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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

Proteo-Genomic Analysis Identifies Two Major Sites of Vulnerability on Ebolavirus Glycoprotein for Neutralizing Antibodies in Convalescent Human Plasma

Three clinically relevant ebolaviruses – Ebola (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) viruses, are responsible for severe disease and occasional deadly outbreaks in Africa. The largest Ebola virus disease (EVD) epidemic to date in 2013-2016 in West Africa highlighted the urgent need for countermeasures, leading to the development and FDA approval of the Ebola virus vaccine rVSV-ZEBOV (Ervebo ® ) in 2020 and two monoclonal antibody (mAb)-based therapeutics (Inmazeb ® [atoltivimab, maftivimab, and odesivimab-ebgn] and Ebanga ® (ansuvimab-zykl) in 2020. The humoral response plays an indispensable role in ebolavirus immunity, based on studies of mAbs isolated from the antibody genes in peripheral blood circulating ebolavirus-specific human memory B cells. However, antibodies in the body are not secreted by circulating memory B cells in the blood but rather principally by plasma cells in the bone marrow. Little is known about the protective polyclonal antibody responses in convalescent plasma. Here we exploited both single-cell antibody gene sequencing and proteomic sequencing approaches to assess the composition of the ebolavirus glycoprotein (GP)-reactive antibody repertoire in the plasma of an EVD survivor. We first identified 1,512 GP-specific mAb variable gene sequences from single cells in the memory B cell compartment. Using mass spectrometric analysis of the corresponding GP-specific plasma IgG, we found that only a portion of the large B cell antibody repertoire was represented in the plasma. Molecular and functional analysis of proteomics-identified mAbs revealed recognition of epitopes in three major antigenic sites - the GP head domain, the glycan cap, and the base region, with a high prevalence of neutralizing and protective mAb specificities that targeted the base and glycan cap regions on the GP. Polyclonal plasma antibodies from the survivor reacted broadly to EBOV, BDBV, and SUDV GP, while reactivity of the potently neutralizing mAbs we identified was limited mostly to the homologous EBOV GP. Together these results reveal a restricted diversity of neutralizing humoral response in which mAbs targeting two antigenic sites on GP – glycan cap and base – play a principal role in plasma-antibody-mediated protective immunity against EVD.

59 BASIC BIOLOGICAL SCIENCES↗

INSD-Hemodynamics

Hemodynamics (potentially will support Digital Astronaut program): Hemodynamics (potentially will support Digital Astronaut program): During long-duration space missions, astronauts have to adapt themselves to.altered circumstance of microgravity. Blood circulation undergoes significant adaptation during and after space flight. The blood flow through an anatomical Circle of Willis configuration is simulated to provide means for studying gravitational effects on the brain circulation.

Cetin, Kiris↗

Some potential blood flow experiments for space

Blood is a colloidal suspension of cells, predominantly erythrocytes, (red cells) in an aqueous solution called plasma. Because the red cells are more dense than the plasma, and because they tend to aggregate, erythrocyte sedimentation can be significant when the shear stresses in flowing blood are small. This behavior, coupled with equipment restrictions, has prevented certain definitive fluid mechanical studies from being performed with blood in ground-based experiments. Among such experiments, which could be satisfactorily performed in a microgravity environment, are the following: (1) studies of blood flow in small tubes, to obtain pressure-flow rate relationships, to determine if increased red cell aggregation can be an aid to blood circulation, and to determine vessel entrance lengths, and (2) studies of blood flow through vessel junctions (bifurcations), to obtain information on cell distribution in downstream vessels of (arterial) bifurcations, and to test flow models of stratified convergent blood flows downstream from (venous) bifurcations.

Cokelet, G. R.↗

Development of ultrasonic methods of hemodynamic measurements

A pulsed ultrasonic Doppler velocity meter which can be used (by modifying transducers) as a flowmeter for blood circulation was experimentally studied. Calculations and profiles of turbulent and laminar flow within blood vessels are shown. Graphs and charts of transducers are included.

Histand, M. B.↗

Carotid Baroreflex Function During Prolonged Exercise

Astronauts are often required to work (exercise) at moderate to high intensities for extended periods while performing extra-vehicular activities (EVA). Although the physiologic responses associated with prolonged exercise have been documented, the mechanisms involved in blood pressure regulation under these conditions have not yet been fully elucidated. An understanding of this issue is pertinent to the ability of humans to perform work in microgravity and complies with the emphasis of NASA's Space Physiology and Countermeasures Program. Prolonged exercise at a constant workload is know to result in a progressive decrease in mean arterial pressure (MAP) concomitant with a decrease in stroke volume and a compensatory increase in heart rate. The continuous decrease in MAP during the exercise, which is related to the thermoregulatory redistribution of circulating blood volume to the cutaneous circulation, raises the question as to whether there is a loss of baroreflex regulation of arterial blood pressure. We propose that with prolongation of the exercise to 60 minutes, progressive increases on central command reflect a progressive upward resetting of the carotid baroreflex (CBR) such that the operating point of the CBR is shifted to a pressure below the threshold of the reflex rendering it ineffectual in correcting the downward drift in MAP. In order to test this hypothesis, experiments have been designed to uncouple the global hemodynamic response to prolonged exercise from the central command mediated response via: (1) continuous maintenance of cardiac filling volume by intravenous infusion of a dextran solution; and (2) whole body surface cooling to counteract thermoregulatory cutaneous vasodialation. As the type of work (exercise) performed by astronauts is inherently arm and upper body dependent, we will also examine the physiologic responses to prolonged leg cycling and arm ergometry exercise in the supine positions with and without level lower body negative pressure (-10 torr) to mimic spaceflight- related decreases in cardiac filling volumes.

Raven, P. B.↗

Simulation of Local Blood Flow in Human Brain under Altered Gravity

In addition to the altered gravitational forces, specific shapes and connections of arteries in the brain vary in the human population (Cebral et al., 2000; Ferrandez et al., 2002). Considering the geometric variations, pulsatile unsteadiness, and moving walls, computational approach in analyzing altered blood circulation will offer an economical alternative to experiments. This paper presents a computational approach for modeling the local blood flow through the human brain under altered gravity. This computational approach has been verified through steady and unsteady experimental measurements and then applied to the unsteady blood flows through a carotid bifurcation model and an idealized Circle of Willis (COW) configuration under altered gravity conditions.

Kim, Chang Sung↗

A probe for blood-vessel and spinal interiors

Probe design allows insertion into lumen of blood vessels to perform oximetry and investigate plaque on interior vessel walls. Probe is more accurate than standard oximetry procedures of determining oxygenation of circulating blood.

Frazer, R. E.↗

Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures

The development of orthostatic hypotension and instability immediately after return from spaceflight has been a significant operational problem to astronauts for more than four decades. Significant reductions in stroke volume and peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with reduced circulating blood volume, although cardiac atrophy might also contribute. Space flight and ground based experiments have demonstrated that an inability to provide adequate peripheral vasoconstriction in astronauts that become presyncopal may be associated with several mechanisms including reduced sympathetic nerve activity, arterial smooth muscle atrophy and/or hyporeactivity, hypersensitivity of beta-adrenergic receptors, etc. In addition, an inability to provide adequate tachycardia in presyncopal subjects may be associated with reduced carotid-cardiac baroreflex sensitivity. Based on the current knowledge and understanding of cardiovascular mechanisms that are altered during exposure to microgravity, a major focus of future research should be directed to the systematic evaluation of potential countermeasures that specifically target and restore the function of these mechanisms. Based on a preliminary systematic evaluation presented in this review, acute physical exercise designed to elicit maximal effort, G-suit inflation, artificial gravity, and specific pharmacological interventions, alone or in combination, have shown promise as successful countermeasures that provide protection against post-flight orthostatic intolerance.

Review↗

Consequences of cardiovascular adaptation to spaceflight: implications for the use of pharmacological countermeasures

There is little evidence obtained from space flight to support the notion that occurrence of cardiac dysrhythmias, impaired cardiac and vascular function, and manifestation of asymptomatic cardiovascular disease represent serious risks during space flight. Therefore, the development of orthostatic hypotension and instability immediately after return from spaceflight probably reflect the most significant operational risks associated with the cardiovascular system of astronauts. Significant reductions in stroke volume and lower reserve for increasing peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with less circulating blood volume while inadequate peripheral vasoconstriction may be caused partly by hyporeactivity of receptors that control arterial smooth muscle function. A focus for development of future countermeasures for hemodynamic responses to central hypovolemia includes the potential application of pharmacological agents that specifically target and restore blood volume (e.g., fludrocortisone, electrolyte-containing beverages) and reserve for vasoconstriction (e.g., midodrine, vasopressin). Based on systematic evaluations, acute physical exercise designed to elicit maximal effort or inspiratory resistance have shown promise as successful countermeasures that provide protection against development of orthostatic hypotension and intolerance without potential risks and side effects associated with specific pharmacological interventions.

Non-NASA Center↗

Hematology and immunology studies - The second manned Skylab mission

The hematologic and immunologic functions of the Skylab 3 astronauts were monitored during the preflight, inflight, and postflight phases of the mission. Plasma protein profiles showed high consistency in all phases. A transient suppression of lymphocyte responsiveness was observed postflight. A reduction in the circulating blood volume due to drops in both the plasma volume and red cell mass was found. The loss of red cell mass is most likely a suppressed erythrypoiesis. The functional integrity of the circulating red cells did not appear to be compromised in the course of flight.

Kimzey, S. L.↗

Calibration Experiments Conducted for Noninvasive Blood Glucose Sensing Through the Eye

There are more than 16 million diabetics in the United States and more than 100 million worldwide. Diabetes can lead to severe complications over time such as blindness, renal and cardiovascular diseases, and peripheral neuropathy in the limbs. Poor blood circulation in diabetics can lead to gangrene and the subsequent amputation of extremities. In addition, this pathology is the fourth leading cause of death in the United States. The most effective way to manage diabetes is frequent blood glucose monitoring performed by the patients themselves. However, because of pain, inconvenience, and the fear of developing infections from finger-prick blood tests or implants, many patients monitor their blood glucose levels less frequently than is recommended by their physicians. Therefore, a noninvasive, painless, and convenient method to monitor blood glucose would greatly benefit diabetics. Likewise, detecting, preventing, and treating the untoward effects of prolonged space travel (e.g., a human mission to Mars) in real-time requires the development of noninvasive diagnostic technologies that are compact and powerful. As a "window to the body," the eye offers the opportunity to use light in various forms to detect ocular and systemic abnormalities long before clinical symptoms appear and to help develop preventative and therapeutic countermeasures early. The noninvasive feature of these technologies permits frequent repetition of tests, enabling an evaluation of the response to therapy.

Ansari, Rafat R.↗

Altered baroreflex control of forearm vascular resistance during simulated microgravity

Reflex peripheral vasoconstriction induced by activation of cardiopulmonary baroreceptors in response to reduced central venous pressure (CVP) is a basic mechanism for elevating systemic vascular resistance and defending arterial blood pressure during orthostatically-induced reductions in cardiac filling and output. The sensitivity of the cardiopulmonary baroreflex response [defined as the slope of the relationship between changes in forearm vascular resistance (FVR) and CVP] and the resultant vasoconstriction are closely and inversely associated with the amount of circulating blood volume. Thus, a high-gain FVR response will be elicited by a hypovolemic state. Exposure to microgravity during spaceflight results in reduced plasma volume. It is therefore reasonable to expect that the FVR response to cardiopulmonary baroreceptor unloading would be accentuated following adaptation to microgravity. Such data could provide better insight about the physiological mechanisms underlying alterations in blood pressure control following spaceflight. We therefore exposed eleven men to 6 degrees head-down bedrest for 7 days and measured specific hemodynamic responses to low levels of the lower body negative pressure to determine if there are alterations in cardiopulmonary baroreceptor stimulus-FVR reflex response relationship during prolonged exposure to an analog of microgravity.

NASA Program Space Physiology and Countermeasures↗

Physiological water model development

The water of the human body can be categorized as existing in two main compartments: intracellular water and extracellular water. The intracellular water consists of all the water within the cells and constitutes over half of the total body water. Since red blood cells are surrounded by plasma, and all other cells are surrounded by interstitial fluid, the intracellular compartment has been subdivided to represent these two cell types. The extracellular water, which includes all of the fluid outside of the cells, can be further subdivided into compartments which represent the interstitial fluid, circulating blood plasma, lymph, and transcellular water. The interstitial fluid surrounds cells outside of the vascular system whereas plasma is contained within the blood vessels. Avascular tissues such as dense connective tissue and cartilage contain interstitial water which slowly equilibrates with tracers used to determine extracellular fluid volume. For this reason, additional compartments are sometimes used to represent these avascular tissues. The average size of each compartment, in terms of percent body weight, has been determined for adult males and females. These compartments and the forces which cause flow between them are presented. The kidneys, a main compartment, receive about 25 percent of the cardiac output and filters out a fluid similar to plasma. The composition of this filtered fluid changes as it flows through the kidney tubules since compounds are continually being secreted and reabsorbed. Through this mechanism, the kidneys eliminate wastes while conserving body water, electrolytes, and metabolites. Since sodium accounts for over 90 percent of the cations in the extracellular fluid, and the number of cations is balanced by the number of anions, considering the renal handling sodium and water only should sufficiently describe the relationship between the plasma compartment and kidneys. A kidney function model is presented which has been adapted from a previous model of normal renal function in man. To test the validity of the proposed kidney model, results predicted by the model will be compared to actual data involving injected or ingested fluids and subsequent urine flow rates. Comparison of the model simulation to actual data following the ingestion of 1 liter of water is shown. The model simulation is also shown with actual data following the intravenous infusion of hypertonic saline.

Doty, Susan↗