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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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45 records · Page 3
All sourcesNASA NTRSDOE OSTI
NASA NTRS2015

Free-Energy Calculations. A Mathematical Perspective

Ion channels are pore-forming assemblies of transmembrane proteins that mediate and regulate ion transport through cell walls. They are ubiquitous to all life forms. In humans and other higher organisms they play the central role in conducting nerve impulses. They are also essential to cardiac processes, muscle contraction and epithelial transport. Ion channels from lower organisms can act as toxins or antimicrobial agents, and in a number of cases are involved in infectious diseases. Because of their important and diverse biological functions they are frequent targets of drug action. Also, simple natural or synthetic channels find numerous applications in biotechnology. For these reasons, studies of ion channels are at the forefront of biophysics, structural biology and cellular biology. In the last decade, the increased availability of X-ray structures has greatly advanced our understanding of ion channels. However, their mechanism of action remains elusive. This is because, in order to assist controlled ion transport, ion channels are dynamic by nature, but X-ray crystallography captures the channel in a single, sometimes non-native state. To explain how ion channels work, X-ray structures have to be supplemented with dynamic information. In principle, molecular dynamics (MD) simulations can aid in providing this information, as this is precisely what MD has been designed to do. However, MD simulations suffer from their own problems, such as inability to access sufficiently long time scales or limited accuracy of force fields. To assess the reliability of MD simulations it is only natural to turn to the main function of channels - conducting ions - and compare calculated ionic conductance with electrophysiological data, mainly single channel recordings, obtained under similar conditions. If this comparison is satisfactory it would greatly increase our confidence that both the structures and our computational methodologies are sufficiently accurate. Channel conductance, defined as the ratio of ionic current through the channel to applied voltage, can be calculated in MD simulations by way of applying an external electric field to the system and counting the number of ions that traverse the channel per unit time. If the current is small, a voltage significantly higher than the experimental one needs to be applied to collect sufficient statistics of ion crossing events. Then, the calculated conductance has to be extrapolated to the experimental voltage using procedures of unknown accuracy. Instead, we propose an alternative approach that applies if ion transport through channels can be described with sufficient accuracy by the one-dimensional diffusion equation in the potential given by the free energy profile and applied voltage. Then, it is possible to test the assumptions of the equation, recover the full voltage/current dependence, determine the reliability of the calculated conductance and reconstruct the underlying (equilibrium) free energy profile, all from MD simulations at a single voltage. We will present the underlying theory, model calculations that test this theory and simulations on ion conductance through a channel that has been extensively studied experimentally. To our knowledge this is the first case in which the complete, experimentally measured dependence of the current on applied voltage has been reconstructed from MD simulations.

free energy↗
NASA NTRS2003

Cell output, cell cycle duration and neuronal specification: a model of integrated mechanisms of the neocortical proliferative process

The neurons of the neocortex are generated over a 6 day neuronogenetic interval that comprises 11 cell cycles. During these 11 cell cycles, the length of cell cycle increases and the proportion of cells that exits (Q) versus re-enters (P) the cell cycle changes systematically. At the same time, the fate of the neurons produced at each of the 11 cell cycles appears to be specified at least in terms of their laminar destination. As a first step towards determining the causal interrelationships of the proliferative process with the process of laminar specification, we present a two-pronged approach. This consists of (i) a mathematical model that integrates the output of the proliferative process with the laminar fate of the output and predicts the effects of induced changes in Q and P during the neuronogenetic interval on the developing and mature cortex and (ii) an experimental system that allows the manipulation of Q and P in vivo. Here we show that the predictions of the model and the results of the experiments agree. The results indicate that events affecting the output of the proliferative population affect both the number of neurons produced and their specification with regard to their laminar fate.

Evaluation Studies↗
NASA NTRS1992

Fractal mechanisms in the electrophysiology of the heart

The mathematical concept of fractals provides insights into complex anatomic branching structures that lack a characteristic (single) length scale, and certain complex physiologic processes, such as heart rate regulation, that lack a single time scale. Heart rate control is perturbed by alterations in neuro-autonomic function in a number of important clinical syndromes, including sudden cardiac death, congestive failure, cocaine intoxication, fetal distress, space sickness and physiologic aging. These conditions are associated with a loss of the normal fractal complexity of interbeat interval dynamics. Such changes, which may not be detectable using conventional statistics, can be quantified using new methods derived from "chaos theory.".

NASA Discipline Cardiopulmonary↗
NASA NTRS2003

Mathematical model of diffusion-limited evolution of multiple gas bubbles in tissue

Models of gas bubble dynamics employed in probabilistic analyses of decompression sickness incidence in man must be theoretically consistent and simple, if they are to yield useful results without requiring excessive computations. They are generally formulated in terms of ordinary differential equations that describe diffusion-limited gas exchange between a gas bubble and the extravascular tissue surrounding it. In our previous model (Ann. Biomed. Eng. 30: 232-246, 2002), we showed that with appropriate representation of sink pressures to account for gas loss or gain due to heterogeneous blood perfusion in the unstirred diffusion region around the bubble, diffusion-limited bubble growth in a tissue of finite volume can be simulated without postulating a boundary layer across which gas flux is discontinuous. However, interactions between two or more bubbles caused by competition for available gas cannot be considered in this model, because the diffusion region has a fixed volume with zero gas flux at its outer boundary. The present work extends the previous model to accommodate interactions among multiple bubbles by allowing the diffusion region volume of each bubble to vary during bubble evolution. For given decompression and tissue volume, bubble growth is sustained only if the bubble number density is below a certain maximum.

Evaluation Studies↗
NASA NTRS1993

Alveolar ventilation to perfusion heterogeneity and diffusion impairment in a mathematical model of gas exchange

This study describes a two-compartment model of pulmonary gas exchange in which alveolar ventilation to perfusion (VA/Q) heterogeneity and impairment of pulmonary diffusing capacity (D) are simultaneously taken into account. The mathematical model uses as input data measurements usually obtained in the lung function laboratory. It consists of two compartments and an anatomical shunt. Each compartment receives fractions of alveolar ventilation and blood flow. Mass balance equations and integration of Fick's law of diffusion are used to compute alveolar and blood O2 and CO2 values compatible with input O2 uptake and CO2 elimination. Two applications are presented. The first is a method to partition O2 and CO2 alveolar-arterial gradients into VA/Q and D components. The technique is evaluated in data of patients with chronic obstructive pulmonary disease (COPD). The second is a theoretical analysis of the effects of blood flow variation in alveolar and blood O2 partial pressures. The results show the importance of simultaneous consideration of D to estimate VA/Q heterogeneity in patients with diffusion impairment. This factor plays an increasing role in gas alveolar-arterial gradients as severity of COPD increases. Association of VA/Q heterogeneity and D may produce an increase of O2 arterial pressure with decreasing QT which would not be observed if only D were considered. We conclude that the presented computer model is a useful tool for description and interpretation of data from COPD patients and for performing theoretical analysis of variables involved in the gas exchange process.

NASA Discipline Environmental Health↗
NASA NTRS2001

Entropy generation method to quantify thermal comfort

The present paper presents a thermodynamic approach to assess the quality of human-thermal environment interaction and quantify thermal comfort. The approach involves development of entropy generation term by applying second law of thermodynamics to the combined human-environment system. The entropy generation term combines both human thermal physiological responses and thermal environmental variables to provide an objective measure of thermal comfort. The original concepts and definitions form the basis for establishing the mathematical relationship between thermal comfort and entropy generation term. As a result of logic and deterministic approach, an Objective Thermal Comfort Index (OTCI) is defined and established as a function of entropy generation. In order to verify the entropy-based thermal comfort model, human thermal physiological responses due to changes in ambient conditions are simulated using a well established and validated human thermal model developed at the Institute of Environmental Research of Kansas State University (KSU). The finite element based KSU human thermal computer model is being utilized as a "Computational Environmental Chamber" to conduct series of simulations to examine the human thermal responses to different environmental conditions. The output from the simulation, which include human thermal responses and input data consisting of environmental conditions are fed into the thermal comfort model. Continuous monitoring of thermal comfort in comfortable and extreme environmental conditions is demonstrated. The Objective Thermal Comfort values obtained from the entropy-based model are validated against regression based Predicted Mean Vote (PMV) values. Using the corresponding air temperatures and vapor pressures that were used in the computer simulation in the regression equation generates the PMV values. The preliminary results indicate that the OTCI and PMV values correlate well under ideal conditions. However, an experimental study is needed in the future to fully establish the validity of the OTCI formula and the model. One of the practical applications of this index is that could it be integrated in thermal control systems to develop human-centered environmental control systems for potential use in aircraft, mass transit vehicles, intelligent building systems, and space vehicles.

Models, Biological↗
NASA NTRS2002

Mathematical model of diffusion-limited gas bubble dynamics in unstirred tissue with finite volume

Models of gas bubble dynamics for studying decompression sickness have been developed by considering the bubble to be immersed in an extravascular tissue with diffusion-limited gas exchange between the bubble and the surrounding unstirred tissue. In previous versions of this two-region model, the tissue volume must be theoretically infinite, which renders the model inapplicable to analysis of bubble growth in a finite-sized tissue. We herein present a new two-region model that is applicable to problems involving finite tissue volumes. By introducing radial deviations to gas tension in the diffusion region surrounding the bubble, the concentration gradient can be zero at a finite distance from the bubble, thus limiting the tissue volume that participates in bubble–tissue gas exchange. It is shown that these deviations account for the effects of heterogeneous perfusion on gas bubble dynamics, and are required for the tissue volume to be finite. The bubble growth results from a difference between the bubble gas pressure and an average gas tension in the surrounding diffusion region that explicitly depends on gas uptake and release by the bubble. For any given decompression, the diffusion region volume must stay above a certain minimum in order to sustain bubble growth.

NASA Discipline Environmental Health↗
NASA NTRS1992

Spatial orientation of the vestibular system

1. A simplified three-dimensional state space model of visual vestibular interaction was formulated. Matrix and dynamical system operators representing coupling from the semicircular canals and the visual system to the velocity storage integrator were incorporated into the model. 2. It was postulated that the system matrix for a tilted position was a composition of two linear transformations of the system matrix for the upright position. One transformation modifies the eigenvalues of the system matrix while another rotates the pitch and roll eigenvectors with the head, while maintaining the yaw axis eigenvector approximately spatially invariant. Using this representation, the response characteristics of the pitch, roll, and yaw eye velocity were obtained in terms of the eigenvalues and associated eigenvectors. 3. Using OKAN data obtained from monkeys and comparing to the model predictions, the eigenvalues and eigenvectors of the system matrix were identified as a function of tilt to the side or of tilt to the prone positions, using a modification of the Marquardt algorithm. The yaw eigenvector for right-side-down tilt and for downward pitch cross-coupling was approximately 30 degrees from the spatial vertical. For the prone position, the eigenvector was computed to be approximately 20 degrees relative to the spatial vertical. For both side-down and prone positions, oblique OKN induced along eigenvector directions generated OKAN which decayed to zero along a straight line with approximately a single time constant. This was verified by a spectral analysis of the residual sequence about the straight line fit to the decaying data. The residual sequence was associated with a narrow autocorrelation function and a wide power spectrum. 4. Parameters found using the Marquardt algorithm were incorporated into the model. Diagonal matrices in a head coordinate frame were introduced to represent the direct pathway and the coupling of the visual system to the integrator. Model simulations predicted the behavior of yaw and pitch OKN and OKAN when the animal was upright, as well as the cross-coupling in the tilted position. The trajectories in velocity space were also accurately simulated. 5. There were similarities between the monkey eigenvectors and human perception of the spatial vertical. For side-down tilts and downward eye velocity cross-coupling, there was only an Aubert (A) effect. For upward eye velocity cross-coupling there were both Muller (E) and Aubert (A) effects. The mean of the eigenvectors for upward and downward eye velocities overlay human 1 x g perceptual data.(ABSTRACT TRUNCATED AT 400 WORDS).

NASA Discipline Neuroscience↗
NASA NTRS1998

Refinement of a limit cycle oscillator model of the effects of light on the human circadian pacemaker

In 1990, Kronauer proposed a mathematical model of the effects of light on the human circadian pacemaker. Although this model predicted many general features of the response of the human circadian pacemaker to light exposure, additional data now available enable us to refine the original model. We first refined the original model by incorporating the results of a dose response curve to light into the model's predicted relationship between light intensity and the strength of the drive onto the pacemaker. Data from three bright light phase resetting experiments were then used to refine the amplitude recovery characteristics of the model. Finally, the model was tested and further refined using data from an extensive phase resetting experiment in which a 3-cycle bright light stimulus was presented against a background of dim light. In order to describe the results of the four resetting experiments, the following major refinements to the original model were necessary: (i) the relationship between light intensity (I) and drive onto the pacemaker was reduced from I1/3 to I0.23 for light levels between 150 and 10,000 lux; (ii) the van der Pol oscillator from the original model was replaced with a higher-order limit cycle oscillator so that amplitude recovery is slower near the singularity and faster near the limit cycle; (iii) a direct effect of light on circadian period (tau x) was incorporated into the model such that as I increases, tau x decreases, which is in accordance with "Aschoff's rule". This refined model generates the following testable predictions: it should be difficult to enhance normal circadian amplitude via bright light; near the critical point of a type 0 phase response curve (PRC) the slope should be steeper than it is in a type 1 PRC; and circadian period measured during forced desynchrony should be directly affected by ambient light intensity.

NASA Discipline Regulatory Physiology↗