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At least 307 records · Page 17

Electrical alternans during rest and exercise as predictors of vulnerability to ventricular arrhythmias

This investigation was performed to evaluate the feasibility of detecting repolarization alternans with the heart rate elevated with a bicycle exercise protocol. Sensitive spectral signal-processing techniques are able to detect beat-to-beat alternation of the amplitude of the T wave, which is not visible on standard electrocardiogram. Previous animal and human investigations using atrial or ventricular pacing have demonstrated that T-wave alternans is a marker of vulnerability to ventricular arrhythmias. Using a spectral analysis technique incorporating noise reduction signal-processing software, we evaluated electrical alternans at rest and with the heart rate elevated during a bicycle exercise protocol. In this study we defined optimal criteria for electrical alternans to separate patients from those without inducible arrhythmias. Alternans and signal-averaged electrocardiographic results were compared with the results of vulnerability to ventricular arrhythmias as defined by induction of sustained ventricular tachycardia or fibrillation at electrophysiologic evaluation. In 27 patients alternans recorded at rest and with exercise had a sensitivity of 89%, specificity of 75%, and overall clinical accuracy of 80% (p <0.003). In this patient population the signal-averaged electrocardiogram was not a significant predictor of arrhythmia vulnerability. This is the first study to report that repolarization alternans can be detected with heart rate elevated with a bicycle exercise protocol. Alternans measured using this technique is an accurate predictor of arrhythmia inducibility.

Clinical Trial↗

Manual control in space research on perceptual-motor functions under zero gravity conditions (L-10)

Are human abilities to control vehicles and other machines the same in space as those on Earth? The L-10 Manual Control Experiment of the First Materials Processing Tests (FMPT) started from this question. Suppose a pilot has the task to align the head of a space vehicle toward a target. His actions are to look at the target, to determine the vehicle movement, and to operate the manipulator. If the activity of the nervous system were the same as on Earth, the movements, of the eye and hand would become excessive because the muscles do not have to oppose gravity. The timing and amount of movement must be arranged for appropriate actions. The sensation of motion would also be affected by the loss of gravity because the mechanism of the otolith, the major acceleration sensor, depends on gravity. The possible instability of the sensation of direction may cause mistakes in the direction of control of manipulator movement. Thus, the experimental data can be used for designing man-machine systems in space, as well as for investigation of physiological mechanisms. In this experiment, the direction of vehicle heading is expressed by a light spot on an array of light emitting diodes and the manipulator is of a finger stick type. As the light spot moves up and down, the Japanese Payload Specialist, and the subject, must move the manipulator forward and backward to keep the movement of the light spot within the neighborhood of the central point of the display. The position of the light spot is computed in such a manner that when the stick is kept at the neutral position, a motion whose acceleration is proportional to the angle of deflection is added to the movement of the light spot. The Operator Describing Function, which is an expression of human control characteristics, can be calculated from 2 minutes of raw data of the light spot position and stick deflection. The 2 minutes of operation is called a run, and 8 runs with resting periods composes a session. The on-orbit experiment will be conducted on the second, fourth, and seventh days. One session of experiment of each of these days is conducted following the L-4 experiment, which uses the same apparatus. The Payload Specialist, aided by a Mission Specialist, will take our apparatus from a rack container, set up the apparatus, attach electrodes for measurements of eye movement and muscle activity, conduct the L-4 Visual Stability Experiment, conduct one session of the manual control experiment, and then dissemble and stow the apparatus. In addition to the flight experiment, pre-flight and post-flight experiments will be conducted. The data of three sessions on orbit will reflect adaption of physiological systems to microgravity. The data of post-flight experiments, on the other hand, will reflect re-adaptation of physiological systems to the gravity condition on the ground. Control data collected with and without psychological tension will be scheduled just prior to and long before launch.

Tada, Akira↗

Chapter 14: Dynamic Flux Analysis: An Experimental Approach of Fluxomics

Metabolic flux analysis represents an essential perspective to understand cellular physiology and offers quantitative information to guide pathway engineering. A valuable approach for experimental elucidation of metabolic flux is dynamic flux analysis, which estimates the relative or absolute flow rates through a series of metabolic intermediates in a given pathway. It is based on kinetic isotope labeling experiments, liquid chromatography-mass spectrometry (LC-MS), and computational analysis that relate kinetic isotope trajectories of metabolites to pathway activity. Herein, we illustrate the mathematic principles underlying the dynamic flux analysis and mainly focus on describing the experimental procedures for data generation. This protocol is exemplified using cyanobacterial metabolism as an example, for which reliable labeling data for central carbon metabolites can be acquired quantitatively. This protocol is applicable to other microbial systems as well and can be readily adapted to address different metabolic processes.

BASIC BIOLOGICAL SCIENCES↗

A comparison of CLIPS- and LISP-based approaches to the development of a real-time expert system

This paper describes an ongoing expert system development effort started in 1988 which is evaluating both CLIPS- and LISP- based approaches. The expert system is being developed to a project schedule and is planned for flight on Space Shuttle Mission SLS-2 in 1992. The expert system will help astronauts do the best possible science for a vestibular physiology experiment already scheduled for that mission. The system gathers and reduces data from the experiment, flags 'interesting' results, and proposes changes in the experiment both to exploit the in-flight observations and to stay within the time allowed by Mission Control for the experiment. These tasks must all be performed in real time. Two Apple Macintosh computers are used. The CLIPS- and LISP- based environments are layered above the Macintosh computer Operating System. The 'CLIPS-based' environment includes CLIPS and HyperCard. The LlSP-based environment includes Common LISP, Parmenides (a frame system), and FRuleKit (a rule system). Important evaluation factors include ease of programming, performance against real-time requirements, usability by an astronaut, robustness, and ease of maintenance. Current results on the factors of ease of programming, performance against real-time requirements, and ease of maintenance are discussed.

Frainier, R.↗

An optimized index of human cardiovascular adaptation to simulated weightlessness

Prolonged exposure to weightlessness is known to produce a variety of cardiovascular changes, some of which may influence the astronaut's performance during a mission. In order to find a reliable indicator of cardiovascular adaptation to weightlessness, we analyzed data from nine male subjects after a 24-hour period of normal activity and after a period of simulated weightlessness produced by two hours in a launch position followed by 20 hours of 6 degrees head-down tilt plus pharmacologically induced diuresis (furosemide). Heart rate, arterial pressure, thoracic fluid index, and radial flow were analyzed. Autoregressive spectral estimation and decomposition were used to obtain the spectral components of each variable from the subjects in the supine position during pre- and post-simulated weightlessness. We found a significant decrease in heart rate power and an increase in thoracic fluid index power in the high frequency region (0.2-0.45 Hz) and significant increases in radial flow and arterial pressure powers in the low frequency region (<0.2 Hz) in response to simulated weightlessness. However, due to the variability among subjects, any single variable appeared limited as a dependable index of cardiovascular adaptation to weightlessness. The backward elimination algorithm was then used to select the best discriminatory features from these spectral components. Fisher's linear discriminant and Bayes' quadratic discriminant were used to combine the selected features to obtain an optimal index of adaptation to simulated weightlessness. Results showed that both techniques provided improved discriminant performance over any single variable and thus have the potential for use as an index to track adaptation and prescribe countermeasures to the effects of weightlessness.

NASA Discipline Number 14-10↗

Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate–ribosylation signaling. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of 2533 diverse fragments resulted in 214 unique macrodomain-binders. An additional 60 molecules were selected from docking more than 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several fragment hits were confirmed by solution binding using three biophysical techniques (differential scanning fluorimetry, homogeneous time-resolved fluorescence, and isothermal titration calorimetry). The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.

59 BASIC BIOLOGICAL SCIENCES↗

Functional Data Analysis in Wearable Body Sensor Networks

Improving response time of indirect room-size calorimeters is still an outstanding problem in metabolic research. Accurate estimates of instantaneous rates of gaseous exchange require numerical differentiation of measured gaseousgas concentrations. We propose a new method to estimate the instantaneous gaseousgas exchange rates in indirect calorimetry. In contrast to the previously developed techniques, the method addresses the problem of differentiation of gaseous concentrations as an ill-posed problem. By applying the method of regularization, the problem of differentiation is converted into a well-posed problem resulting in smooth and consistent gaseous exchange rates. The validity of the method is tested on a large dataset of calorimeter experiments which included 313 human experiments along with 231 alcohol combustion experiments. It is demonstrated that the method is able to reliably differentiate between the “unphysiological” process of alcohol combustion and physiological variations produced by human metabolism. The method also allowed unraveling the previously unreported relative kinetics of O2 consumption and Respiratory Quotient (RQ) in humans. It was found that the kinetics of oxidative fuel selection lags behind the energy expenditure in humans exhibiting some sort of oxidative inertia. The time lag varies from 2-3 min up to 30 min, depending on particular individual. No such lag was found in alcohol combustion experiments. In addition to the relative kinetics of substrate oxidation, two statistical indexes reflecting variability of minute-by-minute RQ were estimated. The indexes were the RQ’s standard deviation and RQ’s first-order derivative. Both indexes showed statistically significant difference between human experiments and alcohol combustion experiments. We conclude that the proposed method can consistently extract physiologically-relevant information from noisy calorimetry data and the aforesaid information can provide additional insights into the mechanism of metabolic fuel selection in humans.

60 - APPLIED LIFE SCIENCES↗

The Spatial Standard Observer

The spatial standard observer is a computational model that provides a measure of the visibility of a target in a uniform background image or of the visual discriminability of two images. Standard observers have long been used in science and industry to quantify the discriminability of colors. Color standard observers address the spectral characteristics of visual stimuli, while the spatial standard observer (SSO), as its name indicates, addresses spatial characteristics. The SSO is based on a model of human vision. The SSO was developed in a process that included evaluation of a number of earlier mathematical models that address optical, physiological, and psychophysical aspects of spatial characteristics of human visual perception. Elements of the prior models are incorporated into the SSO, which is formulated as a compromise between accuracy and simplicity. The SSO operates on a digitized monochrome still image or on a pair of such images. The SSO consists of three submodels that operate sequentially on the input image(s): 1. A contrast model, which converts an input monochrome image to a luminance contrast image, wherein luminance values are expressed as excursions from, and normalized to, a mean; 2. A contrast-sensitivity-filter model that includes an oblique-effect filter (which accounts for the decline in contrast sensitivity at oblique viewing angles); and 3. A spatial summation model, in which responses are spatially pooled by raising each pixel to the power beta, adding the results, and raising the sum to the 1/b power. In this model, b=2.9 was found to be a suitable value. The net effect of the SSO is to compute a numerical measure of the perceptual strength of the single image, or of the visible difference (denoted the perceptual distance) between two images. The unit of a measure used in the SSO is the just noticeable difference (JND), which is a standard measure of perceptual discriminability. A target that is just visible has a measure of 1 JND.

Watson, Andrew B.↗

It’s Not What You Take Up, It’s What You Keep: How Discoveries from Diverse Disciplines Directed the Development of the FDG PET/CT Scan

Although imaging glucose metabolism with positron emission tomography combined with X-ray CT (FDG-PET/CT) has become a standard diagnostic modality for the discovery and surveillance of malignant tumors and inflammatory processes, its origins extend back to more than a century of notable discoveries in the fields of inorganic and organic chemistry, nuclear physics, mathematics, biochemistry, solute transport physiology, metabolism, and imaging, accomplished by pioneering and driven investigators, of whom at least ten were recipients of the Nobel Prize. These tangled and diverse roots eventually coalesced into the FDG-PET/CT method, that through its many favorable characteristics inherent in the isotope used ( 18 F), the accurate imaging derived from coincidence detection of positron annihilation radiation combined with computed tomography, and the metabolic trapping of 2-deoxy-2-[ 18 F] fluoro-d-glucose (FDG) in tissues, provides safety, sensitivity, and specificity for tumor and inflammation detection. Here, the authors hope that this article will increase the appreciation among its readers of the insight, creativity, persistence, and drive of the many investigators who made this technique possible. This article is followed by a review of the many applications of FDG-PET/CT to the gastrointestinal tract and hepatobiliary system (Mandelkern in Dig Dis Sci 2022)

2-DG↗

The Complexation Properties of Self-Defensive Microgel-Modified Antimicrobial Surfaces

The complexation of cationic antimicrobials with polyanionic microgels on a biomaterial surface can render that surface self-defensive against bacteria by killing those bacteria which physically contact the antimicrobial-loaded microgels. This killing has been attributed to the contact-driven transfer of antimicrobial from a microgel to a challenging bacterium, though much remains unknown about this process. Here, in this study, we use a combination of experiments and computational modeling to identify key aspects of the complexation phenomena which influence the self-defensive properties. We synthesize poly(acrylic acid) (PAA) microgels (∼2–5 μm diameter) via membrane emulsification and electrostatically deposit them onto polycaprolactone (PCL) coupons or onto glass to form a discontinuous submonolayer. Subsequent microgel loading with colistin or with Sub5 antimicrobial peptide (AMP) causes microgel deswelling. Under physiological conditions Sub5 remains stably sequestered whereas colistin is quickly released. Coarse-grained molecular dynamics (CGMD) simulations confirm stronger Sub5/PAA complexation. CGMD calculations also indicate that Sub5 forms dimers and higher-order structures, a prediction confirmed experimentally by Small-Angle X-ray Scattering (SAXS). Supramolecular structure entropically enhances the complexation strength because of enhanced counterion release per complexation event, and this finding can help identify other antimicrobials well suited for such a nonelutive yet self-defensive strategy. CGMD simulations also show that Sub5 has a higher complexation strength with the Staphylococcus aureus membrane than it does with PAA, confirming that there is a thermodynamic driving force for antimicrobial transfer. Such self-defensive surfaces significantly reduce S. aureus colonization (over 90% reduction relative to unmodified controls) in an in vitro hematogenous contamination model and remain cyto-compatible as evidenced by mesenchymal stem cell spreading and proliferation.

36 MATERIALS SCIENCE↗

Acquisition of quantitative physiological data and computerized image reconstruction using a single scan TV system

A single-scan radiography system has been interfaced to a minicomputer, and the combined system has been used with a variety of fluoroscopic systems and image intensifiers available in clinical facilities. The system's response range is analyzed, and several applications are described. These include determination of the gray scale for typical X-ray-fluoroscopic-television chains, measurement of gallstone volume in patients, localization of markers or other small anatomical features, determinations of organ areas and volumes, computer reconstruction of tomographic sections of organs in motion, and computer reconstruction of transverse axial body sections from fluoroscopic images. It is concluded that this type of system combined with a minimum of statistical processing shows excellent capabilities for delineating small changes in differential X-ray attenuation.

Baily, N. A.↗

Modeling Visual, Vestibular and Oculomotor Interactions in Self-Motion Estimation

A computational model of human self-motion perception has been developed in collaboration with Dr. Leland S. Stone at NASA Ames Research Center. The research included in the grant proposal sought to extend the utility of this model so that it could be used for explaining and predicting human performance in a greater variety of aerospace applications. This extension has been achieved along with physiological validation of the basic operation of the model.

Perrone, John↗

Variability in surface ECG morphology: signal or noise?

Using data collected from canine models of acute myocardial ischemia, we investigated two issues of major relevance to electrocardiographic signal averaging: ECG epoch alignment, and the spectral characteristics of the beat-to-beat variability in ECG morphology. With initial digitization rates of 1 kHz, an iterative a posteriori matched filtering alignment scheme, and linear interpolation, we demonstrated that there is sufficient information in the body surface ECG to merit alignment to a precision of 0.1 msecs. Applying this technique to align QRS complexes and atrial pacing artifacts independently, we demonstrated that the conduction delay from atrial stimulus to ventricular activation may be so variable as to preclude using atrial pacing as an alignment mechanism, and that this variability in conduction time be modulated at the frequency of respiration and at a much lower frequency (0.02-0.03Hz). Using a multidimensional spectral technique, we investigated the beat-to-beat variability in ECG morphology, demonstrating that the frequency spectrum of ECG morphological variation reveals a readily discernable modulation at the frequency of respiration. In addition, this technique detects a subtle beat-to-beat alternation in surface ECG morphology which accompanies transient coronary artery occlusion. We conclude that physiologically important information may be stored in the variability in the surface electrocardiogram, and that this information is lost by conventional averaging techniques.

NASA Discipline Cardiopulmonary↗

A two-year program of aerobics and weight training enhances bone mineral density of young women

Previous research suggests that physical activity may have a beneficial effect on bone mineral density (BMD) in women. This relationship was explored in a 2-year, randomized, intervention trial investigating the efficacy of exercise and calcium supplementation on increasing peak bone mass in young women. One hundred and twenty-seven subjects (ages of 20-35 years) were randomly assigned either to an exercise program that contained both aerobics and weight training components or to a stretching program. Calcium supplementation (up to 1500 mg/day including dietary intake) or placebo was given in a double-blinded design to all subjects. Spinal trabecular BMD was determined using quantitative computed tomography (QCT). Spinal integral, femoral neck, and trochanteric BMD were measured by dual X-ray absorptiometry (DXA) and calcaneal BMD by single photon absorptiometry (SPA). Fitness variables included maximal aerobic capacity (VO2max), and isokinetic muscle performance of the trunk and thigh. Measurements were made at baseline, 1 year, and 2 years. Sixty-three subjects (32 exercise, 31 stretching) completed the study, and all the measured bone parameters indicated a positive influence of the exercise intervention. There were significant positive differences in BMD between the exercise and stretching groups for spinal trabecular (2.5%), femoral neck (2.4%), femoral trochanteric (2.3%), and calcaneal (6.4%) measurements. The exercise group demonstrated a significant gain in BMD for spinal integral (1.3 +/- 2.8%, p < 0.02), femoral trochanteric (2.6 +/- 6.1%, p < 0.05), and calcaneal (5.6 +/- 5.1, p < 0.01) measurements. In contrast to exercise, the calcium intervention had no positive effect on any of the bone parameters. In regard to fitness parameters, the exercise group completed the study with significant gains in VO2max and isokinetic (peak torque) values for the knee flexion and extension and trunk extension. This study indicates that over a 2-year period, a combined regimen of aerobics and weight training has beneficial effects on BMD and fitness parameters in young women. However, the addition of daily calcium supplementation does not add significant benefit to the intervention.

Randomized Controlled Trial↗

Virtual Reality Simulation of the Effects of Microgravity in Gastrointestinal Physiology

The ultimate goal of this research is to create an anatomically accurate three-dimensional (3D) simulation model of the effects of microgravity in gastrointestinal physiology and to explore the role that such changes may have in the pharmacokinetics of drugs given to the space crews for prevention or therapy. To accomplish this goal the specific aims of this research are: 1) To generate a complete 3-D reconstructions of the human GastroIntestinal (GI) tract of the male and female Visible Humans. 2) To develop and implement time-dependent computer algorithms to simulate the GI motility using the above 3-D reconstruction.

Compadre, Cesar M.↗

Helping Video Games Rewire "Our Minds"

Biofeedback-modulated video games are games that respond to physiological signals as well as mouse, joystick or game controller input; they embody the concept of improving physiological functioning by rewarding specific healthy body signals with success at playing a video game. The NASA patented biofeedback-modulated game method blends biofeedback into popular off-the- shelf video games in such a way that the games do not lose their entertainment value. This method uses physiological signals (e.g., electroencephalogram frequency band ratio) not simply to drive a biofeedback display directly, or periodically modify a task as in other systems, but to continuously modulate parameters (e.g., game character speed and mobility) of a game task in real time while the game task is being performed by other means (e.g., a game controller). Biofeedback-modulated video games represent a new generation of computer and video game environments that train valuable mental skills beyond eye-hand coordination. These psychophysiological training technologies are poised to exploit the revolution in interactive multimedia home entertainment for the personal improvement, not just the diversion, of the user.

Pope, Alan T.↗

Integrated Software Systems for Crew Management During Extravehicular Activity in Planetary Terrain Exploration

Initial planetary explorations with the Apollo program had a veritable ground support army monitoring the safety and health of the 12 astronauts who performed lunar surface extravehicular activities (EVAs). Given the distances involved, this will not be possible on Mars. A spacesuit for Mars must be smart enough to replace that army. The next generation suits can do so using 2 software systems serving as virtual companions, LEGACI (Life support, Exploration Guidance Algorithm and Consumable Interrogator) and VIOLET (Voice Initiated Operator for Life support and Exploration Tracking). The system presented in this study integrates data inputs from a suite of sensors into the MIII suit s communications, avionics and informatics hardware for distribution to remote managers and data analysis. If successful, the system has application not only for Mars but for nearer term missions to the Moon, and the next generation suits used on ISS as well. Field tests are conducted to assess capabilities for next generation spacesuits at Johnson Space Center (JSC) as well as the Mars and Lunar analog (Devon Island, Canada). LEGACI integrates data inputs from a suite of noninvasive biosensors in the suit and the astronaut (heart rate, suit inlet/outlet lcg temperature and flowrate, suit outlet gas and dewpoint temperature, pCO2, suit O2 pressure, state vector (accelerometry) and others). In the Integrated Walkback Suit Tests held at NASA-JSC and the HMP tests at Devon Island, communication and informatics capabilities were tested (including routing by satellite from the suit at Devon Island to JSC in Houston via secure servers at VCU in Richmond, VA). Results. The input from all the sensors enable LEGACI to compute multiple independent assessments of metabolic rate, from which a "best" met rate is chosen based on statistical methods. This rate can compute detailed information about the suit, crew and EVA performance using test-derived algorithms. VIOLET gives LEGACI voice activation capability, allowing the crew to query the suit, and receive feedback and alerts that will lead to corrective action. LEGACI and VIOLET can also automatically control the astronaut's cooling and consumable use rate without crew input if desired. These findings suggest that non-invasive physiological and environmental sensors supported with data analysis can allow for more effective management of mission task performance during EVA. Integrated remote and local view of data metrics allow crewmember to receive real time feedback in synch with mission control in preventing performance shortcomings for EVA in exploration missions.

Kuznetz, Lawrence↗

Hindsight logging for model training

In modern Machine Learning, model training is an iterative, experimental process that can consume enormous computation resources and developer time. To aid in that process, experienced model developers log and visualize program variables during training runs. Exhaustive logging of all variables is infeasible, so developers are left to choose between slowing down training via extensive conservative logging, or letting training run fast via minimalist optimistic logging that may omit key information. As a compromise, optimistic logging can be accompanied by program checkpoints; this allows developers to add log statements post-hoc, and "replay" desired log statements from checkpoint---a process we refer to as hindsight logging. Unfortunately, hindsight logging raises tricky problems in data management and software engineering. Done poorly, hindsight logging can waste resources and generate technical debt embodied in multiple variants of training code. In this paper, we present methodologies for efficient and effective logging practices for model training, with a focus on techniques for hindsight logging. Our goal is for experienced model developers to learn and adopt these practices. To make this easier, we provide an open-source suite of tools for Fast Low-Overhead Recovery (flor) that embodies our design across three tasks: (i) efficient background logging in Python, (ii) adaptive periodic checkpointing, and (iii) an instrumentation library that codifies hindsight logging for efficient and automatic record-replay of model-training. Model developers can use each flor tool separately as they see fit, or they can use flor in hands-free mode, entrusting it to instrument their code end-to-end for efficient record-replay. Our solutions leverage techniques from physiological transaction logs and recovery in database systems. Evaluations on modern ML benchmarks demonstrate that flor can produce fast checkpointing with small user-specifiable overheads (e.g. 7%), and still provide hindsight log replay times orders of magnitude faster than restarting training from scratch.

Computer Science↗