Search NASA⌕ Search

SEARCH · Search NASA

Results for “HUMAN REACTION”

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 343 records · Page 19

Analysis of Exercise Loads to Inform Vibration Isolation System Design

BACKGROUND: This study was conducted with the primary interest of providing data that would inform Vibration Isolation and Stabilization (VIS) system design and performance for the European Enhanced Exploration Exercise Device (E4D). In preparation for the International Space Station (ISS) in-flight demonstration, a list of critical Human Health Countermeasures (HHC) exercises was compiled [1]. The goal of this study was to assess the ground reaction forces and moments imposed by an exercising subject in each of the six VIS Degrees of Freedom (DOFs) during a comprehensive set of these critical exercises performed on the E4D. METHODS AND RESULTS: The ISS in-flight demonstration list of critical exercises included seated aerobic rowing, bent-over rowing, cycling, front squats, back squats, conventional deadlifts, Romanian deadlifts, heel raises, overhead presses, reverse chops, and power clean presses. At the NASA Johnson Space Center (JSC) Prototype Immersive Technology (PIT) laboratory, motion capture data were collected on critical E4D exercises for six subjects. At the NASA JSC Active Response Gravity Offload System (ARGOS) facility, additional motion capture and load cell data were collected on offloaded trials for four subjects. Select data were extrapolated to represent a 5th percentile female subject and a 95th percentile male subject. A previous investigation comparing the forces obtained from the load cell and from motion capture based data found a satisfactory level of agreement between the two measurements [2]. The motion capture based data were analyzed for this study since it is driven by the subject’s trajectory alone, automatically excluding any forces exerted on the subject by the ARGOS offloading harness. The OpenSim [3, 4] biomechanical simulation inverse kinematics tool was used to calculate the joint angles based on the locations of motion capture markers placed at key positions on the subject’s body. An OpenSim plugin was then used to obtain the forces and moments generated by the subject during each trial, with the moments computed relative to the equilibrium location of the subject’s feet [5]. The force of gravity was also removed to simulate the loads generated by the exercise when performed in microgravity. The load plots for each trial were generated and visually analyzed to obtain the magnitudes of the peak loads for each exercise in each DOF. The typical period of exercise for each trial was also estimated and used to calculate the frequency for each trial. The exercise loads data was then organized in multiple ways to capture different aspects of the data. As a result of this study, we present a summary of the load magnitudes observed during these critical exercises utilizing the E4D.

C A Bell↗

MPLA as an Innovative Immune Countermeasure

Spaceflight perturbs the human immune system. Among other manifestations, crewmembers may experience latent herpes viruses reactivation due to impaired lymphocyte function, as well as allergic/hypersensitivity reactions. Considering future space travel will be of longer duration (thereby increasing stress, exposure to radiation, etc…) with no rapid return option, it is of paramount importance to develop a countermeasure(s) to immune dysregulation. Monophosphoryl lipid A (MPLA) is a derivative of lipopolysaccharide (LPS), a potent inflammatory agent that can cause septic shock. MPLA possesses the immune-stimulatory effects of LPS without the adverse inflammatory effects. We hypothesize that treating immune cells with MPLA will boost their function enough to overcome the inhibitory effects of microgravity. While MPLA has been tested as an adjuvant extensively in mice and preliminarily for human vaccines, it has never been assessed for efficacy in microgravity.

Makedonas, George↗

Insights into regulatory T-cell and type-I interferon roles in determining abacavir-induced hypersensitivity or immune tolerance

Introduction Clinical use of several small molecule drugs may lead to severe T-cell-mediated idiosyncratic drug hypersensitivity reactions (iDHR) linked to HLA alleles, including abacavir (ABC) with HLA-B*57:01. Due to study limitations in humans, pathogenic networks in iDHR remain elusive. HLA transgenic murine models have been proposed to bridge knowledge gaps in tolerance and susceptibility to drugs. Methods Mice expressing HLA-B*57:01 and Foxp3-DTR/EGFP were generated to selectively deplete regulatory T-cells (Treg) with diphtheria toxin. ABC was administered for 8 days alone or together with cell- and cytokine-depleting antibodies. Cellular and transcriptomic responses were analyzed by RNA, flow cytometry and fluorescence methods. Results While CD8 + T-cell responses to ABC require HLA presentation, ABC also triggered mitochondrial stress in macrophagesin vitro, independently of HLA.In vivo, Treg were the primary mechanism of drug tolerance controlling HLA presentation and costimulation by antigen presenting cells. Treg ablation uncovered immune adverse events linked to activation and proliferation of both drug-specific and bystander CD8 + T-cells through CD28-mediated pathways with support from CD4 + non-Treg. Type-I interferon (IFN-I) and cellular-stress pathways influenced the fate of lymph node cells responding to ABC, implicating innate immune cells such as macrophages and plasmacytoid dendritic cells in the development of T-cell responses against the drug. IFN-I and IL-2 were necessary for CD8 + T-cell differentiation and ABC-induced adverse reactions. Conclusions This study unveils novel immune mechanisms driven by drug and host-related factors required forin vivoreactions and sheds light on potential biomarker and therapeutic targets for managing and preventing severe and life-threatening iDHR.

Immunology↗

Molecular evidence of simian virus 40 infections in children

Recent studies have detected simian virus 40 (SV40) DNA in certain human tumors and normal tissues. The significance of human infections by SV40, which was first discovered as a contaminant of poliovirus vaccines used between 1955 and 1963, remains unknown. The occurrence of SV40 infections in unselected hospitalized children was evaluated. Polymerase chain reaction and DNA sequence analyses were done on archival tissue specimens from patients positive for SV40 neutralizing antibody. SV40 DNA was identified in samples from 4 of 20 children (1 Wilms' tumor, 3 transplanted kidney samples). Sequence variation among SV40 regulatory regions ruled out laboratory contamination of specimens. This study shows the presence of SV40 infections in pediatric patients born after 1982.

Non-NASA Center↗

Weightlessness

Significance of gravitation forces in regulating homeostasis is discussed, along with weightlessness effects on humans and a state of reduced weight (subgravity), such as on the moon. Biomedical effects of weightlessness adaptation to zero G and readaptation to terrestrial gravitation are described for the nervous system, cardiovascular system, metabolism, and musculoskeletal system. Reactions caused primarly by: (1) changes in the afferent nervous system, (2) lack of hydrostatic blood pressure, (3) lack of weight on the musculoskeletal system, and (4) exposure limits derived from the effects of prolonged weightlessness on humans are reviewed. Protection of humans from adverse effects of weightlessness is considered; Skylab missions are also summarized.

I. D. Pestov↗

Electrocatalytic nitrate reduction: controlling adsorbate affinity to tailor reaction products

Every year, Haber-Bosch nitrogen fixation to form ammonia releases immense volumes of CO2. At the same time, nitrate contamination from untreated wastewater threatens human health across the US. Development of circular processes to efficiently upgrade waste nitrate for reuse is critical to sustainably address this growing environmental hazard. Electrochemical reduction of nitrate operates at ambient temperatures and pressures, and can leverage distributed renewable energy sources and water as a hydrogen source for ammonia production. However, current catalysts lack electron efficiency in reducing nitrate versus water, lack selectivity in forming ammonia as a product, or rely on expensive rare metals, making widespread implementation unfeasible. To overcome these limitations, this proposal seeks a mechanistic understanding of nitrate electrochemical reduction on earth abundant metals and their alloys, with the goal of identifying active-site properties that improve both Faradaic efficiency and product selectivity. This insight will extend to other electrocatalytic reductive process that compete with water reduction.

30 DIRECT ENERGY CONVERSION↗

NEXTorch: A Design and Bayesian Optimization Toolkit for Chemical Sciences and Engineering

Automation and optimization of chemical systems require well-informed decisions on what experiments to run to reduce time, materials, and/or computations. Data-driven active learning algorithms have emerged as valuable tools to solve such tasks. Bayesian optimization, a sequential global optimization approach, is a popular active-learning framework. Past studies have demonstrated its efficiency in solving chemistry and engineering problems. Here we introduce NEXTorch, a library in Python/PyTorch, to facilitate laboratory or computational design using Bayesian optimization. NEXTorch offers fast predictive modeling, flexible optimization loops, visualization capabilities, easy interfacing with legacy software, and multiple types of parameters and data type conversions. It provides GPU acceleration, parallelization, and state-of-the-art Bayesian optimization algorithms and supports both automated an d human-in-the-loop optimization. The comprehensive online documentation introduces Bayesian optimization theory and several examples from catalyst synthesis, reaction condition optimization, parameter estimation, and reactor geometry optimization. NEXTorch is open-source and available on GitHub

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Science Goal Driven Automation for NASA Missions: The Science Goal Monitor

Infusion of automation technologies into NASA s future missions will be essential not only to achieve substantial reduction in mission operations staff and costs, but also in order to both effectively handle an exponentially increasing volume of scientific data and to successfully meet dynamic, opportunistic scientific goals and objectives. Current spacecraft operations cannot respond to science driven events, such as intrinsically variable or short-lived phenomena in a timely manner. For such investigations, we must teach our platforms to dynamically understand, recognize, and react to the scientists goals. While much effort has gone into automating routine spacecraft operations to reduce human workload and hence costs, applying intelligent automation to the science side, i.e., science data acquisition, data analysis and reactions to that data analysis in a timely and still scientifically valid manner, has been relatively under-emphasized.

Korathkar, Anuradha↗

Science Goal Monitor: Science Goal Driven Automation for NASA Missions

Infusion of automation technologies into NASA s future missions will be essential because of the need to: (1) effectively handle an exponentially increasing volume of scientific data, (2) successfully meet dynamic, opportunistic scientific goals and objectives, and (3) substantially reduce mission operations staff and costs. While much effort has gone into automating routine spacecraft operations to reduce human workload and hence costs, applying intelligent automation to the science side, i.e., science data acquisition, data analysis and reactions to that data analysis in a timely and still scientifically valid manner, has been relatively under-emphasized. In order to introduce science driven automation in missions, we must be able to: capture and interpret the science goals of observing programs, represent those goals in machine interpretable language; and allow spacecrafts onboard systems to autonomously react to the scientist's goals. In short, we must teach our platforms to dynamically understand, recognize, and react to the scientists goals. The Science Goal Monitor (SGM) project at NASA Goddard Space Flight Center is a prototype software tool being developed to determine the best strategies for implementing science goal driven automation in missions. The tools being developed in SGM improve the ability to monitor and react to the changing status of scientific events. The SGM system enables scientists to specify what to look for and how to react in descriptive rather than technical terms. The system monitors streams of science data to identify occurrences of key events previously specified by the scientist. When an event occurs, the system autonomously coordinates the execution of the scientist s desired reactions. Through SGM, we will improve om understanding about the capabilities needed onboard for success, develop metrics to understand the potential increase in science returns, and develop an operational prototype so that the perceived risks associated with increased use of automation can be reduced.

Koratkar, Anuradha↗

Feasibility of Suited 10-km Ambulation "Walkback" on the Moon

This viewgraph presentation reviews a study that examined the feasibility of having astronauts walk about 10 kilometers to the base in the event of a breakdown of the lunar rover. This was done in part to examine the possibility of having a single rover on the lunar exploration missions. Other objectives of the study are to: (1) Understand specific biomedical and human performance limitations of the suit compared to matched shirt-sleeve controls; (2) Collect metabolic and ground-reaction force data to develop an EVA simulator for use on future prebr eathe protocol verification tests (3) Provide data to estimate consum ables usage for input to suit and portable life support system (PLSS) design (4) Assess the cardiovascular and resistance exercise associa ted with partialgravity EVA for planning appropriate exploration exer cise countermeasures

Norcross, Jason↗

Investigation of HZETRN 2010 as a Tool for Single Event Effect Qualification of Avionics Systems - Part II

An accurate prediction of spacecraft avionics single event effect (SEE) radiation susceptibility is key to ensuring a safe and reliable vehicle. This is particularly important for long-duration deep space missions for human exploration where there is little or no chance for a quick emergency return to Earth. Monte Carlo nuclear reaction and transport codes such as FLUKA can be used to generate very accurate models of the expected in-flight radiation environment for SEE analyses. A major downside to using a Monte Carlo-based code is that the run times can be very long (on the order of days). A more popular choice for SEE calculations is the CREME96 deterministic code, which offers significantly shorter run times (on the order of seconds). However, CREME96, though fast and easy to use, has not been updated in several years and underestimates secondary particle shower effects in spacecraft structural shielding mass. Another modeling option to consider is the deterministic code HZETRN 20104, which includes updates to address secondary particle shower effects more accurately. This paper builds on previous work by Rojdev, et al. to compare the use of HZETRN 2010 against CREME96 as a tool to verify spacecraft avionics system reliability in a space flight SEE environment. This paper will discuss modifications made to HZETRN 2010 to improve its performance for calculating SEE rates and compare results with both in-flight SEE rates and other calculation methods.

Rojdev, Kristina↗

Selective norepinephrine reuptake inhibition as a human model of orthostatic intolerance

BACKGROUND: Observations in patients with functional mutations of the norepinephrine transporter (NET) gene suggest that impaired norepinephrine uptake may contribute to idiopathic orthostatic intolerance. METHODS AND RESULTS: We studied the effect of the selective NET blocker reboxetine and placebo in a randomized, double-blind, crossover fashion on cardiovascular responses to cold pressor testing, handgrip testing, and a graded head-up tilt test (HUT) in 18 healthy subjects. In a subset, we determined isoproterenol and phenylephrine sensitivities. Subjects ingested 8 mg reboxetine or placebo 12 hours and 1 hour before testing. In the supine position, heart rate was 65+/-2 bpm with placebo and 71+/-3 bpm with reboxetine. At 75 degrees HUT, heart rate was 84+/-3 and 119+/-4 bpm with placebo and with reboxetine (P<0.0001). Mean arterial pressure was 85+/-2 with placebo and 91+/-2 mm Hg with reboxetine while supine (P<0.01) and 88+/-2 mm Hg and 90+/-3 mm Hg at 75 degrees HUT. Blood pressure responses to cold pressor and handgrip testing were attenuated with reboxetine. Reboxetine increased the sensitivity to the chronotropic effect of isoproterenol and the pressor effect of phenylephrine. Vasovagal reactions occurred in 9 subjects on placebo and in 1 subject on reboxetine. CONCLUSIONS: Selective NET blockade creates a phenotype that resembles idiopathic orthostatic intolerance. This observation supports the hypothesis that disordered norepinephrine uptake mechanisms can contribute to human cardiovascular disease. Our study also suggests that NET inhibition might be useful in preventing vasovagal reactions.

Non-NASA Center↗

One Pot Synthesis of Cyan Emitting CdZnSSe Quantum Dots for Human Centric Lighting

A one pot synthesis of blue and green emissive CdZnSSe quantum dots (QDs) from thio- and selenoureas and Cd and Zn carboxylates is optimized using high throughput robotic optimization. A large set of spectral data (N = 192) is used to train machine learning models that accurately predict the photoluminescence emission wavelength (λmax) and full-width half-maximum, and the relative photoluminescence quantum yield (PLQY) from the S:Se and Zn:Cd stoichiometries and reaction time. ZnS shells are deposited on the crude QD heterostructures using 4-tert-butylbenzyl mercaptan, a more reactive source of sulfide that enables shell growth below the temperature where ion diffusion in the QD can broaden its optical spectrum (≤275 °C). These optimized procedures provide gram quantities of blue-green emitting QDs (PLQY = 85–99%) in a single reaction vessel. A solid state lighting device (4260 K) that incorporates cyan emissive QDs achieved a higher luminous efficacy of 179 lm/W and melanopic daylight efficiency ratio (0.71) than existing commercial human centric lighting devices.

Jordan, Abraham J↗

A Multiplexed Quantitative Analysis of Germline Single Amino Acid Variants by Targeted Proteomics in Nondepleted Human Plasma

Single amino acid variants (SAAVs) in protein sequences are often a direct result of single-nucleotide polymorphisms (SNPs). Certain germline SAAVs have shown biological relevance in different disease conditions but lack precise quantification in circulation, which could hinder functional investigations and progress in biomarker development. Here, we have developed a multiplexed liquid chromatography-selected reaction monitoring (LC-SRM) assay that monitors 5 wild-type and variant peptide pairs (Complement Factor B: CFB-R32Q/R32W, Clusterin: CLU-N317H, Fetuin B: FETUB-K360R, and Kininogen: KNG1-L212P) in nondepleted human plasma. The assay was optimized for imprecision, linearity, stability, and calibration assessments with CVs of under 20%. The wild-type and variant peptide pairs were characterized in a set of healthy individual plasma samples. These target identifications were also validated by SNP genotyping with more than 99% accuracy. For all protein targets, we observed significantly lower concentrations of WT species in the presence variant peptides. In CFB, the concentration of R32Q was significantly lower than its counterpart R32W variant and WT species. Furthermore, our results distinguished phenotypes of homozygosity and heterozygosity of the SAAV presence through direct concentration level characterization. These findings provide some insights into how SAAVs affect quantitative assessments of target peptides. The assay demonstrates a platform for proteogenomic analyses with potential applications in both research and clinical settings.

genetics↗

Gene Expression Profile Analysis as a Prognostic Indicator of Normal Tissue Response to Simulated Space Radiations

This project was funded as a pilot project to determine the feasibility of using gene expression profiles to characterize the response of human cells to exposure to particulate radiations such as those encountered in the spaceflight environment. We proposed to use microarray technology to examine the gene expression patterns of a bank of well-characterized human fibroblast cell cultures. These fibroblast cultures were derived from breast or head and neck cancer patients who exhibited normal, minimal, or severe normal tissue reactions following low LET radiation exposure via radiotherapy. Furthermore, determination of SF2 values from fibroblasts cultured from these individuals were predictive of risk for severe late reactions. We hypothesized that by determining the expression of thousands of genes we could identify gene expression patterns that reflect how normal tissues respond to high Z and energy (HZE) particles, that is, that there are molecular signatures for HZE exposures. We also hypothesized that individuals who are intrinsically radiosensitive may elicit a unique response. Because this was funded as a pilot project we focused our initial studies on logistics and appropriate experimental design, and then to test our hypothesis that there is a unique molecular response to specific particles, in this case C and Fe, for primary human skin fibroblasts.

Story, Michael↗

Transcription factor FOXC1 positively regulates SFRP1 expression in androgenetic alopecia

Androgenetic alopecia (AGA) is the most common type of hair loss dysfunction. Secreted frizzled related protein 1 (SFRP1) is found to be associated with hair loss, but its role in AGA and the regulation mechanism of its transcription level is unclear. The aim of our study is to explore the expression of SFRP1 in AGA samples and its transcriptional mechanism. Male frontal and occipital scalp hair follicles from AGA patients were collected, and human dermal papilla cells (DPCs) were isolated and cultured. SFRP1 gene was cloned and constructed into recombinant plasmids to perform dual-luciferase reporter assay. Transcription factor binding sites were predicted through the Jaspar website and further confirmed by the chromatin immunoprecipitation (ChIP) assay. Expression of genes in DPCs was determined by immunofluorescence (IF) staining, quantitative real-time PCR (qRT-PCR) and western blotting. Our findings showed that SFRP1 was highly expressed in DPCs of AGA patients. The core promoter region of SFRP1 was from −100 to +50 bp and was found to be positively regulated by forkhead box C1 (FOXC1), a transcription factor related to hair growth, both at mRNA and protein level in DPCs. Our study suggests that FOXC1 plays an important role in regulating SFRP1 transcription, which may provide new insights into the development of therapeutic strategies for the treatment of AGA.

60 APPLIED LIFE SCIENCES↗

Accelerating countermeasure candidate discovery for A-series chemical warfare agent exposure

The recent alleged use of A-series chemical warfare agents (CWAs) highlights the urgent need to better understand their inhibition of cholinesterase enzymes and the reported shortcomings of traditional oxime countermeasures. Here, using high-throughput (HT) mass spectrometry (MS) technologies, we characterized the largely unknown inhibition kinetics of A-series CWAs on human acetylcholinesterase (hAChE) and its reactivation by oximes, achieving label-free quantitation at rates of up to 7,000 reactions per hour. Our findings indicate i) A-series agents exhibit inhibitory potencies similar to traditional CWAs like sarin and VX, and ii) bipyridinium-based oximes can reactivate A-series-adducted hAChE in vitro, challenging prior reports on oxime efficacy. These results underscore the need for continued exploration of countermeasure candidates against A-series CWAs and demonstrate the potential of HT-MS for rapidly and safely characterizing emerging toxic chemicals.

acetylcholinesterase↗

Polyglutaraldehyde - A new reagent for coupling proteins to microspheres and for labeling cell-surface receptors

Glutaraldehyde polymerized in basic aqueous solutions was found to react with low molecular weight amines, immunoglobulins and hemoglobin. The polyglutaraldehyde was covalently bound to hydrophilic microspheres. The rate of addition of proteins to the polyglutaraldehyde-derivatized microspheres was investigated spectrophotometrically as a function of pH and temperature. The reaction of polyglutaraldehyde was found to be faster than that of the monomer. The findings led to successful labeling of human lymphocyte subpopulations.

Rembaum, A.↗