Search NASASearch

SEARCH · Search NASA

Results for “TIME FACTOR”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8

Supportability Issues and Approaches for Exploration Missions

Maintaining and repairing spacecraft systems hardware to achieve required levels of operational availability during long-duration exploration missions will be challenged by limited resupply opportunities, constraints on the mass and volume available for spares and other maintenance-related provisions, and extended communications times. These factors will force the adoption of new approaches to the integrated logistics support of spacecraft systems hardware. For missions beyond the Moon, all spares, equipment, and supplies must either be prepositioned prior to departure from Earth of human crews or carried with the crews. The mass and volume of spares must be minimized by enabling repair at the lowest hardware levels, imposing commonality and standardization across all mission elements at all hardware levels, and providing the capability to fabricate structural and mechanical spares as required. Long round-trip communications times will require increasing levels of autonomy by the crews for most operations including spacecraft maintenance. Effective implementation of these approaches will only be possible when their need is recognized at the earliest stages of the program, when they are incorporated in operational concepts and programmatic requirements, and when diligence is applied in enforcing these requirements throughout system design in an integrated way across all contractors and suppliers. These approaches will be essential for the success of missions to Mars. Although limited duration lunar missions may be successfully accomplished with more traditional approaches to supportability, those missions will offer an opportunity to refine these concepts, associated technologies, and programmatic implementation methodologies so that they can be most effectively applied to later missions.

Watson, J. K.

Post-suspension hypotension is attenuated in Sprague-Dawley rats by prostacyclin synthase inhibition

Cardiovascular deconditioning, sometimes manifested in astronauts during standing postflight, may be related to the impairment of autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, we examined the cardiovascular responses to 7-day 30 degrees tail-suspension and a subsequent 6-h post-suspension period in conscious male Sprague-Dawley rats to determine the role of prostacyclin in the observed post-suspension reduction in mean arterial pressure (MAP). The specific prostacyclin synthase inhibitor U-51605 (0.3 mg/kg), or saline, was administered intravenously prior to release from suspension and at 2 and 4 h post-suspension. During 7 days of suspension, MAP did not change, however, there was a post-suspension reduction in MAP which was associated with significant increases in plasma prostacyclin and nitric oxide. U-51605 attenuated the observed post-suspension hypotension and reduced plasma prostacyclin levels, but not nitric oxide levels. The baroreflex sensitivity for heart rate was modified by U-51605: increased MAP threshold and effective MAP range. Thus, the post-suspension reduction in mean arterial pressure may be due to overproduction of prostacyclin and/or other endothelium-dependent relaxing factors and alteration in baroreflex activity.

Non-NASA Center

Comparisons of luminaires: Efficacies and system design

Lighting designs for architectural (aesthetic) purposes, vision and safety, and plant growth have many features in common but several crucial ones that are not. The human eye is very sensitive to the color (wavelength) of light, whereas plants are less so. There are morphological reactions, particularly to the red and blue portions of the light spectrum but, in general, plants appear to accept and use light for photosynthesis everywhere over the PAR region of the spectrum. In contrast, the human eye interprets light intensity on a logarithmic scale, making people insensitive to significant differences of light intensity. As a rough rule, light intensity must change by 30 to 50% for the human eye to recognize the difference. Plants respond much more linearly to light energy, at least at intensities below photosynthetic saturation. Thus, intensity differences not noticeable to the human eye can have significant effects on total plant growth and yield, and crop timing. These factors make luminaire selection and lighting system design particularly important when designing supplemental lighting systems for plant growth. Supplemental lighting for plant growth on the scale of commercial greenhouses is a relatively expensive undertaking. Light intensities are often much higher than required for task (vision) lighting, which increases both installation and operating costs. However, and especially in the northern regions of the United States (and Canada, Europe, etc.), supplemental lighting during winter may be necessary to produce certain crops (e.g., tomatoes) and very useful to achieve full plant growth potential and crop timing with most other greenhouse crops. Operating costs over the life of a luminaire typically will exceed the initial investment, making lighting efficacy a major consideration. This report reviews tests completed to evaluate the efficiencies of various commercially-available High-Pressure Sodium luminaires, and then describes the results of using a commercial lighting design computer program, Lumen-Micro, to explore how to place luminaires within greenhouses and plant growth chambers to achieve light (PAR) uniformity and relatively high lighting efficacies. Several suggestions are presented which could encourage systematic design of plant lighting systems.

Albright, L. D.

Intracellular magnetophoresis of amyloplasts and induction of root curvature

High-gradient magnetic fields (HGMFs) were used to induce intracellular magnetophoresis of amyloplasts. The HGMFs were generated by placing a small ferromagnetic wedge into a uniform magnetic field or at the gap edge between two permanent magnets. In the vicinity of the tip of the wedge the dynamic factor of the magnetic field, delta(H2/2), was about 10(9) Oe2.cm-1, which subjected the amyloplasts to a force comparable to that of gravity. When roots of 2-d-old seedlings of flax (Linum usitatissimum L.) were positioned vertically and exposed to an HGMF, curvature away from the wedge was transient and lasted approximately 1 h. Average curvature obtained after placing magnets, wedge and seedlings on a 1-rpm clinostat for 2 h was 33 +/- 5 degrees. Roots of horizontally placed control seedlings without rotation curved about 47 +/- 4 degrees. The time course of curvature and changes in growth rate were similar for gravicurvature and for root curvature induced by HGMFs. Microscopy showed displacement of amyloplasts in vitro and in vivo. Studies with Arabidopsis thaliana (L.) Heynh. showed that the wild type responded to HGMFs but the starchless mutant TC7 did not. The data indicate that a magnetic force can be used to study the gravisensing and response system of roots.

Non-NASA Center

Decision-Aiding and Optimization for Vertical Navigation of Long-Haul Aircraft

Most decisions made in the cockpit are related to safety, and have therefore been proceduralized in order to reduce risk. There are very few which are made on the basis of a value metric such as economic cost. One which can be shown to be value based, however, is the selection of a flight profile. Fuel consumption and flight time both have a substantial effect on aircraft operating cost, but they cannot be minimized simultaneously. In addition, winds, turbulence, and performance x,ary widely with altitude and time. These factors make it important and difficult for pilots to (a) evaluate the outcomes associated with a particular trajectory before it is flown and (b) decide among possible trajectories. The two elements of this problem considered here are (1) determining, what constitutes optimality, and (2) finding optimal trajectories. Pilots and dispatchers from major U.S. airlines were surveyed to determine which attributes of the outcome of a flight they considered the most important. Avoiding turbulence-for passenger comfort topped the list of items which were not safety related. Pilots' decision making about the selection of flight profile on the basis of flight time, fuel burn, and exposure to turbulence was then observed. Of the several behavioral and prescriptive decision models invoked to explain the pilots' choices, utility maximization is shown to best reproduce the pilots' decisions. After considering more traditional methods for optimizing trajectories, a novel method is developed using a genetic algorithm (GA) operating on a discrete representation of the trajectory search space. The representation is a sequence of command altitudes, and was chosen to be compatible with the constraints imposed by Air Traffic Control, and with the training given to pilots. Since trajectory evaluation for the GA is performed holistically, a wide class of objective functions can be optimized easily. Also, using the GA it is possible to compare the costs associated with different airspace design and air traffic management policies. A decision aid is proposed which would combine the pilot's notion of optimility with the GA-based optimization, provide the pilot with a number of alternative pareto-optimal trajectories, and allow him to consider un-modelled attributes and constraints in choosing among them. A solution to the problem of displaying alternatives in a multi-attribute decision space is also presented.

Patrick, Nicholas J. M.

Decision-Aiding and Optimization for Vertical Navigation of Long-Haul Aircraft

Most decisions made in the cockpit are related to safety, and have therefore been proceduralized in order to reduce risk. There are very few which are made on the basis of a value metric such as economic cost. One which can be shown to be value based, however, is the selection of a flight profile. Fuel consumption and flight time both have a substantial effect on aircraft operating cost, but they cannot be minimized simultaneously. In addition, winds, turbulence, and performance vary widely with altitude and time. These factors make it important and difficult for pilots to (a) evaluate the outcomes associated with a particular trajectory before it is flown and (b) decide among possible trajectories. The two elements of this problem considered here are: (1) determining what constitutes optimality, and (2) finding optimal trajectories. Pilots and dispatchers from major u.s. airlines were surveyed to determine which attributes of the outcome of a flight they considered the most important. Avoiding turbulence-for passenger comfort-topped the list of items which were not safety related. Pilots' decision making about the selection of flight profile on the basis of flight time, fuel burn, and exposure to turbulence was then observed. Of the several behavioral and prescriptive decision models invoked to explain the pilots' choices, utility maximization is shown to best reproduce the pilots' decisions. After considering more traditional methods for optimizing trajectories, a novel method is developed using a genetic algorithm (GA) operating on a discrete representation of the trajectory search space. The representation is a sequence of command altitudes, and was chosen to be compatible with the constraints imposed by Air Traffic Control, and with the training given to pilots. Since trajectory evaluation for the GA is performed holistically, a wide class of objective functions can be optimized easily. Also, using the GA it is possible to compare the costs associated with different airspace design and air traffic management policies. A decision aid is proposed which would combine the pilot's notion of optimality with the GA-based optimization, provide the pilot with a number of alternative pareto-optimal trajectories, and allow him to consider unmodelled attributes and constraints in choosing among them. A solution to the problem of displaying alternatives in a multi-attribute decision space is also presented.

Patrick, Nicholas J. M.

Platelet factor XIII increases the fibrinolytic resistance of platelet-rich clots by accelerating the crosslinking of alpha 2-antiplasmin to fibrin

Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha 2-antiplasmin (alpha 2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha 2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha 2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha 2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha 2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis.

Non-NASA Center

Instrument Display Visual Angles for Conventional Aircraft and the MQ-9 Ground Control Station

Aircraft instrument panels should be designed such that primary displays are in optimal viewing location to minimize pilot perception and response time. Human Factors engineers define three zones (i.e. cones ) of visual location: 1) "Easy Eye Movement" (foveal vision); 2) "Maximum Eye Movement" (peripheral vision with saccades), and 3) "Head Movement (head movement required). Instrument display visual angles were measured to determine how well conventional aircraft (T-34, T-38, F- 15B, F-16XL, F/A-18A, U-2D, ER-2, King Air, G-III, B-52H, DC-10, B747-SCA) and the MQ-9 ground control station (GCS) complied with these standards, and how they compared with each other. Selected instrument parameters included: attitude, pitch, bank, power, airspeed, altitude, vertical speed, heading, turn rate, slip/skid, AOA, flight path, latitude, longitude, course, bearing, range and time. Vertical and horizontal visual angles for each component were measured from the pilot s eye position in each system. The vertical visual angles of displays in conventional aircraft lay within the cone of "Easy Eye Movement" for all but three of the parameters measured, and almost all of the horizontal visual angles fell within this range. All conventional vertical and horizontal visual angles lay within the cone of Maximum Eye Movement. However, most instrument vertical visual angles of the MQ-9 GCS lay outside the cone of Easy Eye Movement, though all were within the cone of Maximum Eye Movement. All the horizontal visual angles for the MQ-9 GCS were within the cone of "Easy Eye Movement". Most instrument displays in conventional aircraft lay within the cone of Easy Eye Movement, though mission-critical instruments sometimes displaced less important instruments outside this area. Many of the MQ-9 GCS systems lay outside this area. Specific training for MQ-9 pilots may be needed to avoid increased response time and potential error during flight. The learning objectives include: 1) Know three physiologic cones of eye/head movement; 2) Understand how instrument displays comply with these design principles in conventional aircraft and an uninhabited aerial vehicle system. Which of the following is NOT a recognized physiologic principle of instrument display design? Cone of Easy Eye Movement 2) Cone of Binocular Eye Movement 3) Cone of Maximum Eye Movement 4) Cone of Head Movement 5) None of the above. Answer: # 2) Cone of Binocular Eye Movement

Kamine, Tovy Haber

Solar Flare Abundances of Potassium, Argon, and Sulphur

The absolute coronal abundances of potassium has been determined for the first time from X-ray solar flare line and continuous spectra together with absolute and relative abundances of Ar and S. Potassium is of importance in the continuing debate concerning the nature of the coronal/photospheric element abundance ratios which are widely considered to depend on first ionization potential since it has the lowest FIP of any common element in the Sun. The measurements were obtained with the RESIK crystal spectrometer on the Coronas-F spacecraft. A differential emission measure DEM = const. x exp (-(beta)T(sub e) was found to be the most consistent with the data out of three models considered. We find that the coronal ratio [K/H] = 3.7 x 10(exp - 7), a factor 3 times photospheric, in agreement with other observations using line-to-line ratios. Our measured value for the coronal ratio [Ar/H] = 1.5 x 10(exp -6) is significantly less than photospheric, indicating that there is a slight depletion of this high-FIP element in the corona. For S (an intermediate-FIP element) we obtained [S/H] = 2.2 x 10(exp - 5), approximately the same as in previous work.

Oegerle, William

Instrument Display Visual Angles for Conventional Aircraft and the MQ-9 Ground Control Station

Aircraft instrument panels should be designed such that primary displays are in optimal viewing location to minimize pilot perception and response time. Human Factors engineers define three zones (i.e. "cones") of visual location: 1) "Easy Eye Movement" (foveal vision); 2) "Maximum Eye Movement" (peripheral vision with saccades), and 3) "Head Movement" (head movement required). Instrument display visual angles were measured to determine how well conventional aircraft (T-34, T-38, F- 15B, F-16XL, F/A-18A, U-2D, ER-2, King Air, G-III, B-52H, DC-10, B747-SCA) and the MQ-9 ground control station (GCS) complied with these standards, and how they compared with each other. Methods: Selected instrument parameters included: attitude, pitch, bank, power, airspeed, altitude, vertical speed, heading, turn rate, slip/skid, AOA, flight path, latitude, longitude, course, bearing, range and time. Vertical and horizontal visual angles for each component were measured from the pilot s eye position in each system. Results: The vertical visual angles of displays in conventional aircraft lay within the cone of "Easy Eye Movement" for all but three of the parameters measured, and almost all of the horizontal visual angles fell within this range. All conventional vertical and horizontal visual angles lay within the cone of "Maximum Eye Movement". However, most instrument vertical visual angles of the MQ-9 GCS lay outside the cone of "Easy Eye Movement", though all were within the cone of "Maximum Eye Movement". All the horizontal visual angles for the MQ-9 GCS were within the cone of "Easy Eye Movement". Discussion: Most instrument displays in conventional aircraft lay within the cone of "Easy Eye Movement", though mission-critical instruments sometimes displaced less important instruments outside this area. Many of the MQ-9 GCS systems lay outside this area. Specific training for MQ-9 pilots may be needed to avoid increased response time and potential error during flight.

Bendrick, Gregg A.

Extracellular matrix and growth factors in branching morphogenesis

The unifying hypothesis of the NSCORT in gravitational biology postulates that the ECM and growth factors are key interrelated components of a macromolecular regulatory system. The ECM is known to be important in growth and branching morphogenesis of embryonic organs. Growth factors have been detected in the developing embryo, and often the pattern of localization is associated with areas undergoing epithelial-mesenchymal interactions. Causal relationships between these components may be of fundamental importance in control of branching morphogenesis.

Non-NASA Center

Long-term (6-wk) hindlimb suspension inhibits spermatogenesis in adult male rats

The International Space Station will allow extended habitation in space and long-term exposure to microgravity (microG). A concern is the impact of long-term microG exposure on the ability of species to reproduce. The model often used to simulate microG is rat hindlimb suspension (HLS), where the hindlimbs are elevated above the cage floor with a tail harness. Experiments described here are the first to examine the effect of long-term HLS on testicular function in adult male rats. Free-roaming (controls), animals with only the tail harnessed but hindlimbs in contact with the cage floor (TO), and HLS animals were tested for 6 wk. Cryptorchidism was prevented in TO and HLS animals by partial constriction of the inguinal canal with sutures. All parameters were compared at the end of the 6-wk experiment. Testicular weights and spermatogenesis were significantly reduced by HLS, such that no spermatogenic cells beyond round spermatids were present and epididymides were devoid of mature sperm. In many tubules, loss of all germ cells, except a few spermatogonia, resulting in histopathology similar to the Sertoli cell, was observed. Spermatogenesis appeared unaffected in control and TO animals. Sertoli and Leydig cell appearance, testosterone, luteinizing hormone, and follicle-stimulating hormone levels, and epididymal and seminal vesicle weight were unchanged by HLS. Cortisone was not elevated by HLS; thus stress may not be a factor. These results demonstrate that spermatogenesis is severely inhibited by long-term HLS, whereas testicular androgen production is not. These results have significant implications regarding serious effects of long-term exposure to microG on the reproductive capability of scrotal mammals, including humans.

NASA Discipline Cell Biology

Renal stone risk assessment during Space Shuttle flights

PURPOSE: The metabolic and environmental factors influencing renal stone formation before, during, and after Space Shuttle flights were assessed. We established the contributing roles of dietary factors in relationship to the urinary risk factors associated with renal stone formation. MATERIALS AND METHODS: 24-hr. urine samples were collected prior to, during space flight, and following landing. Urinary and dietary factors associated with renal stone formation were analyzed and the relative urinary supersaturation of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were calculated. RESULTS: Urinary composition changed during flight to favor the crystallization of calcium-forming salts. Factors that contributed to increased potential for stone formation during space flight were significant reductions in urinary pH and increases in urinary calcium. Urinary output and citrate, a potent inhibitor of calcium-containing stones, were slightly reduced during space flight. Dietary intakes were significantly reduced for a number of variables, including fluid, energy, protein, potassium, phosphorus and magnesium. CONCLUSIONS: This is the first in-flight characterization of the renal stone forming potential in astronauts. With the examination of urinary components and nutritional factors, it was possible to determine the factors that contributed to increased risk or protected from risk. In spite of the protective components, the negative contributions to renal stone risk predominated and resulted in a urinary environment that favored the supersaturation of stone-forming salts. Dietary and pharmacologic therapies need to be assessed to minimize the potential for renal stone formation in astronauts during/after space flight.

STS Shuttle Project

Occurrence of Equatorial F Region Irregularities: Evidence for Tropospheric Seeding

We present a new gap-free version of the seasonal and longitudinal 0 (s/l) variations of P(sub EFI), the equatorial F region irregularity (EFI) occurrence probability, based on data from the AE-E spacecraft. The agreement of this and three earlier partial P(sub EFI) patterns verifies all four. We reinterpret another earlier gap-ridden pattern, that of D(bar)(sub RSF), a topside ionogram index of average darkening by range spread F. We compare it with P(sub EFI) and, using ionosonde radio science considerations, we conclude that D(bar)(sub RSF) = P(sub EFI) times a factor depending on the average number of topside plasma bubbles visible to the ionosonde. The s/l variations of D(baar)(sub RSF) thus imply s/l variations in the average spacing of bubbles, whose seeds have an occurrence probability pattern P(sub seed). For discussion we assume P(sub EFI) = P(sub inst)P(sub seed) is the pattern of F region instability. The P(sub EFI) pattern, which is by definition independent of seed and/or bubble spacing, is far too complex to be explained by the dominant paradigm, that of changes in P(sub inst) by simple changes in the F region altitude and/or north-south asymmetry. We examine evidence behind this dominance, and find it unconvincing. Both the asymmetry and sunset-node/altitude hypotheses of 1984 and 1985, respectively, seem to be partly based on misunderstood data, and their features appear displaced in time and space from those of our repeatable P(sub EFI) pattern. In contrast, if P(sub seed) variations influence the P(sub EFI) pattern and depend on thermospheric gravity waves from tropospheric convection near the dip equator, then the seasonal maxima (minima) Of P(sub EFI) could be explained, since they all occur above relatively warm (cold) surface features, where convection is maximal (minimal). Also, the hypothesis of the dominance of the P(sub seed) term could explain an unusual December/January P(sub EFI) maximum in the deep, wide, normal Pacific minimum in the one data set obtained in El Nino years. Based on the experiments we consider, we predict that the s/l variations Of P(sub seed) will be found to be similar to those of P(sub EFI) and largely to explain them. Finally, we find reasons, based on the similarity of the D(sub RSF) variations to s/l patterns of the average scintillation index, for not using, as is commonly done, such scintillation patterns as substitutes for P(sub EFI) or P(sub inst) patterns.

McClure, J. P.

Airline chair-rest deconditioning: induction of immobilisation thromboemboli?

Air passenger miles will likely double by year 2020. The altered and restrictive environment in an airliner cabin can influence haematological homeostasis in passengers and crew. Flight-related deep venous thromboemboli (DVT) have been associated with at least 577 deaths on 42 of 120 airlines from 1977 to 1984 (25 deaths/million departures), whereas many such cases go unreported. However, there are four major factors that could influence formation of possible flight-induced DVT: sleeping accommodations (via sitting immobilisation); travellers' medical history (via tissue injury); cabin environmental factors (via lower partial pressure of oxygen and lower relative humidity); and the more encompassing chair-rest deconditioning (C-RD) syndrome. There is ample evidence that recent injury and surgery (especially in deconditioned hospitalised patients) facilitate thrombophlebitis and formation of DVT that may be exacerbated by the immobilisation of prolonged air travel.In the healthy flying population, immobilisation factors associated with prolonged (>5 hours) C-RD such as total body dehydration, hypovolaemia and increased blood viscosity, and reduced venous blood flow (pooling) in the legs may facilitate formation of DVT. However, data from at least four case-controlled epidemiological studies did not confirm a direct causative relationship between air travel and DVT, but factors such as a history of vascular thromboemboli, venous insufficiency, chronic heart failure, obesity, immobile standing position, more than three pregnancies, infectious disease, long-distance travel, muscular trauma and violent physical effort were significantly more frequent in DVT patients than in controls. Thus, there is no clear, direct evidence yet that prolonged sitting in airliner seats, or prolonged experimental chair-rest or bed-rest deconditioning treatments cause DVT in healthy people.

Review, Tutorial

An operational approach to long-duration mission behavioral health and performance factors

NASA's participation in nearly 10 yr of long-duration mission (LDM) training and flight confirms that these missions remain a difficult challenge for astronauts and their medical care providers. The role of the astronaut's crew surgeon is to maximize the astronaut's health throughout all phases of the LDM: preflight, in flight, and postflight. In support of the crew surgeon, the NASA-Johnson Space Center Behavioral Health and Performance Group (JSC-BHPG) has focused on four key factors that can reduce the astronaut's behavioral health and performance. These factors are defined as: sleep and circadian factors; behavioral health factors; psychological adaptation factors; and human-to-system interface (the interface between the astronaut and the mission workplace) factors. Both the crew surgeon and the JSC-BHPG must earn the crewmember's trust preflight to encourage problem identification and problem solving in these four areas. Once on orbit, the crew medical officer becomes a valuable extension of the crew surgeon and BHPG on the ground due to the crew medical officer's constant interaction with crewmembers and preflight training in these four factors. However, the crew surgeon, BHPG, and the crew medical officer need tools that will help predict, prevent, monitor, and respond to developing problems. Objective data become essential when difficult mission termination decisions must be made. The need for behavioral health and performance tool development creates an environment rich for collaboration between operational healthcare providers and researchers. These tools are also a necessary step to safely complete future, more autonomous exploration-class space missions.

Review

Evaluation of pGL1-TNF-alpha therapy in combination with radiation

Long-term control of high-grade brain tumors is rarely achieved with current therapeutic regimens. In this study a new plasmid-based human tumor necrosis factor-alpha (TNF-alpha) expression vector was synthesized (pGL1-TNF-alpha) and evaluated together with radiation in the aggressive, rapidly growing C6 rat glioma model. pGL1-TNF-alpha was successfully transfected into C6 cells in vitro using a cationic polyamine method. Expression was detected up to 7 days and averaged 0.4 ng of TNF-alpha in the culture medium from 1x10(5) cells. The expressed protein was biologically functional, as evidenced by growth inhibition of L929, a TNF-alpha-susceptible cell line. Using fluorescence-labeled monoclonal antibodies and laser scanning cytometry, we confirmed that both the P55 and P75 receptors for TNF-alpha were present on the C6 cell membrane. However, the receptors were present at low density and P55 was expressed more than the P75 receptor. These findings were in contrast to results obtained with TNF-alpha-susceptible L929 cells. Tests in athymic mice showed that pGL1-TNF-alpha administered intratumorally 16-18 h before radiation (each modality given three times) significantly inhibited C6 tumor progression (P<0.05). This effect was more than additive, because pGL1-TNF-alpha alone did not slow tumor growth and radiation alone had little effect on tumor growth. These results indicate that pGL1-TNF-alpha has potential to augment the antitumor effects of radiation against a tumor type that is virtually incurable.

Non-NASA Center

Mechanisms for vasopressin effects on intraocular pressure in anesthetized rats

Continuous intracameral infusions of a balanced salt solution (0.175 microliter min-1) have been reported to raise intraocular pressure (IOP) in anesthetized rats. Palm et al. (1995) previously reported that this effect was attenuated significantly by inclusion of arginine-vasopressin (AVP, 10 ng 0.175 microliter-1) in the infusate. This study used experimental and computer simulation methods to investigate factors underlying these changes in IOP. First, constant intracameral infusions of artificial cerebrospinal fluid (aCSF) at different fixed rates (0.049-0.35 microliter min-1) were used to estimate the outflow resistance. Secondly, IOP responses were measured during an 2 hr intracameral infusion of either aCSF or AVP that was the sum of a small constant component (0.05 microliter min-1) and a larger periodic component (0.25 microliter min-1, cycling for 4 min on, then 4 min off); the mean infusion rate was 0.175 microliter min-1. As shown previously for 0.175 microliter min-1 constant infusions, the periodic aCSF infusion induced a significant rise in IOP that was attenuated by AVP administration. Complex demodulation analysis and the estimated gain parameter of a second order transfer function fit to the periodic responses indicated that outflow resistance increased significantly during the infusions in both aCSF and AVP groups, but that the indices of resistance did not differ significantly between aCSF and AVP infused eyes. This finding implies that changes in outflow resistance do not explain the difference in IOP responses to intracameral aCSF and AVP. The two responses differed significantly, though, in damping factors, such that the aCSF responses were considerably more underdamped than the AVP responses. It is hypothesized that aCSF-induced increase in IOP reflects both (1) a small component reflecting increased outflow resistance and (2) a larger non-resistive component. Since the non-resistive component is insensitive to pretreatment with acetazolamide, it is suggested that the aCSF-induced elevation in IOP reflects primarily vascular perfusion changes that are reduced by local vasoconstrictor actions of AVP. The latter mechanism likely maintains vascular perfusion of the globe when intraocular hypertension develops.

NASA Discipline Cardiopulmonary