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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.

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At least 37 records · Page 2

Flexible radioluminescence imaging for FDG-guided surgery

Purpose: Flexible radioluminescence imaging (Flex-RLI) is an optical method for imaging {sup 18}F-fluorodeoxyglucose (FDG)-avid tumors. The authors hypothesize that a gadolinium oxysulfide: terbium (GOS:Tb) flexible scintillator, which loosely conforms to the body contour, can enhance tumor signal-to-background ratio (SBR) compared with RLI, which utilizes a flat scintillator. The purpose of this paper is to characterize flex-RLI with respect to alternative modalities including RLI, beta-RLI (RLI with gamma rejection), and Cerenkov luminescence imaging (CLI). Methods: The photon sensitivity, spatial resolution, and signal linearity of flex-RLI were characterized with in vitro phantoms. In vivo experiments utilizing 13 nude mice inoculated with the head and neck (UMSCC1-Luc) cell line were then conducted in accordance with the institutional Administrative Panel on Laboratory Animal Care. After intravenous injection of {sup 18}F-FDG, the tumor SBR values for flex-RLI were compared to those for RLI, beta-RLI, and CLI using the Wilcoxon signed rank test. Results: With respect to photon sensitivity, RLI, beta-RLI, and flex-RLI produced 1216.2, 407.0, and 98.6 times more radiance per second than CLI. Respective full-width half maximum values across a 0.5 mm capillary tube were 6.9, 6.4, 2.2, and 1.5 mm, respectively. Flex-RLI demonstrated a near perfect correlation with {sup 18}F activity (r = 0.99). Signal uniformity for flex-RLI improved after more aggressive homogenization of the GOS powder with the silicone elastomer during formulation. In vivo, the SBR value for flex-RLI (median 1.29; interquartile range 1.18–1.36) was statistically greater than that for RLI (1.08; 1.02–1.14; p < 0.01) by 26%. However, there was no statistically significant difference in SBR values between flex-RLI and beta-RLI (p = 0.92). Furthermore, there was no statistically significant difference in SBR values between flex-RLI and CLI (p = 0.11) in a more limited dataset. Conclusions: Flex-RLI provides high quality images with SBRs comparable to those from CLI and beta-RLI in a single 10 s acquisition.

60 APPLIED LIFE SCIENCES↗

Study of the epidermis ablation effect on the efficiency of optical clearing of skin in vivo {sup *}

We present the results of a comparative analysis of optical immersion clearing of skin in laboratory animals in vivo with and without preliminary ablation of epidermis. Laser ablation is implemented using a setup based on a pulsed erbium laser ( λ = 2940 nm). The size of the damaged region amounted to 6 × 6 mm, the depth being smaller than 50 μm. As an optical clearing agent (OCA), use is made of polyethylene glycol (PEG-300). Based on optical coherence tomography, we use the single scattering model to estimate the scattering coefficient in the process of optical clearing in 2 regions at depths of 50−170 μm and 150−400 μm. The results show that skin surface ablation leads to the local oedema of the affected region that increases the scattering coefficient. However, the intense evaporation of water from the ablation zone facilitates the optical clearing at the expense of tissue dehydration, particularly in the upper layers. The assessment of the optical clearing efficiency shows that the efficiency exceeding 30% can be achieved at a depth from 50 to 170 μm in 120 min after ablation, as well as after the same ablation with subsequent application of PEG-300, which increases the efficiency of the immersion method by almost 1.8 times. At a depth from 150 to 400 μm, dehydration of upper layers cannot completely compensate for an increase in light scattering by dermis after epidermis ablation. The additional effect of OCA enhances the optical clearing of skin at the expense of improving the refractive index matching between dermis components, but the maximal efficiency of optical clearing in 120 min does not exceed 6%. (biophotonics)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Transcriptional profiling of rat white adipose tissue response to 2,3,7,8-tetrachlorodibenzo-ρ-dioxin

Polychlorinated dibenzodioxins are environmental contaminants commonly produced as a by-product of industrial processes. The most potent of these, 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), is highly lipophilic, leading to bioaccumulation. White adipose tissue (WAT) is a major site for energy storage, and is one of the organs in which TCDD accumulates. In laboratory animals, exposure to TCDD causes numerous metabolic abnormalities, including a wasting syndrome. We therefore investigated the molecular effects of TCDD exposure on WAT by profiling the transcriptomic response of WAT to 100 μg/kg of TCDD at 1 or 4 days in TCDD-sensitive Long-Evans (Turku/AB; L-E) rats. A comparative analysis was conducted simultaneously in identically treated TCDD-resistant Han/Wistar (Kuopio; H/W) rats one day after exposure to the same dose. We sought to identify transcriptomic changes coinciding with the onset of toxicity, while gaining additional insight into later responses. More transcriptional responses to TCDD were observed at 4 days than at 1 day post-exposure, suggesting WAT shows mostly secondary responses. Two classic AHR-regulated genes, Cyp1a1 and Nqo1, were significantly induced by TCDD in both strains, while several genes involved in the immune response, including Ms4a7 and F13a1 were altered in L-E rats alone. We compared genes affected by TCDD in rat WAT and human adipose cells, and observed little overlap. Interestingly, very few genes involved in lipid metabolism exhibited altered expression levels despite the pronounced lipid mobilization from peripheral fat pads by TCDD in L-E rats. Of these genes, the lipolysis-associated Lpin1 was induced slightly over 2-fold in L-E rat WAT on day 4. - Highlights: • Exposure to TCDD causes wasting syndrome in L-E rats but not in H/W rats. • We examined the transcriptome of TCDD-treated L-E and H/W rat white adipose tissue. • L-E WAT demonstrated altered abundance of several genes involved in immune response. • Few genes had altered abundance in both L-E rat WAT and human adipocytes (hMADS). • Pmepa1 was induced in both L-E WAT and differentiated hMADS cells.

60 APPLIED LIFE SCIENCES↗

Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with {sup 177}Lu- and {sup 90}Y-BR96 mAbs

Purpose: Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study. Methods: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with {sup 90}Y- and {sup 177}Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body. Results: A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for {sup 177}Lu and 12.5 Gy for {sup 90}Y. Conclusions: There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom weight, ranging from 225 g to 300 g, appeared to have no substantial effect for the estimated absorbed dose.

61 RADIATION PROTECTION AND DOSIMETRY↗

Equine cytochrome P450 2B6 — Genomic identification, expression and functional characterization with ketamine

Ketamine is an anesthetic and analgesic regularly used in veterinary patients. As ketamine is almost always administered in combination with other drugs, interactions between ketamine and other drugs bear the risk of either adverse effects or diminished efficacy. Since cytochrome P450 enzymes (CYPs) play a pivotal role in the phase I metabolism of the majority of all marketed drugs, drug–drug interactions often occur at the active site of these enzymes. CYPs have been thoroughly examined in humans and laboratory animals, but little is known about equine CYPs. The characterization of equine CYPs is essential for a better understanding of drug metabolism in horses. We report annotation, cloning and heterologous expression of the equine CYP2B6 in V79 Chinese hamster fibroblasts. After computational annotation of all CYP2B genes, the coding sequence (CDS) of equine CYP2B6 was amplified by RT-PCR from horse liver total RNA and revealed an amino acid sequence identity of 77% and a similarity of 93.7% to its human ortholog. A non-synonymous variant c.226G>A in exon 2 of the equine CYP2B6 was detected in 97 horses. The mutant A-allele showed an allele frequency of 82%. Two further variants in exon 3 were detected in one and two horses of this group, respectively. Transfected V79 cells were incubated with racemic ketamine and norketamine as probe substrates to determine metabolic activity. The recombinant equine CYP2B6 N-demethylated ketamine to norketamine and produced metabolites of norketamine, such as hydroxylated norketamines and 5,6-dehydronorketamine. V{sub max} for S-/and R-norketamine formation was 0.49 and 0.45 nmol/h/mg cellular protein and K{sub m} was 3.41 and 2.66 μM, respectively. The N-demethylation of S-/R-ketamine was inhibited concentration-dependently with clopidogrel showing an IC{sub 50} of 5.63 and 6.26 μM, respectively. The functional importance of the recorded genetic variants remains to be explored. Equine CYP2B6 was determined to be a CYP enzyme involved in ketamine and norketamine metabolism, thus confirming results from inhibition studies with horse liver microsomes. Clopidogrel seems to be a feasible inhibitor for equine CYP2B6. The specificity still needs to be established with other single equine CYPs. Heterologous expression of single equine CYP enzymes opens new possibilities to substantially improve the understanding of drug metabolism and drug interactions in horses. -- Highlights: ► We annotate, express and functionally characterize equine CYP2B6. ► 3 genetic variants within this gene are described. ► Equine CYP2B6 N-demethylates ketamine and metabolizes norketamine. ► Equine CYP2B6 can be inhibited by clopidogrel.

60 APPLIED LIFE SCIENCES↗

Pulmonary Toxicity Studies of Lunar Dusts in Rodents

NASA will build an outpost on the lunar surface for long-duration human habitation and research. The surface of the Moon is covered by a layer of fine, reactive dust, and the living quarters in the lunar outpost are expected to be contaminated by lunar dust. NASA established the Lunar Airborne Dust Toxicity Advisory Group (LADTAG) to evaluate the risk of exposure to the dust and to establish safe exposure limits for astronauts working in the lunar habitat. Because the toxicity of lunar dust is not known, LADTAG has recommended investigating its toxicity in the lungs of laboratory animals. After receiving this recommendation, NASA directed the JSC Toxicology Laboratory to determine the pulmonary toxicity of lunar dust in exposed rodents. The rodent pulmonary toxicity studies proposed here are the same as those proposed by the LADTAG. Studies of the pulmonary toxicity of a dust are generally done first in rodents by intratracheal instillation (ITI). This toxicity screening test is then followed by an inhalation study, which requires much more of the test dust and is labor intensive. We succeeded in completing an ITI study on JSC-1 lunar dust simulant in mice (Lam et al., Inhalation Toxicology 14:901-916, 2002, and Inhalation Toxicology 14: 917-928, 2002), and have conducted a pilot ITI study to examine the acute toxicity of an Apollo lunar (highland) dust sample. Preliminary results obtained by examining lung lavage fluid from dust-treated mice show that lunar dust was somewhat toxic (more toxic than TiO2, but less than quartz dust). More extensive studies have been planned to further examine lung lavage fluid for biomarkers of toxicity and lung tissues for histopathological lesions in rodents exposed to aged and activated lunar dust samples. In these studies, reference dusts (TiO2 and quartz) of known toxicities and have industrial exposure limits will be studied in parallel so the relative toxicity of lunar dust can be determined. The ITI results will also be useful for choosing an exposure concentration for the animal inhalation study on a selected lunar dust sample, which is included as a part of this proposal. The animal inhalation exposure will be conducted with lunar dust simulant prior to the study with the lunar dust. The simulant exposure will ensure that the study techniques used with actual lunar dust will be successful. The results of ITI and inhalation studies will reveal the toxicological risk of exposures and are essential for setting exposure limits on lunar dust for astronauts living in the lunar habitat.

Lam, Chiu-wing↗

Group Housing During Hindlimb Unloading to Simulate Weightlessness

The rodent hindlimb unloading (HU) model was developed in the 1980s to faciliate the study of mechanisms, responses, and treatments for the adverse effects of spaceflight. A number of variations on unloading systems and cage designs have been developed, although most entail individually housing the HU animals. In this study, we performed hindlimb unloading under group housing conditions. Our preliminary results indicate that HU animals that were group housed for 30 days, displayed musculoskeletal decrements associated with disuse, and further, body weights did not differ compared to age-matched controls. In conclusion, group housing of HU mice provides a novel means to simulate weightlessness under conditions that more closely resemble living conditions of Rodent Research Project ISS flight hardware habitats, and minimizes the social stress of isolation, which is consistent with current animal welfare standards (Guide for the Care and Use of Laboratory Animals: Eighth Edition, National Research Council).

group housing↗

Apparatus and methodology for fire gas characterization by means of animal exposure

While there is a great deal of information available from small-scale laboratory experiments and for relatively simple mixtures of gases, considerable uncertainty exists regarding appropriate bioassay techniques for the complex mixture of gases generated in full-scale fires. Apparatus and methodology have been developed based on current state of the art for determining the effects of fire gases in the critical first 10 minutes of a full-scale fire on laboratory animals. This information is presented for its potential value and use while further improvements are being made.

Marcussen, W. H.↗

Technology development activities for housing research animals on Space Station Freedom

The development and design of animal facilities are described in terms of the technological needs for NASA's Biological Flight Research Laboratory. Animal habitats are presented with illustrations which encompass waste-collection techniques for microgravity conditions that reduce the need for crew participation. The technology is intended to be highly compatible with animal morphology, and airflow is employed as the primary mechanism of waste control. The airflow can be utilized in the form of localized high-speed directed flow that simultaneously provides a clean animal habitat and low airflow rates. The design of an animal-habitat testbed is presented which capitalizes on contamination-control mechanisms and suitable materials for microgravity conditions. The developments in materials and technologies represent significant contributions for the design of the centrifuge facilities for the Space Station Freedom.

Jenner, Jeffrey W.↗

Efficacy of Naloxone as a Treatment for an Acute Exposure to Aerosolized Carfentanil

Carfentanil (CRF) is a powerful synthetic opioid that is approximately 100 times more potent than fentanyl and 10,000 times more potent than morphine. CRF originally was intended to be used as a sedative for big game animals in a veterinary setting, but is becoming increasingly common in the illicit drug trade. The increased use of CRF by people has put strain on first responders, who need to administer increased doses of naloxone (Naracan®, Evzio®), an FDA‐approved opioid antagonist, to counteract the effects. First responders may also worry about the potential of self‐exposure through inhalation or dermal contact with CRF. We set out to study the effectiveness of naloxone against a potentially lethal dose of inhaled CRF in male ferrets. Ferrets were implanted with telemetry devices to study cardiac parameters and exposed to aerosolized CRF in a whole‐body plethysmography chamber to record respiratory parameters. We observed profound depression of respiration which resulted in the animals becoming apneic 23% ± 9% of the time during exposure. We also observed cardiac abnormalities, in the form of premature junctional contractions (PJCs), in the ferrets during the apneic periods. At our acute exposure dose, which was lethal in 9% of our animals, ferrets were unresponsive and incapacitated for 105.6 ± 20.0 minutes following the end of exposure. Naloxone, when administered intramuscularly at human equivalent doses ranging from 4 to 40 mg, significantly reduced the time that ferrets were incapacitated following exposure. Although we saw no significant difference in the reduction of time that the animals were incapacitated between the treatment groups (average times between treatment and revival ranged from 6.5 to 9.7 minutes), higher doses of naloxone did revive a portion of the ferrets quicker than the lower doses (some as soon as 1.5–3.5 minutes post‐treatment). We also observed that naloxone was able to significantly reduce the amount of apneic episodes in CRF‐exposed ferrets and resolved the observed cardiac PJCs. Our results suggest that naloxone is a viable treatment against the effects of a potentially lethal dose of inhaled CRF in ferrets. These data have the potential to inform and aid treatment strategies for an acute inhalation exposure to synthetic opioids. Support or Funding Information Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the US Army. This research complied with the Animal Welfare Act and implementing Animal Welfare Regulations and adhered to the principles noted in The Guide for the Care and Use of Laboratory Animals. This research was supported by DTRA RD‐CB. M.R. and N.A.A. were supported in part by an appointment to the Postgraduate Research Participation Program at the US Army Medical Research Institute of Chemical Defense administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and USAMRMC. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

McCranor, Bryan J.↗

Gravitational Effects on Reproduction, Growth, and Development of Mammals

The broad objective of this research program is to determine the role which gravity plays in the growth and development of mammalian animals. Current studies are focused on the effects of graded hypergravitatinal field intensities on mice, rats and other small sized laboratory animals using the chronic centrifugation technique. They include studies on reproduction and prenatal and postnatel growth and development. Among the important questions addressed are: (1) what stage or stages in animal development are affected by hypergravity and what are the effects? (2) is there a minimum or critical body size for hypergravity to produce a significant effect on growth and development? (3) are there field intensity thresholds for the preceding questions? From analysis of the body masses at birth of rats conceived and allowed to undergo gestation under 2.1G and under normal gravity (1G), it was found that there was no significant difference between the two groups. Futhermore, their growth rates postnatally were the same until they reached a body mass of approximately 50 grams when the 2.1G group showed a significantly slower rate. Results from these studies support the conclusion that prenatal as well as the early postnatal stages of growth and development of the rat are refractory to hyper-G.

Oyama, J.↗

Mechanistic Comparison between Gastric Bypass vs. Duodenal Switch with Sleeve Gastrectomy in Rat Models

Both gastric bypass (GB) and duodenal switch with sleeve gastrectomy (DS) have been widely used as bariatric surgeries, and DS appears to be superior to GB. The aim of this study was to better understand the mechanisms leading to body weight loss by comparing these two procedures in experimental models of rats. Animals were subjected to GB, DS or laparotomy (controls), and monitored by an open-circuit indirect calorimeter composed of comprehensive laboratory animal monitoring system and adiabatic bomb calorimeter. Body weight loss was greater after DS than GB. Food intake was reduced after DS but not GB. Energy expenditure was increased after either GB or DS. Fecal energy content was increased after DS but not GB. GB induced body weight loss by increasing energy expenditure, whereas DS induced greater body weight loss by reducing food intake, increasing energy expenditure and causing malabsorption in rat models.

59 BASIC BIOLOGICAL SCIENCES↗

The History of the Animal Care Program at NASA Johnson Space Center

This slide presentation reviews the work of the Animal Care Program (ACP). Animals have been used early in space exploration to ascertain if it were possible to launch a manned spacecraft. The program is currently involved in many studies that assist in enhancing the scientific knowledge of the effect of space travel. The responsibilities of the ACP are: (1) Organize and supervise animal care operations & activities (research, testing & demonstration). (2) Maintain full accreditation by the International Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) (3) Ensure protocol compliance with IACUC recommendations (4) Training astronauts for in-flight animal experiments (5) Maintain accurate & timely records for all animal research testing approved by JSC IACUC (6) Organize IACUC meetings and assist IACUC members (7) Coordinate IACUC review of the Institutional Program for Humane Care and Use of Animals (every 6 mos)

Khan-Mayberry, Noreen↗

The neurochemical and neuropharmacological basis of motion sickness

An apparatus suitable for producing motion sickness in laboratory animals and constructed at the university is herein described. The apparatus is a modified version of that previously described by Fox and Daunton. It consists of a 66-inch steel arm anchored at the center to a wooden platform and attached to a motor that makes the arm move in a see-saw fashion. At each end of the steel arm is mounted an aluminum disc that can be rotated by a motorized device. Detachable cages are mounted on each disc for animal holding. The animal can then be exposed to rotational motion by rotation of the aluminum disc, or to see-saw motion simultaneously (Cross-coupled). The apparatus is presently being used in our laboratory to study the neuropharmacological basis of motion sickness in the rat. The device can be adapted for use with other animal species by modifying the cage mounted on the aluminum discs.

Walker, C. A.↗

An analysis of particle track effects on solid mammalian tissues

Relative biological effectiveness (RBE) and quality factor (Q) at extreme values of linear energy transfer (LET) have been determined on the basis of experiments with single-cell systems and specific tissue responses. In typical single-cell systems, each heavy particle (Ar or Fe) passes through a single cell or no cell. In experiments on animal tissues, however, each heavy particle passes through several cells, and the LET can exceed 200 keV micrometers-1 in every cell. In most laboratory animal tissue systems, however, only a small portion of the hit cells are capable of expressing the end-point being measured, such as cell killing, mutation or carcinogenesis. The following question was therefore addressed: do RBEs and Q factors derived from single-cell experiments properly account for the damage at high LET when multiple cells are hit by HZE tracks? A review is offered in which measured radiation effects and known tissue properties are combined to estimate on the one hand, the number of cells at risk, p3n, per track, where n is the number of cells per track based on tissue and organ geometry, and p3 is the probability that a cell in the track is capable of expressing the experimental end-point. On the other hand, the tissue and single-cell responses are compared by determining the ratio RBE in tissue/RBE in corresponding single cells. Experimental data from the literature indicate that tissue RBEs at very high LET (Fe and Ar ions) are higher than corresponding single-cell RBEs, especially in tissues in which p3n is high.

Non-NASA Center↗

Implanted telemeter for electrocardiogram and body temperature

Measuring system requiring one blocking oscillator to generate modulated pulse repetition rate is implantable in the bodies of small animals. Device has life of two years and transmission range of about three feet. EKG sensing unit also is used to sense electromyogram or electrooculogram of laboratory animals.

Barrows, W. F.↗

Serotonin, atherosclerosis, and collateral vessel spasm

Studies on animal models demonstrate that platelet products contribute to vascular spasm in ischemic syndromes and that this is reversible with administration of ketanserin and thromboxane synthesis inhibitors. Laboratory animals (dogs, rabbits, and rats) that had femoral artery ligations exhibited supersensitivity to serotonin within days in their collateral blood vessels. This supersensitivity lasted at least 6 months. The response to serotonin was reversed by ketanserin, but not by 5HT-1 antagonists. Supersensitivity does not extend to norepinephrine, and alpha blockers do not influence the response to serotonin. It appears that platelet activation by endothelial injury contributes to ischemia through blood vessel occlusion and vascular spasm. When platelet activation occurs in vivo, blood vessel occlusion and vascular spasm are reversible in part by using ketanserin or agents that block thromboxane synthesis or its action. Combining both classes of agents reverses spasm completely. These findings support existing evidence that platelet products contribute to vascular disease, and provide an approach to improved management with currently available pharmacologic agents.

Review, Tutorial↗

Data Visualization and Animation Lab (DVAL) overview

The general capabilities of the Langley Research Center Data Visualization and Animation Laboratory is described. These capabilities include digital image processing, 3-D interactive computer graphics, data visualization and analysis, video-rate acquisition and processing of video images, photo-realistic modeling and animation, video report generation, and color hardcopies. A specialized video image processing system is also discussed.

Stacy, Kathy↗