ALBERT

Description: It has been proposed that the omega-6 fatty acids increase the rate of tumor growth. Here we test that hypothesis in the PC-3 human prostate tumor. We found that the essential fatty acids, linoleic acid (LA) and arachidonic acid (AA), and the AA metabolite PGE(2) stimulate tumor growth while oleic acid (OA) and the omega-3 fatty acid, eicosapentaenoic acid (EPA) inhibited growth. In examining the role of AA in growth response, we extended our studies to analyze changes in early gene expression induced by AA. We demonstrate that c-fos expression is increased within minutes of addition in a dose-dependent manner. Moreover, the immediate early gene cox-2 is also increased in the presence of AA in a dose-dependent manner, while the constitutive cox-1 message was not increased. Three hours after exposure to AA, the synthesis of PGE(2) via COX-2 was also increased. Previous studies have demonstrated that AA was primarily delivered by low density lipoprotein (LDL) via its receptor (LDLr). Since it is known that hepatomas, acute myelogenous leukemia and colorectal tumors lack normal cholesterol feedback, we examined the role of the LDLr in growth regulation of the PC-3 prostate cancer cells. Analysis of ldlr mRNA expression and LDLr function demonstrated that human PC-3 prostate cancer cells lack normal feedback regulation. While exogenous LDL caused a significant stimulation of cell growth and PGE(2) synthesis, no change was seen in regulation of the LDLr by LDL. Taken together, these data show that normal cholesterol feedback of ldlr message and protein is lost in prostate cancer. These data suggest that unregulated over-expression of LDLr in tumor cells would permit increased availability of AA, which induces immediate early genes c-fos and cox-2 within minutes of uptake.

Description: Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20-35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0-79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only approximately 6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep.

Description: When one considers space missions to the outer edges of our solar system and far beyond, our sun cannot be relied on to produce the required spacecraft (s/c) power. Solar energy diminishes as the square of the distance from the Sun. At Mars it is only 43% of that at earth. At Jupiter, it falls off to only 3.6% of Earth's. By the time we get out to Pluto, solar energy is only .066% what it is on Earth. Beyond the orbit of Mars, it is not practical to depend on solar power for a s/c. However, the farther out we go the more power we need to heat the s/c and to transmit data back to Earth over the long distances. On Earth, knowledge is power. In the outer solar system, power is knowledge. Solar arrays only operate at 19% efficiency, are very vulnerable to damage from radiation and temperature extremes, and cannot be used for even nearby missions that operate in extended darkness, or under the surface of a planet or moon. Twenty-six U.S. space missions, from the Transit to Cassini, have used radioisotope power systems and heater units to take s/c to the far reaches of our solar system and have demonstrated an outstanding record of safety and reliability. Radioisotope thermoelectric generators (RTG's) have proven to be safe, reliable, maintenance-free, and capable of providing both thermal and electrical power for decades under the harsh environments of deep space. RTG's have no problem operating in the high radiation belts of space, the extreme temperatures, or the severe dust storms of Mars, and they have proven to be the most reliable power source ever flown on U.S. s/c. For example, the two Pioneer s/c operated for more than two decades and the Voyager s/c may last for 40 years. RTG's are not nuclear reactors, they serve only as power generators and are not involved in the propulsion of the s/c. They operate on the principle of thermoelectric generation that converts heat directly into electricity, they have no moving parts, are extremely reliable, and have met or exceeded all safety and performance expectations. Federal laws and regulations require analysis and evaluation of the safety risks and any potential environmental impacts. Extensive safety testing of RTG's and RTG components has been performed by the U.S. Department of Energy (DOE) to demonstrate the ability to survive accidents related to Space Shuttle launches and assure that the systems would be safe under all accident conditions, including accidents at or near the launch pad or during orbital reentry. Many design improvements have been made over the four decades that RTG's have been flown on space missions. This paper outlines the operation and safety standards of RTG's and the advanced developments expected to be used on future deep space missions such as the Europa Orbiter, Pluto/Kuiper Express, Solar Probe, Europa Lander, and Titan Explorer missions.

Description: Endogenous circadian clocks are robust regulators of physiology and behavior. Synchronization or entrainment of biological clocks to environmental time is adaptive and important for physiological homeostasis and for the proper timing of species-specific behaviors. We studied subjects in the laboratory for up to 55 days each to determine the ability to entrain the human clock to a weak circadian synchronizing stimulus [scheduled activity-rest cycle in very dim (approximately 1.5 lux in the angle of gaze) light-dark cycle] at three approximately 24-h periods: 23.5, 24.0, and 24.6 h. These studies allowed us to test two competing hypotheses as to whether the period of the human circadian pacemaker is near to or much longer than 24 h. We report here that imposition of a sleep-wake schedule with exposure to the equivalent of candle light during wakefulness and darkness during sleep is usually sufficient to maintain circadian entrainment to the 24-h day but not to a 23.5- or 24.6-h day. Our results demonstrate functionally that, in normally entrained sighted adults, the average intrinsic circadian period of the human biological clock is very close to 24 h. Either exposure to very dim light and/or the scheduled sleep-wake cycle itself can entrain this near-24-h intrinsic period of the human circadian pacemaker to the 24-h day.