verifying by test that spaceflight hardware can withstand the anticipated shock environment is considered essential to mission success. The Earth Observing System (EOS) AM-1 spacecraft for NASA's Mission to Planet Earth is scheduled to be launched on an Atlas IIAS vehicle in 1999, and the NASA Lewis Research Center is the launch vehicle integrator for this NASA Goddard Space Flight Center spacecraft. The EOS spacecraft was subjected to numerous ground shock tests to verify that its scientific instruments and avionics components will withstand the shock-induced vibration produced when the spacecraft separates from the launch vehicle. Shock test data from these tests represent the third largest available pyroshock database in the United States. Future spacecraft missions will directly benefit from the knowledge gained from these tests. The payload separation system used for EOS is a new system that operates by firing six separation nuts. This system was tested to verify its functional operation and to characterize the resulting shock levels. The launch vehicle contractor (Lockheed Martin Astronautics) and spacecraft contractor (Lockheed Martin Missiles & Space) completed 16 separation test firings. This resulted in an unusually large amount of pyroshock data. Typically, only one or two pyroshock test firings are performed for a spacecraft mission. Because of the size of this separation system shock database, engineers were able to perform unique statistical analyses to characterize the distribution of the test data. For example, it was proven that the shock data follow a lognormal distribution, a concept often assumed but rarely proven. The test-to-test repeatability of the shock source level was analyzed, and the effects of various test configurations and separation nut production lots were examined and quantified. Engineers investigated the change in shock level as the shock traveled from the spacecraft separation interface to the avionics components of the upper stage and analyzed the effects of the structural fidelity (simulator versus real) of the components and their weight on vibrational response. In addition, the shock attenuation with distance and across joints was quantified and compared with concepts originally generated in 1970, and the effects of separation nut preload and firing sequences effects were examined. Because of this EOS shock testing and the analyses performed at NASA Lewis, a significant amount of new information on pyroshock and its characteristics is now available to the aerospace industry. We hope that this information will help future spacecraft test planners to perform better and cheaper spacecraft separation shock tests and to better understand their test data.

Description: The advent of the World Wide Web (Web) and the ability to easily put data repositories on-line has resulted in a proliferation of digital libraries.

Description: Acoustic measurements from eight pre-Cassini Titan IV flights, and an acoustic test of a Cassini simulator and Titan payload fairing (PLF), were used to derive acoustic flight and test criteria for the Cassini spacecraft. The flight and ground test data were used or modified to account for the following factors: (a) noise-spike contamination of flight data, (b) spatial and flight-to-flight variations of flight data, (c) application of a thicker banier-blanket to the PLF for the Cassini mission, (d) effects of locating two Cassini assemblies, the Huygens Probe, and the High Gain Antenna (HGA), near the PLF, and (e) higher thrust of upgraded Titan solid rocket motors (SRMS) for the Cassini mission. An overall sound pressure level (OA SPL) of 145 dB was verified for the protoflight acoustic test criteria for the Cassini spacecraft. Cassini flight liftoff data showed an average OA SPL of 133 dB.