Automatic analysis of the human gait with a hybrid computer system.
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Adult↗
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Results for “Computers, Hybrid”
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A hybrid computer model of stochastic activity of the neurone.
The authors describe a hybrid computer neurone model intended for the investigation of stochastic transformations effected by neurones in correlation to some of their physiological parameters. The model is designed so as to give the best possible characterization of the internal dynamics of a neurone with minimum limiting conditions. It allows the generation of suitable input stochastic processes or operates with input processes obtained experimentally in the living neurone and it carries out basic statistical tests of the output stochastic process.
Computers, Hybrid↗
Interactions among ventilation, the circulation, and the uptake and distribution of halothane--use of a hybrid computer multiple model: I. The basic model.
The authors describe an 18-compartment hybrid computer multiple model of the uptake and distribution of halothane. This model uses 88 equations and 124 parameter settings. Three submodels are incorporated into the basic model: 1) The mass transport of halothane is simulated on the digital portion of the hybrid computer. 2) A breath-by-breath pulmonary model with two compartments describes air pressure-flow relations in the airway system. 3) A beat-to-beat cardiovascular model with 15 compartments describes in detail blood pressure-flow relations. In addition, a baroreceptor-heart rate loop is included: an increase in arterial pressure causes a decrease in heart rate. The slope of the baroreceptor response is progressively decreased by halothane until at 2 per cent there is no response. The model of halothane uptake and distribution is separate from the blood and air pressure-flow models, but is, in effect, driven by them. Myocardial "contractility" (stroke volume) and certain regional vascular resistances can be affected by the concentration of halothane in one or any proportion of any combination of three compartments: arterial blood (arteriolar concentrations), cerebral gray matter, or myocardial. In turn, these factors significantly affect the uptake and distribution of halothane. The responses to three steady-state concentration, as well as to a step change in concentration from 0 to 2 per cent, were examined. Twenty-four outputs were recorded, including halothane concentrations in ten compartments; myocardial "contractility"; left and right ventricular and right atrial pressures; cardiac output; stroke volume, R-R interval; and blood flows in six regions. Two variables--alveolar concentration of halothane and arterial blood pressure--were recorded during a step change of 0 to 5 per cent. The model describes the appropriate steady-state and dynamic cardiovascular responses to halothane. It also demonstrates the complex interrelationships among caridac output, regional blood flow distribution, and the uptake and distribution of halothane. During step change in halothane concentration, most of the responses occur early, a phenomenon also seen in man and goats. Thus, the model is useful not only for representing organ and tissue halothane concentrations, but also for gaining new insights into cardiovascular alterations produced by rapidly changing concentrations of halothane and into the complex interactions between the circulation and the uptake and distribution of halothane.
Anesthesia, Inhalation↗
An introduction to hybrid computers and their application to optimization problems.
The author, who is Secretary of the Analog Section of the British Computer Society, describes the way in which some of the logic components of a parallel logic analog computer function, and goes on to discuss the use of such a computer in optimization problems, as for instance in finding the best estimates of the parameters on compartmentation analysis of isotopic tracer experiments. The increased power which is gained when an analog computer is coupled to (hybridized with) a general purpose digital computer is then discussed, as shown for example in the increased speed of random-search optimization techniques when an analog computer is used to integrate the differential equations, or the improvement in steepest ascent methods when the parallel logic can be used to keep the hill-climb path continuously on the line of steepest ascent. Finally, the use of a hybrid computer in solving partial differential equations is briefly outlined.
Journal Article↗
Interactions among ventilation, the circulation, and the uptake and distribution of halothane--use of a hybrid computer multiple model: II. Spontaneous vs. controlled ventilation, and the effects of CO2.
The authors have described a basic hybrid computer multiple model of the circulation, ventilation, and uptake and distribution of halothane in a companion paper. A multiple model consists of two or more submodels, each of which is complete in itself and could operate independently. In a multiple model, however, each submodel interacts with the others. The present paper describes the addition of a CO2-control loop (submodel), through which the partial pressure of CO2 modulates ventilation, as well a myocardial "contractility," arterial pressure, cardiac output, and regional vascular resistances. The concentration of halothane modifies these CO2-induced modulations. The CO2- and halothane-induced changes in ventilation and circulation in turn modify the uptake and distribution of halothane. Thus, a complex set of interrelationships among the submodels and compartments exists.
Anesthesia, Inhalation↗
Ethyl acrylate risk assessment with a hybrid computational fluid dynamics and physiologically based nasal dosimetry model.
Cytotoxicity in the nasal epithelium is frequently observed in rodents exposed to volatile organic acids and esters by inhalation. An interspecies, hybrid computational fluid dynamics and physiologically based pharmacokinetic (CFD-PBPK) dosimetry model for inhaled ethyl acrylate (EA) is available for estimating internal dose measures for EA, its metabolite acrylic acid (AA), and EA-mediated reductions in tissue glutathione (GSH). Nasal tissue concentrations of AA were previously used as the dose metric for a chronic Reference Concentration (RfC) calculation with this compound. However, EA was more toxic than expected, based on calculated tissue AA concentrations. Unlike AA, EA causes depletion of tissue GSH. We have developed an RfC for EA using tissue GSH depletion in the olfactory epithelium as the primary measure of nasal tissue dose. The hybrid CFD-PBPK model was refined to improve the accuracy of simulations for GSH in rat olfactory tissues. This refined model was used to determine the concentration for continuous human exposures to EA predicted to reduce nasal GSH levels to the same extent as seen in rats exposed to EA at the no-observed-effect level (NOEL). Importantly, AA concentrations in the human nasal olfactory epithelium at the proposed chronic RfC were predicted to be lower than the AA concentrations estimated in the rat at the NOEL. Thus, a chronic RfC based on maintaining GSH in the human nasal olfactory epithelium at levels equivalent to the rat NOEL would also provide an adequate margin of safety with respect to AA concentrations in nasal tissues.
Acrylates↗
Use of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry comparisons of ester vapors.
Numerous inhalation studies have demonstrated that exposure to high concentrations of a wide range of volatile acids and esters results in cytotoxicity to the nasal olfactory epithelium. Previously, a hybrid computational fluid dynamics (CFD) and physiologically based pharmacokinetic (PBPK) dosimetry model was constructed to estimate the regional tissue dose of organic acids in the rodent and human nasal cavity. This study extends this methodology to a representative volatile organic ester, ethyl acrylate (EA). An in vitro exposure of explants of rat olfactory epithelium to EA with and without an esterase inhibitor demonstrated that the organic acid, acrylic acid, released by nasal esterases is primarily responsible for the olfactory cytotoxicity. Estimates of the steady-state concentration of acrylic acid in olfactory tissue were made for the rat nasal cavity by using data from a series of short-term in vivo studies and from the results of CFD-PBPK computer modeling. Appropriate parameterization of the CFD-PBPK model for the human nasal cavity and to accommodate human systemic anatomy, metabolism, and physiology allowed interspecies dose comparisons. The CFD-PBPK model simulations indicate that the olfactory epithelium of the human nasal cavity is exposed to at least 18-fold lower tissue concentrations of acid released from EA than the olfactory epithelium of the rat nasal cavity under the same exposure conditions. The magnitude of this difference varies with the specific exposure scenario that is simulated and with the specific dataset of human esterase activity used for the simulations. The increased olfactory tissue dose in rats relative to humans may be attributed to both the vulnerable location of the rodent olfactory tissue (comprising greater than 50% of the nasal cavity) and the high concentration of rat olfactory esterase activity (comparable to liver esterase activity) relative to human olfactory tissue. These studies suggest that the human olfactory epithelium is protected from vapors of organic esters significantly better than rat olfactory epithelium due to substantive differences in nasal anatomy, nasal and systemic metabolism, systemic physiology, and air flow. Although the accumulation of acrylic acid in the nasal tissues may be a primary concern for nasal irritation and human risk assessment, acute animal inhalation studies to evaluate lethality (LD50-type studies) conducted at very high vapor concentrations of ethyl acrylate indicated that a different mechanism is primarily responsible for mortality. The rodent studies demonstrated that systemic tissue nonprotein sulfhydryl depletion is a primary cause of death at exposure concentrations more than two orders of magnitude above the concentrations that induce nasal irritation. The CFD-PBPK model adequately simulated the severe depletion of glutathione in systemic tissues (e.g., liver and lung) associated with acute inhalation exposures in the 500-1000 ppm range. These results indicate that the CFD-PBPK model can simulate both the low-dose nasal tissue dosimetry associated with irritation and the high-dose systemic tissue dosimetry associated with mortality. In addition, the comparison of simulation results for ethyl acetate and acetone to nasal deposition data suggests that the CFD-PBPK model has general utility as a tool for dosimetry estimates for a wide range of other esters and slowly metabolized vapors.
Acrylates↗
A hybrid computational fluid dynamics and physiologically based pharmacokinetic model for comparison of predicted tissue concentrations of acrylic acid and other vapors in the rat and human nasal cavities following inhalation exposure.
To assist in interspecies dosimetry comparisons for risk assessment of the nasal effects of organic acids, a hybrid computational fluid dynamics (CFD) and physiologically based pharmacokinetic (PBPK) dosimetry model was constructed to estimate the regional tissue dose of inhaled vapors in the rat and human nasal cavity. Application to a specific vapor would involve the incorporation of the chemical-specific reactivity, metabolism, partition coefficients, and diffusivity (in both air and tissue phases) of the vapor. This report describes the structure of the CFD-PBPK model and its application to a representative acidic vapor, acrylic acid, for interspecies tissue concentration comparisons to assist in risk assessment. By using the results from a series of short-term in vivo studies combined with computer modeling, regional nasal tissue dose estimates were developed and comparisons of tissue doses between species were conducted. To make these comparisons, the assumption was made that the susceptibilities of human and rat olfactory epithelium to the cytotoxic effects of organic acids were similar, based on similar histological structure and common mode of action considerations. Interspecies differences in response were therefore assumed to be driven primarily by differences in nasal tissue concentrations that result from regional differences in nasal air flow patterns relative to the species-specific distribution of olfactory epithelium in the nasal cavity. The results of simulations with the seven-compartment CFD-PBPK model suggested that the olfactory epithelium of the human nasal cavity would be exposed to tissue concentrations of acrylic acid similar to that of the rat nasal cavity when the exposure conditions are the same. Similar analysis of CFD data and CFD-PBPK model simulations with a simpler one-compartment model of the whole nasal cavities of rats and humans provides comparable results to averaging over the compartments of the seven-compartment model. These results indicate that the general structure of the hybrid CFD-PBPK model applied in this assessment would be useful for target tissue dosimetry and interspecies dose comparisons for a wide variety of vapors. Because of its flexibility, this CFD-PBPK model is envisioned to be a platform for the construction of case-specific inhalation dosimetry models to simulate in vivo exposures that do not involve significant histopathological damage to the nasal cavity.
Acrylates↗
Implicit motif distribution based hybrid computational kernel for sequence classification.
MOTIVATION: We designed a general computational kernel for classification problems that require specific motif extraction and search from sequences. Instead of searching for explicit motifs, our approach finds the distribution of implicit motifs and uses as a feature for classification. Implicit motif distribution approach may be used as modus operandi for bioinformatics problems that require specific motif extraction and search, which is otherwise computationally prohibitive. RESULTS: A system named P2SL that infer protein subcellular targeting was developed through this computational kernel. Targeting-signal was modeled by the distribution of subsequence occurrences (implicit motifs) using self-organizing maps. The boundaries among the classes were then determined with a set of support vector machines. P2SL hybrid computational system achieved approximately 81% of prediction accuracy rate over ER targeted, cytosolic, mitochondrial and nuclear protein localization classes. P2SL additionally offers the distribution potential of proteins among localization classes, which is particularly important for proteins, shuttle between nucleus and cytosol. AVAILABILITY: http://staff.vbi.vt.edu/volkan/p2sl and http://www.i-cancer.fen.bilkent.edu.tr/p2sl CONTACT: rengul@bilkent.edu.tr.
Algorithms↗
Application of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry extrapolation of acidic vapors in the upper airways.
This study provides a scientific basis for interspecies extrapolation of nasal olfactory irritants from rodents to humans. By using a series of short-term in vivo studies, in vitro studies with nasal explants, and computer modeling, regional nasal tissue dose estimates were made and comparisons of tissue doses between species were conducted. To make these comparisons, this study assumes that human and rodent olfactory epithelium have similar susceptibility to the cytotoxic effects of organic acids based on similar histological structure and common mode of action considerations. Interspecies differences in susceptibility to the toxic effects of acidic vapors are therefore assumed to be driven primarily by differences in nasal tissue concentrations that result from regional differences in nasal air flow patterns relative to the species-specific distribution of olfactory epithelium in the nasal cavity. The acute, subchronic, and in vitro studies have demonstrated that the nasal olfactory epithelium is the most sensitive tissue to the effects of inhalation exposure to organic acids and that the sustentacular cells are the most sensitive cell type of this epithelium. A hybrid computational fluid dynamics (CFD) and physiologically based pharmacokinetic (PBPK) dosimetry model was constructed to estimate the regional tissue dose of organic acids in the rodent and human nasal cavity. The CFD-PBPK model simulations indicate that the olfactory epithelium of the human nasal cavity is exposed to two- to threefold lower tissue concentrations of a representative inhaled organic acid vapor, acrylic acid, than the olfactory epithelium of the rodent nasal cavity when the exposure conditions are the same. The magnitude of this difference varies somewhat with the specific exposure scenario that is simulated. The increased olfactory tissue dose in rats relative to humans may be attributed to the large rodent olfactory surface area (greater than 50% of the nasal cavity) and its highly susceptible location (particularly, a projection of olfactory epithelium extending anteriorly in the dorsal meatus region). In contrast, human olfactory epithelium occupies a much smaller surface area (less than 5% of the nasal cavity), and it is in a much less accessible dorsal posterior location. In addition, CFD simulations indicate that human olfactory epithelium is poorly ventilated relative to rodent olfactory epithelium. These studies suggest that the human olfactory epithelium is protected from irritating acidic vapors significantly better than rat olfactory epithelium due to substantive differences in nasal anatomy and nasal air flow. Furthermore, the general structure of the hybrid CFD-PBPK model used for this study appears to be useful for target tissue dosimetry and interspecies dose comparisons for a wide range of inhaled vapors.
Acrylates↗
Hybrid computations with flux exchange.
We discuss a hybrid scheme that is based on flux exchange between a particle and a continuum system which reside in two slightly overlapping volumes in space. The scheme ensures conservation of mass, momentum and energy between a system of Lennard-Jones particles and a continuum description given by the compressible Navier-Stokes equations. An implementation in two dimensions employing the compressible Navier-Stokes equations to describe the continuum, and the Lennard-Jones potential to describe the particles, is discussed. The accuracy of the coupling scheme is tested successfully for the case of homogeneous flow and discussed for the more general case.
Journal Article↗
Physician- and counselor-tailored hybrid computer interfaces for cancer genetics risk analysis software.
During development of the Strang Breast Cancer Risk Evaluator, different computer interfaces were designed, implemented and tested for useability by physicians and genetics counselors during a counseling session. The current BCRE 2.3 implements a hybrid interface, combining modern GUI (graphical user interface) windows, buttons, and menus with a linear, sequence-of-operations chronological progression reminiscent of interfaces prior to the GUI revolution. Although such hybrids are considered by many interface specialists inappropriate to modern broad-spectrum computer applications, vertical market applications, including this one, can capitalize on such hybridization effectively. The hybrid interface provides multiple visual cues and directions to the user as to the next appropriate action, thereby allowing a physician or counselor to concentrate his/her attention on the patient, returning his/her gaze to the screen at sporadic and widely spaced moments. Hybrid interfaces combine specific interface elements--such as triple-scale checkboxes, text and design metaphors, "next step" helper icons, color-coded content, and color and graphically tailored on-screen reports (all of which constitute GUI elements)--with a strictly linear data accrual, approval, calculation, storage and reporting progression (which sequence constitutes a pre-GUI interface design). A first-generation design is presented: a hybrid combining the visual efficiency of GUI-improved interfaces with the practical efficiencies of stream-lined and linear progressions.
Computer Graphics↗
Influence of mRNA self-structure on hybridization: computational tools for antisense sequence selection.
Antisense targeting, an innovative technology based on preventing biosynthesis through sequence-specific hybridization of mRNA to synthetic oligodeoxynucleotides (ODNs), is used to selectively and transiently downregulate the expression of any gene product. Its potential applications are both investigative (neurobiology and related disciplines) and therapeutic (oncology, virology, genetic diseases), and several antisense-based drugs are currently undergoing clinical trials. However, the reported efficiencies vary and there is still a lack of clarity in the underlying mechanisms of action. A critical factor of antisense efficiency is the issue of target site selection, as both mRNA and ODN molecules exhibit a significant amount of highly heterogeneous self-structure and the region selected for targeting may well be sterically or energetically inaccessible. Because of the prohibitively large chain length, mRNA structural information is not accessible by X-ray crystallography or NMR, making a modeling approach indispensable. I outline how the latest molecular modeling techniques can be employed to establish the secondary (2D) and tertiary (3D) structures into which a given mRNA folds during and after transcription. The aim should be to integrate 2D prediction results achieved by (a) free-energy minimization, (b) kinetic folding simulations, (c) iterative population breeding by genetic algorithms, and (d) phylogenetic comparison techniques. These results can form the input of a 3D structure prediction paradigm based on constraint-satisfying programming, governed by experimental molecular mechanical constraints, and refined by molecular dynamics simulations. Finally, the automated docking (by simulated annealing) of ODN molecules to the mRNA structure can provide information about the accessibility of target mRNA regions for hybridization. To date, the great majority of studies that employ antisense as a tool select their target sequences more or less randomly. Although the wealth of molecular interactions that take place within a cell makes complete predictability unrealistic, the kind of information that can be extracted from such techniques is of relevance to every application of antisense technology, both investigative and therapeutic.
Algorithms↗
An anatomically based hybrid computational model of the human lung and its application to low frequency oscillatory mechanics.
Lung input impedance measured via forced oscillation over low frequency range has been confirmed as sensitive to the degree and the heterogeneity of lung disease. In this study we advanced an image-based, multi-scale computational model for the human lung, which includes upper and central airways, small airways and alveoli tissue unit. A three-dimensional (3-D) realistic model of the upper airway (reconstructed from MRI images) was combined with an anatomically based 3-D model of the central airways (based on MDCT images) to form a 3-D model of the large airways (from mouth to generation 6, incomplete for generations 4-6). The small airway trees distal to the central branches were based on a hypothetical airway tree for a normal healthy lung. A constant phase viscoelastic model was assumed for the alveolar tissue unit. Unsteady airflows in the large airways were simulated based on computational fluid dynamics (CFD). An experimentally measured broadband forcing flow was applied at the mouth. The impedance of the small airways was computed based on a one-dimensional transmission line model. The computed overall dynamic lung resistance and elastance compared very well with experimental values. Results showed that unsteady 3-D simulation and realistic geometry of the upper and large airways up to generations 4-6 can provide a reasonably accurate estimation of lung input impedance. The impedance of the upper airway constitutes a significant part of the total lung input impedance. The resistance of the upper airway accounts for 45-70% of the total lung resistance at frequencies between 0 and 1 Hz, and 70-81% at frequencies between 1 and 8 Hz.
Biological Clocks↗
A hybrid computer technique for detecting sharp EEG transients.
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Analog-Digital Conversion↗
A hybrid computer system for detecting and quantifying spike and wave EEG patterns.
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Analog-Digital Conversion↗
Adaptive systems and hybrid computational intelligence in medicine.
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Algorithms↗
Analyzing transport kinetics with desk-top hybrid computers.
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Biological Transport↗