Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “InBr”

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 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
NASA NTRS2015

Deficits in Sustained Attention and Changes in Dopaminergic Protein Levels Following Exposure to Proton Radiation are Related to Basal Dopaminergic Function

The current report assessed the effects of low-level proton irradiation in inbred adult male Fischer 344 and Lewis rats performing an analog of the human Psychomotor Vigilance Test (PVT), commonly utilized as an object risk assessment tool to quantify fatigue and sustained attention in laboratory, clinical, and operational settings. These strains were used to determine if genetic differences in dopaminergic function would impact radiation-induced deficits in sustained attention. Exposure to head-only proton irradiation (25 or 100 cGy) disrupted rPVT performance in a strain-specific manner, with 25 cGy-exposed Fischer 344 rats displaying the most severe deficits in sustained attention (i.e., decreased accuracy and increased premature responding); Lewis rats did not display behavioral deficits following radiation. Fischer 344 rats displayed greater tyrosine hydroxylase and dopamine transporter levels in the frontal cortex compared to the Lewis rats, even though radiation exposure increased both of these proteins in the Lewis rats only. Tyrosine hydroxylase was decreased in the parietal cortex of both rat strains following radiation exposure, regardless of proton dose. Strain-specific cytokine changes were also found in the frontal cortex, with the Lewis rats displaying increased levels of putative neurotrophic cytokines (e.g., CNTF). These data support the hypothesis that basal dopaminergic function impacts the severity of radiation-induced deficits in sustained attention.

Catherine M Davis↗
NASA NTRSDate not supplied

Quantifying radiation quality for space relevant radiation types: Fitting excess risk models to three combined HZE-irradiated mouse datasets

Radiation health risks are predominantly derived from low linear energy transfer (LET) terrestrial exposures; however, space radiation includes exposure to high-LET and high-charge, high-energy (HZE) particles. Accurately quantifying the differences in radiation quality between the space and terrestrial radiation environments is important for assessing and predicting health risks for astronauts. Weil et al. 2009 and 2014 used two different inbred mouse strains to study differences in hepatocellular carcinoma (HCC) tumorigenesis after exposures to low- and high- LET radiation[1-2]. More recently, Edmondson et al. 2020 provided valuable new tumor data in outbred mice that were exposed to low- and high-LET radiation[3]. The present study aims to rigorously investigate a relative biological effectiveness (RBE) factor by leveraging the HCC tumor data from the three datasets[1-3]. The three experiments were similarly designed, allowing the raw data to be combined into a pooled dataset to estimate excess relative risk (ERR) and excess absolute risk (EAR) models using Bayesian Poisson regression.

Lori J. Chappell↗
NASA NTRS2000

A deficiency in DNA repair and DNA-PKcs expression in the radiosensitive BALB/c mouse

We have studied the efficiency of DNA double strand break (DSB) rejoining in primary cells from mouse strains that show large differences in in vivo radiosensitivity and tumor susceptibility. Cells from radiosensitive, cancer-prone BALB/c mice showed inefficient end joining of gamma ray-induced DSBs as compared with cells from all of the other commonly used strains and F1 hybrids of C57BL/6 and BALB/c mice. The BALB/c repair phenotype was accompanied by a significantly reduced expression level of DNA-PKcs protein as well as a lowered DNA-PK activity level as compared with the other strains. In conjunction with published reports, these data suggest that natural genetic variation in nonhomologous end joining processes may have a significant impact on the in vivo radiation response of mice.

Non-NASA Center↗
NASA NTRS2002

Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton

The structure of the adult skeleton is determined, in large part, by its genome. Whether genetic variations may influence the effectiveness of interventions to combat skeletal diseases remains unknown. The differential response of trabecular bone to an anabolic (low-level mechanical vibration) and a catabolic (disuse) mechanical stimulus were evaluated in three strains of adult mice. In low bone-mineral-density C57BL/6J mice, the low-level mechanical signal caused significantly larger bone formation rates (BFR) in the proximal tibia, but the removal of functional weight bearing did not significantly alter BFR. In mid-density BALB/cByJ mice, mechanical stimulation also increased BFR, whereas disuse significantly decreased BFR. In contrast, neither anabolic nor catabolic mechanical signals influenced any index of bone formation in high-density C3H/HeJ mice. Together, data from this study indicate that the sensitivity of trabecular tissue to both anabolic and catabolic stimuli is influenced by the genome. Extrapolated to humans, these results may explain in part why prophylaxes for low bone mass are not universally effective, yet also indicate that there may be a genotypic indication of people who are at reduced risk of suffering from bone loss.

Non-NASA Center↗
NASA NTRS2002

Pathology effects at radiation doses below those causing increased mortality

Mortality data from experiments conducted at the Argonne National Laboratory (ANL) on the long-term effects of external whole-body irradiation on B6CF(1) mice were used to investigate radiation-induced effects at intermediate doses of (60)Co gamma rays or fission-spectrum neutrons either delivered as a single exposure or protracted over 60 once-weekly exposures. Kaplan-Meier analyses were used to identify the lowest dose in the ANL data (within radiation quality, pattern of exposure, and sex) at which radiation-induced mortality caused by primary tumors could be detected (approximately 1-2 Gy for gamma rays and 10-15 cGy for neutrons). Doses at and below these levels were then examined for radiation-induced shifts in the spectrum of pathology detected at death. To do this, specific pathology events were pooled into larger assemblages based on whether they were cancer, cardiovascular disease or non-neoplastic diseases detected within the lungs and pleura, liver and biliary tract, reproductive organs, or urinary tract. Cancer and cardiovascular disease were further subdivided into categories based on whether they caused death, contributed to death, or were simply observed at death. Counts of how often events falling within each of these combined pathology categories occurred within a mouse were then used as predictor variables in logistic regression to determine whether irradiated mice could be distinguished from control mice. Increased pathology burdens were detected in irradiated mice at doses lower than those causing detectable shifts in mortality-22 cGy for gamma rays and 2 cGy for neutrons. These findings suggest that (1) models based on mortality data alone may underestimate radiation effects, (2) radiation may have adverse health consequences (i.e. elevated health risks) even when mortality risks are not detected, and (3) radiation-induced pathologies other than cancer do occur, and they involve multiple organ systems.

Non-NASA Center↗
NASA NTRS2003

Tetracycline-inducible system for regulation of skeletal muscle-specific gene expression in transgenic mice

Tightly regulated control of over-expression is often necessary to study one aspect or time point of gene function and, in transgenesis, may help to avoid lethal effects and complications caused by ubiquitous over-expression. We have utilized the benefits of an optimized tet-on system and a modified muscle creatine kinase (MCK) promoter to generate a skeletal muscle-specific, doxycycline (Dox) controlled over-expression system in transgenic mice. A DNA construct was generated in which the codon optimized reverse tetracycline transactivator (rtTA) was placed under control of a skeletal muscle-specific version of the mouse MCK promoter. Transgenic mice containing this construct expressed rtTA almost exclusively in skeletal muscles. These mice were crossed to a second transgenic line containing a bi-directional promoter centered on a tet responder element driving both a luciferase reporter gene and a tagged gene of interest; in this case the calpain inhibitor calpastatin. Compound hemizygous mice showed high level, Dox dependent muscle-specific luciferase activity often exceeding 10,000-fold over non-muscle tissues of the same mouse. Western and immunocytochemical analysis demonstrated similar Dox dependent muscle-specific induction of the tagged calpastatin protein. These findings demonstrate the effectiveness and flexibility of the tet-on system to provide a tightly regulated over-expression system in adult skeletal muscle. The MCKrtTA transgenic lines can be combined with other transgenic responder lines for skeletal muscle-specific over-expression of any target gene of interest.

NASA Discipline Musculoskeletal↗
NASA NTRS2002

Body mass, energy intake, and water consumption of rats and humans during space flight

Alteration of metabolism has been suggested as a major limiting factor to long-term space flight. In humans and primates, a negative energy balance has been reported. The metabolic response of rats to space flight has been suggested to result in a negative energy balance. We hypothesized that rats flown in space would maintain energy balance as indicated by maintenance of caloric intake and body mass gain. Further, the metabolism of the rat would be similar to that of laboratory-reared animals. We studied the results from 15 space flights lasting 4 to 19 d. There was no difference in average body weight (206 +/- 13.9 versus 206 +/- 14.8 g), body weight gain (5.8 +/- 0.48 versus 5.9 +/- 0.56 g/d), caloric intake (309 +/- 21.0 versus 309 +/- 20.1 kcal/kg of body mass per day), or water intake (200 +/- 8.6 versus 199 +/- 9.3 mL/kg of body mass per day) between flight and ground control animals. Compared with standard laboratory animals of similar body mass, no differences were noted. The observations suggested that the negative balance observed in humans and non-human primates may be due to other factors in the space-flight environment.

Non-NASA Center↗
NASA NTRS2002

Dietary nucleotides prevent decrease in cellular immunity in ground-based microgravity analog

Microgravity and stress of spaceflights result in immune dysfunction. The role of nutrition, especially nucleotide supplementation, has become an area of intensive research and significant interest in immunomodulation for maintenance of cellular immune responses. The studies presented here evaluate the plausibility of administering nucleotides to obviate immune dysfunction in an Earth-based in vivo analog of microgravity as studied in anti-orthostatic tail suspension (AOS) of mice. Mice were divided into three housing groups: group, isolation, and AOS. Mice were fed either control chow diet (CD), or RNA-, adenine-, or uracil-supplemented CD for the 1-wk duration of the experiments. In AOS mice, supplemental nucleotides significantly increased in vivo lymph node proliferation and ex vivo lymphoproliferation response to alloantigen and mitogens, respectively, and interleukin-2 and interferon-gamma production. A lower corticosterone level was observed in uracil-supplemented CD compared with CD. These results suggest that exogenous nucleotide supplementation, especially uracil, of normal diet is beneficial in the maintenance and restoration of the immune response during the microgravity analog conditions.

NASA Center JSC↗
NASA NTRS2002

Persistent Ehrlichia chaffeensis infection occurs in the absence of functional major histocompatibility complex class II genes

Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the rickettsia Ehrlichia chaffeensis. We investigated the impact of two genes that control macrophage and T-cell function on murine resistance to E. chaffeensis. Congenic pairs of wild-type and toll-like receptor 4 (tlr4)- or major histocompatibility complex class II (MHC-II)-deficient mice were used for these studies. Wild-type mice cleared the infection within 2 weeks, and the response included macrophage activation and the synthesis of E. chaffeensis-specific Th1-type immunoglobulin G response. The absence of a functional tlr4 gene depressed nitric oxide and interleukin 6 secretion by macrophages and resulted in short-term persistent infections for > or =30 days. In the absence of MHC-II alleles, E. chaffeensis infections persisted throughout the entire 3-month evaluation period. Together, these data suggest that macrophage activation and cell-mediated immunity, orchestrated by CD4(+) T cells, are critical for conferring resistance to E. chaffeensis.

NASA Discipline Cell Biology↗
NASA NTRS2001

Risk analysis: divergent models and convergent interpretations

Material presented at a NASA-sponsored workshop on risk models for exposure conditions relevant to prolonged space flight are described in this paper. Analyses used mortality data from experiments conducted at Argonne National Laboratory on the long-term effects of external whole-body irradiation on B6CF1 mice by 60Co gamma rays and fission neutrons delivered as a single exposure or protracted over either 24 or 60 once-weekly exposures. The maximum dose considered was restricted to 1 Gy for neutrons and 10 Gy for gamma rays. Proportional hazard models were used to investigate the shape of the dose response at these lower doses for deaths caused by solid-tissue tumors and tumors of either connective or epithelial tissue origin. For protracted exposures, a significant mortality effect was detected at a neutron dose of 14 cGy and a gamma-ray dose of 3 Gy. For single exposures, radiation-induced mortality for neutrons also occurred within the range of 10-20 cGy, but dropped to 86 cGy for gamma rays. Plots of risk relative to control estimated for each observed dose gave a visual impression of nonlinearity for both neutrons and gamma rays. At least for solid-tissue tumors, male and female mortality was nearly identical for gamma-ray exposures, but mortality risks for females were higher than for males for neutron exposures. As expected, protracting the gamma-ray dose reduced mortality risks. Although curvature consistent with that observed visually could be detected by a model parameterized to detect curvature, a relative risk term containing only a simple term for total dose was usually sufficient to describe the dose response. Although detectable mortality for the three pathology end points considered typically occurred at the same level of dose, the highest risks were almost always associated with deaths caused by tumors of epithelial tissue origin.

Non-NASA Center↗
NASA NTRS1986

Different reactivity to angiotensin II of peripheral and renal arteries in spontaneously hypertensive rats: effect of acute and chronic angiotensin converting enzyme inhibition

We assessed renal blood flow and pressor responses to graded angiotensin II doses in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats ingesting a diet containing 1.6% sodium basally and after acute and chronic angiotensin converting enzyme (ACE) inhibition with captopril. In the basal state the pressor response to angiotensin II was enhanced (P<0.0005) and the renal vascular response was blunted (P<0.005) in SHR compared with WKY rats. After acute captopril administration the pressor response was enhanced in both strains, and the difference between them was maintained, while the renal vascular response was enhanced in both, but more in SHR, so that the renal vascular response in the SHR became larger than in WKY (P<0.0001). Chronic captopril treatment blunted both pressor and renal responses in WKY rats, but only the pressor response in SHR. The renal vessels of SHR seem to be different from those of WKY rats in reaction to exogenous angiotensin II, and in response to both acute administration of captopril (probably acting through blockade of angiotensin II production) and chronic administration of captopril (probably acting mainly through accumulation of kinin or production of prostaglandins).

NASA Discipline Number 21-50↗
NASA NTRS1995

Radiogenic cell transformation and carcinogenesis

Radiation carcinogenesis is one of the major biological effects considered important in the risk assessment for space travel. Various biological model systems, including both cultured cells and animals, have been found useful for studying the carcinogenic effects of space radiations, which consist of energetic electrons, protons and heavy ions. The development of techniques for studying neoplastic cell transformation in culture has made it possible to examine the cellular and molecular mechanisms of radiation carcinogenesis. Cultured cell systems are thus complementary to animal models. Many investigators have determined the oncogenic effects of ionizing and nonionizing radiation in cultured mammalian cells. One of the cell systems used most often for radiation transformation studies is mouse embryonic cells (C3H10T1/2), which are easy to culture and give good quantitative dose-response curves. Relative biological effectiveness (RBE) for heavy ions with various energies and linear energy transfer (LET) have been obtained with this cell system. Similar RBE and LET relationship was observed by investigators for other cell systems. In addition to RBE measurements, fundamental questions on repair of sub- and potential oncogenic lesions, direct and indirect effect, primary target and lesion, the importance of cell-cell interaction and the role of oncogenes and tumor suppressor genes in radiogenic carcinogenesis have been studied, and interesting results have been found. Recently several human epithelial cell systems have been developed, and ionizing radiation have been shown to transform these cells. Oncogenic transformation of these cells, however, requires a long expression time and/or multiple radiation exposures. Limited experimental data indicate high-LET heavy ions can be more effective than low-LET radiation in inducing cell transformation. Cytogenetic and molecular analyses can be performed with cloned transformants to provide insights into basic genetic mechanism(s) of radiogenic transformation of human epithelial cells.

NASA Discipline Radiation Health↗
NASA NTRS2001

Stimulated single fiber electromyography in the mouse: techniques and normative data

As the number of new transgenic mouse models of human neuromuscular disease continues to increase, the development of sophisticated electrophysiologic techniques for assessing the peripheral nervous system in these models has become important. Neuromuscular junction (NMJ) dysfunction, in particular, is often not detectable by morphologic or other techniques. To enable sensitive testing of murine NMJ function, we developed and tested a method for stimulated single fiber electromyography (S-SFEMG) in the gastrocnemius muscles of anesthetized mice. Jitter was assessed by measuring the mean consecutive latency difference (MCD) of single fiber responses to sciatic nerve stimulation at 2 HZ. Mean MCD values in normothermic mice were in the range of 6-8 micros for different strains, with no MCD values exceeding 25 micros. Reduced core temperature (to 29 degrees--30 degrees C) resulted in increased jitter, whereas intubation and mechanical ventilation of mice did not alter these values. Intraperitoneal and intravenous injection of vecuronium, however, resulted in progressively increased jitter followed by blocking in continuously monitored fibers. These observations validate the utility of S-SFEMG in mice as an index of NMJ function under a variety of physiologic conditions, and suggest that a high safety factor for neuromuscular transmission exists at mouse NMJs. Copyright 2001 John Wiley & Sons, Inc.

Non-NASA Center↗
NASA NTRS2000

Eosinophilia of dystrophin-deficient muscle is promoted by perforin-mediated cytotoxicity by T cell effectors

Previous investigations have shown that cytotoxic T lymphocytes (CTLs) contribute to muscle pathology in the dystrophin-null mutant mouse (mdx) model of Duchenne muscular dystrophy through perforin-dependent and perforin-independent mechanisms. We have assessed whether the CTL-mediated pathology includes the promotion of eosinophilia in dystrophic muscle, and thereby provides a secondary mechanism through which CTLs contribute to muscular dystrophy. Quantitative immunohistochemistry confirmed that eosinophilia is a component of the mdx dystrophy. In addition, electron microscopic observations show that eosinophils traverse the basement membrane of mdx muscle fibers and display sites of close apposition of eosinophil and muscle membranes. The close membrane apposition is characterized by impingement of eosinophilic rods of major basic protein into the muscle cell membrane. Transfer of mdx splenocytes and mdx muscle extracts to irradiated C57 mice by intraperitoneal injection resulted in muscle eosinophilia in the recipient mice. Double-mutant mice lacking dystrophin and perforin showed less eosinophilia than was displayed by mdx mice that expressed perforin. Finally, administration of prednisolone, which has been shown previously to reduce the concentration of CTLs in dystrophic muscle, produced a significant reduction in eosinophilia. These findings indicate that eosinophilia is a component of the mdx pathology that is promoted by perforin-dependent cytotoxicity of effector T cells. However, some eosinophilia of mdx muscle is independent of perforin-mediated processes.

NASA Discipline Musculoskeletal↗
NASA NTRS2000

Effects of 2-deoxy-D-glucose administration on cytokine production in BDF1 mice

Physical exercise and diet changes have been shown to affect immune parameters, and similar effects are also induced by the administration of a nonmetabolizable glucose analog, 2-deoxy-D-glucose (2-DG). The present study was designed to characterize the effects of glucoprivation induced by 2-DG administration on concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in the blood and interferon-gamma (IFN-gamma), IL-2, and IL-4 in vitro production by partially purified T splenocytes in BDF1 mice. Mice (n = 8 per group) were injected intraperitoneally one or three times with 0, 500, 750, or 1000 mg/kg of 2-DG, and blood and spleens were collected 2 h after the last injection. Partially purified T splenocytes were cultured 24 h in the presence of concanavalin A (ConA). A significant increase in the corticosterone levels with the amount of 2-DG injected was observed after one or three injections (p<0.05). The amount of 2-DG injected was associated with an increase in TNF-alpha, IL-1beta, and IL-6 concentrations in the blood of mice after one or three injections of 2-DG (p<0.05). A significant decrease in in vitro proliferation of partially purified splenocytes in the presence of ConA was associated with a decrease in IFN-gamma production in the culture supernatants and an increase in IL-1 receptor expression on the cell surface (p<0.05).

NASA Discipline Regulatory Physiology↗
NASA NTRS1999

Cross-linking staphylococcal enterotoxin A bound to major histocompatibility complex class I is required for TNF-alpha secretion

The mechanism of how superantigens function to activate cells has been linked to their ability to bind and cross-link the major histocompatibility complex class II (MHCII) molecule. Cells that lack the MHCII molecule also respond to superantigens, however, with much less efficiency. Therefore, the purpose of this study was to confirm that staphylococcal enterotoxin A (SEA) could bind the MHCI molecule and to test the hypothesis that cross-linking SEA bound to MHCII-deficient macrophages would induce a more robust cytokine response than without cross-linking. We used a capture enzyme-linked immunosorbent assay and an immunprecipitation assay to directly demonstrate that MHCI molecules bind SEA. Directly cross-linking MHCI using monoclonal antibodies or cross-linking bound SEA with an anti-SEA antibody or biotinylated SEA with avidin increased TNF-alpha and IL-6 secretion by MHCII(-/-) macrophages. The induction of a vigorous macrophage cytokine response by SEA/anti-SEA cross-linking of MHCI offers a mechanism to explain how MHCI could play an important role in superantigen-mediated pathogenesis. Copyright 1999 Academic Press.

NASA Discipline Musculoskeletal↗
NASA NTRS1999

Antiorthostatic suspension stimulates profiles of macrophage activation in mice

The antiorthostatic suspension model simulates certain physiological effects of spaceflight. We have previously reported BDF1 mice suspended by the tail in the antiorthostatic orientation for 4 days express high levels of resistance to virulent Listeria monocytogenesinfection. In the present study, we examined whether the increased resistance to this organism correlates with profiles of macrophage activation, given the role of the macrophage in killing this pathogen in vivo. We infected BDF1 mice with a lethal dose of virulent L. monocytogenes on day 4 of antiorthostatic suspension and 24 h later constructed profiles of macrophage activation. Viable listeria could not be detected in mice suspended in the antiorthostatic orientation 24 h after infection. Flow cytometric analysis revealed the numbers of granulocytes and mononuclear phagocytes in the spleen of infected mice were not significantly altered as a result of antiorthostatic suspension. Splenocytes from antiorthostatically suspended infected mice produced increased titers of IL-1. Serum levels of neopterin, a nucleotide metabolite secreted by activated macrophages, were enhanced in mice infected during antiorthostatic suspension, but not in antiorthostatically suspended naive mice. Splenic macrophages from mice infected on day 4 of suspension produced enhanced levels of lysozyme. In contrast to the results from antiorthostatically suspended infected mice, macrophages from antiorthostatically suspended uninfected mice did not express enhanced bactericidal activities. The collective results indicate that antiorthostatic suspension can stimulate profiles of macrophage activation which correlate with increased resistance to infection by certain classes of pathogenic bacteria.

Non-NASA Center↗
NASA NTRS1998

Effects of 2-deoxy-D-glucose administration on immune parameters in mice

Physical exercise and diet alterations have been shown to affect immune parameters. Similar effects are also induced by the administration of the non-metabolizable glucose analog, 2-deoxy-D-glucose (2-DG). The current study was designed to characterize the effects of glucoprivation induced by 2-DG administration on leukocyte subset distribution and function. BDF1 mice (n = 8 per group) were injected intraperitoneally one or three times with 0, 500, 750, 1000 or 1500 mg/kg of 2-DG. Two hours after the last injection of 2-DG, immunological parameters were analyzed. A dose-dependent increase in plasma glucose concentrations of mice injected once with up to 1500 mg/kg of 2-DG was observed (p < 0.001). After either one or three injections of up to 1500 mg/kg of 2-DG, corticosterone levels, leukocyte counts in the spleen, and CD3+ cells in the thymus increased. In vitro proliferation of partially purified lymphocytes from the spleen in the presence of both concanavalin-A and lipopolysaccharide decreased in a dose dependent manner (p < 0.05). In addition, after three injections, the proportion of both thymocytes and splenocytes bearing alphabeta-TCR increased as the concentration of 2-DG increased (p < 0.01). These results demonstrate that 2-DG administration induced dose-dependent changes in both thymus and spleen cell distribution and function.

NASA Discipline Regulatory Physiology↗