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At least 379 records · Page 21

Cutaneous and local radiation injuries

The threat of a large-scale radiological or nuclear (R/N) incident looms in the present-day climate, as noted most recently in an editorial in Scientific American (March 2021). These large-scale incidents are infrequent but affect large numbers of people. Smaller-scale R/N incidents occur more often, affecting smaller numbers of people. There is more awareness of acute radiation syndrome (ARS) in the medical community; however, ionising radiation-induced injuries to the skin are much less understood. Here, this article will provide an overview of radiation-induced injuries to the skin, deeper tissues, and organs. The history and nomenclature; types and causes of injuries; pathophysiology; evaluation and diagnosis; current medical management; and current research of the evaluation and management are presented. Cutaneous radiation injuries (CRI) or local radiation injuries (LRI) may lead to cutaneous radiation syndrome, a sub-syndrome of ARS. These injuries may occur from exposure to radioactive particles suspended in the environment (air, soil, water) after a nuclear detonation or an improvised nuclear detonation (IND), a nuclear power plant incident, or an encounter with a radioactive dispersal or exposure device. These incidents may also result in a radiation-combined injury; a chemical, thermal, or traumatic injury, with radiation exposure. Skin injuries from medical diagnostic and therapeutic imaging, medical misadministration of nuclear medicine or radiotherapy, occupational exposures (including research) to radioactive sources are more common but are not the focus of this manuscript. Diagnosis and evaluation of injuries are based on the scenario, clinical picture, and dosimetry, and may be assisted through advanced imaging techniques. Research-based multidisciplinary therapies, both in the laboratory and clinical trial environments, hold promise for future medical management. Great progress is being made in recognising the extent of injuries, understanding their pathophysiology, as well as diagnosis and management; however, research gaps still exist.

61 RADIATION PROTECTION AND DOSIMETRY↗

Fluorescent and Bioluminescent Reporter Mouse-Adapted Ebola Viruses Maintain Pathogenicity and Can Be Visualized in Vivo

Abstract Ebola virus (EBOV) causes lethal disease in humans but not in mice. Here, we generated recombinant mouse-adapted (MA) EBOVs, including 1 based on the previously reported serially adapted strain (rMA-EBOV), along with single-reporter rMA-EBOVs expressing either fluorescent (ZsGreen1 [ZsG]) or bioluminescent (nano-luciferase [nLuc]) reporters, and dual-reporter rMA-EBOVs expressing both ZsG and nLuc. No detriment to viral growth in vitro was seen with inclusion of MA-associated mutations or reporter proteins. In CD-1 mice, infection with MA-EBOV, rMA-EBOV, and single-reporter rMA-EBOVs conferred 100% lethality; infection with dual-reporter rMA-EBOV resulted in 73% lethality. Bioluminescent signal from rMA-EBOV expressing nLuc was detected in vivo and ex vivo using the IVIS Spectrum CT. Fluorescent signal from rMA-EBOV expressing ZsG was detected in situ using handheld blue-light transillumination and ex vivo through epi-illumination with the IVIS Spectrum CT. These data support the use of reporter MA-EBOV for studies of Ebola virus in animal disease models.

Immunology↗

Triton: Environmental Monitoring Technology Development, Collision Risk Data Collection (Final Report)

In this project, we assembled a sensor suite that combines a scientific echosounder (sonar) system with video and acoustic cameras (secondary sensors). The sensor suite generates data that is amenable to automated target detection algorithms and can provide inputs to animal encounter models. We developed software (archiving software) to collect data simultaneously from all sensors in the suite, analyze the sonar data automatically in near real-time to identify time periods when targets of interest were present, and automatically archive data from the secondary sensors for these time periods. The product of the archiving software is a data set for the secondary sensors, containing data only for the times when targets of interest were determined to be present by the sonar. We performed controlled field testing to verify the operation of the sensor suite and the archiving software.

47 OTHER INSTRUMENTATION↗

Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice

Romosozumab, a humanized monoclonal antibody specific for sclerostin (SOST), has been approved for treatment of postmenopausal women with osteoporosis at a high risk for fracture. Previous work in sclerostin global knockout (Sost-/- ) mice indicated alterations in immune cell development in the bone marrow (BM), which could be a possible side effect in romosozumab-treated patients. Here, we examined the effects of short-term sclerostin depletion in the BM on hematopoiesis in young mice receiving sclerostin antibody (Scl-Ab) treatment for 6 weeks, and the effects of long-term Sost deficiency on wild-type (WT) long-term hematopoietic stem cells transplanted into older cohorts of Sost-/- mice. Our analyses revealed an increased frequency of granulocytes in the BM of Scl-Ab-treated mice and WT→Sost -/- chimeras, indicating myeloid-biased differentiation in Sost-deficient BM microenvironments. This myeloid bias extended to extramedullary hematopoiesis in the spleen and was correlated with an increase in inflammatory cytokines TNFα, IL-1α, and MCP-1 in Sost-/- BM serum. Additionally, we observed alterations in erythrocyte differentiation in the BM and spleen of Sost-/- mice. Taken together, our current study indicates novel roles for Sost in the regulation of myelopoiesis and control of inflammation in the BM.

59 BASIC BIOLOGICAL SCIENCES↗

A Natural Bias Approach to Cardinal Spline Curves

The cardinal spline approach to defining interpolatory curves is of interest in the application of computer graphics to modelling and animation problems. The formulation of this interpolation problem (C) a vector valued function V is obtained which forms a C1 map from 0,n into the plane in such a way that V(i) and V prime (i) attain prespecified (vector) values P sub i and T sub i for the integers i=0, 1,...n. The intent is that the planar curves V(s) pass through each point P sub i in the direction corresponding to T sub i. In actual practice it is common for only the interpolation points P sub i to be user specified. Suitable tangents T sub i are then provided by some heuristic to complete the specification of (C). A convex control polygon yields a convex interpolant. Examples exist where the interpolant fails to be convex if the tangents are left unbiased.

Fletcher, G. Y.↗

Design, development and testing of an ambient lighting simulator for external illumination of a transport simulator cockpit

Researchers at the NASA-Langley Research Center several years ago began to examine concepts for a facility which could simulate the full range of lighting conditions encountered in flight. The purpose of this facility was to evaluate advanced technology display devices in a cockpit environment. The Aircraft Cockpit Ambient Lighting Simulation System (ACALSS) has been developed to meet that need. The ACALSS surrounds a wide-body part-task simulator cockpit, the Advanced Display Evaluation Cockpit, and interfaces with a VAX 11/780 computer, which is used to host both a math model of a modern transport aircraft and a solar motion model (which animates a servoed sun simulator). Several concepts were evaluated and an efficient design using an ellipsoid reflector and Fresnel luminaires was selected for implementation.

Batson, Vernon M.↗

Utilization of Space Station Freedom for technology research

Space Station Freedom presents a unique opportunity for technology developers to conduct research in the space environment. Research can be conducted in the pressurized volume of the Space Station's laboratories or attached to the Space Station truss in the vacuum of space. Technology developers, represented by the Office of Aeronautics and Space Technology (OAST), will have 12 percent of the available Space Station resources (volume, power, data, crew, etc.) to use for their research. Most technologies can benefit from research on Space Station Freedom and all these technologies are represented in the OAST proposed traffic model. This traffic model consists of experiments that have been proposed by technology developers but not necessarily selected for flight. Experiments to be flown in space will be selected through an Announcement of Opportunity (A.O.) process. The A.O. is expected to be released in August, 1992. Experiments will generally fall into one of the 3 following categories: (1) Individual technology experiments; (2) Instrumented Space Station; and (3) Guest investigator program. The individual technology experiments are those that do not instrument the Space Station nor directly relate to the development of technologies for evolution of Space Station or development of advanced space platforms. The Instrumented Space Station category is similar to the Orbiter Experiments Program and allows the technology developer to instrument subsystems on the Station or develop instrumentation packages that measure products or processes of the Space Station for the advancement of space platform technologies. The guest investigator program allows the user to request data from Space Station or other experiments for independent research. When developing an experiment, a developer should consider all the resources and infrastructure that Space Station Freedom can provide and take advantage of these to the maximum extent possible. Things like environment, accommodations, carriers, and integration should all be taken into account. In developing experiments at Langley Research Center, an iterative approach is proving useful. This approach uses Space Station utilization and subsystem experts to advise and critique experiment designs to take advantage of everything the Space Station has to offer. Also, solid object modeling and animation computer tools are used to fully visualize the experiment and its processes. This process is very useful for attached payloads and allows problems to be detected early in the experiment design phase.

Avery, Don E.↗

Hey! What's Space Station Freedom?

This video, 'Hey! What's Space Station Freedom?', has been produced as a classroom tool geared toward middle school children. There are three segments to this video. Segment One is a message to teachers presented by Dr. Jeannine Duane, New Jersey, 'Teacher in Space'. Segment Two is a brief Social Studies section and features a series of Presidential Announcements by President John F. Kennedy (May 1961), President Ronald Reagan (July 1982), and President George Bush (July 1989). These historical announcements are speeches concerning the present and future objectives of the United States' space programs. In the last segment, Charlie Walker, former Space Shuttle astronaut, teaches a group of middle school children, through models, computer animation, and actual footage, what Space Station Freedom is, who is involved in its construction, how it is to be built, what each of the modules on the station is for, and how long and in what sequence this construction will occur. There is a brief animation segment where, through the use of cartoons, the children fly up to Space Station Freedom as astronauts, perform several experiments and are given a tour of the station, and fly back to Earth. Space Station Freedom will take four years to build and will have three lab modules, one from ESA and another from Japan, and one habitation module for the astronauts to live in.

Vonehrenfried, Dutch↗

Virtual egocenters as a function of display geometric field of view and eye station point

The accurate location of one's virtual egocenter in a geometric space is of critical importance for immersion technologies. This experiment was conducted to investigate the role of field of view (FOV) and observer station points in the perception of the location of one's egocenter (the personal viewpoint) in virtual space. Rivalrous cues to the accurate location of one's egocenter may be one factor involved in simulator sickness. Fourteen subjects viewed an animated 3D model, of the room in which they sat, binocularly, from Eye Station Points (ESP) of either 300 or 800 millimeters. The display was on a 190 by 245 mm monitor, at a resolution of 320 by 200 pixels with 256 colors. They saw four models of the room designed with four geometric field of view (FOVg) conditions of 18, 48, 86, and 140 degrees. They drew the apparent paths of the camera in the room on a bitmap of the room as seen from infinity above. Large differences in the paths of the camera were seen as a function of both FOVg and ESP. Ten of the subjects were then asked to find the position for each display that minimized camera motion. The results fit well with predictions from an equation that took the ratio of human FOV (roughly 180 degrees) to FOVg times the Geometric Eye Point (GEP) of the imager: Zero Station Point = (180/FOVg)*GEP

Psotka, Joseph↗

Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels

BACKGROUND: Although abnormal L-arginine NO signaling contributes to endothelial dysfunction in the aging cardiovascular system, the biochemical mechanisms remain controversial. L-arginine, the NO synthase (NOS) precursor, is also a substrate for arginase. We tested the hypotheses that arginase reciprocally regulates NOS by modulating L-arginine bioavailability and that arginase is upregulated in aging vasculature, contributing to depressed endothelial function. METHODS AND RESULTS: Inhibition of arginase with (S)-(2-boronoethyl)-L-cysteine, HCl (BEC) produced vasodilation in aortic rings from young (Y) adult rats (maximum effect, 46.4+/-9.4% at 10(-5) mol/L, P<0.01). Similar vasorelaxation was elicited with the additional arginase inhibitors N-hydroxy-nor-L-arginine (nor-NOHA) and difluoromethylornithine (DFMO). This effect required intact endothelium and was prevented by 1H-oxadiazole quinoxalin-1-one (P<0.05 and P<0.001, respectively), a soluble guanylyl cyclase inhibitor. DFMO-elicited vasodilation was greater in old (O) compared with Y rat aortic rings (60+/-6% versus 39+/-6%, P<0.05). In addition, BEC restored depressed L-arginine (10(-4) mol/L)-dependent vasorelaxant responses in O rings to those of Y. Arginase activity and expression were increased in O rings, whereas NOS activity and cyclic GMP levels were decreased. BEC and DFMO suppressed arginase activity and restored NOS activity and cyclic GMP levels in O vessels to those of Y. CONCLUSIONS: These findings demonstrate that arginase modulates NOS activity, likely by regulating intracellular L-arginine availability. Arginase upregulation contributes to endothelial dysfunction of aging and may therefore be a therapeutic target.

Non-NASA Center↗

Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy

BACKGROUND: Myocardial regeneration via stem-cell mobilisation at the time of myocardial infarction is known to occur, although the mechanism for stem-cell homing to infarcted tissue subsequently and whether this approach can be used for treatment of ischaemic cardiomyopathy are unknown. We investigated these issues in a Lewis rat model (ligation of the left anterior descending artery) of ischaemic cardiomyopathy. METHODS: We studied the effects of stem-cell mobilisation by use of granulocyte colony-stimulating factor (filgrastim) with or without transplantation of syngeneic cells. Shortening fraction and myocardial strain by tissue doppler imaging were quantified by echocardiography. FINDINGS: Stem-cell mobilisation with filgrastim alone did not lead to engraftment of bone-marrow-derived cells. Stromal-cell-derived factor 1 (SDF-1), required for stem-cell homing to bone marrow, was upregulated immediately after myocardial infarction and downregulated within 7 days. 8 weeks after myocardial infarction, transplantation into the peri-infarct zone of syngeneic cardiac fibroblasts stably transfected to express SDF-1 induced homing of CD117-positive stem cells to injured myocardium after filgrastim administration (control vs SDF-1-expressing cardiac fibroblasts mean 7.2 [SD 3.4] vs 33.2 [6.0] cells/mm2, n=4 per group, p<0.02) resulting in greater left-ventricular mass (1.24 [0.29] vs 1.57 [0.27] g) and better cardiac function (shortening fraction 9.2 [4.9] vs 17.2 [4.2]%, n=8 per group, p<0.05). INTERPRETATION: These findings show that SDF-1 is sufficient to induce therapeutic stem-cell homing to injured myocardium and suggest a strategy for directed stem-cell engraftment into injured tissues. Our findings also indicate that therapeutic strategies focused on stem-cell mobilisation for regeneration of myocardial tissue must be initiated within days of myocardial infarction unless signalling for stem-cell homing is re-established.

NASA Discipline Cardiopulmonary↗

Loss of T cell precursors after spaceflight and exposure to vector-averaged gravity

Using fetal thymus organ culture (FTOC), we examined the effects of spaceflight and vector-averaged gravity on T cell development. Under both conditions, the development of T cells was significantly attenuated. Exposure to spaceflight for 16 days resulted in a loss of precursors for CD4+, CD8+, and CD4+CD8+ T cells in a rat/mouse xenogeneic co-culture. A significant decrease in the same precursor cells, as well as a decrease in CD4-CD8- T cell precursors, was also observed in a murine C57BL/6 FTOC after rotation in a clinostat to produce a vector-averaged microgravity-like environment. The block in T cell development appeared to occur between the pre-T cell and CD4+CD8+ T cell stage. These data indicate that gravity plays a decisive role in the development of T cells.

Flight Experiment↗

A comparative bear model for immobility-induced osteopenia

The National Institutes of Health (NIH) and the National Aeronautics and Space Administration (NASA) are seeking solutions to the human problem of osteopenia, or immobility-induced bone loss. Bears, during winter dormancy, appear uniquely exempted from the debilitating effects of immobility osteopenia. NIH and ESA, Inc. are creating a large database of metabolic information on human ambulatory and bedrest plasma samples for comparison with metabolic data obtained from bear plasma samples collected in different seasons. The database generated from NASA's HR113 human bedrest study showed a clear difference between plasma samples of ambulatory and immobile subjects through cluster analysis using compounds determined by high performance liquid chromatography with coulometric electrochemical array detection (HPLC-EC). We collected plasma samples from black bears (Ursus americanus) across 4 seasons and from 3 areas and subjected them to similar analysis, with particular attention to compounds that changed significantly in the NASA human study. We found seasonal differences in 28 known compounds and 33 unknown compounds. A final database contained 40 known and 120 unknown peaks that were reliably assayed in all bear and human samples; these were the primary data set for interspecies comparison. Six unidentified compounds changed significantly but differentially in wintering bears and immobile humans. The data are discussed in light of current theories regarding dormancy, starvation, and anabolic metabolism. Work is in progress by ESA Laboratories on a larger database to confirm these findings prior to a chemical isolation and identification effort. This research could lead to new pharmaceuticals or dietary interventions for the treatment of immobility osteopenia.

NASA Discipline Musculoskeletal↗

An evaluation of the use of new Doppler methods for detecting longitudinal function abnormalities in a pacing-induced heart failure model

BACKGROUND: Doppler tissue echocardiography and color M-mode Doppler flow propagation velocity have proven useful in evaluating cross-sections of patients with left ventricular (LV) dysfunction, but experience with serial changes is limited. Purpose and methods: We tested their use by evaluating the temporal changes of LV function in a pacing-induced congestive heart failure model. Rapid ventricular pacing was initiated and maintained in 20 dogs for 4 weeks. Echocardiography was performed at baseline and weekly during brief pacing cessation. RESULTS: With rapid pacing, LV volume significantly increased and ejection fraction (57%-28%), stroke volume (37-18 mL), and mitral annulus systolic velocity (16.1-6.6 cm/s) by Doppler tissue echocardiography significantly decreased, with ejection fraction and mitral annulus systolic velocity closely correlated (r = 0.706, P <.0001). In contrast to the mitral inflow velocities, mitral annulus early diastolic velocity decreased steadily (12.3-7.3 cm/s) resulting in a dramatic decrease in mitral annulus early/late (1.22-0.57) diastolic velocity with no tendency toward pseudonormalization. The color M-mode Doppler flow propagation velocity also showed significant steady decrease (57-24 cm/s) throughout the pacing period. Multiple regression analysis chose mitral annulus systolic velocity (r = 0.895, P <.0001) and propagation velocity (r = 0.782, P <.0001) for the most important factor predicting LV systolic and diastolic function, respectively. CONCLUSIONS: Doppler tissue echocardiography and color M-mode Doppler flow could evaluate the serial deterioration in LV dysfunction throughout the pacing period. These were more useful in quantifying progressive LV dysfunction than conventional ehocardiographic techniques, and were probably relatively independent of preload. These techniques could be suitable for longitudinal evaluation in addition to the cross-sectional study.

Evaluation Studies↗

Mechanical properties and fiber type composition of chronically inactive muscles

A role for neuromuscular activity in the maintenance of skeletal muscle properties has been well established. However, the role of activity-independent factors is more difficult to evaluate. We have used the spinal cord isolation model to study the effects of chronic inactivity on the mechanical properties of the hindlimb musculature in cats and rats. This model maintains the connectivity between the motoneurons and the muscle fibers they innervate, but the muscle unit is electrically "silent". Consequently, the measured muscle properties are activity-independent and thus the advantage of using this model is that it provides a baseline level (zero activity) from which regulatory factors that affect muscle cell homeostasis can be defined. In the present paper, we will present a brief review of our findings using the spinal cord isolation model related to muscle mechanical and fiber type properties.

Non-NASA Center↗

Evidence for vestibular regulation of autonomic functions in a mouse genetic model

Physiological responses to changes in the gravitational field and body position, as well as symptoms of patients with anxiety-related disorders, have indicated an interrelationship between vestibular function and stress responses. However, the relative significance of cochlear and vestibular information in autonomic regulation remains unresolved because of the difficulties in distinguishing the relative contributions of other proprioceptive and interoceptive inputs, including vagal and somatic information. To investigate the role of cochlear and vestibular function in central and physiological responses, we have examined the effects of increased gravity in wild-type mice and mice lacking the POU homeodomain transcription factor Brn-3.1 (Brn-3bPou4f3). The only known phenotype of the Brn-3.1(-/-) mouse is related to hearing and balance functions, owing to the failure of cochlear and vestibular hair cells to differentiate properly. Here, we show that normal physiological responses to increased gravity (2G exposure), such as a dramatic drop in body temperature and concomitant circadian adjustment, were completely absent in Brn-3.1(-/-) mice. In line with the lack of autonomic responses, the massive increase in neuronal activity after 2G exposure normally detected in wild-type mice was virtually abolished in Brn-3.1(-/-) mice. Our results suggest that cochlear and vestibular hair cells are the primary regulators of autonomic responses to altered gravity and provide genetic evidence that these cells are sufficient to alter neural activity in regions involved in autonomic and neuroendocrine control.

Non-NASA Center↗

Energetics of muscle contraction: the whole is less than the sum of its parts

Understanding muscle energetics is a problem in optimizing supply of ATP to the demands of ATPases. The complexity of reactions and their fluxes to achieve this balance is greatly reduced by recognizing constraints imposed by the integration of common metabolites at fixed stoichiometry among modular units. ATPase is driven externally. Oxidative phosphorylation and glycogenolysis are the suppliers. We focus on their regulation which involves different controls, but reduces to two principles that enable facile experimental analysis of the supply and demand fluxes. The ratio of concentration of phosphocreatine (PCr) to ATP, not their individual values, sets the range of achievable concentrations of ADP in resting and active muscle (at fixed pH) in different cell types. This principle defines the fraction of available flux of oxidative phosphorylation utilized (at fixed enzyme activities). Then the kinetics of PCr recovery defines the kinetics of oxygen supply and substrate utilization. The second principle is the constancy of PCr and H(+) (lactate) production by glycogenolysis due to the coupling of ATPase and glycolysis. This principle enables glycogenolytic flux to be measured from intracellular proton loads. Further simplification occurs because the magnitude of the interacting fluxes and metabolite concentrations are specified within narrow limits when both the resting and active fluxes are quantified. Thus there is a small set of rules for assessing and understanding the thermodynamics and kinetics of muscle energetics.

NASA Program Biomedical Research and Countermeasur↗