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At least 289 records · Page 16

Human performance in the modern cockpit

This panel was organized by the Aerospace Human Factors Committee to illustrate behavioral research on the perceptual, cognitive, and group processes that determine crew effectiveness in modern cockpits. Crew reactions to the introduction of highly automated systems in the cockpit will be reported on. Automation can improve operational capabilities and efficiency and can reduce some types of human error, but may also introduce entirely new opportunities for error. The problem solving and decision making strategies used by crews led by captains with various personality profiles will be discussed. Also presented will be computational approaches to modeling the cognitive demands of cockpit operations and the cognitive capabilities and limitations of crew members. Factors contributing to aircrew deviations from standard operating procedures and misuse of checklist, often leading to violations, incidents, or accidents will be examined. The mechanisms of visual perception pilots use in aircraft control and the implications of these mechanisms for effective design of visual displays will be discussed.

Dismukes, R. K.↗

Structural Basis for "Flip-Flop" Action of Human Pyruvate Dehydrogenase

The derivative of vitamin B1, thiamin pyrophosphate is a cofactor of pyruvate dehydrogenase, a component enzyme of the mitochondrial pyruvate dehydrogenase multienzyme complex that plays a major role in directing energy metabolism in the cell. This cofactor is used to cleave the C(sup alpha)-C(=O) bond of pyruvate followed by reductive acetyl transfer to lipoyl-dihydrolipoamide acetyltransferase. In alpha(sub 2)beta(sub 2)-tetrameric human pyruvate dehydrogenase, there are two cofactor binding sites, each of them being a center of independently conducted, although highly coordinated enzymatic reactions. The dynamic nonequivalence of two, otherwise chemically equivalent, catalytic sites can now be understood based on the recently determined crystal structure of the holo-form of human pyruvate dehydrogenase at 1.95A resolution. The structure of pyruvate dehydrogenase was determined using a combination of MAD phasing and molecular replacement followed by rounds of torsion-angles molecular-dynamics simulated-annealing refinement. The final pyruvate dehydrogenase structure included coordinates for all protein amino acids two cofactor molecules, two magnesium and two potassium ions, and 742 water molecules. The structure was refined to R = 0.202 and R(sub free) = 0.244. Our structural analysis of the enzyme folding and domain assembly identified a simple mechanism of this protein motion required for the conduct of catalytic action.

Ciszak, Ewa↗

Load compensating reactions to perturbations at wrist joint in normal man

The electromyographic responses to step torque loads were studied in flexors and extensors at the human wrist. Based on temporal bursting patterns and functional behavior, the response was divided into four temporal components. Two early components, the myotatic (30-60 ms) late myotatic (60-120 ms) appears to be reflex response. The third postmyotatic component (120-200 ms) appear to be a triggered reaction, preceeding the fourth, stabilizing component (200-400 ms). A comparison of response at the wrist with similar data at the ankle provides the basis for a generalized classification of the response in various muscles to torque step perturbations.

Jaeger, R. J.↗

Rational design, synthesis, and evaluation of uncharged, “smart” bis-oxime antidotes of organophosphate-inhibited human acetylcholinesterase

Organophosphate (OP) intoxications from nerve agent and OP pesticide exposures are managed with pyridinium aldoxime–based therapies whose success rates are currently limited. The pyridinium cation hampers uptake of OPs into the central nervous system (CNS). Furthermore, it frequently binds to aromatic residues of OP-inhibited acetylcholinesterase (AChE) in orientations that are nonproductive for AChE reactivation, and the structural diversity of OPs impedes efficient reactivation. Improvements of OP antidotes need to include much better access of AChE reactivators to the CNS and optimized orientation of the antidotes' nucleophile within the AChE active-center gorge. On the basis of X-ray structures of a CNS-penetrating reactivator, monoxime RS194B, reversibly bound to native and venomous agent X (VX)–inhibited human AChE, here we created seven uncharged acetamido bis-oximes as candidate antidotes. Both oxime groups in these bis-oximes were attached to the same central, saturated heterocyclic core. Diverse protonation of the heterocyclic amines and oxime groups of the bis-oximes resulted in equilibration among up to 16 distinct ionization forms, including uncharged forms capable of diffusing into the CNS and multiple zwitterionic forms optimal for reactivation reactions. Conformationally diverse zwitterions that could act as structural antidote variants significantly improved in vitro reactivation of diverse OP-human AChE conjugates. Oxime group reorientation of one of the bis-oximes, forcing it to point into the active center for reactivation, was confirmed by X-ray structural analysis. Finally, our findings provide detailed structure-activity properties of several CNS-directed, uncharged aliphatic bis-oximes holding promise for use as protonation-dependent, conformationally adaptive, “smart” accelerated antidotes against OP toxicity.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Matters of simulation of the semicircular canal system

A scale model of the human semicircular canal system was developed based on the theory of dynamic similitude. This enlarged model makes it convenient to conduct tests on the vestibular processes and dynamics in the semicircular canals. Tests revealed hydromechanical interaction between canals, with asymmetry of the conditions of movement of the endolymph in the canals in opposite directions. A type of vestibular reactions, occurring with angular oscillations of the head, was predicted and demonstrated using this model and human test subjects.

Gurfinkel, V. S.↗

Characterization and structure of the human lysine-2-oxoglutarate reductase domain, a novel therapeutic target for treatment of glutaric aciduria type 1

In humans, a single enzyme 2-aminoadipic semialdehyde synthase (AASS) catalyses the initial two critical reactions in the lysine degradation pathway. This enzyme evolved to be a bifunctional enzyme with both lysine-2-oxoglutarate reductase (LOR) and saccharopine dehydrogenase domains (SDH). Moreover, AASS is a unique drug target for inborn errors of metabolism such as glutaric aciduria type 1 that arise from deficiencies downstream in the lysine degradation pathway. While work has been done to elucidate the SDH domain structurally and to develop inhibitors, neither has been done for the LOR domain. Here, we purify and characterize LOR and show that it is activated by alkylation of cysteine 414 by N-ethylmaleimide. We also provide evidence that AASS is rate-limiting upon high lysine exposure of mice. Finally, we present the crystal structure of the human LOR domain. Our combined work should enable future efforts to identify inhibitors of this novel drug target.

59 BASIC BIOLOGICAL SCIENCES↗

Supercritical water oxidation of products of human metabolism

Although the efficient destruction of organic material was demonstrated in the supercritical water oxidation process, the reaction kinetics and mechanisms are unknown. The kinetics and mechanisms of carbon monoxide and ammonia oxidation in and reaction with supercritical water were studied experimentally. Experimental oxidation of urine and feces in a microprocessor controlled system was performed. A minaturized supercritical water oxidation process for space applications was design, including preliminary mass and energy balances, power, space and weight requirements.

Tester, Jefferson W.↗

Prebiotic properties of Bacillus coagulans MA-13: production of galactoside hydrolyzing enzymes and characterization of the transglycosylation properties of a GH42 β-galactosidase

The spore-forming lactic acid bacterium Bacillus coagulans MA-13 has been isolated from canned beans manufacturing and successfully employed for the sustainable production of lactic acid from lignocellulosic biomass. Among lactic acid bacteria, B. coagulans strains are generally recognized as safe (GRAS) for human consumption. Low-cost microbial production of industrially valuable products such as lactic acid and various enzymes devoted to the hydrolysis of oligosaccharides and lactose, is of great importance to the food industry. Specifically, α- and β-galactosidases are attractive for their ability to hydrolyze not-digestible galactosides present in the food matrix as well as in the human gastrointestinal tract. In this work we have explored the potential of B. coagulans MA-13 as a source of metabolites and enzymes to improve the digestibility and the nutritional value of food. A combination of mass spectrometry analysis with conventional biochemical approaches has been employed to unveil the intra- and extra- cellular glycosyl hydrolase (GH) repertoire of B. coagulans MA-13 under diverse growth conditions. The highest enzymatic activity was detected on β-1,4 and α-1,6-glycosidic linkages and the enzymes responsible for these activities were unambiguously identified as β-galactosidase (GH42) and α-galactosidase (GH36), respectively. Whilst the former has been found only in the cytosol, the latter is localized also extracellularly. The export of this enzyme may occur through a not yet identified secretion mechanism, since a typical signal peptide is missing in the α-galactosidase sequence. A full biochemical characterization of the recombinant β-galactosidase has been carried out and the ability of this enzyme to perform homo- and hetero-condensation reactions to produce galacto-oligosaccharides, has been demonstrated. Probiotics which are safe for human use and are capable of producing high levels of both α-galactosidase and β-galactosidase are of great importance to the food industry. In this work we have proven the ability of B. coagulans MA-13 to over-produce these two enzymes thus paving the way for its potential use in treatment of gastrointestinal diseases.

59 BASIC BIOLOGICAL SCIENCES↗

The acidity of atmospheric particles and clouds

Acidity, defined as pH, is a central component of aqueous chemistry. In the atmosphere, the acidity of condensed phases (aerosol particles, cloud water, and fog droplets) governs the phase partitioning of semivolatile gases such as HNO 3 , NH 3 , HCl, and organic acids and bases as well as chemical reaction rates. It has implications for the atmospheric lifetime of pollutants, deposition, and human health. Despite its fundamental role in atmospheric processes, only recently has this field seen a growth in the number of studies on particle acidity. Even with this growth, many fine-particle pH estimates must be based on thermodynamic model calculations since no operational techniques exist for direct measurements. Current information indicates acidic fine particles are ubiquitous, but observationally constrained pH estimates are limited in spatial and temporal coverage. Clouds and fogs are also generally acidic, but to a lesser degree than particles, and have a range of pH that is quite sensitive to anthropogenic emissions of sulfur and nitrogen oxides, as well as ambient ammonia. Historical measurements indicate that cloud and fog droplet pH has changed in recent decades in response to controls on anthropogenic emissions, while the limited trend data for aerosol particles indicate acidity may be relatively constant due to the semivolatile nature of the key acids and bases and buffering in particles. This paper reviews and synthesizes the current state of knowledge on the acidity of atmospheric condensed phases, specifically particles and cloud droplets. It includes recommendations for estimating acidity and pH, standard nomenclature, a synthesis of current pH estimates based on observations, and new model calculations on the local and global scale.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Additively Manufactured Wind Tunnel Balances for Propulsive Force Measurement

Propulsive forces and moments during powered descent are not understood well enough to design an entry, decent, and landing vehicle with high confidence using solely computational fluid dynamics modelling (CFD). Therefore, wind tunnel testing is required to quantify uncertainties in computational modeling and simulation. Wind tunnel balances are structural, high-precision, multi-axis force transducers that provide direct measurement of these aerodynamic forces and moments, however their complex designs make them costly and time consuming to produce and approaches used to manufacture them have not changed significantly since the 1960s. This work demonstrates that additive manufacturing (AM) can be used to manufacture wind tunnel balances with significantly reduced fabrication time and expense. Moreover, the design flexibility afforded by the additive manufacturing process has the potential to enable new capabilities with respect to measuring propulsion forces during entry, decent, and landing testing. Here we present two novel balance designs enabled by AM. One will provide direct measurement of aerodynamic interference forces and moments on powered descent models (retropropulsion forces) to support CFD validation and further development of Mars human landing vehicle concepts. The second design will be used to characterize a reaction control system during entry descent and landing testing over a wide Mach number range.

Wind tunnel balance↗

Additively Manufactured Balances for Propulsive Force Measurement

Propulsive forces and moments during powered descent are not understood well enough to design an entry, decent, and landing vehicle with high confidence using solely computational fluid dynamics modelling (CFD). Therefore, wind tunnel testing is required to quantify uncertainties in computational modeling and simulation. Wind tunnel balances are structural, high-precision, multi-axis force transducers that provide direct measurement of these aerodynamic forces and moments, however their complex designs make them costly and time consuming to produce and approaches used to manufacture them have not changed significantly since the 1960s. This work demonstrates that additive manufacturing (AM) can be used to manufacture wind tunnel balances with significantly reduced fabrication time and expense. Moreover, the design flexibility afforded by the additive manufacturing process has the potential to enable new capabilities with respect to measuring propulsion forces during entry, decent, and landing testing. Here we present two novel balance designs enabled by AM. One will provide direct measurement of aerodynamic interference forces and moments on powered descent models (retropropulsion forces) to support CFD validation and further development of Mars human landing vehicle concepts. The second design will be used to characterize a reaction control system during entry decent and landing testing over a wide Mach number range.

Wind tunnel balance↗

Ozone Production and Precursor Emission from Wildfires in Africa

Tropospheric ozone (O3) negatively impacts human health and is also a greenhouse gas. It is formed photochemically by reactions of nitrogen oxides (NOx) and volatile organic compounds (VOCs), of which wildfires are an important source. This study presents data from research flights sampling wildfires in West and Central African savannah regions, both close to the fires and after the emissions had been transported several days over the tropical North Atlantic Ocean. Emission factors (EFs) in g kg-1 for NOx (as NO), six VOCs and formaldehyde were calculated from enhancement to mole fractions in data taken close to the fires. For NOx, the emission factor was calculated as 2.05±0.43 g kg-1 for Senegal and 1.20±0.28 g kg-1 for Uganda, both higher than the average value of 1.13±0.6 g kg-1 for previous studies of African savannah regions. For most VOCs (except acetylene), EFs in Uganda were lower by factors of 20-50% compared to Senegal, with almost all the values below those in the literature. O3 enhancement in the fire plumes was investigated by examining the ΔO3/ΔCO enhancement ratio, with values ranging from 0.07 - 0.14 close to the fires up to 0.25 for measurements taken over the Atlantic Ocean up to 200 hours downwind. In addition, measurements of O3 and its precursors were compared to the output of a global chemistry transport model (GEOS-CF) for the flights over the Atlantic Ocean. Normalised mean bias (NMB) comparison between the measured and modelled data was good outside of the fire plumes, with CO showing a model under-prediction of 4.6% and O3 a slight over-prediction of 0.7% (both within the standard deviation of the data). For NOx the agreement was poorer, with an under-prediction of 9.9% across all flights. Inside the fire plumes the agreement between modelled and measured values is worse, with the model being biased significantly lower for all three species. In total across all flights, there was an under-prediction of 29.4%, 16.5% and 37.5% for CO, O3 and NOx respectively. Finally, the measured ΔO3/ΔCO enhancement ratios were compared those in the model for the equivalent flight data, with the model showing a lower value of 0.17±0.03 compared to an observed value of 0.29±0.05. The results detailed here show that the O3 burden to the North Atlantic Ocean from African wildfires may be underestimated and that further study is required to better study the O3 precursor emissions and chemistry.

James D Lee↗

Carrier-assisted One-pot Sample Preparation for Targeted Proteomics Analysis of Small Numbers of Human Cells

Protein analysis of small numbers of human cells is primarily achieved by targeted proteomics with antibody-based immunoassays, which have inherent limitations (e.g., low multiplex and unavailability of antibodies for new proteins). Mass spectrometry (MS)-based targeted proteomics has emerged as an alternative because it is antibody-free, high multiplex, and has high specificity and quantitation accuracy. Recent advances in MS instrumentation make MS-based targeted proteomics possible for multiplexed quantification of highly abundant proteins in single cells. However, there is a technical challenge for effective processing of single cells with minimal sample loss for MS analysis. To address this issue, we have recently developed a convenient protein carrier-assisted one-pot sample preparation coupled with liquid chromatography (LC) - selected reaction monitoring (SRM) termed cLC-SRM for targeted proteomics analysis of small numbers of human cells. This method capitalizes on using the combined excessive exogenous protein as a carrier and low-volume one-pot processing to greatly reduce surface adsorption losses as well as high-specificity LC-SRM to effectively address the increased dynamic concentration range due to the addition of exogeneous carrier protein. Its utility has been demonstrated by accurate quantification of most moderately abundant proteins in small numbers of cells (e.g., 10-100 cells) and highly abundant proteins in single cells. The easy-to-implement features and no need for specific devices make this method readily accessible to most proteomics laboratories. In this study, we have provided a detailed protocol for cLC-SRM analysis of small numbers of human cells including cell sorting, cell lysis and digestion, LC-SRM analysis, and data analysis. Further improvements in detection sensitivity and sample throughput are needed towards targeted single-cell proteomics analysis. We anticipate that cLC-SRM will be broadly applied to biomedical research and systems biology with the potential of facilitating precision medicine.

60 APPLIED LIFE SCIENCES↗

Molecular analysis and comparison of radiation-induced large deletions of the HPRT locus in primary human skin fibroblasts

Genetic alterations in gamma-ray- and alpha-particle-induced HPRT mutants were examined by multiplex polymerase chain reaction (PCR) analysis. A total of 39-63% of gamma-ray-induced and 31-57% of alpha-particle-induced mutants had partial or total deletions of the HPRT gene. The proportion of these deletion events was dependent on radiation dose, and at the resolution limits employed there were no significant differences between the spectra induced by equitoxic doses of alpha particles (0.2-0.4 Gy) and gamma rays (3 Gy). The molecular nature of the deletions was analyzed by the use of sequence tagged site (STS) primers and PCR amplification as a "probe" for specific regions of the human X chromosome within the Xq26 region. These STSs were closely linked and spanned regions approximately 1.7 Mbp from the telomeric side and 1.7 Mbp from the centromeric side of the HPRT gene. These markers include: DXS53, 299R, DXS79, yH3L, 3/19, PR1, PR25, H2, yH3R, 1/44, 1/67, 1/1, DXS86, D8C6, DXS10 and DXS144. STS analyses indicated that the maximum size of total deletions in radiation-induced HPRT mutants can be greater than 2.7 Mbp and deletion size appears to be dependent on radiation dose. There were no apparent differences in the sizes of the deletions induced by alpha particles or gamma rays. On the other hand, deletions containing portions of the HPRT gene were observed to be 800 kbp or less, and the pattern of the partial deletion induced by alpha particles appeared to be different from that induced by gamma rays.

NASA Discipline Radiation Health↗

A low, adaptive dose of gamma-rays reduced the number and altered the spectrum of S1- mutants in human-hamster hybrid AL cells

We examined the effects of a low, adaptive dose of 137Cs-gamma-irradiation (0.04 Gy) on the number and kinds of mutants induced in AL human-hamster hybrid cells by a later challenge dose of 4 Gy. The yield of S1- mutants was significantly less (by 53%) after exposure to both the adaptive and challenge doses compared to the challenge dose alone. The yield of hprt- mutants was similarly decreased. Incubation with cycloheximide (CX) or 3-aminobenzamide largely negated the decrease in mutant yield. The adaptive dose did not perturb the cell cycle, was not cytotoxic, and did not of itself increase the mutant yield above background. The adaptive dose did, however, alter the spectrum of S1- mutants from populations exposed only to the adaptive dose, as well as affecting the spectrum of S1- mutants generated by the challenge dose. The major change in both cases was a significant increase in the proportion of complex mutations compared to small mutations and simple deletions.

Non-NASA Center↗

Chemoselective and Site-Selective Reductions Catalyzed by a Supramolecular Host and a Pyridine–Borane Cofactor

Supramolecular catalysts emulate the mechanism of enzymes to achieve large rate accelerations and precise selectivity under mild and aqueous conditions. While significant strides have been made in the supramolecular host-promoted synthesis of small molecules, applications of this reactivity to chemoselective and site-selective modification of complex biomolecules remain virtually unexplored. We report here a supramolecular system where coencapsulation of pyridine-borane with a variety of molecules including enones, ketones, aldehydes, oximes, hydrazones, and imines effects efficient reductions under basic aqueous conditions. Furthermore, upon subjecting unprotected lysine to the host-mediated reductive amination conditions, we observed excellent ε-selectivity, indicating that differential guest binding within the same molecule is possible without sacrificing reactivity. Inspired by the post-translational modification of complex biomolecules by enzymatic systems, we then applied this supramolecular reaction to the site-selective labeling of a single lysine residue in an 11-amino acid peptide chain and human insulin.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

NASA Ares I Launch Vehicle Roll and Reaction Control Systems Overview

NASA's Ares I launch vehicle, consisting of a five segment solid rocket booster first stage and a liquid bi-propellant J-2X engine upper stage, is the vehicle that's been chosen to return humans to the moon, mars, and beyond. This paper provides an overview of the work that has taken place on the Ares I launch vehicle roll and reaction control systems. Reaction control systems are found on many launch vehicles and provide a vehicle with a three degree of freedom stabilization during the mission. The Ares I baseline configuration currently consists of a first stage roll control system that will provide the vehicle with a method of counteracting the roll torque that is expected during launch. An upper stage reaction control system will allow the upper stage three degrees of freedom control as needed. Design assessments and trade studies are being conducted on the roll and reaction control systems including: propellant selection, thruster arrangement, pressurization system configuration, and system component trades. Other vehicle considerations and issues include thruster plume impingement, thruster module aerothermal and aerodynamic effects, and system integration. This paper concludes by summarizing the process of down selecting to the current baseline configuration for the Ares I roll and reaction control systems.

Popp, Chris↗

Observed differences in learning ability of heart rate self-regulation as a function of hypnotic susceptibility

Three groups of eight male and female subjects (aged 20-27 yr) categorized by low and high hypnotic susceptibility were taught to control their heart rates by means of an appropriate autogenic therapy/biofeedback technique. The experimental groups were trained by autogenic therapy and biofeedback, while the control group received only biofeedback. Significant differences are observed in all psychological test scores between subjects of high and low hypnotic susceptibility. The results confirm that (1) there are qualitative and quantitative differences between the performance of individuals with high and low hypnotic susceptibility; (2) interindividual-variability tests yield data relevant to individual performance in visceral learning tasks; (3) the combined autogenic therapy/biofeedback/verbal feedback technique is suitable for conditioning large stable autonomic responses in humans; and (4) this kind of conditioning is effective in eliminating or alleviating physiological reactions to some environmental stressors.

Cowings, P. S.↗