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At least 19 records

Suppression of human anti-inflammatory plasma cytokines IL-10 and IL-1RA with elevation of proinflammatory cytokine IFN-gamma during the isolation of the Antarctic winter

Cellular immune function has been shown to be decreased and latent virus shedding to be increased in human beings isolated during the Antarctic winter, a model used for assessing some effects of space flight. However, the balance of proinflammatory (IFN-gamma) and anti-inflammatory (IL-10 and IL-1RA) cytokines has not previously been evaluated. We therefore sought to determine whether isolation during the Antarctic winter would alter the proinflammatory and anti-inflammatory cytokine balance. Cytokine levels were measured with ELISA in monthly plasma samples from January through September 1999 in 21 study subjects in the Antarctic and 7 control subjects on Macquarie Island. There was a significant time-dependent increase in plasma IFN-gamma (P =.039) as well as decreases in IL-10 (P =.042) and IL-1RA (P =.053) in the study subjects compared with the control subjects. The study subjects also had significantly increased plasma IFN-gamma levels (P < or =.045) but decreased IL-10 and IL-1RA levels (P < or =.036) at individual time points of isolation. Isolation of human beings in the Antarctic appears to shift the plasma cytokine balance toward a proinflammatory profile. These observations are consistent with T-cell activation that might be due to activation of latent viruses, and they could hold importance for determining the risks of space flight.

NASA Discipline Regulatory Physiology↗

Early immune response and regulation of IL-2 receptor subunits

Affymetrix oligonucleotide arrays were used to monitor expression of 8796 genes and probe sets in activated T-cells; analysis revealed that 217 genes were significantly upregulated within 4 h. Induced genes included transcription factors, cytokines and their receptor genes. Analysis by semi-quantitative RT-PCR confirmed the significant induction of IL-2, IL-2R(gamma) and IL-2R(alpha). Forty-eight of the 217 induced genes are known to or predicted to be regulated by a CRE promoter/enhancer. We found that T-cell activation caused a significant increase in CREB phosphorylation furthermore, inhibition of the PKC pathway by GF109203 reduced CREB activation by 50% and inhibition of the PKA pathway caused a total block of CREB phosphorylation and significantly reduced IFN(gamma), IL-2 and IL-2R(alpha) gene expression by approximately 40% (p<0.001). PKC(theta) plays a major role in T-cell activation: inhibition of PKC significantly reduced the expression of IFN(gamma), IL-2 and IL-2R(alpha). Since PKC blocked activation of CREB, we studied potential cross-talk between the PKC and the PKA/MAPK pathways, PMA-stimulated Jurkat cells were studied with specific signal pathway inhibitors. Extracellular signal-regulated kinase-2 (ERK2) pathway was found to be significantly activated greater than seven-fold within 30 min; however, there was little activation of ERK-1 and no activation of JNK or p38 MAPK. Inhibition of the PKA pathway, but not the PKC pathway, resulted in inhibition of ERK1/2 activation at all time points, inhibition of MEK1 and 2 significantly blocked expression of IL-2 and IL-2R(alpha). Gene expression of IL-2R(alpha) and IFN(gamma) was dependent on PKA in S49 wt cells but not in kin- mutants. Using gel shift analysis, we found that forskolin activation of T-cells resulted in activation of AP1 sites; this increase in nuclear extract AP1 was significantly blocked by MEK1 inhibitor U0126. Taken together, these results suggest that the PKA in addition to PKC and MAPK pathways plays a role in early T-cell activation and induction of IL-2, IL-2R(alpha) and IFN(gamma) gene expression.

Non-NASA Center↗

Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight

BACKGROUND: The extent to which sleep loss may predispose astronauts to a state of altered immunity during extended space travel prompts evaluation with ground-based models. OBJECTIVE: We sought to measure plasma levels of selected cytokines and their receptors, including the putative sleep-regulation proteins soluble TNF-alpha receptor (sTNF-alpha R) I and IL-6, in human subjects undergoing 2 types of sleep deprivation during environmental confinement with performance demands. METHODS: Healthy adult men (n = 42) were randomized to schedules that varied in severity of sleep loss: 4 days (88 hours) of partial sleep deprivation (PSD) involving two 2-hour naps per day or 4 days of total sleep deprivation (TSD). Plasma samples were obtained every 6 hours across 5 days and analyzed by using enzyme-linked immunoassays for sTNF-alpha RI, sTNF-alpha RII, IL-6, soluble IL-2 receptor, IL-10, and TNF-alpha. RESULTS: Interactions between the effects of time and sleep deprivation level were detected for sTNF-alpha RI and IL-6 but not for sTNF-alpha RII, soluble IL-2 receptor, IL-10, and TNF-alpha. Relative to the PSD condition, subjects in the TSD condition had elevated plasma levels of sTNF-alpha RI on day 2 (P =.04), day 3 (P =.01), and across days 2 to 4 of sleep loss (P =.01) and elevated levels of IL-6 on day 4 (P =.04). CONCLUSIONS: Total sleep loss produced significant increases in plasma levels of sTNF-alpha RI and IL-6, messengers that connect the nervous, endocrine, and immune systems. These changes appeared to reflect elevations of the homeostatic drive for sleep because they occurred in TSD but not PSD, suggesting that naps may serve as the basis for a countermeasures approach to prolonged spaceflight.

Non-NASA Center↗

Modeling of Instrument Landing System (ILS) localizer signal on runway 25L at Los Angeles International Airport

A joint NASA/FAA flight test has been made to record instrument landing system (ILS) localizer receiver signals for use in mathematically modeling the ILS localizer for future simulation studies and airplane flight tracking tasks. The flight test was conducted on a portion of the ILS localizer installed on runway 25L at the Los Angeles International Airport. The tests covered the range from 10 to 32 n.mi. from the localizer antenna. Precision radar tracking information was compared with the recorded localizer deviation data. Data analysis showed that the ILS signal centerline was offset to the left of runway centerline by 0.071 degrees and that no significant bends existed on the localizer beam. Suggested simulation models for the ILS localizer are formed from a statistical analysis.

Hueschen, Richard M.↗

Algorithms and logic for incorporating ILS NASA TCV B-737 airplane area navigation system

The algorithms and logic for use in the implementation of instrument landing system (ILS) localizer deviation signals for the generation of navigation and guidance information are presented. The navigation position estimates, based on range information from a randomly chosen distance measuring equipment (DME) and ILS localizer deviation information, are illustrated. The ILS volumetric coverage and DME geometric checks are described and their addition to area navigation systems with minimum software modification are discussed.

Knox, C. E.↗

A comparison of two position estimate algorithms that use ILS localizer and DME information. Simulation and flight test results

Simulation and flight tests were conducted to compare the accuracy of two algorithms designed to compute a position estimate with an airborne navigation computer. Both algorithms used ILS localizer and DME radio signals to compute a position difference vector to be used as an input to the navigation computer position estimate filter. The results of these tests show that the position estimate accuracy and response to artificially induced errors are improved when the position estimate is computed by an algorithm that geometrically combines DME and ILS localizer information to form a single component of error rather than by an algorithm that produces two independent components of error, one from a DMD input and the other from the ILS localizer input.

Knox, C. E.↗

Alterations in TNF- and IL-related gene expression in space-flown WI38 human fibroblasts

Spaceflight, just like aging, causes profound changes in musculoskeletal parameters, which result in decreased bone density and muscular weakness. As these conditions decrease our ability to conduct long-term manned space missions, and increase bone frailty in the elderly, the identification of genes responsible for the apparition of these physiological changes will be of great benefit. Thus, we developed and implemented a new microarray approach to investigate the changes in normal WI38 human fibroblast gene expression that arise as a consequence of space flight. Using our microarray, we identified changes in the level of expression of 10 genes, belonging to either the tumor necrosis factor- (TNF) or interleukin- (IL) related gene families in fibroblasts when WI38 cells exposed to microgravity during the STS-93 Space Shuttle mission were compared with ground controls. The genes included two ligands from the TNF superfamily, TWEAK and TNFSF15; two TNF receptor-associated proteins, NSMAF and PTPN13; three TNF-inducible genes, ABC50, PTX3, and SCYA13; TNF-alpha converting enzyme, IL-1 receptor antagonist, and IL-15 receptor alpha chain. Most of these are involved in either the regulation of bone density, and as such the development of spaceflight osteopenia, or in the development of proinflammatory status.

manned↗

Piloted simulation study of an ILS approach of a twin-pusher business/commuter turboprop aircraft configuration

A six-degree-of-freedom nonlinear simulation of a twin-pusher, turboprop business/commuter aircraft configuration representative of the Cessna ATPTB (Advanced turboprop test bed) was developed for use in piloted studies with the Langley General Aviation Simulator. The math models developed are provided, simulation predictions are compared with with Cessna flight-test data for validation purposes, and results of a handling quality study during simulated ILS (instrument landing system) approaches and missed approaches are presented. Simulated flight trajectories, task performance measures, and pilot evaluations are presented for the ILS approach and missed-approach tasks conducted with the vehicle in the presence of moderate turbulence, varying horizontal winds and engine-out conditions. Six test subjects consisting of two research pilots, a Cessna test pilot, and three general aviation pilots participated in the study. This effort was undertaken in cooperation with the Cessna Aircraft Company.

Riley, Donald R.↗

Jet transport noise - A comparison of predicted and measured noise for ILS and two-segment approaches

Centerline noise measured during standard ILS and two-segment approaches in DC-8-61 aircraft were compared with noise predicted for these procedures using an existing noise prediction technique. Measured data is considered to be in good agreement with predicted data. Ninety EPNdB sideline locations were calculated from flight data obtained during two-segment approaches and were compared with predicted 90 EPNdB contours that were computed using three different models for excess ground attenuation and a contour with no correction for ground attenuation. The contour not corrected for ground attenuation was in better agreement with the measured data.

White, K. C.↗

Flight test investigation of the vortex wake characteristics behind a Boeing 727 during two-segment and normal ILS approaches

A series of flight tests were performed to evaluate the vortex wake characteristics of a Boeing 727 (B727-200) aircraft during conventional and two-segment ILS approaches. Flights of the B727, equipped with smoke generators for vortex marking, were flown wherein its vortex wake was intentionally encountered by a Lear Jet model 23 (LR-23) or a Piper Twin Comanche (Pa-30); and its vortex location during landing approach was measured using a system of photo-theodolites. The tests showed that at a given separation distance there were no differences in the upsets resulting from deliberate vortex encounters during the two types of approaches. Timed mappings of the position of the landing configuration vortices showed that they tended to descend approximately 91 meters (300 feet) below the flight path of the B727. The flaps of the B727 have a dominant effect on the character of the trailed wake vortex. The clean wing produces a strong, concentrated vortex. As the flaps are lowered, the vortex system becomes more diffuse. Pilot opinion and roll acceleration data indicate that 4.5 nautical miles would be a minimum separation distance at which roll control could be maintained during parallel encounters of the B727's landing configuration wake by small aircraft.

Garodz, L. J.↗

Characteristics of wake vortex generated by a Boeing 727 jet transport during two-segment and normal ILS approach flight paths

A series of flight tests was conducted to evaluate the vortex wake characteristics of a Boeing 727 (B727-200) aircraft during conventional and two-segment ILS approaches. Twelve flights of the B727, which was equipped with smoke generators for vortex marking, were flown and its vortex wake was intentionally encountered by a Lear Jet model 23 (LR-23) and a Piper Twin Comanche (PA-30). Location of the B727 vortex during landing approach was measured using a system of photo-theodolites. The tests showed that at a given separation distance there were no readily apparent differences in the upsets resulting from deliberate vortex encounters during the two types of approaches. Timed mappings of the position of the landing configuration vortices showed that they tended to descend approximately 91 m(300 ft) below the flight path of the B727. The flaps of the B727 have a dominant effect on the character of the trailed wake vortex. The clean wing produces a strong, concentrated vortex but as the flaps are lowered, the vortex system becomes more diffuse. Pilot opinion and roll acceleration data indicate that 4.5 n.mi. would be a minimum separation distance at which roll control of light aircraft (less than 5,670 kg (12,500 lb) could be maintained during parallel encounters of the B727's landing configuration wake. This minimum separation distance is generally in scale with results determined from previous tests of other aircraft using the small roll control criteria.

Kurkowski, R. L.↗

Preliminary report on airline pilot scan patterns during simulated ILS approach

A series of ILS approaches using seven airline-rated Boeing 737 pilots in an FAA qualified simulator have been conducted. The test matrix included both manual and coupled approaches with and without atmospheric turbulence in Category II weather. A nonintrusive oculometer system was used to track the pilot's eye-point-of-regard throughout the approach. The results indicate that, in general, the pilots use a different scan technique for the manual and coupled conditions; however, the introduction of atmospheric turbulence does not greatly affect the scan behavior in either case. A comparison is made between the objective measures of the instrument scan (oculometer data) and the pilots' opinions of their instrument use. The data show a high degree of consistency among pilots for both the quantitative data and the qualitative data (pilots' opinions). However, there is a slightly lower agreement between the quantitative and qualitative measures.

Spady, A. A., Jr.↗

Determination of ILS category 2 decision height window requirements

A method for determining the appropriate longitudinal and lateral decision height dispersion limits for any airplane/control system combination during an instrument landing approach is presented. An example is worked out to clarify the steps required. It is shown that the current longitudinal decision height dispersion limits are well suited for a DC-8 with the example control system, but that the lateral limits are too loose to guarantee acceptable touchdowns with the example system subjected to recommended wind and shear disturbances.

Johnson, W. A.↗

Pilot performance with a simulated ILS independence pictorial display

As part of a general investigation of the effectiveness of pictorial displays for manual control and monitoring of aircraft approaches and landings, a simulator study was conducted in which pilot performance with three pictorial displays was evaluated. These displays differed in the type of guidance symbology added to the basic perspective runway display. The effect of decreased resolution and update rate of the runway image on pilot performance was also determined. The results indicate that for pictorial displays with added guidance symbology, there was a marked improvement in pilot performance compared to results of a previous study in which the display consisted of only a runway image and aircraft attitude.

Palmer, E.↗